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The comparative toxicology of ethyl- and methylmercury.

Neurotoxicity and renotoxicity were compared in rats given by gastric gavage five daily doses of 8.0 mg Hg/kg methyl- or ethylmercuric chloride or 9.6 mg Hg/kg ethylmercuric chloride. Three or 10 days after the last treatment day rats treated with either 8.0 or 9.6 mg Hg/kg ethylmercury had higher total or organic mercury concentrations in blood and lower concentrations in kidneys and brain than methylmercury-treated rats. In each of these tissues the inorganic mercury concentration was higher after ethyl- than after methylmercury. Weight loss relative to the expected body weight and renal damage was higher in ethylmercury-treated rats than in rats given equimolar doses of methylmercury. These effects became more severe when the dose of ethylmercury was increased by 20%. Thus in renotoxicity the renal concentration of inorganic mercury seems to be more important than the concentration of organic or total mercury. In methylmercury-treated rats damage and inorganic mercury deposits were restricted to the P2 region of the proximal tubules, while in ethylmercury-treated rats the distribution of mercury and damage was more widespread. There was little difference in the neurotoxicities of methylmercury and ethylmercury when effects on the dorsal root ganglia or coordination disorders were compared. Based on both criteria, an equimolar dose of ethylmercury was less neurotoxic than methylmercury, but a 20% increase in the dose of ethylmercury was enough to raise the sum of coordination disorder scores slightly and ganglion damage significantly above those in methylmercury-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The comparative renotoxicology of phenylmercury and mercuric chloride.

The acute renotoxicity of HgCl2 and phenylmercuric acetate (PhHgAc) was compared at two intraperitoneal dose levels: 0.5 and 1.0 mg Hg/kg. There was no difference in the type of proximal tubular damage caused by the two mercurials, but 1.0 mg Hg/kg as PhHgAc produced approximately the same degree of damage as 0.5 mg Hg/kg as HgCl2. At the selected dose levels only HgCl2, but not PhHgAc increased the urinary excretion of alkaline phosphatase. At 12 and 24 h after PhHgAc the content of mercury was higher in blood and lower in the kidneys and urine than after the administration of equimolar doses of HgCl2. As the difference in the rectal mercury contents of HgCl2 and PhHgAc treated groups declined with time, difference in renotoxicity seems to relate only to renal mercury taken up within 24 h of administration. It is suggested that the slower renal extraction of mercury - as in regenerating kidneys (Tandon and Magos 1980) - was responsible for the lower degree of renotoxicity in phenylmercury treated rats.

Alkaline Phosphatase↗

Myosin composition and functional properties of smooth muscle from the uterus of pregnant and non-pregnant rats.

The myosin heavy chain stoichiometry and the force-velocity relation have been determined in the myometrium of the non-pregnant and pregnant rat. The relative proportions of the slower migrating heavy chain (MHC1) greatly exceeded that of the faster migrating heavy chain (MHC2) as shown by electrophoresis on SDS 4%-polyacrylamide gels. The ratios of MHC1/MHC2 were 2.2/1 in the non-pregnant rats, 2.6/1 in the pregnant rat, and contrasted with 0.8/1 in the rat portal vein. This stoichiometry was unchanged by extracting the myosin from the smooth muscle as native myosin in a salt extract, as dissociated myosin using sodium dodecyl sulphate (SDS) or by isolating the native myosin first by a non-dissociating (pyrophosphate) electrophoresis step and subsequently analysing the protein bands on the SDS 4%-polyacrylamide gel. Although the unequal proportions of the heavy chains suggested the possibility that the native myosin molecule may be arranged as homodimeric heavy chains, no evidence for or against the existence of native myosin isoforms could be obtained by electrophoresing native myosin extracts on pyrophosphate-polyacrylamide gels. The force-velocity relations of the intact electrically stimulated myometrium from the non-pregnant and pregnant rats gave isometric force of 45 and 135 mN/mm2 and Vmax of 0.71 and 0.52 lengths/s (37 degrees C) when measured at 95% of optimal length, whereas in chemically skinned uterine strips at 22 degrees C Vmax was 0.09 and 0.13 lengths/s, respectively. The length-force relationship was of similar shape in the non-gravid and gravid skinned tissues. The energetic tension cost (ATP-turnover/active stress) in skinned fibres was also similar. The mechanical and metabolic characteristics of the gravid and non-gravid uterus found in the present study do not suggest an obvious difference in the intrinsic properties of the myosin, although significant functional alterations in the tissue appear during pregnancy. This corresponds to the lack of a difference in the pattern of the heavy chains.

Adenosine Triphosphate↗

Cyclic-AMP mediated relaxation of chemically skinned fibers of smooth muscle.

Smooth muscle from guinea pig taenia coli was chemically skinned with Triton X-100 and stored in ATP-salt solution containing 50% glycerol at -20 degrees C. Fiber bundles were relaxed at Ca2+-concentrations below 10(-7) M, but contracted at 10(-6) M Ca2+. The isometric tension developed could be partly relaxed by the addition of c-AMP (in the presence of NaF), and it could also be inhibited following preincubation with the catalytic subunit of c-AMP dependent protein kinase. The inhibitory effect was much more pronounced at intermediate Ca2+-concentrations (e.g. 10(-6)) than at concentrations producing a maximum contraction, suggesting that Ca-sensitivity had been lowered. Sodium fluoride which was required to potentiate the c-AMP effects was found to have a slight relaxing effect per se. The c-AMP effect may be mediated through activation of cyclic AMP-dependent kinase, producing, phosphorylation of the myosin light chain kinase which, according to Adelstein et al. (1978), may result in a net dephosphorylation of the myosin light chains and a concomittant inhibition of the contractile response.

Adenosine Triphosphatases↗

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

Acadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1 +/- 45.3, 314.8 +/- 50.9, and 399.4 +/- 47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was -0.1 +/- 6.2%, 11.1 +/- 13.8%, 12.9 +/- 8.6%, and -3.2 +/- 6.8%, respectively (p = NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.

Aged↗

Primary structure of Beijing duck apolipoprotein A-1.

The primary structure of Beijing duck apolipoprotein A-1 was determined by sequencing peptide fragments derived from tryptic and endoproteinase Asp-N digestion of the protein, and alignment with homologous chicken apo A-1. All of the peptide fragments were isolated by high-pressure liquid chromatography (HPLC) with a Vydac C18 column using a trifluoroacetic acid (TFA) buffer system. The N-terminus of the protein was determined to be aspartic acid by directly sequencing 52 residues of the intact protein. The C-terminus was alanine. The protein contains 240 amino acid residues. By analysis of the whole protein and its tryptic peptides, a six amino acid (Arg-Tyr-Phe-Trp-Gln-His) prosegment was determined. No cross-reactivity between duck and human apo A-1 with a goat antiserum against human apo A-1 was found. Sequence analysis of apo A-1 of other species indicates that amino acid substitutions in rat are more extensive than in other mammals. Isoleucine residues in apo A-1 are inversely correlated to the homology of human to other species, except dog.

Amino Acid Sequence↗

Sex differences in pervasive developmental disorders.

Assessed differences in sex ratio, severity of associated mental retardation, and various metrics of severity of autism in autistic, PDD-NOS, and developmentally disordered (non-PDD) cases. Males with autism were more frequent than females, particular at higher IQ levels. The three clinical groups differed, in expected ways, in the various measures of severity of autism with the PDD-NOS cases being intermediate between the strictly diagnosed autistic group and the non-PDD developmental disordered group. Sex differences were primarily confined to IQ; sex differences in other metrics of severity of autism were not prominent. Implications for future research are discussed.

Adolescent↗

Structural homology between hard alpha-keratin and the intermediate filament proteins desmin and vimentin.

Although it has been assumed that the microfibrils in hard -keratin are members of the class of structures known as intermediate filaments (IF), no firm chemical evidence relating the low-sulfur proteins in hard -keratin to other IF proteins has yet been published. We now present primary sequence data for two components from wool keratin which show striking similarities with two IF proteins, desmin and vimentin. The sequences show marked homology, a heptad repeat and a 9.5-residue periodicity in the linear disposition of the acidic and the basic residues. These data thus provide the first evidence that the low-sulfur proteins in hard -keratin and the other IF proteins do indeed have both a similar structure and a common evolutionary origin.

Amino Acid Sequence↗

Comparison of X-ray and gamma-ray dose-response curves for pink somatic mutations in Tradescantia clone 02.

Microdosimetric data indicate that the mean specific energy, eta, produced by individual charged particles from X-rays and gamma rays is different for the two radiation qualities by nearly a factor of two. In order to test whether this influences the initial, linear component in the dose-effect relations, a comparison was made between dose-response curves for pink somatic mutations in Tradescantia clone 02 stamen hairs following X and gamma irradiations. Absorbed doses ranged from 2.66 to 300 rad.The results are in agreement with predictions made on the basis of microdosimetric data. At low doses gamma rays are substantially less effective than X-rays. The RBE of gamma rays vs. X-rays at low doses was approximately 0.6, a value lower than those usually reported in other experimental systems.

Cesium Radioisotopes↗

Transient appearance of a fast myosin heavy chain epitope in slow-type muscle fibres during stretch hypertrophy of the anterior latissimus dorsi muscle in the adult chicken.

Myosin expression during hypertrophy of the chicken anterior latissimus dorsi (ALD) muscle was investigated by immunocytochemical procedures using monoclonal antibodies to the fast and slow isoforms of the myosin heavy chain (myosin HC). Antifast antibody 1F9 bound to the adult fast HC of pectoralis muscle and cross-reacted with the HC found in early developing muscle. Antislow antibody 3D1 bound exclusively to the HC of slow myosin 2 (SM2). Stretch hypertrophy of the ALD was produced by attaching a weight to the wing; there was no evidence for a change in fibre number in the muscle. Between 4 and 6 days of stretch there appeared a dramatic increase in the number of fibres staining with the antifast antibody which reached a peak between 12 and 19 days. By this time between 28 and 52% of the fibres in the stretched ALD stained to varying degrees with the antifast antibody compared with much less than 1% in the unstretched control ALD. Most antifast-stained fibres in the stretched muscle also stained with the antislow antibody; the contralateral control muscle showed mostly antislow staining except for the very small number of strongly antifast-stained fibres. By 50 days in some birds and by 80 days in all birds antifast staining had returned to normal. Analysis of the isomyosin composition of the ALD by native gel electrophoresis did not reveal a significant increase in fast myosin content of the hypertrophied muscle even though immunocytochemical staining may have suggested otherwise.

Animals↗