Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:001400 (PRP)
 1,320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PEA is a potent inhibitor (Ki approximately 13 microM) of human platelet aggregation induced by epinephrine. This led us to perform an SAR study of a congeneric series of compounds in an effort to identify the molecular components of epinephrine critical to its aggregating effect upon human platelets. Phenylethanolamine was similar to PEA in inhibitory potency. However, hydroxylation of the phenyl ring diminished the inhibitory effect (Ki tyramine approximately 87 microM; Ki octopamine approximately 88 microM). Dopamine, the weakest inhibitor (Ki approximately 150 microM), was a partial agonist capable of inducing platelet aggregation in some samples of PRP. The order of potency of catecholamines as aggregating agents was epinephrine greater than norepinephrine greater than Epinine greater than dopamine. Phenylephrine, the prototype alpha-agonist, did not induce aggregation but was a potent inhibitor (Ki approximately 12 microM) of the aggregation induced by epinephrine. Isoproterenol, the prototype beta-agonist, was neither an aggregant nor an inhibitor of epinephrine-induced platelet aggregation. These findings suggest that the binding of epinephrine to the alpha-adrenergic receptor responsible for platelet aggregation is accomplished by the N-methyl amino group whereas intrinsic aggregating activity is a function of the catechol moiety.
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PMID:Structure activity relationships between catecholamines and the alpha-adrenergic receptor responsible for the aggregation of human platelets by epinephrine. 21 17

The clinical picture, family history and laboratory findings of 100 patients with von Willebrand's disease (VWD) have been studied in Italy in a multicentre survey from two rural areas with a known high incidence of the disease and from two large cities (Rome and Milan). Bleeding time, procoagulant factor-VIII (VIIIAHF) assay, platelet retention and PRP-ristocetin aggregation were measured in each centre, and plasma samples were frozen and subsequently assayed for factor VIII-related antigen (VIIIAGN) and ristocetin co-factor (VIIIVWF) in one laboratory (Milan). On the basis of the inheritance pattern, clinical severity of the disease and laboratory findings, patients with VWD were separated into two groups. In 17 patients the absence of a family history of bleeding, a high incidence of parental consanguinity and involvement of both sexes suggested an autosomal recessive mode of inheritance; the unusual severity of the disease with markedly abnormal results of all six laboratory measurements (and frequent reduced levels of VIIIAGN and VIIIVWF in the unaffected parents) were consistent with the homozygous state. In 83 patients, the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity. In these, VIIIVWF was usually much lower than VIIIAHF and VIIIAGN. The findings suggest that although some patients may present with simultaneous abnormalities of all six studied laboratory measurements, the majority show a variation in the spectrum of the abnormal results, without any obvious simple pattern.
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PMID:Spectrum of von Willebrand's Disease: a study of 100 cases. Italian Working Group. 30 Jun 28

We have tested a platelet aggregation inhibitor in the incubation fluid of deendothelialized fragments of the rat aorta and compared it with that of "intact" fragments. Some of the properties of the aortic inhibitor, and its effects on platelet adhesion to collagen fibrils, on platelet factor-3 (PF-3) availability, and on the activated partial thromboplastin time (APTT) and thrombin time (TT) were also evaluated in comparison with similar effects exerted by PGI2. We found that the incubation fluid of deendothelialized aortic samples contained inhibitor activity comparable with that of "intact" samples. The aortic inhibitor had similar properties to PGI2. The aortic inhibitor and PGI2 slightly inhibited light transmission changes of EDTA-PRP following exposure to collagen. However, scanning electron microscopy showed no appreciable difference in platelet adhesion to collagen fibrils. PGI2 and the aortic inhibitor inhibited Kaolin-induced PF-3 availability, but did not prolong the APTT or TT.
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PMID:Generation of a PGI2-like activity by deendothelialized rat aorta. 38 19

The potencies of prostaglandins (PG) I2, PGD2 and PGE1 as inhibitors of human platelet aggregation induced by threshold concentrations of four aggregating agents were determined in platelet-rich plasma from normal individuals who had not ingested aspirin. The order of activity against ADP, adrenaline and collagen was always PGI2 greater than PGD2 greater than PGE1. However, PGD2 and PGE1 were almost equipotent with PGI2 when tested against arachidonic acid (AA). The threshold inhibitory effects of PGD2, PGE1 and PGI2 could be over come by increasing the concentrations of the aggregating agents AA, collagen or ADP. Adrenaline was found to be different from the other aggregating agents. It could overcome inhibition of platelet aggregation by PGD2 but could not overcome inhibition by PGI2 or PGE1. These facts support the hypothesis that platelet receptors for PGI2 and PGE1 are similar to each other and different from the receptor(s) for PGD2. PRP obtained from normal subjects after the ingestion of aspirin exhibited only one wave of aggregation in response to ADP, adrenaline or collagen, PGI2, PGD2 and PGE1 were all powerful inhibitors of this single wave of aggregation. The inhibitory activity of all three prostaglandins at threshold concentrations was overcome by increasing the concentration of ADP or collagen but not by increasing the concentration of adrenaline.
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PMID:Prostaglandins as inhibitors of human platelet aggregation. 39 96

The individual and combined effects of PGD2, PGI2 and an aortic proteoglycan on human platelet aggregation and plasma clotting were studied. PGI2 was at least 10 times more potent than PGD2 in inhibiting platelet aggregation. Small doses of prostaglandins inhibited ADP- and thrombin-induced aggregation, but only prolonged aggregation time without affecting the extent of arachidonic acid (AA)-induced aggregation. Small doses of prostaglandins did not affect thrombin-induced clotting of PRP. Large doses of prostaglandins abolished platelet aggregation and prolonged the onset of thrombin-induced clotting. The aortic proteoglycan (APG) had no appreciable effect on ADP- or AA-induced aggregation. Small doses of APG abolished thrombin-induced clotting, while large doses of APG suppressed both clotting and aggregation induced by thrombin. PGI2 and PGD2 showed additive inhibition of platelet aggregation regardless how the aggregation was induced. APG and prostaglandins showed additive inhibition of only thrombin-induced aggregation. APG, but not any of the prostaglandins, prolonged clotting time of PPP. This prolongation was not potentiated by PGI2 or PGD2.
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PMID:Combined effect of prostaglandins and an aortic proteoglycan on platelet aggregation and plasma clotting. 39 32

The relationship of intimal smooth muscle cell proliferation in the permanently occluded rat carotid artery to the presence or absence of luminal platelets was examined. Blood was rinsed from the arterial lumen immediately after occlusion and was replaced by autologous, citrated platelet-rich plasma (PRP, 6 to 20 X 10(5) platelets/microliter) or filtered platelet-poor plasma (PPP, less than 100 platelets/microliter). Occluded arteries were studied after 1 to 28 days by light and electron microscopy. Events occurring within the first 2 days included fibrin clot formation, endothelial degeneration and denudation, transmural migration of polymorphonucelar leukocytes and monocytes, and, in PRP-filled arteries, degranulation and disappearance of platelets. By 7 days a neointima was formed by macrophages and undifferentiated cells. The latter cells had some features of vascular smooth muscle cells and were apparently derived from medial cells which traversed the internal elastic lamina. After 14 days, identifiable smooth muscle cells emerged as the predominant cell type in a rapidly growing intimal plaque. No differences could be discerned between arteries originally filled with PRP or PPP. This experimental model is similar to atherosclerosis in dimensions of avascular area and in coexistence of degenerative, inflammatory, and proliferative processes. Cell proliferation deep within an atherosclerotic plaque could be initiated by factors other than platelets, perhaps by products of inflammatory cells.
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PMID:Smooth muscle cell proliferation in the occluded rat carotid artery: lack of requirement for luminal platelets. 42 40

In order to find the basic defect in the Hermansky-Pudlak Syndrome (HPS), biochemical studies of platelets and leucocytes were undertaken. Glutathione levels of platelets were normal and regeneration of GSH similar to controls occurred after incubation with diamide (a specific agent for GSH oxidation). Phospholipid and fatty acid composition of HPS platelets was normal. The amount of peroxides found in platelet membranes was not elevated. A subnormal aggregation with arachidonic acid could be obtained in PRP using a high concentration of arachidonic acid (2 mM), but normal malondialdehyde levels were measured, suggesting a normal prostaglandin synthesis in HPS platelets. Glutathion peroxidase and p-phenylenediamide-mediated peroxidase (PPD-peroxidase) were normal in leucocytes of 1 HPS patient. Lysosomal enzymes as far as investigated were normal.
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PMID:Biochemical studies in Hermansky-Pudlak syndrome. 49 77

Employing the Haemonetics Blood Processor (IFC), a relatively pure platelet concentrate can be prepared by collecting only the first portion of the PRP leaving the centrifuge bowl (Fraction I). A subsequent fraction containing RBC and WBC contaminants (Fraction II) can be purified by means of a second centrifugation, using a conventional blood bank centrifuge (Fraction II), if transfusion of these contaminants would be detrimental to the recipient. Utilising the new 1.4% Na3-citrate anticoagulant, platelet metabolic parameters (ATP, ADP, AMP, lactate and pyruvate) as well as O2-uptake, were determined in Fraction I and II prepared from 10 normal healthy subjects. In contrast to previous studies reporting marked dysfunction in platelets contained in Fraction II when standard ACD-A was used during IFC, we observed no significant difference (Student's t test) in the present study between Fractions I and II, in regard to platelet metabolism, when using the new anticoagulant. It is further concluded that the second centrifugal manipulation does not exert a detrimental effect on platelet metabolism.
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PMID:The utilisation of a new strength citrate anticoagulant during centrifugal plateletpheresis. III. Assessment of in vitro platelet metabolism. 49 71

The hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 microM ADP, were not inhibited by 500 microM adenosine, a concentration that greatly reduced the effect of 300 microM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.
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PMID:Collagen-induced platelet aggregation:--evidence against the essential role of platelet adenosine diphosphate. 54 29

Changes in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariectomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 microM ADP showed a statistically significant decrease in comparison with the preoperation value (P less than 0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P less than 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.
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PMID:Changes in platelet aggregability after ovariectomy. 54 38


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