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Biomedical subjects

D K Wilson

Publications and source records attributed to D K Wilson.

50 records · Page 3Linked to original sources
PubMed1989

Substrate specificity and affinity of a protein modulated by bound water molecules.

Water molecules influence molecular interactions in all biological systems, yet it is extremely difficult to understand their effects in precise atomic detail. Here we present evidence, based on highly refined atomic structures of the complexes of the L-arabinose-binding protein with L-arabinose, D-fucose and D-galactose, that bound water molecules, coupled with localized conformational changes, can govern substrate specificity and affinity. The atoms common to the three sugars are identically positioned in the binding site and the same nine strong hydrogen bonds are formed in all three complexes. Two hydrogen-bonded water molecules in the site contribute further to tight binding of L-arabinose but create an unfavourable interaction with the methyl group of D-fucose. Equally tight binding of D-galactose is attained by the replacement of one of the hydrogen-bonded water molecules by its--CH2OH group, coordinated with localized structural changes which include a shift and redirection of the hydrogen-bonding interactions of the other water molecule. These observations illustrate how ordered water molecules can contribute directly to the properties of proteins by influencing their interaction with ligands.

Arabinose↗
PubMed1989

Inhibitors of sterol synthesis. Chemical synthesis, structure, and biological activities of (25R)-3 beta,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one, a metabolite of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one.

3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one (I) is a potent inhibitor of sterol synthesis with significant hypocholesterolemic activity. (25R)-3 beta,26-Dihydroxy-5 alpha-cholest-8(14)-en-15-one (II) has been shown to be a major metabolite of I after incubation with rat liver mitochondria. Described herein is the chemical synthesis of II from diosgenin. As part of this synthesis, improved conditions are described for the conversion of diosgenin to (25R)-26-hydroxycholesterol. Benzoylation of the latter compound gave (25R)-cholest-5-ene-3 beta,26-diol 3 beta,26-dibenzoate which, upon allylic bromination followed by dehydrobromination, gave (25R)-cholesta-5,7-diene-3 beta,26-diol 3 beta,26-dibenzoate. Hydrogenation-isomerization of the delta 5.7-3 beta,26-dibenzoate to (25R)-5 alpha-cholest-8(14)-ene-3 beta,26-diol 3 beta,26-bis(cyclohexanecarboxylate) followed by controlled oxidation with CrO3-dimethylpyrazole gave (25R)-3 beta,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one 3 beta,26-bis(cyclohexanecarboxylate). Acid hydrolysis of the delta 8(14)-15-ketosteryl diester gave II. 13C NMR assignments are given for all synthetic intermediates and several major reaction byproducts. The structure of II was unequivocally established by X-ray crystal analysis. II was found to be highly active in the suppression of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured mammalian cells and to inhibit oleoyl coenzyme A-dependent esterification of cholesterol in jejunal microsomes.

Animals↗
PubMed1988

Preliminary X-ray analysis of crystals of murine adenosine deaminase.

We have obtained single crystals of a cloned mammalian adenosine deaminase (Mr = 41,000), a key enzyme in purine degradation and in normal development of the immune system, that are suitable for high-resolution structural analysis. The crystals belong to the space group C2 with unit cell parameters a = 101.68 A (1 A = 0.1 nm), b = 94.38 A, c = 85.51 A, and beta = 96.54 degrees. The asymmetric unit contains two enzyme molecules.

Adenosine Deaminase↗
PubMed1988

Concerning the structure of 3 beta-benzoyloxy-5 beta-cholesta-8,14-diene, a major byproduct in the chemical synthesis of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one.

The X-ray crystal structure of 3 beta-(p-bromobenzoyloxy)-5 beta-cholesta-8,14-diene (space group P21, a = 10.698 A, b = 9.487 A, c = 15.024 A, beta = 96.05 degrees, Z = 2) was determined by the heavy atom method and refined to R = 0.075. This heavy atom derivative was synthesized from 5 beta-cholesta-8,14-diene-3 beta-ol, the benzoate ester of which was previously shown to be the major byproduct in the low-temperature isomerization of 7-dehydrocholesteryl benzoate in HCl/chloroform. The work presented here establishes unequivocally that the configuration of this isomerization byproduct at C-5 is 5 beta-H and that the configuration at C-17 was unchanged.

Anticholesteremic Agents↗
PubMed1988

Crystal structure of 3 beta-benzoyloxy-6 alpha-chloro-5 alpha-cholest-7-ene, a key intermediate in the chemical synthesis of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one.

The X-ray crystal structure of 3 beta-benzoyloxy-6 alpha-chloro-5 alpha-cholest-7-ene (IV) was determined by the heavy atom method and refined to R = 0.063 (space group P21, a = 11.364, b = 11.089, c = 12.232, beta = 99.43 degrees, Z = 2). IV was previously shown to be an important intermediate in the acid-catalyzed isomerization of 7-dehydrocholesteryl benzoate. The present work unequivocally establishes the location of the double bond and the configuration of the chlorine of IV, information which is essential to the correct formulation of the mechanism of this reaction.

Anticholesteremic Agents↗
PubMed1987

Sex differences in weight loss among adults with type II diabetes mellitus.

The treatment of choice for Type II or non-insulin-dependent diabetes mellitus is a behavioral program for the management of weight. However, compliance with this lifelong dietary regimen is often poor. In the current investigation male and female adults with diagnosed Type II diabetes were randomly assigned to either a behavior modification, a cognitive modification, a cognitive-behavior modification, or a control group. Patients were evaluated in terms of weight, percentage of body fat, and glycosylated hemoglobin measures. Men lost significantly more weight than women and subjects in the behavior modification group lost more weight and demonstrated greater decreases in diabetes control than subjects in the cognitive-behavior modification, cognitive, and control groups. A significant interaction indicated that diabetic men may benefit more from behavioral weight reduction programs than diabetic women. Several explanations for these findings are considered.

Adult↗
PubMed1985

Acute effects of oxygen treatment upon information processing in hypoxemic COPD patients.

The present study investigated the effects of oxygen therapy upon human information processing for hypoxemic COPD patients. Each of ten patients was admitted to a general clinical research center for a two-day period. In a randomly counter-balanced factorial design, patients breathed either room air or enriched oxygen for either six hours or 20 minutes prior to testing. The tests evaluated speed of information processing, ability to detect correct sequence of tones, and serial memory. In addition, patients were evaluated on critical flicker fusion and story recall. The results suggested that acute oxygen therapy does not reverse information processing deficits observed in hypoxemic COPD patients.

Aged↗
PubMedDate not supplied

Effects of diet and exercise interventions on control and quality of life in non-insulin-dependent diabetes mellitus.

Evidence suggests that diet and exercise are associated with improved glucose tolerance for patients with non-insulin-dependent diabetes mellitus (NIDDM). Seventy-six volunteer adult patients with NIDDM were each assigned to one of four programs: diet, exercise, diet plus exercise, or education (control). Each program required ten weekly meetings. Detailed evaluations were completed prior to the program and after three, six, 12, and 18 months. Evaluations included various psychosocial measures, measures of the quality of life, and fasting blood glucose, glycosylated hemoglobin, and relative weight determinations. Of the 76 original participants, 70 completed the 18-month follow-up study. At 18 months, the combination diet-and-exercise group had achieved the greatest reductions in glycosylated hemoglobin measures. In addition, this group showed significant improvements on a general quality of life measure. These improvements were largely uncorrelated with changes in weight. The authors conclude that the combination of dietary change and physical conditioning benefits NIDDM patients, and that the benefits may be independent of substantial weight loss.

Activities of Daily Living↗
PubMedDate not supplied

Validation of smoking abstinence in newly diagnosed cardiovascular patients.

Three methods of assessing smoking status among newly diagnosed cardiovascular (CV) patients were compared: self-reports, collateral reports (spouse, friend, etc.), and saliva cotinine assays. Self-reported smoking status was assessed as the average number of cigarettes smoked per day at baseline, 3, 6, 9, and 12 months into treatment, and at a 6-month posttreatment follow-up. The majority of patients had quit smoking within 6 months prior to participating in the program. All participants were informed at the onset of the study and at the time of each assessment that their self-reports of smoking abstinence would be validated through collateral reports and possibly saliva cotinine analyses. Less than 5% (13 of 274) of the subjects' self-reports showed discrepancies with collateral reports. Analyses of saliva cotinine assays in a subsample of subjects, however, indicated that 16% (13 of 81) of the saliva cotinine tests were discrepant with the collateral reports. Thus, the saliva cotinine analyses picked up an additional 11% false negatives, as compared to collateral reports. It is concluded that the use of collateral reports as an index of smoking status may be an overestimate of actual quit rates. The overall discrepancy rate for this study, however, was fairly low and suggests that patients' self-reports may be reliable when they have already quit on their own and/or are notified in advance of verification procedures.

Adult↗
PubMedDate not supplied

Prospective evaluation of HDL cholesterol changes after diet and physical conditioning programs for patients with type II diabetes mellitus.

High-density lipoprotein (HDL) cholesterol is known to be low in patients with diabetes mellitus. Low HDL levels are correlated with premature cardiovascular mortality in several major epidemiologic studies and many investigators believe increases in HDL cholesterol may reduce the risk of coronary heart disease. We evaluated dietary and exercise interventions in relation to HDL cholesterol in patients with type II diabetes mellitus. Sixty-five volunteers were randomly assigned to one of four experimental conditions: diet, exercise, diet plus exercise, or education control. Three months after entering the program, those exposed to the dietary intervention had significant increases in HDL cholesterol. HDL increases for the other two treatment groups did not differ significantly from the education control.

Body Weight↗