Maternal factors in onset of Huntington disease.

Analyses of father-offspring and mother-offspring similarity in onset age suggest that nuclear genes account for a significant portion of the modification of onset age in Huntington disease. The effects of non-nuclear modifiers are supported by the finding that the offspring of affected women have significantly older mean ages of onset than offspring of affected men irrespective of the onset age in the parent. The absence of increased father-daughter similarity indicates that modification is not X-linked. The absence of reproductive advantage for late-onset individuals and the absence of a multigenerational maternal-lineage effect suggest that the modifying effect of the sex of the affected parent occurs in a single parental generation. Offspring of affected women with onset between ages 35 and 49 had a significantly older mean onset age than their mothers. This suggests that a protective effect may be conferred upon the offspring of affected women.     

Ammonium uptake in Rhodopseudomonas capsulata

Investigations of the uptake of ammonium (NH ₄ ⁺ ) by Rhodopseudomonas capsulata B100 supported the presence of an NH ₄ ⁺ transport system. Experimentally NH ₄ ⁺ was determined by electrode or indophenol assay and saturation kinetics were observed with two apparent K _m's of 1.7 M and 11.1 M (pH 6.8, 30°) and a V _max at saturation of 50–60 nmol/min·mg protein. The optimum pH and temperature were 7.0 and 33° C, respectively. The Q₁₀ quotient was calculated to be 1.9 at 100 M NH ₄ ⁺ , indicating enzymatic involvement. In contrast to the wild type, B100, excretion of NH ₄ ⁺ , not uptake, was observed in a glutamine auxotroph, R. capsulata G29, which is derepressed for nitrogenase and lacks glutamine synthetase activity. G29R1, a revertant of G29, also took up NH ₄ ⁺ at the same rate as wild type and had fully restored glutamine synthetase activity. Partially restored derivatives, G29R5 and G29R6, grew more slowly than wild type on NH ₄ ⁺ as the nitrogen source, remained derepressed for nitrogenase in the presence of NH ₄ ⁺ , and displayed rates of NH ₄ ⁺ uptake in proportion to their glutamine synthetase activity. Ammonium uptake and glutamine synthetase activity were also restored in R. capsulata G29 exconjugants which had received the plasmid pPS25, containing the R. capsulata glutamine synthetase structural gene. These data suggest that NH ₄ ⁺ transport is tightly coupled to assimilation.Abbreviations used CHES cyclohexylaminoethanesulfonic acid - GS glutamine synthetase - SDS sodium dodecylsulfate     

Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups.

Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.     

The appearance of phospholipase activity in the human macrophage-like cell line U937 during dimethyl sulfoxide induced differentiation

The human histiocyte cell line, U937, with monocyte characteristics, can be induced to differentiate into macrophage-like cells when exposed to growth medium containing 1.5% DMSO. Following three days of exposure, DMSO-treated but not control U937 cells can be stimulated to release endogenous arachidonic acid from their phospholipids. Maximum release of the unsaturated fatty acid occurs with 10 microM calcium ionophore in the presence but not in the absence of exogenously added calcium ion. In addition, DMSO-treated but not control U937 cells exhibit phospholipase activity when exposed to human IgG and then anti-human immunoglobulin. These data suggest that with respect to arachidonic acid metabolism U937 cells differentiate into functional macrophage-like cells when exposed to DMSO.     

Oxidative destruction of DNA by the adriamycin-iron complex

The 2:1 adriamycin-Fe(III) complex is able to bind to DNA and to catalyze its oxidative destruction. The binding of the drug-metal complex to DNA is indicated by characteristic spectral changes which are different from those seen with adriamycin intercalation and by the propensity of the drug-metal complex to precipitate DNA. Furthermore, intercalated adriamycin appears not to be available for iron binding. The resulting ternary complex is quite stable: it is not disrupted by incubation in the presence of EDTA and can be isolated by using Sephadex G-50 column chromatography. Disruption of the ternary complex requires vigorous conditions (extraction with phenol at 60 degrees C). The adriamycin-iron complex in free solution has the capacity to catalyze the reduction of oxygen by thiols. The DNA-bound drug-metal complex preserves this capacity over a wide range of complex/DNA ratios. As a consequence of this thiol-dependent oxygen reduction, DNA is cleaved. This thiol-dependent DNA cleavage has been shown to require hydrogen peroxide as an intermediate product. These results have led us to propose that the thiol-dependent DNA cleavage reaction has two stages involving (1) reduction of oxygen leading to hydrogen peroxide and then (2) peroxide-dependent DNA cleavage. An unusual property of this reaction is that the cleavage is not random but gives rise to a defined 2300 base pair fragment.     

Selenocysteine lyase activity in a cysteine-requiring mutant ofEscherichia coli K-12

Selenocysteine lyase activity was detected in crude extracts from a cysteine-requiring mutant ofEscherichia coli K-12. The level of activity was the same whether cells had been grown aerobically or anaerobically, with or without selenocysteine. Selenocysteine lyase catalyzes the conversion of selenocysteine to alanine and elemental Se, a reaction that is followed by a nonenzymatic reduction of the Se to hydrogen selenide. Both of these end products were identified in this study. With cysteine as the substrate, alanine and H₂S were formed, but only at levels 50% less than the products formed from selenocysteine. Selenocysteine lyase has been identified in a number of mammals and bacteria; its presence in a cysK mutant ofE. coli K-12 suggests a common route whereby hydrogen selenide, derived from selenocysteine, can then be assimilated into selenoproteins.