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Biomedical subjects

S G Thompson

Publications and source records attributed to S G Thompson.

At least 127 records · Page 7Linked to original sources

The effect of physiological levels of fibrinogen on platelet aggregation.

Results from the Northwick Park Heart Study (NPHS) suggest that physiological levels of plasma fibrinogen may influence platelet aggregability. This possibility has been further studied by the addition of purified fibrinogen to the blood of 17 study participants with low plasma fibrinogen levels. The results, which were highly consistent between different individuals, showed that fibrinogen increases aggregability as measured by the ADP ED50, the dose of adenosine diphosphate at which aggregation proceeds at half its maximum velocity. However, an increasing plasma fibrinogen level was associated with decreasing aggregability measured by another parameter, the ADP EMR (estimated maximum response). Although the balance of evidence is that the plasma fibrinogen level enhances aggregability, these conflicting results emphasize the limitation of any simple concept of "platelet aggregability".

Adenosine Diphosphate↗

Methods in dose response platelet aggregometry.

A standardized method for performing dose response platelet aggregation has been developed, and has been used in about 1000 subjects in a large prospective study of ischaemic heart disease. A computer program has been used to fit a sigmoidal relationship between primary aggregation response rate and the log dose of aggregating reagent. Estimates of the parameters of the sigmoid curve are used to characterize an individual's platelet aggregability. Methods for investigating the maintenance of long-term quality control have also been developed.

Adenosine Diphosphate↗

Sources of variability in dose response platelet aggregometry.

An experiment designed to assess the components of variability of a number of measures of platelet aggregability showed that the ADP ED50 (the estimated dose of adenosine diphosphate at which primary aggregation occurs at half its maximum velocity) had the least method error of any of the parameters measured, but that none had a very high between-person component of variability. A simultaneous comparison of a syringe technique and a free-flowing technique for venepuncture revealed no differential effects on the aggregation parameters measured. An enforced increase in the stirring speed in the aggregometer led to an experiment which showed that such a change did not apparently affect the ED50s.

Adenosine Diphosphate↗

Epidemiological characteristics of platelet aggregability.

The epidemiological characteristics of platelet aggregability were established in 958 participants in the Northwick Park Heart Study. The main analyses were based on the dose of adenosine diphosphate at which primary aggregation occurred at half its maximum velocity. Aggregability increased with age in both sexes, was greater in whites than blacks (particularly among men), and tended to decrease with the level of habitual alcohol consumption. Aggregability was, however, greater in women than men and in nonsmokers than smokers. There was no relation between aggregability on the one hand and obesity, current or past oral contraceptive use, menopausal state, or blood cholesterol and triglyceride concentrations on the other. Aggregability was somewhat, though not significantly, higher in men with a history of ischaemic heart disease and in those with electrocardiographic evidence of ischaemia than in those without. There was a strong association between the plasma fibrinogen concentration and aggregability. The widely held concept of platelet aggregability and its implications is probably an oversimplification. In the prevention of thrombosis it may be as useful to consider modifying external influences on platelet behaviour, such as plasma fibrinogen concentration or thrombin production, as it is to rely solely on platelet active agents.

Adenosine Diphosphate↗

GABA-transaminase and glutamic acid decarboxylase changes in the brain of rats treated with pyrithiamine.

Pyrithiamine, a thiamine phosphokinase inhibitor, was fed to rats on a thiamine-deficient diet, producing weight loss, ataxia and loss of righting reflex in 10 days. Some rats were then sacrificed; others were returned to a normal diet, to be sacrificed only when their weight had returned to pre-experimental levels. Rats were sacrificed for assay of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) activities in homogenates of eight brain regions or were perfused for gamma-aminobutyric acid transaminase (GABA-T) histochemistry. GAD activity was significantly reduced in symptomatic rats in the thalamus greater than cerebellum greater than midbrain greater than pons/medulla. GABA-T staining was similarly reduced, with greatest losses in the thalamus greater than inferior colliculus greater than pons greater than medulla. ChAT activity was not significantly altered in any brain area. Following return to a normal diet. GAD activity was significantly recovered in all areas except the thalamus. GABA-T staining recovered, at least partially, in all areas affected.

4-Aminobutyrate Transaminase↗

Assay of factor VII activity by two techniques: evidence for increased conversion of VII to alpha VIIa in hyperlipidaemia, with possible implications for ischaemic heart disease.

Factor VII was assayed in healthy adults and pregnant women by a coagulation method (VIIc) and a procedure (VIIt) based upon activation of factor X. Although VIIc and VIIt were highly correlated (r 0.8) they apparently measured different aspects of VII activity. This difference was related to plasma lipid concentrations. Plasma VIIc showed independent positive associations in vivo with VIIt, cholesterol and triglyceride concentrations, but was unaffected by in vitro adjustment of plasma lipoprotein concentrations. The difference between assays might be due to differing reactivities of VII. The VIIc assay measures VII in its in vivo proportions as the single-chain protein and fully active double-chain form (alpha VIIa). In VIIt, all VII is converted to alpha VIIa before measurement. Thus an increase in VIIc but not VIIt with increasing lipid concentrations reflects an increased proportion of VII as alpha VIIa, possibly secondary to activation of the contact system. This effect may explain at least part of the increased VIIc and normal VIIt in pregnancy, and the increased VIIc of hyperlipidaemias in general. The relative values of VIIc and VIIt are proposed as a measure of flux within the coagulation system, and as a measure of coagulability in hyperlipidaemia and other states.

Adult↗

Blood pressure and the menstrual cycle.

A retrospective analysis of data from 207 non-pregnant premenopausal women showed that the mean level of systolic blood pressure varied with the stage of the menstrual cycle, being higher on days 17-26, the part of the luteal phase during which the peak of progestogen levels develops, than during the luteal phase as a whole, and significantly higher than the mean for all other days of the cycle. The mean levels were 125.4 mmHg (SE 1.76) for days 17-26, 122.5 (SE 1.25) for days 15-28 and 120.1 (SE 1.07) for days 1-16, 27 and 28. This finding supported the hypothesis that endogenous progestogen might have a hypertensive effect, as does exogenous progestogen. However, a second study designed to confirm this finding failed to do so, showing no cyclical change in the level of blood pressure. The subjects in the first study may have been subject to greater psychological stress when the measurements were made than were those in the second, a possibility supported by the large difference in pressure between the two studies. The discrepancy between the two sets of results could be explained if the effect possibly associated with progestogen levels in the retrospective study was due not to a hypertensive action per se but to a progestogen-related increased reaction to stress.

Adolescent↗

Regional distribution in rat brain of 1-pyrroline-5-carboxylate dehydrogenase and its localization to specific glial cells.

A possible alternative route for production of a small glutamate pool in brain is from proline or ornithine to 1-pyrroline-5-carboxylate (P5C) and thence to glutamate. The conversion from ornithine to P5C is catalyzed by ornithine delta-aminotransferase (OrnT) whereas that from proline is catalyzed by proline oxidase (PrO). The conversion of P5C to glutamate is catalyzed by 1-pyrroline-5-carboxylate dehydrogenase (PDH). Biochemical assays of PDH and PrO in various rat brain regions indicate no positive correlation between the two enzymes nor between either activity and high-affinity glutamate uptake or the regional distribution of OrnT. We have localized PDH and PrO histochemically by modifications of the Van Gelder [J. Neurochem. 12, 231-237, (1965)] method for gamma-aminobutyric acid (GABA) transaminase. The enzymes were found only in certain types of glial cells; the best stained were the Bergmann glial cells of the cerebellum but, for PDH, there was also good staining of astrocytes in the dentate area of the hippocampus. Since both these areas are believed to have heavy glutamate innervation and numerous GABA interneurons, these findings may reflect an alternative route of glutamate production in glial cells near some glutamate and/or GABA tracts but they do not support this as a possible route for glutamate formation in most brain regions. The findings do, however, provide further evidence for chemical specialization of glial cells.

Animals↗

Plasma concentrations of pituitary and testicular hormones of fertile and infertile men.

The serum concentrations of prolactin (PRL), follicle stimulating hormone (FSH) and luteinizing hormone (LH) and the plasma concentrations of testosterone, 5-alpha-dihydrotestosterone (DHT) and oestradiol were measured in 80 infertile men and 38 men of known fertility. The infertile men had a lower mean concentration of prolactin and a higher mean concentration of FSH than the fertile controls. The mean FSH was particularly high in infertile men without antisperm antibodies but with oligospermia (sperm density up to 20 million/ml), who also had a higher mean serum LH level than the fertile controls. Both FSH and LH showed an inverse relationship with sperm density. There were no significant differences in plasma testosterone, DHT or oestradiol between fertile and infertile men. In both the fertile and infertile groups strong positive associations were found between the concentrations of FSH and LH, and between testosterone and DHT. Weaker relationships were found between DHT and oestradiol, and between testosterone and PRL. In the fertile men, positive associations were also found between LH and testosterone, and between oestradiol and both FSH and LH. Testosterone and oestradiol were associated only in infertile men. The relevance of these findings to the aetiology of male infertility is discussed.

Dihydrotestosterone↗

Factor VIII in pregnancy and birthweight.

Blood samples taken at 28 and 34 weeks of pregnancy from 495 women were assayed for factor VIII clotting activity (VIIIC) and factor VIII related antigen (VIIIR) to examine the distribution of these factors and to determine whether there was any relationship with birthweight. There was a small positive relationship of little clinical value between factor VIIIR and birthweight only when birthweight was adjusted for gestational age, sex of infant and parity. In pregnancies resulting in a male infant the level of factor VIIIC was lower at 34 weeks gestation than in pregnancies resulting in a female infant. A greater rise in the ratio of VIIIR/VIIIC was observed in women who had any type of hypertension when compared with normotensive pregnancies, but this was not associated with lower birthweight. Both factors VIIIR and VIIIC at 28 weeks gestation were lower for multiparous than for primiparous women, and were lower for those with eventual greater gestation at birth. Asian women had higher mean factor VIIIC than Caucasian women, a finding independent of the fact that women with blood group O had lower mean levels of factors VIIIR and VIIIC than women of other blood groups.

Adolescent↗

Production and characterization of monoclonal antibody to gentamicin.

Splenocytes from BALB/c mice immunized with a gentamicin-hemocyanin conjugate were fused with X63-Ag8.653 murine myeloma cells to produce hybridomas that secreted monoclonal antibody to gentamicin. Sixteen positive clones were obtained. The monoclonal antibody chosen for a gentamicin immunoassay has been characterized with respect to class, subclass, type of light chain, electrophoretic homogeneity, and binding affinity. Gentamicin monoclonal antibody purified from mouse ascites fluid was analyzed by immunoelectrophoresis, double immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and polyacrylamide gel electrophoresis (PAGE). The results show that the antibody is an IgG2a (kappa). Two bands were detected when the purified antibody was electrophoresed on polyacrylamide gels: a major band and a less mobile minor component (5.6% of the major band). Both were IgG2a (kappa). The major band contained antibody which bound 2.1 moles of the substrate-labeled gentamicin derivative, beta-galactosyl-umbelliferone sisomicin, per mole of IgG, whereas one mole of the minor band bound only 0.095 moles of the substrate-labeled conjugate. The antibody has an affinity constant of 1.22 X 10(10) M-1.

Animals↗

Menopausal status and haemostatic variables.

The incidence of ischaemic heart disease (IHD) is higher in postmenopausal women than in premenopausal women of the same age. The difference may be partly explicable in terms of differences between premenopausal and postmenopausal women in haemostatic function. This possibility has been studied in 833 White women in the Northwick Park Heart Study (NPHS). Mean levels of factor VIIC, fibrinogen, and cholesterol were between 6% and 10% higher in postmenopausal women than in premenopausal women of the same age. When allowances were made for associations between these variables, the difference between the two groups in cholesterol was no longer evident. By analogy with NPHS data on men, the differences in factor VIIC, fibrinogen, and cholesterol would increase the risk of fatal IHD in postmenopausal women by about 40% compared with the risk in premenopausal women of the same age.

Age Factors↗

A comparative study of zinc, copper, cadmium, and lead levels in fertile and infertile men.

Eighty infertile men and 38 men of known fertility were studied for investigation of both the importance of zinc, copper, cadmium, and lead to fertility and the possible interrelationships between these trace elements. The infertile men had higher mean concentrations of plasma copper than those of proven fertility. The difference was statistically significant (P less than 0.01) but was of small magnitude (approximately 1.5 mumol mean difference). The concentrations of plasma zinc, erythrocyte zinc, whole blood lead and cadmium, and seminal plasma zinc and copper did not differ significantly between infertile and fertile men. There was a significant positive relationship between sperm density and seminal plasma zinc concentration in the fertile, but not in the infertile, men. The infertile men with antisperm antibodies or counts greater than 20 million/ml had significantly higher mean levels of seminal plasma zinc than infertile men with oligospermia. The higher semen zinc in these two groups may reflect an abnormal fragility of the spermatozoa, resulting in the release of zinc, but the absence of significant overall differences between fertile and infertile men suggests that measurement of the concentration of zinc in plasma or zinc and copper in seminal plasma has little value in the routine investigation of infertility.

Adult↗

Evaluation of the Vita-Stat automatic blood pressure recorder. A comparison with the Random-Zero sphygmomanometer.

A total of 408 adult volunteers at Northwick Park Hospital, England, participated in an evaluation of the Vita-Stat automatic blood pressure (BP) recorder. During a five-day period in March 1981, readings of BP obtained by two Vita-Stat machines were compared with measurements obtained by two trained observers using Random-Zero sphygmomanometers. The order in which BP readers were obtained was randomized. A significant effect of order on systolic BP was removed from comparisons between techniques. For diastolic BP values, there was close agreement between the different measurement techniques and each was associated with a similar degree of repeatability between duplicate recordings. In contrast, both Vita-Stat machines seriously overestimated systolic BP and there was substantially more variability between duplicate readings of systolic BP obtained with the Vita-Stat machines than for Random-Zero values. The use of either Vita-Stat machine for population screening would have correctly identified almost all those with a high BP but would have led to considerable overdiagnosis of systolic hypertension. Despite their limitations, the accuracy of diastolic BP estimates and considerations of cost and convenience suggest that Vita-Stat machines might be useful as initial screening tools for detection of persons with high diastolic BP. However, the use of a particular Vita-Stat machine should be preceded by an evaluation of the machine against a standard method of BP estimation.

Adolescent↗

Substrate-labeled fluorescent immunoassay for measuring dibekacin concentrations in serum and plasma.

We have developed a homogeneous substrate-labeled fluorescent immunoassay for the measurement of dibekacin concentrations in serum and plasma. The fluorogenic enzyme substrate beta-galactosyl-umbelliferone was covalently attached to tobramycin, an aminoglycoside structurally similar to dibekacin, to prepare a fluorogenic drug reagent (FDR). The FDR is nonfluorescent under assay conditions, but fluoresces upon hydrolysis by beta-galactosidase. However, binding of the FDR by antiserum to the cross-reactive drug kanamycin prevents enzyme hydrolysis. The fixed level of FDR competes with dibekacin within the sample for the limiting number of antibody-binding sites in the reaction mixture. Unbound FDR is hydrolyzed by beta-galactosidase to release a fluorescent product that is proportional to the dibekacin concentration in the sample. The assay exhibits good precision, standard curve reproducibility, recovery, sensitivity, and correlation with a comparative method. Additionally, the substrate-labeled fluorescent immunoassay is rapid and easy to perform.

Binding Sites, Antibody↗

Gentamicin substrate-labeled fluorescent immunoassay containing monoclonal antibody.

The current substrate-labeled fluorescent immunoassay for gentamicin has been modified by substituting monoclonal antibodies for conventional antiserum to gentamicin. The standard curve generated with gentamicin monoclonal antibody was essentially linear from 0 to 12 micrograms/ml, could detect 0.4 micrograms of gentamicin per ml, and had overall intra- and interassay precision values (coefficients of variation) of 1.9 and 5.0%, respectively. The substrate-labeled fluorescent immunoassay produced with gentamicin monoclonal antibody gave results with clinical specimens comparable (r = 0.991) to those obtained with the commercially available substrate-labeled fluorescent immunoassay and also with an enzyme immunoassay, a radioimmunoassay, and a fluorescent immunoassay. This technologically state-of-the-art assay employs both a nonisotopic label and monoclonal antibodies. It offers excellent precision, sensitivity, lot-to-lot reproducibility, linearity, and reagent stability.

Antibodies, Monoclonal↗