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Biomedical subjects

A Eldor

Publications and source records attributed to A Eldor.

At least 145 records · Page 8Linked to original sources
PubMed1989

Structural and immunological properties of myosin from human platelet external and internal membranes.

Our previous studies indicate that platelets contain two myosin isoforms, one of them localized in the membrane while the other in the cytoplasmic compartment. Structural and functional differences of these myosins have been characterized. In this study two platelet membrane subfractions, the external and the internal membranes, were isolated simultaneously from a crude membrane fraction and their purity was characterized using specific marker enzymes. Myosin was shown to be present in both membrane fractions and its structural and immunological properties were investigated. The electrophoretic mobilities of myosin in both membrane preparations were identical to the mobility of its cytoplasmic counterpart. Two-dimensional peptide mapping of the iodinated tryptic peptides of the myosin heavy chains indicated that at least one peptide is missing in the maps of the myosins from the external and internal membranes as compared to their soluble counterpart. Our data suggest that myosin is located in three distinct platelet compartments: cytosol, external and internal membranes. The same myosin isoform is located in the two membrane compartments, while the isoform found in the cytosol is different. The observed variations in the structure of the two isoforms may reflect differences in their respective physiological functions.

Blood Platelets↗
PubMed1989

Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells.

The effects of radiation on the release of mitogenic factors into the media of cultured endothelial cells of bovine, porcine, and human origins were studied. Although unirradiated controls revealed a significant background activity, single doses of irradiation (20-60 Gy) resulted in a dose-related increased release of growth factor activity, measured by the mitogenic effects of the conditioned media on both 3T3 mouse fibroblasts and unirradiated endothelial cells serving as target cells. Receptor binding competition assays for the platelet-derived growth factor receptor revealed that 12-28% of the total mitogenic activity was due to platelet-derived growth factor-like mitogens. Mitogenic assays using endothelial cells and specific antibody mediated inhibition assays suggested that another component of the mitogenic activity was due to a fibroblast growth factor-like factor. Although radiation resulted in a significant increase in cell death, the enhanced growth factor activities did not appear to result from cell lysis-related leakage of intracellular stores of growth factor. Instead, our data suggest that the growth factors were synthesized de novo and secreted at elevated levels by the cells which maintained postradiation a high level of metabolic activity. Time course studies demonstrated that the growth factors accumulation in the conditioned media started within the first 24 h after radiation and reached a plateau within 72 h after treatment. Radiation-induced release of endothelial cell-derived growth factors may be involved in the pathogenesis of both early vascular damage and the late fibrosis which represents a prominent feature of late radiation damage in normal tissues.

Animals↗
PubMed1989

Platelet survival in patients with beta-thalassemia.

Thromboembolic events associated with significant morbidity and mortality have been observed in patients with beta-thalassemia major (TM). These include arterial as well as venous thrombosis and the development of early arteriosclerosis. To elucidate the possibility that TM patients may develop a hypercoagulable state we carried out a study of platelet kinetics on ten patients with TM and four patients with thalassemia intermedia (TI). Autologous platelets were labeled with indium-111-oxine, and the platelet lifespan (PLS) was determined. A significant shortening of PLS was observed in 13 out of 14 patients examined. The mean PLS (+/- 1 SD) in ten patients (8 TM, 2 TI) who underwent splenectomy was 107 +/- 36 hr (control splenectomized 248 + 51 hr) (P less than .001) and in four nonsplenectomized patients (2 TM, 2 TI) was 102 +/- 64 hr (control 224 + 23 hr) (P less than .01). The short PLS in addition to reported findings of increased circulating platelet aggregates and the decreased response of TM platelets to aggregating agents suggests in vivo platelet activation in thalassemic patients.

Adolescent↗
PubMed1989

Altered structural and functional properties of myosins, from platelets of idiopathic scoliosis patients.

Platelets of patients with idiopathic scoliosis (IS) have been shown to have decreased capacity to aggregate and secrete in response to certain agonists. Similarities between the contractile protein system of platelets and muscle have made the platelets a popular model for muscle disease. We attempted to characterize the function and structure of myosin in platelets of IS patients. Blood was obtained from seven IS patients and seven matched non-scoliotic healthy controls. The mean Cobb angle measurement of the IS patients was 35.4 degrees with a mean Risser sign of 2.2. Washed platelets were isolated from the blood, and the contractile proteins from the membrane and the cytosol compartments were isolated and analyzed by two-dimensional peptide mapping. As previously reported (J Biol Chem 258:9290, 1983), peptide maps of normal platelets revealed that the heavy chain of myosin located in the platelet membrane lacks one major spot relative to the cytoplasmic myosin. In IS patients the cytoplasmic myosin lacks the same peptide that is missing in the membrane myosin of normal individuals. In addition, the ATPase specific activity of the cytoplasmic myosin from IS platelets was significantly lower compared with the activity of the cytoplasmic myosin from normal platelets. These results suggest the presence of a fundamental abnormality of IS platelet contractile proteins.

Adenosine Triphosphatases↗
PubMed1989

Successful pregnancies of two patients with relapsing thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a severe multisystemic disorder of unknown origin. The association of relapsing TTP with pregnancy is rare but well documented and high mortality rates of mothers and fetuses have been reported so far. Since the introduction of plasma therapy for treating the acute exacerbations of the disease, overall mortality rates have decreased significantly. It is now evident that the manifestations of the disease may reappear even after long disease-free intervals and as many as a third of the recovering patients may develop a relapse. Presented are two TTP patients with relapsing TTP complicating their pregnancies. Prophylactic treatment with aspirin and dipyridamole during their last three successful pregnancies prevented or minimized the severity of TTP relapses. The course of these pregnancies and the management of such patients is discussed.

Adult↗
PubMed1989

Megakaryocyte function and dysfunction.

More than a hundred years have passed since platelets were recognized as cells and their haemostatic functions discovered. However, the process of platelet production is still not understood. The location, the mechanism and the regulation of thrombopoiesis remain elusive. Megakaryocytes are known to be the source of platelets. Investigations of megakaryocytes have revealed their normal functions and some of the abnormalities present in various diseases which affect platelets. In recent years, new techniques of cell isolation and tissue culture have been developed and have made possible advances in characterizing megakaryocyte precursors and differentiation. The primary function of megakaryocytes is to synthesize and assemble platelet components and organelles. Although debated for a long time, new data seems to indicate that the lung may be a central locus of platelet production. The new techniques for megakaryocyte investigations have barely begun to be of use in the study of abnormal platelet production in disease.

Animals↗
PubMed1989

Perturbation of endothelial functions by ionizing irradiation: effects on prostaglandins, chemoattractants and mitogens.

Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inflammatory changes, and late tissue fibrosis. These processes may be mediated by endothelial products released as a result of cellular injury. Using EC cultures, we show that ionizing irradiation affects one of the major vascular defense mechanisms against platelet activation, thrombosis, and atherosclerosis--the capacity to produce PGI2. Dose- and time-related damage to enzymes of the arachidonic acid cascade were demonstrated. Radiation damage is associated with oxidant stress and production of free radicals. The oxygen radical scavenger, vitamin C, was found to protect the capacity of irradiated ECs to produce PGI2. Radiation injury often induces an acute inflammatory response. We found that irradiated ECs release a chemotactic factor for neutrophils, which is a lipid product of the lipoxygenase pathway. Late radiation-induced tissue fibrosis and the capacity of radiation to enhance arteriosclerosis may involve participation of mitogens released from perturbed and damaged ECs. We show that conditioned medium of irradiated ECs contain larger amounts of newly synthesized mitogens capable of stimulating the proliferation of fibroblasts, SMCs, and ECs. Hence, it may be assumed that the mitogenic activity released by irradiated ECs includes both PDGF and FGF-like mitogens.

Animals↗
PubMed1989

Cytocidal effect caused by the envelope glycoprotein of a newly isolated avian hemangioma-inducing retrovirus.

We isolated a field strain of avian hemangioma retrovirus (AHV) which induces a cytopathic effect (CPE) on cultured avian and mammalian cells shortly after infection. The kinetics of cell killing were dependent on the multiplicity of infection. The CPE on avian and mammalian cells was independent of virus replication, because UV-irradiated virus led to cell death as well. Biochemical and genetic experiments indicated that AHV env gene products were responsible for the CPE. Partially purified AHV envelope glycoproteins (gp85), but not those of the Rous sarcoma virus Prague C strain, induced a CPE. Rous-associated virus type 1, in which the env region was replaced by the AHV gp85 region, induced a CPE on avian and mammalian cultured cells. Therefore, we suggest that CPE is induced by AHV via interaction between viral gp85 and the cell membrane. This mode of CPE is unique among avian sarcoma-leukemia viruses.

Alpharetrovirus↗
PubMed1989

Successful splenectomy in May-Hegglin anomaly: report of a case with platelet kinetic studies.

Bleeding diathesis is not necessarily one of the conspicuous and serious characteristics of the macrothrombocytopenic syndromes, which include the May-Hegglin anomaly. Nevertheless, occasionally prolonged bleeding time may endanger organs or even life. We report a case of a young girl with severe thrombocytopenia due to May-Hegglin anomaly, who was facing blindness because of intraocular haemorrhages. Being unable to intervene in the pathogenesis of the disease, we performed splenectomy after proving splenic sequestration of platelets. This procedure allowed the performance of a successful bilateral vitrectomy.

Blood Platelets↗
PubMed1989

Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties.

We have analyzed the binding of thrombin, a serine protease with central roles in hemostasis, to the subendothelial extracellular matrix (ECM) produced by cultured endothelial cells. This substrate provides a thrombogenic surface where hemostasis is initiated. Binding was saturable and equilibrium was achieved after 3 h incubation with 125I-alpha-thrombin. Scatchard analysis of thrombin binding revealed the presence of 5.1 X 10(9) binding sites per squared millimeter ECM, with an apparent Kd of 13 nM. The catalytically blocked enzyme, diisofluorophosphate (DIP)-alpha-thrombin competed efficiently with 125I-alpha-thrombin, indicating that the binding was independent of its catalytic site. Moreover, high concentrations of the synthetic tetradecapeptide, representing residues 367-380 of thrombin B chain (the macrophage mitogenic domain of thrombin), competed with thrombin binding to ECM, indicating that the binding site may reside in the vicinity of "loop B" region. Thrombin binds to dermatan sulfate in the ECM, as demonstrated by the inhibition of 125I-alpha-thrombin binding to ECM pretreated with chondroitinase ABC, but not with heparitinase or chondroitinase AC. This stands in contrast to 125I-FGF (fibroblast growth factor) binding to ECM, which was inhibited by heparitinase but not by chondroitinase ABC, ECM-bound thrombin exhibits an exposed proteolytic site as monitored by the Chromozyme TH assay and by its ability to convert fibrinogen to a fibrin clot and to induce platelet activation as indicated by 14C-serotonin release. ECM-bound thrombin failed to form a complex with its major circulating inhibitor-antithrombin III (AT III), compared with rapid complex formation with soluble thrombin. We propose that thrombin binds to subendothelial ECM where it remains functionally active, localized, and protected from inactivation by circulating inhibitors.

Amides↗
PubMed1989

Functional, biochemical, and structural anomalies in platelets of patients with idiopathic scoliosis.

Idiopathic scoliosis (IS) is the most common type of lateral curvature of the spine, the etiology of which is unknown. Among the various pathological changes that have been reported in IS are platelet anomalies. Since the platelets are not involved mechanically in the spinal deformity, platelet disorders may reflect a basic cellular pathology and not a secondary change attributed to the spinal curvature. In the present review, a summary of the platelet anomalies in idiopathic scoliosis is presented. The accumulated data indicate the existence of profound functional anomalies in platelets of patients with IS. An attempt is made to clarify the different anomalies and to try to link them together.

Blood Platelets↗
PubMed1988

Generation of lipid neutrophil chemoattractant by irradiated bovine aortic endothelial cells.

Radiation injury to blood vessels is associated with an acute inflammatory process. We investigated the capacity of cultured bovine aortic endothelial cells (BAEC) to produce chemotactic factors after radiation injury. BAEC in serum-free media were irradiated with a cobalt-60 Gammacell 220 and the cell supernatants were assayed for chemotactic activity for human neutrophils in a Boyden chamber. There was a rapid release of chemotactic activity into the BAEC supernatants which was dependent both on the dose of radiation (5 to 40 Gy) and the time between irradiation and sample collection. In contrast, isolation of BAEC lysates by freeze-thawing was not associated with the presence of similar chemotactic activity. The chemotactic activity released from the irradiated BAEC was not destroyed by boiling nor by treatment with trypsin. The release of the chemotactic activity was, however, inhibited by the addition of a lipoxygenase inhibitor but not by the addition of a cyclooxygenase inhibitor before the irradiation. The chemotactic activity was recovered from the cell supernatants in the lipid phase after extraction with chloroform/methanol. Furthermore, the chloroform/methanol extracts co-eluted with authentic leukotriene B4 when the BAEC were prelabeled with [14C] arachidonic acid. However, we were unable to detect endogenous leukotriene B4 with RIA. Instead, the only detectable endogenous lipid present in the supernatants was 13-hydroxyoctadecadienoic acid which is derived from linoleic acid via the lipoxygenase pathway. 13-Hydroxyoctadecadienoic acid, however, had no chemotactic activity. These findings suggest that endothelial cells rapidly release a chemotactic agent after irradiation, the release of which is associated with a lipoxygenase pathway. The release of this chemotactic activity may account in part for the acute inflammatory response that is observed after ionizing irradiation.

Animals↗
PubMed1988

Permanent neurological complications in patients with thrombotic thrombocytopenic purpura.

According to previous clinical studies, the neurological manifestations observed in patients with thrombotic thrombocytopenic purpura (TTP) are considered to be transient. The introduction of plasma therapy in 1977 as major treatment modality for TTP has changed the prognosis of the disease. In a clinical survey of 38 patients with TTP who received plasma therapy, we have observed five patients who developed permanent neurological deficits despite their prompt recovery from TTP. In this study, we describe the new complication of TTP and summarize the neurological manifestations observed in these patients during their first episode of TTP and during the relapses, which occurred in 12 of them.

Adult↗