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Biomedical subjects

S J Machin

Publications and source records attributed to S J Machin.

At least 199 records · Page 11Linked to original sources
PubMed1984

A study of the possible role of mesothelium as a surface for flowing blood.

Mouse mesothelium has been examined as a surface for supporting blood flow. We have examined ten pieces of intact mesothelium and ten pieces of damaged mesothelium following 10 min exposure to flowing blood in a Baumgartner chamber. Scanning electron microscopy of the intact specimens demonstrated no adhering blood platelets, whereas the damaged specimens were found to be covered with large numbers of adhering platelets. In addition we have demonstrated that undamaged mesothelium does not appear to be morphologically altered after exposure to blood, and that undamaged mesothelium produces significantly more prostacyclin than damaged control. These findings support that mesothelial cells hold promise as a lining for prosthetic vascular implants.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Cigarette smoking and platelet adhesion.

Non-abraded rabbit endothelium has been exposed to human blood taken from male non-smoking volunteers before and after the smoking of two medium tar cigarettes, in an in vitro system using a Baumgartner chamber. In each case the blood was allowed to circulate for 10 min at a constant flow rate. Blood from 10 volunteers has been tested in this way. Scanning electron microscopy of the endothelial surfaces demonstrates large numbers of adherent platelets when 'post-smoking blood' is used, but very few and in some cases none with the 'pre-smoking' blood. As a further control to ensure that this phenomenon did not occur as a result from changes in the vessel related to the time during which it had been removed from its normal physiological environment, blood from further non-smoking volunteers was passed over seven of the remaining pieces of vessel at the completion of these runs. Platelets were either absent or very few in number, as with the pre-smoking samples.

Animals↗
PubMed1984

Preservation of platelet function in cryopreserved platelet concentrates with prostacyclin.

Prostacyclin (Epoprostenol) or a stable prostacyclin analogue (ZK 36,374) were added to platelet concentrates prior to cryopreservation. This resulted in significantly better preserved function of the thawed platelet concentrate, assessed by platelet aggregation to various concentrations of ADP, collagen and ristocetin, compared to control cryopreserved platelet concentrates. The use of prostacyclin or one of its stable analogues should be considered to reduce platelet activation and subsequent loss of function during the various manipulative procedures when preparing standard and cryopreserved platelet concentrates.

Blood Platelets↗
PubMed1984

Platelet impedance aggregation in whole blood and its inhibition by antiplatelet drugs.

Platelet aggregation was studied in citrated whole blood by an electrical impedance method. Blood samples from normal volunteers were studied with the aim of finding a suitable method for the routine study of samples from patients. An erratic tracing and low maximum aggregation were seen in samples with a high normal haematocrit. Optimal aggregation was seen when blood was diluted to a haematocrit of .300; isotonic saline was a better diluent than platelet poor plasma. No appreciable differences were seen when the platelet count was diluted down to 50 X 10(9)/l, after which there was a progressive reduction in response. Dose response curves were obtained, and normal ranges for ADP, collagen, and sodium arachidonate were determined. Acetylsalicylic acid had a more pronounced effect on ADP aggregation than on collagen. Prostacyclin (Epoprostenol) and the synthetic prostacyclin analogue ZK 36,374 both showed dose dependent inhibition of aggregation, but the duration of effect of the latter was much longer (greater than 6 h).

Adenosine Diphosphate↗
PubMed1983

Synthesis of thromboxane B2 in uraemia and the effects of dialysis.

The generation of thromboxane B2 (TxB2) from its natural precursor, arachidonic acid, was studied in vitro in order to assess further the prostaglandin pathway in the platelets of patients with chronic renal failure. Some, but not all patients with conservatively treated uraemia synthesised significantly less TxB2 then controls and the same patients were also hypo-aggregable to arachidonic acid. The synthesis of TxB2 appeared normal in a group of patients on chronic ambulatory peritoneal dialysis (CAPD). In contrast, a group of patients on long-term maintenance haemodialysis produced significantly greater amounts of TxB2 and were hyper-aggregable to arachidonic acid, a finding which may be relevant to the high incidence of atherosclerosis and vascular disease in these patients.

Adult↗
PubMed1983

A new congenital defect of platelet secretion: impaired responsiveness of the platelets to cytoplasmic free calcium.

A 16-year-old boy with a bleeding disorder since infancy has a long bleeding time, normal platelet count and morphology and normal plasma factor-VIII activities. His platelets undergo normal shape change and primary aggregation in response to ADP but show defective 5-hydroxytryptamine (5-HT) secretion and aggregation in response to adrenaline, sodium arachidonate, U44069, PAF-acether, A23187 and low concentrations of collagen. Thrombin and higher concentrations of collagen produce a normal response. Secretion of beta-thromboglobulin and platelet factor 4 parallels that of 5-HT. Thromboxane B2 is produced normally in response to exogenous arachidonate and to stimulation by thrombin, collagen and A23187 in all concentrations tested. The patient's endoperoxides and thromboxane A2 aggregate aspirin-treated platelets, though his platelets are themselves unresponsive. Cyclic AMP is present at normal concentration in the patient's unstimulated platelet-rich plasma, and PGI2 inhibits platelet aggregation by ADP and thrombin in a normal dose-related plasma, and PGI2 inhibits platelet aggregation by ADP and thrombin in a normal dose-related manner. Platelet ultrastructure, 5-HT uptake and content of adenine nucleotides, platelet factor 4 and beta-thromboglobulin are all within normal limits. When the patient's platelets were loaded with the fluorescent dye quin 2, which serves as an indicator of cytoplasmic free calcium ions, their responses to thrombin, whether in the presence or virtual absence of extracellular Ca2+, were entirely normal in respect of free calcium ions, secretion, shape-change and aggregation. In response to ionomycin, however, a normal increase in free calcium ions was accompanied by normal shape-change but virtually no aggregation or 5-HT secretion. The platelet calmodulin content was normal. These findings show that the defect in this patient's platelets is of utilization of cytoplasmic Ca2+ for secretion and aggregation, rather than of Ca2+ uptake or mobilization of Ca2+ from intracellular storage sites. It is suggested that the most likely site of the defect is the phosphorylation of one of the proteins concerned in the secretory mechanism.

Adolescent↗
PubMed1983

Defective platelet aggregation to the calcium ionophore A23187 in a patient with a lifelong bleeding disorder.

A patient with a lifelong bleeding disorder is presented with a prolonged bleeding time and abnormal aggregation and secretion responses to arachidonic acid, thromboxane A2, PAF-acether and the divalent calcium ionophore A23187. Platelet alpha and dense granule contents and morphology appear normal. The proposed defect is due to an abnormality of a platelet intracellular calcium dependent process.

Arachidonic Acids↗
PubMed1982

Effects of cigarette smoking on the ultrastructure of rat thoracic aorta and its ability to produce prostacyclin.

Following exposure of rats to graded doses of fresh cigarette smoke, the aortic endothelium examined by scanning electron microscopy regularly showed alterations. These essentially consisted of areas of blebbing and microvillus-like projections from the luminal surface, and the presence in the majority of cases, of micro-thrombi in the low shear areas just proximal to intercostal branches. Aortas from rats exposed to smoke showed a reduction in prostacyclin production in vitro and platelets from these animals aggregated more readily than did those of controls.

Animals↗
PubMed1982

A plasma factor inhibiting prostacyclin-like activity in thrombotic thrombocytopenic purpura.

The plasma from a patient with thrombotic thrombocytopenic purpura contained a low molecular weight dialysable factor which inhibited the synthesis and release or activity of prostacyclin-like activity from vascular tissue. This factor was not an immunoglobulin or complement component. Following fresh plasma infusions the ability of the patient's plasma to stimulate the release of prostacyclin-like activity returned but no clinical improvement occurred.

Adult↗
PubMed1982

Abnormal prostacyclin metabolism in the hemolytic uremic syndrome: equivocal effect of prostacyclin infusions.

In a child with the hemolytic uremic syndrome, plasma 6 keto-prostaglandin F1 alpha levels remained undetectable throughout the acute phase of the disease. The patient's plasma failed to stimulate prostacyclin production by "exhausted" rat aorta rings. In vitro study of the patient's vessels indicated that they retained the capacity to synthesize prostacyclin from exogenous arachidonic acid but that their endogenous arachidonic acid stores were either depleted or non-available. The response to repeated infusion of exogenous prostacyclin was equivocal, suggesting that abnormal prostacyclin metabolism in the hemolytic uremic syndrome may not be the only factor in its pathogenesis.

Child, Preschool↗
PubMed1981

Thromboxane synthetase inhibition as antithrombotic strategy.

The imidazole derivative UK-37 248, a thromboxane synthetase inhibitor, reduces the in-vitro formation of thromboxane B2 and hydroxyheptadecatrienoic acid by washed platelets, and this is compensated for by an increased production of prostaglandins E2 and F2 alpha; arachidonic acid challenged platelets pretreated with UK-37 248 also stimulate the production of prostacyclin by aspirin pretreated cultured endothelial cells. In a double-blind placebo controlled study to examine the in vivo properties of UK-37 248, human volunteers ingested 200 mg of the compound. Their serum thromboxane B2 levels dropped and their plasma 6-keto-prostaglandin F1 alpha values rose. Arachidonic acid induced platelet aggregation was completely inhibited whereas that elicited by adenosine-5'-diphosphate was unaffected. By reducing formation of pro-aggregatory tromboxane A2 and increasing production of anti-aggregatory prostacyclin, thromboxane synthetase inhibitors may be better than aspirin as antithrombotic agents.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Arterial thrombosis, intrauterine death and "lupus" antiocoagulant: detection of immunoglobulin interfering with prostacyclin formation.

In a 31-year-old woman with a history of recurrent arterial thrombosis, both of whose pregnancies had resulted in intrauterine death at 23 and 24 weeks, a "lupus" anticoagulant was identified. The patient's IgG fraction, containing the lupus anticoagulant, reduced the release of prostacyclin (PGI2) from rat aorta rings or pregnant human myometrium. This inhibitory effect was abolished in the presence of arachidonic acid. The production of 6-keto-PGF1 alpha by cultured bovine endothelial cells was also decreased in the presence of the patient's IgG fraction. The plasma level of 6-keto-PGF1 alpha was reduced. An antibody in this patient may interfere with the production or release of PGI2 by the vessel wall, possibly by interfering with the availability of arachidonic acid. This mechanism could play a role in this patient's arterial disease and obstetric problems.

Adult↗