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Biomedical subjects

J Barnard

Publications and source records attributed to J Barnard.

At least 55 records · Page 3Linked to original sources

Reversal of increased microvascular permeability associated with ischemia-reperfusion: role of cAMP.

Ischemia-reperfusion (IR) is a form of oxidant injury known to increase microvascular permeability in the lung. Agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) levels have been shown to have beneficial effects in several models of oxidant lung injury associated with increased microvascular permeability. We investigated the role of adenylate cyclase activation with isoproterenol (ISO) or forskolin (FSK) in reversing the increased microvascular permeability associated with IR. ISO or FSK administered after 45 min of ischemia and 46 min of reperfusion caused a reduction in the capillary filtration coefficient (Kfc) from 1.25 +/- 0.13 to 0.53 +/- 0.08 and 0.55 +/- 0.10 ml.min-1.cmH2O-1.100 g tissue-1, respectively, at 90 min of reperfusion. This reduction in Kfc was accompanied by a rise in perfusate cAMP levels from 16.5 +/- 4.9 and 31.2 +/- 11.9 pmol/ml at 45 min of reperfusion to 444.2 +/- 147.8 and 276.1 +/- 91.0 pmol/ml at 105 min of reperfusion in lungs treated with ISO or FSK, respectively, at 46 min of reperfusion. Dibutyryl cAMP (DBcAMP), a membrane-permeable cAMP analogue, mimicked the permeability effect by reducing Kfc to 0.67 +/- 0.15 at 90 min of reperfusion. Significant hemodynamic changes occurred but were small and cannot explain the observed effect on Kfc. Photomicrographs from lungs treated with ISO or FSK revealed a reversal of the morphological manifestations of increased microvascular permeability. We conclude that the increased microvascular permeability associated with IR can be reversed by ISO, FSK, and DBcAMP and that cAMP produced by the lung contributes to the observed reversal.

Animals↗

Angiotensin-converting enzyme inhibitors in patients with bronchial responsiveness and asthma.

Twenty-one subjects with known bronchial hyperreactivity were prospectively randomized in double-blind fashion to receive one of two angiotensin-converting enzyme inhibitors (ACE-I), enalapril or spirapril, for three weeks. Spirometry and methacholine provocation were performed prior to, during, and following ACE-I usage. Three of 21 subjects developed a nonproductive cough. However, only one subject wheezed slightly. Spirometry and bronchial reactivity (PD20) were unchanged throughout the study.

Adolescent↗

AIDS and the nurse.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Levels of uracil DNA glycosylase and AP endonuclease in murine B- and T-lymphocytes do not change with age.

Two DNA repair enzyme activities, uracil DNA glycosylase and AP endonuclease, were measured in extracts of T- and B-lymphocytes isolated from mice ranging in age from 3 to 24 months. T- and B-lymphocytes had roughly equal levels of AP endonuclease which did not change appreciably with age. T-lymphocytes had roughly twice as high a level of uracil DNA glycosylase as B-lymphocytes; these levels were not affected by age either. This constancy with age contrasts dramatically with increases in both enzymes--roughly 3-fold on a protein basis or 50-fold on a per cell basis--in a transformed line (MPC-11) derived from a carcinogen-induced lymphocytoma. These results are similar to those obtained with cultured murine fibroblasts, wherein a relative constancy was noted with passage of non-transformed cells, followed by dramatic changes upon transformation (La Belle, M & Linn, S, Mutat res 132 (1984) 51). Hence these enzyme assays do not support the notion of a drop in base excision DNA repair capacity as being a causative factor in aging, but suggest instead that DNA repair properties might differ dramatically in transformed vs non-transformed cells.

Aging↗

Class III alleles and high-risk MHC haplotypes in type I diabetes mellitus, Graves' disease and Hashimoto's thyroiditis.

By typing a large quantity of family-based material for HLA-B, HLA-DR, C4, C2 and factor B, we were able to derive four-gene complement haplotypes (C4A, C4B, C2, BF) and six-gene MHC haplotypes (HLA-B, complement, HLA-DR). Fourteen six-gene MHC haplotypes showed linkage disequilibrium but exact frequencies could not be determined because it was not always possible to assign null C4 alleles in families where null genes were not clearly seen to segregate. Comparison of unrelated type I diabetes, Graves' disease and Hashimoto's thyroiditis patients with healthy unrelated controls revealed the following MHC allele associations: C4B*3, HLA-DR3 and HLA-DR4 with type I diabetes; BF*F1 and HLA-DR3 with Graves' disease; HLA-DR4 with Hashimoto's thyroiditis. By typing families of type I diabetes and Graves' disease patients we were able to derive two high-risk DR3+ MHC haplotypes for both type I diabetes and Graves' disease. These are HLA-B8 C4A*Q0 C4B*1 BF*S HLA-DR3 and HLA-B18 C4A*3 C4B*Q0 BF*F1 HLA-DR3, and these haplotypes account for most of the associations between these diseases and HLA-DR3. The MHC haplotype HLA-B15 C4A*3 C4B*3 BF*S HLA-DR4 also carries high risk for type I diabetes in this group of patients. Our data suggest that other DR4+ haplotypes, probably containing C4A*3 C4B*1, carry increased risk for type I diabetes whereas haplotypes containing DR4 and C4 C4A*3 C4B*Q0 do not. Our phenotype data suggest that DR4 in Hashimoto's thyroiditis is frequently associated with HLA-B44, C4A*3, C4B*1 and BF*S.

Alleles↗

Epidemic hypochlorhydria.

During a study of gastric secretion four out of six previously healthy subjects developed hypochlorhydria after a transient illness with nausea, vomiting, and abdominal pain. Mean basal and peak acid outputs were 0 and 2.3 mmol (84 mg)/h one month after the onset of illness and 1.5 and 27.0 mmol/h (55 and 984 mg/h) at eight months' follow up. Two of the subjects were followed up at 18 months, when mean basal and peak acid outputs were 3.9 and 33.5 mmol/h (142 and 1221 mg/h). No endoscopic abnormality was seen at one and eight months, but biopsies showed active superficial gastritis, which resolved in one subject and became chronic in two. Schilling tests performed in three subjects at eight months showed diminished retention of vitamin B12. During hypochlorhydria a 24 hour intragastric analysis was performed for total and nitrate reducing bacteria, pH, and concentrations of nitrite and total and stable N-nitroso compounds. Of the 48 samples of gastric juice examined, 47 had bacterial growth of more than 10(6) organisms/ml and 46 had growth of nitrate reducing bacteria of more than 10(5) organisms/ml. Mean intragastric nitrite concentrations were 10 times higher than in a group of eight healthy controls. Both mean total and mean stable N-nitroso compound concentrations, however, were not appreciably different from those in controls. Although community transmission was a possibility, serological screening and electron microscopy of gastric biopsy specimens failed to show an infective cause. Transmission of an unidentified enteric pathogen via a contaminated pH electrode was therefore suspected. Thus gastric juice should not be returned to the stomach after contact with a contaminated glass electrode as this is a possible cause of atrophic gastritis.

Achlorhydria↗

Intragastric N-nitrosation is unlikely to be responsible for gastric carcinoma developing after operations for duodenal ulcer.

Three groups of patients studied after operations which had cured their duodenal ulcer were compared with a control group (no operation, n = 8). The surgical procedures included: proximal gastric vagotomy (n = 7), truncal vagotomy and pyloroplasty (n = 7), truncal vagotomy and antrectomy (n = 8). Samples of gastric juice were aspirated half hourly or hourly over 24 hours for measurement of pH, counts of all identified bacteria, nitrite and total N-nitrosocompounds. Although the pH over 24 hours was significantly higher after proximal gastric vagotomy (p less than 0.05) and truncal vagotomy and antrectomy (p less than 0.001) than controls, there was no difference between truncal vagotomy and pyloroplasty and controls. Counts of nitrate reducing bacteria over 24 hours were also significantly higher after truncal vagotomy and antrectomy than controls (p less than 0.1) but no differences were observed between the other groups. Only after truncal vagotomy and antrectomy was nitrite over 24 hours significantly increased compared with controls (p less than 0.01). Despite these higher values after truncal vagotomy and antrectomy, there was no significant difference in total N-nitrosocompounds between any of the four groups. Whereas bacterial counts and nitrite increased with pH, no correlation was found between total N-nitrosocompounds and pH. These results provide no evidence that exposure to total N-nitrosocompounds is increased after operations for duodenal ulcer.

Bacteria↗

Intragastric acidity, bacteria, nitrite, and N-nitroso compounds before, during, and after cimetidine treatment.

Eight healthy subjects were studied half-hourly or hourly for 24 h periods before, during, and after cimetidine treatment. No significant differences in intragastric bacterial counts or bacterial species or in intragastric nitrite or N-nitroso-compound concentrations were found as a result of cimetidine treatment. Bacterial counts and nitrite concentrations tended to increase with pH, but N-nitroso-compound concentrations did not. This study provides no evidence that cimetidine treatment may increase the risk of gastric carcinoma by raising N-nitroso-compound concentrations.

Bacteria↗

Pulmonary function changes in ozone-interaction of concentration and ventilation.

A total of 28 healthy young subjects have been exposed for 2 h to ozone (0.37-0.75 ppm) under conditions of either rest or intermittent light exercise (sufficient to increase the respiratory minute volume by a factor of 2.5). All pulmonary function tests (vital capacity, forced expiratory volume, maximum expiratory flow-volume curve, slope of phase III of alveolar nitrogen plateau) showed a significant deterioration relative to parallel control experiments. Responses were related to the dose of ozone as calculated from the product of concentration, exposure time, and respiratory minute volume during exposure, changes at 1 h averaging approximately one-half those seen at 2 h.

Adult↗

HL-A antigens in Graves' disease and Hashimoto's thyroiditis.

An increased frequency of HL-A 1 and HL-A 8 was found in patients with Graves' disease and Hashimoto's thyroiditis, whem compared to a control group from the same geographic area, and drawn from a pool of subjects attending one diagnostic centre. Furthermore, an increased incidence of W15 and W17 was found in Hashimoto's thyroiditis; however, these were not detected in any patient with Graves' disease.

Female↗