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Biomedical subjects

A G Clark

Publications and source records attributed to A G Clark.

At least 199 records · Page 11Linked to original sources
PubMed1986

A numerical simulation of the one-locus, multiple-allele fertility model.

Numerical simulations were performed to determine the equilibrium behavior of the one-locus fertility model in which fitness is considered as a property of a pair of mating diploids. A series of patterns of "fertility matrices" were considered for a single locus with two to six alleles. From these simulations, 19 different statistics were collected that characterize, at equilibrium, the heterozygosity, the mean fitness and the fate of populations begun at the allele-frequency centroid. For more than one-half of the trajectories produced by random fertility matrices, there was a decrease in the mean fitness at some time on the way to equilibrium. The mean number of alleles maintained at equilibrium increased only slightly with matrix dimension. Despite the potential for fertility models to display multiple stable equilibria, random fertility models maintain fewer distinct stable points than do random one-locus viability models. Pleiotropic models were also considered with fertility and viability selection operating sequentially within each generation. Most of the equilibrium statistics (with the exception of mean fertility) for the pleiotropic model were intermediate between the corresponding random viability and fertility models.

Alleles↗
PubMed1986

24-hour intragastric pH: continuous monitoring or nasogastric aspiration?

Hourly gastric aspiration has commonly been used to assess the efficacy of antisecretory compounds. We have compared continuous ambulatory 24-hour pH monitoring using a radiotelemetry capsule with standard nasogastric aspiration. Eight studies were performed on four male duodenal ulcer patients in remission receiving either placebo or an antisecretory agent. A significant correlation was found between capsule and aspirate pH measurements (r = 0.88, p less than 0.01). Radiotelemetry capsule measurements clearly showed the onset of action of an antisecretory drug, and the buffering effect of food. Radiotelemetric pH monitoring is shown to be as good as gastric sampling in the measurement of 24-hour intragastric acidity, allows continuous measurement of pH during normal activity and can accurately assess the effect of drugs on gastric acidity.

Anti-Ulcer Agents↗
PubMed1985

Enhanced survival in antibiotic-treated murine fecal peritonitis by administration of copovithane, a selective immunostimulative polymer.

The purpose of this study was to determine the effect of an immunostimulative polymer, Copovithane (Cpv), plus antibiotics (netilmicin and clindamycin) in a murine model of fecal peritonitis. Cpv augments humoral immunity with little effect on T cells and is nontoxic. Cpv 100 mg/kg iv administered at the onset of sepsis increased median survival time (MST) by 40-55% over untreated controls. Four experiments were performed. Cpv in combination with antibiotics when given at the time of onset of sepsis was significantly more effective than antibiotics alone (MST 235 vs 105 hr, P less than 0.05 at 144, 168, 192, 216 hr). In the second and third experiments Cpv alone and with antibiotics was administered 15 hr after the onset of sepsis. Cpv significantly augmented survival over controls in the second experiment (MST 87 vs 60 hr, P less than 0.025 at 96 hr). Cpv plus antibiotics was significantly better than antibiotics alone in the third experiment (MST 111 vs 64 hr, P less than 0.05 at 72 hr, P less than 0.005 at 120 hr). In the final experiment, Cpv did not inhibit growth of 20 bacterial species in agar and liquid media. Cpv significantly enhances survival in murine fecal peritonitis even when administered after the onset of sepsis; furthermore Cpv plus antibiotics in established peritonitis produces longer survival than antibiotics alone. Synthetic immunomodulators such as Cpv could eventually play a significant role in the management of peritoneal infection in humans.

Animals↗
PubMed1985

Natural selection with nuclear and cytoplasmic transmission. II. Tests with Drosophila from diverse populations.

Observations of intraspecific variation in organelle DNA have prompted a renewed interest in the evolutionary consequences of cytoplasmically transmitted factors. Attempts to quantify the significance of cytoplasmic effects are frequently limited by the difficulty in partitioning the cause of reciprocal cross differences among a series of possibilities. In the experiment reported here the nuclear genomes of a set of six lines of Drosophila melanogaster from diverse geographic locations were replaced in a series of cytoplasms. The segregation of the SM5 balancer chromosome was scored in a factorial design, and the data allowed a partitioning of variance such that cytoplasmic effects were distinguished from maternal effects and meiotic drive. An attempt was made to avoid the confounding problem of hybrid dysgenesis by performing the entire experiment (including chromosomal extractions) in a P cytotype. Results indicated a significant contribution of cytoplasm to the variance in SM5 segregation. Error variance showed an increasing trend as the experiment proceeded, and additional tests indicated that this was due to an accumulation of chromosomal mutations. These findings are interpreted in light of the population genetic theory that addresses the maintenance of cytoplasmic polymorphism.

Analysis of Variance↗
PubMed1985

Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.

We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.

Animals↗
PubMed1985

Laboratory infection of chicken eggs with Campylobacter jejuni by using temperature or pressure differentials.

Fertile chicken eggs were infected in our laboratory with Campylobacter jejuni suspensions by using temperature or pressure differential methods of inoculation. After 2 days of incubation, over 90% of the eggs carried C. jejuni when iron was present in the inoculum. This percentage declined rapidly until by day 8, less than 10% of the eggs were detectably infected. However, up to 11% of hatched, healthy chicks carried C. jejuni in their intestinal tracts. The isolated organisms were of the same serotype as the initial inoculum. C. jejuni was recovered without difficulty when the intestinal tracts of chicks were enriched, but recovery from early dead-in-shell or infertile eggs was poor. This poor recovery and the rapid decline of C. jejuni after 2 days of egg incubation suggest that the vibrio is sensitive to some part of the incubating egg or to the temperature of prolonged incubation. It was impossible to predict which eggs would yield infected chicks on the basis of the number of organisms taken up by each egg, and no correlation existed between the number of organisms taken up and the efficiency of the hatch, i.e., the hatch ratio. If iron was omitted from the inoculum broth, the egg infection rate at day 2 was lower.

Animals↗
PubMed1985

The use of multiple restriction fragment length polymorphisms in prenatal risk estimation. I. X-linked diseases.

An analytical procedure for estimating the risk of X-linked diseases based on presence/absence of a series of restriction sites is presented. Multiple-locus linkage phase of the carrier mother is first inferred from previous offspring, from parents, and by molecular means. Bayesian risk estimates are then obtained using this information and the recombination-segregation distribution. The improvement afforded by using multiple flanking markers rather than a single marker is dramatic. Whereas the upper bound on the probability that a family will be informative using a single diallelic X-linked marker is .5, in the case of m markers, the bound on the probability of an informative family becomes 1 - .5m. With a single linked marker, the precision in the risk estimate is bounded by the frequency of recombination, whereas the requirement of very tight linkage is relaxed somewhat when multiple flanking markers are used. Recombination interference and multiple-locus linkage disequilibria can further improve the risk estimates, but it is important to understand how the statistical confidence in these parameters affects the reliability of the risk estimates.

Chromosome Mapping↗
PubMed1984

Purification and properties of glutathione S-transferases from larvae of Wiseana cervinata.

The glutathione S-transferases from the porina moth, Wiseanna cervinata, were purified by affinity chromatography, cation-exchange chromatography and preparative isoelectrofocusing. The major transferase (IV) was purified to homogeneity by a factor of 530-fold with a yield of 83%. Other transferases present were purified to a smaller degree (approx. 50-fold) to a stage of near-homogeneity. The transferases examined all had Mr values about 45 000-50 000. They appeared to be homodimers of either of two types of subunit, of Mr 22 800 and 24 600. Enzymes consisting of the different types of subunit were not immunologically cross-reactive. The major enzyme fractions separated by cation-exchange chromatography were both active with 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, ethacrynic acid and iodomethane, but were inactive with 4-nitropyridine N-oxide, 1,2-epoxy-3-(p-nitrophenoxy)propane, bromosulphophthalein and p-nitrobenzyl chloride. The kinetics of the enzyme-catalysed reaction with enzyme IV were non-Michaelean with respect to both substrates. Both products were inhibitory. The results appear to be compatible with a random steady-state mechanism. It is concluded that these enzymes are very similar, in their physical and chemical constitution, in their catalytic properties and in their relationships with each other, to those enzymes that have been isolated from vertebrate organisms.

Amino Acids↗
PubMed1984

Kinetic studies on a glutathione S-transferase from the larvae of Costelytra zealandica.

Of the glutathione S-transferases from the New Zealand grass grub (Costelytra zealandica) active in conjugating the model substrate 1-chloro-2,4-dinitrobenzene, the most active was isolated in a functionally homogeneous form. This had an isoelectric point of 8.7. Preliminary evidence suggests that it is a homodimer with subunits of Mr 23 500. The dependence of the enzyme-catalysed reaction on substrate concentration was analysed in terms of the rate equation characteristic of Ordered Bi Bi or Rapid-Equilibrium Random mechanisms. Evidence was found for a critical ionizing event at pH 9.3 at 37 degrees C. This event appears to involve a twofold change in charge on the enzyme, which may be the result of co-operative ionizations rather than independent ionizations. This appears to affect neither the binding of the aromatic substrate to the enzyme, nor the maximum catalytic velocity of the enzyme-catalysed reaction. The variation of the kinetics with temperature was studied. Apparent thermodynamic parameters characteristic of the reaction were derived. The possible relevance of the temperature-dependence of the enzyme-catalysed reaction in vivo is discussed.

Animals↗
PubMed1984

Restrictions to posture in working environments.

This paper reviews some typical industrial work postures which have to be adopted as a result of either poorly designed machinery or workplace layout. Brief case studies of investigations carried out by the Materials Handling Research Unit (MHRU) are described. They illustrate the dangers associated with the postures and work environments which have been found to contribute to high incidences of industrial back injury. The handling problems considered by this paper will include those associated with cable drums, 200 litre drums, sacks and workstation design.

Journal Article↗
PubMed1984

Effect of glucagon on ureteric peristalsis in man, pig, rabbit and rat.

The effect of glucagon on ureteric peristalsis in man, pig, rabbit and rat has been studied using specially shaped perspex blocks containing silver/silver chloride bipolar electrodes. In all subjects the ureteric electrical activity was recorded during laparotomy. Glucagon was administered as a single intravenous dose of 14 micrograms per kilogram in man and in doses of between 6.25 and 160 micrograms per kilogram in the other species. The mean (+/- S.E.M.) peristaltic rates per minute were: man 4.85 (+/- 0.66), pig 2.04 (+/- 0.36), rabbit 3.78 (+/- 0.23) and rat 5.02 (+/- 0.16). Glucagon was found to have no significant effect on ureteric peristalsis in man, rabbit or rat, whilst in the pig a variable effect was seen.

Action Potentials↗
PubMed1984

Natural selection with nuclear and cytoplasmic transmission. I. A deterministic model.

A deterministic model allowing variation at a nuclear genetic locus in a population segregating two cytoplasmic types is formulated. Additive, multiplicative and symmetric viability matrices are analyzed for existence and stability of equilibria. The protectedness of polymorphisms in both nuclear genes and cytoplasmic types is also investigated in the general model. In no case is a complete polymorphism protected with this deterministic model. Results are discussed in light of the extensive variation in mtDNA that has recently been reported.

Animals↗
PubMed1984

Effect of D-tryptophan on hemolysin production in Vibrio parahaemolyticus.

Production of the Kanagawa hemolysin by a strain of Vibrio parahaemolyticus isolated from a gastroenteritis patient was found to correlate with the presence in cell lysates of two unidentified compounds, designated X and Y. The two compounds were present in cell lysates of the organism grown in peptone at the optimal pH for hemolysin synthesis but were not present when cell lysates were grown in peptone at a constant pH of 8.0. They were also absent in cells grown in synthetic medium at pH 6.2 without the addition of D-tryptophan, a condition under which hemolysin is not produced. Both X and Y were present intracellularly only from the time that D-tryptophan was added to synthetic medium, a known method of inducing hemolysin synthesis.

Chromatography, High Pressure Liquid↗
PubMed1982

Serum 1,25-dihydroxyvitamin D levels in subjects with X-linked hypophosphatemic rickets and osteomalacia.

In order to determine whether a defect in vitamin D metabolism might play a role in the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia (XLH), we compared the serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level in 52 normal subjects and 37 patients with XLH. In untreated patients, adults were found to have values similar to age-matched controls, while youths had values similar to growth-rate-matched controls but significantly lower than the levels of age-matched controls who were growing at a normal rate. In contrast, treated XLH patients of all ages had serum levels significantly lower than both controls and untreated XLH patients. Further, the serum levels of 1,25(OH)2D in these treated patients had a significant inverse linear correlation with serum 25-(OH)D concentrations. We propose that subjects with XLH have serum 1,25(OH)2D levels within appropriate age- and growth-rate-matched normal ranges. However, in the presence of hypophosphatemia, we would have anticipated elevated levels of 1,25(OH)2D; viewed in this light the serum 1,25(OH)2D levels are inadequate, suggesting the presence of a relative deficiency of this active vitamin D metabolite.

Adolescent↗