Showing papers by "Ronald Klein published in 1973"

Serum Uric Acid: Its Relationship to Coronary Heart Disease Risk Factors and Cardiovascular Disease, Evans County, Georgia

Abstract: Analysis of serum uric acid (SUA) data obtained during the second examination of 2,530 persons in Evans County, Georgia, revealed a mean SUA level of 5.7 and 5.6 mg/100 ml for white and black males, respectively, and 4.8 and 4.9 mg/100 ml for white and black females, respectively. The SUA level and ponderal index were negatively correlated in all four race-sex groups. The prevalence of hypertension was greater in hyperuricemics as compared to normouricemics in all race-sex groups. Increased prevalence of coronary heart disease in hyperuricemics was secondary to increased body size. We review hypotheses concerning the relationships between SUA and coronary risk factors, hypertension, and coronary heart disease.

THE UPTAKE OF METHYL MERCURY (203Hg) IN DIFFERENT TISSUES RELATED TO ITS NEUROTOXIC EFFECTS

Abstract: Rats were treated by subcutaneous injection of methyl mercury hydroxide containing the radioactive isotope 203Hg. The Hg concentration of organ samples was determined by radioassay at the end of one to four weeks of treatment. Of parts of the nervous system, spinal dorsal root ganglia contained the highest concentration of Hg, followed closely by the cerebral cortex and the cerebellum, then the subcontical part of the forebrain. Spinal cord, spinal roots and peripheral nerves contained significantly less Hg than the sensory ganglia. There was no difference in the Hg content of dorsal and ventral roots. Hg levels of non-neural tissues are also presented. The amount of blood remaining in organ samples was estimated, and a correction was applied to allow for the Hg contained in the residual blood. On autoradiograms made of tissues of animals treated with Me-203Hg, there were more reduced grains of silver over gray matter than over white matter and more in neurons than in glia, satellite or Schwann cells. The results are consistent with the idea derived from other investigations that spinal ganglia are the primary targets of poisoning by MeHg+, and that sensory axons degenerate because their parent cell bodies are damaged. Differences in the amount of poison accumulated by cells appear to play a part in determining the selectivity of its effect, but cannot be the only cause of variations of sensitivity of tissues.

Electrophysiology of methyl mercury poisoning

Abstract: Rats were treated by s.c. injections of methyl mercury hydroxide (MeHg+) for three to four weeks until they developed ataxia and abnormal reflexes of the hindlegs. In these animals the compound action potential evoked in dorsal roots by stimulation of the sciatic nerve showed retardation of the conduction velocity, elevation of the (extracellular) threshold and, most conspicuously, a reduction of amplitude and "area." The compound action potential of ventral roots was only minimally affected. Upon intracellular stimulation of individual spinal ganglion cells, there was evidence neither of elevation of the rheobase, nor of a change of resting membrane potential or of membrane resistance. The intracellularly recorded spike potential of many poisoned sensory ganglion cells was strikingly prolonged, and these abnormal spikes showed a "plateau" or "shoulder" indicating retarded repolarization. There was evidence of minor weakening of skeletal muscle when stimulated through its motor nerve, which could have been caused by the loss of a small number of motor units, and consequent scattered focal denervation atrophy. It is concluded from these observations, and from other publications, that MeHg+ poisoning affects sensory ganglion cell bodies first, with secondary degeneration of sensory axons. Neurons with axons of large caliber appeared to be lost in larger numbers than smaller ones. Clinical electroneurography may be a valuable tool for following the course of poisoning by alkyl mercurials after diagnosis is firmly establisimed, but not for early detection of suspected cases.

Effects of methylmercury on microsomal mixed-function oxidase components of rodents.

Abstract: Preliminary treatment of rats with methylmercury hydroxide (10 mg/kg/day for 2 days) decreased hepatic cytochrome P-450 content by 52%, type I substrate (piperonyl butoxide) binding spectra by 40%, and type II substrate (aniline and metyrapone) binding spectra by 59% and 66%, respectively Decreased cytochrome P-450 levels were apparently caused by increased degradation of the fast-phase component of the biphasic CO-binding pigment degradation curve When chlordane, which decreases the degradation rate of the fast-phase component, was administered in conjunction with methylmercury hydroxide, the net effect was a degradation rate similar to controls A control experiment was devised to demonstrate that the biphasic degradation curves were not influenced by heme exchange during preparation of subcellular particles from control, chlordane-treated, or methylmercurytreated rats Rats exhibited the greatest methylmercury-induced decrease in cytochrome P-450 content, followed by mice and guinea pigs Male rat liver P-450 was decreased more than that from female rats Methylmercury was converted in substantial quantities to inorganic mercury in rats, mice, and guinea pigs Microsomal mercury levels were highest in guinea pigs, followed by mice and rats ACKNOWLEDGMENTS Mercury analytical services were provided under contract by Dr Paul Mushak, Department of Pathology, University of North Carolina, Chapel Hill Thanks are extended to Miss Pat Singletary for excellent technical assistance

Methyl mercury ototoxicity: a model for the surface preparation technique.

Abstract: A critical review of recent articles in which the surface preparation technique was employed is presented. Many of the reports were deficient in terms of five important criteria which would insure reproducibility of experiments, comparability of results from different investigators, and detection of a low level of cellular pathology. These criteria are: inclusion of concurrent controls; use of adequate number of control and treated animals to insure the detection of meaningful treatment-control differences; adequate examination of controls; quantitative expression of cellular pathology, and the use of statistical analyses to test for significant differences. When these criteria were employed, methyl mercury was identified as a unique ototoxic agent. It caused a low level of outer hair cell pathology in all four turns of the guinea pig cochlea. Statistically significant damage occurred in the outer row of outer hair cells at 2½ turns from the cochlear base (P <.01) and in the inner row at 3½ turns (P <.05). When damage for all rows at each turn was considered, methyl mercury produced significant damage (P <.05) at 2½ turns from the cochlear base.