Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta3”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources
PubMed2005

Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

Adult↗
PubMed1999

The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans.

STUDY OBJECTIVES: To determine whether the polymorphic dinucleotide repeats found in intron 4 of the endothelial cell nitric oxide synthase (ecNOS) gene and the platelet GPIIIa PLA(1)/A(2) polymorphism are associated with myocardial infarction (MI) and venous thromboembolism (VTE) in African Americans. Because these two genes may interact physiologically, the third objective was to determine if there was a relationship between the polymorphisms with respect to MI and VTE. DESIGN: A hospital-based case-control study. After informed consent was obtained, blood used for DNA extraction was drawn from the subjects. SETTING: The study was conducted in the Anticoagulant Clinic and the Cardiology Clinic at Grady Memorial Hospital in Atlanta Georgia. PATIENTS: Subjects were recruited from African-American patients with a reported history of MI (n = 110) or VTE (n = 91). Control subjects (n = 185) without a history of cardiovascular or venous disease were recruited from an outpatient clinic. MEASUREMENTS AND RESULTS: The 393 ecNOS allele was more common among MI cases (36%; p = 0.01) and VTE cases (35%; p = 0.04) than among control subjects (26%). There was no association between the GPIIIa genotypes and either MI or VTE. However, among the MI subjects, there was a strong association between the ecNOS 393/393 genotype and the Pl(A2) allele. It was also found that the frequency of the 393 allele was higher in African-American persons (0.26) compared with what has been reported for Australian Caucasians (0. 14) and Japanese (0.10). CONCLUSIONS: The 393 allele but not the Pl(A2) allele was significantly associated with both MI and VTE in African Americans. Homozygosity for the 393 allele was significantly associated to the diagnosis of MI prior to the age of 45. The combination of the 393 allele and a Pl(A2) allele was also highly associated with MI. The frequency of the 393 allele was significantly higher in African Americans than what has been reported for other populations. This study furthers not only extends the association of the 393 allele to VTE but has demonstrated an interaction with the Pl(A2) allele with respect to MI.

Adult↗
PubMed2005

Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation.

Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore, an immunohistochemical and morphometric study was performed on BM biopsies in 20 patients before and at standardized intervals (days 30 through 384) following SCT. In responding patients, a total regression of the pretransplant increased fibrosis was completed in the posttransplant period after about six months, while the extent of osteosclerosis did not change significantly during observation time. The quantity of CD61+ megakaryocytes including precursors was strikingly variable after SCT and, by using planimetric methods, atypical microforms exhibiting a dysplastic aspect could be demonstrated. These anomalies may be responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were increased before transplantation, however, their number declined rapidly to normal values in responding patients. Nucleated erythroid precursors revealed a decreased amount before and after SCT accounting for anemia. Large clusters of this cell lineage indicated an initial hematopoietic reconstitution comparable with the expansion of the neutrophil granulopoiesis. Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover.

Adolescent↗
PubMed2002

HPA-1 carrier status and thrombocytopenia in preterm infants with a birth weight below 1500 grams.

OBJECTIVE: In cohorts of infants with proven neonatal alloimmune thrombocytopenia (NAIT) an unusual high rate of preterm infants has been reported, raising the question of whether NAIT contributes to the high rate of intracranial hemorrhage in preterm infants. METHODS: We genotyped the HPA-1-allele in a large cohort of term (n = 205) and very low birth weight infants (VLBW-infants, n = 299) with polymerase-chain-reaction and restriction enzyme digestion. RESULTS: HPA-1a/b is the only fetal HPA-1-genotype in which alloimmunization and NAIT could occur. Genotype distribution did not differ between term and VLBW-infants (p = 0.26). Furthermore, neither HPA-1a/b genotype nor platelet count at birth were of significant prognostic value in predicting subsequent intracranial haemorrhage or death in VLBW-infants (p = 0.93 and p = 0.19 respectively). CONCLUSION: Our data did not support the hypothesis that routine screening of preterm infants or their mothers for HPA-1-genotype is of additional value in the care of these infants.

Antigens, Human Platelet↗
PubMed2005

A case report of neonatal alloimmune thrombocytopenic purpura: the importance of correct diagnosis for future pregnancies.

CONTEXT: Neonatal alloimmune thrombocytopenic purpura (NAITP) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet antigens inherited from the father. Intracranial hemorrhage leading to death or permanent neurological disability may occur in the fetus. CASE REPORT: A healthy 30-year-old woman gave birth to her first baby by cesarean after an uneventful 36-week pregnancy. Ten hours after birth, the infant presented severe petechiae, with platelet count of 8 x 10(3)/microl. The mother's platelet count was normal (180 x 10(3)/microl). The infant re ceived intravenous immunoglobulin and was discharged 18 days later, with platelet count of 100 x 10(3)/microl. The cause of thrombocytopenia was not elucidated at that time. One year later, the infant died of neuroblastoma. Since the parents wanted another child, they were referred for investigation of this thrombocytopenia. Platelet genotyping and platelet antibody screening were performed, showing total HPA-1 system mismatch between mother (HPA-1b1b) and father (HPA-1a1a), with anti-HPA-1a antibodies in the mother's serum. We concluded that the first baby was born with NAITP. Thus, in the second pregnancy, the mother was treated with several infusions of intravenous immunoglobulin. Careful ultrasound monitoring was performed, with normal results for mother and fetus throughout the pregnancy. The second baby was born by cesarean at 39 weeks, presenting 92 x 10(3) platelets/microl six hours after birth. The baby's platelets were genotyped as HPA-1a1b and the mother's serum again showed anti-HPA-1a antibodies. No clinical bleeding was observed. Intravenous immunoglobulin therapy was an effective treatment for preventing NAITP in the second baby.

Adult↗
PubMed2005

Aspirin resistance: an evaluation of current evidence and measurement methods.

Aspirin resistance is a poorly characterized phenomenon, whereby certain patients do not benefit from the antithrombotic effect of aspirin. The frequency of aspirin resistance is unknown, but estimates range from 5-60%. The mechanism of aspirin resistance also is unknown; proposed mechanisms are poor patient compliance, poor aspirin absorption, increased isoprostane activity, platelet hypersensitivity to agonists, increased cyclooxygenase-2 activity, a cyclooxygenase-1 polymorphism, and the platelet alloantigen 2 polymorphism of platelet glycoprotein IIIa. Aspirin resistance appears to be dose related in some patients and therefore may be overcome with high doses. Evidence indicates that aspirin resistance is a dynamic state, with significant intrapatient variability in aspirin sensitivity with time. To date, a sensitive and specific assay of aspirin effect that reliably predicts treatment failure has not emerged. However, several commercially available products are being marketed for this purpose without convincing clinical data. Despite a wealth of literature on the topic, aspirin resistance remains an enigma. Further investigation is needed regarding strategies to identify and treat patients resistant to aspirin.

Antigens, Human Platelet↗
PubMed2003

Differences between peripheral blood and cord blood in the kinetics of lineage-restricted hematopoietic cells: implications for delayed platelet recovery following cord blood transplantation.

Cord blood (CB) cells are a useful source of hematopoietic cells for transplantation. The hematopoietic activities of CB cells are different from those of bone marrow and peripheral blood (PB) cells. Platelet recovery is significantly slower after transplantation with CB cells than with cells from other sources. However, the cellular mechanisms underlying these differences have not been elucidated. We compared the surface marker expression profiles of PB and CB hematopoietic cells. We focused on two surface markers of hematopoietic cell immaturity, i.e., CD34 and AC133. In addition to differences in surface marker expression, the PB and CB cells showed nonidentical differentiation pathways from AC133(+)CD34(+) (immature) hematopoietic cells to terminally differentiated cells. The majority of the AC133(+)CD34(+) PB cells initially lost AC133 expression and eventually became AC133(-)CD34(-) cells. In contrast, the AC133(+)CD34(+) CB cells did not go through the intermediate AC133(-)CD34(+) stage and lost both markers simultaneously. Meanwhile, the vast majority of megakaryocyte progenitors were of the AC133(-)CD34(+) phenotype. We conclude that the delayed recovery of platelets after CB transplantation is due to both subpopulation distribution and the process of differentiation from AC133(+)CD34(+) cells.

AC133 Antigen↗
PubMed2004

The role of the platelet glycoprotein IIb/IIIa in thrombosis and haemostasis.

Haemostasis is a finely balanced and complex process ideally initiated only in response to disruption of the vascular endothelium as a means of preventing loss of blood from an injured vessel. Deviations from the ideal can lead to serious disease. Firstly, thrombosis, which arises as a consequence of inappropriate platelet-platelet interactions at a region of vessel damaged by atherosclerosis, can lead to occlusion of the affected vessel as in myocardial infarction or stroke. Secondly, loss of the ability of platelets to form aggregates leads to Glanzmann's thrombasthenia (GT) with a tendency to bleed for prolonged periods following injury. Glycoprotein IIb/IIIa (GPIIb/IIIa) plays a major role in the regulation of platelet adhesion and aggregation during haemostasis. Upon platelet activation by an agonist a signalling process is initiated, termed "inside-out" signalling, which gives rise to conformational changes within GPIIb/IIIa. These conformational changes increase the affinity of the receptor for its primary ligand, fibrinogen. Bound fibrinogen then acts as a bridging molecule facilitating the interaction of adjacent platelets. Upon fibrinogen binding GPIIb/IIIa undergoes further conformational changes and through a process termed "outside-in" signalling the receptor signals in to the platelet ultimately resulting in acceleration of the aggregation process. Qualitative or quantitative abnormalities in GPIIb/IIIa give rise to GT, a recessive bleeding disorder, and analysis of affected individuals has provided invaluable insights into the structure/function relationship of this receptor. Due to its critical role in mediating platelet aggregate formation GPIIb/IIIa has become a primary target for the development of antithrombotic agents.

Animals↗
PubMed2001

Increased prevalence of microthromboses in retinal capillaries of diabetic individuals.

In diabetic retinopathy, capillary nonperfusion and eventual obliteration can lead to retinal ischemia and sight-threatening neovascularization. The occurrence of retinal microthrombosis in human diabetes has long been suspected and occasionally observed but never systematically demonstrated. We used trypsin digestion to isolate the intact vascular network from retinas obtained postmortem from nine diabetic donors (age 64 +/- 11 years, duration of diabetes 6 +/- 4 years; mean +/- SD) and eight age-matched nondiabetic donors. Topographically matched sectors (each one-sixth of retina) of diabetic and nondiabetic retinas were tested sequentially with antibodies to fibrin cross-linking factor XIII and platelet glycoprotein (GP)-IIIa to identify fibrin-platelet thrombi. In some trypsin digests, we also examined vascular cell apoptosis. The retina from a nondiabetic donor, 24 years of age, who had died of trauma, was used to exclude confounding influences caused by the postmortem period. When compared with those of nondiabetic donors, the retinas of diabetic donors showed double the number of capillary segments with colocalized immunostaining for factor XIII and GPIIIa (P = 0.02). The total area of the positive segments was fourfold greater in the diabetic than in the nondiabetic donors (P = 0.02) and correlated with the duration of diabetes (r = 0.71, P < 0.05). Large thrombi were six times more frequent in the diabetic donors (P = 0.03), and there was a significant topographical association of microthrombosis with apoptotic cells in both diabetic and nondiabetic vessels (P = 0.0001). Hence, diabetes of short duration was found to be associated with a greater than normal number and size of platelet-fibrin thrombi in the retinal capillaries. These thrombi can contribute to capillary obliteration and retinal ischemia and may be a practical target for early drug intervention.

Adult↗
PubMed1999

Multiprobe RNase protection assay with internally labeled radioactive probes, generated by RT-PCR and nested PCR.

RNase Protection Assay (RPAs) is a highly sensitive and reproducible method of quantitating the levels of specific mRNA transcripts. The introduction of the commercially available Multiprobe RPAs allow comparing and quantifying the expression of up to different mRNA species in a single sample of 1-20 micrograms of total RNA. To generate probes which are not commercially available, we prepared highly specific probes by RT-PCR and nested PCR. Then, after ligation of a T7 promoter, another PCR was performed with a primer set consisting of a specific sense primer and antisense T7 primer. Only the antisense strand of the double stranded PCR-product contained the T7-promoter sequence on its 5' end, allowing in vitro transcription and internal labeling with [alpha-32]UTP. Probe concentration was determined in a scintillation counter and equal counts were introduced in the assay. In vitro transcription of the PCR generated probes resulted in radioactive probes with a very high specific activity, allowing simultaneous analysis of 70 different RNA samples. RPA could be performed under the same conditions as recommended for the commercially available probe sets, avoiding time consuming optimization of reaction conditions. Negative controls consisted of yeast RNA and sense RNA probes. Positive controls were single stranded templates, generated by asymmetric PCR. Dilution series revealed a high reproducibility and the potential of this technique to semi-quantitate mRNA in different RNA samples. In conclusion, probes may be generated by RT-PCR and nested PCR that will work with the commercially available Multiprobe RPAs. The high probe yield allows analysis of a great number of samples using the same set of probes with a high reproducibility.

Antigens, CD↗
PubMedDate not supplied

Anti-Bak(a) neonatal alloimmune thrombocytopenia: possible prevention by intravenous immunoglobulin.

Neonatal alloimmune thrombocytopenia (NAIT) most commonly involves antibodies directed against the PlA1 antigen, but other platelet specific alloantigens have been associated with it. We describe the case of a mother whose first three infants developed NAIT secondary to anti-Bak(a) antibodies, while her fourth infant did not. The three affected infants were treated postnatally with platelet transfusions. The fourth infant was treated antenatally with one dose of intravenous immunoglobulin (IVIg) given to the mother. Postpartum analysis revealed the infant's platelets to be Bak(a)-positive but negative for elevated IgG. Maternal serum reacted with neonatal platelets in vitro, but cord serum was negative for antiplatelet antibodies. These clinical observations do not prove the efficacy of IVIg; however, they raise several questions: Why wasn't this infant thrombocytopenic? Why didn't the umbilical cord contain maternal antibody? Was the single dose of IVIg responsible for preventing NAIT? IVIg is currently under investigation in a clinical trial evaluating its effectiveness in preventing NAIT in mothers with anti-PlA1 antibodies, where it has shown some success. There have been no reports of the use against anti-Bak(a) antibodies. We suggest that a weekly dose schedule may not be necessary for all affected pregnancies, and antibodies with specificity other than anti-PlA1 may require less vigorous therapy.

Adult↗
PubMed1998

MER53, a non-autonomous DNA transposon associated with a variety of functionally related defense genes in the human genome.

We report a new medium reiteration frequency repeat MER53 present in human and mammalian genomes. A 189 bp MER53 consensus sequence has been reconstructed based on the computer analysis of GenBank sequences. TA target site duplication and terminal inverted repeats indicate that the MER53 repeat is a non-autonomous DNA transposon related to the mariner family. Two MER53 repeats were found integrated within different mobile elements. We have found that most of the genes harboring the MER53 repeat are involved in the host defense system. The reasons for this non-random distribution of the repeat are discussed.

Animals↗
PubMed1996

Serine 752 in the cytoplasmic domain of the beta 3 integrin subunit is not required for alpha v beta 3 postreceptor signaling events.

A naturally occurring point mutation (Ser752Pro substitution) in the beta subunit cytoplasmic domain of the platelet fibrinogen receptor GPIIb-IIIa (integrin alpha IIb beta 3), causing Glanzmann's thrombasthenia, has been shown to abrogate bidirectional transmembrane signaling of GPIIb-IIIa when expressed in heterologous cells (Chen YP, 1994, Blood 84, 1857-1865). As the vitronectin receptor alpha v beta 3 constitutively mediates cell attachment to RGD containing extracellular matrix proteins, the purpose of this study was to explore the regulatory role of Ser752 in alpha v beta 3 vitronectin receptor function, by cotransfecting recombinant human alpha v cDNA together with human beta 3 mutant cDNA into Chinese hamster ovary (CHO) cells. CHO cells expressing wild type human alpha v beta 3 acquired the ability to attach and spread on fibrinogen and von Willebrand factor, in contrast to non transfected CHO cells that only bound to vitronectin and fibronectin. Overexpression of a truncated recombinant beta 3 subunit (beta 3 delta 744) generated alpha v (hamster) beta 3 (human) chimers that mediated attachment but lost the ability to promote cell spreading on vitronectin, von Willebrand factor and fibrinogen, and to concentrate in focal contact sites, demonstrating a negative effect of beta 3 delta 744 on alpha v beta 3 dependent postreceptor occupancy events. Transfection of beta 3Ser752Pro reproduced the same negative effect as beta 3 delta 744, whereas beta 3Ser752Ala restored normal receptor function by allowing pronounced attachment and spreading on fibrinogen and von Willebrand factor. Our results provide evidence that (1) the C-terminal cytoplasmic domain of beta 3 (amino acids 744-762) is essential for alpha v beta 3 integrin postreceptor occupancy events; (2) within this domain, the Ser752Pro mutation affects alpha v beta 3 postreceptor occupancy events by preventing cell spreading and focal contact localization; (3) the defective receptor function of the vitronectin receptor alpha v beta 3 is due to the presence of Pro752, rather than the absence of Ser752, as a Ser to Ala substitution at position 752 restores normal beta 3 integrin cell spreading and adhesive plaque formation.

Alanine↗
PubMed1996

Identification of a new biological function for the integrin alpha v beta 3: initiation of fibronectin matrix assembly.

Fibronectin matrix assembly is a complex cellular process initiated by specific fibronectin-binding cell surface receptors. Although the integrin alpha 5 beta 1 has been implicated in the assembly of fibronectin matrices, fibroblastic cells derived from alpha 5 integrin null mutant embryos assemble a fibronectin matrix. Thus, alternative receptors must support this process. Although the platelet integrin alpha IIb beta 3 supports fibronectin matrix assembly, its expression is restricted to platelets. We report that alpha v beta 3 integrin, a fibronectin receptor expressed on many cell types provides an alternative pathway for the assembly of soluble fibronectin into the extracellular matrix. This process occurs independent of alpha 5 beta 1, is also modulated by activation, and the resulting matrix is biochemically indistinguishable from that assembled under the control of alpha 5 beta 1. Matrix assembly requires binding to the RGD site in the 10th type III repeat of fibronectin, as well as the participation of the amino-terminal matrix assembly domain. The participation of two distinct integrins in fibronectin matrix assembly suggests a model for the involvement of integrins in a dual system of extracellular matrix assembly and recognition controlled by intracellular activation of extracellular receptors.

Animals↗
PubMed1990

Posttransfusion purpura: conversion of PLA1-negative platelets to the PLA1-positive phenotype by stored plasma is not due to the presence of soluble PLA1 antigen.

Three previous articles have reported a PLA1 antigen in the plasma of stored blood which is capable of binding to PLA1-negative platelets in the presence of divalent cations, rendering them PLA1 positive. Such a mechanism could explain the enigma of posttransfusion purpura (PTP), i.e., severe thrombocytopenia in a healthy subject with PLA1-negative platelets secondary to the infusion of blood containing PLA1-positive platelets. We find that the PLA1 antigen of stored blood is due to the presence of platelet fragments which can be removed by centrifugation and that divalent cation-chelating agents play no role in the apparent binding of these fragments to platelets. The apparent conversion of PLA1-negative platelets to the PLA1-positive phenotype by incubation with stored plasma from a PLA1-positive subject is due to the cosedimentation of platelet fragments with the platelets. No soluble PLA1 antigen was found in the plasma of five patients with acute posttransfusion purpura.

Antigens, Human Platelet↗
PubMed2004

Association of the gene polymorphisms of platelet glycoprotein Ia and IIb/IIIa with myocardial infarction and extent of coronary artery disease in the Korean population.

Platelet membrane receptor glycoproteins (GP) are essential for the platelet activation process, and the genetic polymorphisms in the genes that encode platelet glycoproteins have been proposed to influence the risk of acute coronary syndrome and atherosclerosis. In this study, we investigated the role of GPIa, HPA-1 and HPA-3 polymorphisms as putative risk factors for myocardial infarction (MI) and the extent of coronary artery disease. We selected 1,073 subjects who underwent coronary angiography; 242 had normal or minimal coronary atherosclerosis, and 831 patients had significant coronary artery disease (CAD). The genotype was determined by the methods of single base extension for C807T/G873A polymorphisms of GPIa, and restriction fragment length polymorphism for HPA-1 and HPA-3. The C807T and G873A polymorphisms of GPIa showed complete linkage in the Korean population. For HPA-1 gene polymorphism, only the HPA-1a/a (PlA1/A1) genotype was observed in 192 selected subjects from our study population. The distribution of GPIa (C807T/G873A) and HPA-3 genotypes did not differ significantly between normal subjects and CAD subjects. No significant association between MI and both gene polymorphisms was present. However, for the subgroup analysis of young male patients whose age was less than 56 years, the genotype frequency of HPA-3b/b was significantly lower in patients with MI compared to patients without a history of MI (7.5% vs. 20.0%, p=0.04). The odds ratio for HPA-3 b homozygosity versus the HPA-3a carrier was 0.32 (95% CI, 0.10- 0.99, p=0.04). Conclusively, HPA-3 polymorphism was associated with MI in Korean individuals younger than 56 years of age, but other polymorphisms of GP, which we studied, were not associated with both the extent of coronary atherosclerosis or MI.

Aged↗