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Biomedical subjects

R C Brown

Publications and source records attributed to R C Brown.

At least 109 records · Page 6Linked to original sources

Binding and degradation of NH2-terminal parathyroid hormone by opossum kidney cells.

The binding and cellular processing of NH2-terminal parathyroid (PTH) hormone by confluent monolayers of opossum kidney (OK) cells was characterized using radiolabeled PTH peptide analogues. Time- and temperature-dependent specific binding of 125I-labeled (Nle-8,18, Tyr-34)-NH2-bovine(b)PTH-(1-34) was accompanied by the appearance of degraded radiolabel in the cell medium. Degrading activity was observed to be a specific consequence of binding by PTH receptors. Degrading activity was inhibited by monensin, chloroquine, and NH4+ but not by chymotrypsin inhibitors. Acid washing demonstrated that greater than 80% of total cell-associated specific binding at equilibrium was located in a rapidly internalized (acid-resistant) pool. Monensin pretreatment led to increased acid-resistant binding, presumably through inhibition of turnover of internalized receptor ligand and indicated that the degradation of radiolabel was probably associated with processing of the receptor-ligand complex. Release of intact radiolabel from the acid-resistant pool indicated that some of the internalized peptide was recycled out of the cell in an undegraded form (retroendocytosis). Acid-resistant binding and degradation of 125I-(Nle-8,18, Tyr-34)-NH2-bPTH-(3-34) was minimal, indicating that this ligand was not internalized. It is concluded that the binding and internalization of PTH-(1-34) fragment by confluent OK cells is a specific receptor-mediated process. Cellular processing of PTH-(1-34) conforms to established models of internalization by receptor-mediated endocytosis.

Animals↗

Renal insufficiency and secondary hyperparathyroidism in elderly patients.

Glomerular filtration rate (GFR) is frequently reduced in elderly people. However, the effect of this on mineral metabolism in this population has received little attention. GFR, serum intact parathyroid hormone (PTH) and vitamin D metabolites were measured in 37 patients admitted to hospital for various reasons. In 20 patients with GFR greater than 50 mL/min, an elevated serum intact PTH concentration (greater than 5.4 pmol/L) was found in two, while in 17 patients with GFR less than 50 mL/min PTH was elevated in 13. One of this group was hypercalcaemic and presumed to have primary hyperparathyrodism. Adjusted calcium was normal in all other patients. Two patients had a low serum 25-hydroxyvitamin D concentration (less than 9 nmol/L) suggesting vitamin D insufficiency while a further five had a reduced 1,25-dihydroxyvitamin D concentration, four of these having a GFR less than 50 mL/min. We conclude that hyperparathyrodism is common in hospitalized elderly patients, particularly in those with mild to moderate renal insufficiency. This may contribute to bone mineral loss in such patients.

Aged↗

Dietary magnesium depletion: p-nitroanisole metabolism and glucuronidation in rat hepatocytes and hepatic microsomal membranes.

Male Sprague-Dawley rats were pair fed either a control magnesium diet (480 mg/kg) or a magnesium-deficient diet (30 mg/kg) for 10 days to produce magnesium depletion. Serum magnesium concentration declined 60%, but tissue magnesium deficiency was not apparent. Hepatic parenchymal cells and microsomal membranes were isolated to evaluate in vitro metabolism of p-nitroanisole and conjugation of its metabolite, p-nitrophenol (pNP). O-Demethylation of p-nitroanisole was decreased slightly in both magnesium depletion hepatocytes and microsomal membranes. However, pNP glucuronide formation was specifically decreased 50% in the magnesium depletion cells at all p-nitroanisole concentrations. Similar results were found in the microsomal reaction system measuring pNP conjugation. Thus, early stages of magnesium depletion may result in a specific decrease in the pNP UDP-glucuronyl transferase activity.

Animals↗

Surface modification can affect the carcinogenicity of asbestos.

A sample of amosite asbestos was modified by effectively adding C8 and C18 hydrocarbon chains to the fibre surfaces. The altered fibres interacted less readily with cells in vitro and were less cytotoxic. In whole animals the number of mesotheliomas produced by the C8 material was the same as that with the parent material but the tumours occurred earlier. The C18 derivatized fibre was markedly less active in the production of tumours. This is the first report demonstrating that similar size fibres with differing surfaces have different pathogenic properties.

Animals↗

Seroprevalence and clinical manifestations of HIV-1 infection in Kananga, Zaire.

The objective of this study was to ascertain the seroprevalence and clinical manifestations of HIV-1 infection in Kananga, Zaire, in 1988. In the city of Kananga (population 300,000), eight out of 258 (3.1%) consecutive, asymptomatic, prenatal patients were seropositive. Of 452 consecutive blood donors at our institution, eight (1.8%) were seropositive. Sixty per cent of 299 consecutive, seropositive, clinically ill adults presented with chronic diarrhea, fever or weight loss (Centers for Disease Control group IVA). The male-to-female ratio of symptomatic, seropositive patients was 1:1.5. Women who indicated on a socioeconomic questionnaire that they engaged in 'commerce' (meaning possibly that they were petty traders, wholesale brokers, or prostitutes) were more often HIV-seropositive than women who did not engage in 'commerce' (P less than 0.001).

Adolescent↗

Interaction of amosite and surface-modified amosite with a V79-4 (Chinese hamster lung) cell line.

We have been examining a number of chemically modified mineral fibers, derived from amosite asbestos, by in vitro methods to clarify the role of the fiber surface in determining biological activity. The various fibers have identical size distributions but differ in their affinities for components of the cell membrane. They were treated with boiling toluene or chemically modified by treatment with alkyldimethylchlorosilanes (R = C8, C18) that react with free-surface hydroxyl groups to form the corresponding siloxanes. Fibers in MEM supplemented with 15% fetal calf serum were added to a suspension of V79-4 cells labeled with tritiated thymidine and the mixture was incubated. Aliquots of this mixture were spun down on a density gradient to determine the degree of cell-fiber interaction. At 37 degrees C native amosite (UICC standard) stuck to cells within 15 min of incubation, and the amount of sticking was maximum within 70 min. Decreasing the temperature decreased the amount of sticking, and at 20 degrees C no sticking was observable. The chemically modified amosite and the amosite treated with boiling toluene did not stick to the cells even after 70 min. Soaking the toluene-treated amosite with aqueous solutions at room temperature for 48 hr produced a material that had the same sticking properties as the original untreated fiber. These results indicate that the silanol content, and possibly the degree of hydration of the fiber surface, is important for a fiber to stick to a cell surface.

Animals↗

Factitious microcalcifications in breast biopsy material: laboratory-induced error by use of tattoo powder for specimen mammography.

A xeromammogram led to the surgical excision of a calcified breast lesion on a 66-year-old female. Before specimen mammography was performed, the excised tissue was oriented with tattoo pigment. The specimen mammogram then revealed multiple calcifications caused by unsuspected radio-opaque material in the tattoo pigment, and the original calcifications were obscured. This case demonstrates the hazards involved utilizing tattoo powders for orienting xeromammographically discovered specimens.

Aged↗

Hyperparathyroidism, hypertension and loop diuretic medication in renal transplant recipients.

The associations between serum parathyroid hormone (PTH), blood pressure and hypotensive medication were analysed in 282 renal transplant recipients. Among patients with a normal concentration of serum creatinine there was no correlation between serum PTH and blood pressure but in those receiving hypotensive medication serum PTH was appropriately twofold greater than in those not taking hypotensive medication. Analysis revealed that the dominant contribution to this association was a specific association with loop diuretic therapy. When all patients were stratified according to creatinine clearance, serum PTH was always greater in patients receiving loop diuretics but this difference was particularly striking in the patients with the poorest graft function. It is postulated that loop diuretics exacerbate the hyperparathyroidism which complicates renal disease.

Adult↗

Elevated serum intact parathyroid hormone levels in elderly patients with hip fracture.

It has been postulated that secondary hyperparathyroidism contributes to bone loss and the high incidence of hip fractures in the elderly population, but there are no data on serum intact parathyroid hormone concentrations in these patients. In this study, serum intact parathyroid hormone (PTH) levels have been measured in 39 elderly patients with hip fracture; in addition, serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 concentrations have been measured. Twenty patients (51.3%) had elevated serum intact PTH concentrations whilst five (12.8%) had abnormally low serum 25-hydroxyvitamin D3 levels and serum 1,25-dihydroxyvitamin D3 was reduced in only two. These results provide the first direct evidence for secondary hyperparathyroidism in elderly patients with hip fracture. Vitamin D deficiency is unlikely to be the sole cause of secondary hyperparathyroidism in these subjects and calcium deficiency by itself may also contribute.

Aged↗

Measurement of circulating parathyroid hormone.

The measurement of parathyroid hormone (PTH) is important in the investigation of disorders of mineral metabolism. Though the first immunoassay for PTH was described more than 25 years ago, it is only recently that methods have been developed which provide the required sensitivity and specificity to detect small changes in hormone secretion in normal subjects. These new methods take advantage of modern labelled antibody technology and have already been shown capable of yielding improvements in the diagnosis and monitoring of disorders which involve changes in PTH secretion. In addition, they are now providing fresh insight into the basic physiology of PTH secretion.

Humans↗