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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 397 records · Page 22Linked to original sources
PubMed1993

Homology with Saccharomyces cerevisiae RNA14 suggests that phenotypic suppression in Drosophila melanogaster by suppressor of forked occurs at the level of RNA stability.

The suppressor of forked [su(f)] locus of Drosophila melanogaster encodes at least one cell-autonomous vital function. Mutations at su(f) can affect the expression of unlinked genes where retroviral-like transposable elements are inserted. Changes in phenotype are correlated with changes in mRNA profiles, indicating that su(f) affects the production and/or stability of mRNAs. We have cloned the su(f) gene by P-element transposon tagging. Alterations in the DNA map of eight lethal alleles were detected in a 4.3-kb region. P-element-mediated transformation using a fragment including this interval rescued all aspects of the su(f) mutant phenotype. The gene is transcribed to produce a major 2.6-kb RNA and minor RNAs of 1.3 and 2.9 kb, which are present throughout development, being most abundant in embryos, pupae, and adult females. The major predicted gene product is an 84- kD protein that is homologous to RNA14 of Saccharomyces cerevisiae, a vital gene where mutation affects mRNA stability. This suggests that phenotypic modification by su(f) occurs at the level of RNA stability.

Amino Acid Sequence↗
PubMed1993

The effect of carbohydrate ingestion on performance during a 30-km race.

Seven experienced endurance runners completed a 30-km road race on two occasions separated by 10 days. On each occasion the subjects consumed 250 ml of either a 5% carbohydrate (CHO) solution or nonflavored tap water (W) immediately prior to the start of the race, and 150 ml of the assigned fluid every 5 km thereafter. Performance time for the CHO trial was faster compared with the time recorded for the W trial (128.3 +/- 19.9 min vs. 131.2 +/- 18.7 min [p < 0.01] respectively). Running speed was maintained throughout the race in the CHO trial, whereas a decrease in the running speed occurred after 25 km (p < 0.05) in the W trial. No difference was found between the two trials in blood glucose concentration, plasma electrolyte concentrations, body weight loss, change in plasma volume, and rating of perceived exertion. Blood lactate concentration was higher at 25 km during the CHO trial compared with the W trial (p < 0.01), but plasma FFA and glycerol concentrations were lower at 30 km during the CHO trial than during the W trial (p < 0.05). In conclusion, this study shows that performance time for a 30-km road race is improved after ingesting a 5% CHO solution.

Adult↗
PubMed1993

Carbohydrate intake and recovery from prolonged exercise.

The influence of increased carbohydrate intake on endurance capacity was investigated following a bout of prolonged exercise and 22.5 hrs of recovery. Sixteen male subjects were divided into two matched groups, which were then randomly assigned to either a control (C) or a carbohydrate (CHO) condition. Both groups ran at 70% VO2max on a level treadmill for 90 min or until volitional fatigue, whichever came first (T1), and 22.5 hours later they ran at the same % VO2max for as long as possible to assess endurance capacity (T2). During the recovery, the carbohydrate intake of the CHO group was increased from 5.8 (+/- 0.5) to 8.8 (+/- 0.1) g kg-1 BW. This was achieved by supplementing their normal diet with a 16.5% glucose polymer solution. An isocaloric diet was prescribed for the C group, in which additional energy was provided in the form of fat and protein. Run times over T1 did not differ between the groups. However, over T2 the run time of the C group was reduced by 15.57 min (p < 0.05), whereas those in the CHO group were able to match their T1 performance. Blood glucose remained stable throughout T1 and T2 in both groups. In contrast, blood lactate, plasma FFA, glycerol, ammonia, and urea increased. Thus, a high carbohydrate diet restored endurance capacity within 22.5 hrs whereas an isocaloric diet without additional carbohydrate did not.

Adult↗
PubMed1993

Ammonium metabolism and protection from urease mediated destruction in Helicobacter pylori infection.

AIM: To investigate further the intracellular ammonium metabolism of Helicobacter pylori and the mechanism of its urease mediated destruction. METHODS: The mechanism of the in vitro destruction of H pylori was investigated by incubating it in buffer solutions, at pH 6.0, containing isocitrate or alpha ketoglutarate in addition to urea concentrations which had previously been shown to destroy H pylori. RESULTS: The median (range) 5 minute survival of H pylori in 0.2 mol/l citrate buffer (pH 6.0) in the absence of urea was 88% (18-184%) and was similar to its survival in 0.2 mol/l isocitrate buffer in the absence of urea, median 88% (15-274%). In the presence of 50 mmol/l urea the survival of H pylori in the citrate buffer was reduced, 9.9% (0-146%), compared with its survival in isocitrate buffer with the same concentration of urea 37% (0-274%) (p < 0.01). A 72 hour preincubation of the organism with 10 mmol/l alpha ketoglutarate also increased the 5 minute survival of the organism in 0.2 mol/l citrate buffer containing 50 mmol/l urea to 36% (9-145%) compared with its survival in the same buffer but without preincubation with alpha ketoglutarate 0% (0-62%). CONCLUSION: The protection of H pylori from rapid destruction by the supply of compounds used in the intracellular metabolism of the ammonium shows that the urease mediated destruction of H pylori can be explained by intracellular depletion of alpha ketoglutarate as a result of over production of ammonium by uncontrolled urease activity.

Ammonia↗
PubMed1993

Human muscle metabolism during intermittent maximal exercise.

Eight male subjects volunteered to take part in this study. The exercise protocol consisted of ten 6-s maximal sprints with 30 s of recovery between each sprint on a cycle ergometer. Needle biopsy samples were taken from the vastus lateralis muscle before and after the first sprint and 10 s before and immediately after the tenth sprint. The energy required to sustain the high mean power output (MPO) that was generated over the first 6-s sprint (870.0 +/- 159.2 W) was provided by an equal contribution from phosphocreatine (PCr) degradation and anaerobic glycolysis. Indeed, within the first 6-s bout of maximal exercise PCr concentration had fallen by 57% and muscle lactate concentration had increased to 28.6 mmol/kg dry wt, confirming significant glycolytic activity. However, in the tenth sprint there was no change in muscle lactate concentration even though MPO was reduced only to 73% of that generated in the first sprint. This reduced glycogenolysis occurred despite the high plasma epinephrine concentration of 5.1 +/- 1.5 nmol/l after sprint 9. In face of a considerable reduction in the contribution of anaerobic glycogenolysis to ATP production, it was suggested that, during the last sprint, power output was supported by energy that was mainly derived from PCr degradation and an increased aerobic metabolism.

Adenosine Triphosphate↗
PubMed1993

A Double-Blind Placebo-controlled Trial of Ursodeoxycholic Acid in the Prevention of Gallstones during Weight Loss after Vertical Banded Gastroplasty.

One hundred and seven patients whose gallbladder was normal at the time of vertical banded gastroplasty (VBG) were considered for entry into a randomized placebo-controlled double-blind study to determine the effectiveness of ursodeoxycholic acid (UDCA) in preventing cholelithiasis during the period of weight loss. Twenty-one patients (20%) developed gallstones in the six-week period post-VBG and prior to randomization and were therefore excluded. Eighty-six patients were randomized at 6 weeks to active medication or placebo. Of these, 61 patients (71 %) completed the study. Twenty-five patients (29%) failed to complete the study because of incompliance, intolerance to the medication or pregnancy; 17 of these were in the active treatment group and eight were in the placebo group. None of the 27 patients treated with UDCA developed gallstones, whereas eight of 34 (24%) patients taking placebo developed gallstones. This difference was statistically significant (p = 0.0061). These results suggest that UDCA is fully effective in preventing gallstone formation following VBG in patients who follow the prescribed regimen.

Journal Article↗
PubMed1993

Cholesterol crystallization-promoters in human bile: comparative potencies of immunoglobulins, alpha 1-acid glycoprotein, phospholipase C, and aminopeptidase N1.

Concanavalin A (Con A)-binding glycoproteins accelerate the rate of cholesterol crystal formation as a prelude to gallstone formation. Immunoglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha 1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of the six putative promoters and examined their comparative effects by adding equal amounts to a cholesterol crystal growth assay. The effects of immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the potency of these proteins was in the following order: IgM > IgA = AAG > IgG. APN and pcPLC showed no effect on cholesterol crystal growth at their apparent physiological concentrations. In subtractive experiments, only a minor loss (< 10%) of net promoting activity from that of the whole Con A-bound fraction was observed after immunoabsorptive removal of pcPLC, APN, or immunoglobulins. Total removal of AAG, however, showed a far greater loss (/33%) of the net promoting activity. These data indicate that AAG accounts for the greatest portion of net biliary Con A-bound promoting activity derived from currently defined and well-identified glycoproteins. However, more than 60% of total Con A-binding promoting activity remains unaccounted for, indicating the presence of other important and still unidentified promoters in human bile.

Aminopeptidases↗
PubMed1992

Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion.

HIV use the CD4 molecule as their primary cellular receptor. Residues in the N-terminal domain (D1) of CD4 are crucial to HIV attachment through the gp120 envelope component. However, other regions of CD4 appear to be required subsequently for virus- and cell-cell fusion. Little is understood of the post-binding steps which may differ between HIV variants. We report a novel anti-CD4 mAb that does not block CD4/gp120 binding, but that does efficiently block both viral infection and cell-cell syncytia formation, and define its contact site as residues in CD4 D2 using both mouse/human CD4 chimeras and CD4 substitution mutants. We also investigated the basis for its antiviral effect. Using the CD4 D2 specific mAb, we identify another conserved step in HIV infection, as evidenced by its ability to neutralize a broad range of primary isolates and T cell-line passaged strains. Monovalent forms of the mAb were used to determine if its activity was due to masking of the D2 epitope, to steric inhibition, or bivalency. Our data indicate that both binding site and bivalency of the mAb underlie its potency. The need for bivalency is not simply explained by affinity, because monovalent forms can displace the intact mAb and reverse its protective effect. These results provide evidence that binding of the D2-specific mAb prevents structural alterations necessary for membrane fusion.

Animals↗
PubMed1992

Lipoamide dehydrogenase from Azotobacter vinelandii: site-directed mutagenesis of the His450-Glu455 diad. Kinetics of wild-type and mutated enzymes.

Three amino acid residues in the active site of lipoamide dehydrogenase from Azotobacter vinelandii were replaced with other residues. His450, the active-site base, was replaced with Ser, Tyr or Phe. Pro451, from X-ray analysis found to be in cis conformation positioning the backbone carbonyl of His450 close to N3 of the flavin, was changed to Ala. Glu455, from X-ray analysis expected to be involved in modulating the pKa of the base (His450), was replaced with Asp and Gln. The general conclusion is that mutation of the His-Glu diad impairs intramolecular electron transfer between the disulfide/dithiol and the FADH-/FAD. The wild-type enzyme functions according to a ping-pong mechanism in the physiological reaction in which the formation of NADH is rate-limiting. Above pH 8.0 the enzyme is strongly inhibited by the product NADH. The pH dependence of the steady-state kinetics using the NAD+ analog 3-acetylpyridine adenine dinucleotide (AcPyAde+) reveals a pKa of 8.1 in the pKm AcPyAde+ plot indicating that this pKa is related to the deprotonation of His450 [Benen, J., Berkel van, W., Zak, Z., Visser, T., Veeger, C. & Kok de, A. (1991) Eur. J. Biochem. 202, 863-872] and to the inhibition by NADH. The mutations considerably affect turnover. Enzymes with the mutations Pro451----Ala, His450----Phe and His450----Tyr appear to be almost inactive in both directions. Enzyme His450----Ser is minimally active, V at the pH optimum being 0.5% of wild-type activity in the physiological reaction. Rapid reaction kinetics show that for the His450-mutated enzymes the reductive half reaction using reduced 6,8-thioctic acid amide [Lip(SH)2] is rate-limiting and extremely slow when compared using reduced 6,8-thioctic acid amide [Lip(SH)2] is rate-limiting and extremely slow when compared to the wild-type enzyme. For enzyme Pro451----Ala it is concluded that the loss of activity is due to over-reduction by Lip(SH)2 and NADH. The Glu455-mutated enzymes are catalytically competent but show strong inhibition by the product NADH (enzyme Glu455----Asp more than Glu455----Gln). The inhibition can largely be overcome by using AcPyAde+ instead of NAD+ in the physiological reaction. The rapid reaction kinetics obtained for enzymes Glu455----Asp and Glu455----Gln deviate from the wild-type enzyme. It is concluded that this difference is due to cooperativity between the active sites in this dimeric enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Azotobacter vinelandii↗