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.     

Recommendations from the Consensus Conference on Hypertension in the Elderly.

Since 1978 there have been dramatic advances in the understanding of the pathophysiologic features of unstable angina pectoris and in the availability of new therapies of proven efficacy. Coronary artery spasm has been shown to be an important mechanism of acute myocardial ischemia in patients with unstable angina, and coronary thrombosis has been established as an early event in the development of acute myocardial infarction and, possibly, sudden death. Intravenous nitrates and oral calcium antagonists have been made available and are now widely used. Acetylsalicylic acid has been shown to be of benefit. Improved techniques of myocardial preservation and the introduction of percutaneous transluminal coronary angioplasty have modified the surgical management of coronary artery disease.     

On the O2 flash yields of two cyanophytes

We explored O₂ flash yield in two cyanophytes, Anacystis nidulans and Agmenellum quadruplicatum. On a rate-measuring electrode, a single flash gave a contour of O₂ evolution with a peak at about 10 ms which was maximum (100) for 680 nm background light. On 625 nm illumination the peak was smaller (62) but was followed by an increased tail of O₂ attributed to enhancement of the background. After a period of darkness, repetitive flashes (5 Hz) gave a highly damped initial oscillation in individual flash yields which finally reached steady state at 94% of the yield for 680 nm illumination. When O₂ of repetitive flashes was measured as an integrated flash yield the results was distinctive and similar to that for a continuous light 1 (680 nm). An apparent inhibition of respiration which persisted into the following dark period was taken as evidence for the Kok effect. With a concentration-measuring electrode, integrated flash yield vs. flash rate showed the same nonlinear behavior as O₂ rate vs. intensity of light 1. We draw three conclusions about the two cyanophytes. (a) The plastoquinone pool is substantially reduced in darkness. (b) Because of a high ratio of reaction centers, reaction center 1 / reaction center 2, for the two photoreactions, saturating flashes behave as light 1. (c) Because repetitive flashes are light 1, they also give a Kok effect which must be guarded against in measurements designed to count reaction centers.     

Synthesis of a shortened pro-alpha 2(I) chain and decreased synthesis of pro-alpha 2(I) chains in a proband with osteogenesis imperfecta

Synthesis of type I procollagen was examined in skin fibroblasts from a proband with a lethal variant of osteogenesis imperfecta. The fibroblasts synthesized shortened pro-alpha 2(I) chains and these shortened chains accounted for all the pro-alpha 2(I) chains synthesized by the cells. In addition, there was a decrease in the relative rate of synthesis of pro-alpha 2(I) chains. Fragmentation of the shortened pro-alpha 2(I) chains with vertebrate collagenase and cyanogen bromide demonstrated that the shortening was in alpha 2(I)-CB3,5A, a fragment from about the middle of the chain containing amino acid residues 361 to 775. Based on the relative mobility in electrophoretic gels, the shortening was about 20 amino acid residues. The decreased synthesis of pro-alpha 2(I) chains was demonstrated by an increase in the ratio for the rates of synthesis of pro-alpha 1(I):pro-alpha 2(I) chains. It was associated with an increase in the ratio of mRNAs for pro-alpha 1(I):pro-alpha 2(I) in the cells. Fibroblasts from the father also demonstrated a decreased synthesis of pro-alpha 2(I) chains as reflected by an increase in the ratio of newly synthesized pro-alpha 1(I):pro-alpha 2(I) chains. No shortened pro-alpha 2(I) chains were seen in fibroblasts from either the father or the mother. The observations suggested that the proband inherited a nonfunctioning pro-alpha 2(I) gene from her father and that the gene for the shortened pro-alpha 2(I) chain probably arose from a sporadic mutation.