The use of sodium resonium in pseudohypoaldosteronism.
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Humans↗
Biomedical subjects
M Kershaw
Publications and source records attributed to M Kershaw.
Consumer audit. Eye opener.
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Attitude to Health↗
Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats.
Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced. Microscopic lesions included degeneration of the seminiferous tubular cells, pyknosis or absence of germ cells, and hypospermia in the epididymis. Rats of the 600 ppm group had a slight decrease in thymic weight and a transient decrease in body weight. Results of the acute, 2-wk, and 13-wk inhalation studies indicate DMES concentrations of 1000 ppm and higher produce narcosis that rapidly disappears following exposure. Repeated exposure of rats to DMES at either 3000 ppm for 2 wk or 2000 ppm for 13 wk caused testicular atrophy and hypospermia in male rats. Female rats exposed to 2000 ppm for 13 wk had delayed estrous cycles. Toxicological effects in rats of the 600 ppm group were minimal and equivocal. The 160 ppm concentration was a no-observable-effect level (NOEL) for 13 wk of exposure to DMES.
Administration, Inhalation↗
Increased hypothalamic content of preproneuropeptide-Y messenger ribonucleic acid in streptozotocin-diabetic rats.
Neuropeptide-Y (NPY) is a 36-amino acid C-terminally amidated peptide found within the hypothalamus that can potently stimulate carbohydrate feeding. Moreover, the hypothalamic content of NPY can be modulated by peripheral hetabolic status. To further evaluate the regulation of NPY synthesis in states of altered metabolic homeostasis, we measured the hypothalamic content of prepro-NPY mRNA in streptozocin (STZ)-diabetic, STZ-diabetic insulin-replaced, and control rats by both nuclease protection and in situ hybridization analyses. Adult male Sprague-Dawley rats received a single injection of STZ (100 mg/kg, ip) or citric acid (control). Beginning 72 h later one group of STZ-treated animals received daily injections of insulin (4 U Ultralente/day). All animals were killed 17-19 days after STZ or control treatment. STZ-treated animals were hyperglycernic and showed growth failure compared to control rats. Glycemic control was restored by insulin replacement, as was partial growth. Nuclease protection analysis revealed an approximately 3- to 4-fold increase in prepro-NPY mRNA levels in the samples from STZ-treated rats vs. control. This increase was returned to control values by insulin replacement. In situ hybridization analysis revealed the STZ-induced increase in hypothalamic prepro-NPY mRNA was detectable in the arcuate nucleus at levels that were in agreement with the nuclease protection results, but that NPY expression in other brain regions appeared to be either unaffected or decreased after STZ treatment. These data suggest that hypothalamic NPY expression is modulated by peripheral metabolic status and provide further explanation for the hyperphagia accompanying STZ-induced diabetes.
Animals↗
Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation.
Neuropeptide Y (NPY) is a potent orexigenic agent capable of producing hyperphagia and obesity. NPY-containing neurons project from the hypothalmic arcuate nucleus to the paraventricular nucleus, an area known to be sensitive to the orexigenic effects of NPY. In this study we investigated the possibility that preproNPY messenger RNA (mRNA) content may be altered in obese Zucker rats compared to that of their lean littermates. Total RNA was isolated from hypothalamic dissections from male and female, obese and lean Zucker rats. RNA was also isolated from dissections of: olfactory bulb, entorhinal cortex, hippocampus, and striatum of female obese and lean rats. PreproNPY mRNA content was determined by solution hybridization-RNase protection analysis. The results revealed a 2- to 3-fold increase in preproNPY mRNA levels in the hypothalamus of obese animals compared to lean. The increase was observed in both sexes and was specific to the hypothalamus. In situ hybridization localized this increase to the arcuate nucleus. An additional RNase protection study was pursued to investigate the effects of 72 h food deprivation on hypothalamic preproNPY mRNA levels in lean and obese animals. Lean animals displayed an approximate 2-fold increase in preproNPY mRNA content, whereas obese animals showed no significant increase after food deprivation. These data are consistent with the hypothesis that NPY projections within the hypothalamus are involved in regulating feeding behavior and weight gain, and that disturbed regulation of hypothalamic NPY expression may play a role in the etiology of obesity in the genetically obese Zucker rat.
Animals↗
Reactivity of monoclonal antibody P1 with glomerular basement membrane in thin-membrane nephropathy.
A monoclonal antibody, P1, possessing antiglomerular basement membrane specificity similar to that of naturally-occurring Goodpasture antibody, was used to study renal biopsy material from patients with thin-membrane nephropathy. Immunofluorescence and immunoperoxidase techniques were employed to detect tissue localisation after sections had been incubated with P1. Staining of glomerular and tubular basement membranes in the 14 patients with thin-membrane nephropathy was similar to that in 10 subjects with various other renal diseases, whereas three patients with Alport's syndrome all gave diminished or absent staining, as has been reported previously. These observations confirm that Goodpasture antigen is present in the basement membranes in thin-membrane nephropathy and that it reacts normally with P1 antibody. They also add to the evidence that the lesions of thin-membrane nephropathy and Alport's syndrome are fundamentally different. The staining method may be used as a differential diagnostic test.
Adult↗
Use of a monoclonal antibody in differential diagnosis of children with haematuria and hereditary nephritis.
In a retrospective, double-blind study, paraffin-embedded renal biopsy sections from 44 children with haematuria were examined to see whether a mouse monoclonal antibody (MCA-P1) against glomerular basement membrane (GBM) could identify a subgroup of patients with hereditary glomerulonephritis (Alport's syndrome) in whom the Goodpasture antigen was abnormal. There was strong linear binding of MCA-P1 to GBM in all of 29 patients with no evidence of hereditary nephritis and in 2 patients in whom the diagnosis of hereditary nephritis was thought possible but not definite on available clinicopathological evidence. In contrast, 12 of 13 patients with strong evidence of hereditary nephritis showed no binding (9) or greatly reduced binding (3). These findings suggest that a major subgroup of patients with hereditary glomerulonephritis have biochemical abnormalities of the GBM involving Goodpasture antigen and that MCA-P1 is useful in the differential diagnosis of children with haematuria.
Adolescent↗
A 2,4-dichlorophenyl diazonium-based method for total bilirubin without interference from indican in uremic sera.
Comparison of total bilirubin quantification by a 2,4-dichlorophenyl diazonium method (2,4-DCPD) with a Jendrassik-Grof type of method showed excellent correlation for randomly selected sera. However, sera from uremic patients on chronic hemodialysis showed a marked positive bias for the 2,4-DCPD result as compared with the Jendrassik-Grof result. The mean difference was 5.3 mg/L, and resulted in about 20% of the hemodialysis patients having bilirubin values greater than 13 mg/L, the upper limit of our reference range. Indican in uremic sera reportedly reacts with certain diazo reagents, so we investigated indican's reactivity in the above methods. In vitro addition of indican caused no interference in the Jendrassik-Grof method, but produced a significant positive interference in the 2,4-DCPD method, 1 mmol of indican per liter appearing as about 36 mg of total bilirubin per liter. Long reaction times with the 2,4-DCPD reagent accentuate the problem. By shortening the reaction time with the 2,4-DCPD reagent to 1.7 min, we find that the indican interference can be eliminated, without affecting quantification of total bilirubin in either normal or uremic sera.
Bilirubin↗
Urinary urea: are currently available methods adequate for revival of an almost abandoned test?
Measurement of urinary urea excretion has been suggested as a means of estimating nitrogen balance in hospitalized patients who are malnourished. Because proficiency-testing surveys show gross variations in mean urea as determined by various automated methods and extremely poor precision occasionally, we compared urinary urea measurements and ammonia interference in three widely used methods. The coupled urease/glutamate dehydrogenase method (used in the DuPont aca) showed positive interference from ammonia, as expected; with the diacetylmonoxime (Technicon (12/60) and the urease conductivity (Beckman ASTRA) methods we saw no such interference. Generally, interference by ammonia is less than 10%, but (rarely) it may exceed 25%. However, if urine specimens are properly diluted and potential sources of interference recognized, all three methods appear capable of providing clinically useful data.
Ammonia↗
Acute interstitial nephritis complicating Legionnaires' Disease.
An acute interstitial nephritis was found in a patient with sudden renal failure and lung infection caused by Legionella pneumophilia. Our patient regained and maintained normal renal function after a short period of dialysis support. The diagnosis should be considered in any patient with a chest infection complicated by acute renal failure especially if confusion is disproportionate to the degree of uremia.
Acute Disease↗
Amyloid P-component is a constituent of normal human glomerular basement membrane.
Glomerular and other vascular basement membranes were found to contain an antigen that was immunochemically indistinguishable from serum amyloid P-component. There was no immunological cross-reactivity between antisera to serum amyloid P-component and to collagen types I, III, IV, or V. The amyloid P-component antigen was confined to the endothelial aspect, the lamina rara interna, of glomerular basement membrane. It could not be eluted by high-ionic-strength saline, EDTA, dithiothreitol, or either polar or nonpolar detergents, but was released into solution when isolated glomerular basement membrane was digested by highly purified bacterial collagenase. Most of these P-component molecules and their constituent polypeptide chains were of higher molecular weight and lower isoelectric point than serum amyloid P-component. These findings indicate that, as well as being a normal plasma protein and a universal constituent of amyloid deposits, P-component is also a normal matrix glycoprotein of basement membrane in which it is covalently linked to collagen and/or other matrix proteins. This may be relevant both to the pathogenesis of amyloidosis and to other aspects of physiology and pathology of basement membranes.
Amyloid↗
Renal isotransplantation without immunosuppression.
Four renal isografts have been performed and all have had satisfactory function for 7 1/2 to 17 2/3 years without prophylactic or therapeutic immunosuppression. Three of these patients originally had glomerulonephritis, and in one there was histologic evidence of recurrent disease, 7 1/2 years after transplantation, without proteinura and without change in renal function. Although this experience is small, it suggests that prophylactic immunosuppression is not appropriate for recipients of renal isografts.
Diseases in Twins↗
Mixed connective tissue disease with associated glomerulonephritis and hypocomplementaemia.
Mixed connective tissue disease is an increasingly recognized entity in which renal disease is thought to be unusual and associated hypocomplementaemia even more uncommon. A patient is described who had both these features and who also illustrates many of the characteristic features of this syndrome. The response to steroids of the systemic sclerosis component is well shown and an additional feature of interest is the family history of other connective tissue diseases.
Adult↗
Increased circulating creatine kinase isoenzyme BB in a patient with metastatic prostatic carcinoma gave spuriously high isoenzyme MB values with the Harleco UltraZyme kit.
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Aged↗
Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH maintenance of cellular viability during pubertal spermatogenesis.
The potential for follicle-stimulating hormone (FSH) to promote germ-cell survival and the cellular sites of FSH action were studied using a gonadally maturing (pubertal), hypophysectomized (Hx) rat model in which residual testosterone (T) activity was blocked by injections of an androgen-receptor antagonist, flutamide. Recombinant human FSH was given to androgen-deprived and androgen-blocked male rats at 27 days of age to determine maintenance of individual germ-cell types at 35 days of age. Follicle-stimulating hormone significantly increased testis weights and tubular diameters as compared with Hx and Hx-flutamide controls, although testis weights in FSH-treated animals were significantly lower than in pituitary-intact animals. Morphometric assays to determine ratios of germ cells to Sertoli cells and to determine the number of germ cells present per hour of development showed that the population of type A spermatogonia in the early stages of the cycle was not responsive to FSH. Follicle-stimulating hormone had a marked ability to maintain cell viability in the rapid, successive divisions that begin in the latter part of the cycle and that continue through the next cycle (i.e., from type A1 to A4 and from intermediate spermatogonia to type B spermatogonia to preleptotene spermatocytes to leptotene/zygotene spermatocytes to young pachytene spermatocytes). The data also suggest T responsiveness of these cell types since the Hx-FSH-flutamide group showed lower cell viability at the aforementioned steps when compared with the Hx-FSH group. Too few cell types were present at subsequent phases of spermatogenesis to allow a sensitive determination of FSH activity in the maintenance of cell viability. The data show the potential of FSH in the absence or relative absence of T activity to maintain cell viability. These data support the concept of overlapping and synergistic (or additive) effects of T and FSH in the immature rat and identify the cellular sites of FSH action.
Androgen Antagonists↗