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Telen, Marilyn Jo

Overview:

Dr. Telen is recognized as an expert in the biochemistry and molecular genetics of blood group antigens and the pathophysiological mechanisms of vaso-occlusion in sickle cell disease. She is the Director of the Duke Comprehensive Sickle Cell Center.

Dr. Telen's laboratory focuses on structure/function analysis of membrane proteins expressed by erythroid cells, as well as the role of these proteins in non-erythroid cells. Proteins are also studied in transfectant systems, and research focuses especially on adhesion receptors. The goals of this work are (1) to understand the mechanism and role of red cell adhesion to leukocytes and endothelium in sickle cell disease; (2) to understand the signaling mechanisms leading to activation (and inactivation) of red cell adhesion molecules; (3) to understand the molecular basis of blood group antigen expression, and (4) to understand the interactions of erythroid membrane proteins with other cells and with extracellular matrix..

Recent investigations have focused on the role of signaling pathways in the upregulation of sickle red cell adhesion. Present studies include (1) investigation of beta-adrenergic signaling pathway responsible for activation of B-CAM/LU and LW adhesion receptors; (2) understanding how nitric oxide and ATP downregulate sickle red cell adhesion; (3) studying the effect of these processes in animal models.

Dr. Telen is also involved in a large multicenter study looking for genetic polymorphisms that affect clinical outcomes in sickle cell disease, as well as a multi-center study investigating the mechanisms and treatment of pulmonary hypertension in sickle cell disease.


Key Words:

Adhesion molecules
Erythrocyte membrane
Sickle cell disease
Transfusion medicine
Immunohematology
CD44
B-CAM/LU
Genetic polymorphisms

Positions:

Wellcome Clinical Professor of Medicine in Honor of R. Wayne Rundles, M.D., in the School of Medicine

Medicine, Hematology
School of Medicine

Professor of Medicine

Medicine, Hematology
School of Medicine

Associate Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 0

M.D. — New York University

News:

Grants:

Transcriptomic, therapeutic and genetic investigations of sickle cell nephropathy

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 18, 2016
End Date
July 31, 2019

High-throughput Metabolite Profiling and Genetic Analyses

Administered By
Medicine, Hematology
AwardedBy
Doris Duke Charitable Foundation
Role
Principal Investigator
Start Date
September 01, 2015
End Date
August 31, 2018

PFIZER B0401016

Administered By
Medicine, Hematology
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
March 16, 2015
End Date
March 15, 2018

AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE SAFETY OF RIVIPANSEL (GMI-1070) IN THE TREATMENT OF ONE OR MORE VASOOCCLUSIVE CRISES IN HOSPITALIZED SUBJECTS WITH SICKLE CELL DISEASE.

Administered By
Medicine, Hematology
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
March 01, 2016
End Date
February 28, 2018

CSA - Pfizer 212511 B5201002 Phase 3 Randomized Multicenter Trial

Administered By
Medicine, Hematology
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
December 01, 2015
End Date
November 30, 2017

Improving Pain in Sickle Cell Patients With Targeted Antithrombotic Therapy

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
December 01, 2014
End Date
November 30, 2017

Factor XIII and Fibrinogen: Mechanisms of Genetic Risk in SCD-Related Priapism

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2017

Use of Mobile Technology to Improve Acute Care Utilization in Sickle Cell Disease

Administered By
Medicine, Hematology
AwardedBy
Agency for Healthcare Research and Quality
Role
Co Investigator
Start Date
June 15, 2015
End Date
May 31, 2017

Duke-UNC Clinical Hematology and Transfusion Research Career Development Program

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 28, 2006
End Date
April 30, 2017

Role of RBC NO and ATP in Sickle Vasculopathy

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 2012
End Date
June 30, 2016

Extension of Hematologic & Clinical Genotype-Phenotype Associations in SCD Using Exome Chip & Metabolomic Analysis

Administered By
Medicine, Hematology
AwardedBy
Doris Duke Charitable Foundation
Role
Principal Investigator
Start Date
September 01, 2013
End Date
September 01, 2015

Instrumentation for Quantitative Phosphoproteomics and Acetylomics

Administered By
Duke Center for Genomic and Computational Biology
AwardedBy
National Institutes of Health
Role
Major User
Start Date
May 15, 2014
End Date
May 14, 2015

Lateral Flow Hemoglobinopathies Test Development

Administered By
Medicine, Hematology
AwardedBy
BioMedomics, Inc.
Role
Principal Investigator
Start Date
March 31, 2014
End Date
September 30, 2014

Impaired release of antiadhesive ATP from stored RBCs: a novel transfusion lesion

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Clinical Investigator
Start Date
April 01, 2012
End Date
May 28, 2014

Phase II Study of Propranolol as Anti-Adhesive Therapy in SCD

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 30, 2009
End Date
July 31, 2013

PROPRANOLOL AS ANTI-ADHESIVE THERAPY IN SCD

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 15, 2010
End Date
November 30, 2012

Duke/UNC Comprehensive Sickle Cell Center

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2003
End Date
March 31, 2012

Training in the Genome Sciences and the Hemoglobinopathies

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Co-Director
Start Date
May 01, 2006
End Date
January 31, 2012

Training in the Genome Sciences and the Hemoglobinopathies

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Co-Director
Start Date
May 01, 2006
End Date
January 30, 2012

Relationship of Depression to SCD Severity, Health Care Utilization and QoL

Administered By
Medicine, Hematology
AwardedBy
Agency for Healthcare Research and Quality
Role
Co Investigator
Start Date
August 15, 2008
End Date
July 31, 2011

Pulmonary Hypertension in SCD

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 15, 2005
End Date
May 31, 2011

The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2008
End Date
April 30, 2011

Duke-UNC Sickle Cell Disease Clinical Research Network

Administered By
Duke Clinical Research Institute
AwardedBy
National Heart, Lung, and Blood Institute
Role
Principal Investigator
Start Date
April 17, 2006
End Date
March 31, 2011

Outcome Modifying Genes in Sickle Cell Diseases

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2001
End Date
July 31, 2008

Activation of Sickle Red Cell Adhesion

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2003
End Date
June 30, 2007

Adrenergic Receptor Variants and RBC Adhesion in SCD

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 15, 2004
End Date
April 30, 2007

Minority Invest Post-Bacc Res. Supp. - T Jackson

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2001
End Date
July 31, 2006

Factors Involved in B-CAM/LU-Mediated Adhesion

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1999
End Date
July 31, 2003

Sickle Cell Adhesion

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 13, 1997
End Date
June 30, 2003

Transfusion Medicine And Related Areas

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1975
End Date
June 30, 1999

Molecular Targets Of The In Lu Gene

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1987
End Date
December 31, 1997

Molecular Targets Of The In(Lu) Gene

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1993
End Date
June 30, 1997

Molecular Targets Of The In (Lu) Gene

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1987
End Date
June 30, 1997

Transfusion Medicine And Related Areas

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1975
End Date
June 30, 1996

Transfusion Medicine And Related Areas

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1975
End Date
June 30, 1996

Phosphatidylinositol-Anchored Blood Group Antigens

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1994
End Date
June 30, 1995

Erythrocyte Protein Antigens Regulated By In-Lu

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1992
End Date
November 30, 1993

Erythrocyte Protein Antigens Regulated By In(Lu)

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 15, 1991
End Date
November 30, 1993

Erythrocyte Protein Antigens Regulated By In(Lu)

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1992
End Date
June 30, 1993

Erythrocyte Blood Group Antigens Regulated By In(Lu)

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1986
End Date
November 01, 1988

Erythrocyte Blood Group Antigens Regulated By In (Lu)

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1985
End Date
November 01, 1987
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Awards:

Traditional Fulbright Scholarship. Council for International Exchange of Scholars.

Type
National
Awarded By
Council for International Exchange of Scholars
Date
January 01, 2010

Publications:

Thrombospondin-1 gene polymorphism is associated with estimated pulmonary artery pressure in patients with sickle cell anemia.

Authors
Jacob, SA; Novelli, EM; Isenberg, JS; Garrett, ME; Chu, Y; Soldano, K; Ataga, KI; Telen, MJ; Ashley-Koch, A; Gladwin, MT; Zhang, Y; Kato, GJ
MLA Citation
Jacob, SA, Novelli, EM, Isenberg, JS, Garrett, ME, Chu, Y, Soldano, K, Ataga, KI, Telen, MJ, Ashley-Koch, A, Gladwin, MT, Zhang, Y, and Kato, GJ. "Thrombospondin-1 gene polymorphism is associated with estimated pulmonary artery pressure in patients with sickle cell anemia." American journal of hematology 92.3 (March 2017): E31-E34. (Letter)
PMID
28033687
Source
epmc
Published In
American Journal of Hematology
Volume
92
Issue
3
Publish Date
2017
Start Page
E31
End Page
E34
DOI
10.1002/ajh.24635

Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.

Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Here, we demonstrate that sevuparin inhibits the adhesion of human sickle red blood cells (SS-RBCs) to stimulated cultured endothelial cells in vitro. Importantly, sevuparin prevents vaso-occlusion and normalizes blood flow in an in vivo mouse model of SCD vaso-occlusion. Analyses by surface plasmon resonance (SPR) and fluorescence correlation spectroscopy (FCS) demonstrate that sevuparin binds to P- and L-selectins, thrombospondin, fibronectin and von Willebrand factor, all of which are thought to contribute to vaso-occlusion in SCD. Despite low anticoagulation activity, sevuparin has anti-adhesive efficacy similar to the low molecular weight heparin tinzaparin both in vitro and in vivo. These results suggest that the anti-adhesive properties rather than the anticoagulant effects of heparinoids are critical for the treatment of vaso-occlusion in SCD. Therefore, sevuparin is now being evaluated in SCD patients hospitalized for treatment of VOC.

Authors
Telen, MJ; Batchvarova, M; Shan, S; Bovee-Geurts, PH; Zennadi, R; Leitgeb, A; Brock, R; Lindgren, M
MLA Citation
Telen, MJ, Batchvarova, M, Shan, S, Bovee-Geurts, PH, Zennadi, R, Leitgeb, A, Brock, R, and Lindgren, M. "Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion." British journal of haematology 175.5 (December 2016): 935-948.
PMID
27549988
Source
epmc
Published In
British Journal of Haematology
Volume
175
Issue
5
Publish Date
2016
Start Page
935
End Page
948
DOI
10.1111/bjh.14303

Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease.

Despite Food and Drug Administration (FDA) approval of hydroxyurea to reduce the frequency of vaso-occlusive episodes, sickle cell disease (SCD) has continued to be treated primarily with analgesics for pain relief. However, elucidation of the multiple pathophysiologic mechanisms leading to vaso-occlusion and tissue injury in SCD has now resulted in a burgeoning effort to identify new treatment modalities to prevent or ameliorate the consequences of the disease. Development of new drugs as well as investigation of drugs previously used in other settings have targeted cell adhesion, inflammatory pathways, upregulation of hemoglobin F, hemoglobin polymerization and sickling, coagulation, and platelet activation. Although these efforts have not yet yielded drugs ready for FDA approval, several early studies have been extremely encouraging. Moreover, the marked increase in clinical pharmaceutical research addressing SCD and the new and old drugs in the pipeline make it reasonable to expect that we will soon have new treatments for SCD.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease." Blood 127.7 (February 2016): 810-819. (Review)
PMID
26758919
Source
epmc
Published In
Blood
Volume
127
Issue
7
Publish Date
2016
Start Page
810
End Page
819
DOI
10.1182/blood-2015-09-618553

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2)-like 2), an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN) in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin) in a dose-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH) that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02) on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10) from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients. Trial registration: ClinicalTrials.gov NCT01715480.

Authors
Doss, JF; Jonassaint, JC; Garrett, ME; Ashley-Koch, AE; Telen, MJ; Chi, J-T
MLA Citation
Doss, JF, Jonassaint, JC, Garrett, ME, Ashley-Koch, AE, Telen, MJ, and Chi, J-T. "Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease." PloS one 11.4 (January 2016): e0152895-.
PMID
27071063
Source
epmc
Published In
PloS one
Volume
11
Issue
4
Publish Date
2016
Start Page
e0152895
DOI
10.1371/journal.pone.0152895

Genome-Wide Evaluation of Epistasis with APOL1 Risk Variants in Sickle Cell Disease Nephropathy

Authors
Garrett, ME; Soldano, KL; Anderson, BR; Telen, MJ; Ashley-Koch, AE
MLA Citation
Garrett, ME, Soldano, KL, Anderson, BR, Telen, MJ, and Ashley-Koch, AE. "Genome-Wide Evaluation of Epistasis with APOL1 Risk Variants in Sickle Cell Disease Nephropathy." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Correction: In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

Authors
Anderson, BR; Howell, DN; Soldano, K; Garrett, ME; Katsanis, N; Telen, MJ; Davis, EE; Ashley-Koch, AE
MLA Citation
Anderson, BR, Howell, DN, Soldano, K, Garrett, ME, Katsanis, N, Telen, MJ, Davis, EE, and Ashley-Koch, AE. "Correction: In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress." PLoS genetics 11.9 (September 17, 2015): e1005459-.
PMID
26379250
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
9
Publish Date
2015
Start Page
e1005459
DOI
10.1371/journal.pgen.1005459

In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

African Americans have a disproportionate risk for developing nephropathy. This disparity has been attributed to coding variants (G1 and G2) in apolipoprotein L1 (APOL1); however, there is little functional evidence supporting the role of this protein in renal function. Here, we combined genetics and in vivo modeling to examine the role of apol1 in glomerular development and pronephric filtration and to test the pathogenic potential of APOL1 G1 and G2. Translational suppression or CRISPR/Cas9 genome editing of apol1 in zebrafish embryos results in podocyte loss and glomerular filtration defects. Complementation of apol1 morphants with wild-type human APOL1 mRNA rescues these defects. However, the APOL1 G1 risk allele does not ameliorate defects caused by apol1 suppression and the pathogenicity is conferred by the cis effect of both individual variants of the G1 risk haplotype (I384M/S342G). In vivo complementation studies of the G2 risk allele also indicate that the variant is deleterious to protein function. Moreover, APOL1 G2, but not G1, expression alone promotes developmental kidney defects, suggesting a possible dominant-negative effect of the altered protein. In sickle cell disease (SCD) patients, we reported previously a genetic interaction between APOL1 and MYH9. Testing this interaction in vivo by co-suppressing both transcripts yielded no additive effects. However, upon genetic or chemical induction of anemia, we observed a significantly exacerbated nephropathy phenotype. Furthermore, concordant with the genetic interaction observed in SCD patients, APOL1 G2 reduces myh9 expression in vivo, suggesting a possible interaction between the altered APOL1 and myh9. Our data indicate a critical role for APOL1 in renal function that is compromised by nephropathy-risk encoding variants. Moreover, our interaction studies indicate that the MYH9 locus is also relevant to the phenotype in a stressed microenvironment and suggest that consideration of the context-dependent functions of both proteins will be required to develop therapeutic paradigms.

Authors
Anderson, BR; Howell, DN; Soldano, K; Garrett, ME; Katsanis, N; Telen, MJ; Davis, EE; Ashley-Koch, AE
MLA Citation
Anderson, BR, Howell, DN, Soldano, K, Garrett, ME, Katsanis, N, Telen, MJ, Davis, EE, and Ashley-Koch, AE. "In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress." PLoS genetics 11.7 (July 6, 2015): e1005349-.
Website
http://hdl.handle.net/10161/10832
PMID
26147622
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
7
Publish Date
2015
Start Page
e1005349
DOI
10.1371/journal.pgen.1005349

Alloimmunization in sickle cell disease: Changing antibody specificities and association with chronic pain and decreased survival

© 2014 AABB.Background Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD. Study Design and Methods Adult SCD patients were enrolled in a study of outcome-modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical, and laboratory findings; end-organ damage; and overall disease severity were then compared between alloimmunized and nonalloimmunized patients. Results Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vasoocclusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short-acting narcotics (p = 0.006), long-acting narcotics (p = 0.013), or both (p = 0.03). Additionally, alloimmunized patients had poorer survival (hazard ratio, 1.92; p = 0.01) and were more likely to have avascular necrosis (p = 0.024), end-organ damage (p = 0.049), and red blood cell autoantibodies (p < 0.001), even after controlling for the effects of age, sex, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD-related complications, such as acute chest syndrome or stroke. Conclusion Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain.

Authors
Telen, MJ; Afenyi-Annan, A; Garrett, ME; Combs, MR; Orringer, EP; Ashley-Koch, AE
MLA Citation
Telen, MJ, Afenyi-Annan, A, Garrett, ME, Combs, MR, Orringer, EP, and Ashley-Koch, AE. "Alloimmunization in sickle cell disease: Changing antibody specificities and association with chronic pain and decreased survival." Transfusion 55.6 (June 1, 2015): 1378-1387.
Source
scopus
Published In
Transfusion
Volume
55
Issue
6
Publish Date
2015
Start Page
1378
End Page
1387
DOI
10.1111/trf.12940

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival.

Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD.Adult SCD patients were enrolled in a study of outcome-modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical, and laboratory findings; end-organ damage; and overall disease severity were then compared between alloimmunized and nonalloimmunized patients.Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vasoocclusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short-acting narcotics (p = 0.006), long-acting narcotics (p = 0.013), or both (p = 0.03). Additionally, alloimmunized patients had poorer survival (hazard ratio, 1.92; p = 0.01) and were more likely to have avascular necrosis (p = 0.024), end-organ damage (p = 0.049), and red blood cell autoantibodies (p < 0.001), even after controlling for the effects of age, sex, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD-related complications, such as acute chest syndrome or stroke.Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain.

Authors
Telen, MJ; Afenyi-Annan, A; Garrett, ME; Combs, MR; Orringer, EP; Ashley-Koch, AE
MLA Citation
Telen, MJ, Afenyi-Annan, A, Garrett, ME, Combs, MR, Orringer, EP, and Ashley-Koch, AE. "Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival." Transfusion 55.6 Pt 2 (June 2015): 1378-1387.
PMID
25444611
Source
epmc
Published In
Transfusion
Volume
55
Issue
6 Pt 2
Publish Date
2015
Start Page
1378
End Page
1387
DOI
10.1111/trf.12940

Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use.

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.

Authors
Telen, MJ; Wun, T; McCavit, TL; De Castro, LM; Krishnamurti, L; Lanzkron, S; Hsu, LL; Smith, WR; Rhee, S; Magnani, JL; Thackray, H
MLA Citation
Telen, MJ, Wun, T, McCavit, TL, De Castro, LM, Krishnamurti, L, Lanzkron, S, Hsu, LL, Smith, WR, Rhee, S, Magnani, JL, and Thackray, H. "Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use." Blood 125.17 (April 2015): 2656-2664.
PMID
25733584
Source
epmc
Published In
Blood
Volume
125
Issue
17
Publish Date
2015
Start Page
2656
End Page
2664
DOI
10.1182/blood-2014-06-583351

Validation of a novel point of care testing device for sickle cell disease.

Sickle cell disease is one of the most common inherited blood disorders. Universal screening and early intervention have significantly helped to reduce childhood mortality in high-resource countries. However, persons living in low-resource settings are often not diagnosed until late childhood when they present with clinical symptoms. In addition, confirmation of disease in affected individuals in the urgent care setting is limited in both high- and low-resource areas, often leading to delay in treatment. All of the current diagnostic methods rely on advanced laboratory systems and are often prohibitively expensive and time-consuming in low-resource settings. To address this need, the Sickle SCAN™ test has been developed to diagnose sickle cell disease and sickle cell trait at the point of care without electricity or advanced equipment.This study was conducted to evaluate and validate the diagnostic accuracy of the Sickle SCAN™ test, a novel point of care test for sickle cell disease. Thus, we describe the laboratory testing and clinical validation of the Sickle SCAN™ test in individuals >1 year of age using capillary blood. The Sickle SCAN™ test was created using advanced, qualitative lateral flow technology using capillary blood to identify the presence of hemoglobin A, S, and C allowing for detection of results with the naked eye.Laboratory testing using venous blood demonstrated 99 % sensitivity and 99 % specificity for the diagnosis of HbSS, HbAS, HbSC, HbAC, and HbAA. Seventy-one subjects underwent capillary blood sampling at the point of care for further validation. This test detected the correct A, S, and C presence with an overall diagnostic accuracy of 99 % at the bedside.The Sickle SCAN™ test has the potential to significantly impact the diagnosis and treatment for sickle cell disease worldwide as well as enhance genetic counseling at the point of care. Further validation testing will be conducted in newborns in resource-poor settings in upcoming studies.

Authors
Kanter, J; Telen, MJ; Hoppe, C; Roberts, CL; Kim, JS; Yang, X
MLA Citation
Kanter, J, Telen, MJ, Hoppe, C, Roberts, CL, Kim, JS, and Yang, X. "Validation of a novel point of care testing device for sickle cell disease." BMC medicine 13 (January 2015): 225-.
PMID
26377572
Source
epmc
Published In
BMC Medicine
Volume
13
Publish Date
2015
Start Page
225
DOI
10.1186/s12916-015-0473-6

A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.

Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, we used high-throughput sequencing to identify both short (18-24 nt) and long (>200 nt) RNAs in mature erythrocytes.Analysis of the short RNA transcriptome with miRDeep identified 287 known and 72 putative novel microRNAs. Unexpectedly, we also uncover an extensive repertoire of long erythrocyte RNAs that encode many proteins critical for erythrocyte differentiation and function. Additionally, the erythrocyte long RNA transcriptome is significantly enriched in the erythroid progenitor transcriptome. Joint analysis of both short and long RNAs identified several loci with co-expression of both microRNAs and long RNAs spanning microRNA precursor regions. Within the miR-144/451 locus previously implicated in erythroid development, we observed unique co-expression of several primate-specific noncoding RNAs, including a lncRNA, and miR-4732-5p/-3p. We show that miR-4732-3p targets both SMAD2 and SMAD4, two critical components of the TGF-β pathway implicated in erythropoiesis. Furthermore, miR-4732-3p represses SMAD2/4-dependent TGF-β signaling, thereby promoting cell proliferation during erythroid differentiation.Our study presents the most extensive profiling of erythrocyte RNAs to date, and describes primate-specific interactions between the key modulator miR-4732-3p and TGF-β signaling during human erythropoiesis.

Authors
Doss, JF; Corcoran, DL; Jima, DD; Telen, MJ; Dave, SS; Chi, J-T
MLA Citation
Doss, JF, Corcoran, DL, Jima, DD, Telen, MJ, Dave, SS, and Chi, J-T. "A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes." BMC genomics 16 (January 2015): 952-.
PMID
26573221
Source
epmc
Published In
BMC Genomics
Volume
16
Publish Date
2015
Start Page
952
DOI
10.1186/s12864-015-2156-2

Biomarkers and recent advances in the management and therapy of sickle cell disease.

Although production of hemoglobin S, the genetic defect that causes sickle cell disease (SCD), directly affects only red blood cells, the manifestations of SCD are pervasive, and almost every cell type and organ system in the body can be involved. Today, the vast majority of patients with SCD who receive modern health care reach adulthood thanks to vaccine prophylaxis and improvements in supportive care, including transfusion. However, once patients reach adulthood, they commonly experience recurrent painful vaso-occlusive crises and frequently have widespread end-organ damage and severely shortened life expectancies. Over the last several decades, research has elucidated many of the mechanisms whereby abnormal red blood cells produce such ubiquitous organ damage. With these discoveries have come new ways to measure disease activity. In addition, new pharmaceutical interventions are now being developed to address what has been learned about disease mechanisms.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Biomarkers and recent advances in the management and therapy of sickle cell disease." F1000Research 4 (January 2015). (Review)
PMID
27508053
Source
epmc
Published In
F1000 Research
Volume
4
Publish Date
2015
DOI
10.12688/f1000research.6615.1

Genes Associated with Survival in Adult Sickle Cell Disease

Authors
Elmariah, H; Garrett, ME; Soldano, KL; Ataga, KI; Eckman, JR; Telen, MJ; Ashley-Koch, AE
MLA Citation
Elmariah, H, Garrett, ME, Soldano, KL, Ataga, KI, Eckman, JR, Telen, MJ, and Ashley-Koch, AE. "Genes Associated with Survival in Adult Sickle Cell Disease." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Evidence for a Dominant Negative Effect Conferred By the APOL1 G2 Sickle Cell Nephropathy Risk Allele in an in Vivo Model

Authors
Anderson, BR; Davis, EE; Telen, MJ; Ashley-Koch, AE
MLA Citation
Anderson, BR, Davis, EE, Telen, MJ, and Ashley-Koch, AE. "Evidence for a Dominant Negative Effect Conferred By the APOL1 G2 Sickle Cell Nephropathy Risk Allele in an in Vivo Model." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Genome-Wide Association Study of Glomerular Filtration Rate in a Cohort of Sickle Cell Disease Patients

Authors
Garrett, ME; Soldano, KL; Anderson, BR; Orringer, EP; Eckman, JR; Telen, MJ; Ashley-Koch, AE
MLA Citation
Garrett, ME, Soldano, KL, Anderson, BR, Orringer, EP, Eckman, JR, Telen, MJ, and Ashley-Koch, AE. "Genome-Wide Association Study of Glomerular Filtration Rate in a Cohort of Sickle Cell Disease Patients." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Genes Associated with Alloimmunization to Blood Group Antigens in Sickle Cell Disease

Authors
Milton, JN; Ashley-Koch, AE; Garrett, ME; Soldano, KL; Orringer, EP; Sebastiani, P; Dworkis, DA; Quillen, K; Steinberg, MH; Telen, MJ
MLA Citation
Milton, JN, Ashley-Koch, AE, Garrett, ME, Soldano, KL, Orringer, EP, Sebastiani, P, Dworkis, DA, Quillen, K, Steinberg, MH, and Telen, MJ. "Genes Associated with Alloimmunization to Blood Group Antigens in Sickle Cell Disease." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Effects of Sulforaphane Obtained from Broccoli Sprout Homogenate in Patients with Sickle Cell Disease (SCD)

Authors
Doss, J; Jonassaint, J; Shah, N; Telen, MJ; Chi, J-TA
MLA Citation
Doss, J, Jonassaint, J, Shah, N, Telen, MJ, and Chi, J-TA. "Effects of Sulforaphane Obtained from Broccoli Sprout Homogenate in Patients with Sickle Cell Disease (SCD)." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis

Authors
Wun, T; Telen, MJ; Krishnamurti, L; McCavit, TL; DeCastro, LM; Flanner, H; Kuypers, FA; Larkin, SK; Rhee, S; Magnani, JL; Thackray, HM
MLA Citation
Wun, T, Telen, MJ, Krishnamurti, L, McCavit, TL, DeCastro, LM, Flanner, H, Kuypers, FA, Larkin, SK, Rhee, S, Magnani, JL, and Thackray, HM. "Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Correction: Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

MLA Citation
"Correction: Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia." PLoS ONE 9.10 (October 17, 2014): e111690-e111690.
Source
crossref
Published In
PloS one
Volume
9
Issue
10
Publish Date
2014
Start Page
e111690
End Page
e111690
DOI
10.1371/journal.pone.0111690

Reply: Practice guideline for pulmonary hypertension in sickle cell: direct evidence needed before universal adoption.

Authors
Klings, ES; Machado, RF; Morris, CR; Gordeuk, VR; Kato, GJ; Ataga, KI; Castro, O; Hsu, L; Telen, MJ; Krishnamurti, L; Steinberg, MH; Gladwin, MT
MLA Citation
Klings, ES, Machado, RF, Morris, CR, Gordeuk, VR, Kato, GJ, Ataga, KI, Castro, O, Hsu, L, Telen, MJ, Krishnamurti, L, Steinberg, MH, and Gladwin, MT. "Reply: Practice guideline for pulmonary hypertension in sickle cell: direct evidence needed before universal adoption." American journal of respiratory and critical care medicine 190.2 (July 2014): 238-240. (Letter)
PMID
25025360
Source
epmc
Published In
American journal of respiratory and critical care medicine
Volume
190
Issue
2
Publish Date
2014
Start Page
238
End Page
240
DOI
10.1164/rccm.201404-0733le

Factors associated with survival in a contemporary adult sickle cell disease cohort.

In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were enrolled since 2002 at three university hospitals in the southeast United States. Subjects were followed up for a median of 9.3 years. At enrollment, clinical parameters were collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage. Levels of soluble adhesion molecules were measured for a subset of 87 subjects. The relationship of clinical characteristics to survival was determined using regression analysis. Median age at enrollment was 32 years. Median survival was 61 years for all subjects. Median survival for Hb SS and Sβ(0) was 58 years and for Hb SC and Sβ(+) was 66 years. Elevated white blood count, lower estimated glomerular filtration rate, proteinuria, frequency of pain crises, pulmonary hypertension, cerebrovascular events, seizures, stroke, sVCAM-1, and short-acting narcotics use were significantly associated with decreased survival. Forty-two percent of subjects were on hydroxyurea therapy, which was not associated with survival. SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sβ(0) and SS. Not only were comorbidities individually associated with decreased survival but also an additive effect was observed, thus, those with a greater number of negative endpoints had worse survival (P < 0.0001). The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial.

Authors
Elmariah, H; Garrett, ME; De Castro, LM; Jonassaint, JC; Ataga, KI; Eckman, JR; Ashley-Koch, AE; Telen, MJ
MLA Citation
Elmariah, H, Garrett, ME, De Castro, LM, Jonassaint, JC, Ataga, KI, Eckman, JR, Ashley-Koch, AE, and Telen, MJ. "Factors associated with survival in a contemporary adult sickle cell disease cohort." American journal of hematology 89.5 (May 2014): 530-535.
PMID
24478166
Source
epmc
Published In
American Journal of Hematology
Volume
89
Issue
5
Publish Date
2014
Start Page
530
End Page
535
DOI
10.1002/ajh.23683

Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors

The pathophysiology of vasoocclusion is thought to involve a wide variety of adhesive interactions involving erythrocytes, leukocytes, and the endothelium. Selectins are expressed by leukocytes, platelets, and the endothelium, among other tissues. They contribute to a wide variety of physiologically important cell-cell interactions, including adhesion of all types of blood cells to the endothelium. In vitro, in vivo, and early-phase clinical studies suggest that E-selectin and pan-selectin inhibitors may be promising new therapeutic agents for the treatment of vasoocclusion in sickle cell disease. © 2014 Elsevier Inc.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors." Hematology/Oncology Clinics of North America 28.2 (April 1, 2014): 341-354. (Review)
Source
scopus
Published In
Hematology/Oncology Clinics of North America
Volume
28
Issue
2
Publish Date
2014
Start Page
341
End Page
354
DOI
10.1016/j.hoc.2013.11.010

Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors.

The pathophysiology of vasoocclusion is thought to involve a wide variety of adhesive interactions involving erythrocytes, leukocytes, and the endothelium. Selectins are expressed by leukocytes, platelets, and the endothelium, among other tissues. They contribute to a wide variety of physiologically important cell-cell interactions, including adhesion of all types of blood cells to the endothelium. In vitro, in vivo, and early-phase clinical studies suggest that E-selectin and pan-selectin inhibitors may be promising new therapeutic agents for the treatment of vasoocclusion in sickle cell disease.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors." Hematology/oncology clinics of North America 28.2 (April 2014): 341-354.
PMID
24589270
Source
epmc
Published In
Hematology/Oncology Clinics of North America
Volume
28
Issue
2
Publish Date
2014
Start Page
341
End Page
354
DOI
10.1016/j.hoc.2013.11.010

An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease.

In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality.A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations. Target audiences include all clinicians who take care of patients with SCD.Mortality risk stratification guides decision making. An increased risk for mortality is defined as a TRV equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH. For patients identified as having increased mortality risk, we make a strong recommendation for hydroxyurea as first-line therapy and a weak recommendation for chronic transfusions as an alternative therapy. For all patients with SCD with elevated TRV alone or elevated NT-pro-BNP alone, and for patients with SCD with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance, we make a strong recommendation against PAH-specific therapy. However, for select patients with SCD with RHC-confirmed PH who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, we make a weak recommendation for either prostacyclin agonist or endothelin receptor antagonist therapy and a strong recommendation against phosphodiesterase-5 inhibitor therapy.Evidence-based recommendations for the management of patients with SCD with increased mortality risk are provided, but will require frequent reassessment and updating.

Authors
Klings, ES; Machado, RF; Barst, RJ; Morris, CR; Mubarak, KK; Gordeuk, VR; Kato, GJ; Ataga, KI; Gibbs, JS; Castro, O; Rosenzweig, EB; Sood, N; Hsu, L; Wilson, KC; Telen, MJ; Decastro, LM; Krishnamurti, L; Steinberg, MH; Badesch, DB; Gladwin, MT
MLA Citation
Klings, ES, Machado, RF, Barst, RJ, Morris, CR, Mubarak, KK, Gordeuk, VR, Kato, GJ, Ataga, KI, Gibbs, JS, Castro, O, Rosenzweig, EB, Sood, N, Hsu, L, Wilson, KC, Telen, MJ, Decastro, LM, Krishnamurti, L, Steinberg, MH, Badesch, DB, and Gladwin, MT. "An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease." American journal of respiratory and critical care medicine 189.6 (March 2014): 727-740.
PMID
24628312
Source
epmc
Published In
American journal of respiratory and critical care medicine
Volume
189
Issue
6
Publish Date
2014
Start Page
727
End Page
740
DOI
10.1164/rccm.201401-0065st

Factors associated with survival in a contemporary adult sickle cell disease cohort

In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were enrolled since 2002 at three university hospitals in the southeast United States. Subjects were followed up for a median of 9.3 years. At enrollment, clinical parameters were collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage. Levels of soluble adhesion molecules were measured for a subset of 87 subjects. The relationship of clinical characteristics to survival was determined using regression analysis. Median age at enrollment was 32 years. Median survival was 61 years for all subjects. Median survival for Hb SS and Sβ0 was 58 years and for Hb SC and Sβ+ was 66 years. Elevated white blood count, lower estimated glomerular filtration rate, proteinuria, frequency of pain crises, pulmonary hypertension, cerebrovascular events, seizures, stroke, sVCAM-1, and short-acting narcotics use were significantly associated with decreased survival. Forty-two percent of subjects were on hydroxyurea therapy, which was not associated with survival. SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sβ0 and SS. Not only were comorbidities individually associated with decreased survival but also an additive effect was observed, thus, those with a greater number of negative endpoints had worse survival (P<0.0001). The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial. © 2014 Wiley Periodicals, Inc.

Authors
Elmariah, H; Garrett, ME; De Castro, LM; Jonassaint, JC; Ataga, KI; Eckman, JR; Ashley-Koch, AE; Telen, MJ
MLA Citation
Elmariah, H, Garrett, ME, De Castro, LM, Jonassaint, JC, Ataga, KI, Eckman, JR, Ashley-Koch, AE, and Telen, MJ. "Factors associated with survival in a contemporary adult sickle cell disease cohort." American Journal of Hematology 89.5 (January 1, 2014): 530-535.
Source
scopus
Published In
American Journal of Hematology
Volume
89
Issue
5
Publish Date
2014
Start Page
530
End Page
535
DOI
10.1002/ajh.23683

Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia.

Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.ClinicalTrials.gov NCT00911495.

Authors
Wun, T; Styles, L; DeCastro, L; Telen, MJ; Kuypers, F; Cheung, A; Kramer, W; Flanner, H; Rhee, S; Magnani, JL; Thackray, H
MLA Citation
Wun, T, Styles, L, DeCastro, L, Telen, MJ, Kuypers, F, Cheung, A, Kramer, W, Flanner, H, Rhee, S, Magnani, JL, and Thackray, H. "Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia." PloS one 9.7 (January 2014): e101301-.
PMID
24988449
Source
epmc
Published In
PloS one
Volume
9
Issue
7
Publish Date
2014
Start Page
e101301
DOI
10.1371/journal.pone.0101301

Teaching evidence-based medicine in the former Soviet Union: lessons learned.

Between 2009 and 2012, I taught principles of evidence-based medicine and clinical research in Russia, Tatarstan, Moldova, and Kazakhstan. The Soviet Union left a medical legacy characterized by balkanization of top tier medicine in highly specialized centers, so there was little capability for multidiscipinary care. In addition, the authoritarian government led to a persistently top-down tradition of medical education and practice, which one of my Russian colleagues aptly named "eminence-based medicine." After the fall of the Soviet Union, funding for science and medical research was drastically cut, leading to a struggle for resources and politicization of resource decisions. At present, prejudices and beliefs about disease and treatment persist untested, limited English language competency impedes acquisition of new knowledge, and restriction of resources cripples innovation. Yet none of these conditions are unknown to us in the United States. Physicians may resist evidence that challenges long-held beliefs, and patients want us to make decisions based on their individual case, not evidence arising from studying other people. As physicians, we need to understand how to communicate with and frame our arguments so that they can be understood and received favorably. Can we draw lessons from trying to teach evidence-based medicine in the former Soviet Union?

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Teaching evidence-based medicine in the former Soviet Union: lessons learned." Transactions of the American Clinical and Climatological Association 125 (January 2014): 88-102.
PMID
25125721
Source
epmc
Published In
Transactions of the American Clinical and Climatological Association
Volume
125
Publish Date
2014
Start Page
88
End Page
102

Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors." Hematology/Oncology Clinics of North America 28.2 (2014): 341-354.
Source
scopus
Published In
Hematology/Oncology Clinics of North America
Volume
28
Issue
2
Publish Date
2014
Start Page
341
End Page
354

GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease

Authors
Telen, MJ; Wun, T; McCavit, TL; De Castro, LM; Krishnamurti, L; Lanzkron, S; Hsu, LL; Smith, WR; Rhee, S; Magnani, JL; Thackray, H
MLA Citation
Telen, MJ, Wun, T, McCavit, TL, De Castro, LM, Krishnamurti, L, Lanzkron, S, Hsu, LL, Smith, WR, Rhee, S, Magnani, JL, and Thackray, H. "GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

Effects Of GMI 1070, a Pan-Selectin Inhibitor, On Pain Intensity and Opioid Utilization In Sickle Cell Disease

Authors
De Castro, LM; Wun, T; Lanzkron, S; Smith, WR; Hassell, KL; Kutlar, A; Smith-Whitley, K; Rhee, S; Telen, MJ; Thackray, H
MLA Citation
De Castro, LM, Wun, T, Lanzkron, S, Smith, WR, Hassell, KL, Kutlar, A, Smith-Whitley, K, Rhee, S, Telen, MJ, and Thackray, H. "Effects Of GMI 1070, a Pan-Selectin Inhibitor, On Pain Intensity and Opioid Utilization In Sickle Cell Disease." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

In Vivo Modeling Of Genetic Mechanisms Associated With Sickle Cell Disease Nephropathy

Authors
Anderson, BR; Davis, EE; Telen, MJ; Ashley-Koch, AE
MLA Citation
Anderson, BR, Davis, EE, Telen, MJ, and Ashley-Koch, AE. "In Vivo Modeling Of Genetic Mechanisms Associated With Sickle Cell Disease Nephropathy." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso-Occlusion In Vivo

Authors
Batchvarova, M; Shan, S; Zennadi, R; Lindgren, M; Leitgeb, A; Tamsen, PS; Telen, MJ
MLA Citation
Batchvarova, M, Shan, S, Zennadi, R, Lindgren, M, Leitgeb, A, Tamsen, PS, and Telen, MJ. "Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso-Occlusion In Vivo." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients.

Patients with sickle cell disease (SCD) present with a wide range of clinical complications. Understanding this clinical heterogeneity offers the prospects to tailor the right treatments to the right patients and also guide the development of novel therapies. Several environmental (eg, nutrition) and nonenvironmental (eg, fetal hemoglobin levels, α-thalassemia status) factors are known to modify SCD severity. To find new genetic modifiers of SCD severity, we performed a gene-centric association study in 1514 African American participants from the Cooperative Study of Sickle Cell Disease (CSSCD) for acute chest syndrome (ACS) and painful crisis. From the initial results, we selected 36 single nucleotide polymorphism (SNPs) and genotyped them for replication in 387 independent patients from the CSSCD, 318 SCD patients recruited at Georgia Health Sciences University, and 449 patients from the Duke SCD cohort. In the combined analysis, an association between ACS and rs6141803 reached array-wide significance (P = 4.1 × 10(-7)). This SNP is located 8.2 kilobases upstream of COMMD7, a gene highly expressed in the lung that interacts with nuclear factor-κB signaling. Our results provide new leads to gaining a better understanding of clinical variability in SCD, a "simple" monogenic disease.

Authors
Galarneau, G; Coady, S; Garrett, ME; Jeffries, N; Puggal, M; Paltoo, D; Soldano, K; Guasch, A; Ashley-Koch, AE; Telen, MJ; Kutlar, A; Lettre, G; Papanicolaou, GJ
MLA Citation
Galarneau, G, Coady, S, Garrett, ME, Jeffries, N, Puggal, M, Paltoo, D, Soldano, K, Guasch, A, Ashley-Koch, AE, Telen, MJ, Kutlar, A, Lettre, G, and Papanicolaou, GJ. "Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients." Blood 122.3 (July 18, 2013): 434-442.
PMID
23719301
Source
pubmed
Published In
Blood
Volume
122
Issue
3
Publish Date
2013
Start Page
434
End Page
442
DOI
10.1182/blood-2013-01-478776

IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies.

BACKGROUND: The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. PURPOSE: The purpose of this report is to describe our Network's experiences with protocol development, implementation, and analysis, including overall study design, the value of pain assessments rather than 'crisis' resolution as trial endpoints, and alternative statistical analysis strategies. METHODS: The Improving Pain Management and Outcomes with Various Strategies (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial comparing two PCA-dosing strategies in adults and children with SCD and acute pain conducted by the SCD Clinical Research Network. The specified primary endpoint was a 25-mm change in a daily average pain intensity using a Visual Analogue Scale, and a number of related pain intensity and pain interference measures were selected as secondary efficacy outcomes. A time-to-event analysis strategy was planned for the primary endpoint. RESULTS: Of 1116 individuals admitted for pain at 31 participating sites over a 6-month period, 38 were randomized and 4 withdrawn. The trial was closed early due to poor accrual, reflecting a substantial number of challenges encountered during trial implementation. LIMITATIONS: While some of the design issues were unique to SCD or analgesic studies, many of the trial implementation challenges reflected the increasing complexity of conducting clinical trials in the inpatient setting with multiple care providers and evolving electronic medical record systems, particularly in the context of large urban academic medical centers. LESSONS LEARNED: Complicated clinical organization of many sites likely slowed study initiation. More extensive involvement of research staff and site principal investigator in the clinical care operations improved site performance. During the subsequent data analysis, alternative statistical approaches were considered, the results of which should inform future efficacy assessments and increase future trial recruitment success by allowing substantial reductions in target sample size. CONCLUSIONS: A complex randomized analgesic trial was initiated within a multisite disease network seeking to provide an evidence base for clinical care. A number of design considerations were shown to be feasible in this setting, and several pain intensity and pain interference measures were shown to be sensitive to time- and treatment-related improvements. While the premature closure and small sample size precluded definitive conclusions regarding treatment efficacy, this trial furnishes a template for design and implementation considerations that should improve future SCD analgesic trials.

Authors
Dampier, CD; Smith, WR; Wager, CG; Kim, H-Y; Bell, MC; Miller, ST; Weiner, DL; Minniti, CP; Krishnamurti, L; Ataga, KI; Eckman, JR; Hsu, LL; McClish, D; McKinlay, SM; Molokie, R; Osunkwo, I; Smith-Whitley, K; Telen, MJ; Sickle Cell Disease Clinical Research Network (SCDCRN),
MLA Citation
Dampier, CD, Smith, WR, Wager, CG, Kim, H-Y, Bell, MC, Miller, ST, Weiner, DL, Minniti, CP, Krishnamurti, L, Ataga, KI, Eckman, JR, Hsu, LL, McClish, D, McKinlay, SM, Molokie, R, Osunkwo, I, Smith-Whitley, K, Telen, MJ, and Sickle Cell Disease Clinical Research Network (SCDCRN), . "IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies." Clin Trials 10.2 (April 2013): 319-331.
PMID
23539110
Source
pubmed
Published In
Clinical Trials
Volume
10
Issue
2
Publish Date
2013
Start Page
319
End Page
331
DOI
10.1177/1740774513475850

Sickle erythrocytes target cytotoxics to hypoxic tumor microvessels and potentiate a tumoricidal response.

Resistance of hypoxic solid tumor niches to chemotherapy and radiotherapy remains a major scientific challenge that calls for conceptually new approaches. Here we exploit a hitherto unrecognized ability of sickled erythrocytes (SSRBCs) but not normal RBCs (NLRBCs) to selectively target hypoxic tumor vascular microenviroment and induce diffuse vaso-occlusion. Within minutes after injection SSRBCs, but not NLRBCs, home and adhere to hypoxic 4T1 tumor vasculature with hemoglobin saturation levels at or below 10% that are distributed over 70% of the tumor space. The bound SSRBCs thereupon form microaggregates that obstruct/occlude up to 88% of tumor microvessels. Importantly, SSRBCs, but not normal RBCs, combined with exogenous prooxidant zinc protoporphyrin (ZnPP) induce a potent tumoricidal response via a mutual potentiating mechanism. In a clonogenic tumor cell survival assay, SSRBC surrogate hemin, along with H(2)O(2) and ZnPP demonstrate a similar mutual potentiation and tumoricidal effect. In contrast to existing treatments directed only to the hypoxic tumor cell, the present approach targets the hypoxic tumor vascular environment and induces injury to both tumor microvessels and tumor cells using intrinsic SSRBC-derived oxidants and locally generated ROS. Thus, the SSRBC appears to be a potent new tool for treatment of hypoxic solid tumors, which are notable for their resistance to existing cancer treatments.

Authors
Terman, DS; Viglianti, BL; Zennadi, R; Fels, D; Boruta, RJ; Yuan, H; Dreher, MR; Grant, G; Rabbani, ZN; Moon, E; Lan, L; Eble, J; Cao, Y; Sorg, B; Ashcraft, K; Palmer, G; Telen, MJ; Dewhirst, MW
MLA Citation
Terman, DS, Viglianti, BL, Zennadi, R, Fels, D, Boruta, RJ, Yuan, H, Dreher, MR, Grant, G, Rabbani, ZN, Moon, E, Lan, L, Eble, J, Cao, Y, Sorg, B, Ashcraft, K, Palmer, G, Telen, MJ, and Dewhirst, MW. "Sickle erythrocytes target cytotoxics to hypoxic tumor microvessels and potentiate a tumoricidal response." PLoS One 8.1 (2013): e52543-.
Website
http://hdl.handle.net/10161/11164
PMID
23326340
Source
pubmed
Published In
PloS one
Volume
8
Issue
1
Publish Date
2013
Start Page
e52543
DOI
10.1371/journal.pone.0052543

Novel optical signature for sickle cell trait red blood cells

We identified unique optical signatures for sickle cell trait, a condition where heterozygous individuals are carriers for the hemoglobin allele that causes sickle cell anemia, by using wide-field interferometric microscopy. © OSA 2012.

Authors
Satterwhite, LL; Shaked, NT; Cyr, DD; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Satterwhite, LL, Shaked, NT, Cyr, DD, Telen, MJ, Truskey, GA, and Wax, A. "Novel optical signature for sickle cell trait red blood cells." Frontiers in Optics, FIO 2012 (December 1, 2012).
Source
scopus
Published In
Frontiers in Optics, FIO 2012
Publish Date
2012

Effect of propranolol as antiadhesive therapy in sickle cell disease.

Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β-adrenergic receptor and protein kinase A-dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso-occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose-escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso-occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine-stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that β-blockers may have a role as antiadhesive therapy for SCD.

Authors
De Castro, LM; Zennadi, R; Jonassaint, JC; Batchvarova, M; Telen, MJ
MLA Citation
De Castro, LM, Zennadi, R, Jonassaint, JC, Batchvarova, M, and Telen, MJ. "Effect of propranolol as antiadhesive therapy in sickle cell disease." Clin Transl Sci 5.6 (December 2012): 437-444.
PMID
23253664
Source
pubmed
Published In
Clinical and Translational Science
Volume
5
Issue
6
Publish Date
2012
Start Page
437
End Page
444
DOI
10.1111/cts.12005

Pan-Selectin Antagonist GMI-1070 Affects Biomarkers of Adhesion, Activation and the Coagulation Cascade in Sickle Cell Adults At Steady State

Authors
Magnani, JL; Kuypers, FA; Patton, JT; Larkin, SK; Styles, L; DeCastro, LM; Telen, MJ; Wun, T; Thackray, H
MLA Citation
Magnani, JL, Kuypers, FA, Patton, JT, Larkin, SK, Styles, L, DeCastro, LM, Telen, MJ, Wun, T, and Thackray, H. "Pan-Selectin Antagonist GMI-1070 Affects Biomarkers of Adhesion, Activation and the Coagulation Cascade in Sickle Cell Adults At Steady State." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Characterization of the hypercoagulable state in patients with sickle cell disease.

BACKGROUND: The pathophysiology of sickle cell disease (SCD) is complex, with increasing evidence of a pronounced prothrombotic state. OBJECTIVE: We investigated thrombin generation in SCD utilizing calibrated automated thrombography (CAT) and D-dimer, with subsequent correlation to clinical disease. PATIENT/METHODS: The study included 51 patients homozygous for hemoglobin S, either admitted for vaso-occlusive crisis (VOC) (n=34) or while in steady state and being seen in outpatient clinic (n=37). Twenty patients had blood drawn during both VOC and steady state. Mean values for CAT and D-dimer were compared between groups. Mean values for patients with and without clinical complications such as avascular necrosis and stroke were also compared. Linear regression was used to evaluate correlation to number of hospitalizations and for all pediatric patients, transcranial doppler (TCD) velocities. RESULTS: The mean D-dimer during VOC (2743 ± 3118 ng/ml) was significantly higher than during steady state (1151 ± 802, p<0.0001). Comparison of crisis and steady state by CAT also revealed a significant difference in all phases of thrombin generation, including mean endogenous thrombin potential (1381 ± 295 nM vs 923 ± 316, p<0.0001) and peak thrombin generated (284 ± 9 vs 223 ± 18, p=0.0002). There were no significant differences in mean values for the clinical outcomes examined in adults. In pediatric patients, however, increased TCD velocities correlated with steady state D-dimer (r(2)=0.32, p=0.02) and thrombin-antithrombin complex (r(2)=0.28, p=0.04. CONCLUSION: Hypercoagulable markers distinguish between patients with SCD during and between VOC, but do not correlate with specific clinical phenotypes.

Authors
Shah, N; Thornburg, C; Telen, MJ; Ortel, TL
MLA Citation
Shah, N, Thornburg, C, Telen, MJ, and Ortel, TL. "Characterization of the hypercoagulable state in patients with sickle cell disease." Thromb Res 130.5 (November 2012): e241-e245.
PMID
22959127
Source
pubmed
Published In
Thrombosis Research
Volume
130
Issue
5
Publish Date
2012
Start Page
e241
End Page
e245
DOI
10.1016/j.thromres.2012.08.307

Kikuchi-Fugimoto's disease in sickle cell disease: report of 2 cases.

Kikuchi-Fugimoto's Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is most frequently seen in young women and has been associated with autoimmune disorders such as polymyositis and systemic lupus erythematosus. It is generally a self-limiting disease with recovery time ranging from weeks to months. A typical presentation of KFD includes painful cervical lymphadenopathy, usually consisting of unilateral involvement of the posterior cervical chain. To date, this condition has not been described in patients with sickle cell disease. We present 2 cases of KFD, 1 in a patient with sickle beta(o)-thalassemia (Sbeta(o)thal) and 1 in a patient with sickle cell anemia with hereditary persistence of fetal hemoglobin (HbS-HPFH). Both patients were young-adult African American females who presented with fever and unilateral tender cervical lymphadenopathy. Extensive infectious disease testing, including cultures and viral serologies, were all negative. Imaging was negative for abscesses. The first patient had a preceding history of benign carcinoid tumor and idiopathic thrombocytopenic purpura. The second patient had no history of autoimmune syndromes but was on hydroxyurea therapy at the time of her presentation; the first had never taken hydroxyurea. Treatment strategies included prednisone therapy in the first case and watchful monitoring in the second. Recovery time was approximately 2 months for each patient. Both developed thyroid disease subsequent to their episode of KFD. Currently, both patients are asymptomatic with no recurrence of KFD or active autoimmune disease.

Authors
Crawford, RD; Kalhagen, L; Wang, E; Telen, MJ
MLA Citation
Crawford, RD, Kalhagen, L, Wang, E, and Telen, MJ. "Kikuchi-Fugimoto's disease in sickle cell disease: report of 2 cases." J Natl Med Assoc 104.9-10 (September 2012): 459-462.
PMID
23342821
Source
pubmed
Published In
Journal of the National Medical Association
Volume
104
Issue
9-10
Publish Date
2012
Start Page
459
End Page
462

Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans.

Authors
Bae, HT; Baldwin, CT; Sebastiani, P; Telen, MJ; Ashley-Koch, A; Garrett, M; Hooper, WC; Bean, CJ; Debaun, MR; Arking, DE; Bhatnagar, P; Casella, JF; Keefer, JR; Barron-Casella, E; Gordeuk, V; Kato, GJ; Minniti, C; Taylor, J; Campbell, A; Luchtman-Jones, L; Hoppe, C; Gladwin, MT; Zhang, Y; Steinberg, MH
MLA Citation
Bae, HT, Baldwin, CT, Sebastiani, P, Telen, MJ, Ashley-Koch, A, Garrett, M, Hooper, WC, Bean, CJ, Debaun, MR, Arking, DE, Bhatnagar, P, Casella, JF, Keefer, JR, Barron-Casella, E, Gordeuk, V, Kato, GJ, Minniti, C, Taylor, J, Campbell, A, Luchtman-Jones, L, Hoppe, C, Gladwin, MT, Zhang, Y, and Steinberg, MH. "Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans." Blood 120.9 (August 30, 2012): 1961-1962. (Letter)
PMID
22936743
Source
pubmed
Published In
Blood
Volume
120
Issue
9
Publish Date
2012
Start Page
1961
End Page
1962
DOI
10.1182/blood-2012-06-432849

Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance.

Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.

Authors
LaMonte, G; Philip, N; Reardon, J; Lacsina, JR; Majoros, W; Chapman, L; Thornburg, CD; Telen, MJ; Ohler, U; Nicchitta, CV; Haystead, T; Chi, J-T
MLA Citation
LaMonte, G, Philip, N, Reardon, J, Lacsina, JR, Majoros, W, Chapman, L, Thornburg, CD, Telen, MJ, Ohler, U, Nicchitta, CV, Haystead, T, and Chi, J-T. "Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance." Cell Host Microbe 12.2 (August 16, 2012): 187-199.
PMID
22901539
Source
pubmed
Published In
Cell Host and Microbe
Volume
12
Issue
2
Publish Date
2012
Start Page
187
End Page
199
DOI
10.1016/j.chom.2012.06.007

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark of SCD. ERK1/2 remained active in SS but not normal RBCs. β(2)-adrenergic receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs via PKA- and tyrosine kinase p72(syk)-dependent pathways. ERK signaling is implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the endothelium. SS RBC adhesion and phosphorylation of both ERK and ICAM-4 all decreased with continued cell exposure to epinephrine, implying that activation of ICAM-4-mediated SS RBC adhesion is temporally associated with ERK1/2 activation. Furthermore, recombinant ERK2 phosphorylated α- and β-adducins and dematin at the ERK consensus motif. Cytoskeletal protein 4.1 also showed dynamic phosphorylation but not at the ERK consensus motif. These results demonstrate that ERK activation induces phosphorylation of cytoskeletal proteins and the adhesion molecule ICAM-4, promoting SS RBC adhesion to the endothelium. Thus, blocking RBC ERK1/2 activation, such as that promoted by catecholamine stress hormones, could ameliorate SCD pathophysiology.

Authors
Zennadi, R; Whalen, EJ; Soderblom, EJ; Alexander, SC; Thompson, JW; Dubois, LG; Moseley, MA; Telen, MJ
MLA Citation
Zennadi, R, Whalen, EJ, Soderblom, EJ, Alexander, SC, Thompson, JW, Dubois, LG, Moseley, MA, and Telen, MJ. "Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium." Blood 119.5 (February 2012): 1217-1227.
PMID
22147898
Source
epmc
Published In
Blood
Volume
119
Issue
5
Publish Date
2012
Start Page
1217
End Page
1227
DOI
10.1182/blood-2011-03-344440

GMI-1070: Pan-selectin antagonist treatment of sickle cell disease

GMI-1070 is a rationally designed carbohydrate molecule created as an antagonist of all selectin proteins. Selectins are adhesion molecules expressed by many hematopoietic and endothelial cells. They mediate early stages of cell adhesion and are therefore critical in a wide variety of cell-cell interactions, including hematopoietic stem cell interactions with the bone marrow microenvironment, lymphocyte homing to lymphoid tissue, inflammatory leukocyte adhesion to the endothelium, and cancer cell adhesion during metastasis. In sickle cell disease, both red cell and leukocyte adhesion appears to be at least partially selectin-dependent, suggesting that blockade of selectin-mediated interactions might ameliorate or prevent vaso-occlusive events. GMI-1070 has been shown to have activity in many of these processes in a variety of in vitro and in vivo models. In addition, it has been tested in humans in phase I studies, and it is now undergoing phase II evaluation in the setting of sickle cell disease vaso-occlusive events. This compound thus represents one of the earliest attempts at anti-adhesive therapy in sickle cell disease. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "GMI-1070: Pan-selectin antagonist treatment of sickle cell disease." Drugs of the Future 37.6 (January 1, 2012): 403-413. (Review)
Source
scopus
Published In
Drugs of the future
Volume
37
Issue
6
Publish Date
2012
Start Page
403
End Page
413
DOI
10.1358/dof.2012.037.06.1790307

A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5 × 10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08 × 10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.

Authors
Milton, JN; Sebastiani, P; Solovieff, N; Hartley, SW; Bhatnagar, P; Arking, DE; Dworkis, DA; Casella, JF; Barron-Casella, E; Bean, CJ; Hooper, WC; DeBaun, MR; Garrett, ME; Soldano, K; Telen, MJ; Ashley-Koch, A; Gladwin, MT; Baldwin, CT; Steinberg, MH; Klings, ES
MLA Citation
Milton, JN, Sebastiani, P, Solovieff, N, Hartley, SW, Bhatnagar, P, Arking, DE, Dworkis, DA, Casella, JF, Barron-Casella, E, Bean, CJ, Hooper, WC, DeBaun, MR, Garrett, ME, Soldano, K, Telen, MJ, Ashley-Koch, A, Gladwin, MT, Baldwin, CT, Steinberg, MH, and Klings, ES. "A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia." PLoS One 7.4 (2012): e34741-.
PMID
22558097
Source
pubmed
Published In
PloS one
Volume
7
Issue
4
Publish Date
2012
Start Page
e34741
DOI
10.1371/journal.pone.0034741

Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease

We have applied wide-field digital interferometric techniques to quantitatively image sickle red blood cells (RBCs) [1] in a noncontact label-free manner, and measure the nanometer-scale fluctuations in their thickness as an indication of their stiffness. The technique can simultaneously measure the fluctuations for multiple spatial points on the RBC and thus yields a map describing the stiffness of each RBC in the field of view. Using this map, the local rigidity regions of the RBC are evaluated quantitatively. Since wide-field digital interferometry is a quantitative holographic imaging technique rather than one-point measurement, it can be used to simultaneously evaluate cell transverse morphology plus thickness in addition to its stiffness profile. Using this technique, we examine the morphology and dynamics of RBCs from individuals who suffer from sickle cell disease, and find that the sickle RBCs are significantly stiffer than healthy RBCs. Furthermore, we show that the technique is sensitive enough to distinguish various classes of sickle RBCs, including sickle RBCs with visibly-normal morphology, compared to the stiffer crescent-shaped sickle RBCs. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Shaked, NT; Satterwhite, LL; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Telen, MJ, Truskey, GA, and Wax, A. "Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease." 2012.
Source
scival
Published In
Proceedings of SPIE
Volume
8227
Publish Date
2012
DOI
10.1117/12.907659

GMI-1070: Pan-selectin antagonist treatment of sickle cell disease

GMI-1070 is a rationally designed carbohydrate molecule created as an antagonist of all selectin proteins. Selectins are adhesion molecules expressed by many hematopoietic and endothelial cells. They mediate early stages of cell adhesion and are therefore critical in a wide variety of cell-cell interactions, including hematopoietic stem cell interactions with the bone marrow microenvironment, lymphocyte homing to lymphoid tissue, inflammatory leukocyte adhesion to the endothelium, and cancer cell adhesion during metastasis. In sickle cell disease, both red cell and leukocyte adhesion appears to be at least partially selectin-dependent, suggesting that blockade of selectin-mediated interactions might ameliorate or prevent vaso-occlusive events. GMI-1070 has been shown to have activity in many of these processes in a variety of in vitro and in vivo models. In addition, it has been tested in humans in phase I studies, and it is now undergoing phase II evaluation in the setting of sickle cell disease vaso-occlusive events. This compound thus represents one of the earliest attempts at anti-adhesive therapy in sickle cell disease. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "GMI-1070: Pan-selectin antagonist treatment of sickle cell disease." Drugs of the Future 37.6 (2012): 403-413.
Source
scival
Published In
Drugs of the future
Volume
37
Issue
6
Publish Date
2012
Start Page
403
End Page
413
DOI
10.1358/dof.2012.37.6.1790307

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

Authors
Dampier, CD; Smith, WR; Kim, H-Y; Wager, CG; Bell, MC; Minniti, CP; Keefer, J; Hsu, L; Krishnamurti, L; Mack, AK; McClish, D; McKinlay, SM; Miller, ST; Osunkwo, I; Seaman, P; Telen, MJ; Weiner, DL; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN),
MLA Citation
Dampier, CD, Smith, WR, Kim, H-Y, Wager, CG, Bell, MC, Minniti, CP, Keefer, J, Hsu, L, Krishnamurti, L, Mack, AK, McClish, D, McKinlay, SM, Miller, ST, Osunkwo, I, Seaman, P, Telen, MJ, Weiner, DL, and Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN), . "Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes." Am J Hematol 86.12 (December 2011): E70-E73. (Letter)
PMID
21953763
Source
pubmed
Published In
American Journal of Hematology
Volume
86
Issue
12
Publish Date
2011
Start Page
E70
End Page
E73
DOI
10.1002/ajh.22176

An Elevated Tricuspid Regurgitant Jet Velocity in Sickle Cell Disease Is Associated with Polymorphisms in Genes Impacting Innate Immunity

Authors
Bae, HT; Baldwin, CT; Gladwin, MT; Ashley-Koch, AE; Garrett, M; Soldano, K; Taylor, JG; Kato, GJ; Telen, MJ; Sebastiani, P; Steinberg, MH; Klings, ES
MLA Citation
Bae, HT, Baldwin, CT, Gladwin, MT, Ashley-Koch, AE, Garrett, M, Soldano, K, Taylor, JG, Kato, GJ, Telen, MJ, Sebastiani, P, Steinberg, MH, and Klings, ES. "An Elevated Tricuspid Regurgitant Jet Velocity in Sickle Cell Disease Is Associated with Polymorphisms in Genes Impacting Innate Immunity." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
240
End Page
240

Inflammatory Polymorphisms Link the Risk of Acute Chest Syndrome with Asthma in Adults with Sickle Cell Disease

Authors
Barber, LA; Soldano, K; Garrett, M; Orringer, EP; Eckman, JR; Telen, MJ; Ashley-Koch, AE
MLA Citation
Barber, LA, Soldano, K, Garrett, M, Orringer, EP, Eckman, JR, Telen, MJ, and Ashley-Koch, AE. "Inflammatory Polymorphisms Link the Risk of Acute Chest Syndrome with Asthma in Adults with Sickle Cell Disease." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
493
End Page
493

Sickle Red Blood Cell Induced Adhesion of Neutrophils to Endothelial Cells and Biologic Correlates of Leukocyte Activation

Authors
Boateng, LA; Zennadi, R; Telen, MJ
MLA Citation
Boateng, LA, Zennadi, R, and Telen, MJ. "Sickle Red Blood Cell Induced Adhesion of Neutrophils to Endothelial Cells and Biologic Correlates of Leukocyte Activation." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
486
End Page
486

Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion.

OBJECTIVE: Transfusion of red blood cells has been linked to disappointing clinical outcomes in the critically ill, but specific mechanisms of organ dysfunction after transfusion remain poorly understood. We tested the hypothesis that red blood cell storage impairs the ability of red blood cells to release adenosine-5'-triphosphate and that impaired adenosine-5'-triphosphate release was injurious in vivo, in part through increased red blood cell adhesion. DESIGN: Prospective, controlled, mechanistic study. SETTING: University research laboratory. SUBJECTS: Human and mouse blood donors; nude mouse transfusion recipients. INTERVENTIONS: Manipulation of adenosine-5'-triphosphate release, supplemental adenosine-5'-triphosphate, and antibodies to red blood cell and endothelial adhesion receptors were used in vitro and in vivo to probe the roles of released adenosine-5'-triphosphate and adhesion in responses to (transfused) red blood cells. MEASUREMENTS AND MAIN RESULTS: The ability of stored red blood cells to release adenosine-5'-triphosphate declined markedly within 14 days after collection despite relatively stable levels of adenosine-5'-triphosphate within the red blood cells. Inhibiting adenosine-5'-triphosphate release promoted the adhesion of stored red blood cells to endothelial cells in vitro and red blood cell sequestration in the lungs of transfused mice in vivo. Unlike transfusion of fresh human red blood cells, stored red blood cell transfusion in mice decreased blood oxygenation and increased extravasation of red blood cells into the lung's alveolar air spaces. Similar findings were seen with transfusion of fresh red blood cells treated with the adenosine-5'-triphosphate release inhibitors glibenclamide and carbenoxolone. These findings were prevented by either coinfusion of an adenosine-5'-triphosphate analog or pretransfusion incubation of the red blood cells with an antibody against the erythrocyte adhesion receptor Landsteiner-Wiener (intercellular adhesion molecule-4). CONCLUSIONS: The normal flow of red blood cells in pulmonary microvessels depends in part on the release of antiadhesive adenosine-5'-triphosphate from red blood cells, and storage-induced deficiency in adenosine-5'-triphosphate release from transfused red blood cells may promote or exacerbate microvascular pathophysiology in the lung, in part through increased red blood cell adhesion.

Authors
Zhu, H; Zennadi, R; Xu, BX; Eu, JP; Torok, JA; Telen, MJ; McMahon, TJ
MLA Citation
Zhu, H, Zennadi, R, Xu, BX, Eu, JP, Torok, JA, Telen, MJ, and McMahon, TJ. "Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion." Crit Care Med 39.11 (November 2011): 2478-2486.
PMID
21765360
Source
pubmed
Published In
Critical Care Medicine
Volume
39
Issue
11
Publish Date
2011
Start Page
2478
End Page
2486
DOI
10.1097/CCM.0b013e318225754f

MYH9 and APOL1 are both associated with sickle cell disease nephropathy.

Renal failure occurs in 5-18% of sickle cell disease (SCD) patients and is associated with early mortality. At-risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The myosin, heavy chain 9, non-muscle (MYH9) and apolipoprotein L1 (APOL1) genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans. We genotyped 26 single nucleotide polymorphisms (SNPs) in MYH9 and 2 SNPs in APOL1 (representing the G1 and G2 tags) in 521 unrelated adult (18-83 years) SCD patients screened for proteinuria. Using logistic regression, SNPs were evaluated for association with proteinuria. Seven SNPs in MYH9 and one in APOL1 remained significantly associated with proteinuria after multiple testing correction (P < 0·0025). An MYH9 risk haplotype (P = 0·001) and the APOL1 G1/G2 recessive model (P < 0·0001) were strongly associated with proteinuria, even when accounting for the other. Glomerular filtration rate was negatively correlated with proteinuria (P < 0·0001), and was significantly predicted by an interaction between MYH9 and APOL1 in age-adjusted analyses. Our data provide insight into the pathobiology of renal dysfunction in SCD, suggesting that MYH9 and APOL1 are both associated with risk.

Authors
Ashley-Koch, AE; Okocha, EC; Garrett, ME; Soldano, K; De Castro, LM; Jonassaint, JC; Orringer, EP; Eckman, JR; Telen, MJ
MLA Citation
Ashley-Koch, AE, Okocha, EC, Garrett, ME, Soldano, K, De Castro, LM, Jonassaint, JC, Orringer, EP, Eckman, JR, and Telen, MJ. "MYH9 and APOL1 are both associated with sickle cell disease nephropathy." Br J Haematol 155.3 (November 2011): 386-394.
PMID
21910715
Source
pubmed
Published In
British Journal of Haematology
Volume
155
Issue
3
Publish Date
2011
Start Page
386
End Page
394
DOI
10.1111/j.1365-2141.2011.08832.x

RNA aptamer therapy for vaso-occlusion in sickle cell disease.

Patients with sickle cell disease (SCD) often suffer painful vaso-occlusive episodes caused in part by the adhesion of sickle erythrocytes (SS-RBC) to the vascular endothelium. To investigate inhibition of SS-RBC adhesion as a possible treatment for vaso-occlusion, 2 adhesion molecules, α(v)β(3) and P-selectin, were targeted by high-affinity RNA aptamers. An in vitro flow chamber assay was used to test the antiadhesion activity of α(v)β(3) aptamer clone 17.16. Human SS-RBC were passed across a confluent monolayer of thrombin-stimulated human umbilical vein endothelial cells (HUVEC) at a constant rate. α(v)β(3) aptamer reduced SS-RBC adhesion to activated endothelial cells to the level seen with untreated HUVEC. An aptamer reactive with complement component 8 was used as a negative control and exerted no inhibition, confirming the specificity of α(v)β(3) aptamer (P=0.04). At 2 dyn/cm(2) shear stress, 30 nM α(v)β(3) aptamer showed maximal effect in decreasing SS-RBC adhesion to HUVEC. The antiadhesive activity of the P-selectin aptamer clone PF377 was also tested using HUVEC pretreated with IL-13 to upregulate expression of P-selectin as seen in activated endothelial cells. At 1 dyn/cm(2) shear stress, 60 nM of P-selectin aptamer had antiadhesion activity similar to heparin, a known inhibitor of SS-RBC adhesion to P-selectin. A negative control did not prevent adhesion (P=0.05). These data show the potential utility of aptamers to block endothelial adhesion molecules to prevent or treat vaso-occlusion in SCD.

Authors
Burnette, AD; Nimjee, SM; Batchvarova, M; Zennadi, R; Telen, MJ; Nishimura, J-I; Sullenger, BA
MLA Citation
Burnette, AD, Nimjee, SM, Batchvarova, M, Zennadi, R, Telen, MJ, Nishimura, J-I, and Sullenger, BA. "RNA aptamer therapy for vaso-occlusion in sickle cell disease." Nucleic Acid Ther 21.4 (August 2011): 275-283.
PMID
21793788
Source
pubmed
Published In
Nucleic Acid Therapeutics
Volume
21
Issue
4
Publish Date
2011
Start Page
275
End Page
283
DOI
10.1089/nat.2010.0270

Comparison of thrombin generation of sickle cell patients in crisis and steady state using the thrombin generation assay (TGA)

Authors
Shah, N; Telen, MJ; Ortel, TL
MLA Citation
Shah, N, Telen, MJ, and Ortel, TL. "Comparison of thrombin generation of sickle cell patients in crisis and steady state using the thrombin generation assay (TGA)." HAEMOPHILIA 17.3 (May 2011): 557-557.
Source
wos-lite
Published In
Haemophilia
Volume
17
Issue
3
Publish Date
2011
Start Page
557
End Page
557

Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry.

We have applied wide-field digital interferometry (WFDI) to examine the morphology and dynamics of live red blood cells (RBCs) from individuals who suffer from sickle cell anemia (SCA), a genetic disorder that affects the structure and mechanical properties of RBCs. WFDI is a noncontact, label-free optical microscopy approach that can yield quantitative thickness profiles of RBCs and measurements of their membrane fluctuations at the nanometer scale reflecting their stiffness. We find that RBCs from individuals with SCA are significantly stiffer than those from a healthy control. Moreover, we show that the technique is sensitive enough to distinguish classes of RBCs in SCA, including sickle RBCs with apparently normal morphology, compared to the stiffer crescent-shaped sickle RBCs. We expect that this approach will be useful for diagnosis of SCA and for determining efficacy of therapeutic agents.

Authors
Shaked, NT; Satterwhite, LL; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Telen, MJ, Truskey, GA, and Wax, A. "Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry." J Biomed Opt 16.3 (March 2011): 030506-. (Letter)
PMID
21456860
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
16
Issue
3
Publish Date
2011
Start Page
030506
DOI
10.1117/1.3556717

Erratum: Costs and length of stay for patients with and without sickle cell disease after hysterectomy, appendectomy, or knee replacement

Authors
Kamble, S; Telen, MJ; Dinan, MA; Grussemeyer, CA; Reed, SD
MLA Citation
Kamble, S, Telen, MJ, Dinan, MA, Grussemeyer, CA, and Reed, SD. "Erratum: Costs and length of stay for patients with and without sickle cell disease after hysterectomy, appendectomy, or knee replacement." American Journal of Hematology 86.10 (2011): 903--.
Source
scival
Published In
American Journal of Hematology
Volume
86
Issue
10
Publish Date
2011
Start Page
903-
DOI
10.1002/ajh.22121

Erratum: Outcomes of inpatients with and without sickle cell disease after high-volume surgical procedures

Authors
Dinan, MA; Chou, C-H; Hammill, BG; Graham, FL; Schulman, KA; Telen, MJ; Reed, SD
MLA Citation
Dinan, MA, Chou, C-H, Hammill, BG, Graham, FL, Schulman, KA, Telen, MJ, and Reed, SD. "Erratum: Outcomes of inpatients with and without sickle cell disease after high-volume surgical procedures." American Journal of Hematology 86.10 (2011): 906-908.
Source
scival
Published In
American Journal of Hematology
Volume
86
Issue
10
Publish Date
2011
Start Page
906
End Page
908
DOI
10.1002/ajh.22120

The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: Results of the multi-centre CHAMPS trial

In a phase-II multi-centre double-blinded trial, we evaluated haematological effects of oral hydroxycarbamide (HC) and magnesium (Mg) in patients with HbSC, aged 5-53years old. Subjects were randomized to HC+placebo, Mg+placebo, HC+Mg, or placebo+placebo. The primary endpoint was the proportion of hyperdense red blood cells after 8weeks. Thirty-six subjects were evaluable, but the study was terminated early because of slow enrollment. In the combined HC groups, mean cell volume and HbF were increased, but differences were not seen in hyperdense red cells or vaso-occlusive events. Mg had no effects. Further investigation of hydroxycarbamide as monotherapy in HbSC disease is warranted. © 2011 Blackwell Publishing Ltd.

Authors
Wang, WC; Brugnara, C; Snyder, C; Wynn, L; Rogers, Z; Kalinyak, K; Brown, C; Qureshi, A; Bigelow, C; Neumayr, L; Smith-Whitley, K; Chui, DHK; Delahunty, M; Woolson, R; Steinberg, M; Telen, M; Kesler, K
MLA Citation
Wang, WC, Brugnara, C, Snyder, C, Wynn, L, Rogers, Z, Kalinyak, K, Brown, C, Qureshi, A, Bigelow, C, Neumayr, L, Smith-Whitley, K, Chui, DHK, Delahunty, M, Woolson, R, Steinberg, M, Telen, M, and Kesler, K. "The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: Results of the multi-centre CHAMPS trial." British Journal of Haematology 152.6 (2011): 771-776.
PMID
21275961
Source
scival
Published In
British Journal of Haematology
Volume
152
Issue
6
Publish Date
2011
Start Page
771
End Page
776
DOI
10.1111/j.1365-2141.2010.08523.x

Red Blood Cell Release Of ATP Prevents Endothelial Adhesion: Implications For Post-Transfusion Lung Dysfunction

Authors
Zhu, H; Zennadi, R; Xu, B; Eu, JP; Torok, J; Telen, MJ; McMahon, TJ
MLA Citation
Zhu, H, Zennadi, R, Xu, B, Eu, JP, Torok, J, Telen, MJ, and McMahon, TJ. "Red Blood Cell Release Of ATP Prevents Endothelial Adhesion: Implications For Post-Transfusion Lung Dysfunction." AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 183 (2011).
Source
wos-lite
Published In
American journal of respiratory and critical care medicine
Volume
183
Publish Date
2011

Anti-Inflammatory Markers Are Associated with Glomerular Filtration Rate In Adults with Sickle Cell Disease

Authors
Barber, LA; Garrett, M; Soldano, K; Orringer, EP; Eckman, JR; Telen, MJ; Ashley-Koch, AE
MLA Citation
Barber, LA, Garrett, M, Soldano, K, Orringer, EP, Eckman, JR, Telen, MJ, and Ashley-Koch, AE. "Anti-Inflammatory Markers Are Associated with Glomerular Filtration Rate In Adults with Sickle Cell Disease." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
693
End Page
694

Hydroxyurea Induces Genome-Wide Epigenetic Changes In Sickle Cell Disease.

Authors
Ashley-Koch, AE; Garrett, M; Soldano, K; Barber, LA; Telen, MJ
MLA Citation
Ashley-Koch, AE, Garrett, M, Soldano, K, Barber, LA, and Telen, MJ. "Hydroxyurea Induces Genome-Wide Epigenetic Changes In Sickle Cell Disease." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1101
End Page
1101

Genetic Variation In MYH9 Is Associated with Sickle Cell Disease Nephropathy

Authors
Okocha, E; Garrett, M; Soldano, K; De Castro, LM; Jonassaint, J; Orringer, EP; Eckman, JR; telen, MJ; Ashley-Koch, AE
MLA Citation
Okocha, E, Garrett, M, Soldano, K, De Castro, LM, Jonassaint, J, Orringer, EP, Eckman, JR, telen, MJ, and Ashley-Koch, AE. "Genetic Variation In MYH9 Is Associated with Sickle Cell Disease Nephropathy." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
692
End Page
692

GMI-1070, a Pan-Selectin Inhibitor: Safety and PK In a Phase 1/2 Study In Adults with Sickle Cell Disease.

Authors
Styles, L; Wun, T; De Castro, LM; Telen, MJ; Kramer, W; Flanner, H; Magnani, JL; Thackray, H
MLA Citation
Styles, L, Wun, T, De Castro, LM, Telen, MJ, Kramer, W, Flanner, H, Magnani, JL, and Thackray, H. "GMI-1070, a Pan-Selectin Inhibitor: Safety and PK In a Phase 1/2 Study In Adults with Sickle Cell Disease." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
685
End Page
686

S-Nitrosylation of Rap1and Relationship to Rap1 Activity and Disease Status In SCD

Authors
Tutaeva, V; Thompson, JW; Foster, MW; Moseley, MA; Holly, SP; Delahunty, M; Parise, LV; Telen, MJ
MLA Citation
Tutaeva, V, Thompson, JW, Foster, MW, Moseley, MA, Holly, SP, Delahunty, M, Parise, LV, and Telen, MJ. "S-Nitrosylation of Rap1and Relationship to Rap1 Activity and Disease Status In SCD." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1098
End Page
1098

Initial Experience with the IMPROVE Trial-a Phase III Analgesic Trial for Hospitalized Sickle Cell Painful Episodes

Authors
Dampier, C; Smith, WR; Wager, C; Bell, M; Eckman, JR; Hsu, LL; McClish, D; McKinlay, S; Minitti, C; Molokie, R; Smith-Whitley, K; Telen, MJ; Weiner, D; Miller, S
MLA Citation
Dampier, C, Smith, WR, Wager, C, Bell, M, Eckman, JR, Hsu, LL, McClish, D, McKinlay, S, Minitti, C, Molokie, R, Smith-Whitley, K, Telen, MJ, Weiner, D, and Miller, S. "Initial Experience with the IMPROVE Trial-a Phase III Analgesic Trial for Hospitalized Sickle Cell Painful Episodes." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1100
End Page
1100

Relationship of Soluble Adhesion Receptors to Red Cell Apoptosis In SCD

Authors
Mutucumarana, CP; Chandler, C; Telen, MJ; Delahunty, M
MLA Citation
Mutucumarana, CP, Chandler, C, Telen, MJ, and Delahunty, M. "Relationship of Soluble Adhesion Receptors to Red Cell Apoptosis In SCD." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
694
End Page
694

Factors Associated with Heterocellular Aggregate Formation In Sickle Cell Disease.

Authors
Agrawal, S; Delahunty, M; Telen, MJ
MLA Citation
Agrawal, S, Delahunty, M, and Telen, MJ. "Factors Associated with Heterocellular Aggregate Formation In Sickle Cell Disease." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1101
End Page
1101

Atypical Activation of Plasma Membrane-Bound ERK1/2 Is Associated with Regulation of Sickle Red Cell Adhesion to Endothelium

Authors
Zennadi, R; Telen, MJ
MLA Citation
Zennadi, R, and Telen, MJ. "Atypical Activation of Plasma Membrane-Bound ERK1/2 Is Associated with Regulation of Sickle Red Cell Adhesion to Endothelium." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
122
End Page
122

microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease.

Although individuals with homozygous sickle cell disease (HbSS) share the same genetic mutation, the severity and manifestations of this disease are extremely heterogeneous. We have previously shown that the microRNA expression in normal and HbSS erythrocytes exhibit dramatic differences. In this study, we identify a subset of HbSS patients with higher erythrocytic miR-144 expression and more severe anemia. HbSS erythrocytes are known to have reduced tolerance for oxidative stress, yet the basis for this phenotype remains unknown. This study reveals that miR-144 directly regulates nuclear factor-erythroid 2-related factor 2, a central regulator of cellular response to oxidative stress, and modulates the oxidative stress response in K562 cell line and primary erythroid progenitor cells. We further demonstrate that increased miR-144 is associated with reduced NRF2 levels in HbSS reticulocytes and with decreased glutathione regeneration and attenuated antioxidant capacity in HbSS erythrocytes, thereby providing a possible mechanism for the reduced oxidative stress tolerance and increased anemia severity seen in HbSS patients. Taken together, our findings suggest that erythroid microRNAs can serve as genetic modifiers of HbS-related anemia and can provide novel insights into the clinical heterogeneity and pathobiology of sickle cell disease.

Authors
Sangokoya, C; Telen, MJ; Chi, J-T
MLA Citation
Sangokoya, C, Telen, MJ, and Chi, J-T. "microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease." Blood 116.20 (November 18, 2010): 4338-4348.
PMID
20709907
Source
pubmed
Published In
Blood
Volume
116
Issue
20
Publish Date
2010
Start Page
4338
End Page
4348
DOI
10.1182/blood-2009-04-214817

Placenta growth factor in sickle cell disease: association with hemolysis and inflammation.

Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.

Authors
Brittain, JE; Hulkower, B; Jones, SK; Strayhorn, D; De Castro, L; Telen, MJ; Orringer, EP; Hinderliter, A; Ataga, KI
MLA Citation
Brittain, JE, Hulkower, B, Jones, SK, Strayhorn, D, De Castro, L, Telen, MJ, Orringer, EP, Hinderliter, A, and Ataga, KI. "Placenta growth factor in sickle cell disease: association with hemolysis and inflammation." Blood 115.10 (March 11, 2010): 2014-2020.
PMID
20040765
Source
pubmed
Published In
Blood
Volume
115
Issue
10
Publish Date
2010
Start Page
2014
End Page
2020
DOI
10.1182/blood-2009-04-217950

Functions of Blood Group Antigens

Authors
Stamler, JS; Telen, MJ
MLA Citation
Stamler, JS, and Telen, MJ. "Functions of Blood Group Antigens." (March 10, 2010): 276-286. (Chapter)
Source
scopus
Publish Date
2010
Start Page
276
End Page
286
DOI
10.1002/9781444318531.ch22

Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster.

In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or beta thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E-08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression.

Authors
Solovieff, N; Milton, JN; Hartley, SW; Sherva, R; Sebastiani, P; Dworkis, DA; Klings, ES; Farrer, LA; Garrett, ME; Ashley-Koch, A; Telen, MJ; Fucharoen, S; Ha, SY; Li, C-K; Chui, DHK; Baldwin, CT; Steinberg, MH
MLA Citation
Solovieff, N, Milton, JN, Hartley, SW, Sherva, R, Sebastiani, P, Dworkis, DA, Klings, ES, Farrer, LA, Garrett, ME, Ashley-Koch, A, Telen, MJ, Fucharoen, S, Ha, SY, Li, C-K, Chui, DHK, Baldwin, CT, and Steinberg, MH. "Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster." Blood 115.9 (March 4, 2010): 1815-1822.
PMID
20018918
Source
pubmed
Published In
Blood
Volume
115
Issue
9
Publish Date
2010
Start Page
1815
End Page
1822
DOI
10.1182/blood-2009-08-239517

Adherence to hydroxyurea therapy in children with sickle cell anemia.

OBJECTIVES: To assess adherence to hydroxyurea therapy in children with sickle cell anemia (SCA), evaluate the association between adherence and hematologic profile, and identify barriers and facilitators of adherence. STUDY DESIGN: Children with SCA (n=75) receiving hydroxyurea were recruited for a single-institution cross-sectional study. The primary outcome was association between treatment adherence and percent fetal hemoglobin (HbF). RESULTS: Good adherence was estimated at 82% with visual analog scale, 84% with Morisky score, 85% with medical provider report, 77% with clinic visits, and 49% on the basis of pharmacy refills. Increase in HbF was moderately associated with good adherence as measured with the parent/proxy Morisky score (r=-0.39; 95% CI, -0.58-0.17; P < .01) and prescription refills (r=0.39; 95% CI, 0.16-0.57; P < .01). The number of pharmacy refills and the Morisky score explained 23% of the variation in HbF response. CONCLUSIONS: Adherence was > or =75% with 4 of 5 measures. Pharmacy refills and the Modified Morisky Scale may be used to identify children at high risk for poor response because of non-adherence and children with good adherence with poor response because of individual pharmacodynamics. Future research should prospectively compare adherence measures and evaluate methods to improve treatment adherence.

Authors
Thornburg, CD; Calatroni, A; Telen, M; Kemper, AR
MLA Citation
Thornburg, CD, Calatroni, A, Telen, M, and Kemper, AR. "Adherence to hydroxyurea therapy in children with sickle cell anemia." J Pediatr 156.3 (March 2010): 415-419.
PMID
19880135
Source
pubmed
Published In
The Journal of Pediatrics
Volume
156
Issue
3
Publish Date
2010
Start Page
415
End Page
419
DOI
10.1016/j.jpeds.2009.09.044

Dose of prophylactic platelet transfusions and prevention of hemorrhage.

BACKGROUND: We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS: We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS: In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). CONCLUSIONS: Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.)

Authors
Slichter, SJ; Kaufman, RM; Assmann, SF; McCullough, J; Triulzi, DJ; Strauss, RG; Gernsheimer, TB; Ness, PM; Brecher, ME; Josephson, CD; Konkle, BA; Woodson, RD; Ortel, TL; Hillyer, CD; Skerrett, DL; McCrae, KR; Sloan, SR; Uhl, L; George, JN; Aquino, VM; Manno, CS; McFarland, JG; Hess, JR; Leissinger, C; Granger, S
MLA Citation
Slichter, SJ, Kaufman, RM, Assmann, SF, McCullough, J, Triulzi, DJ, Strauss, RG, Gernsheimer, TB, Ness, PM, Brecher, ME, Josephson, CD, Konkle, BA, Woodson, RD, Ortel, TL, Hillyer, CD, Skerrett, DL, McCrae, KR, Sloan, SR, Uhl, L, George, JN, Aquino, VM, Manno, CS, McFarland, JG, Hess, JR, Leissinger, C, and Granger, S. "Dose of prophylactic platelet transfusions and prevention of hemorrhage." N Engl J Med 362.7 (February 18, 2010): 600-613.
PMID
20164484
Source
pubmed
Published In
The New England journal of medicine
Volume
362
Issue
7
Publish Date
2010
Start Page
600
End Page
613
DOI
10.1056/NEJMoa0904084

Costs and length of stay for patients with and without sickle cell disease after hysterectomy, appendectomy, or knee replacement.

Authors
Kamble, S; Telen, MJ; Dinan, MA; Grussemeyer, CA; Reed, SD
MLA Citation
Kamble, S, Telen, MJ, Dinan, MA, Grussemeyer, CA, and Reed, SD. "Costs and length of stay for patients with and without sickle cell disease after hysterectomy, appendectomy, or knee replacement." Am J Hematol 85.1 (January 2010): 79-81. (Letter)
PMID
20029954
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
1
Publish Date
2010
Start Page
79
End Page
81
DOI
10.1002/ajh.21576

Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease.

Sickle cell disease (SCD) is associated with early mortality. We sought to determine the incidence, cause, and risk factors for death in an adult population of patients with SCD. All patients aged >/=18 years seen at the Adult Sickle Cell Center at Duke University Medical Center between January 2000 and April 2005 were enrolled. Forty-three patients (21 males and 22 females) died during the study period. The median age of survival was 39 years for females (95% CI: 34-56), 40 years for males (95% CI: 34-48), and 40 years overall (95% CI: 35-48). Cardiac causes of death accounted for 25.6% (11/43 patients); pulmonary, 14.0% (six patients); other SCD related, 32.6% (14 patients); unknown, 14.0% (six patients); and others, 14.0% (six patients). Pulseless electrical activity arrest, pulmonary emboli, multiorgan failure, and stroke were the most frequent causes of death. Among the deceased patients, the most common premorbid conditions were cardiopulmonary: acute chest syndrome/pneumonia (58.1%), Pulmonary hypertension (pHTN; 41.9%), systemic HTN (25.6%), congestive heart failure (25.6%), myocardial infarction (20.9%), and arrhythmias (14.0%). Tricuspid regurgitant jet velocity was significantly higher (3.1 m/sec vs. 2.6 m/sec, P < 0.001) and hemoglobin significantly lower (8.3 g/dL vs. 9.2 g/dL, P < 0.05) in deceased patients when compared with patients who lived, respectively. With improved preventive and therapeutic advances, including hydroxyurea therapy, acute complications such as infection are no longer the leading cause of death; instead, causes of death and premorbid conditions are shifting to chronic cardiopulmonary complications. Further, arrhythmia leading to premature death is under-recognized in SCD and warrants further investigation.

Authors
Fitzhugh, CD; Lauder, N; Jonassaint, JC; Telen, MJ; Zhao, X; Wright, EC; Gilliam, FR; De Castro, LM
MLA Citation
Fitzhugh, CD, Lauder, N, Jonassaint, JC, Telen, MJ, Zhao, X, Wright, EC, Gilliam, FR, and De Castro, LM. "Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease." Am J Hematol 85.1 (January 2010): 36-40.
PMID
20029950
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
1
Publish Date
2010
Start Page
36
End Page
40
DOI
10.1002/ajh.21569

Definitions of the phenotypic manifestations of sickle cell disease.

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed.

Authors
Ballas, SK; Lieff, S; Benjamin, LJ; Dampier, CD; Heeney, MM; Hoppe, C; Johnson, CS; Rogers, ZR; Smith-Whitley, K; Wang, WC; Telen, MJ; Investigators, Comprehensive Sickle Cell Centers,
MLA Citation
Ballas, SK, Lieff, S, Benjamin, LJ, Dampier, CD, Heeney, MM, Hoppe, C, Johnson, CS, Rogers, ZR, Smith-Whitley, K, Wang, WC, Telen, MJ, Investigators, and Comprehensive Sickle Cell Centers, . "Definitions of the phenotypic manifestations of sickle cell disease." Am J Hematol 85.1 (January 2010): 6-13.
PMID
19902523
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
1
Publish Date
2010
Start Page
6
End Page
13
DOI
10.1002/ajh.21550

Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study.

We conducted a genome-wide association study (GWAS) to discover single nucleotide polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265 patients with either "severe" or "mild" disease based on a network model of disease severity. We analyzed data using single SNP analysis and a novel SNP set enrichment analysis (SSEA) developed to discover clusters of associated SNPs. Single SNP analysis discovered 40 SNPs that were strongly associated with sickle cell severity (odds for association >1,000); of the 32 that we could analyze in an independent set of 163 patients, five replicated, eight showed consistent effects although failed to reach statistical significance, whereas 19 did not show any convincing association. Among the replicated associations are SNPs in KCNK6 a K(+) channel gene. SSEA identified 27 genes with a strong enrichment of significant SNPs (P < 10(-6)); 20 were replicated with varying degrees of confidence. Among the novel findings identified by SSEA is the telomere length regulator gene TNKS. These studies are the first to use GWAS to understand the genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia as estimated by an integrated model of severity. Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work.

Authors
Sebastiani, P; Solovieff, N; Hartley, SW; Milton, JN; Riva, A; Dworkis, DA; Melista, E; Klings, ES; Garrett, ME; Telen, MJ; Ashley-Koch, A; Baldwin, CT; Steinberg, MH
MLA Citation
Sebastiani, P, Solovieff, N, Hartley, SW, Milton, JN, Riva, A, Dworkis, DA, Melista, E, Klings, ES, Garrett, ME, Telen, MJ, Ashley-Koch, A, Baldwin, CT, and Steinberg, MH. "Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study." Am J Hematol 85.1 (January 2010): 29-35.
PMID
20029952
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
1
Publish Date
2010
Start Page
29
End Page
35
DOI
10.1002/ajh.21572

The relationship of opioid analgesia to quality of life in an adult sickle cell population

Background: Pain is a limiting factor in the daily life activities of sickle cell disease (SCD) patients. Although opioid analgesics are widely used, to date there have been no studies on the relationship of daily opioid use to quality of life (QoL) measures in this population. Objective: To determine the relationship of opioid analgesia to QoL in adults with SCD. Design: There were 185 outpatients with various SCD genotypes evaluated. Data were collected by patient interviews as well as review of medical records. QoL as determined by the Medical Outcome Study 36-item Short Form Survey (SF-36) was the main outcome measured. Results: QoL outcomes were not lower in the classically more severe homozygous SS individuals when compared with the heterozygous SC patients. However, SF-36 scores were significantly lower in individuals using opioids daily compared with those who did not, in all age groups and for all diagnoses. When controlling for hydroxyurea use, the negative association between opioid use and QoL scores remained unchanged. QoL scores were significantly higher in those who were either on no medications or on hydroxyurea alone, as compared with those who were on opioids alone or on hydroxyurea and opioids concurrently. Disease severity scores were not different between medication groups. Conclusions: SCD patients on daily opioids had poorer QoL scores than those who were not on opioids, independent of disease severity. Hydroxyurea had a positive impact on QoL, although that effect was not observed in patients also using chronic opioids. Prospective studies are needed to define the relationship of opioid use to QoL and the significance of the interaction of both drugs in SCD. © 2010 Elsevier Inc. All rights reserved.

Authors
Adam, SS; Telen, MJ; Jonassaint, CR; Castro, LMD; Jonassaint, JC
MLA Citation
Adam, SS, Telen, MJ, Jonassaint, CR, Castro, LMD, and Jonassaint, JC. "The relationship of opioid analgesia to quality of life in an adult sickle cell population." Health Outcomes Research in Medicine 1.1 (2010): e29-e37.
Source
scival
Published In
Health Outcomes Research in Medicine
Volume
1
Issue
1
Publish Date
2010
Start Page
e29
End Page
e37
DOI
10.1016/j.ehrm.2010.04.002

Genome-Wide Studies in Sickle Cell Anemia Show Associations Between SNPs in the Olfactory Receptor Gene Cluster and Fetal Hemoglobin Concentration

Authors
Timofeev, N; Milton, JN; Hartley, SW; Sherva, R; Sebastiani, P; Dworkis, DA; Klings, ES; Farrer, L; Telen, MJ; Ashley-Koch, AE; Garrett, ME; Chui, DHK; Baldwin, CT; Steinberg, MH
MLA Citation
Timofeev, N, Milton, JN, Hartley, SW, Sherva, R, Sebastiani, P, Dworkis, DA, Klings, ES, Farrer, L, Telen, MJ, Ashley-Koch, AE, Garrett, ME, Chui, DHK, Baldwin, CT, and Steinberg, MH. "Genome-Wide Studies in Sickle Cell Anemia Show Associations Between SNPs in the Olfactory Receptor Gene Cluster and Fetal Hemoglobin Concentration." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
339
End Page
339

Polymorphisms in TNF alpha Are Associated with Cerebrovascular Events in Sickle Cell Disease.

Authors
Barber, LA; Ashley-Koch, AE; Garrett, ME; Soldano, KL; Telen, MJ
MLA Citation
Barber, LA, Ashley-Koch, AE, Garrett, ME, Soldano, KL, and Telen, MJ. "Polymorphisms in TNF alpha Are Associated with Cerebrovascular Events in Sickle Cell Disease." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
617
End Page
617

Use of a Computer Based Neurocognitive Software Program in Asymptomatic Neurologically Intact Adults with Sickle Cell Disease.

Authors
Crawford, RD; Feliu, M; Edwards, CL; Telen, MJ
MLA Citation
Crawford, RD, Feliu, M, Edwards, CL, and Telen, MJ. "Use of a Computer Based Neurocognitive Software Program in Asymptomatic Neurologically Intact Adults with Sickle Cell Disease." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
612
End Page
612

Retrospective Review of the Natural History of Pulmonary Hypertension in Sickle Cell Disease Demonstrates That Progressive Enlargement of the Left Atrium Is a Strong Predictor of Death.

Authors
Silbermins, D; Calatroni, A; Jonassaint, J; Telen, MJ; De Castro, LM
MLA Citation
Silbermins, D, Calatroni, A, Jonassaint, J, Telen, MJ, and De Castro, LM. "Retrospective Review of the Natural History of Pulmonary Hypertension in Sickle Cell Disease Demonstrates That Progressive Enlargement of the Left Atrium Is a Strong Predictor of Death." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
613
End Page
614

Comparison of Thrombin Generation of Sickle Cell Patients in Microparticle Rich and Microparticle Poor Plasma Using Thrombin Generation Assay (TGA).

Authors
Shah, N; Telen, MJ; Ortel, TL
MLA Citation
Shah, N, Telen, MJ, and Ortel, TL. "Comparison of Thrombin Generation of Sickle Cell Patients in Microparticle Rich and Microparticle Poor Plasma Using Thrombin Generation Assay (TGA)." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1004
End Page
1004

In-Hospital Outcomes Among Sickle Cell Patients with Acute Chest Syndrome: Results From a National Database.

Authors
Kamble, S; Reed, SD; Grussemeyer, C; Telen, MJ
MLA Citation
Kamble, S, Reed, SD, Grussemeyer, C, and Telen, MJ. "In-Hospital Outcomes Among Sickle Cell Patients with Acute Chest Syndrome: Results From a National Database." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
557
End Page
557

Genetic Polymorphisms in NEDD4L Are Associated with Pulmonary Hypertension of Sickle Cell Anemia.

Authors
Klings, ES; Dworkis, DA; Sedgewick, A; Hartley, SW; Allison, A-K; Telen, MJ; Kato, GJ; Gladwin, M; Sebastiani, P; Baldwin, CT; Steinberg, MH
MLA Citation
Klings, ES, Dworkis, DA, Sedgewick, A, Hartley, SW, Allison, A-K, Telen, MJ, Kato, GJ, Gladwin, M, Sebastiani, P, Baldwin, CT, and Steinberg, MH. "Genetic Polymorphisms in NEDD4L Are Associated with Pulmonary Hypertension of Sickle Cell Anemia." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1006
End Page
1006

Effects of Hydroxyurea (HU) and Magnesium Pidolate (Mg) in Hemoglobin SC Disease (HbSC): the "CHAMPS" Trial

Authors
Wang, WC; Snyder, C; Brugnara, C; Telen, MJ; Steinberg, MH; Wynn, LW; McAfee, J; Rogers, ZR; Kalinyak, K; Joiner, CH; Kesler, K
MLA Citation
Wang, WC, Snyder, C, Brugnara, C, Telen, MJ, Steinberg, MH, Wynn, LW, McAfee, J, Rogers, ZR, Kalinyak, K, Joiner, CH, and Kesler, K. "Effects of Hydroxyurea (HU) and Magnesium Pidolate (Mg) in Hemoglobin SC Disease (HbSC): the "CHAMPS" Trial." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
338
End Page
338

The Complex Relationship Between Sickle Cell Disease and Depression

Authors
Adam, SS; Flahiff, C; Abrams, MR; Telen, MJ; De Castro, LM
MLA Citation
Adam, SS, Flahiff, C, Abrams, MR, Telen, MJ, and De Castro, LM. "The Complex Relationship Between Sickle Cell Disease and Depression." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1014
End Page
1015

Outcomes of inpatients with and without sickle cell disease after high-volume surgical procedures.

In this study, we examined differences in inpatient costs, length of stay, and in-hospital mortality between hospitalizations for patients with and without sickle cell disease (SCD) undergoing high-volume surgical procedures. We used Clinical Classification Software (CCS) codes to identify discharges in the 2002-2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project for patients who had undergone either cholecystectomy or hip replacement. We limited the non-SCD cohort to hospitals where patients with SCD had undergone the same procedure. We compared inpatient outcomes using summary statistics and generalized linear regression analysis to adjust for patient, hospital, and procedural characteristics. Overall, the median age of surgical patients with SCD was more than three decades less than the median age of patients without SCD undergoing the same procedure. In recognition of the age disparity, we limited the analyses to patients aged 18 to 64 years. Nonetheless, patients with SCD undergoing cholecystectomy or hip replacement were 12.1 and 14.4 years younger, had inpatient stays that were 73% and 82% longer, and incurred costs that were 46% and 40% higher per discharge than patients without SCD, respectively. Inpatient mortality for these procedures was low, approximately 0.6% for cholecystectomy and 0.2% for hip replacement and did not differ significantly between patients with and without SCD. Multivariable regression analyses revealed that higher inpatient costs among patients with SCD were primarily attributable to longer hospital stays. Patients with SCD who underwent cholecystectomy or hip replacement required more health care resources than patients without SCD. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

Authors
Dinan, MA; Chou, C-H; Hammill, BG; Graham, FL; Schulman, KA; Telen, MJ; Reed, SD
MLA Citation
Dinan, MA, Chou, C-H, Hammill, BG, Graham, FL, Schulman, KA, Telen, MJ, and Reed, SD. "Outcomes of inpatients with and without sickle cell disease after high-volume surgical procedures." Am J Hematol 84.11 (November 2009): 703-709.
PMID
19787790
Source
pubmed
Published In
American Journal of Hematology
Volume
84
Issue
11
Publish Date
2009
Start Page
703
End Page
709
DOI
10.1002/ajh.21520

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Authors
Afenyi-Annan, A; Ashley-Koch, A; Telen, MJ
MLA Citation
Afenyi-Annan, A, Ashley-Koch, A, and Telen, MJ. "Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean." Br J Haematol 145.2 (April 2009): 266-267. (Letter)
PMID
19208101
Source
pubmed
Published In
British Journal of Haematology
Volume
145
Issue
2
Publish Date
2009
Start Page
266
End Page
267
DOI
10.1111/j.1365-2141.2009.07588.x

Prolonged Survival despite High Disease Burden in Elderly (>= 55) Patients with Hb SS or Hb S beta 0 Thalassemia

Authors
Silbermins, D; De Castro, LM; Ashley-Koch, AE; Jonassaint, JC; Garrett, ME; Eckman, JR; Orringer, EP; Telen, MJ
MLA Citation
Silbermins, D, De Castro, LM, Ashley-Koch, AE, Jonassaint, JC, Garrett, ME, Eckman, JR, Orringer, EP, and Telen, MJ. "Prolonged Survival despite High Disease Burden in Elderly (>= 55) Patients with Hb SS or Hb S beta 0 Thalassemia." BLOOD 112.11 (November 16, 2008): 264-264.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
264
End Page
264

Genomic Approaches to Identifying Risk for Pulmonary Artery Hypertension among Individuals with Sickle Cell Disease.

Authors
Silbermins, D; De Castro, LM; Jonassaint, JC; Hsu, SD; Telen, MJ; Chi, J-T
MLA Citation
Silbermins, D, De Castro, LM, Jonassaint, JC, Hsu, SD, Telen, MJ, and Chi, J-T. "Genomic Approaches to Identifying Risk for Pulmonary Artery Hypertension among Individuals with Sickle Cell Disease." BLOOD 112.11 (November 16, 2008): 514-514.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
514
End Page
514

Adherence with Hydroxyurea in Children with Sickle Cell Disease

Authors
Thornburg, CD; Calatroni, A; Herzberg, B; Telen, MJ; Kemper, A
MLA Citation
Thornburg, CD, Calatroni, A, Herzberg, B, Telen, MJ, and Kemper, A. "Adherence with Hydroxyurea in Children with Sickle Cell Disease." BLOOD 112.11 (November 16, 2008): 69-69.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
69
End Page
69

Erythrocyte Adhesion and Phosphatidylserine Exposure in HbSC Disease: Baseline Data from the CHAMPS Study.

Authors
Telen, MJ; Delahunty, M; Snyder, C; Wang, WC
MLA Citation
Telen, MJ, Delahunty, M, Snyder, C, and Wang, WC. "Erythrocyte Adhesion and Phosphatidylserine Exposure in HbSC Disease: Baseline Data from the CHAMPS Study." BLOOD 112.11 (November 16, 2008): 861-861.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
861
End Page
861

Does Living Closer to a Medical Care Center Matter in Sickle Cell Disease?

Authors
Jonassaint, JC; Jonassaint, CR; Flahiff, CM; Ball, A; Adam, SS; Telen, MJ; De Castro, LM
MLA Citation
Jonassaint, JC, Jonassaint, CR, Flahiff, CM, Ball, A, Adam, SS, Telen, MJ, and De Castro, LM. "Does Living Closer to a Medical Care Center Matter in Sickle Cell Disease?." BLOOD 112.11 (November 16, 2008): 323-324.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
323
End Page
324

Obstetric and Gynecological History in Sickle Cell Disease Females

Authors
Adam, SS; Jonassaint, JC; Abrams, MR; Jonassaint, CR; Telen, MJ; De Castro, LM
MLA Citation
Adam, SS, Jonassaint, JC, Abrams, MR, Jonassaint, CR, Telen, MJ, and De Castro, LM. "Obstetric and Gynecological History in Sickle Cell Disease Females." BLOOD 112.11 (November 16, 2008): 867-868.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
867
End Page
868

Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium.

Infusion of epinephrine-activated human sickle erythrocytes (SS RBCs) into nude mice promotes both SS RBC and murine leukocyte adhesion to vascular endothelium in vivo. We hypothesized that interaction of epinephrine-stimulated SS RBCs with leukocytes leads to activation of leukocytes, which then adhere to endothelial cells (ECs). In exploring the underlying molecular mechanisms, we have found that coincubation in vitro of epinephrine-treated SS RBCs with human peripheral blood mononuclear cells (PBMCs) results in robust adhesion of PBMCs to ECs. Sham-treated SS RBCs had a similar but less pronounced effect, whereas neither sham- nor epinephrine-treated normal RBCs activated PBMC adhesion. PBMC activation was induced via at least 2 RBC adhesion receptors, LW and CD44. In response to SS RBCs, leukocyte CD44 and beta2 integrins mediated PBMC adhesion to ECs, a process that involved endothelial E-selectin and fibronectin. SS RBCs activated adhesion of both PBMC populations, lymphocytes and monocytes. Thus, our findings reveal a novel mechanism that may contribute to the pathogenesis of vaso-occlusion in sickle cell disease, in which SS RBCs act via LW and CD44 to stimulate leukocyte adhesion to endothelium, and suggest that RBC LW and CD44 may serve as potential targets for antiadhesive therapy designed to prevent vaso-occlusion.

Authors
Zennadi, R; Chien, A; Xu, K; Batchvarova, M; Telen, MJ
MLA Citation
Zennadi, R, Chien, A, Xu, K, Batchvarova, M, and Telen, MJ. "Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium." Blood 112.8 (October 15, 2008): 3474-3483.
PMID
18664622
Source
pubmed
Published In
Blood
Volume
112
Issue
8
Publish Date
2008
Start Page
3474
End Page
3483
DOI
10.1182/blood-2008-01-134346

Surgical and obstetric outcomes in adults with sickle cell disease.

BACKGROUND: Sickle cell disease patients are more likely than the general population to undergo surgery and usually do so at a younger age. Female sickle cell disease patients also have special gynecological and obstetric issues related to their disease. METHODS: We collected data through standardized clinical report forms, patient interviews, and medical records from 509 adult sickle cell disease patients. Logistic regression was used to estimate the association between multiple variables and each of the surgery types. We also determined the prevalence and outcomes of pregnancy in 284 women with sickle cell disease in this population. RESULTS: Almost 50% of patients aged 18-27 years had had a cholecystectomy. Mean corpuscular hemoglobin, total bilirubin, and lactate dehydrogenase were significantly higher in the postcholecystectomy group; 9.5% of 504 individuals had undergone splenectomy. Hematocrit, body mass index, and red blood cell count were significantly higher in the postsplenectomy group. Hip replacement had been performed in 9.2% of individuals, with the prevalence increasing as early as the fourth decade and continuing to increase through the sixth decade of life. A history of pregnancy was present in 190 women (67%). Of 410 pregnancies, only 53.9% resulted in live births, 16.6% were voluntarily terminated, and 29.5% were complicated by miscarriage, still birth, or ectopic implantation. CONCLUSIONS: Sickle cell disease continues to have a strong effect on the mean age for common surgeries and impacts pregnancy outcomes. We conclude that this population has a unique surgical and obstetric history that should be further studied to provide insight into potentially more effective preventive approaches to end-organ damage.

Authors
Adam, S; Jonassaint, J; Kruger, H; Kail, M; Orringer, EP; Eckman, JR; Ashley-Koch, A; Telen, MJ; De Castro, LM
MLA Citation
Adam, S, Jonassaint, J, Kruger, H, Kail, M, Orringer, EP, Eckman, JR, Ashley-Koch, A, Telen, MJ, and De Castro, LM. "Surgical and obstetric outcomes in adults with sickle cell disease." Am J Med 121.10 (October 2008): 916-921.
PMID
18823864
Source
pubmed
Published In
American Journal of Medicine
Volume
121
Issue
10
Publish Date
2008
Start Page
916
End Page
921
DOI
10.1016/j.amjmed.2008.04.040

It really IS the red cell.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "It really IS the red cell." Blood 112.3 (August 1, 2008): 459-460.
PMID
18650459
Source
pubmed
Published In
Blood
Volume
112
Issue
3
Publish Date
2008
Start Page
459
End Page
460
DOI
10.1182/blood-2008-05-155754

Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease.

Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFbeta superfamily, including activin A receptor, type II-like 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFbeta pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the beta-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication.

Authors
Ashley-Koch, AE; Elliott, L; Kail, ME; De Castro, LM; Jonassaint, J; Jackson, TL; Price, J; Ataga, KI; Levesque, MC; Weinberg, JB; Orringer, EP; Collins, A; Vance, JM; Telen, MJ
MLA Citation
Ashley-Koch, AE, Elliott, L, Kail, ME, De Castro, LM, Jonassaint, J, Jackson, TL, Price, J, Ataga, KI, Levesque, MC, Weinberg, JB, Orringer, EP, Collins, A, Vance, JM, and Telen, MJ. "Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease." Blood 111.12 (June 15, 2008): 5721-5726.
PMID
18187665
Source
pubmed
Published In
Blood
Volume
111
Issue
12
Publish Date
2008
Start Page
5721
End Page
5726
DOI
10.1182/blood-2007-02-074849

The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.

BACKGROUND: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). METHODS AND FINDINGS: Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. CONCLUSIONS: In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases.

Authors
Chen, S-Y; Wang, Y; Telen, MJ; Chi, J-T
MLA Citation
Chen, S-Y, Wang, Y, Telen, MJ, and Chi, J-T. "The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. (Published online)" PLoS One 3.6 (June 4, 2008): e2360-.
Website
http://hdl.handle.net/10161/4495
PMID
18523662
Source
pubmed
Published In
PloS one
Volume
3
Issue
6
Publish Date
2008
Start Page
e2360
DOI
10.1371/journal.pone.0002360

Lack of Duffy antigen expression is associated with organ damage in patients with sickle cell disease.

BACKGROUND: The Duffy glycoprotein (Fy) on red blood cells (RBCs) has been hypothesized to promote clearance of inflammatory cytokines, which may play a role in the pathogenesis of vasoocclusion in sickle cell disease (SCD). Persons with the African-type Fy(a-b-) phenotype--whose RBCs lack expression of Duffy--may less efficiently clear inflammatory cytokines. Therefore, the Duffy-negative genotype may be associated with more severe disease among patients with SCD. STUDY DESIGN AND METHODS: Genotyping was performed on blood samples from 249 adult patients with HbSS at the Duffy gene (FY) locus GATA site (rs2814778) that determines RBC expression of Duffy antigens. Patients with discordant genotype and phenotype data were excluded (n = 12). Differences in demographic, clinical and laboratory findings, end-organ damage, and overall disease severity were compared between FY+ and FY- patients. RESULTS: Of the 237 patients studied, 174 (73%) were FY-. FY+ patients had a higher mean white blood cell (WBC) count (13.2 x 10(9) +/- 4.1 x 10(9)/L vs. 11.8 x 10(9) +/- 3.3 x 10(9)/L; p = 0.03) and higher rates of treatment with hydroxyurea (72% vs. 49%; p = 0.002). In contrast, FY- status was strongly associated with chronic organ damage (85% of FY- patients vs. 65% of FY+ patients; p = 0.018) and proteinuria (32% vs. 12%; p = 0.02). These associations remained, even after controlling for the effects of age and sex. CONCLUSIONS: Duffy genotype may be a potential biomarker for the development of end-organ damage in SCD, particularly kidney dysfunction. The association of both WBC counts and hydroxyurea use with Duffy expression provides another avenue for investigation of the biologic role of this protein.

Authors
Afenyi-Annan, A; Kail, M; Combs, MR; Orringer, EP; Ashley-Koch, A; Telen, MJ
MLA Citation
Afenyi-Annan, A, Kail, M, Combs, MR, Orringer, EP, Ashley-Koch, A, and Telen, MJ. "Lack of Duffy antigen expression is associated with organ damage in patients with sickle cell disease." Transfusion 48.5 (May 2008): 917-924.
PMID
18248572
Source
pubmed
Published In
Transfusion
Volume
48
Issue
5
Publish Date
2008
Start Page
917
End Page
924
DOI
10.1111/j.1537-2995.2007.01622.x

β2-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion

Sickle red cell (SS RBC) adhesion is thought to contribute to sickle cell disease (SCD) pathophysiology. SS RBC adhesion to laminin increases in response to adrenaline stimulation of β2-adrenergic receptors (β2ARs) and adenylate cyclase (ADCY6), and previous evidence suggests such activation occurs in vivo. We explored whether polymorphisms of the β2AR and ADCY6 genes (ADRB2 and ADCY6, respectively) affect RBC adhesion to laminin. We found that the β2AR arg 16→gly substitution and two non-coding ADCY6 polymorphisms were associated with elevated adhesion. We postulate that ADRB2 and ADCY6 polymorphisms may influence SCD severity through the mechanism of RBC adhesion. © 2008 The Authors.

Authors
Eyler, CE; Jackson, T; Elliott, LE; De Castro, LM; Jonassaint, J; Ashley-Koch, A; Telen, MJ
MLA Citation
Eyler, CE, Jackson, T, Elliott, LE, De Castro, LM, Jonassaint, J, Ashley-Koch, A, and Telen, MJ. "β2-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion." British Journal of Haematology 141.1 (April 1, 2008): 105-108.
Source
scopus
Published In
British Journal of Haematology
Volume
141
Issue
1
Publish Date
2008
Start Page
105
End Page
108
DOI
10.1111/j.1365-2141.2008.07008.x

Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease.

Authors
Johnson, C; Telen, MJ
MLA Citation
Johnson, C, and Telen, MJ. "Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease." Haematologica 93.4 (April 2008): 481-485.
PMID
18379005
Source
pubmed
Published In
Haematologica
Volume
93
Issue
4
Publish Date
2008
Start Page
481
End Page
485
DOI
10.3324/haematol.12734

beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion.

Sickle red cell (SS RBC) adhesion is thought to contribute to sickle cell disease (SCD) pathophysiology. SS RBC adhesion to laminin increases in response to adrenaline stimulation of beta(2)-adrenergic receptors (beta(2)ARs) and adenylate cyclase (ADCY6), and previous evidence suggests such activation occurs in vivo. We explored whether polymorphisms of the beta(2)AR and ADCY6 genes (ADRB2 and ADCY6, respectively) affect RBC adhesion to laminin. We found that the beta(2)AR arg(16)-->gly substitution and two non-coding ADCY6 polymorphisms were associated with elevated adhesion. We postulate that ADRB2 and ADCY6 polymorphisms may influence SCD severity through the mechanism of RBC adhesion.

Authors
Eyler, CE; Jackson, T; Elliott, LE; De Castro, LM; Jonassaint, J; Ashley-Koch, A; Telen, MJ
MLA Citation
Eyler, CE, Jackson, T, Elliott, LE, De Castro, LM, Jonassaint, J, Ashley-Koch, A, and Telen, MJ. "beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion." Br J Haematol 141.1 (April 2008): 105-108.
PMID
18324973
Source
pubmed
Published In
British Journal of Haematology
Volume
141
Issue
1
Publish Date
2008
Start Page
105
End Page
108
DOI
10.1111/j.1365-2141.2008.07008.x

Role and regulation of sickle red cell interactions with other cells: ICAM-4 and other adhesion receptors.

Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent. We now know that SS RBCs express numerous adhesion molecules, and that many of these can undergo activation. SS RBCs exposed briefly to epinephrine show markedly increased adhesion to both laminin and endothelial cells. In vivo, infusion of epinephrine-activated but not unstimulated SS RBCs causes RBC adhesion, vaso-occlusion, organ trapping, and shortened RBC survival in the circulation. Epinephrine treatment of SS RBCs before infusion also induces adhesion of murine leukocytes to vascular walls. Indeed, in vitro, SS RBCs can activate leukocyte adhesion and cytokine production. We now have demonstrated both in vitro and in vivo evidence for the importance of RBC signaling and have also shown that SS RBC adhesion is determined by genetic polymorphisms in the signaling pathway that activates adhesion. These advances will hopefully lead to new therapeutic modalities for sickle cell disease.

Authors
Zennadi, R; De Castro, L; Eyler, C; Xu, K; Ko, M; Telen, MJ
MLA Citation
Zennadi, R, De Castro, L, Eyler, C, Xu, K, Ko, M, and Telen, MJ. "Role and regulation of sickle red cell interactions with other cells: ICAM-4 and other adhesion receptors." Transfus Clin Biol 15.1-2 (February 2008): 23-28.
PMID
18502676
Source
pubmed
Published In
Transfusion Clinique et Biologique
Volume
15
Issue
1-2
Publish Date
2008
Start Page
23
End Page
28
DOI
10.1016/j.tracli.2008.04.009

Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes.

Screening for pulmonary hypertension (pHTN) has not yet become routine in sickle cell disease (SCD), despite clinical evidence of its high prevalence and associated mortality. Our objectives are to identify clinical conditions and laboratory findings predictive of/or associated with pHTN. One hundred twenty-five adult outpatients with Hb SS, SC, SOArab, Sbeta(0), or Sbeta(+) thalassemia, who underwent echocardiography and/or right heart catheterization due to cardiorespiratory symptoms, were studied. pHTN was identified in 36% (28/77) of SS/Sbeta(0) and in 25% (12/48) of SC/SOArab/Sbeta(+) patients studied. In SS/Sbeta(0) patients, pHTN was associated with low hemoglobin, low GFR, increasing age, no history of treatment with hydroxyurea and a history of leg ulcers, with trends for associations with higher total bilirubin, LDH levels, systolic systemic blood pressure, history of avascular necrosis, seizures, and cerebrovascular events. Twelve (40%) of the SS/Sbeta(0) patients with pHTN had >or= 1+ proteinuria. (P<0.039). The presence of proteinuria correlated with lower GFR and had a high positive predictive value (0.60) for pHTN in subjects with SS/Sbeta(0). The data also provided evidence that pHTN in this population is associated with right heart failure, with echocardiographic evidence of right ventricle enlargement and pericardial effusion. This study confirmed that even relatively mild elevations in pulmonary pressure are associated with high prospective mortality (hazard ratio: 15.9). We concluded that pHTN has a high prevalence in all Hb S related syndromes and is associated with increased mortality in SS/Sbeta(0). Kidney dysfunction, as indicated by proteinuria or decreased GFR, also represents sufficient reason to screen for pHTN.

Authors
De Castro, LM; Jonassaint, JC; Graham, FL; Ashley-Koch, A; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, JC, Graham, FL, Ashley-Koch, A, and Telen, MJ. "Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes." Am J Hematol 83.1 (January 2008): 19-25.
PMID
17724699
Source
pubmed
Published In
American Journal of Hematology
Volume
83
Issue
1
Publish Date
2008
Start Page
19
End Page
25
DOI
10.1002/ajh.21058

Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.

End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-based nonmyeloablative SCT from HLA-identical matched siblings. To prevent fludarabine toxicity, the patient with ESRD underwent aggressive dialysis following adjusted fludarabine dosing. Pharmacokinetics of the fludarabine metabolite F-Ara-A was studied on the patient with ESRD and 2 additional patients with normal renal function. Both patients with SCD achieved full donor erythroid chimerism, have normal blood counts, and are on no immunosuppressive medications. With a 20% dose reduction followed by daily dialysis, we achieved fludarabine drug exposure that is nearly identical to that achieved in patients with normal renal function. We conclude that fludarabine-based nonmyeloablative allogeneic SCT for adult patients with SCD is feasible, even in the setting of ESRD.

Authors
Horwitz, ME; Spasojevic, I; Morris, A; Telen, M; Essell, J; Gasparetto, C; Sullivan, K; Long, G; Chute, J; Chao, N; Rizzieri, D
MLA Citation
Horwitz, ME, Spasojevic, I, Morris, A, Telen, M, Essell, J, Gasparetto, C, Sullivan, K, Long, G, Chute, J, Chao, N, and Rizzieri, D. "Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics." Biol Blood Marrow Transplant 13.12 (December 2007): 1422-1426.
PMID
18022571
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
12
Publish Date
2007
Start Page
1422
End Page
1426
DOI
10.1016/j.bbmt.2007.08.050

Blocking adhesion of sickle erythrocytes to endothelial P-selectin using an RNAaptamer

Authors
Nishimura, J-I; Burnette, AD; Oney, S; Batchvarova, M; Delahunty, M; Zennadi, R; Sullenger, BA; Telen, MJ
MLA Citation
Nishimura, J-I, Burnette, AD, Oney, S, Batchvarova, M, Delahunty, M, Zennadi, R, Sullenger, BA, and Telen, MJ. "Blocking adhesion of sickle erythrocytes to endothelial P-selectin using an RNAaptamer." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
51A
End Page
51A

Sickle RBCs stimulate human monocyte cytokine expression

Authors
Xu, K; Telen, MJ
MLA Citation
Xu, K, and Telen, MJ. "Sickle RBCs stimulate human monocyte cytokine expression." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
668A
End Page
669A

The relationship of opiate analgesia to quality of life in an adult sickle cell population

Authors
Adam, SS; Jonassaint, JC; Jonassaint, CR; De Castro, LM; Telen, MJ
MLA Citation
Adam, SS, Jonassaint, JC, Jonassaint, CR, De Castro, LM, and Telen, MJ. "The relationship of opiate analgesia to quality of life in an adult sickle cell population." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
670A
End Page
670A

The effects of chronic opiates pain therapy in sickle cell anemia

Authors
Jonassaint, CR; Jonassaint, JC; Ashley-Koch, A; Adam, SS; Telen, MJ; De Castro, LM
MLA Citation
Jonassaint, CR, Jonassaint, JC, Ashley-Koch, A, Adam, SS, Telen, MJ, and De Castro, LM. "The effects of chronic opiates pain therapy in sickle cell anemia." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
997A
End Page
997A

Further investigation of the role of factor XIII in priapism associated with SCD

Authors
El Khatib, A; Ashley-Koch, A; Kail, M; Collins, A; Jonassaint, J; Adam, SS; Ataga, KI; Eckman, JR; Orringer, EP; Greenberg, CS; Telen, MJ
MLA Citation
El Khatib, A, Ashley-Koch, A, Kail, M, Collins, A, Jonassaint, J, Adam, SS, Ataga, KI, Eckman, JR, Orringer, EP, Greenberg, CS, and Telen, MJ. "Further investigation of the role of factor XIII in priapism associated with SCD." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
998A
End Page
998A

Evolution of adverse changes in stored RBCs.

Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O(2) desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1-6 degrees C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 x 10(-4) at 3 h vs. 6.5 x 10(-4) (fresh) mol S-nitrosothiol (SNO)/mol Hb tetramer (P = 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 x 10(-5) at 3 h vs. 9.0 x 10(-5) (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even "fresh" blood may have developed adverse biological characteristics.

Authors
Bennett-Guerrero, E; Veldman, TH; Doctor, A; Telen, MJ; Ortel, TL; Reid, TS; Mulherin, MA; Zhu, H; Buck, RD; Califf, RM; McMahon, TJ
MLA Citation
Bennett-Guerrero, E, Veldman, TH, Doctor, A, Telen, MJ, Ortel, TL, Reid, TS, Mulherin, MA, Zhu, H, Buck, RD, Califf, RM, and McMahon, TJ. "Evolution of adverse changes in stored RBCs." Proc Natl Acad Sci U S A 104.43 (October 23, 2007): 17063-17068.
PMID
17940021
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
104
Issue
43
Publish Date
2007
Start Page
17063
End Page
17068
DOI
10.1073/pnas.0708160104

Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo.

Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial alphavbeta3 integrin. To determine the contribution of LW activation to vaso-occlusive events in vivo, we investigated whether in vitro treatment of SS RBCs by epinephrine resulted in vaso-occlusion in intact microvasculature after RBC infusion into nude mice. Epinephrine enhanced human SS but not normal RBC adhesion to murine endothelial cells in vitro and to endothelium in vivo, promoting vaso-occlusion and RBC organ sequestration. Murine sickle RBCs also responded to epinephrine with increased adhesion to postcapillary endothelium in nude mice. Epinephrine-induced SS RBC adhesion, vaso-occlusion, and RBC organ trapping could be prevented by the beta-adrenergic receptor (beta-AR) antagonist, propranolol. Infusion of soluble recombinant LW also significantly reduced adhesion and vaso-occlusion. In addition, epinephrine-treated SS RBCs induced activation of murine leukocyte adhesion to endothelium as well. We conclude that LW activation by epinephrine via beta-AR stimulation can promote both SS RBC and leukocyte adhesion as well as vaso-occlusion, suggesting that both epinephrine and LW play potentially pathophysiological roles in SCD.

Authors
Zennadi, R; Moeller, BJ; Whalen, EJ; Batchvarova, M; Xu, K; Shan, S; Delahunty, M; Dewhirst, MW; Telen, MJ
MLA Citation
Zennadi, R, Moeller, BJ, Whalen, EJ, Batchvarova, M, Xu, K, Shan, S, Delahunty, M, Dewhirst, MW, and Telen, MJ. "Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo." Blood 110.7 (October 1, 2007): 2708-2717.
PMID
17609430
Source
pubmed
Published In
Blood
Volume
110
Issue
7
Publish Date
2007
Start Page
2708
End Page
2717
DOI
10.1182/blood-2006-11-056101

Genetic polymorphisms associated with priapism in sickle cell disease.

Priapism occurs in 30-45% of male patients with sickle cell disease (SCD), but the possible influence of genetic risk factors on the incidence of priapism is not well understood. We examined genetic polymorphisms in 199 unrelated, adult (>18 years), male patients with Hb SS and Hb Sbeta(0)-thalassaemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation and cell signalling. Additionally, we examined genes involved in nitric oxide biology (NOS2, NOS3, SLC4A1), as well as polymorphisms in the klotho (KL) gene, which has previously been associated with priapism. Strong evidence of association was found for single nucleotide polymorphisms in transforming growth factor-beta receptor, type III (TGFBR3) (rs7526590; P = 0.00058), aquaporin (AQP1) (rs10244884; P = 0.00068), integrin alphav (ITGAV) (rs3768780; P = 0.00090), and the A1 subunit of coagulation factor XIII (F13A1) (hcv1860621; P = 0.00156). Associations with TGFBR3, AQP1, and ITGAV remained significant after adjusting for multiple testing, using the Benjamini-Hochberg procedure. Our data suggest that genes involved in the TGFbeta pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.

Authors
Elliott, L; Ashley-Koch, AE; De Castro, L; Jonassaint, J; Price, J; Ataga, KI; Levesque, MC; Brice Weinberg, J; Eckman, JR; Orringer, EP; Vance, JM; Telen, MJ
MLA Citation
Elliott, L, Ashley-Koch, AE, De Castro, L, Jonassaint, J, Price, J, Ataga, KI, Levesque, MC, Brice Weinberg, J, Eckman, JR, Orringer, EP, Vance, JM, and Telen, MJ. "Genetic polymorphisms associated with priapism in sickle cell disease." Br J Haematol 137.3 (May 2007): 262-267.
PMID
17408468
Source
pubmed
Published In
British Journal of Haematology
Volume
137
Issue
3
Publish Date
2007
Start Page
262
End Page
267
DOI
10.1111/j.1365-2141.2007.06560.x

Role of adhesion molecules and vascular endothelium in the pathogenesis of sickle cell disease.

A number of lines of evidence now support the hypothesis that vaso-occlusion and several of the sequelae of sickle cell disease (SCD) arise, at least in part, from adhesive interactions of sickle red blood cells, leukocytes, and the endothelium. Both experimental and genetic evidence provide support for the importance of these interactions. It is likely that future therapies for SCD might target one or more of these interactions.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Role of adhesion molecules and vascular endothelium in the pathogenesis of sickle cell disease." Hematology Am Soc Hematol Educ Program (2007): 84-90. (Review)
PMID
18024614
Source
pubmed
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Publish Date
2007
Start Page
84
End Page
90
DOI
10.1182/asheducation-2007.1.84

A comparison of inpatient outcomes between sickle cell disease and non-sickle cell disease patients undergoing high-volume surgical procedures

Authors
Chou, CH; Reed, SD; Telen, MJ; Schulman, KA
MLA Citation
Chou, CH, Reed, SD, Telen, MJ, and Schulman, KA. "A comparison of inpatient outcomes between sickle cell disease and non-sickle cell disease patients undergoing high-volume surgical procedures." VALUE IN HEALTH 10.3 (2007): A152-A153.
Source
wos-lite
Published In
Value in Health
Volume
10
Issue
3
Publish Date
2007
Start Page
A152
End Page
A153
DOI
10.1016/S1098-3015(10)69001-8

Genetic polymorphisms associated with priapism in sickle cell disease.

Authors
Elliott, L; Ashley-Koch, AE; Jonassaint, J; Price, J; Galloway, J; Ataga, KI; Levesque, MC; Weinberg, JB; Eckman, JR; Orringer, EP; Vance, JM; Telen, MJ
MLA Citation
Elliott, L, Ashley-Koch, AE, Jonassaint, J, Price, J, Galloway, J, Ataga, KI, Levesque, MC, Weinberg, JB, Eckman, JR, Orringer, EP, Vance, JM, and Telen, MJ. "Genetic polymorphisms associated with priapism in sickle cell disease." BLOOD 108.11 (November 16, 2006): 236A-237A.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
236A
End Page
237A

Current prevalence of specific clinical outcomes in adult patients with HbSS or Hb S beta(0) thalassemia.

Authors
De Castro, LM; Lennon-Graham, FC; Ashley-Koch, AG; Jonassaint, JC; Eckman, JJ; Orringer, EP; Telen, MJ
MLA Citation
De Castro, LM, Lennon-Graham, FC, Ashley-Koch, AG, Jonassaint, JC, Eckman, JJ, Orringer, EP, and Telen, MJ. "Current prevalence of specific clinical outcomes in adult patients with HbSS or Hb S beta(0) thalassemia." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
353A
End Page
353A

Effect of single dose in vivo propranolol therapy on in vitro adhesion of human SS RBC.

Authors
De Castro, LM; Jonassaint, JC; Johnson, JG; Batchvarova, M; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, JC, Johnson, JG, Batchvarova, M, and Telen, MJ. "Effect of single dose in vivo propranolol therapy on in vitro adhesion of human SS RBC." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
363A
End Page
363A

Blocking adhesion of sickle erythrocytes to endothelial alpha V beta 3 using RNA aptamer.

Authors
Nishimura, J-I; Burnette, AD; Batchvarova, M; Nimjee, SM; Zennadi, R; Sullenger, BA; Telen, MJ
MLA Citation
Nishimura, J-I, Burnette, AD, Batchvarova, M, Nimjee, SM, Zennadi, R, Sullenger, BA, and Telen, MJ. "Blocking adhesion of sickle erythrocytes to endothelial alpha V beta 3 using RNA aptamer." BLOOD 108.11 (November 16, 2006): 206A-207A.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
206A
End Page
207A

Mechanism of soluble laminin-mediated enhancement of sickle red cell adhesion to endothelial cells.

Authors
Ko, MS; Xu, KK; Telen, MJ
MLA Citation
Ko, MS, Xu, KK, and Telen, MJ. "Mechanism of soluble laminin-mediated enhancement of sickle red cell adhesion to endothelial cells." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
364A
End Page
364A

Interaction of activated sickle red cell LW with leukocytes induces leukocyte adhesion to endothelium via CD44-E-selectin.

Authors
Zennadi, R; Chien, C; Batchvarova, M; Telen, MJ
MLA Citation
Zennadi, R, Chien, C, Batchvarova, M, and Telen, MJ. "Interaction of activated sickle red cell LW with leukocytes induces leukocyte adhesion to endothelium via CD44-E-selectin." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
361A
End Page
361A

Prevention and diagnosis of delayed haemolytic transfusion reactions.

Authors
Engelfriet, CP; Reesink, HW; Fontão-Wendel, R; Lazar, A; Cardoso, RA; Olyntho, S; Achkar, R; Wendel, S; Pisacka, M; Taaning, E; Koski, T; Matilainen, J; Kretschmer, V; Karger, R; Politis, C; Katsea, P; Malamou, V; Aprili, G; Piccoli, P; Gandini, G; Franchini, M; Schonewille, H; Brand, A; Solheim, BG; Flesland, O; Seyfried, H; Michalewska, B; Letowska, M; Tissot, J-D; Milkins, C; Knowles, S; DeSilva, M; Contreras, M; Stainsby, D; Combs, MR; Arney, RS; Telen, MJ
MLA Citation
Engelfriet, CP, Reesink, HW, Fontão-Wendel, R, Lazar, A, Cardoso, RA, Olyntho, S, Achkar, R, Wendel, S, Pisacka, M, Taaning, E, Koski, T, Matilainen, J, Kretschmer, V, Karger, R, Politis, C, Katsea, P, Malamou, V, Aprili, G, Piccoli, P, Gandini, G, Franchini, M, Schonewille, H, Brand, A, Solheim, BG, Flesland, O, Seyfried, H, Michalewska, B, Letowska, M, Tissot, J-D, Milkins, C, Knowles, S, DeSilva, M, Contreras, M, Stainsby, D, Combs, MR, Arney, RS, and Telen, MJ. "Prevention and diagnosis of delayed haemolytic transfusion reactions." Vox Sang 91.4 (November 2006): 353-368.
PMID
17105616
Source
pubmed
Published In
Vox Sanguinis
Volume
91
Issue
4
Publish Date
2006
Start Page
353
End Page
368
DOI
10.1111/j.1423-0410.2006.00812_1.x

Allolimmunization and clinical disease severity in sickle cell disease

Authors
Afenyi-Annan, AN; Graham, FL; Galloway, J; Price, J; Combs, MR; Vance, JM; Ashley-Koch, A; Telen, MJ
MLA Citation
Afenyi-Annan, AN, Graham, FL, Galloway, J, Price, J, Combs, MR, Vance, JM, Ashley-Koch, A, and Telen, MJ. "Allolimmunization and clinical disease severity in sickle cell disease." September 2006.
Source
wos-lite
Published In
Transfusion
Volume
46
Issue
9
Publish Date
2006
Start Page
129A
End Page
129A

Duffy genotype is associated with sickle cell nephropathy

Authors
Afenyi-Annan, AN; Graham, FL; Galloway, J; Price, J; Combs, MR; Vance, JM; Ashley-Koch, A; Telen, MJ
MLA Citation
Afenyi-Annan, AN, Graham, FL, Galloway, J, Price, J, Combs, MR, Vance, JM, Ashley-Koch, A, and Telen, MJ. "Duffy genotype is associated with sickle cell nephropathy." September 2006.
Source
wos-lite
Published In
Transfusion
Volume
46
Issue
9
Publish Date
2006
Start Page
2A
End Page
3A

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Authors
Snell, M; Chau, C; Hendrix, D; Fox, R; Downes, KA; Creger, R; Meyerson, H; Telen, MJ; Laughlin, MJ; Lazarus, HM; Yomtovian, R
MLA Citation
Snell, M, Chau, C, Hendrix, D, Fox, R, Downes, KA, Creger, R, Meyerson, H, Telen, MJ, Laughlin, MJ, Lazarus, HM, and Yomtovian, R. "Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation." Bone Marrow Transplant 38.2 (July 2006): 135-140.
PMID
16751785
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
38
Issue
2
Publish Date
2006
Start Page
135
End Page
140
DOI
10.1038/sj.bmt.1705409

The Lutheran glycoprotein: a multifunctional adhesion receptor.

The Lutheran blood group system, which comprises one of the largest families of human red blood cell (RBC) antigens, resides on two immunoglobulin superfamily (IgSF) proteins: Lutheran and basal cell adhesion molecule (B-CAM). These two glycoproteins arise via alternative splicing of mRNA from a single gene and differ in structure only in the lengths of their cytoplasmic tails. Both are expressed on RBCs as well as a variety of other cell types, and they are overexpressed on sickle RBCs (SS RBC). B-CAM/Lu is the critical receptor for SS RBC adhesion to the extracellular matrix protein laminin, an interaction thought to contribute to the pathogenesis of sickle cell-related vasoocclusive events. Recent work has also shown that B-CAM/Lu on RBCs can undergo activation as a result of adrenergic signaling pathways. The high affinity of B-CAM/Lu for laminin is also thought to contribute to various developmental processes, including organogenesis, vascular development, erythropoiesis, and smooth muscle development and organization. Interestingly, the B-CAM spliceoform seems to be overexpressed by a variety of different malignant tumors and may be involved, along with other adhesion receptor proteins, in malignant transformation and tumor metastasis. Studies of B-CAM/Lu have thus expanded from defining antigen-specific polymorphisms to investigations of processes involved in sickle cell disease, human development, and cancer biology.

Authors
Eyler, CE; Telen, MJ
MLA Citation
Eyler, CE, and Telen, MJ. "The Lutheran glycoprotein: a multifunctional adhesion receptor." Transfusion 46.4 (April 2006): 668-677. (Review)
PMID
16584446
Source
pubmed
Published In
Transfusion
Volume
46
Issue
4
Publish Date
2006
Start Page
668
End Page
677
DOI
10.1111/j.1537-2995.2006.00779.x

LW protein: a promiscuous integrin receptor activated by adrenergic signaling.

The LW blood group antigen glycoprotein, although part of the Rh macromolecular complex, is nonetheless a member of the intercellular adhesion molecule (ICAM) family. Thus, while it is only rarely clinically important in the setting of transfusion and pregnancy, LW is likely to contribute to red cell adhesion in a variety of settings, including during hematopoiesis, as well as in vascular disorders. The best documentation of a pathophysiological role for LW in human disease is in sickle cell disease, where it contributes to red cell adhesion to endothelial cells and the development of vaso-occlusion, the hallmark of that disease. LW may also contribute to other intravascular processes, such as both venous and arterial thrombosis, due to its ability to interact with both activated platelets as well as leukocytes. The evidence that LW itself can undergo activation on red cells holds promise that pharmacotherapeutic maneuvers may be found to prevent such pathophysiologic interactions.

Authors
Delahunty, M; Zennadi, R; Telen, MJ
MLA Citation
Delahunty, M, Zennadi, R, and Telen, MJ. "LW protein: a promiscuous integrin receptor activated by adrenergic signaling." Transfus Clin Biol 13.1-2 (March 2006): 44-49. (Review)
PMID
16564726
Source
pubmed
Published In
Transfusion Clinique et Biologique
Volume
13
Issue
1-2
Publish Date
2006
Start Page
44
End Page
49
DOI
10.1016/j.tracli.2006.02.022

Prevention and diagnosis of delayed haemolytic transfusion reactions

Authors
Engelfriet, CP; Reesink, HW; Fontao-Wendel, R; Lazar, A; Olyntho, S; Cardoso, RA; Achkar, R; Wendel, S; Pisacka, M; Taaning, E; Koski, T; Matilainen, J; Kretschmer, V; Karger, R; Politis, C; Katsea, P; Malamou, V; Aprili, G; Piccoli, P; Gandini, G; Franchini, M; Schonewille, H; Brand, A; Solheim, BG; Flesland, O; Seyfried, H; Michalewska, B; Letowska, M; Tissot, J-D; Milkins, C; Knowles, S; DeSilva, M; Contreras, M; Stainsby, D; Combs, MR; Arney, RS; Telen, MJ
MLA Citation
Engelfriet, CP, Reesink, HW, Fontao-Wendel, R, Lazar, A, Olyntho, S, Cardoso, RA, Achkar, R, Wendel, S, Pisacka, M, Taaning, E, Koski, T, Matilainen, J, Kretschmer, V, Karger, R, Politis, C, Katsea, P, Malamou, V, Aprili, G, Piccoli, P, Gandini, G, Franchini, M, Schonewille, H, Brand, A, Solheim, BG, Flesland, O, Seyfried, H, Michalewska, B, Letowska, M, Tissot, J-D, Milkins, C, Knowles, S, DeSilva, M, Contreras, M, Stainsby, D, Combs, MR, Arney, RS, and Telen, MJ. "Prevention and diagnosis of delayed haemolytic transfusion reactions." VOX SANGUINIS 91.4 (2006): 353-368.
Source
wos-lite
Published In
Vox Sanguinis
Volume
91
Issue
4
Publish Date
2006
Start Page
353
End Page
368
DOI
10.1111/j.1423-0410.2006.00812.x

Priapism in SCD: Clinical and genetic correlations.

Authors
Ashley-Koch, AE; De Castro, LM; Lennon-Graham, F; Jonassaint, J; Jackson, TL; Price, J; Galloway, J; Jones, S; Randall, E; Packman, C; Knupp, C; Eckman, JR; Redding-Lallinger, R; Orringer, EP; Vance, JM; Telen, MJ
MLA Citation
Ashley-Koch, AE, De Castro, LM, Lennon-Graham, F, Jonassaint, J, Jackson, TL, Price, J, Galloway, J, Jones, S, Randall, E, Packman, C, Knupp, C, Eckman, JR, Redding-Lallinger, R, Orringer, EP, Vance, JM, and Telen, MJ. "Priapism in SCD: Clinical and genetic correlations." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
887A
End Page
887A

Clinical and genetic profiles of the aging sickle cell patient.

Authors
Ashley-Koch, AE; De Castro, LM; Lennon-Graham, F; Jonassaint, J; Jackson, TL; Price, J; Galloway, J; Jones, S; Randall, E; Packman, C; Knupp, C; Eckman, JR; Orringer, EP; Vance, JM; Telen, MJ
MLA Citation
Ashley-Koch, AE, De Castro, LM, Lennon-Graham, F, Jonassaint, J, Jackson, TL, Price, J, Galloway, J, Jones, S, Randall, E, Packman, C, Knupp, C, Eckman, JR, Orringer, EP, Vance, JM, and Telen, MJ. "Clinical and genetic profiles of the aging sickle cell patient." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
26A
End Page
26A

The relationship of plasma laminin levels to anemia and the effect of soluble laminin on sickle red cell adhesion in SCD.

Authors
Ko, M; De Castro, LM; Jonassaint, JC; Batchvarova, M; Zennadi, R; Telen, MJ
MLA Citation
Ko, M, De Castro, LM, Jonassaint, JC, Batchvarova, M, Zennadi, R, and Telen, MJ. "The relationship of plasma laminin levels to anemia and the effect of soluble laminin on sickle red cell adhesion in SCD." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
657A
End Page
657A

Left sided heart dysfunction in sickle cell disease: Echocardiographic and genetic studies.

Authors
De Castro, LM; Jonassaint, JC; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, JC, and Telen, MJ. "Left sided heart dysfunction in sickle cell disease: Echocardiographic and genetic studies." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
27A
End Page
27A

Adhesive characteristics of hemoglobin SC red blood cells.

Authors
Chien, AC; Zennadi, R; De Castro, LM; Telen, MJ
MLA Citation
Chien, AC, Zennadi, R, De Castro, LM, and Telen, MJ. "Adhesive characteristics of hemoglobin SC red blood cells." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
23B
End Page
24B

Morbidity and associated sudden death in sickle cell disease.

Authors
Fitzhugh, C; Lauder, N; Jonassaint, J; Gilliam, FR; Telen, MJ; De Castro, LM
MLA Citation
Fitzhugh, C, Lauder, N, Jonassaint, J, Gilliam, FR, Telen, MJ, and De Castro, LM. "Morbidity and associated sudden death in sickle cell disease." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
661A
End Page
661A

Role of LW and AKAP79 in beta-adrenergic receptor signaling-induced sickle red blood cell adhesion.

Authors
Zennadi, R; Moeller, BJ; Dewhirst, MW; Telen, MJ
MLA Citation
Zennadi, R, Moeller, BJ, Dewhirst, MW, and Telen, MJ. "Role of LW and AKAP79 in beta-adrenergic receptor signaling-induced sickle red blood cell adhesion." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
889A
End Page
889A

Transfusion management in sickle cell disease.

Sickle cell disease (SCD) is the most commonly inherited hemoglobinopathy in the United States. Blood transfusion is a critical part of the multidisciplinary approach necessary in the management of SCD; however, blood transfusions are not without complications. The successful use of transfusion as a treatment strategy in SCD requires the critical review and knowledge of transfusion methods, generally accepted indications, clinical situations in which transfusion generally is not considered, the selection of blood products, and strategies to prevent transfusion-related complications.

Authors
Wanko, SO; Telen, MJ
MLA Citation
Wanko, SO, and Telen, MJ. "Transfusion management in sickle cell disease." Hematol Oncol Clin North Am 19.5 (October 2005): 803-vi. (Review)
PMID
16214645
Source
pubmed
Published In
Hematology/Oncology Clinics of North America
Volume
19
Issue
5
Publish Date
2005
Start Page
803
End Page
vi
DOI
10.1016/j.hoc.2005.07.002

Characterization of a novel prothrombin variant, Prothrombin C20209T, as a modifier of thrombotic risk among African-Americans.

Authors
Itakura, H; Telen, MJ; Hoppe, CC; White, DAE; Zehnder, JL
MLA Citation
Itakura, H, Telen, MJ, Hoppe, CC, White, DAE, and Zehnder, JL. "Characterization of a novel prothrombin variant, Prothrombin C20209T, as a modifier of thrombotic risk among African-Americans." J Thromb Haemost 3.10 (October 2005): 2357-2359. (Letter)
PMID
16194213
Source
pubmed
Published In
Journal of Thrombosis and Haemostasis
Volume
3
Issue
10
Publish Date
2005
Start Page
2357
End Page
2359
DOI
10.1111/j.1538-7836.2005.01562.x

Kidd antigen suppression and production of anti-Jk(a),-Jk3 in pregnancy: A case report

Authors
Combs, MR; Arney, RS; Parrott, SW; Wester, ES; Olsson, ML; Telen, MJ
MLA Citation
Combs, MR, Arney, RS, Parrott, SW, Wester, ES, Olsson, ML, and Telen, MJ. "Kidd antigen suppression and production of anti-Jk(a),-Jk3 in pregnancy: A case report." September 2005.
Source
wos-lite
Published In
Transfusion
Volume
45
Issue
3
Publish Date
2005
Start Page
5A
End Page
5A

Delayed serological transfusion reactions and the gel test: A five year experience

Authors
Combs, MR; Arney, RS; Bennett, DH; Telen, MJ
MLA Citation
Combs, MR, Arney, RS, Bennett, DH, and Telen, MJ. "Delayed serological transfusion reactions and the gel test: A five year experience." September 2005.
Source
wos-lite
Published In
Transfusion
Volume
45
Issue
3
Publish Date
2005
Start Page
123A
End Page
123A

Comparison of gel and polyethylene glycol for the detection of alloantibodies associated with delayed serological transfusion reactions

Authors
Combs, MR; Arney, RS; Telen, MJ
MLA Citation
Combs, MR, Arney, RS, and Telen, MJ. "Comparison of gel and polyethylene glycol for the detection of alloantibodies associated with delayed serological transfusion reactions." September 2005.
Source
wos-lite
Published In
Transfusion
Volume
45
Issue
3
Publish Date
2005
Start Page
138A
End Page
139A

Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU.

Vaso-occlusion is a hallmark of sickle cell disease. Agonist-induced activation of sickle red blood cells (SS RBCs) promotes their adhesion to vascular proteins, potentially contributing to vasoocclusion. Previously, we described a cyclic adenosine monophosphate (cAMP)-dependent increase in SS RBC adhesion to laminin. Here, we investigated whether Rap1, a small guanosine triphosphatase (GTPase) known to promote integrin-mediated adhesion in other cells, was involved in this signaling pathway. We found that agonists known to induce cAMP signaling promoted the GTP-bound, active state of Rap1 in SS RBCs. The cAMP-dependent exchange factor Epac (exchange protein directly activated by cAMP) is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog 8CPT-2-Me (8-(4-cholorophenylthio)-2'-O-methyl-cAMP) activated Rap1 and promoted SS RBC adhesion to laminin. This 8CPT-2-Me-stimulated adhesion was integrin independent, since it was insensitive to RGD peptide or antibodies against the only known integrin on SS RBCs, alpha4beta1. However, this adhesion was completely inhibited by either a soluble version of basal cell adhesion molecule/Lutheran (BCAM/LU) or a BCAM/LU adhesion-blocking anti-body. Surprisingly, 8CPT-2-Me-activated Rap1 did not promote SS RBC adhesion to a known alpha4beta1 ligand, vascular cell adhesion molecule 1 (VCAM-1). These results demonstrate that Epac-induced Rap1 activation in SS RBCs promotes BCAM/LU-mediated adhesion to laminin. Thus, Epac-mediated Rap1 activation may represent an important signaling pathway for promoting SS RBC adhesion.

Authors
Murphy, MM; Zayed, MA; Evans, A; Parker, CE; Ataga, KI; Telen, MJ; Parise, LV
MLA Citation
Murphy, MM, Zayed, MA, Evans, A, Parker, CE, Ataga, KI, Telen, MJ, and Parise, LV. "Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU." Blood 105.8 (April 15, 2005): 3322-3329.
PMID
15613546
Source
pubmed
Published In
Blood
Volume
105
Issue
8
Publish Date
2005
Start Page
3322
End Page
3329
DOI
10.1182/blood-2004-07-2881

Erythrocyte adhesion receptors: blood group antigens and related molecules.

During the second half of the 20th century, blood bankers quickly expanded our knowledge of human erythrocyte blood group antigens. By the dawn of the 21st century, several hundred blood group antigen polymorphisms had been identified. Hot on the heels of the serologists, membrane biochemists and molecular geneticists defined both the biochemical and genetic bases of most of these antigens. Perhaps to their surprise, this work has led to the discovery of functionally diverse and important membrane proteins expressed on the surface of red cells, including numerous adhesion molecules. Red cells express an unexpected number of such adhesion receptors, some of which contribute to human disease, as well as to normal red cell development. And perhaps most interestingly, study of these molecules has elucidated ways in which even mature red cells respond to external stimuli, such as adrenergic hormones.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Erythrocyte adhesion receptors: blood group antigens and related molecules." Transfus Med Rev 19.1 (January 2005): 32-44. (Review)
PMID
15830326
Source
pubmed
Published In
Transfusion Medicine Reviews
Volume
19
Issue
1
Publish Date
2005
Start Page
32
End Page
44

Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions.

The possible role of physiologic stress hormones in enhancing adhesion of sickle erythrocytes (SS RBCs) to endothelial cells (ECs) in sickle cell disease (SCD) has not been previously explored. We have now found that up-regulation of intracellular cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) by epinephrine significantly increased sickle but not normal erythrocyte adhesion to both primary and immortalized ECs. Inhibition of serine/threonine phosphatases also enhanced sickle erythrocyte adhesion at least partially through a PKA-dependent mechanism. Adhesion was mediated through LW (intercellular adhesion molecule-4 [ICAM-4], CD242) blood group glycoprotein, and immunoprecipitation studies showed that LW on sickle but not on normal erythrocytes undergoes increased PKA-dependent serine phosphorylation as a result of activation. The major counter receptor for LW was identified as the alphavbeta3 integrin on ECs. These data suggest that adrenergic hormones such as epinephrine may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress.

Authors
Zennadi, R; Hines, PC; De Castro, LM; Cartron, J-P; Parise, LV; Telen, MJ
MLA Citation
Zennadi, R, Hines, PC, De Castro, LM, Cartron, J-P, Parise, LV, and Telen, MJ. "Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions." Blood 104.12 (December 1, 2004): 3774-3781.
PMID
15308566
Source
pubmed
Published In
Blood
Volume
104
Issue
12
Publish Date
2004
Start Page
3774
End Page
3781
DOI
10.1182/blood-2004-01-0042

Genetic polymorphisms associated with risk for pulmonary hypertension and proteinuria in sickle cell disease.

Authors
Ashley-Koch, AE; De Castro, L; Lennon-Graham, F; Jonassaint, J; Jackson, TL; Price, J; Galloway, J; Ataga, KI; Orringer, EP; Vance, JM; Telen, MJ
MLA Citation
Ashley-Koch, AE, De Castro, L, Lennon-Graham, F, Jonassaint, J, Jackson, TL, Price, J, Galloway, J, Ataga, KI, Orringer, EP, Vance, JM, and Telen, MJ. "Genetic polymorphisms associated with risk for pulmonary hypertension and proteinuria in sickle cell disease." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
464A
End Page
464A

Pulmonary hypertension in SS, SC and so thalassemia: Prevalence, associated clinical syndromes, and mortality.

Authors
De Castro, LM; Jonassaint, JC; Graham, FL; Ashley-Koch, A; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, JC, Graham, FL, Ashley-Koch, A, and Telen, MJ. "Pulmonary hypertension in SS, SC and so thalassemia: Prevalence, associated clinical syndromes, and mortality." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
462A
End Page
462A

Effects of single nucleotide polymorphisms of the beta(2) adrenergic receptor and of adenylate cyclase on sickle red cell adhesion to laminin

Authors
Eyler, CE; Jackson, TL; De Castro, LM; Zennadi, R; Vance, JM; Ashley-Koch, A; Telen, MJ
MLA Citation
Eyler, CE, Jackson, TL, De Castro, LM, Zennadi, R, Vance, JM, Ashley-Koch, A, and Telen, MJ. "Effects of single nucleotide polymorphisms of the beta(2) adrenergic receptor and of adenylate cyclase on sickle red cell adhesion to laminin." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
969A
End Page
970A

Epinephrine-induced sickle red cell adhesion and vaso-occlusion in vivo is inhibited by the beta-adrenoceptor blocker propranolol

Authors
Zennadi, R; Moeller, BJ; Whalen, EJ; Dewhirst, MW; Telen, MJ
MLA Citation
Zennadi, R, Moeller, BJ, Whalen, EJ, Dewhirst, MW, and Telen, MJ. "Epinephrine-induced sickle red cell adhesion and vaso-occlusion in vivo is inhibited by the beta-adrenoceptor blocker propranolol." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
107A
End Page
107A

Protein kinases associated with activation of sickle red blood cell adhesion

Authors
Zennadi, R; Whalen, EJ; Telen, MJ
MLA Citation
Zennadi, R, Whalen, EJ, and Telen, MJ. "Protein kinases associated with activation of sickle red blood cell adhesion." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
970A
End Page
970A

Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer.

Molecular events underlying the progression of malignant tumors through the surrounding tissue are largely mediated by membrane-bound adhesion molecules. Basal-cell adhesion molecule (B-CAM), a 90-kDa laminin receptor of the immunoglobulin superfamily, is induced in some epithelial malignancies. Its function in these tumors, however, still remains obscure. We demonstrated that expression of B-CAM is very weak, if detectable at all, in normal epidermis but is strongly induced in both basal cell carcinomas and squamous cell carcinomas of the skin, and most pronounced at the basal surface of the tumor nests. Interestingly, the only known B-CAM ligand, laminin, was markedly upregulated within corresponding microanatomical sites surrounding the tumor nests, suggesting that both molecules may interact there. Consistent with this hypothesis, we were able to directly demonstrate binding of a B-CAM/Fc chimeric molecule to the peritumoral stroma in situ. Finally, in proof-of-principle experiments, human B-CAM was overexpressed both in murine and in human fibroblasts. The haptotactic migration of these novel B-CAM+ cell populations on a laminin matrix was significantly increased (P = 0.02) as compared to mock-transfected cells when integrin-mediated adhesion was blocked by chelation of divalent cations. Thus, our findings provide the first direct experimental evidence that interactions of B-CAM and laminin may be involved in progression of epithelial skin tumors.

Authors
Drewniok, C; Wienrich, BG; Schön, M; Ulrich, J; Zen, Q; Telen, MJ; Hartig, RJ; Wieland, I; Gollnick, H; Schön, MP
MLA Citation
Drewniok, C, Wienrich, BG, Schön, M, Ulrich, J, Zen, Q, Telen, MJ, Hartig, RJ, Wieland, I, Gollnick, H, and Schön, MP. "Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer." Arch Dermatol Res 296.2 (July 2004): 59-66.
PMID
15278364
Source
pubmed
Published In
Archives of Dermatological Research
Volume
296
Issue
2
Publish Date
2004
Start Page
59
End Page
66
DOI
10.1007/s00403-004-0481-4

B-CAM/LU expression and the role of B-CAM/LU activation in binding of low- and high-density red cells to laminin in sickle cell disease.

Red blood cells from patients with sickle cell disease (SS RBC) adhere to laminin and over-express the high-affinity laminin receptor basal cell adhesion molecule/Lutheran protein (B-CAM/LU). This receptor has recently been shown to undergo activation in vitro through a protein kinase A-dependent mechanism. Low-density SS RBC express two-thirds more B-CAM/LU than high-density SS RBC. However, high-density SS RBC have been identified as most adherent to laminin under flow conditions. We investigated the ability of low- and high-density SS RBC to interact with laminin under various conditions and explored factors that might be responsible for the differences in B-CAM/LU-laminin interaction between high- and low-density SS RBC. We confirmed that high-density SS RBC adhere to laminin more strongly than low-density SS RBC under flow conditions. However, low-density SS RBC bind soluble laminin most strongly and are the most adherent to laminin under static conditions. Soluble recombinant Lutheran extracellular domain protein completely blocked SS RBC adhesion to laminin under both static and flow conditions. The protein kinase A inhibitor 14-22 amide inhibited adhesion to laminin during flow by high-density SS RBC from patients with strongly adherent cells but had no effect on adhesion observed after a static phase. Deletion of the cytoplasmic domain of B-CAM as well as mutation of the juxtamembranous tyrosine residue failed to reduce B-CAM-mediated adhesion to laminin by transfected MEL cells. These studies confirm that B-CAM/LU is the most critical receptor mediating adhesion to laminin under both static and flow conditions. Dense SS RBC are most adherent to laminin despite bearing fewer laminin receptors, apparently due to a reversible protein kinase A-dependent process that is unlikely to involve direct phosphorylation of B-CAM/LU. Our results also suggest that the nature of the interaction of B-CAM/LU with laminin may be different under static and flow conditions.

Authors
Zen, Q; Batchvarova, M; Twyman, CA; Eyler, CE; Qiu, H; De Castro, LM; Telen, MJ
MLA Citation
Zen, Q, Batchvarova, M, Twyman, CA, Eyler, CE, Qiu, H, De Castro, LM, and Telen, MJ. "B-CAM/LU expression and the role of B-CAM/LU activation in binding of low- and high-density red cells to laminin in sickle cell disease." Am J Hematol 75.2 (February 2004): 63-72.
PMID
14755370
Source
pubmed
Published In
American Journal of Hematology
Volume
75
Issue
2
Publish Date
2004
Start Page
63
End Page
72
DOI
10.1002/ajh.10442

Examination of a VCAM1 polymorphism as a risk modifier for clinical outcomes in sickle cell disease.

Authors
Telen, MJ; Ashley-Koch, AE; Zhang, L; Jonassaint, J; Rainey, S; Motley, R; Jones, S; Galloway, J; Uchiyama, T; Eckman, JR; Orringer, EP; Vance, JM
MLA Citation
Telen, MJ, Ashley-Koch, AE, Zhang, L, Jonassaint, J, Rainey, S, Motley, R, Jones, S, Galloway, J, Uchiyama, T, Eckman, JR, Orringer, EP, and Vance, JM. "Examination of a VCAM1 polymorphism as a risk modifier for clinical outcomes in sickle cell disease." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
29B
End Page
29B

B-CAM/LU polymorphisms: Effect on sickle cell disease outcomes and cell adhesion.

Authors
De Castro, LM; Jonassaint, JC; Rainey, S; Motley, R; Jones, S; Galloway, J; Zhang, L; Uchiyama, T; Eckman, JR; Orringer, EP; Ashley-Koch, AE; Vance, JM; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, JC, Rainey, S, Motley, R, Jones, S, Galloway, J, Zhang, L, Uchiyama, T, Eckman, JR, Orringer, EP, Ashley-Koch, AE, Vance, JM, and Telen, MJ. "B-CAM/LU polymorphisms: Effect on sickle cell disease outcomes and cell adhesion." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
28B
End Page
28B

In vitro exposure to epinephrine causes in vivo adhesion of human sickle red blood cells to vascular endothelium in nude mice: A new model for studying vaso-occlusion.

Authors
Zennadi, R; Moeller, BJ; Zen, Q; Dewhirst, MW; Telen, MJ
MLA Citation
Zennadi, R, Moeller, BJ, Zen, Q, Dewhirst, MW, and Telen, MJ. "In vitro exposure to epinephrine causes in vivo adhesion of human sickle red blood cells to vascular endothelium in nude mice: A new model for studying vaso-occlusion." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
261A
End Page
261A

Sickle RBCs form microaggregates in autologous plasma following epinephrine stimulation: A role for endogenous, soluble laminin.

Authors
Hines, PC; Okafor, C; Zen, Q; Telen, MJ; Ataga, KI; Orringer, EP; Parise, LV
MLA Citation
Hines, PC, Okafor, C, Zen, Q, Telen, MJ, Ataga, KI, Orringer, EP, and Parise, LV. "Sickle RBCs form microaggregates in autologous plasma following epinephrine stimulation: A role for endogenous, soluble laminin." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
82A
End Page
82A

cAMP-dependent activation of sickle red blood cell adhesion is associated with LW serine and tyrosine phosphorylation.

Authors
Zennadi, R; Cartron, JP; Telen, MJ
MLA Citation
Zennadi, R, Cartron, JP, and Telen, MJ. "cAMP-dependent activation of sickle red blood cell adhesion is associated with LW serine and tyrosine phosphorylation." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
263A
End Page
263A

The small GTPase rapl activates BCAM/LU-dependent but not alpha 4 beta l-dependent adhesion in sickle red blood cells: Evidence for divergent adhesive pathways.

Authors
Murphy, MM; Evans, A; Zayed, MA; Brittain, JE; Orringer, EP; Ataga, KI; Eyler, CE; Telen, MJ; Parise, LV
MLA Citation
Murphy, MM, Evans, A, Zayed, MA, Brittain, JE, Orringer, EP, Ataga, KI, Eyler, CE, Telen, MJ, and Parise, LV. "The small GTPase rapl activates BCAM/LU-dependent but not alpha 4 beta l-dependent adhesion in sickle red blood cells: Evidence for divergent adhesive pathways." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
82A
End Page
82A

Examination of VCAM1 as a modulator of stroke risk in sickle cell disease

Authors
Telen, MJ; Ashley-Koch, AE; Zhang, L; Jonassaint, J; Rainey, S; Motley, R; Jones, S; Galloway, J; Uchiyama, T; Eckman, JR; Orringer, EP; Vance, JM
MLA Citation
Telen, MJ, Ashley-Koch, AE, Zhang, L, Jonassaint, J, Rainey, S, Motley, R, Jones, S, Galloway, J, Uchiyama, T, Eckman, JR, Orringer, EP, and Vance, JM. "Examination of VCAM1 as a modulator of stroke risk in sickle cell disease." November 2003.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
73
Issue
5
Publish Date
2003
Start Page
569
End Page
569

B-CAM/LU modifies sickle cell disease severity

Authors
De Castro, LM; Jonassaint, J; Rainey, S; Motley, R; Jones, S; Galloway, J; Zhang, L; Uchiyama, T; Eckman, JR; Orringer, EP; Ashley-Koch, AE; Vance, JM; Telen, MJ
MLA Citation
De Castro, LM, Jonassaint, J, Rainey, S, Motley, R, Jones, S, Galloway, J, Zhang, L, Uchiyama, T, Eckman, JR, Orringer, EP, Ashley-Koch, AE, Vance, JM, and Telen, MJ. "B-CAM/LU modifies sickle cell disease severity." November 2003.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
73
Issue
5
Publish Date
2003
Start Page
569
End Page
569

Recipient alloimmunization against bone marrow donor red cells in an infant with severe combined immunodeficiency (SCID)

Authors
Combs, MR; Allen, J; Buckley, R; Telen, MJ
MLA Citation
Combs, MR, Allen, J, Buckley, R, and Telen, MJ. "Recipient alloimmunization against bone marrow donor red cells in an infant with severe combined immunodeficiency (SCID)." September 2003.
Source
wos-lite
Published In
Transfusion
Volume
43
Issue
9
Publish Date
2003
Start Page
52A
End Page
52A

Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion.

The vasoocclusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) red blood cell (RBC) adhesion to the vascular wall. SS RBCs, but not unaffected (AA) RBCs, adhere avidly to multiple components of the vascular wall, including laminin. Here we report a novel role for epinephrine and cyclic adenosine monophosphate (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor, basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in SS RBCs and increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)-dependent manner, with the low-density population being the most responsive. Epinephrine-stimulated adhesion to laminin, mediated primarily via the beta 2-adrenergic receptor, occurred in SS RBC samples from 46% of patients and was blocked by recombinant, soluble BCAM/Lu, implicating this receptor as a target of cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS RBC adhesion by a cAMP-dependent pathway and suggest that components of this pathway, particularly PKA, the beta 2-adrenergic receptor, and BCAM/Lu, should be further explored as potential therapeutic targets to inhibit SS RBC adhesion.

Authors
Hines, PC; Zen, Q; Burney, SN; Shea, DA; Ataga, KI; Orringer, EP; Telen, MJ; Parise, LV
MLA Citation
Hines, PC, Zen, Q, Burney, SN, Shea, DA, Ataga, KI, Orringer, EP, Telen, MJ, and Parise, LV. "Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion." Blood 101.8 (April 15, 2003): 3281-3287.
PMID
12506027
Source
pubmed
Published In
Blood
Volume
101
Issue
8
Publish Date
2003
Start Page
3281
End Page
3287
DOI
10.1182/blood-2001-12-0289

Erythrocyte adhesion in sickle cell disease.

The vaso-occlusive process in patients with sickle cell disease is complex and is likely to involve interactions between hemoglobin S red blood cells (SS RBCs) and vascular endothelium, as well as between SS RBCs and leukocytes. Vaso-occlusive events lead to recurrent pain and a wide spectrum of end-organ damage, including pulmonary hypertension and renal failure. However, the triggers inducing adhesion and vaso-occlusion are only now being elucidated. Investigators have characterized the ability of a number of RBC surface structures to adhere to both endothelial cells and components of the subendothelial extracellular matrix. In addition, evidence is accumulating to suggest that SS RBC adhesion receptors undergo activation under physiologic conditions. An understanding of these mechanisms at the molecular level should ultimately allow development of new preventive and treatment strategies to abrogate vaso-occlusive events.

Authors
Parise, LV; Telen, MJ
MLA Citation
Parise, LV, and Telen, MJ. "Erythrocyte adhesion in sickle cell disease." Curr Hematol Rep 2.2 (March 2003): 102-108. (Review)
PMID
12901140
Source
pubmed
Published In
Current hematology reports
Volume
2
Issue
2
Publish Date
2003
Start Page
102
End Page
108

Paroxysmal cold hemoglobinuria and cardiopulmonary bypass.

Paroxysmal cold hemoglobinuria, a cold-reactive autoimmune disease associated with the Donath-Landsteiner antibody, has not been described in patients undergoing cardiac surgery. We report a case of mitral valve replacement in a woman with a positive Donath-Landsteiner antibody and a history of recurrent hemolysis and hemoglobinuria secondary to cold exposure. Successful perioperative management is described, as is a discussion of paroxysmal cold hemoglobinuria.

Authors
Kypson, AP; Warner, JJ; Telen, MJ; Milano, CA
MLA Citation
Kypson, AP, Warner, JJ, Telen, MJ, and Milano, CA. "Paroxysmal cold hemoglobinuria and cardiopulmonary bypass." Ann Thorac Surg 75.2 (February 2003): 579-581.
PMID
12607681
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
75
Issue
2
Publish Date
2003
Start Page
579
End Page
581

Modulation by epinephrine of PKA-dependent signaling pathways in sickle red blood cells induces activation of LW binding to endothelial cell alpha v beta 3 integrin.

Authors
Zennadi, R; Hines, PM; De Castro, LM; Cartron, JP; Parise, LV; Telen, MJ
MLA Citation
Zennadi, R, Hines, PM, De Castro, LM, Cartron, JP, Parise, LV, and Telen, MJ. "Modulation by epinephrine of PKA-dependent signaling pathways in sickle red blood cells induces activation of LW binding to endothelial cell alpha v beta 3 integrin." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
118A
End Page
118A

Relationship of sickle red blood cell laminin binding to disease activity.

Authors
De Castro, LM; Palmer, L; Jonassaint, JC; Telen, MJ
MLA Citation
De Castro, LM, Palmer, L, Jonassaint, JC, and Telen, MJ. "Relationship of sickle red blood cell laminin binding to disease activity." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
450A
End Page
451A

Donor chimerism after T-Cell depleted (TCD)-Non-Myeloablative allogeneic SCT (NST) in hemoglobinopathies.

Authors
Isola, LM; Chao, JN; Weinberg, S; Fruchtman, SM; Atweh, G; McCune, S; Telen, MJ; DeCastro, LM; Long, GD; Vredenburgh, JJ; Gasparetto, C; Liesveld, J; Rowley, S; Rizzieri, DA
MLA Citation
Isola, LM, Chao, JN, Weinberg, S, Fruchtman, SM, Atweh, G, McCune, S, Telen, MJ, DeCastro, LM, Long, GD, Vredenburgh, JJ, Gasparetto, C, Liesveld, J, Rowley, S, and Rizzieri, DA. "Donor chimerism after T-Cell depleted (TCD)-Non-Myeloablative allogeneic SCT (NST) in hemoglobinopathies." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
401B
End Page
402B

B-CAM/LU mediates laminin-independent cell-cell adhesion under both static and flow conditions.

Authors
Qin, Z; Cho, J; Lekwauwa, RE; Zennadi, R; Telen, MJ
MLA Citation
Qin, Z, Cho, J, Lekwauwa, RE, Zennadi, R, and Telen, MJ. "B-CAM/LU mediates laminin-independent cell-cell adhesion under both static and flow conditions." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
451A
End Page
451A

Delayed transfusion reactions and allo- and autoantibody production in sickle cell patients following erythrocytapheresis.

Authors
Combs, MR; Decastro, CM; Telen, MJ
MLA Citation
Combs, MR, Decastro, CM, and Telen, MJ. "Delayed transfusion reactions and allo- and autoantibody production in sickle cell patients following erythrocytapheresis." September 2002.
Source
wos-lite
Published In
Transfusion
Volume
42
Issue
9
Publish Date
2002
Start Page
26S
End Page
26S

Red cell antigens as functional molecules and obstacles to transfusion.

Blood group antigens (BGAs) can act as functional molecules but also can evoke autoantibodies and alloantibodies, causing autoimmune hemolytic anemia, hemolytic disease of the newborn and hemolytic transfusion reactions. In Section I, Dr. Marilyn Telen discusses physiologic and pathologic functions of RBC BGA-bearing molecules. She reviews some associations of BGAs with RBC membrane integrity and hemolytic anemia; association of BGAs with enzymatic and transport functions; and adhesion molecules expressed by RBCs, especially with reference to their pathophysiological role in sickle cell disease. In Section II, Dr. Lawrence Petz discusses the problems of providing blood for patients who have RBC autoantibodies. He provides an algorithm for excluding the presence of "hidden" alloantibodies, when all units appear to be incompatible due to the autoantibody. He emphasizes that clinicians should be aware of these approaches and not accept "the least incompatible unit." In Section III, Dr. George Garratty describes two processes, in development, that produce RBCs that result in RBCs that can be described as "universal" donor or "stealth" RBCs. The first process involves changing group A, B, or AB RBCs into group O RBCs by removing the immunospecific sugars responsible for A and B specificity by using specific enzymes. The second process involves covering all BGAs on the RBC surface using polyethylene glycol (PEG). Results of in vitro and in vivo studies on these modified RBCs are discussed.

Authors
Garratty, G; Telen, MJ; Petz, LD
MLA Citation
Garratty, G, Telen, MJ, and Petz, LD. "Red cell antigens as functional molecules and obstacles to transfusion." Hematology Am Soc Hematol Educ Program (2002): 445-462. (Review)
PMID
12446436
Source
pubmed
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Publish Date
2002
Start Page
445
End Page
462

Red cell signaling pathways cause increased sickle cell adhesion to non-activated endothelial cells.

Authors
Zennadi, R; Telen, MJ
MLA Citation
Zennadi, R, and Telen, MJ. "Red cell signaling pathways cause increased sickle cell adhesion to non-activated endothelial cells." BLOOD 98.11 (November 16, 2001): 484A-484A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
484A
End Page
484A

Sickle red cell B-CAM/LU mediates adhesion to multiple sites of laminin under different conditions.

Authors
Zen, Q; Twyman, CA; Telen, MJ
MLA Citation
Zen, Q, Twyman, CA, and Telen, MJ. "Sickle red cell B-CAM/LU mediates adhesion to multiple sites of laminin under different conditions." BLOOD 98.11 (November 16, 2001): 484A-485A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
484A
End Page
485A

Principles and problems of transfusion in sickle cell disease.

Sickle cell disease (SCD) is associated with red blood cell (RBC) abnormalities and moderate to severe anemia, and blood transfusion is naturally a mainstay of treatment. However, transfusion therapy for SCD may incur special and distinctive adverse effects. Thus, it is important to understand the indications for and goals of transfusion therapy and to be aware of the potential side effects of therapy. Years of unsystematic clinical observations, followed by more carefully designed and in some cases randomized studies, have contributed substantially to our knowledge of transfusion therapy in SCD. However, much remains unknown and areas of controversy persist. In addition, serologic barriers pose enduring roadblocks to the optimization of transfusion therapy for patients with SCD, and the syndrome of massive hemolytic transfusion reactions and hyperhemolysis in SCD persists as a life-threatening complication for which appropriate clinical management is not yet defined.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Principles and problems of transfusion in sickle cell disease." Semin Hematol 38.4 (October 2001): 315-323. (Review)
PMID
11605166
Source
pubmed
Published In
Seminars in Hematology
Volume
38
Issue
4
Publish Date
2001
Start Page
315
End Page
323

Antibodies exhibiting dosage in gel

Authors
Jewett-Keefe, B; Combs, MR; Telen, MJ
MLA Citation
Jewett-Keefe, B, Combs, MR, and Telen, MJ. "Antibodies exhibiting dosage in gel." TRANSFUSION 41.9 (September 2001): 107S-107S.
Source
wos-lite
Published In
Transfusion
Volume
41
Issue
9
Publish Date
2001
Start Page
107S
End Page
107S

An unusual Rh antibody apparently reactive with an epitope encoded by RHD exon 2

Authors
Combs, MR; Jewett-Keefe, B; Telen, MJ
MLA Citation
Combs, MR, Jewett-Keefe, B, and Telen, MJ. "An unusual Rh antibody apparently reactive with an epitope encoded by RHD exon 2." TRANSFUSION 41.9 (September 2001): 10S-10S.
Source
wos-lite
Published In
Transfusion
Volume
41
Issue
9
Publish Date
2001
Start Page
10S
End Page
10S

The use of polyethylene glycol in adsorptions: More evidence that antibodies may be missed

Authors
Combs, MR; Eveland, D; Jewett-Keefe, B; Telen, MJ
MLA Citation
Combs, MR, Eveland, D, Jewett-Keefe, B, and Telen, MJ. "The use of polyethylene glycol in adsorptions: More evidence that antibodies may be missed." TRANSFUSION 41.9 (September 2001): 30S-30S.
Source
wos-lite
Published In
Transfusion
Volume
41
Issue
9
Publish Date
2001
Start Page
30S
End Page
30S

Molecular defects underlying the Kell null phenotype.

Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5' splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5' splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.

Authors
Lee, S; Russo, DC; Reiner, AP; Lee, JH; Sy, MY; Telen, MJ; Judd, WJ; Simon, P; Rodrigues, MJ; Chabert, T; Poole, J; Jovanovic-Srzentic, S; Levene, C; Yahalom, V; Redman, CM
MLA Citation
Lee, S, Russo, DC, Reiner, AP, Lee, JH, Sy, MY, Telen, MJ, Judd, WJ, Simon, P, Rodrigues, MJ, Chabert, T, Poole, J, Jovanovic-Srzentic, S, Levene, C, Yahalom, V, and Redman, CM. "Molecular defects underlying the Kell null phenotype." J Biol Chem 276.29 (July 20, 2001): 27281-27289.
PMID
11375401
Source
pubmed
Published In
The Journal of biological chemistry
Volume
276
Issue
29
Publish Date
2001
Start Page
27281
End Page
27289
DOI
10.1074/jbc.M103433200

Use of red blood cell units containing alloantibodies (multiple letters)

Authors
Staley, JC; Combs, MR; Bennett, DH; Telen, MJ
MLA Citation
Staley, JC, Combs, MR, Bennett, DH, and Telen, MJ. "Use of red blood cell units containing alloantibodies (multiple letters)." Immunohematology 17.2 (2001): 58--.
Source
scival
Published In
Immunohematology
Volume
17
Issue
2
Publish Date
2001
Start Page
58-

Cardiac metastasis from a transitional cell carcinoma: a case report.

We report the case of a patient with a metastatic tumor in the right ventricle, apparently derived from a transitional cell carcinoma. The patient presented with severe hypoxemia as a result of right-to-left shunt due to the position of the tumor and a patent foramen ovale. The clinical course of this case is presented and the pathophysiology of the physiological effects caused by the metastatic tumor is discussed. The literature concerning cardiac metastases is reviewed.

Authors
Lin, WC; Telen, MJ
MLA Citation
Lin, WC, and Telen, MJ. "Cardiac metastasis from a transitional cell carcinoma: a case report." Med Oncol 17.2 (May 2000): 147-150.
PMID
10871822
Source
pubmed
Published In
Medical Oncology
Volume
17
Issue
2
Publish Date
2000
Start Page
147
End Page
150

Red blood cell surface adhesion molecules: their possible roles in normal human physiology and disease.

Human erythrocytes express a relatively large number of known adhesion receptors, despite the fact that red blood cells (RBCs) are generally considered to be nonadhesive for endothelial cell surfaces. Some of these adhesion receptors are expressed by many other tissues, while others have more limited tissue distribution. Some adhesion receptors, including CD36 and VLA-4, are only expressed by immature erythroid cells, while others are present on mature erythrocytes. The structure and function of these proteins is reviewed here. LW, CD36, CD58, and CD147 have been shown in other tissues to mediate cell-cell interaction. Other receptors, such as CD44, VLA-4, and B-CAM/LU, can mediate adhesion to components of extracellular matrix. In addition, their roles in normal erythropolesis, as well as in the pathophysiology of human disease, are summarized. The most convincing evidence for a pathophysiologic role for any of these receptors on erythrocytes comes from studies of cells from patients homozygous for hemoglobin S, as RBC adhesion is thought to contribute to vaso-occlusion. Thus, receptors such as B-CAM/LU may become targets for future therapy aimed at preventing or ameliorating this thrombotic process.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Red blood cell surface adhesion molecules: their possible roles in normal human physiology and disease." Semin Hematol 37.2 (April 2000): 130-142. (Review)
PMID
10791882
Source
pubmed
Published In
Seminars in Hematology
Volume
37
Issue
2
Publish Date
2000
Start Page
130
End Page
142

Large-scale use of red blood cell units containing alloantibodies.

Many transfusion services are reluctant to accept red blood cell (RBC) units containing antibodies. We evaluated the impact of accepting routine shipments of our region's inventory of alloantibody- positive RBC units over a 4-month period. All patients' samples received up to 30 days after transfusion of such units were evaluated for the presence of passively acquired antibody, and labor and reagent costs were determined. During the study period, we received 259 alloantibody-containing RBC units, and 253 of these were transfused to 187 patients. Follow-up samples were received on 99 of these 187 patients, and 10 of these patients had detectable passive antibody in posttransfusion antibody screening tests. Two patients had anti-C and -D and eight patients had anti-D. Due to our negotiation of a small discount for antibody-containing units and the use of 20 units based on labeled phenotype rather than antigen typing in our laboratory, we experienced a net savings of $3814 over the 4-month period. This savings was achieved despite some additional costs incurred, including costs of data entry and additional testing on patients' samples. We concluded that large-scale use of RBC units from donors with alloantibodies is safe and likely to have a minimal impact on a busy transfusion service's workload and costs. Furthermore, nationwide use of such units would help alleviate projected blood shortages.

Authors
Combs, MR; Bennett, DH; Telen, MJ
MLA Citation
Combs, MR, Bennett, DH, and Telen, MJ. "Large-scale use of red blood cell units containing alloantibodies." Immunohematology 16.3 (2000): 120-123.
PMID
15373616
Source
pubmed
Published In
Immunohematology / American Red Cross
Volume
16
Issue
3
Publish Date
2000
Start Page
120
End Page
123

Laminin binding and B-CAM/LU expression by high and low density reticulocytes vs mature red cells in sickle cell disease.

Authors
Zen, Q; Twyman, CA; Telen, MJ
MLA Citation
Zen, Q, Twyman, CA, and Telen, MJ. "Laminin binding and B-CAM/LU expression by high and low density reticulocytes vs mature red cells in sickle cell disease." BLOOD 94.10 (November 15, 1999): 675A-675A.
Source
wos-lite
Published In
Blood
Volume
94
Issue
10
Publish Date
1999
Start Page
675A
End Page
675A

Management of massive delayed hemolytic transfusion reactions in patients with sickle cell disease.

Authors
Telen, MJ; Combs, M
MLA Citation
Telen, MJ, and Combs, M. "Management of massive delayed hemolytic transfusion reactions in patients with sickle cell disease." TRANSFUSION 39.10 (October 1999): 97S-97S.
Source
wos-lite
Published In
Transfusion
Volume
39
Issue
10
Publish Date
1999
Start Page
97S
End Page
97S

Identification and characterization of another non-integrin IgSF membrane protein receptor for laminin

Authors
Zen, Q; Riddle, ME; Fong, AM; Patel, DD; Paulsen, DM; Truskey, G; Telen, MJ
MLA Citation
Zen, Q, Riddle, ME, Fong, AM, Patel, DD, Paulsen, DM, Truskey, G, and Telen, MJ. "Identification and characterization of another non-integrin IgSF membrane protein receptor for laminin." FASEB JOURNAL 13.7 (April 23, 1999): A1360-A1360.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
13
Issue
7
Publish Date
1999
Start Page
A1360
End Page
A1360

Critical factors in basal cell adhesion molecule/lutheran-mediated adhesion to laminin.

Basal cell adhesion molecule (B-CAM) and Lutheran (LU) are two spliceoforms of a single immunoglobulin superfamily protein containing five Ig domains and comprise the sickle (SS) red cell receptor for laminin. We have now analyzed laminin binding to murine erythroleukemia cells transfected with various human B-CAM/LU constructs. B-CAM and LU bound equally well to laminin, indicating that the longer cytoplasmic tail of LU is not required for binding. However, binding of soluble laminin did require the presence of the membrane-proximal fifth immunoglobulin superfamily (IgSF) domain of LU, while deletion of IgSF domains 1, 2, 3, or 4 individually or together did not abrogate laminin binding. Under flow conditions, MEL cells expressing B-CAM, LU, and LU lacking domains 1, 2, 3, or 4 adhered to immobilized laminin with critical shear stresses over 10 dynes/cm2. However, MEL cells expressing LU lacking domain 5 bound to laminin poorly (critical shear stress = 2.3 dynes/cm2). Moreover, expression of only IgSF domain 5 of LU was sufficient to mediate MEL cell adhesion to immobilized laminin (critical shear stress >10 dynes/cm2). Finally, Scatchard analysis showed that SS red cells had an average of 67% more B-CAM/LU than normal red cells, and low density red cells from sickle cell disease patients expressed 40-55% more B-CAM/LU than high density SS red cells. B-CAM/LU copy number thus may also play a role in the abnormal adhesion of SS red cells to laminin.

Authors
Zen, Q; Cottman, M; Truskey, G; Fraser, R; Telen, MJ
MLA Citation
Zen, Q, Cottman, M, Truskey, G, Fraser, R, and Telen, MJ. "Critical factors in basal cell adhesion molecule/lutheran-mediated adhesion to laminin." J Biol Chem 274.2 (January 8, 1999): 728-734.
PMID
9873008
Source
pubmed
Published In
The Journal of biological chemistry
Volume
274
Issue
2
Publish Date
1999
Start Page
728
End Page
734

Caring for patients with sickle cell disease in North Carolina.

Authors
Telen, MJ; Harris, G; Whitworth, E
MLA Citation
Telen, MJ, Harris, G, and Whitworth, E. "Caring for patients with sickle cell disease in North Carolina." N C Med J 60.1 (January 1999): 14-17.
PMID
9951281
Source
pubmed
Published In
North Carolina Medical Journal
Volume
60
Issue
1
Publish Date
1999
Start Page
14
End Page
17

Large-scale use of red blood cell units containing alloantibodies.

Authors
Combs, MR; Bennett, DH; Telen, MJ
MLA Citation
Combs, MR, Bennett, DH, and Telen, MJ. "Large-scale use of red blood cell units containing alloantibodies." TRANSFUSION 38.10 (October 1998): 69S-69S.
Source
wos-lite
Published In
Transfusion
Volume
38
Issue
10
Publish Date
1998
Start Page
69S
End Page
69S

Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.

Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors.

Authors
Udani, M; Zen, Q; Cottman, M; Leonard, N; Jefferson, S; Daymont, C; Truskey, G; Telen, MJ
MLA Citation
Udani, M, Zen, Q, Cottman, M, Leonard, N, Jefferson, S, Daymont, C, Truskey, G, and Telen, MJ. "Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin." J Clin Invest 101.11 (June 1, 1998): 2550-2558.
PMID
9616226
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
101
Issue
11
Publish Date
1998
Start Page
2550
End Page
2558
DOI
10.1172/JCI1204

Erratum: (The Journal of Clinical Investigation (June 1998) 101:11 (2550-2558))

Authors
Udani, M; Zen, Q; Cottman, M; Leonard, N; Jefferson, S; Daymont, C; Truskey, G; Telen, MJ
MLA Citation
Udani, M, Zen, Q, Cottman, M, Leonard, N, Jefferson, S, Daymont, C, Truskey, G, and Telen, MJ. "Erratum: (The Journal of Clinical Investigation (June 1998) 101:11 (2550-2558))." Journal of Clinical Investigation 102.1 (1998): 269--.
Source
scival
Published In
Journal of Clinical Investigation
Volume
102
Issue
1
Publish Date
1998
Start Page
269-

B-CAM/LU protein: A single IgSF domain and copy number but not the cytoplasmic region are critical for laminin binding.

Authors
Zen, Q; Udani, M; Cottman, M; Fraser, R; Truskey, G; Telen, MJ
MLA Citation
Zen, Q, Udani, M, Cottman, M, Fraser, R, Truskey, G, and Telen, MJ. "B-CAM/LU protein: A single IgSF domain and copy number but not the cytoplasmic region are critical for laminin binding." BLOOD 90.10 (November 15, 1997): 2685-2685.
Source
wos-lite
Published In
Blood
Volume
90
Issue
10
Publish Date
1997
Start Page
2685
End Page
2685

Leukocyte phenotypic changes in an in vitro model of ABO hemolytic transfusion reaction.

BACKGROUND: ABO antigen-antibody interaction in the presence of peripheral blood leukocytes (white cells) results in the production of a variety of proinflammatory cytokines. However, although tumor necrosis factor alpha has been shown to be derived at least primarily from monocytes, the range of cells activated by this process has not previously been reported. Therefore, changes in mononuclear cell surface antigen expression were studied, to determine which subsets of white cells appeared to be activated in the setting of ABO incompatibility. STUDY DESIGN AND METHODS: Group O peripheral blood mononuclear cells (PBMCs) were incubated in autologous plasma with group A or O red cells (RBCs) for up to 24 hours. White cell expression of activation and adhesion markers was measured at 2 and 24 hours by flow cytometry, using direct or indirect fluorescein or phycoerythrin labeling. RESULTS: Expression of lymphocyte activation markers CD25, CDw108, and CD109 was equivalent when PBMCs incubated with group A and O RBCs were compared. However, after 2 hours, mean fluorescence of CD14 on PBMCs incubated with group A RBCs was 65 percent of that on PBMCs incubated with group O RBCs and remained similarly decreased at 24 hours. CD44 expression was upregulated on PBMCs exposed to both group A and O RBCs, but it was increased significantly more on monocytes exposed to group A RBCs. The ability to bind hyaluronic acid was induced in approximately 42 percent of CD14+ monocytes exposed to group A RBCs but in no cells exposed to group O RBCs. CONCLUSION: Downregulation of CD14 and increased binding of hyaluronic acid reflects monocyte activation in this model. No evidence of lymphocyte activation was found, supporting the hypothesis that ABO transfusion reactions primarily activate monocytes.

Authors
Udani, M; Rao, N; Telen, MJ
MLA Citation
Udani, M, Rao, N, and Telen, MJ. "Leukocyte phenotypic changes in an in vitro model of ABO hemolytic transfusion reaction." Transfusion 37.9 (September 1997): 904-909.
PMID
9308635
Source
pubmed
Published In
Transfusion
Volume
37
Issue
9
Publish Date
1997
Start Page
904
End Page
909

Expression of cell adhesion molecule CD44 in primary tumors of the liver: an immunohistochemical study.

CD44, a widely distributed integral membrane protein, has been implicated in tumor invasion and metastatic spread in some human carcinomas and lymphomas. In this study, 35 cases of hepatocellular carcinoma from 32 patients (11 cholangiocarcinomas, 9 hepatic adenomas, and 5 cases of focal nodular hyperplasia, a non-neoplastic lesion) were examined by immunohistochemical methods for expression of CD44. The mouse monoclonal antibody A3D8 was used on formalin-fixed, paraffin-embedded tissue; this antibody does not distinguish between standard CD44 and splice variants. Positive membrane staining was seen in 13 of 35 cases of hepatocellular carcinoma (12 of 32 patients), 8 of 11 cases of cholangiocarcinoma, and 1 of 9 cases of hepatic adenoma. The strongest staining for CD44 was seen in two cases of fibrolamellar carcinoma, but CD44 expression was otherwise not related to degree of tumor differentiation. All five cases of focal nodular hyperplasia were negative for CD44. In non-neoplastic liver, hepatocytes were negative; sinusoidal lining cells and portal lymphocytes were positive; bile ducts and proliferating bile ductules were focally positive in some cases. Anatomic stage at time of presentation was similar in both groups of patients, with most patients presenting with stage III or IV disease. A trend towards slightly longer survival in patients whose hepatocellular carcinomas were CD44 negative was noted. These results show that aberrant CD44 expression is present in a subset of hepatocellular carcinomas and in most cholangio-carcinomas. The relationship between CD44 expression and tumor spread is unclear in this group of tumors, but is unlikely to be a simple association between CD44 expression and metastatic potential.

Authors
Washington, K; Telen, MJ; Gottfried, MR
MLA Citation
Washington, K, Telen, MJ, and Gottfried, MR. "Expression of cell adhesion molecule CD44 in primary tumors of the liver: an immunohistochemical study." Liver 17.1 (February 1997): 17-23.
PMID
9062875
Source
pubmed
Published In
Liver
Volume
17
Issue
1
Publish Date
1997
Start Page
17
End Page
23

Coordinator's report--section 2D3.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Coordinator's report--section 2D3." Transfus Clin Biol 4.1 (1997): 137-138.
PMID
9095520
Source
pubmed
Published In
Transfusion Clinique et Biologique
Volume
4
Issue
1
Publish Date
1997
Start Page
137
End Page
138

BCAM/LU protein: A novel laminin receptor overexpressed by sickle erythrocytes

Authors
Udani, M; Jefferson, S; Daymont, C; Zen, Q; Telen, MJ
MLA Citation
Udani, M, Jefferson, S, Daymont, C, Zen, Q, and Telen, MJ. "BCAM/LU protein: A novel laminin receptor overexpressed by sickle erythrocytes." BLOOD 88.10 (November 15, 1996): 13-13.
Source
wos-lite
Published In
Blood
Volume
88
Issue
10
Publish Date
1996
Start Page
13
End Page
13

Biologic functions of blood group antigens.

In the past few years, we have learned a great deal about the biologic function of structures bearing blood group antigens. Some blood group antigen-bearing proteins function as major transport channels within the erythrocyte membrane; these include the anion transporter (band 3: Diego and Wright antigens), the water channel (aquaporin: Colton antigens), and the urea transporter (Kidd antigens). At least two erythrocyte blood group antigen proteins have complement regulatory functions: the complement receptor type 1 (CR1, CD35: Knops antigens) and decay accelerating factor (DAF, CD55: Cromer antigens). Some blood group antigens reside on proteins with known receptor functions, such as the chemokine receptor (Duffy) and the hyaluronan receptor (Indian). The Cartwright antigens reside on an enzyme, acetylcholinesterase, and the Kell antigens reside on a protein that belongs to the CALLA-related family of neutral metalloproteinases. Finally, some blood group antigens reside on proteins that serve crucial structural functions necessary to normal erythrocyte lifespan and morphology. These proteins include band 3, glycophorins C/D (bearing the Gerbich antigens), and the Rh proteins. Both oligosaccharide and protein blood group antigens may act as receptors for bacterial, viral, and parasitic infectious agents.

Authors
Mudad, R; Telen, MJ
MLA Citation
Mudad, R, and Telen, MJ. "Biologic functions of blood group antigens." Curr Opin Hematol 3.6 (November 1996): 473-479. (Review)
PMID
9372120
Source
pubmed
Published In
Current Opinion in Hematology
Volume
3
Issue
6
Publish Date
1996
Start Page
473
End Page
479

Erythrocyte blood group antigens: polymorphisms of functionally important molecules.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Erythrocyte blood group antigens: polymorphisms of functionally important molecules." Semin Hematol 33.4 (October 1996): 302-314. (Review)
PMID
8916304
Source
pubmed
Published In
Seminars in Hematology
Volume
33
Issue
4
Publish Date
1996
Start Page
302
End Page
314

Erythroid-specific regulation of the CD44 in antigen gene promoter.

Authors
Cobourn, SD; Telen, MJ
MLA Citation
Cobourn, SD, and Telen, MJ. "Erythroid-specific regulation of the CD44 in antigen gene promoter." TRANSFUSION 36.9 (September 1996): S189-S189.
Source
wos-lite
Published In
Transfusion
Volume
36
Issue
9
Publish Date
1996
Start Page
S189
End Page
S189

Expression of human blood group antigens by human and murine cell lines.

Authors
Zervos, FC; Katz, R; Udani, M; Telen, MJ
MLA Citation
Zervos, FC, Katz, R, Udani, M, and Telen, MJ. "Expression of human blood group antigens by human and murine cell lines." TRANSFUSION 36.9 (September 1996): S190-S190.
Source
wos-lite
Published In
Transfusion
Volume
36
Issue
9
Publish Date
1996
Start Page
S190
End Page
S190

Introduction of the term ''partial D''

Authors
Issitt, PD; Telen, MJ
MLA Citation
Issitt, PD, and Telen, MJ. "Introduction of the term ''partial D''." TRANSFUSION 36.8 (August 1996): 761-762.
Source
wos-lite
Published In
Transfusion
Volume
36
Issue
8
Publish Date
1996
Start Page
761
End Page
762

A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding.

CD44 is a widely expressed integral membrane protein that acts as a receptor for hyaluronan (HA) and is proposed to be important to cell-extracellular matrix interaction. The Indian (In) blood group antigens reside on CD44, and most individuals express the Inb antigen. Homozygosity for the Ina allele occurs as a rare event and is associated with production of alloantibody to the common Inb antigen after transfusion or pregnancy. The present study demonstrates that a single point mutation (G252 --> C) causes an Arg46 --> Pro substitution, which is responsible for the Inb/Ina polymorphism. Additional mutations were found in In(a+b-) cDNA but were not necessary to the antigenic phenotype as determined in site-directed mutagenesis studies. In studies using CD44 chimeric constructs, Arg46 has previously been shown to be crucial for maintenance of HA-binding ability to a CD44 peptide. However, the present study demonstrates that the Arg46 --> Pro substitution does not reduce HA binding to the intact CD44 protein, which contains two proposed extracellular HA-binding motifs. Down-regulation of HA binding to In(a+b-) CD44 by anti-CD44 monoclonal antibody (mAb) ligands, however, was weakened, although all mAbs tested bound In(a+b-) and In(a-b+) CD44 equally well. Competitive inhibition studies using human anti-Inb also showed that some mAbs that inhibit HA binding to CD44 may do so by interacting with a domain separate from, but affecting the structure of, the Inb epitope.

Authors
Telen, MJ; Udani, M; Washington, MK; Levesque, MC; Lloyd, E; Rao, N
MLA Citation
Telen, MJ, Udani, M, Washington, MK, Levesque, MC, Lloyd, E, and Rao, N. "A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding." J Biol Chem 271.12 (March 22, 1996): 7147-7153.
PMID
8636151
Source
pubmed
Published In
The Journal of biological chemistry
Volume
271
Issue
12
Publish Date
1996
Start Page
7147
End Page
7153

D, weak D (Du), and partial D: the molecular story unfolds.

Authors
Issitt, PD; Telen, MJ
MLA Citation
Issitt, PD, and Telen, MJ. "D, weak D (Du), and partial D: the molecular story unfolds." Transfusion 36.2 (February 1996): 97-100.
PMID
8614975
Source
pubmed
Published In
Transfusion
Volume
36
Issue
2
Publish Date
1996
Start Page
97
End Page
100

Erythroid progenitors express a CD44 variant with reduced hyaluronic acid binding ability and reduced expression of the epitope associated with Hemophilus influenzae hemagglutination

Authors
Udani, M; Rao, N; Cobourn, S; Licker, J; Kurtzberg, J; Telen, MJ
MLA Citation
Udani, M, Rao, N, Cobourn, S, Licker, J, Kurtzberg, J, and Telen, MJ. "Erythroid progenitors express a CD44 variant with reduced hyaluronic acid binding ability and reduced expression of the epitope associated with Hemophilus influenzae hemagglutination." BLOOD 86.10 (November 15, 1995): 1876-1876.
Source
wos-lite
Published In
Blood
Volume
86
Issue
10
Publish Date
1995
Start Page
1876
End Page
1876

Modulation of hyaluronan binding to CD44H.

Authors
Udani, M; Rao, N; Telen, MJ
MLA Citation
Udani, M, Rao, N, and Telen, MJ. "Modulation of hyaluronan binding to CD44H." BLOOD 86.10 (November 15, 1995): 1877-1877.
Source
wos-lite
Published In
Blood
Volume
86
Issue
10
Publish Date
1995
Start Page
1877
End Page
1877

JMH variants: serologic, clinical, and biochemical analyses in two cases.

BACKGROUND: JMH is a high-frequency red cell blood group antigen that resides on a 76- to 80-kDa glycosylphosphatidylinositol-linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH-variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH-variant antigen and produced alloanti-JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies and human antibodies to JMH were used in hemagglutination, radioimmunoassay, and Western blot testing of red cells from two JMH-variant patients; antiserum from one of these patients was also used in biochemical studies. In addition, in vivo survival of JMH-positive red cells was studied in the same patient. RESULTS: Biochemically, both examples of red cells with the JMH-variant phenotype expressed a JMH protein with a molecular weight similar to that of the normal JMH protein. For both patients, family studies suggested an autosomal recessive pattern of inheritance. Survival study demonstrated reduced in vivo red cell survival in one patient. CONCLUSION: JMH-variant phenotypes express a protein of normal molecular weight and are inherited in an autosomal recessive pattern. Furthermore, individuals with this phenotype can produce clinically significant antibodies.

Authors
Mudad, R; Rao, N; Issitt, PD; Roy, RB; Combs, MR; Telen, MJ
MLA Citation
Mudad, R, Rao, N, Issitt, PD, Roy, RB, Combs, MR, and Telen, MJ. "JMH variants: serologic, clinical, and biochemical analyses in two cases." Transfusion 35.11 (November 1995): 925-930.
PMID
8604490
Source
pubmed
Published In
Transfusion
Volume
35
Issue
11
Publish Date
1995
Start Page
925
End Page
930

Clinical problem-solving: costly errors.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Clinical problem-solving: costly errors." N Engl J Med 333.16 (October 19, 1995): 1080-1081. (Letter)
PMID
7675064
Source
pubmed
Published In
The New England journal of medicine
Volume
333
Issue
16
Publish Date
1995
Start Page
1080
End Page
1081

AN ANTI-JMH CAUSING IN-VIVO RED-CELL DESTRUCTION

Authors
ISSITT, PD; COMBS, MR; MUDAD, R; TELEN, MJ
MLA Citation
ISSITT, PD, COMBS, MR, MUDAD, R, and TELEN, MJ. "AN ANTI-JMH CAUSING IN-VIVO RED-CELL DESTRUCTION." TRANSFUSION 35.10 (October 1995): S86-S86.
Source
wos-lite
Published In
Transfusion
Volume
35
Issue
10
Publish Date
1995
Start Page
S86
End Page
S86

LEUKOCYTE PHENOTYPIC CHANGES IN AN IN-VITRO MODEL OF ABO HEMOLYTIC TRANSFUSION REACTION

Authors
UDANI, M; RAO, N; TELEN, MJ
MLA Citation
UDANI, M, RAO, N, and TELEN, MJ. "LEUKOCYTE PHENOTYPIC CHANGES IN AN IN-VITRO MODEL OF ABO HEMOLYTIC TRANSFUSION REACTION." TRANSFUSION 35.10 (October 1995): S185-S185.
Source
wos-lite
Published In
Transfusion
Volume
35
Issue
10
Publish Date
1995
Start Page
S185
End Page
S185

DOMBROCK PROTEIN - A MONOCYTE ACTIVATION MARKER

Authors
UDANI, M; RAO, N; TELEN, MJ
MLA Citation
UDANI, M, RAO, N, and TELEN, MJ. "DOMBROCK PROTEIN - A MONOCYTE ACTIVATION MARKER." TRANSFUSION 35.10 (October 1995): S182-S182.
Source
wos-lite
Published In
Transfusion
Volume
35
Issue
10
Publish Date
1995
Start Page
S182
End Page
S182

ACANTHOCYTOSIS ASSOCIATED WITH PARTIAL CD44 DEFICIENCY

Authors
TELEN, MJ; NELSON, J; ANDERSON, N; KAPLAN, C; UDANI, M
MLA Citation
TELEN, MJ, NELSON, J, ANDERSON, N, KAPLAN, C, and UDANI, M. "ACANTHOCYTOSIS ASSOCIATED WITH PARTIAL CD44 DEFICIENCY." TRANSFUSION 35.10 (October 1995): S238-S238.
Source
wos-lite
Published In
Transfusion
Volume
35
Issue
10
Publish Date
1995
Start Page
S238
End Page
S238

EXPRESSION OF THE CELL-ADHESION MOLECULE CD44 IN PRIMARY TUMORS OF THE LIVER

Authors
WASHINGTON, MK; TELEN, MJ; GOTTFRIED, MR
MLA Citation
WASHINGTON, MK, TELEN, MJ, and GOTTFRIED, MR. "EXPRESSION OF THE CELL-ADHESION MOLECULE CD44 IN PRIMARY TUMORS OF THE LIVER." HEPATOLOGY 22.4 (October 1995): 1606-1606.
Source
wos-lite
Published In
Hepatology
Volume
22
Issue
4
Publish Date
1995
Start Page
1606
End Page
1606

Evidence that CDw108 membrane protein bears the JMH blood group antigen.

BACKGROUND: CDw108 is a cluster-of-differentiation antigen that resides on a glycosylphosphatidylinositol (GPI)-linked protein; it has not previously been shown to be expressed on red cells. JMH is a high-frequency red cell blood group antigen that resides on a GPI-linked protein of molecular weight similar to that bearing CDw108. The purpose of this study was to investigate whether CDw108 is expressed on red cells and whether it resides on the same membrane protein as does JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies to CDw108, MEM-121 and MEM-150, as well as a murine monoclonal antibody and human antibodies to JMH were used in radioimmunoassay, inhibition assay, Western blotting, and monoclonal antibody-specific immobilization of erythrocyte antigen assay. RESULTS: MEM-121 and MEM-150 were found to bind to red cells, and MEM-150 blocked binding of human anti-JMH to red cells. Anti-CDw108 and anti-JMH identified red cell membrane proteins that were of similar size and that were absent from JMH-negative red cells on Western blotting. MEM-150 and MEM-121 also immobilized the same protein that reacted with human anti-JMH. CONCLUSION: CDw108 is expressed on red cells and resides on the same GPI-linked membrane protein as does the JMH blood group antigen.

Authors
Mudad, R; Rao, N; Angelisova, P; Horejsi, V; Telen, MJ
MLA Citation
Mudad, R, Rao, N, Angelisova, P, Horejsi, V, and Telen, MJ. "Evidence that CDw108 membrane protein bears the JMH blood group antigen." Transfusion 35.7 (July 1995): 566-570.
PMID
7631388
Source
pubmed
Published In
Transfusion
Volume
35
Issue
7
Publish Date
1995
Start Page
566
End Page
570

Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol-anchored protein that carries Gregory, Holley, and Dombrock blood group antigens.

BACKGROUND: The high-frequency Hy and Gya antigens have been shown to reside on the same protein. Gy(a-) Hy-negative red cells are also Do(a-b-). A mouse monoclonal antibody, 5B10, was produced with specificity related to the human Gregory, Holley, and Dombrock blood group antigens. STUDY DESIGN AND METHODS: The antibody reacted in direct hemagglutination assays, and its specificity was investigated by radioimmunoassay, inhibition assay, and Western blotting. RESULTS: The 5B10 antibody failed to bind to abnormal paroxysmal nocturnal hemoglobinuria red cells and human erythroleukemia cell line K562, but it was weakly reactive with HEL cells. Red cells, but not other circulating hematopoietic cells, express the 5B10 antigen. The 5B10 antibody had a specificity similar but not identical to that of Gya. Gy(a-) Hy-negative red cells reacted extremely weakly with 5B10 antibody, but Gy(a-) Hy-negative red cells treated with a variety of proteases bound 5B10 antibody strongly. This suggests that these cells express a variant form of the protein recognized by 5B10. CONCLUSION: Identification of a monoclonal antibody to this glycosylphosphatidylinositol-linked protein opens a new avenue for investigation of the biochemistry, genetics, and function of the glycosylphosphatidylinositol-linked protein that bears the Gya, Hy, and Do antigens.

Authors
Rao, N; Udani, M; Nelson, J; Reid, ME; Telen, MJ
MLA Citation
Rao, N, Udani, M, Nelson, J, Reid, ME, and Telen, MJ. "Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol-anchored protein that carries Gregory, Holley, and Dombrock blood group antigens." Transfusion 35.6 (June 1995): 459-464.
PMID
7770894
Source
pubmed
Published In
Transfusion
Volume
35
Issue
6
Publish Date
1995
Start Page
459
End Page
464

Location of WESb on decay-accelerating factor.

Authors
Telen, MJ; Rao, N; Lublin, DM
MLA Citation
Telen, MJ, Rao, N, and Lublin, DM. "Location of WESb on decay-accelerating factor." Transfusion 35.3 (March 1995): 278-. (Letter)
PMID
7533342
Source
pubmed
Published In
Transfusion
Volume
35
Issue
3
Publish Date
1995
Start Page
278

Erythrocyte blood group antigens: not so simple after all.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Erythrocyte blood group antigens: not so simple after all." Blood 85.2 (January 15, 1995): 299-306. (Review)
PMID
7529059
Source
pubmed
Published In
Blood
Volume
85
Issue
2
Publish Date
1995
Start Page
299
End Page
306

Blood group antigens on complement receptor/regulatory proteins.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Blood group antigens on complement receptor/regulatory proteins." Transfus Med Rev 9.1 (January 1995): 20-28. (Review)
PMID
7536497
Source
pubmed
Published In
Transfusion Medicine Reviews
Volume
9
Issue
1
Publish Date
1995
Start Page
20
End Page
28

Identification of the Tcb allele of the Cromer blood group gene by PCR and RFLP analysis.

The Cromer blood group antigens reside on the complement regulatory protein, decay-accelerating factor (DAF). The Cromer system comprises 10 antigens, 3 of which are of low incidence. When an individual is homozygous for the allele encoding one of these low-incidence antigens, they are liable to produce an antibody to the antithetical high-frequency antigen if challenged by pregnancy or transfusion. These antibodies are often difficult to identify, because of the lack of readily available antigen-negative cells and typing sera. In blacks, about 5 percent of individuals carry the rare Tcb Cromer allele. We have shown that the presence of the low-incidence Tcb allele can be detected by polymerase chain reaction (PCR) amplification of a fragment of the gene encoding DAF, followed by allele-specific restriction enzyme digestion.

Authors
Udani, MN; Anderson, N; Rao, N; Telen, MJ
MLA Citation
Udani, MN, Anderson, N, Rao, N, and Telen, MJ. "Identification of the Tcb allele of the Cromer blood group gene by PCR and RFLP analysis." Immunohematology 11.1 (1995): 1-4.
PMID
15447069
Source
pubmed
Published In
Immunohematology / American Red Cross
Volume
11
Issue
1
Publish Date
1995
Start Page
1
End Page
4

Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal nocturnal hemoglobinuria.

Human erythrocyte cell surface molecules that are attached to the cell membrane by glycosyl-phosphatidylinositol (GPI) anchors include the complement regulatory proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), as well as the proteins that bear the Cartwright, Dombrock, and JMH blood group antigens. The acquired hematopoietic stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) results from the absence or marked deficiency in expression of GPI-anchored proteins in affected hematopoietic cells. PNH usually if not always results from a somatic mutation of an X-linked gene called PIG-A; the product of the PIG-A gene is a glycosyl transferase necessary for construction of the GPI anchor. DAF is a ubiquitously expressed protein present in many tissues, including gastrointestinal epithelia, corneal epithelia, and serosa of urinary and reproductive organs. DAF is a 70 kD glycoprotein containing complement regulatory short consensus repeats (SCRs); its gene is located in the regulation of complement activation (RCA) gene cluster on chromosome 1 and is about 40 kb in size. The Cromer blood group antigens, which reside on DAF, include 10 currently defined antigens, of which seven are of high incidence. The molecular basis of the Cr (a-) phenotype has been determined to be a single base pair substitution in DAF SCR4 (G-->C, leading to an ala193 to pro amino acid substitution). The Tc alpha antigen appears to be determined by the amino acid sequence of SCR1, with the Tc (a-b+) phenotype arising from a base pair substitution of G55-->T, leading to an arg18 to leu amino acid substitution. The null phenotype for Cromer antigens occurs when DAF is completely absent; only one example has been completely studied on the molecular level. That individual is homozygous for a point mutation in SCR1 (G314-->A) that creates a stop codon (TGA) in place of one normally encoding trp53 (TGG) and thus prevents further translation of the mRNA. The Dr(a-) phenotype expresses reduced quantities of DAF (approximately 40% of normal levels), as well as a polymorphism of DAF. Lack of the Dr alpha antigen has been proved to result from a single point mutation in SCR3 (C-->T in codon 165) that leads to a single amino acid substitution (ser-->leu). The Cartwright (Yt) antigens reside on acetylcholinesterase (AChE). In erythroid cells, a small exon that encodes the signal for attachment of the GPI anchor is retained in a tissue-specific process.(ABSTRACT TRUNCATED AT 400 WORDS)

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal nocturnal hemoglobinuria." Transfus Clin Biol 2.4 (1995): 277-290. (Review)
PMID
8542026
Source
pubmed
Published In
Transfusion Clinique et Biologique
Volume
2
Issue
4
Publish Date
1995
Start Page
277
End Page
290

Lutheran antigens, CD44-related antigens, and Lutheran regulatory genes.

The Lutheran (Lu) blood group antigens are a family of human erythrocyte antigens which reside on two closely-related erythrocyte integral membrane proteins. Sixteen Lutheran or so-called para-Lutheran antigens have thus far been described, and human antisera to many of them have been shown to immunoblot two proteins, of 78 and 85 kDa. Lu cDNA encodes an integral membrane protein of 597 amino acids that is a member of the Ig superfamily. Lu proteins comprise five Ig superfamily domains, along with a single transmembrane domain and a cytoplasmic domain of about 60 amino acids. The two proteins seen in biochemical studies of red cell membranes appear to be derived from 2 mRNA species that differ only in their 3' ends, suggesting that they arise from alternate splicing of a single preRNA. Three genetic backgrounds for the Lu(a-b-) [Lu null] phenotype have been described. A recessive Lu null phenotype is rarely observed as a result of homozygosity for two amorphic LU alleles. However, the most common Lu(a-b-) phenotype appears to be caused by an independently segregating, dominant gene, designated In (Lu), which inhibits expression of all Lutheran antigens to nearly undetectable levels. This gene also affects the expression of other cell surface proteins and blood group antigens that are genetically unlinked to the Lutheran locus, including CD44 and MER2. CD44, a member of the cartilage link family of proteins, bears the In and AnWj blood group antigens. A widely distributed protein CD44 is expressed at normal levels on all tissues except erythrocytes in the presence of the In (Lu) gene. A second Lutheran regulatory gene, XS2, is responsible for the third Lu(a-b-) phenotype, which exhibits an X-linked inheritance pattern. The XS2 gene down-regulates but does not abolish expression of LU genes and does not affect expression of CD44.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Lutheran antigens, CD44-related antigens, and Lutheran regulatory genes." Transfus Clin Biol 2.4 (1995): 291-301. (Review)
PMID
8542027
Source
pubmed
Published In
Transfusion Clinique et Biologique
Volume
2
Issue
4
Publish Date
1995
Start Page
291
End Page
301

EVIDENCE THAT CDW108 MEMBRANE-PROTEIN BEARS THE JMH BLOOD-GROUP ANTIGEN

Authors
MUDAD, R; RAO, N; ANGELISOVA, P; HOREJSI, V; TELEN, MJ
MLA Citation
MUDAD, R, RAO, N, ANGELISOVA, P, HOREJSI, V, and TELEN, MJ. "EVIDENCE THAT CDW108 MEMBRANE-PROTEIN BEARS THE JMH BLOOD-GROUP ANTIGEN." BLOOD 84.10 (November 15, 1994): A237-A237.
Source
wos-lite
Published In
Blood
Volume
84
Issue
10
Publish Date
1994
Start Page
A237
End Page
A237

Molecular mapping of the Cromer blood group Cra and Tca epitopes of decay accelerating factor: toward the use of recombinant antigens in immunohematology.

Cromer blood group antigens reside on the complement regulatory protein decay accelerating factor (DAF, CD55). This glycosyl-phosphatidylinositol-anchored glycoprotein is widely distributed, especially among cell types in contact with plasma. Numerous Cromer blood group antigens have been defined using alloantibodies induced by transfusion or pregnancy. However, few pairs of antithetical antigens have been described in this system, presumably because of the rarity of the low-frequency alleles. Analysis of polymerase chain reaction-amplified genomic DNA showed that the Cr(a-) phenotype has a Ala193-->Pro substitution in short consensus repeat 4 (SCR4) of DAF, and the Tc(a-b+) phenotype has a Arg18-->Leu substitution in SCR1 of DAF. The locations of Cra and Tca epitopes were confirmed by analysis of Chinese hamster ovary cell transfectants expressing a Cr(a-) allele-specific transfectant and a chimeric protein containing only SCR1 of DAF, respectively. Overall, these studies further show the usefulness of an approach based on recombinant proteins in mapping blood group antigen epitopes and identifying blood group antibodies.

Authors
Telen, MJ; Rao, N; Udani, M; Thompson, ES; Kaufman, RM; Lublin, DM
MLA Citation
Telen, MJ, Rao, N, Udani, M, Thompson, ES, Kaufman, RM, and Lublin, DM. "Molecular mapping of the Cromer blood group Cra and Tca epitopes of decay accelerating factor: toward the use of recombinant antigens in immunohematology." Blood 84.9 (November 1, 1994): 3205-3211.
PMID
7524769
Source
pubmed
Published In
Blood
Volume
84
Issue
9
Publish Date
1994
Start Page
3205
End Page
3211

Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas.

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. The expression of CD44 in 23 gastric adenocarcinoma and 12 peptic ulcer disease (PUD) resection specimens and gastric carcinoma cell lines HS746t and KATO III was examined by immunohistochemistry using the murine monoclonal antibody A3D8 on formalin-fixed, paraffin-embedded tissue or cells. Western blot analysis of whole cell lysates of KATO III and HS746t cells showed protein bands at 85 to 90 kd with KATO III cells expressing an additional band at 145 kd. In normal stomach gastric epithelium was negative. In PUD foveolar epithelium was focally positive, but staining did not correlate with the extent of gastritis. In carcinoma cases intensity of staining was progressively stronger comparing intestinal metaplasia with dysplasia with intramucosal carcinoma. Invasive carcinoma was invariably more strongly positive than dysplasia or intramucosal carcinoma. Twelve adenocarcinomas were weakly positive and 11 were strongly positive. The staining intensity of metastases (12 cases) was the same or weaker than the primary tumor. For the 12 patients whose carcinomas were weakly positive, mean length of survival for the six who died was 23.3 months. Five of the 11 patients whose carcinomas strongly expressed CD44 died within the study period with a mean length of survival of 11.0 months. A key consequence of CD44 overexpression in gastric carcinomas may be development of the invasive phenotype and strong expression may indicate a poorer prognosis.

Authors
Washington, K; Gottfried, MR; Telen, MJ
MLA Citation
Washington, K, Gottfried, MR, and Telen, MJ. "Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas." Hum Pathol 25.10 (October 1994): 1043-1049.
PMID
7523275
Source
pubmed
Published In
Human Pathology
Volume
25
Issue
10
Publish Date
1994
Start Page
1043
End Page
1049

DEMONSTRATION BY MONOCLONAL-ANTIBODY IMMOBILIZATION OF ERYTHROCYTE ANTIGENS AND DOT-BLOT THAT BOTH THE IN AND ANJW BLOOD-GROUP ANTIGENS RESIDE ON CD44

Authors
RAO, N; UDANI, M; TELEN, MJ
MLA Citation
RAO, N, UDANI, M, and TELEN, MJ. "DEMONSTRATION BY MONOCLONAL-ANTIBODY IMMOBILIZATION OF ERYTHROCYTE ANTIGENS AND DOT-BLOT THAT BOTH THE IN AND ANJW BLOOD-GROUP ANTIGENS RESIDE ON CD44." TRANSFUSION 34.10 (October 1994): S25-S25.
Source
wos-lite
Published In
Transfusion
Volume
34
Issue
10
Publish Date
1994
Start Page
S25
End Page
S25

EXPRESSION OF PHOSPHATIDYLINOSITOL-LINKED PROTEINS AND BLOOD-GROUP ANTIGENS IN DIABETIC-PATIENTS

Authors
WHITTAKER, DS; TELEN, MJ
MLA Citation
WHITTAKER, DS, and TELEN, MJ. "EXPRESSION OF PHOSPHATIDYLINOSITOL-LINKED PROTEINS AND BLOOD-GROUP ANTIGENS IN DIABETIC-PATIENTS." TRANSFUSION 34.10 (October 1994): S63-S63.
Source
wos-lite
Published In
Transfusion
Volume
34
Issue
10
Publish Date
1994
Start Page
S63
End Page
S63

FURTHER EVIDENCE USING MONOCLONAL-ANTIBODY IMMOBILIZATION OF ERYTHROCYTE ANTIGENS THAT THE HY, GY(A), AND DO(B) ANTIGENS RESIDE ON THE SAME PROTEIN

Authors
RAO, N; TELEN, MJ
MLA Citation
RAO, N, and TELEN, MJ. "FURTHER EVIDENCE USING MONOCLONAL-ANTIBODY IMMOBILIZATION OF ERYTHROCYTE ANTIGENS THAT THE HY, GY(A), AND DO(B) ANTIGENS RESIDE ON THE SAME PROTEIN." TRANSFUSION 34.10 (October 1994): S25-S25.
Source
wos-lite
Published In
Transfusion
Volume
34
Issue
10
Publish Date
1994
Start Page
S25
End Page
S25

MOLECULAR-GENETIC BASIS OF THE IN-A/B POLYMORPHISM

Authors
WASHINGTON, MK; UDANI, M; RAO, N; LLOYD, E; TELEN, MJ
MLA Citation
WASHINGTON, MK, UDANI, M, RAO, N, LLOYD, E, and TELEN, MJ. "MOLECULAR-GENETIC BASIS OF THE IN-A/B POLYMORPHISM." TRANSFUSION 34.10 (October 1994): S62-S62.
Source
wos-lite
Published In
Transfusion
Volume
34
Issue
10
Publish Date
1994
Start Page
S62
End Page
S62

Molecular basis of reduced or absent expression of decay-accelerating factor in Cromer blood group phenotypes.

The human erythrocyte blood group system Cromer consists of high-incidence and low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement activation on cell surfaces. In the Cromer phenotypes Dr(a-) and Inab there is reduced or absent expression of DAF, respectively. This study investigated the molecular basis of the reduced DAF expression by polymerase chain reaction amplification of genomic DNA and RNA/cDNA obtained from Epstein-Barr virus-transformed lymphoblastoid cell lines. Sequence analysis of the Inab propositus showed a single nucleotide substitution in exon 2 of the DAF gene and at the corresponding position in the cDNA, G314-->A resulting in Trp53-->Stop. This truncation near the amino terminus explains the complete absence of surface DAF in the Inab phenotype. A similar analysis was performed for two Dr(a-) individuals, including KZ, who was previously reported to be Inab phenotype but is now shown by immunochemical and serologic methods to be Dr(a-) phenotype. A single nucleotide change was found in exon 5 of the DAF gene, C649-->T resulting in Ser165-->Leu, which we had previously shown to lead to loss of the Dra epitope. However, two species of cDNA were found, one encoding full-length DAF with the single amino acid change and the more abundant species having a 44-nucleotide deletion. The 44 nucleotide deletion includes the single polymorphic site, which creates a cryptic branch point in the Dr(a-) allele that leads to use of a downstream cryptic acceptor splice site. This shifts the reading frame and leads to a premature stop codon that precludes membrane anchoring. Thus, the single point mutation in the Dr(a-) phenotype results in a novel use of alternative splicing and provides a molecular explanation for both the antigenicity and the reduced DAF expression seen in this phenotype.

Authors
Lublin, DM; Mallinson, G; Poole, J; Reid, ME; Thompson, ES; Ferdman, BR; Telen, MJ; Anstee, DJ; Tanner, MJ
MLA Citation
Lublin, DM, Mallinson, G, Poole, J, Reid, ME, Thompson, ES, Ferdman, BR, Telen, MJ, Anstee, DJ, and Tanner, MJ. "Molecular basis of reduced or absent expression of decay-accelerating factor in Cromer blood group phenotypes." Blood 84.4 (August 15, 1994): 1276-1282.
PMID
7519480
Source
pubmed
Published In
Blood
Volume
84
Issue
4
Publish Date
1994
Start Page
1276
End Page
1282

Tissue culture of epithelium derived from Barrett's oesophagus.

Barrett's oesophagus is a preneoplastic condition in which the squamous mucosa of the oesophagus is replaced by columnar epithelium. Epithelial cells of Barrett's oesophagus were isolated from resected oesophagus specimens by two methods not previously applied to the culture of Barrett's oesophagus cells. These techniques included trypsinisation of small fragments of mucosa, followed by plating in tissue culture dishes, and a direct tissue explant technique. A modified MCDB-153 growth medium was used. Primary trypsin technique cultures were plated on uncoated plastic, or plastic coated with type I collagen, type IV collagen, or fibronectin. Growth on type IV collagen and fibronectin plates was slower but produced less contamination from fibroblasts. By 20-40 days most cultures formed confluent monolayers made up of cells with epithelial morphology. The cells were cytokeratin positive, vimentin negative, and contained alcian blue positive vacuoles, confirming their epithelial origin and suggesting their derivation from Barrett's oesophagus. Electron microscopy showed tonofilaments, microvilli, and desmosomes. Cells proliferated through up to eight subcultures before growth slowed and cells showed senescent changes. This study shows that epithelial cells from Barrett's oesophagus can be grown by comparatively simple tissue culture techniques. These methods can provide sufficient material for a variety of molecular biology and biochemical studies of epithelial cells from Barrett's oesophagus.

Authors
Washington, K; Gottfried, MR; Telen, MJ
MLA Citation
Washington, K, Gottfried, MR, and Telen, MJ. "Tissue culture of epithelium derived from Barrett's oesophagus." Gut 35.7 (July 1994): 879-883.
PMID
8063213
Source
pubmed
Published In
Gut
Volume
35
Issue
7
Publish Date
1994
Start Page
879
End Page
883

EXPRESSION OF CD44 ISOFORMS DURING ERYTHROID-DIFFERENTIATION

Authors
COBOURN, SD; LICKER, JK; KURTZBERG, J; TELEN, MJ
MLA Citation
COBOURN, SD, LICKER, JK, KURTZBERG, J, and TELEN, MJ. "EXPRESSION OF CD44 ISOFORMS DURING ERYTHROID-DIFFERENTIATION." CLINICAL RESEARCH 42.2 (April 1994): A131-A131.
Source
wos-lite
Published In
Clinical Research
Volume
42
Issue
2
Publish Date
1994
Start Page
A131
End Page
A131

Recent advances in immunohematology.

Knowledge of the biochemistry and genetics of erythrocyte blood group antigens has been growing rapidly over the past several years. Last year, the molecular basis for the major Rh blood group antigens was delineated. In addition, the genetic and biochemical bases of several other blood group antigens were identified. One of the most interesting matches of blood group antigens to a functional membrane protein was that of the Diego antigens to the erythrocyte anion channel (band 3) protein. In addition, knowledge of the molecular basis of blood group antigens is now leading rapidly to the usefulness of molecular techniques in identifying blood group genotypes and even blood group antibody specificities. This knowledge has also broadened our understanding of the pathogenesis of erythrocyte disorders associated with null blood group phenotypes. The diagnosis and treatment of autoimmune hemolytic anemia has seen slow but steady progress. New techniques appear promising as methods for distinguishing clinically important from benign autoantibodies. The molecular targets for erythrocyte autoantibodies were also largely identified. Treatment of autoimmune hemolytic anemia is also slowly being improved with the use of agents such as intravenous gammaglobulin, danazol, and immunosuppressive agents, all of which have also been important in the treatment of autoimmune thrombocytopenic purpura.

Authors
Telen, MJ; Rao, N
MLA Citation
Telen, MJ, and Rao, N. "Recent advances in immunohematology." Curr Opin Hematol 1.2 (March 1994): 143-150. (Review)
PMID
9371273
Source
pubmed
Published In
Current Opinion in Hematology
Volume
1
Issue
2
Publish Date
1994
Start Page
143
End Page
150

Rh-related antigen CD47 is the signal-transducer integrin-associated protein.

Integrin-associated protein (IAP) is a 50-kDa membrane protein with an amino-terminal immunoglobulin domain and a carboxyl-terminal multiply membrane-spanning region. It is physically and functionally associated with the integrin alpha v beta 3 vitronectin receptor and is involved in the increase in intracellular calcium concentration, which occurs upon cell adhesion to extracellular matrix. Oxidative burst in neutrophils can be induced or inhibited via IAP. Surprisingly, IAP is also expressed on erythrocytes, which have no known integrins. IAP has been shown to be identical to OA3, an ovarian carcinoma antigen. We now show that IAP expression is reduced on Rhnull erythrocytes. The IAP structural gene is mapped to q13.1-2 on human chromosome 3, within a region known to contain a gene encoding the Rh-associated 1D8 antigen. By expression studies on human erythrocytes and IAP transfectants, IAP is shown to be identical to the 1D8 antigen and to CD47, a cell surface protein with broad tissue distribution, reduced in expression on Rhnull erythrocytes. Two CD47 antibodies recognize the immunoglobulin domain of IAP, as does antibody 1D8. These studies suggest the possibility that IAP and the Rh polypeptides may share a pathway for membrane expression on erythrocytes. Furthermore, decreased expression of IAP on Rhnull cells may contribute to the these cells' abnormal cation permeabilities. These studies demonstrate an unexpected link between integrin signal transduction and erythrocyte membrane structure.

Authors
Lindberg, FP; Lublin, DM; Telen, MJ; Veile, RA; Miller, YE; Donis-Keller, H; Brown, EJ
MLA Citation
Lindberg, FP, Lublin, DM, Telen, MJ, Veile, RA, Miller, YE, Donis-Keller, H, and Brown, EJ. "Rh-related antigen CD47 is the signal-transducer integrin-associated protein." J Biol Chem 269.3 (January 21, 1994): 1567-1570.
PMID
8294396
Source
pubmed
Published In
The Journal of biological chemistry
Volume
269
Issue
3
Publish Date
1994
Start Page
1567
End Page
1570

Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.

CD44 molecules are comprised of multiple alternatively spliced forms and are associated with diverse functions such as mediation of carcinoma metastasis and T cell coactivation. To study the function of individual CD44 isoforms, we have transfected CD44 isoforms into CD44-negative Jurkat T cells and produced cloned Jurkat cell lines that are stably transfected with either a CD44 isoform containing no alternatively spliced insert (CD44H) or a CD44 variant (CD44E) containing an insert of 132 amino acids derived from exons 12, 13, and 14 of the CD44 gene. We found that neither CD44H- nor CD44E-transfected Jurkat T cells constitutively bound hyaluronan (HA), whereas PMA treatment induced Jurkat cells transfected with CD44H but not CD44E to bind HA. CD44 mAb against noninsert regions of the CD44 extracellular domain (A3D8, A1G3) and polyclonal antisera against the COOH-terminal extracellular glycosaminoglycan region of CD44H (anti-6A serum) both induced CD44H-transfected cells to bind HA, whereas only one CD44 mAb (A1G3) induced CD44E-transfected Jurkat T cells to bind HA. Studies of Jurkat cells transfected with CD44H forms with truncations of the CD44 cytoplasmic domain demonstrated that the cytoplasmic COOH-terminal 52 amino acids were critical for binding of HA to the CD44 extracellular domain. Thus, these data underscore the importance of the CD44 cytoplasmic domain in the function of the extracellular portion of CD44H, and demonstrate a role for ligation of human CD44 isoforms at multiple distinct sites in regulation of expression of CD44 binding to HA.

Authors
Liao, HX; Levesque, MC; Patton, K; Bergamo, B; Jones, D; Moody, MA; Telen, MJ; Haynes, BF
MLA Citation
Liao, HX, Levesque, MC, Patton, K, Bergamo, B, Jones, D, Moody, MA, Telen, MJ, and Haynes, BF. "Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies." J Immunol 151.11 (December 1, 1993): 6490-6499.
PMID
7504022
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
151
Issue
11
Publish Date
1993
Start Page
6490
End Page
6499

INVESTIGATION OF THE HOLLEY GREGORY DOMBROCK BLOOD-GROUP ANTIGEN PROTEIN USING A NOVEL MONOCLONAL-ANTIBODY

Authors
RAO, N; REID, ME; TELEN, MJ
MLA Citation
RAO, N, REID, ME, and TELEN, MJ. "INVESTIGATION OF THE HOLLEY GREGORY DOMBROCK BLOOD-GROUP ANTIGEN PROTEIN USING A NOVEL MONOCLONAL-ANTIBODY." BLOOD 82.10 (November 15, 1993): A267-A267.
Source
wos-lite
Published In
Blood
Volume
82
Issue
10
Publish Date
1993
Start Page
A267
End Page
A267

RELATIONSHIP OF THE ANWJ BLOOD-GROUP ANTIGEN TO EXPRESSION OF CD-44

Authors
TELEN, MJ; RAO, N; UDANI, M; LIAO, HX; HAYNES, BF
MLA Citation
TELEN, MJ, RAO, N, UDANI, M, LIAO, HX, and HAYNES, BF. "RELATIONSHIP OF THE ANWJ BLOOD-GROUP ANTIGEN TO EXPRESSION OF CD-44." TRANSFUSION 33.9 (September 1993): S48-S48.
Source
wos-lite
Published In
Transfusion
Volume
33
Issue
9
Publish Date
1993
Start Page
S48
End Page
S48

CHARACTERIZATION OF A MONOCLONAL-ANTIBODY THAT DETECTS AN ANTIGEN-RELATED TO GREGORY

Authors
RAO, N; BUMGARNER, J; TELEN, MJ
MLA Citation
RAO, N, BUMGARNER, J, and TELEN, MJ. "CHARACTERIZATION OF A MONOCLONAL-ANTIBODY THAT DETECTS AN ANTIGEN-RELATED TO GREGORY." TRANSFUSION 33.9 (September 1993): S48-S48.
Source
wos-lite
Published In
Transfusion
Volume
33
Issue
9
Publish Date
1993
Start Page
S48
End Page
S48

THE ANWJ BLOOD-GROUP ANTIGEN HAEMOPHILUS-INFLUENZAE RECEPTOR RESIDES ON A HIGH-MOLECULAR-WEIGHT PROTEIN EXPRESSED BY CD44 TRANSFECTANTS

Authors
TELEN, MJ; RAO, N; UDANI, M; LIAO, HX; HAYNES, BF
MLA Citation
TELEN, MJ, RAO, N, UDANI, M, LIAO, HX, and HAYNES, BF. "THE ANWJ BLOOD-GROUP ANTIGEN HAEMOPHILUS-INFLUENZAE RECEPTOR RESIDES ON A HIGH-MOLECULAR-WEIGHT PROTEIN EXPRESSED BY CD44 TRANSFECTANTS." CLINICAL RESEARCH 41.2 (April 1993): A161-A161.
Source
wos-lite
Published In
Clinical Research
Volume
41
Issue
2
Publish Date
1993
Start Page
A161
End Page
A161

Human erythrocyte acetylcholinesterase bears the Yta blood group antigen and is reduced or absent in the Yt(a-b-) phenotype.

The Cartwright (Yt) blood group antigens have previously been shown likely to reside on a phosphatidylinositol-linked erythrocyte membrane protein. In this study, an unusual individual whose red blood cells (RBCs) were of the previously unreported Yt(a-b-) phenotype were used, along with normal Yt(a+) cells, to investigate serologically and biochemically the relationship of the Yta antigen to known phosphatidylinositol-linked erythrocyte proteins. Yt(a-b-) RBCs expressed normal amounts of various phosphatidyl-inositol-linked proteins except acetylcholinesterase. Further, human anti-Yta reacted with acetylcholinesterase in immunoprecipitation and immunoblotting studies. Thus, acetylcholinesterase is now identified as the protein bearing the Yt blood group antigens.

Authors
Rao, N; Whitsett, CF; Oxendine, SM; Telen, MJ
MLA Citation
Rao, N, Whitsett, CF, Oxendine, SM, and Telen, MJ. "Human erythrocyte acetylcholinesterase bears the Yta blood group antigen and is reduced or absent in the Yt(a-b-) phenotype." Blood 81.3 (February 1, 1993): 815-819.
PMID
8427972
Source
pubmed
Published In
Blood
Volume
81
Issue
3
Publish Date
1993
Start Page
815
End Page
819

MORE ABOUT USE OF THE TERM DR(B) - REPLY

Authors
LUBLIN, DM; TELEN, MJ
MLA Citation
LUBLIN, DM, and TELEN, MJ. "MORE ABOUT USE OF THE TERM DR(B) - REPLY." TRANSFUSION 33.2 (February 1993): 182-182.
Source
wos-lite
Published In
Transfusion
Volume
33
Issue
2
Publish Date
1993
Start Page
182
End Page
182

EXPRESSION OF THE CELL-ADHESION MOLECULE CD44 IN GASTRIC ADENOCARCINOMAS

Authors
WASHINGTON, MK; GOTTFRIED, MR; TELEN, MJ
MLA Citation
WASHINGTON, MK, GOTTFRIED, MR, and TELEN, MJ. "EXPRESSION OF THE CELL-ADHESION MOLECULE CD44 IN GASTRIC ADENOCARCINOMAS." LABORATORY INVESTIGATION 68.1 (January 1993): A52-A52.
Source
wos-lite
Published In
Laboratory Investigation
Volume
68
Issue
1
Publish Date
1993
Start Page
A52
End Page
A52

PRIMARY CULTURES OF EPITHELIUM DERIVED FROM BARRETTS-ESOPHAGUS

Authors
WASHINGTON, MK; GOTTFRIED, MR; TELEN, MJ
MLA Citation
WASHINGTON, MK, GOTTFRIED, MR, and TELEN, MJ. "PRIMARY CULTURES OF EPITHELIUM DERIVED FROM BARRETTS-ESOPHAGUS." LABORATORY INVESTIGATION 68.1 (January 1993): A53-A53.
Source
wos-lite
Published In
Laboratory Investigation
Volume
68
Issue
1
Publish Date
1993
Start Page
A53
End Page
A53

Monoclonal antibody recognizing a unique Rh-related specificity.

A mouse IgG1 monoclonal antibody (MAb) UMRh, was prepared by immunizing Balb/c mice with the Jurkat T cell acute lymphoblastic leukemia (T-ALL) cell line. The MAb UMRh is directed against a widely distributed Rh-related cell surface antigen, present on red blood cells (RBCs) expressing the more common Rh phenotypes. The antigen has reduced expression on RBCs of -D-, DCW-/DCW-, Rhmod and Rhnull phenotypes. UMR immunoblotted a unique pattern on RBC membrane preparations of two bands at 40 and 43 kD and a diffuse pattern extending upward to about 55 kD. The UMRh antigen is also present on peripheral blood mononuclear cells, granulocytes, platelets, leukemic cells of T cell, B cell and myeloid origins, hematopoietic stem cells, and two tumor lines (lung and colon carcinoma). The number of UMRh sites per RBC (CDe/ce) was determined to be 5,519 copies/cell, whereas the sites on a -D- phenotype RBC were 1,096 copies/cell. A T-ALL line (CEM) expressed 333,364 copies/cell and a myeloid line (KG-1) expressed 90,913 copies/cell. Several Rh-related murine MAbs have been described, but our data indicates that UMRh recognizes a previously uncharacterized Rh-related specificity.

Authors
Poss, MT; Swanson, JL; Telen, MJ; Lasky, LC; Vallera, DA
MLA Citation
Poss, MT, Swanson, JL, Telen, MJ, Lasky, LC, and Vallera, DA. "Monoclonal antibody recognizing a unique Rh-related specificity." Vox Sang 64.4 (1993): 231-239.
PMID
7685970
Source
pubmed
Published In
Vox Sanguinis
Volume
64
Issue
4
Publish Date
1993
Start Page
231
End Page
239

More about use of the term Drb [3]

Authors
Lewis, M; McAlpine, PJ; Lublin, DM; Telen, MJ
MLA Citation
Lewis, M, McAlpine, PJ, Lublin, DM, and Telen, MJ. "More about use of the term Drb [3]." Transfusion 33.2 (1993): 182--.
PMID
7679228
Source
scival
Published In
Transfusion
Volume
33
Issue
2
Publish Date
1993
Start Page
182-

NEW AND EVOLVING TECHNIQUES FOR ANTIBODY AND ANTIGEN IDENTIFICATION

Authors
TELEN, MJ
MLA Citation
TELEN, MJ. "NEW AND EVOLVING TECHNIQUES FOR ANTIBODY AND ANTIGEN IDENTIFICATION." 1993.
Source
wos-lite
Published In
ALLOIMMUNITY: 1993 AND BEYOND
Publish Date
1993
Start Page
117
End Page
139

SEROLOGICAL AND BIOCHEMICAL-CHARACTERIZATION OF A JMH VARIANT PHENOTYPE

Authors
ISSITT, PD; ROY, RB; COMBS, MR; BUMGARNER, J; RAO, N; TELEN, MJ
MLA Citation
ISSITT, PD, ROY, RB, COMBS, MR, BUMGARNER, J, RAO, N, and TELEN, MJ. "SEROLOGICAL AND BIOCHEMICAL-CHARACTERIZATION OF A JMH VARIANT PHENOTYPE." TRANSFUSION 32.8 (October 1992): S55-S55.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S55
End Page
S55

DIFFICULTIES IN SEPARATING 2 CELL-POPULATIONS IN A NEW CHIMERA

Authors
ISSITT, PD; COMBS, MR; SAMMONS, TD; SIZEMORE, JC; TELEN, MJ
MLA Citation
ISSITT, PD, COMBS, MR, SAMMONS, TD, SIZEMORE, JC, and TELEN, MJ. "DIFFICULTIES IN SEPARATING 2 CELL-POPULATIONS IN A NEW CHIMERA." TRANSFUSION 32.8 (October 1992): S55-S55.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S55
End Page
S55

MAPPING AND CHARACTERIZATION OF THE CRA EPITOPE OF DECAY ACCELERATING FACTOR

Authors
TELEN, MJ; RAO, N; THOMPSON, ES; LUBLIN, DM
MLA Citation
TELEN, MJ, RAO, N, THOMPSON, ES, and LUBLIN, DM. "MAPPING AND CHARACTERIZATION OF THE CRA EPITOPE OF DECAY ACCELERATING FACTOR." TRANSFUSION 32.8 (October 1992): S47-S47.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S47
End Page
S47

BIOCHEMICAL INVESTIGATION OF THE 2 PROTEIN SPECIES BEARING LUTHERAN ANTIGENS

Authors
TELEN, MJ; WOODLAND, MJ; RAO, N
MLA Citation
TELEN, MJ, WOODLAND, MJ, and RAO, N. "BIOCHEMICAL INVESTIGATION OF THE 2 PROTEIN SPECIES BEARING LUTHERAN ANTIGENS." TRANSFUSION 32.8 (October 1992): S48-S48.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S48
End Page
S48

MOLECULAR-BASIS OF REDUCED OR ABSENT EXPRESSION OF DECAY ACCELERATING FACTOR IN DR(A-) AND INAB PHENOTYPES OF CROMER BLOOD-GROUP

Authors
LUBLIN, DM; MALLINSON, G; REID, ME; POOLE, J; THOMPSON, ES; FERDMAN, BR; TELEN, MJ; ANSTEE, DJ; TANNER, MJA
MLA Citation
LUBLIN, DM, MALLINSON, G, REID, ME, POOLE, J, THOMPSON, ES, FERDMAN, BR, TELEN, MJ, ANSTEE, DJ, and TANNER, MJA. "MOLECULAR-BASIS OF REDUCED OR ABSENT EXPRESSION OF DECAY ACCELERATING FACTOR IN DR(A-) AND INAB PHENOTYPES OF CROMER BLOOD-GROUP." TRANSFUSION 32.8 (October 1992): S47-S47.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S47
End Page
S47

THE CARTWRIGHT NEGATIVE PHENOTYPE - AN ACQUIRED PHENOMENON ASSOCIATED WITH ANTI-YTAB-LIKE ANTIBODY

Authors
OXENDINE, SM; TELEN, MJ; RAO, N; HARE, V; FRIESEN, C; STORRY, J; PIERCE, JA; WHITSETT, CF
MLA Citation
OXENDINE, SM, TELEN, MJ, RAO, N, HARE, V, FRIESEN, C, STORRY, J, PIERCE, JA, and WHITSETT, CF. "THE CARTWRIGHT NEGATIVE PHENOTYPE - AN ACQUIRED PHENOMENON ASSOCIATED WITH ANTI-YTAB-LIKE ANTIBODY." TRANSFUSION 32.8 (October 1992): S18-S18.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
8
Publish Date
1992
Start Page
S18
End Page
S18

WHAT IS A BLOOD-GROUP ANTIGEN - REPLY

Authors
LUBLIN, DM; TELEN, MJ
MLA Citation
LUBLIN, DM, and TELEN, MJ. "WHAT IS A BLOOD-GROUP ANTIGEN - REPLY." TRANSFUSION 32.5 (June 1992): 493-493.
Source
wos-lite
Published In
Transfusion
Volume
32
Issue
5
Publish Date
1992
Start Page
493
End Page
493

Reply

Authors
COMBS, MARTHARAE; ISSI-IT, PETERD; TELEN, MARILYNJ
MLA Citation
COMBS, MARTHARAE, ISSI-IT, PETERD, and TELEN, MARILYNJ. "Reply." Transfusion 32.4 (May 1992): 391-391.
Source
crossref
Published In
Transfusion
Volume
32
Issue
4
Publish Date
1992
Start Page
391
End Page
391
DOI
10.1111/j.1537-2995.1992.tb02678.x

ERYTHROCYTE ACETYLCHOLINESTERASE BEARS THE CARTWRIGHT BLOOD-GROUP ANTIGENS

Authors
TELEN, MJ; WHITSETT, CF
MLA Citation
TELEN, MJ, and WHITSETT, CF. "ERYTHROCYTE ACETYLCHOLINESTERASE BEARS THE CARTWRIGHT BLOOD-GROUP ANTIGENS." CLINICAL RESEARCH 40.2 (April 1992): A170-A170.
Source
wos-lite
Published In
Clinical Research
Volume
40
Issue
2
Publish Date
1992
Start Page
A170
End Page
A170

Isolation of the JMH antigen on a novel phosphatidylinositol-linked human membrane protein.

JMH is a high-frequency human erythrocyte blood group antigen. Previous work has shown that JMH is absent from complement-sensitive erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH); such cells have a broad defect in expression of phosphatidylinositol (PI)-linked proteins. Using both human JMH antisera and a JMH-like murine monoclonal antibody, we have identified a 76-Kd membrane protein present in JMH-positive but not JMH-negative erythrocytes. A similar 76-Kd JMH protein was also identified on a human lymphoid T-cell line, HSB-2. Using PI-specific phospholipase C, a small amount of JMH antigen could be cleaved from intact erythrocytes and immunoprecipitated from the supernate of treated erythrocytes, thus confirming that the protein bearing the JMH antigen is anchored by a PI-linkage to the erythrocyte membrane. This protein was further shown not to be identical to decay accelerating factor (70 Kd), a previously identified PI-anchored protein of somewhat similar molecular weight.

Authors
Bobolis, KA; Moulds, JJ; Telen, MJ
MLA Citation
Bobolis, KA, Moulds, JJ, and Telen, MJ. "Isolation of the JMH antigen on a novel phosphatidylinositol-linked human membrane protein." Blood 79.6 (March 15, 1992): 1574-1581.
PMID
1372190
Source
pubmed
Published In
Blood
Volume
79
Issue
6
Publish Date
1992
Start Page
1574
End Page
1581

What is a blood group antigen? [2]

Authors
Daniels, G; Lublin, DM; Telen, MJ
MLA Citation
Daniels, G, Lublin, DM, and Telen, MJ. "What is a blood group antigen? [2]." Transfusion 32.5 (1992): 492-493.
PMID
1626353
Source
scival
Published In
Transfusion
Volume
32
Issue
5
Publish Date
1992
Start Page
492
End Page
493

Auto-anti-M causing immune hemolysis in vitro

Authors
Chapman, J; Murphy, MF; Waters, AH; Combs, MR; Issitt, PD; Telen, MJ
MLA Citation
Chapman, J, Murphy, MF, Waters, AH, Combs, MR, Issitt, PD, and Telen, MJ. "Auto-anti-M causing immune hemolysis in vitro." Transfusion 32.4 (1992): 391--.
PMID
1585447
Source
scival
Published In
Transfusion
Volume
32
Issue
4
Publish Date
1992
Start Page
391-

Phosphatidylinositol-glycan linked proteins of the erythrocyte membrane.

The human erythrocyte bears a number of proteins anchored to the outer membrane surface via a phosphatidylinositol-glycan linkage. This class of proteins includes several complement regulatory proteins (including decay-accelerating factor, CD59 antigen (protectin), and C8 binding protein) as well as several enzymes and at least one protein important in cell-cell interaction. In addition, a number of blood group antigens have been identified to reside on proteins with phosphatidylinositol anchors. One blood group (Cromer) resides on DAF. Study of variants in this blood group system has led to interesting information about the function and expression of this protein. Several other blood groups, such as JMH and Holley/Gregory, appear to reside on as yet unidentified phosphatidylinositol-linked proteins. In paroxysmal nocturnal haemoglobinuria, a variable proportion of red cells fail to express or express weakly all phosphatidylinositol-linked proteins. The origin of this deficiency is now being worked out. In addition, individuals with inherited deficiency of DAF or CD59 (protectin) have been identified. Only the latter deficiency leads to a PNH-like syndrome.

Authors
Telen, MJ; Rosse, WF
MLA Citation
Telen, MJ, and Rosse, WF. "Phosphatidylinositol-glycan linked proteins of the erythrocyte membrane." Baillieres Clin Haematol 4.4 (December 1991): 849-868. (Review)
PMID
1724205
Source
pubmed
Published In
Best Practice and Research: Clinical Haematology
Volume
4
Issue
4
Publish Date
1991
Start Page
849
End Page
868

Captopril-enhanced binding of PlA1 (HPA-1a) antibodies in posttransfusion purpura.

A case of posttransfusion purpura is reported in a 90-year-old patient whose PlA1 antibody (anti-HPA-1a) was found to bind better to HPA-1a in the presence of captopril, a drug the patient had taken. Initially, IgG antibodies were found in the serum that reacted with normal platelets, but the binding of the antibody was increased in vitro by captopril, which suggested that captopril was responsible for the thrombocytopenia. However, in vitro studies demonstrated that the patient's platelets were negative for HPA-1a and that anti-HPA-1a was present in the serum, both of which findings were consistent with the diagnosis of posttransfusion purpura. The binding of this antibody was enhanced 50 percent by captopril in vitro, and increased binding in the presence of captopril did not occur when the anti-HPA-1a was removed. Similar results were obtained with serum containing anti-HPA-1a from another patient with posttransfusion purpura. Thus, captopril may increase the binding of anti-HPA-1a and confuse the determination of the cause of acute thrombocytopenia.

Authors
Bepler, G; Hoffman, SE; Thompson, BP; Telen, MJ; Rosse, WF
MLA Citation
Bepler, G, Hoffman, SE, Thompson, BP, Telen, MJ, and Rosse, WF. "Captopril-enhanced binding of PlA1 (HPA-1a) antibodies in posttransfusion purpura." Transfusion 31.8 (October 1991): 752-755.
PMID
1926322
Source
pubmed
Published In
Transfusion
Volume
31
Issue
8
Publish Date
1991
Start Page
752
End Page
755

An auto-anti-M causing hemolysis in vitro.

A 64-year-old white man, who had never received a transfusion, was found to have anti-M in his serum. The antibody agglutinated all M+ red cells in room-temperature tests. When the ionic strength of the test milieu was reduced by use of an additive solution and the tests were incubated at 37 degrees C, the antibody hemolyzed M + N- but not M+N+ red cells. All M+ red cells reacted in indirect antiglobulin tests using polyspecific antiglobulin reagents when such tests followed an initial incubation at room temperature. When red cells and the patient's serum were warmed to 37 degrees C before being mixed, no antibody activity was demonstrable. The antibody was adsorbed to exhaustion onto M+N- and M+N+ red cells (including the patient's own), and its activity was destroyed by dithiothreitol. There was no evidence of in vivo red cell destruction by the autoantibody. No previously reported example of anti-M has been shown to activate complement in conventional in vitro tests. This example was extraordinary in that it caused sufficient complement activation to present as an in vitro hemolysin.

Authors
Combs, MR; O'Rourke, MM; Issitt, PD; Telen, MJ
MLA Citation
Combs, MR, O'Rourke, MM, Issitt, PD, and Telen, MJ. "An auto-anti-M causing hemolysis in vitro." Transfusion 31.8 (October 1991): 756-758.
PMID
1926323
Source
pubmed
Published In
Transfusion
Volume
31
Issue
8
Publish Date
1991
Start Page
756
End Page
758

Molecular basis for elliptocytosis associated with glycophorin C and D deficiency in the Leach phenotype.

Glycophorin C (GPC) and glycophorin D (GPD) are highly glycosylated integral membrane proteins of human erythrocytes encoded by the same gene and associated with expression of Gerbich blood group system antigens. GPC/D deficiency (the Leach phenotype) is a rare condition usually found after identification of Gerbich blood group system antibodies in persons undergoing prenatal or pretransfusion evaluation. In all cases, the Leach phenotype has been associated with elliptocytosis. Characterization of the molecular basis of this phenotype in three previously uninvestigated families has shown that the most common genetic basis of GPC/D deficiency is deletion of exons 3 and 4 of the GPC gene. However, in one family, the Leach phenotype appeared due to a deletion of one nucleotide in exon 3, causing a frameshift mutation in the messenger RNA and premature generation of a stop codon. The GPC and GPD protein sequences are therefore interrupted in the extracellular domain and probably intracellularly degraded.

Authors
Telen, MJ; Le Van Kim, C; Chung, A; Cartron, JP; Colin, Y
MLA Citation
Telen, MJ, Le Van Kim, C, Chung, A, Cartron, JP, and Colin, Y. "Molecular basis for elliptocytosis associated with glycophorin C and D deficiency in the Leach phenotype." Blood 78.6 (September 15, 1991): 1603-1606.
PMID
1884026
Source
pubmed
Published In
Blood
Volume
78
Issue
6
Publish Date
1991
Start Page
1603
End Page
1606

Dr(a-) polymorphism of decay accelerating factor. Biochemical, functional, and molecular characterization and production of allele-specific transfectants.

The Dra antigen belongs to the Cromer-related blood group system, a series of antigens on decay accelerating factor (DAF), a glycosyl-phosphatidylinositol-anchored membrane protein that protects host cells from complement-mediated damage. We studied the rare inherited Dr(a-) phenotype to ascertain the associated biochemical and functional changes in DAF and to characterize the basis for this polymorphism. Radioimmunoassay assay and flow cytometric analysis of Dr(a-) erythrocytes demonstrated 40% of normal surface expression of DAF but normal levels of several other glycosyl-phosphatidylinositol-anchored proteins, distinguishing this phenotype from that of paroxysmal nocturnal hemoglobinuria. Western blots confirmed this reduced DAF expression and indicated a slightly faster mobility of the molecule on SDS-PAGE. Despite the reduced DAF expression, Dr(a-) erythrocytes functioned normally in the complement lysis sensitivity assay. Utilization of the polymerase chain reaction to amplify mononuclear cell genomic DNA from three unrelated Dr(a-) individuals demonstrated that a point mutation underlies the Dr(a-) phenotype: a C to T change in nucleotide 649 resulting in a serine165 to leucine change. This defines the Drb allele of DAF, which can be distinguished from Dra by a Taq I restriction fragment length polymorphism. We created transfected Chinese hamster ovary cell lines expressing either the Dra or the Drb allelic form of DAF. These allele-specific transfectants were tested by inhibition of hemagglutination or flow cytometry and confirmed the specificity of anti-Dra alloantisera. The allele-specific transfectants could form the basis of a new serological approach to immunohematology.

Authors
Lublin, DM; Thompson, ES; Green, AM; Levene, C; Telen, MJ
MLA Citation
Lublin, DM, Thompson, ES, Green, AM, Levene, C, and Telen, MJ. "Dr(a-) polymorphism of decay accelerating factor. Biochemical, functional, and molecular characterization and production of allele-specific transfectants." J Clin Invest 87.6 (June 1991): 1945-1952.
PMID
1710232
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
87
Issue
6
Publish Date
1991
Start Page
1945
End Page
1952
DOI
10.1172/JCI115220

Identification of human erythrocyte blood group antigens on the C3b/C4b receptor.

The Knops/McCoy (Kn/McC) human erythrocyte blood group system belongs to the category of blood group Ag that generate so-called "high titer low avidity" antibodies in immunized transfusion recipients. Screening of red cells lacking certain high titer low avidity Ag demonstrated markedly diminished CR1 expression on McC(d-) and Kn/McC "null" (Kn(a-)McC(a-b-c-d-e-f-] erythrocytes. Additional testing by other methods confirmed these data, and biochemical assays demonstrated no detectable immunoreactive CR1 protein in membranes from Kn/McC null red cells. Human antisera to various Kn/McC Ag were then used to demonstrate that many of these antisera could be used to isolate a protein of identical m.w. to that isolated from the same cells using murine mAb CR1 antisera. Finally, protein isolated by using murine mAb anti-CR1 reacted specifically with anti-Kn/McC antibodies, demonstrating the identity of the Kn/McC and CR1 proteins. Thus, CR1 protein bears the human erythrocyte Kn/McC blood group Ag.

Authors
Rao, N; Ferguson, DJ; Lee, SF; Telen, MJ
MLA Citation
Rao, N, Ferguson, DJ, Lee, SF, and Telen, MJ. "Identification of human erythrocyte blood group antigens on the C3b/C4b receptor." J Immunol 146.10 (May 15, 1991): 3502-3507.
PMID
1827486
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
146
Issue
10
Publish Date
1991
Start Page
3502
End Page
3507

Erythrocyte Webb-type glycophorin C variant lacks N-glycosylation due to an asparagine to serine substitution.

We have analyzed part of the sequence of the human glycophorin C (GPC) gene carried by a Webb blood-group positive donor. Our results indicate that the lack of N-glycosylation of the variant GPC associated with the Webb phenotype is due to a point mutation resulting in an asparagine to serine substitution at amino acid position 8.

Authors
Telen, MJ; Le Van Kim, C; Guizzo, ML; Cartron, JP; Colin, Y
MLA Citation
Telen, MJ, Le Van Kim, C, Guizzo, ML, Cartron, JP, and Colin, Y. "Erythrocyte Webb-type glycophorin C variant lacks N-glycosylation due to an asparagine to serine substitution." Am J Hematol 37.1 (May 1991): 51-52.
PMID
1902622
Source
pubmed
Published In
American Journal of Hematology
Volume
37
Issue
1
Publish Date
1991
Start Page
51
End Page
52

Phosphatidylinositol-linked red blood cell membrane proteins and blood group antigens.

A new class of membrane proteins has recently been described. Unlike integral membrane proteins, which traverse the membrane with one or more hydrophobic peptide domains, the peptide domains of these more newly described proteins are entirely extracellular and are anchored to the cell membrane via a phosphatidylinositol-glycan (GPI) anchor. Erythrocyte membrane proteins of this class include proteins with diverse functions; several, however, are complement regulatory proteins. Moreover, it is the lack of expression of GPI-anchored proteins that is responsible for manifestations of the acquired hematologic disease paroxysmal nocturnal hemoglobinuria. Recently, several investigators have also demonstrated that a number of erythrocyte blood group antigens reside on this class of proteins. These antigens include those of the Cromer blood group, JMH, Holley/Gregory, Cartwright, and Dombrock. The biochemical basis for the Cromer, JMH, and Holley/Gregory antigens have so far been partly delineated.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "Phosphatidylinositol-linked red blood cell membrane proteins and blood group antigens." Immunohematology 7.3 (1991): 65-72.
PMID
15946025
Source
pubmed
Published In
Immunohematology / American Red Cross
Volume
7
Issue
3
Publish Date
1991
Start Page
65
End Page
72

Relationship of the human erythrocyte Wrb antigen to an interaction between glycophorin A and band 3.

The Wrb antigen is a high-frequency human erythrocyte antigen invariably absent from En (a-) erythrocytes, which lack glycophorin A. However, glycophorin A from En (a+) Wr (a+b-) red cells has an amino acid sequence identical to that of glycophorin A from Wr (b+) erythrocytes. Evidence has suggested that the Wrb antigen may require the interaction of glycophorin A with either a lipid moiety or with another erythrocyte-integral membrane protein, band 3. We have investigated the role of band 3 in Wrb expression using murine monoclonal antibodies (MoAbs) with Wrb specificity. These antibodies reacted by radioimmunoassay (RIA) only with cells expressing both glycophorin A and band 3. In immunoprecipitation studies, Wrb antibodies immunoprecipitated both band 3 and glycophorin A, while antibodies specific for band 3 or glycophorin precipitated only the protein with which they were reactive. These data strongly suggest that band 3 is the other membrane component necessary for expression of Wrb and that band 3 and glycophorin A are closely associated in the erythrocyte membrane.

Authors
Telen, MJ; Chasis, JA
MLA Citation
Telen, MJ, and Chasis, JA. "Relationship of the human erythrocyte Wrb antigen to an interaction between glycophorin A and band 3." Blood 76.4 (August 15, 1990): 842-848.
PMID
2383660
Source
pubmed
Published In
Blood
Volume
76
Issue
4
Publish Date
1990
Start Page
842
End Page
848

Evidence that several high-frequency human blood group antigens reside on phosphatidylinositol-linked erythrocyte membrane proteins.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder associated with absence of expression of phosphatidylinositol (PI)-linked membrane proteins from circulating hematopoietic cells of multiple lineages. Recent work demonstrated that decay accelerating factor, one such PI-linked protein, bears the Cromer-related blood group antigens. This study demonstrated that other high incidence antigens, including Cartwright (Yta/Ytb), Holley-Gregory (Hy/Gya), John Milton Hagen (JMH), and Dombrock (Doa/Dob), are absent from the complement-sensitive (PNH III) erythrocytes of patients with PNH. The relatively normal, complement-insensitive erythrocytes from the same patients express these antigens normally. Therefore, these antigens most likely reside on PI-linked proteins absent from PNH III, but not PNH I, erythrocytes.

Authors
Telen, MJ; Rosse, WF; Parker, CJ; Moulds, MK; Moulds, JJ
MLA Citation
Telen, MJ, Rosse, WF, Parker, CJ, Moulds, MK, and Moulds, JJ. "Evidence that several high-frequency human blood group antigens reside on phosphatidylinositol-linked erythrocyte membrane proteins." Blood 75.7 (April 1, 1990): 1404-1407.
PMID
2317557
Source
pubmed
Published In
Blood
Volume
75
Issue
7
Publish Date
1990
Start Page
1404
End Page
1407

THE RELATIONSHIP BETWEEN THE COMPLEMENT RECEPTOR TYPE-1 AND THE KNOPS MCCOY ANTIGEN SYSTEM

Authors
RAO, NC; FERGUSON, DJ; LEE, SF; TELEN, MJ
MLA Citation
RAO, NC, FERGUSON, DJ, LEE, SF, and TELEN, MJ. "THE RELATIONSHIP BETWEEN THE COMPLEMENT RECEPTOR TYPE-1 AND THE KNOPS MCCOY ANTIGEN SYSTEM." CLINICAL RESEARCH 38.2 (April 1990): A303-A303.
Source
wos-lite
Published In
Clinical Research
Volume
38
Issue
2
Publish Date
1990
Start Page
A303
End Page
A303

Relationship of Inb antigen to other antigens on In(Lu)-related p80.

The Ina and Inb antigens have recently been added to the list of diverse erythrocyte blood group antigens whose expression is down-regulated by the In(Lu) gene. Evidence has been provided that these antigens constitute polymorphisms of an erythrocyte glycoprotein previously defined by its reactivity with murine monoclonal antibodies, such as A3D8, and designated In(Lu)-related p80. This study has now confirmed the assignment of the Inb antigen to p80 and has further studied the relationship of the Inb epitope to other p80 epitopes recognized by both monoclonal antibodies as well as polyclonal antiserum produced against purified erythrocyte p80.

Authors
Telen, MJ; Ferguson, DJ
MLA Citation
Telen, MJ, and Ferguson, DJ. "Relationship of Inb antigen to other antigens on In(Lu)-related p80." Vox Sang 58.2 (1990): 118-121.
PMID
1692655
Source
pubmed
Published In
Vox Sanguinis
Volume
58
Issue
2
Publish Date
1990
Start Page
118
End Page
121

A case report: IgG autoanti-N as a cause of severe autoimmune hemolytic anemia.

A 21-year-old white worn was referred for evaluation of hemolytic anemia after a 9-day history of marked hemoglobinuria, jaundice, and weakness. The patient's hematocrit was 18%, despite at least eight transfusions over the previous week, and the reticulocyte count was < 1%. Serologic evaluation revealed a weakly positive direct antiglobulin test with anti-C3 only The serum contained cold and warm-reacting anti-N Dithiothreitol had no effect on either the cold- or the warm-reacting anti-N activity, and radioimmunoassay with monoclonal anti-IgG was strongly positive, indicating that both the cold- and the warm-reacting anti-N reactivity resided in the IgG fraction. The patient was treated with N - 'N' + red cell transfusions, prednisone, and azathioprine and gradually became transfusion independent. Postrecovery typing revealed her red cells to be M+N+S+s+. This constitutes the third case of autoimmune hemolytic anemia associated with IgG autoanti-N. The marked hemoglobinuria and reticulocytopenia are unique features of this case.

Authors
Combs, MR; Telen, MJ; Hall, SE; Rosse, WF
MLA Citation
Combs, MR, Telen, MJ, Hall, SE, and Rosse, WF. "A case report: IgG autoanti-N as a cause of severe autoimmune hemolytic anemia." Immunohematology 6.4 (1990): 83-86.
PMID
15946002
Source
pubmed
Published In
Immunohematology / American Red Cross
Volume
6
Issue
4
Publish Date
1990
Start Page
83
End Page
86

HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature.

While anemia and a positive direct anti-globulin test are each frequently observed in the clinical syndrome of human immunodeficiency virus (HIV) infection, autoimmune hemolytic anemia has rarely been reported in this setting. A case of severe warm autoimmune hemolytic anemia (AIHA) with reticulocytopenia in a patient with AIDS-related complex is reported. Laboratory and clinical findings of severe hemolysis were present, including anhaptoglobinemia, microspherocytosis, splenomegaly, and transfusion dependence. Azidothymidine (AZT) therapy may have exacerbated this patient's anemia. Splenectomy produced a delayed but complete remission of the AIHA despite continuation of AZT therapy. Review of other reports of positive direct antiglobulin tests and autoimmune hemolytic anemia in patients with HIV infections suggests that autoantibodies may be a significant cause of anemia in this population and that the frequent lack of reticulocytosis, despite bone marrow erythroid hyperplasia, may lead to the underdiagnosis of AIHA in HIV-infected patients.

Authors
Telen, MJ; Roberts, KB; Bartlett, JA
MLA Citation
Telen, MJ, Roberts, KB, and Bartlett, JA. "HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature." J Acquir Immune Defic Syndr 3.10 (1990): 933-937. (Review)
PMID
2204697
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
3
Issue
10
Publish Date
1990
Start Page
933
End Page
937

CD44--a molecule involved in leukocyte adherence and T-cell activation.

The study of cell surface molecules that are involved in interactions between immune and non-hematopoietic cells in various microenvironments is currently an area of great interest. One molecule that appears to be involved in multiple steps of normal immune cell function is now called CD44 and has been known previously as Pgp-1, In(Lu)-related p80, Hermes, ECM-III and HUTCH-I. Within the past year, the co-identity of all of these independently discovered molecules has become apparent, and the role of the CD44 molecule in T-cell activation has been discovered. In this review, Barton Haynes and his colleagues bring together numerous divergent lines of investigation on the CD44 molecule, review the many functional roles attributed to it, and present a unifying view of how, with numerous ligands, it may participate in several areas of normal immune cell function.

Authors
Haynes, BF; Telen, MJ; Hale, LP; Denning, SM
MLA Citation
Haynes, BF, Telen, MJ, Hale, LP, and Denning, SM. "CD44--a molecule involved in leukocyte adherence and T-cell activation." Immunol Today 10.12 (December 1989): 423-428. (Review)
PMID
2695102
Source
pubmed
Published In
Immunology Today
Volume
10
Issue
12
Publish Date
1989
Start Page
423
End Page
428
DOI
10.1016/0167-5699(89)90040-6

The Inab phenotype: characterization of the membrane protein and complement regulatory defect.

Recent demonstration that Cromer-related human blood group antigens reside on decay-accelerating factor (DAF) has led to identification of an apparent null phenotype (Inab) for erythrocyte DAF. This study examined expression of other phosphatidylinositol (PI)-anchored proteins by Inab erythrocytes and showed that the PI-linked membrane proteins acetylcholinesterase (AchE) and lymphocyte function-associated antigen-3 (LFA-3) are normally expressed by these cells. Furthermore, studies of the complement sensitivity of Inab RBCs demonstrated them to be abnormally complement sensitive, with an apparent defect in downregulation of C3 convertase activity. Thus, the Inab phenotype appears to represent an instance of hereditary erythrocyte DAF deficiency whose mechanism differs from that of paroxysmal nocturnal hemoglobinuria (PNH) and which is unassociated with clinically evident hemolytic disease.

Authors
Telen, MJ; Green, AM
MLA Citation
Telen, MJ, and Green, AM. "The Inab phenotype: characterization of the membrane protein and complement regulatory defect." Blood 74.1 (July 1989): 437-441.
PMID
2473800
Source
pubmed
Published In
Blood
Volume
74
Issue
1
Publish Date
1989
Start Page
437
End Page
441

Monoclonal antibodies against the CD44 [In(Lu)-related p80], and Pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors.

An 85- to 95 kDa class of lymphocyte surface molecules, defined in man by antibodies of the Hermes series, is involved in lymphocyte binding to high endothelial venules and is likely of central importance in the process of lymphocyte homing. In this report, we have examined the relationship between these Hermes-defined "homing-receptors" and two other 80 to 95 kDa lymphocyte surface molecules that have been extensively studied--CD44 [In(Lu)-related p80] defined by mAb A1G3 and A3D8, and Pgp-1 defined by antibody IM7. Our findings indicate that, in man, similar or identical glycoprotein(s) are recognized by these independently and diversely obtained antibodies. All antibodies showed identical immunohistologic patterns of reactivity on a variety of lymphoid and nonlymphoid human tissues, and demonstrated similar bands on Western blots of both crude tonsil lymphocyte lysates and highly purified Hermes-1 Ag preparations. Similarly, purified CD44/p80 Ag from RBC and human serum bound Hermes-1. Preclearing of tonsil lysates with the Hermes-1 antibody removed antigenic activity for all antibodies. Cross-blocking experiments demonstrated that A3D8, IM7 (anti-Pgp-1), and Hermes-2 antibodies recognize overlapping epitopes. Finally, expression of the epitopes defined by the Hermes-1, Hermes-3, H2-7, and H3-61 antibodies on RBC was shown to be regulated by the In(Lu) gene. These findings unify several different lines of investigation, and suggest the possibility that the CD44/Pgp-1/Hermes class of molecules may serve as cell-cell or cell-substrate adhesion/recognition elements for both hematolymphoid and non-hematolymphoid cell types.

Authors
Picker, LJ; De los Toyos, J; Telen, MJ; Haynes, BF; Butcher, EC
MLA Citation
Picker, LJ, De los Toyos, J, Telen, MJ, Haynes, BF, and Butcher, EC. "Monoclonal antibodies against the CD44 [In(Lu)-related p80], and Pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors." J Immunol 142.6 (March 15, 1989): 2046-2051.
PMID
2646376
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
142
Issue
6
Publish Date
1989
Start Page
2046
End Page
2051

Characterization of the serum In(Lu)-related antigen: identification of a serum protein related to erythrocyte p80.

The In(Lu) gene has been shown previously to downregulate expression by erythrocytes and by a subset of leukocytes of an 80-Kd protein antigen defined by monoclonal antibody (MoAb) A3D8. A3D8 antibody has also been shown by inhibition studies to recognize a serum antigen; this serum antigen is present in reduced amount in serum from In(Lu) donors. The present study demonstrates that the serum antigen recognized by A3D8 antibody also resides on a protein similar in size to the protein present in erythrocyte membranes. Studies using chromatographically purified protein have further shown that this antigen shares many epitopes with that present in RBCs and is therefore likely to be extremely homologous or identical to the erythrocyte In(Lu)-related p80.

Authors
Lucas, MG; Green, AM; Telen, MJ
MLA Citation
Lucas, MG, Green, AM, and Telen, MJ. "Characterization of the serum In(Lu)-related antigen: identification of a serum protein related to erythrocyte p80." Blood 73.2 (February 1989): 596-600.
PMID
2917192
Source
pubmed
Published In
Blood
Volume
73
Issue
2
Publish Date
1989
Start Page
596
End Page
600

Human red cell antigens. V. Expression of In(Lu)-related p80 antigens by recessive-type Lu(a-b-) red cells.

The In(Lu) gene, which inhibits the expression of Lutheran blood group antigens by red cells (RBCs), also down-regulates the expression of an 80-kD glycoprotein, In(Lu)-related p80, by both RBCs and a subset of white cells. This study examined the expression of multiple-RBC p80 epitopes by autosomal and X-linked recessive-type Lu(a-b-) RBCs in order to explore the relationship, if any, between expression of In(Lu)-related p80 and Lutheran antigens. Both autosomal and X-linked types of recessive Lu(a-b-) RBCs expressed near-normal to increased amounts of p80 antigens, as measured by radioimmunoassay. P80 from both types of recessive Lu(a-b-) RBCs had apparently normal molecular weight in denaturing polyacrylamide gels and showed normal sensitivity to digestion by trypsin and chymotrypsin. Thus, the absence of Lutheran antigens on recessive-type Lu(a-b-) RBCs is not associated with decreased or absent p80 antigens. Furthermore, the XS2 gene probably does not act via a mechanism similar to that of the In(Lu) gene, since the expression of p80 remains undiminished in X-linked recessive-type Lu(a-b-) RBCs.

Authors
Telen, MJ; Green, AM
MLA Citation
Telen, MJ, and Green, AM. "Human red cell antigens. V. Expression of In(Lu)-related p80 antigens by recessive-type Lu(a-b-) red cells." Transfusion 28.5 (September 1988): 430-434.
PMID
3420670
Source
pubmed
Published In
Transfusion
Volume
28
Issue
5
Publish Date
1988
Start Page
430
End Page
434

Identification of human erythrocyte blood group antigens on decay-accelerating factor (DAF) and an erythrocyte phenotype negative for DAF.

Decay accelerating factor (DAF) is a glycoprotein present on the surfaces of many types ofcells in contact with plasma, including erythrocytes, leukocytes, and platelets (reviewed in reference 1). A small amount of DAF is also present in serum. Numerous investigators have demonstrated that DAF inhibits the action of C3 convertases on cell surfaces, and its absence has been shown to be at least partially responsible for the abnormal sensitivity to lysis by complement exhibited by erythrocytes of patients with the acquired stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) (2). Hereditary absence of DAF has not been previously described. Tc(a) and Cr(a) are high-frequency human erythrocyte antigens . These antigens are part of a family of blood group antigens, designated Cromer related, which are all absent from the null phenotype cell IFC(-) , or Inab (3). Recently, Spring and colleagues (4) have identified two monoclonal antibodies which bound to high frequency red cell antigens absent from the Inab phenotype. They also demonstrated that these antibodies, as well as several human antisera to Cromer-related antigens, bound to a 70-kD glycoprotein when used to stain immunoblots of human erythrocyte membrane proteins . Because the wide tissue distribution of mAb reactivity, along with some of the biochemical characterization and immunoblotting data, was similar to that of DAF, we investigated whether the Cromer-related antigens Cr(a) and Tc(a) resided on the DAF molecule.

Authors
Telen, MJ; Hall, SE; Green, AM; Moulds, JJ; Rosse, WF
MLA Citation
Telen, MJ, Hall, SE, Green, AM, Moulds, JJ, and Rosse, WF. "Identification of human erythrocyte blood group antigens on decay-accelerating factor (DAF) and an erythrocyte phenotype negative for DAF." J Exp Med 167.6 (June 1, 1988): 1993-1998.
PMID
2455016
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
167
Issue
6
Publish Date
1988
Start Page
1993
End Page
1998

Serological and biochemical characterization of monoclonal antibodies against red cell markers related to expression of Lutheran blood group antigens.

Authors
Telen, MJ; Green, A; Young, T
MLA Citation
Telen, MJ, Green, A, and Young, T. "Serological and biochemical characterization of monoclonal antibodies against red cell markers related to expression of Lutheran blood group antigens." Rev Fr Transfus Immunohematol 31.2 (April 1988): 421-428.
PMID
3212325
Source
pubmed
Published In
Revue Francaise de Transfusion et Immuno-Hematologie
Volume
31
Issue
2
Publish Date
1988
Start Page
421
End Page
428

Biochemical characterization of antibodies submitted as reactive with glycophorin species.

Authors
Telen, MJ; Green, A; Young, T
MLA Citation
Telen, MJ, Green, A, and Young, T. "Biochemical characterization of antibodies submitted as reactive with glycophorin species." Rev Fr Transfus Immunohematol 31.2 (April 1988): 309-315.
PMID
3212311
Source
pubmed
Published In
Revue Francaise de Transfusion et Immuno-Hematologie
Volume
31
Issue
2
Publish Date
1988
Start Page
309
End Page
315

IDENTIFICATION OF HUMAN-BLOOD GROUP ANTIGENS ON DECAY ACCELERATING FACTOR AND DEMONSTRATION OF A NULL PHENOTYPE

Authors
TELEN, MJ; HALL, SE; GREEN, A; ROSSE, WF
MLA Citation
TELEN, MJ, HALL, SE, GREEN, A, and ROSSE, WF. "IDENTIFICATION OF HUMAN-BLOOD GROUP ANTIGENS ON DECAY ACCELERATING FACTOR AND DEMONSTRATION OF A NULL PHENOTYPE." CLINICAL RESEARCH 36.3 (April 1988): A421-A421.
Source
wos-lite
Published In
Clinical Research
Volume
36
Issue
3
Publish Date
1988
Start Page
A421
End Page
A421

Further characterization of erythrocyte p80 and the membrane protein defect of In(Lu) Lu(a-b-) erythrocytes.

We have previously shown that the In(Lu) gene down-regulates expression of an erythrocyte protein antigen identified by murine monoclonal antibody (MoAb) A3D8. In the present study we have examined In(Lu) Lu(a-b-) erythrocytes for expression of additional epitopes on the erythrocyte 80 kilodalton protein (p80) bearing the A3D8 antigen. Using a total of seven additional MoAbs that recognize three epitopes on erythrocyte p80, we have shown that In(Lu) Lu(a-b-) erythrocytes exhibit down-regulation of expression of all three epitopes. In(Lu) erythrocytes also showed a reduction in their reactivity to rabbit antibodies produced against purified p80 from either erythrocytes or lymphocytes. Furthermore the reactivity of the MoAbs was not altered by treatment of the cells with neuraminidase but was substantially reduced by treatment of cells with trypsin or chymotrypsin. The polyclonal anti-p80 sera were shown to react with a fragment of 50,000 daltons, still associated with erythrocyte ghosts, following treatment of the cells with trypsin or chymotrypsin. Treatment of erythrocytes with the thiol-reactive reagent AET decreased their reactivity with the MoAbs but had a variable effect on their reactivity with polyclonal antibodies. Erythrocyte p80 is a glycoprotein with N-linked oligosaccharides, as demonstrated by its binding to concanavalin A (Con A) and Len culinaris lectins. Following Endoglycosidase F treatment, erythrocyte p80 underwent a reduction in apparent mol wt of 11,000. The presence of a reduced amount of an intact p80 glycoprotein, seen by a decrease in reactivity with MoAbs directed at three distinct epitopes and with two different polyclonal antibodies, suggests that the In(Lu) gene interferes with expression by erythrocytes of the entire p80 glycoprotein.

Authors
Telen, MJ; Rogers, I; Letarte, M
MLA Citation
Telen, MJ, Rogers, I, and Letarte, M. "Further characterization of erythrocyte p80 and the membrane protein defect of In(Lu) Lu(a-b-) erythrocytes." Blood 70.5 (November 1987): 1475-1481.
PMID
2444289
Source
pubmed
Published In
Blood
Volume
70
Issue
5
Publish Date
1987
Start Page
1475
End Page
1481

Human red cell antigens. IV. The abnormal sialoglycoprotein of Gerbich-negative red cells.

The minor red cell sialoglycoproteins--beta and gamma (also known as glycophorin C)--are believed to be important to the structural integrity of red cells. The absence of sialoglycoproteins alpha and delta, as seen in En(a-) and S-s-U- cells, respectively, results in cells with normal morphology, but the absence of sialoglycoproteins beta and gamma is associated with elliptocytosis. However, cells that lack Gerbich (Ge) antigens but have an abnormal sialoglycoprotein reactive with antibodies to beta have normal morphology. The authors used a monoclonal antibody specific for beta to explore the nature of this abnormal sialoglycoprotein and its interactions with other membrane proteins. The beta-like sialoglycoprotein of Ge-Yus- red cells appears to react poorly with some antibodies due to steric hindrance by other molecules of sites normally available to immune agglutinins. This steric hindrance is not due to a single interaction with either sialoglycoprotein alpha or delta or band 3. Furthermore, steric hindrance by other molecules does not account for the lack of Ge antigens on these cells.

Authors
Telen, MJ; Bolk, TA
MLA Citation
Telen, MJ, and Bolk, TA. "Human red cell antigens. IV. The abnormal sialoglycoprotein of Gerbich-negative red cells." Transfusion 27.4 (July 1987): 309-314.
PMID
3603658
Source
pubmed
Published In
Transfusion
Volume
27
Issue
4
Publish Date
1987
Start Page
309
End Page
314

Monoclonal antibodies to a human islet cell surface glycoprotein: 4F2 and LC7-2.

Monoclonal antibodies 4F2 and LC7-2 react with a cell surface differentiation antigen expressed by the endocrine cells of the human pancreatic islet, but not by the acinar pancreatic, ductular, vascular, or stromal connective tissue cells. Western immunoblotting procedures demonstrate the reactivity of the monoclonal antibody 4F2 with a 120 kilodalton islet cell protein in detergent-solubilized cell extracts. These two monoclonal antibodies have potential for application in many aspects of islet cell research and diabetes in general.

Authors
Srikanta, S; Telen, M; Posillico, JT; Dolinar, R; Krisch, K; Haynes, BF; Eisenbarth, GS
MLA Citation
Srikanta, S, Telen, M, Posillico, JT, Dolinar, R, Krisch, K, Haynes, BF, and Eisenbarth, GS. "Monoclonal antibodies to a human islet cell surface glycoprotein: 4F2 and LC7-2." Endocrinology 120.6 (June 1987): 2240-2244.
PMID
2436897
Source
pubmed
Published In
Endocrinology
Volume
120
Issue
6
Publish Date
1987
Start Page
2240
End Page
2244
DOI
10.1210/endo-120-6-2240

Human erythrocyte antigens. III. Characterization of a panel of murine monoclonal antibodies that react with human erythrocyte and erythroid precursor membranes.

Human erythrocyte membrane proteins express antigens which serve as markers for erythroid differentiation as well as targets for human blood group alloantibodies. We have produced and characterized a new panel of five monoclonal antibodies to erythrocyte membrane proteins. Three monoclonal antibodies (E3, E4, E5) were specific for erythrocyte glycophorins. One antibody (E3) identified the sialoglycoprotein alpha and beta homologous regions proximal to the plasma membrane, a second antibody (E4) was specific for sialoglycoprotein alpha, while a third (E5) was a sialoglycoprotein-beta-specific antibody. Two antibodies (E6 and TE10) to the 65,000-dalton chymotrypsin cleavage product of band 3 were also produced. These antibodies constitute a new panel of probes for investigation of normal erythroid differentiation, erythroleukemia, and the expression of normal and anomalous blood group antigens.

Authors
Telen, MJ; Scearce, RM; Haynes, BF
MLA Citation
Telen, MJ, Scearce, RM, and Haynes, BF. "Human erythrocyte antigens. III. Characterization of a panel of murine monoclonal antibodies that react with human erythrocyte and erythroid precursor membranes." Vox Sang 52.3 (1987): 236-243.
PMID
3474823
Source
pubmed
Published In
Vox Sanguinis
Volume
52
Issue
3
Publish Date
1987
Start Page
236
End Page
243

EVIDENCE THAT WRB ANTIGEN INVOLVES INTERACTION BETWEEN BAND 3 AND GLYCOPHORIN-A

Authors
TELEN, MJ
MLA Citation
TELEN, MJ. "EVIDENCE THAT WRB ANTIGEN INVOLVES INTERACTION BETWEEN BAND 3 AND GLYCOPHORIN-A." TRANSFUSION 27.6 (1987): 534-534.
Source
wos-lite
Published In
Transfusion
Volume
27
Issue
6
Publish Date
1987
Start Page
534
End Page
534

Human medullary thymocyte p80 antigen and In(Lu)-related p80 antigen reside on the same protein.

Study of human T lymphocyte differentiation antigens with monoclonal antibodies has led to the identification of two antigens shared by erythrocytes and leukocytes. The protein (p80) defined by A1G3 antibody has previously been shown to be acquired during human intrathymic T-cell maturation. The antigen defined by A3D8 antibody has been demonstrated also to reside on an 80 kd protein; expression of the A3D8 antigen on erythrocytes and a subset of leukocytes is regulated by the rare In(Lu) gene. In this study, we demonstrate that the antigens defined by the A1G3 and A3D8 antibodies reside on the same protein and represent closely related but nonidentical epitopes on the p80 molecule. Expression of the A1G3 antigen on erythrocytes and a subset of leukocytes is also down-regulated by the In(Lu) gene. The possible role of the In(Lu) gene in thymocyte differentiation is discussed.

Authors
Telen, MJ; Shehata, H; Haynes, BF
MLA Citation
Telen, MJ, Shehata, H, and Haynes, BF. "Human medullary thymocyte p80 antigen and In(Lu)-related p80 antigen reside on the same protein." Hum Immunol 17.3 (November 1986): 311-324.
PMID
2432047
Source
pubmed
Published In
Human Immunology
Volume
17
Issue
3
Publish Date
1986
Start Page
311
End Page
324

Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria.

Blood of patients with paroxysmal nocturnal hemoglobinuria (PNH) most often contains two or more populations of erythrocytes--one population with normal sensitivity to lysis by complement (PNH I cells) and a second population of moderately abnormal cells (PNH II cells) or markedly abnormal cells (PNH III cells). PNH II and III cells exhibit moderately and markedly increased sensitivity to lysis by complement, respectively, as well as other membrane defects. We have devised a method for isolating pure, intact PNH II and III cells from mixed populations by use of monoclonal antibodies and cell affinity chromatography. Study of purified cell populations has led to the identification of a further subtype, PNH IIIb, of PNH erythrocytes. PNH IIIb erythrocytes are less sensitive to complement lysis than PNH IIIa cells but are lysed by fluid-phase activation of complement, unlike PNH II erythrocytes.

Authors
Chow, FL; Hall, SE; Rosse, WF; Telen, MJ
MLA Citation
Chow, FL, Hall, SE, Rosse, WF, and Telen, MJ. "Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria." Blood 67.4 (April 1986): 893-897.
PMID
3955235
Source
pubmed
Published In
Blood
Volume
67
Issue
4
Publish Date
1986
Start Page
893
End Page
897

THE MEMBRANE GLYCOPROTEIN DEFECT OF IN(LU) LU(A-B-) ERYTHROCYTES (E)

Authors
TELEN, MJ; LETARTE, M
MLA Citation
TELEN, MJ, and LETARTE, M. "THE MEMBRANE GLYCOPROTEIN DEFECT OF IN(LU) LU(A-B-) ERYTHROCYTES (E)." TRANSFUSION 26.6 (1986): 574-574.
Source
wos-lite
Published In
Transfusion
Volume
26
Issue
6
Publish Date
1986
Start Page
574
End Page
574

The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane.

Paroxysmal nocturnal hemoglobinuria (PNH) is a myelodysplastic disease characterized by erythrocytes that show abnormally increased sensitivity to complement-mediated lysis. Complement-sensitive PNH erythrocyte membranes have previously been shown to lack acetylcholinesterase (AchE) activity, but the molecular basis of this deficiency has been unclear. We have used monoclonal antibodies to four different epitopes on the AchE molecule to show that abnormal PNH erythrocytes failed to bind these antibodies. Moreover, abnormal PNH erythrocytes contained no protein immunoprecipitable by these antibodies, while normal complement-insensitive erythrocytes from PNH patients showed normal amounts of immunoprecipitable AchE which had normal electrophoretic mobility. These data suggest that abnormal PNH erythrocytes lack AchE enzyme activity due to the absence of the AchE molecule from the cell membrane.

Authors
Chow, FL; Telen, MJ; Rosse, WF
MLA Citation
Chow, FL, Telen, MJ, and Rosse, WF. "The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane." Blood 66.4 (October 1985): 940-945.
PMID
4041621
Source
pubmed
Published In
Blood
Volume
66
Issue
4
Publish Date
1985
Start Page
940
End Page
945

An antibody to human thymic Hassall's body epithelium recognizes a subset of blood group A antigens.

TE-19, a mouse monoclonal antibody (mAb) against thymic Hassall's body epithelium, was investigated because of its cross-reactivity with human erythrocytes. Antibody TE-19 was found to react only with group A erythrocytes, though it reacted with Hassall's body epithelium from donors of all blood group phenotypes. TE-19 antibody bound preferentially to cells of subgroup A1, and reacted only weakly with A2 and Aint erythrocytes. Although it apparently bound to A antigen with both glycolipid and glycoprotein backbones, TE-19 antibody only reacted with A antigenic moieties containing long or branched chain structures. Analysis of TE-19 reactivity with erythrocyte membrane components using electroblotting and immunostaining techniques showed antibody reactivity with components migrating in the areas of band 4 X 5 and just ahead of the dye front, consistent with membrane glycolipid. It is possible that all human thymic Hassall's bodies contain epithelial cells which, irrespective of the donor's erythrocyte blood group, bear a carbohydrate antigen similar to A antigen.

Authors
Telen, MJ
MLA Citation
Telen, MJ. "An antibody to human thymic Hassall's body epithelium recognizes a subset of blood group A antigens." J Immunogenet 12.1 (February 1985): 3-15.
PMID
2413132
Source
pubmed
Published In
Journal of Immunogenetics
Volume
12
Issue
1
Publish Date
1985
Start Page
3
End Page
15

THE MEMBRANE DEFECT OF GERBICH-NEGATIVE (GE-) ERYTHROCYTES (E)

Authors
TELEN, MJ; BOLK, T
MLA Citation
TELEN, MJ, and BOLK, T. "THE MEMBRANE DEFECT OF GERBICH-NEGATIVE (GE-) ERYTHROCYTES (E)." TRANSFUSION 25.5 (1985): 464-464.
Source
wos-lite
Published In
Transfusion
Volume
25
Issue
5
Publish Date
1985
Start Page
464
End Page
464

Increased efficiency of binding of nascent C3b to the erythrocytes of chronic cold agglutinin disease.

The pathogenesis of chronic cold agglutinin disease (CCAD) has been enigmatic. To determine if abnormal erythrocyte membrane constituents might provide the stimulus for antibody production, we compared the electrophoretic pattern of radiolabeled membrane glycoproteins of four patients with CCAD to that of normal control erythrocytes. For the CCAD erythrocytes, fluorographs revealed the appearance of an abnormal band whose molecular weight was estimated at 126,000 D. Using two-dimensional gel analysis and immunoblotting techniques, it was determined that the 126,000 D glycoprotein consisted predominately of polymeric glycophorin-alpha. Previous investigations had suggested that abnormalities in glycophorin-alpha influence the functional activity of the complement system. When purified complement (C)3 was activated in the fluid-phase by cobra venom factor complexes, CCAD erythrocytes bound nascent C3b 7-27 times more efficiently than normal erythrocytes. Normal erythrocytes could be induced to manifest the appearance of the 126,000 D band, and the increased efficiency of binding of nascent C3b by incubation with CCAD serum or with the purified cold agglutinin antibody plus autologous serum, but not with the purified antibody alone or the purified antibody plus EDTA-chelated autologous serum. These studies demonstrate that the interactions of IgM cold-reacting antibody and complement with glycophorin induce changes in the biophysical properties of the erythrocyte membrane which modify subsequent interactions with complement.

Authors
Parker, CJ; Soldato, CM; Telen, MJ
MLA Citation
Parker, CJ, Soldato, CM, and Telen, MJ. "Increased efficiency of binding of nascent C3b to the erythrocytes of chronic cold agglutinin disease." J Clin Invest 74.3 (September 1984): 1050-1062.
PMID
6236231
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
74
Issue
3
Publish Date
1984
Start Page
1050
End Page
1062
DOI
10.1172/JCI111472

Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes.

We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western blot techniques that the antigen defined by A3D8 was on an 80-kD erythrocyte membrane protein. A second 170-kD protein was coprecipitated with the 80-kD protein but failed to show antigen activity by Western blot analysis. The 170-kD protein, when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in two dimensions, was composed of 50- and 30-kD disulfide-linked subunits. In(Lu) Lu[a-b-) erythrocytes differed from Lu(a+b+) or Lu(a-b+) erythrocytes in that In(Lu) deoxycholate erythrocyte membrane extracts contained trace amounts of immunoprecipitable 80-kD protein compared with detergent-solubilized erythrocyte membrane extracts prepared from Lu(a+b+) or Lu(a-b+) subjects.

Authors
Telen, MJ; Palker, TJ; Haynes, BF
MLA Citation
Telen, MJ, Palker, TJ, and Haynes, BF. "Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes." Blood 64.3 (September 1984): 599-606.
PMID
6466869
Source
pubmed
Published In
Blood
Volume
64
Issue
3
Publish Date
1984
Start Page
599
End Page
606

Monoclonal antibody defines human cell surface protein p80 on intrathymic T cells.

Authors
Haynes, BF; Telen, MJ; PalkerTJ, ; Harden, E; Scearce, RM
MLA Citation
Haynes, BF, Telen, MJ, PalkerTJ, , Harden, E, and Scearce, RM. "Monoclonal antibody defines human cell surface protein p80 on intrathymic T cells." J Immunol 132.5 (May 1984): 2678-. (Letter)
PMID
6425411
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
132
Issue
5
Publish Date
1984
Start Page
2678

Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation.

The thymus is thought to be the primary central lymphoid organ in which T cells mature. Although thymic cortical and medullary compartments are distinct histologically, few antigens have been described that are absolutely acquired during the presumed intrathymic maturation pathway from cortical to medullary thymocytes. In this paper, we describe the acquisition during human intrathymic T cell maturation of a novel protein (p80) defined by a monoclonal antibody (A1G3). Although the p80-A1G3 antigen is distributed throughout the body and is not T cell specific, our study demonstrates that expression of p80-A1G3 antigen in normal human thymus is associated with thymocyte functional maturity and location in the thymus medulla. Moreover, in contrast to other markers of mature human T cells, the p80-A1G3 cell surface protein is not expressed on T6+ cortical thymocytes, and, therefore, is absolutely acquired by medullary thymocytes during T cell maturation. Thus, the p80-A1G3 antigen and the A1G3 antibody provide a heretofore unavailable system for the study of molecular events that transpire during the maturation of thymocytes.

Authors
Haynes, BF; Harden, EA; Telen, MJ; Hemler, ME; Strominger, JL; Palker, TJ; Scearce, RM; Eisenbarth, GS
MLA Citation
Haynes, BF, Harden, EA, Telen, MJ, Hemler, ME, Strominger, JL, Palker, TJ, Scearce, RM, and Eisenbarth, GS. "Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation." J Immunol 131.3 (September 1983): 1195-1200.
PMID
6224850
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
131
Issue
3
Publish Date
1983
Start Page
1195
End Page
1200

Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene.

Our study describes a novel human erythrocyte protein antigen, the expression of which is regulated by the rare Lutheran inhibitor In(Lu) gene. We have produced a monoclonal antibody (A3D8) that bound strongly to erythrocytes from subjects with Lutheran phenotypes Lu(a+b+), Lu(a+b-), and Lu(a-b+) but bound negligibly to erythrocytes from subjects with the dominant form of Lu(a-b-) phenotype, reflecting inheritance of the In(Lu) gene. Importantly, erythrocytes from an individual with the recessive form of Lu(a-b-) phenotype (i.e., absence of the In(Lu) gene and absence of genes encoding for Lutheran antigens) showed reactivity with A3D8 antibody comparable to that seen with Lu(a+) or Lu(b+) erythrocytes. A3D8 antigen activity was also found on all leukocytes and in serum and plasma; this activity also appeared to be regulated by the In(Lu) gene in serum, plasma, and on a subset of leukocytes. Thus, we have identified a human erythrocyte protein whose expression is modified by the In(Lu) gene. This knowledge that such an antigen exists on erythrocytes and in normal plasma should allow further studies into the molecular genetics of the In(Lu) gene and into the functional and structural significance of the A3D8 antigen.

Authors
Telen, MJ; Eisenbarth, GS; Haynes, BF
MLA Citation
Telen, MJ, Eisenbarth, GS, and Haynes, BF. "Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene." J Clin Invest 71.6 (June 1983): 1878-1886.
PMID
6863545
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
71
Issue
6
Publish Date
1983
Start Page
1878
End Page
1886

CHARACTERIZATION AND DISTRIBUTION OF A LUTHERAN ERYTHROCYTE ANTIGEN AS DEFINED BY A MONOCLONAL-ANTIBODY

Authors
TELEN, MJ; EISENBARTH, GS; HAYNES, BF
MLA Citation
TELEN, MJ, EISENBARTH, GS, and HAYNES, BF. "CHARACTERIZATION AND DISTRIBUTION OF A LUTHERAN ERYTHROCYTE ANTIGEN AS DEFINED BY A MONOCLONAL-ANTIBODY." CLINICAL RESEARCH 30.2 (1982): A331-A331.
Source
wos-lite
Published In
Clinical Research
Volume
30
Issue
2
Publish Date
1982
Start Page
A331
End Page
A331

CHARACTERIZATION OF A NOVEL CELL-SURFACE GLYCOPROTEIN COEXPRESSED ON CELLS BEARING THE INSULIN-RECEPTOR AND SELECTIVELY EXPRESSED ON PANCREATIC-ISLET CELLS

Authors
EISENBARTH, GS; TELEN, MJ; PETERSON, C; REIMAN, T; HAYNES, BF
MLA Citation
EISENBARTH, GS, TELEN, MJ, PETERSON, C, REIMAN, T, and HAYNES, BF. "CHARACTERIZATION OF A NOVEL CELL-SURFACE GLYCOPROTEIN COEXPRESSED ON CELLS BEARING THE INSULIN-RECEPTOR AND SELECTIVELY EXPRESSED ON PANCREATIC-ISLET CELLS." CLINICAL RESEARCH 30.2 (1982): A391-A391.
Source
wos-lite
Published In
Clinical Research
Volume
30
Issue
2
Publish Date
1982
Start Page
A391
End Page
A391
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