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Biomedical subjects
Publications and source records attributed to M J Clark.
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Receptor alkylation with 10 microM superfit (SF), an irreversible delta-specific opioid ligand, in rat brain membranes abolished 73% of available binding sites for 3H-DSLET without affecting the stimulation of high affinity GTPase by DSLET. Alkylation with 25 microM SF further decreased the number of low affinity sites and revealed a slight inhibition of GTPase stimulation. Membrane treatment with 75 microM SF abolished high affinity 3H-DSLET binding and reduced GTPase stimulation to below 50% of control accompanied by a 10-fold decrease in the potency of DSLET. Protective alkylation with 25 microM beta-CNA in the presence of DSLET yielded similar results. The findings describe spare delta receptors in their coupling to the GTPase effector component in brain, and reveal possible functional significance of the low affinity ligand binding sites.
The MRC OX-2 antigen is a membrane glycoprotein of about 45,000 Mr present on rat neurons, thymocytes, B cells, follicular dendritic cells, endothelium and smooth muscle. Sequence of cDNA clones indicates it is a member of the Ig superfamily containing 248 amino acids organized like an Ig light chain with a V-like domain and a C-like domain followed by a transmembrane and cytoplasmic sections. There is a sequence with homologies with J-regions but analysis of the gene for human OX-2 shows that this is part of the V-domain exon and there is not a separate J-region exon as in the T cell receptor or Ig chains. The relationship of OX-2 to the other Ig-related neuronal/thymocyte antigen Thy-1 and the evolution of the Ig superfamily are discussed.
The MRC OX-2 antigen is a rat cell surface glycoprotein of mol. wt. 41 000-47 000 found on neurones, thymocytes, B cells, follicular dendritic cells and endothelium. We now report the amino sequence for this antigen as deduced from the nucleotide sequence of cDNA clones detected by use of an oligonucleotide probe. The sequence contains 248 amino acid residues of which 202 residues are likely to be outside the cell with two domains that show homology with immunoglobulins. The N-terminal domain fits best with Ig V domains and Thy-1 antigen while the C-terminal part is like an Ig C domain. Thus the structure overall is similar to an Ig light chain or the T cell receptor beta chain. Three glycosylation sites are identified on each of the MRC OX-2 antigen domains.
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A phase I study of bisantrene using a daily injection for 5 days was undertaken in adult patients with relapsing acute nonlymphoblastic leukemia. Seventeen patients received 27 courses, with daily doses ranging from 75 to 250 mg/m2. Although gastrointestinal toxicity and alopecia were rare, hematological toxicity occurred in 85% of the patients. There was cholestasis unrelated to infectious events in 27% of the courses, as well as reversible renal failure in eight of 27 evaluable courses. Responses (complete + partial) were obtained in 35% +/- 10% of the patients. The recommended dose for phase II study is 200 mg/m2/day X 7.
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The development of body fatness and leanness is examined in an ongoing prospective nutrition and growth study. Individual skinfold thicknesses, relative weights, weight gains, activity levels, and caloric intakes were examined at seven ages between 6 months and 9 years. Changes in body fatness in this group of children provide evidence that the obese infant usually does not become the obese child. Weight gain in infancy is also a poor predictor of 9-year old obesity. Changes from obese to non-obese or lean are often not linear. There is evidence that impending or actual obesity begins at ages 6 to 9 years with some predictability provided as early as age 2 years for girls, age 3 years for boys.
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Late nineteenth-century medico-psychological approaches to the mind-body problem are discussed in relation to psychiatry's theoretical constitution as a distinct 'mind-body' science and practice, and to John Hughlings Jackson's 'doctrine of concomitance'. Psychiatric 'explanations' of the mind-body relation are interpreted as expressions of psychiatry's independent professional interests vis-à-vis neurology and general medicine.
Sacrococcygeal teratoma is a rare cause of dystocia. Reported management strategies to date have yielded few viable infants. In this case report, the infant was partially delivered when extraction was halted. The infant was intubated and resuscitated while preparations for emergency cesarean section were being made. The infant was subsequently delivered abdominally and three years later is normal. Despite absent thoracic cage movement during resuscitation, adequate oxygenation was possible. Increasing use of prenatal ultrasonography should allow early detection, and thus avoid such unanticipated dystocias.
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The synthesis and release of acetylcholine (ACh) was studied in term human placental villous mince in vitro. During a 140-min incubation the placental tissue synthesized ACh at a rate of 2.59 nmol/g/min and released ACh into the medium at a rate of 0.78 nmol/g/min. Consequently there was an increase in tissue levels of ACh from an initial value of 83 to 321 nmol/g. Inhibition of choline acetyltransferase by 2-benzoylethyl trimethylammonium or 4-(1-naphthylvinyl)pyridine depressed the synthesis of ACh by over 75% and blocked the increase in tissue levels of ACh. The IC50 values for the inhibition of ACh synthesis and decrease in tissue levels were close to the IC50 values determined for inhibition of choline acetyltransferase in situ. Neither 2-benzoylethyl trimethylammonium nor 4-(1-naphthylvinyl)pyridine caused a significant effect on ACh release. 2-benzoylethyl trimethylammonium and 4-(1-naphthylvinyl)pyridine were quite effective in inhibiting the uptake of the neutral amino acid, alpha-aminoisobutyric acid, into the tissue. The inhibition of alpha-aminoisobutyric acid uptake paralleled the inhibition of ACh synthesis. These results support the hypothesis of an association between placental cholinergic activity and amino acid transport in the human placenta.
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