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Biomedical subjects

C Slater

Publications and source records attributed to C Slater.

At least 37 records · Page 2Linked to original sources

Helicobacter pylori utilises urea for amino acid synthesis.

Helicobacter pylori has one of the highest urease activities of all known bacteria. Its enzymatic production of ammonia protects the organism from acid damage by gastric juice. The possibility that the urease activity allows the bacterium to utilise urea as a nitrogen source for the synthesis of amino acids was investigated. H. pylori (NCTC 11638) was incubated with 50 mM urea, enriched to 5 atom% excess 15N, that is the excess enrichment of 15N above the normal background, in the presence of either NaCl pH 6.0, or 0.2M citrate pH 6.0. E. coli (NCTC 9001) was used as a urease-negative control. 15N enrichment was detected by isotope ratio mass spectrometry. H. pylori showed intracellular incorporation of 15N in the presence of citrate buffer pH 6.0 but there was no significant incorporation of 15N in unbuffered saline or by E. coli in either pH 6.0 citrate buffer or unbuffered saline. The intracellular fate of the urea-nitrogen was determined by means of gas chromatography/mass spectrometry following incubation with 15N enriched 5 mM urea in the presence of either 0.2 M citrate buffer pH 6.0 or 0.2 M acetate buffer pH 6.0. After 5 min incubation in either buffer the 15N label appeared in glutamate, glutamine, phenylalanine, aspartate and alanine. It appears, therefore, that at pH and urea concentrations typical of the gastric mucosal surface, H. pylori utilises exogenous urea as a nitrogen source for amino acid synthesis. The ammonia produced by H. pylori urease activity thus facilitates the organism's nitrogen metabolism at neutral pH as well as protecting it from acid damage at low pH.

Amino Acids↗

Effect of ibuprofen on the acute-phase response and protein metabolism in patients with cancer and weight loss.

The aim of this study was to determine whether administration of the non-steroidal anti-inflammatory agent ibuprofen might attenuate the acute-phase response in patients with colonic cancer. Cytokines and acute-phase proteins were measured before administration of ibuprofen and again 3 days later, when protein synthesis was measured using 15N-glycine. In patients with cancer, ibuprofen caused a significant reduction in the plasma concentration of all five acute-phase proteins studied. Although interleukin 6 levels were raised, they did not change following administration of ibuprofen. Unlike the situation in patients with cancer who did not receive ibuprofen, whole-body protein kinetics were similar to those of control subjects in patients with cancer who received ibuprofen. Whether or not ibuprofen had been administered, non-export hepatic protein synthesis rates were significantly lower in patients with than in those without cancer. These results suggest that short-term administration of ibuprofen can attenuate accelerated whole-body protein kinetics and the acute-phase response in patients with advanced cancer.

Acute-Phase Proteins↗

Endothelin-1-evoked calcium transients in UMR-106 osteoblastic osteosarcoma cells are mediated through endothelin-A and endothelin-B receptors.

Endothelin (ET) receptor subtypes involved in the modulation of intracellular calcium were studied in UMR-106 osteoblastic osteosarcoma cells. Calcium signaling in UMR-106 cells in suspension was determined with fluo-3-acetoxymethylester fluorescent dye. ET-1 and the ETB-selective agonist sarafotoxin 6c (S6c) elicited rapid calcium transients. Maximally effective concentrations of the ETA-selective antagonist BQ-123 [Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu)] attenuated ET-1-evoked calcium transients by only 50%. BQ-123 had no effect on S6c-stimulated transients. ET-1 and S6c showed homologous desensitization on repeated administration. Pretreatment with ET-1 completely eliminated S6c-evoked calcium transients, whereas S6c pretreatment only partially (50%) attenuated the calcium transient evoked by ET-1. Joint pretreatment with S6c and BQ-123 or pretreatment with the ETA/ETB nonselective antagonist PD-142893 (Ac-D-diphenylalanine-Leu-Asp-Ile-Ile-Trp) eliminated the ET-1-stimulated calcium transient. These cells display both ETA and ETB receptors (60:40), as demonstrated by saturation binding experiments with [125I] ET-1 and the ETB specific agonist, [125I] IRL-1620 (Suc [Glu9, Ala11,15] endothelin-1 [8-21]). This was further confirmed by competition binding experiments using [125I] ET-1 and subtype-selective ligands S6c and BQ-123. These data indicate that ET-1 interacts with both ETA and ETB receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells.

Amino Acid Sequence↗

Effects of nonsteroidal anti-inflammatory drugs on microvascular dynamics.

Techniques of intravital microscopy were used to assess the effect of the nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and ibuprofen, on the microcirculation. Hemodynamics in venules of the rat mesentery were studied in terms of vessel diameter, red blood cell velocity, and leukocyte-endothelium interactions: leukocyte-endothelium adhesion (LEA), white blood cell (WBC) marginating flux, and WBC velocity. Measurements were made during (1) control conditions (topical suffusion with ringer-gelatin drip), (2) topically suffused indomethacin or ibuprofen, (3) an induced inflammatory response (suffusion with the chemoattractant N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)), and (4) concomitant suffusion with FMLP and NSAID. Short term topical suffusion (90 sec) with indomethacin and ibuprofen had little or no effect on control hemodynamics. Five-minute suffusions with indomethacin (5 x 10(-5) to 5 x 10(-4) M) significantly increased LEA while ibuprofen (5 x 10(-3) M) significantly decreased LEA. Topical suffusion with the chemotactic agent FMLP induced inflammation and significantly increased LEA in venules. Treatment with indomethacin during induced inflammation had no effect on the inflammatory reaction in terms of the microvascular hemodynamics measured in this study. Treatment with ibuprofen during induced inflammation significantly reduced LEA and increased red blood cell velocity. In conclusion, although both of the NSAIDs studied here are known to block the cyclooxygenase pathway of arachidonic acid metabolism, the actions of indomethacin and ibuprofen on the inflammatory process are very different with an important effect of ibuprofen being to decrease LEA.

Administration, Topical↗

Effect of diet on performance during recovery from intermittent sprint exercise.

Eighteen games players (9 males, 9 females) performed 30 maximum 6-sprints on a non-motorized treadmill. Each sprint was preceded by a 60-s jog at 40% maximum speed and was followed by a 54-s walk at 20% maximum speed. Thus, the entire test was of 60-min duration. The subjects were then randomly assigned to three groups and repeated the 1-h test 24 h later after consuming either a high, normal or low carbohydrate diet (79 +/- 3, 47 +/- 8, 12 +/- 1% CHO, respectively). During trial 1, mean power output declined from 653 +/- 131 to 600 +/- 158 W during the 30 sprints (P < 0.01) and power output was lower during trial 2 than during trial 1 (n = 18, P < 0.01). During trial 2, there were no differences in sprint performance between the dietary groups for the exercise test as a whole (trial 2 mean power lower than trial 1 by 0.2, 0.5 and 5.0% for the high, normal and low CHO groups, respectively; N.S.), but if only the first nine sprints are considered, then the high CHO group performed better than the low CHO group (P < 0.05). Blood lactate and glucose concentrations were lower during trial 2 than trial 1 by 4.5, 13.8 and 29.0% (lactate) and 14.9, 11.3 and 35.8% (glucose) for the high, normal and low CHO groups, respectively (both P < 0.01). Thus, both the metabolic responses to, and the performance of, maximum intermittent exercise were reduced when the test was repeated after 24 h recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular biology of the skin introduction: approaches and principles.

This issue of Seminars in Dermatology describes our current understanding of the molecular nature of skin diseases. Some would say it is hubris to even contemplate this charge considering the rapid progress in molecular genetics. We implore the gods protecting the nucleotides to look kindly on our efforts. This introductory article discussed some general methodological considerations and techniques and provides a glossary of common terms used in molecular biology, useful for understanding this issue of Seminars in Dermatology. This article is aimed at neophytes to enhance their ability to enter the magical realm of the gene. The articles in this issue describe diseases with a defined defect at the DNA level or diseases in which there is a rapid closing in on the basic defect.

Genetic Techniques↗

A normal male with an inherited deletion of one exon within the DMD gene.

We describe two brothers with identical inherited deletions of one single exon within the middle of the DMD gene; one brother has Becker muscular dystrophy diagnosed at 11 years of age, whereas the older brother is normal at 18. These results have implications for genetic counselling and prenatal diagnosis in families with Becker muscular dystrophy.

Adolescent↗

Macromelanosomes in the early diagnosis of neurofibromatosis.

Skin biopsies of café-au-lait macules from 34 patients with a clinical diagnosis of classical neurofibromatosis were examined histologically and ultrastructurally to determine the presence or absence of macromelanosomes in the epidermal melanocytes and keratinocytes. Sixteen of the 34 patients had macromelanosomes. The presence of macromelanosomes varied with age and ethnic background; they were detected in nine of 12 Whites, six of 10 persons of mixed ancestry, and one of two Blacks. In these populations skin biopsy is useful in early diagnosis of neurofibromatosis. However, none of 10 persons of Indian stock had macromelanosomes. Their total absence in this group may be indicative of genetic heterogeneity.

Child↗

Meningitis in Cape Town children.

A prospective clinical and microbiological survey of 213 children who presented to the teaching hospitals of the Cape Peninsula with meningitis was performed during a winter month. The predominant bacterium isolated was Neisseria meningitidis and this survey uncovered an outbreak of viral meningitis due to echovirus 4 of the Du Toit strain. In comparison with previous studies, the absence of fever in 20% of the cases of meningococcal disease and the isolation of N. meningitidis group B organisms which were resistant to sulphonamides are noted. Cases of N. meningitidis meningitis with initial clinical and cerebrospinal fluid findings indistinguishable from those in echovirus 4 meningitis are presented to emphasize the difficulties encountered in making a differential diagnosis. We recommend that in endemic areas all children with meningitis should be observed in hospital for at least 48 hours until the diagnosis of N. meningitidis has been excluded bacteriologically.

Adolescent↗

Estimates of the demand for health: males in the pre-retirement years.

The demand for health is estimated for black and white males in the pre-retirement years using data from the first wave of 1966 National Longitudinal Survey of men aged 45-59. This survey includes direct measures of the wage rate and family assets. Findings for whites generally corroborate Grossman's initial estimates of the demand for health. In contrast to whites, blacks show a much stronger wage effect and a significant positive effect of wife's education, with no other factors being significant. The issue of reverse causality between the wage and health is addressed via a simultaneous equations health-wage model. Contrary to expected, but consistent with previous findings, the structural model yielded an even larger wage effect.

Black or African American↗

Isolation and characterization of an alpha-tubulin gene from Leishmania enriettii.

An alpha-tubulin gene of Leishmania enriettii has been identified in genomic Southern blots by hybridization with a heterologous alpha-tubulin gene from Drosophila melanogaster. A clone containing this gene has been isolated from a plasmid library of size-selected L. enriettii DNA. It was identified by hybridization with the D. melanogaster tubulin gene. The cloned DNA fragment was characterized by restriction analysis and partial DNA sequence analysis. The cloned DNA fragment is 2 kb in length, bounded by Pst I sites, and appears to contain the entire coding region of the alpha-tubulin gene.

Animals↗

Effect of catabolite repression on the mer operon.

The plasmid-determined mer operon, which provides resistance to inorganic mercury compounds, was subject to a 2.5-fold decrease in expression when glucose was administered at the same time as the inducer HgCl2. This glucose-mediated transient repression of the operon was overcome by the addition of cyclic AMP. Permanent catabolite repression of the operon was observed in the 1.6- to 1.9-fold decrease in expression in mutants lacking either adenyl cyclase (cya) or the catabolite activator protein (crp). The effect of the cya mutation on mer expression could be overcome by the addition of cyclic AMP at the time of induction, In addition to these effects on the whole cells of a wild-type strains, we examined the effect of catabolite repression on the expression of the mercuric ion [Hg(II)] reductase enzyme, assayable in cell extracts, and on the Hg(II) uptake system, assayable in a mutant strain which lacked reductase activity. There was a two- to threefold effect of repression on the Hg(II) reductase enzyme assayable in vitro after induction under catabolite repressing conditions (either with glucose or in the crp and cya mutants). We did not find a similar repressing effect on the induction of the Hg(II) uptake system, which is also determined by the mer operon.

Adenylyl Cyclases↗