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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 235 records · Page 13Linked to original sources
PubMed1980

Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies.

Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pretreatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA-transaminase activity by local intrathalamic injection of ethanolamine-O-sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 microgram) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrahalamic injection of picrotoxin. Muscimol (40 ng--4 microgram) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function.

Animals↗
PubMed1977

Fibrin and fibrinogen proteolysis products: comparison between gel filtration and SDS polyacrylamide electrophoresis analysis.

The proteolysis of purified human fibrinogen, stabilized and non-stabilized fibrin by plasmin were investigated by gel filtration analysis and SDS polyacrylamide electrophoresis of the reaction products. Plasmin proteolysis of fibrinogen followed the sequential steps previously reported and the two analytical methods yielded concordant results. Large molecular weight proteolysis products, of substantially greater molecular weight than native fibrinogen, were identified by gel filtration analysis following dissolution of stabilized and non-stabilized fibrin clots; with further incubation with plasmin, these proteolysis products gradually diminished in size. On the other hand, SDS polyacrylamide electrophoresis of these fibrin digests demonstrated that while non-stabilized fibrin yielded breakdown products similar in size to those obtained after proteolysis of fibrinogen, stabilized fibrin digests showed moieties of greater molecular size estimated to be of molecular weight 400,000 to 800,000. The final breakdown products of stabilized fibrin differed from those of fibrinogen and nonstabilized fibrin in that fragment D was present in the "double D" cross-linked form.

Antigens↗
PubMed1976

Hemostatic alterations accompanying sickle cell pain crises.

Three patients with sickle-cell disease (SSD) were followed, weekly, for 1 1/2 to 2 years, during which time they experienced one or more episodes of crisis. Crisis was associated with reproducible sequential hemostatic alterations indicating intravascular fibrin formation and a marked disturbance in platelet economy. With crisis onset, or possibly before, there was an increase in plasma high-molecular-weight fibrinogen complexes and a transient fall in platelet count, with a subsequent rise in both fibrinogen concentration and platelet count; plasma fibrinogen peaked 1 week after crisis onset and platelet count approximately 2 weeks after onset. Subsidence of crisis was associated with a fall in high-molecular-weight fibrinogen complexes and a subsequent increase in fibrinogen first derivative, an early fibrinogen breakdown product. Hemostatic findings and patient clinical status were generally correlated, the findings during asymptomatic periods being essentially normal. Agents affecting platelet function (aspirin alone or in combination with dipyridamole) appeared to reduce the extent of laboratory abnormality, suggesting potential clinical usefulness in this disorder.

Acute Disease↗
PubMed1976

Coagulation factor XIII concentration in sickle-cell disease.

Plasma factor XIII was assayed serially for a 1 1/2 to 2 year period in four patients with sickle-cell disease (SSD), during which several episodes of SSD crisis were observed. During crisis-free periods, plasma factor XIII concentration was lower than in normal subjects. With crisis onset, there was usually a concomitant fall in platelets and in plasma factor XIII soon after followed by a rise in fibrinogen concentration and platelet count. Following crisis resolution there was an increase in plasma factor XIII concentration peaking 3 weeks after crisis onset and occurring at the time of subsidence of thrombocytosis. It is suggested that the observed changes in plasma factor XIII concentration in SSD patients support the hypothesis that in the early stage of SSD crisis, fibrin deposition and/or thrombosis significantly enhance the role of sickled erythrocytes in producing vascular occlusion and/or organ infarction.

Adult↗
PubMed1975

Association between oral contraceptive use and thromboembolism: a new approach to itsinvestigation based on plasma fibrinogen chromatography.

Longitudunal and cross-dectional blood coagulation studies were made in patients receiving oral contraceptive therapy and in unmedicated women used as control subjects. These studies have included use of a new procedure, plasma fibrinogen chromatgraphy, which, by assay for a high molecular weight fibrinogen complexes in plasma, detects or excludes the presence of small thrombi, even when these are of the clinically silent type. New contraceptives users (n=154) received either Ovulen (100 pg of mestranol) or Demulen (50pg of ethinyl estradiol) and were followed serially for one year. During the cross-sectional study (193 women and 1,350 samples), serial examination was preformed on those taking oral contraceptives for 3 months to 10 years. Over-all, pathologic plasma fibrinogen chromatographic findings, indicative of thrombosis, were detected in 6 per cent of hte control examinations and in 27 per cent samples from oral contraceptive users. These findings suggest that oral contraceptive users developed mainlyclinically silent thrombotic lesions, with four-to-fivefold greater frequency than the control subjects. Consequently, it is inferred that they are at four-to fivefold greaterrisk of developing clinically overt disease, a risk factor estimate in line with that derived by epidemiologic study.

Alpha-Globulins↗