Biomedical subjects
M Williams
Publications and source records attributed to M Williams.
Synthesis, assignment of absolute configuration, and receptor binding studies relevant to the neuroleptic activities of a series of chiral 3-substituted cyproheptadine atropisomers.
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Restrospective correlation of clinical and histologic findings of 189 exchanged kidneys.
Tissues samples from 189 unsuccessful renal allografts, 47 recovered at autopsy and the others removed surgically, were examined histologically by light microscopy. Tissues samples were obtained from cadaver kidneys that had been exchanged regionally for transplantation. Each allograft tissue sample was rated as to extent of pathologic changes denoting rejection and was classified accordingly. Surgical and autopsy reports, as well as clinical data, were then obtained and these were compared with the retrospective pathologic findings of this study. Our pathologic findings agreed with the original pathologic diagnosis as to presence or absence of rejection changes in 180 cases, but disagreed with the clinical diagnosis of rejection in 28 of the 63 cases with minimal or no histologic evidence of rejection. There was less disagreement with the clinical diagnosis for the 87 cases with histologic evidence of rejection which had been judged as sufficient to cause allograft loss, 70 having been clinically diagnosed as rejected. Disagreement occurred most often where the allograft had never functioned or had been lost within 3 months. Retrospective analysis did not disclose any association between rejection histology and preformed antibodies or length of kidney perfusion time. Sufficient allografts appeared to have been lost for reasons other than rejection to cast doubt on the validity of interpreting renal allograft data only by graft survival statistics.
Pyruvate Dehydrogenase Complex from Chloroplasts of Pisum sativum L.
Pyruvate dehydrogenase complex is associated with intact chloroplasts and mitochondria of 9-day-old Pisum sativum L. seedlings. The ratio of the mitochondrial complex to the chloroplast complex activities is about 3 to 1. Maximal rates observed for chloroplast pyruvate dehydrogenase complex activity ranged from 6 to 9 micromoles of NADH produced per milligram of chlorophyll per hour. Osmotic rupture of pea chloroplasts released 88% of the complex activity, indicating that chloroplast pyruvate dehydrogenase complex is a stromal complex. The pH optimum for chloroplast pyruvate dehydrogenase complex was between 7.8 and 8.2, whereas the mitochondrial pyruvate dehydrogenase complex had a pH optimum between 7.3 and 7.7. Chloroplast pyruvate dehydrogenase complex activity was specific for pyruvate, dependent upon coenzyme A and NAD and partially dependent upon Mg(2+) and thiamine pyrophosphate.Chloroplast-associated pyruvate dehydrogenase complex provides a direct link between pyruvate metabolism and chloroplast fatty acid biosynthesis by providing the substrate, acetyl-CoA, necessary for membrane development in young plants.
The effects of maternally administered pethidine or epidural bupivacaine on the fetus and newborn.
The continuous fetal heart rate rate pattern, condition of the baby at birth and its subsequent behaviour were compared in three groups of infants whose mothers received during labour either no drugs, intramuscular pethidine or epidural bupivacaine. The blood levels of pethidine and bupivacaine were measured at delivery in a maternal vein, and umbilical artery and vein, and in the newborn during the first 48 hours of life. The only significant changes in the fetal heart rate pattern occurred in association with maternal hypotension or uterine hyperstimulation. The Apgar scores at one minutes were 7 or less in more infants in the intramuscular pethidine and epidural bupivacaine groups as compared with the controls. There were no differences in the Apgar scores at five minutes. Neonatal behaviour during the first six weeks of life was not significantly affected by pethidine or epidural bupivacaine when compared with the control group. Pethidine and bupivacaine were shown to cross the placenta freely. The half-life of these drugs in the newborn was longer than in the adult.
Characterization of the binding of [3H]muscimol, a potent gamma-aminobutyric acid agonist, to rat brain synaptosomal membranes using a filtration assay.
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Crisis intervention: a social work method.
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The neuropharmacology of a novel gamma-aminobutyric acid analog, kojic amine.
Kojic amine (KA; 2-aminomethyl-5-hydroxy-4H-pyran-4-one), a compound which shares some structural features with gamma-aminobutyric acid (GABA) and muscimol, has been examined in a variety of test systems for GABAmimetic activity. In several in vitro central nervous system receptor binding assays employing rat brain membrane preparations, KA exhibited selective activity to displace 3H-muscimol but with a relatively high IC50 of 4.4 muM. KA did not alter the binding of 3H-diazepam. Iontophoretically applied KA exerted a pronounced (comparable to GABA on the basis of ejection currents)i inhibition of the firing of cerebellar Purkinje cells and spontaneously active or glutamate-activated neurons in the cerebral cortex. The inhibitory effects of KA, which were longer lasting than those of GABA, were antagonized by bicuculline and enhanced in the presence of 2,4-diaminobutyric acid. On the isolated amphibian (Bufo marinus) spinal cord, KA was less than 1/3 as potent as GABA in depolarizing primary afferent terminals. In this preparation KA caused a marked decrease in the dorsal and ventral root potentials evoked by electrical stimulation of an adjacent or corresponding dorsal root. KA is a poor substrate for GABA uptake systems into rat brain synaptosomes, has no effect on GABA release in vitro, and does not inhibit GABA transaminase activity. Altogether, these data suggest that KA does have some GABAmimetic actions (which are perhaps restricted to hyperpolarizing post-synaptic GABA receptors) but also exerts other pharmacological effects as well.
Stroke: the double crisis.
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Stereospecific antidopaminergic and anticholinergic actions of the enantiomers of (+/-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine (CTC), a derivative of cyproheptadine.
(+/-)-CTC, a cyproheptadine derivative, possesses both antidopaminergic and anticholinergic activities which can be resolved, respectively, into its component (-)- and (+)-enantiomers. Both in vivo (antagonism of apomorphine-induced stereotypy, elevation of striatal homovanillic acid) and in vitro (inhibition of [3H]haloperidol binding), (-)-CTC was less active than haloperidol but more potent or equipotent compared to chlorpromazine. (+)-CTC was a more potent anticholinergic agent in vitro (inhibition of [3H]quinuclidinyl benzilate binding) than either thioridazine or clozapine, whereas in vivo (antagonism of the lethal action of physostigmine) the three compounds were similar. Comparison of the racemate with (-)-CTC in several in vivo test procedures to determine the influence of intrinsic anticholinergic activity showed that the presence of the anticholinergic (+)-enantiomer had little effect on the ability of (-)-CTC to antagonize apomorphine or elevate striatal homovanillic acid, whereas the activity of (-)-CTC was reduced in tests for postural asymmetry, avoidance and catalepsy. Stereoselectivity was also observed in terms of the alpha adrenergic blocking activity of CTC (inhibition of [3H]WB 4101 binding) which resides exclusively in the (-)-enantiomer. The ratios of (+)-CTC and (-)-CTC in terms of their anti-alpha adrenergic/antidopaminergic properties were large, suggesting a low propensity for the elicitation of orthostatic hypotension and sedation.
Issues and methological problems in nurse staffing research.
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Fitness testing for adolescents and young adults.
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General practitioners and postgraduate education in the Northern Region.
We describe a survey of general practitioners in the Northern Region which was carried out during the summer of 1977 as the result of a commission from the Education Committee of the North of England Faculty of the Royal College of General Practitioners. Seventy-five per cent of a one in two random sample of general practitioner principals returned a postal questionnaire in which their perceptions of postgraduate education were sought and their behaviour measured by the number of sessions they attended during the previous year at their 'usual' and other postgraduate centres. Almost half the respondents had more than a basic qualification and all but three per cent had held full-time hospital appointments, two thirds of them at the level of senior house officer or above. Their experience as general practitioner principals averaged 15 years and 57 per cent held part-time appointments outside their practices. Only four per cent had not attended any postgraduate events during the previous year but the remaining respondents had attended eight sessions on average, six of which were at their usual centres. Those attending more than the average number of sessions tended to have registered between 1950 and 1969, to work in larger practices, to hold additional appointments, or to be trainers or College tutors. Most of the respondents were conservative in their perceptions of teaching methods, the topics discussed at meetings, and the contributors to postgraduate education but the younger general practitioners and a group of established general practitioners affiliated to the Royal College of General Practitioners held more radical views. They agreed about the primacy of traditional clinical topics but were sceptical of the value of ward rounds and formal lectures and favoured the seminar and clinical attachments. They saw a need for more material about practice management and wanted experienced general practitioners and community paramedical staff as teachers in addition to hospital consultants. Most of the respondents believed that their usual centres were well organized and managed but failed to cater for the special requirements of general practitioners in non-clinical aspects of practice. Lunchtime and evenings were seen as the most convenient for weekday meetings and Sunday as the most convenient day of the week. A majority of respondents believed that post-graduate education had altered their practice of clinical medicine but only 15 per cent believed it had caused changes in their practice organization.
Who considers adolescents--part 2.
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Occurrence of novel branched-chain fatty acids in Refsum's disease.
Two novel branched-chain fatty acids, which appear to be unsaturated analogs of phytanic acid, have been observed in sera and urine of patients with Refsum's disease. They occur in both phospholipids and neutral lipids, and have been isolated and characterized.
Comparison of the performance of deafferented and intact monkeys on continuous and fixed ration schedules of reinforcement.
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Survival, growth and suckling behavior of neonatally bulbectomized rats.
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Biosynthesis of (+)-Tartaric Acid from l-[4-C]Ascorbic Acid in Grape and Geranium.
The metabolic fate of l-[4-(14)C]ascorbic acid has been examined in the grape (Vitis labrusca L.) and lemon geranium (Pelargonium crispum L. L'Hér. cv. Prince Rupert) under conditions comparable to data from l-[1-(14)C]ascorbic acid and l-[6-(14)C]ascorbic acid experiments. In detached grape leaves and immature berries, l-[4-(14)C]ascorbic acid and l-[1-(14)C]ascorbic acid were equivalent precursors to carboxyl labeled (+)-tartaric acid. In geranium apices, l-[4-(14)C]ascorbic acid yielded internal labeled (+)-tartaric acid while l-[6-(14)C]ascorbic acid gave an equivalent conversion to carboxyl labeled (+)-tartaric acid. These findings clearly show that two distinct processes for the synthesis of (+)-tartaric acid from l-ascorbic acid exist in plants identified as (+)-tartaric acid accumulators. In grape leaves and immature berries, (+)-tartaric acid synthesis proceeds via preservation of a four-carbon fragment derived from carbons 1 through 4 of l-ascorbic acid while carbons 3 through 6 yield (+)-tartaric acid in geranium apices.