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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 307 records · Page 17Linked to original sources
PubMed1985

4,5-Dimethylthiazole-N-oxide-S-oxide: a metabolite of chlormethiazole in man.

The metabolic fate of chlormethiazole in healthy male subjects has been investigated following the oral administration of a single dose of chlormethiazole edisylate. Five urinary C-oxidation metabolites were identified and shown to be identical with previously reported metabolites. A novel metabolite, of molecular formula C5H7NO2S, was shown by trimethylsilylation, deuterium exchange, reduction studies and by its i.r., n.m.r. and mass spectrum, to be 4,5-dimethylthiazole-N-oxide-S-oxide. This is the first reported metabolite which involves the oxidation of the two heterocyclic atoms in aromatic rings. The formation and thermal stability of the compound is ascribed to resonance stabilization.

Chemical Phenomena↗
PubMed1985

Cyclic alternating chemotherapy for small cell carcinoma of the lung.

Eighty-two previously untreated patients with small cell cancer of the lung were treated with six cycles of two alternating drug regimens: a new combination of mitomycin, methotrexate, and etoposide; and cyclophosphamide, doxorubicin, and vincristine. No maintenance chemotherapy was used. Consolidative thoracic irradiation and prophylactic cranial irradiation were employed. The median survival time for 32 limited-disease patients was 59 weeks, and for 50 extensive-disease patients was 35 weeks. Four-year survival was 12% for limited-disease patients and 2% for extensive-disease patients. These results were not superior to conventional combination chemotherapy regimens.

Adult↗
PubMed1985

In vivo and in vitro studies of the binding of antibody/dsDNA immune complexes to rabbit and guinea pig platelets.

The in vivo and in vitro binding of prepared antibody/dsDNA immune complexes to rabbit and guinea pig cellular blood components was examined. The in vitro binding in these two nonprimates was almost entirely due to platelets, and required homologous, intact complement; furthermore, no appreciable binding was observed for neutrophils, mononuclear cells, or erythrocytes at normal blood concentrations. The in vivo binding reaction occurred quite rapidly (less than 1 min for maximal binding) and the majority of the injected counts were cleared from the circulation in 3 to 5 min. Over this time period, however, a large fraction of the counts remaining in the circulation also remained bound to the animals' cells (presumably platelets), and this result was most pronounced for complement-fixing immune complexes prepared with high m.w. dsDNA. In vitro studies confirmed that immune complexes prepared with such dsDNA are rather slowly released from the animal platelets in the presence of homologous serum, and this result is in marked contrast to the considerably greater lability of bovine serum albumin/anti-bovine serum albumin immune complexes that are bound to complement receptors on animal and human cells. These observations suggest that the fate of immune-complexed dsDNA in the circulation may be very different from that of free dsDNA, and in the case of nonprimates may involve a platelet-mediated immune complex clearance mechanism analogous to the erythrocyte-mediated immune complex clearance mechanism which is believed to be operative in primates.

Animals↗
PubMed1985

Close encounters in general practice: experiences of a psychotherapy liaison team.

Experiences arising from the work of a multi-disciplinary psychotherapy liaison team in the primary care setting are described. Special emphasis is given to the difficulties encountered in working relationships. Attention is drawn to the complexity of the inter-professional relationship, its unconscious roots, and its influence on the quality of patient care.

Family Practice↗
PubMed1984

Ricin-like plant toxins are evolutionarily related to single-chain ribosome-inhibiting proteins from Phytolacca.

A comparison has been made of the amino-terminal sequences of a number of ribosome-inhibiting proteins (RIPs) and cytotoxins. These include the monomeric enzymes PAP, PAP-S, PAP-II, and dodecandrin and the enzymatic A chains from the heterodimeric toxins ricin and modeccin. We show that these proteins have all evolved from a single ancestor. A statistical analysis is used to show the likely evolutionary relationship among the proteins. A similar analysis was performed on the amino-terminal sequences of ricin, Ricinus agglutinin, and modeccin B chains. These are galactoside-binding proteins associated with the A-chain enzymes. From the two comparisons we propose a scheme for the development of two major classes of proteins. The RIP and sugar-binding genes probably evolved independently. In some plant lines the genes never fused, although the RIP gene replicated and developed into several proteins expressed at various stages of plant maturation. In another line the RIP gene fused with a sugar binding (B-chain) gene to form the class of heterodimeric toxins. In some species this fused gene appears to have multiplied, one or more of the toxin genes mutating to code for a self-dimerizing agglutinin molecule.

Amino Acid Sequence↗
PubMed1984

Reduced maximum capacity of glycolysis in brown adipose tissue of genetically obese, diabetic (db/db) mice and its restoration following treatment with a thermogenic beta-adrenoceptor agonist.

The maximal activities of the key glycolytic enzymes hexokinase and 6-phosphofructokinase, were reduced in brown adipose tissue in db/db mice compared to their lean littermates. Treatment of db/db mice with the thermogenic beta-adrenoceptor agonist, BRL 26830, restored normoglycaemia. The only significant increase in activity of hexokinase and 6-phosphofructokinase in the BRL 26830-treated db/db mice occurred in brown adipose tissue where the total tissue activity increased 10- and 11-fold respectively. These changes together with increased 2-deoxyglucose uptake in vivo suggest that brown adipose tissue can play a quantitatively important role in the removal of glucose from the blood.

Adipose Tissue, Brown↗
PubMed1983

The clinical significance of the effects of cigarette smoking on drug disposition.

Cigarette smoking is one of a number of environmental factors that contribute to interindividual variations in response to an administered drug. Polycyclic aromatic hydrocarbons present in cigarette smoke induce hepatic aryl hydrocarbon hydroxylase and cytochrome P448 and increased levels of these enzymes are responsible for a higher metabolic clearance of drugs which are substrates for these enzymes. The clinical significance of this induction is greatest for those drugs with a low therapeutic index such as theophylline. In some cases a modification of the normal therapeutic dose is justified to maintain adequate control. The magnitude of the effect of cigarette smoking on the induction of hepatic metabolic activity has been linked with age for a number of drugs including theophylline, some benzodiazepines and propranolol. Generally, the inductive effect is smaller in the elderly but, as there is no direct correlation between chronological age and physiological age, it is imperative that age and smoking habits be treated as individual sources of intersubject variation in pharmacokinetics and that this be borne in mind in the evaluation of new drugs and the safe clinical use of existing ones.

Acetaminophen↗
PubMed1982

Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine.

The metabolism of methaqualone to the glucuronides of 5 C-monohydroxy metabolites and to the N-oxide has been studied in 2 groups of healthy young adults phenotyped as extensive and poor metabolisers of debrisoquine. No significant interphenotype differences were observed with respect to the excretion of any of the 6 metabolites. It is probable that the genetic regulation of the pathways leading to these metabolites is at a locus other than that which is responsible for the regulation of the oxidation of debrisoquine, guanoxan, phenacetin, phenytoin and sparteine.

Adult↗
PubMed1982

The influence of the menstrual cycle on the metabolism and clearance of methaqualone.

1 The rate of methaqualone metabolism in women was shown to be significantly increased at the time of ovulation. 2 The apparent first order rate constants for the formation of five C-monohydroxy metabolites of methaqualone on day 15 of the menstrual cycle were approximately double that on day 1. 3 The N-oxidation of methaqualone showed considerable inter-individual variation in its sensitivity to the menstrual cycle, and in a group of ten women the difference in N-oxide excretion between days 1 and 15 was not statistically significant. 4 The serum clearance of methaqualone on day 15 was higher (mean value 94.6 ml min-1 on day 1, 176.0 ml min-1 on day 15), serum half-life shorter (mean t1/2 beta 16.3 h on day 1, 11.6 h on day 15) and the AUC alpha smaller (mean value 44.0 micrograms ml-1 h on day 1, 24.4 micrograms ml-1 h on day 15) than on day 1. 5 The relative importance of the five hydroxy metabolites was unchanged during the menstrual cycle but the C/N oxidation ratio was greater on day 15 than on day 1. 6 The data for methaqualone metabolism in a control group of men was similar to than in women on day 1 of a menstrual cycle.

Adult↗
PubMed1982

The influence of oral contraceptives on the metabolism of methaqualone in man.

1 Oral contraceptives were shown to suppress the mid-cycle increase in methaqualone metabolism observed in premenopausal women not receiving oral contraceptive therapy. No women were identified in whom this suppression was not observed. 2 Combined oestrogen-progestogen contraceptives produced the effect in all nine women studied. The effect was also observed in one woman who was receiving progestogen-only contraceptives. 3 The effect of the combined contraceptives was observed within one month of the commencement of the contraceptive therapy. 4 The results emphasise the need to monitor the effect of the menstrual cycle in women not receiving oral contraceptive therapy when the effects of such therapy is studied. 5 These effects are more likely to be the consequence of an inhibition of hormonal control of hepatic metabolic activity by the synthetic steroids than they are to simple inhibition of hepatic metabolism.

Adult↗
PubMed1982

The effects of an angiotensin blocker (saralasin) on kidney function in dehydrated sheep.

Saralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 micrograms . min-1 into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenous angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.

Angiotensin II↗