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Biomedical subjects

R A Goyer

Publications and source records attributed to R A Goyer.

At least 55 records · Page 3Linked to original sources
PubMed1977

Cadmium-induced enteropathy: comparative toxicity of cadmium chloride and cadmium-thionein.

In protecting the body against the noxious effects of dietary cadmium ions, cadmium is bound to metallothionein in the proximal intestine, and subsequently excreted into the lumen with desquamation of the epithelium. The purpose of this study was to determine the extent to which cadmium in the form of intestinal cadmium-thionein is absorbed from the intestinal lumen and to appraise the toxicity of cadmium-thionein on the intestinal mucosa. With open-ended duodenal perfusion, equivalent amounts of cadmium administered as CdCl2 or cadmium-thionein entered the mucosa, but significantly less cadmium from the perfusate of cadmium-thionein passed into the body. Exposure of the mucosa to CdCl2 for 1 hr led to minor abnormalities in the form of broadening of villi with pseudostratification of epithelium, and swelling of mitochondria, whereas cadmium-thionein produced extensive necrosis of absorptive cells. The results suggest that cadmium-thionein may play a paradoxical role, providing protection against the cadmium ion in the intracellular milieu, but promoting cadmium toxicity when it is present in sufficient amounts in the lumen of the intestine.

Animals↗
PubMed1976

Intracellular effects of chronic arsenic administration on renal proximal tubule cells.

Arsenic is one of the more common toxic elements in the environment. The kidney accumulates this element and plays a major role in its metabolism and excretion. Mitochondria have been found in vitro to be highly sensitive to the toxicity of this element. Combined oxygen electrode and electron microscopic studies were conducted on kidneys of rats exposed to arsenate in the drinking water at concentrations of 40, 85, or 125 ppm for 6 weeks to evaluate in vivo mitochondrial toxicity. Decreased state 3 respiration and respiratory control ratios were observed in kidneys of rats given the 85 and 125 ppm dose levels. Ultrastructural alterations, which consisted of swollen mitochondria and increased numbers of dense autophagic lysosome-like bodies, were confined to proximal tubule cells of these same animals. This study places renal arsenate mitochondrial toxicity into an in vivo context and points to the value of using complementary techniques for assessing the subacute or chronic toxicity of environmental agents.

Animals↗
PubMed1975

Bismuth localization within nuclear inclusions by x-ray microanalysis. Effects of accelerating voltage.

This report details the localization of bismuth by energy-dispersive x-ray microanalysis within characteristic nuclear inclusion bodies of renal tubular lining cells of rats following excessive exposure to this element. Peak to background ratios and analytical detection sensitivities for bismuth were found to vary for 04, 60 or 80 keV electron accelerating voltages. Optimum peak to background ratios were observed at 40 keV due to lower background generation, while greater detection sensitivities were recorded at 80 keV due to enhanced generation of bismuth characteristic x-rays.

Animals↗
PubMed1975

Lead-induced inclusion bodies: results of ethylenediaminetetraacetic acid treatment.

Earlier studies have shown that lead-induced nuclear inclusion bodies are composed of a lead-protein complex. Twenty-four hours after treatment of a lead-poisoned rat with a single dose of ethylenediaminetetraacetic acid (EDTA), urinary excretion of lead is maximally increased and the lead content of the kidneys is significantly decreased. Inclusion bodies in renal cell nuclei at this time are found in various stages of dissolution and migration out of the nucleus. The outer fibrillary margin becomes loosened, and slight disruption occurs at the periphery of the inclusion. Some inclusion bodies appear to be moving through the nuclear membrane. There is an invagination of both inner and outer nuclear membranes. Numerous cytoplasmic vacuoles occur which contain fibrillar material resembling portions of intact nuclear inclusions. Kidney nuclei of rats 24 hours after three daily injections of EDTA have no inclusion bodies. Whether the nuclear-cytoplasmic exchange occurs by dilation of a nuclear pore or by another mode of separation of nuclear membranes cannot be determined. This experiment demonstrates that nuclear inclusion bodies formed in lead poisoning are disrupted and removed from the nuclei by the administration of EDTA. This change corresponds with peak urinary excretion of lead. The sharp increase in urinary lead following EDTA therapy must reflect, at least in part, chelation and excretion of sequestered lead bound to nuclear protein.

Animals↗
PubMed1974

Lead-induced inclusion bodies: composition and probable role in lead metabolism.

Lead-induced inclusion bodies in renal tubular cells of rats have been studied in vitro after isolation by differential centrifugation. The inclusion bodies are insoluble in physiological media but may be dissolved in denaturants like 6M urea and sodium deoxycholate. They contain about 40-50 mug of lead/mg protein, but only about 10% of this is tightly bound. They also contain calcium, iron, zinc, copper, and cadmium. The protein is rich in glutamic and aspartic acids, glycine and cystine. When dissolved in 6M urea, the protein migrates as a single band on acrylamide gel electrophoresis and has a molecular weight of 27,500. It is suggested that the inclusion bodies function as an intracellular depot of nondiffusible lead. Further studies have been directed toward finding a free, unaggregated lead-containing protein fraction. Nuclear proteins from kidneys of lead-toxic rats were separated into NaCl-, Tris-, and NaOH-soluble fractions and an insoluble acidic fraction. A quantitatively small lead-containing protein was found in the 0.14M NaCl fraction. Amino acid composition, electrophoretic mobility, molecular weight, and ability to bind lead are similar to those of insoluble inclusion body protein. The possible role of this soluble lead-binding protein in the formation of nuclear inclusion bodies is at present time not certain. These studies do suggest, however, that protein-bound lead in renal tubular cells may be partitioned between insoluble and nondiffusible morphologically discrete inclusion bodies and a soluble, extractable fraction which is presumably diffusable.

Amino Acids↗