A massive binary black-hole system in OJ 287 and a test of general relativity.

Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space-time curvature effects are first-order deviations from Newton's theory. Binary pulsars provide a means of probing the strong gravitational field around a neutron star, but strong-field effects may be best tested in systems containing black holes. Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi-periodic optical outbursts at 12-year intervals, with two outburst peaks per interval. The latest outburst occurred in September 2007, within a day of the time predicted by the binary black-hole model and general relativity. The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement (within 10 per cent) with the emission of gravitational waves from the system. In the absence of gravitational wave emission the outburst would have happened 20 days later.

Comparison of the action of transforming growth factor-beta 1 and interleukin-1 beta on matrix metabolism in the culture of porcine endothelial cells.

The purpose of the experiment was to evaluate the metabolism of the connective tissue (collagen and proteoglycans) in the endothelial cell culture (enzymatically isolated from porcine aortas). The endothelial cells were activated by 1-10 ng/ml TGF-beta 1 and 250 pg/ml IL-1 beta together and separately. Intensity of proteoglycan synthesis has been evaluated by using radioactive [35S]-sodium sulfate whereas the intensity of collagen was evaluated by incorporation of [3H]-proline. The following conclusions have been drawn as the result of the experiment: 1) TGF-beta 1 stimulates the synthesis of proteoglycans and collagen in endothelial cell culture, whereas IL-1 beta has the opposite action; and 2) TGF-beta 1 reduces IL-1 beta action which hampers the synthesis of proteoglycans and collagen, provided that the culture's preincubation with TGF-beta 1 precedes the incubation with IL-1 beta.

Evaluation of elastin metabolism in children from families with high risk of atherosclerosis.

Markers of elastin metabolism were estimated in sera of children from families with a high risk of atherosclerosis (ATH). There was no statistically significant difference in the serum elastase-like activity between the groups studied. The concentration of elastin-derived peptides was statistically significantly elevated in the ATH group. Anti-elastin antibodies were found to be present in 73% of ATH children, while they circulated in 5% of control subjects only. Antibodies observed in the youngest ATH children were of the IgM type, suggesting the initial stage of the autoimmunization to elastin. The data obtained in this study may indicate an enhanced metabolism of elastin in ATH children.

Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits.

Methionine is converted by the transmethylation/transsulfuration pathway to homocysteine which may exert atherogenic effects by several mechanisms, including lipid peroxidation. Therefore, the excessive dietary methionine may induce the development of atherosclerosis. To test this hypothesis, plasma and aortic thiobarbituric acid reactive substances (TBARS), as well as activities of aortic and erythrocyte superoxide dismutase (SOD), catalase and selenium-dependent glutathione peroxidase (GPX) were measured in rabbits fed a diet enriched with 0.3% methionine for 6 or 9 months. Histological examinations of aortas also were performed. Feeding rabbits a methionine-enriched diet for 6 or 9 months resulted in significant increases in plasma and aortic TBARS levels and aortic antioxidant enzyme activities. However, a decrease in plasma antioxidant activity (AOA) was observed. In erythrocytes, SOD activity increased, catalase remained normal and GPX decreased in the treated animals. Histological examination of aortas showed typical atherosclerotic changes, such as intimal thickening, deposition of cholesterol, and calcification in methionine-fed rabbits. These results confirm that high-methionine diet may induce atherosclerosis in rabbits and indicate disturbances in lipid peroxidation and antioxidant processes as possible mechanisms of its atherogenic influence.

Anti-elastin antibodies in patients with lung cancer.

The aim of this study was to investigate anti-elastin antibodies of the IgG and IgM types in sera of patients suffering from lung cancer, using the DOT immunobinding assay. We studied 96 pathological and 40 control sera. Anti-elastin antibodies were found to be present in 45% of patients with small cell lung cancer, 19% of subjects with adenocarcinoma and not-identified lung tumor and 15% of patients with squamous cell lung cancer. They circulated in 5% of control persons only. The highest values of their titers were observed in the advanced stages of disease. In 55% of anti-elastin antibody positive small cell lung cancer patients, antibodies were of the IgM type, suggesting the initial step of the autoimmunization to elastin.

Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure.

Plasma lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD) and catalase, and serum antioxidant activity (AOA) in uremic patients were examined before and after hemodialysis. An increased level of lipid peroxidation, a decreased serum AOA level, and elevated SOD and normal catalase activity before hemodialysis were observed in uremic patients compared with controls. Hemodialysis was found to produce increased lipid peroxidation, a simultaneous decrease of SOD activity, and lack of any changes in serum AOA and erythrocyte catalase. It is suggested that intensification of lipid peroxidation during hemodialysis could account for accelerated progress of atherosclerosis in patients with renal insufficiency.

Composition of proteoglycans from rabbit aorta in the experimentally induced atherosclerosis.

Proteoglycans (PG) from normal and atherosclerotic rabbits aortas were extracted with 4 M guanidine hydrochloride and digested with collagenase in the presence of protease inhibitors. The contents of uronic acid and hexosamine from PG fractions purified by isopycnic CsCl gradient ultracentrifugation under associative and dissociative conditions were significantly higher in the atherosclerotic aortas (up to 40%) than in the control tissue. The uronic acid/protein ratio increased from 0.7 to 1.3 in the monomers PG fraction of atherosclerotic aortas. Chromatographic separation and electrophoretic analysis of PG monomers indicated the presence of three different subfractions PGI, PGII and PGIII in both groups of animals. The uronic acid/protein ratio in PGI from experimental aorta was increased whereas this ratio in PGIII was decreased compared to contrast tissue. The observed increase of sugar component in the core proteins suggests their over glycosylation.

Concentration of some proteinase inhibitors: alpha 1-antitrypsin and alpha 2-macroglobulin in rabbit blood serum in two models of experimental atherosclerosis.

In rabbits with experimental atherosclerosis induced by a cholesterol-rich diet, alpha 1-antitrypsin concentration was decreased as compared with control, by 34%, whereas alpha 2-macroglobulin concentration was increased by 86%. In animals fed a methionine-rich diet changes in concentration of both inhibitors involved in elastase metabolism were but slight, if any.

The effect of cytostatic drugs on collagen metabolism in guinea pigs.

Azathiprine (0.25 mg/100 g body wt.) and cyclophosphamide (0.2 mg/100 g body wt.) were administered to guinea pigs, orally every day during 4 weeks. Azathioprine caused a decrease in total collagen content in skin, liver and bone and decreased hydroxyproline and hydroxylysine concentration in blood serum, and urinary excretion of collagen catabolites. No effect of cyclophosphamide on total collagen in skin and liver was observed. An increase in collagen content in bone in cyclophosphamide-treated guinea pigs was found. A decrease of hydroxyproline and hydroxylysine in blood serum and urine was observed after cyclophosphamide treatment. The results support the view that cytostatic drugs inhibit collagen metabolism, and azathioprine significantly affects collagen biosynthesis, and cyclophosphamide influences inhibition of catabolic processes of collagen.

Studies on collagenolytic cathepsin activity in rats with experimental collagen-like syndrome.

Collagenolytic cathepsin activity was determined in the heart muscle, liver, kidney spleen, skin samples and leukocytes of normal and hydrazinophthalazine treated rats Isolated collagen susceptibility to the crude liver enzyme action was estimated as well The products of enzymatic degradation were analyzed by polyacrylamide gel electrophoresis. An increase of enzyme activity in all studied organs and leukocytes was observed. It has also been found that the crude liver enzyme is able to degrade the polymeric collagen gamma-chains.

Morphological changes observed after stimulation or inhibition of adrenic system in rats chronically treated with hydrazinophtalazines.

Morphological studies of the heart muscle were carried out in healthy rats as well as treated with hydralazine or binazine after administration of adrenaline, noradrenaline, isoprenaline, regitine or propranolol. Hydrazinophtalazines (25 mg/kg body wt, daily) were given during 7 months. After discontinuation of this treatment the drugs were administered during 15 days. Evident changes (e.g. inflammatory infiltrations, focal necrosis and fibrosis) were found after administration of noradrenaline, adrenaline or isoprenaline. No differences were found in the reactivity to catecholamines in healthy and hydrazinophtalazine-treated rats.

Histopathological changes in experimental drug-induced collagen disease-like syndrome.

Prolonged administration of 1-hydrazinophthalazine (hydralazine) to guinea pigs stimulated the development of collagen disease-like syndrome. Inflammatory changes were found in the heart, kidneys and skin.

Effect of thyroid hormones on activity of nonspecific phosphohydrolases in blood serum, tissues and liver mitochondrial fraction of white rat.

Activity of alkaline and acid phosphatase was determined by the method of Bodansky in blood serum, homogenates of liver, kidney, lung, brain, liver mitochondrial fraction of normal, methylthiouracil-induced hypothyroid, and Thyroideum-induced hyperthyroid rats. The following results were obtained: an increase in both enzymes in all studied materials in hyperthyroidism, and a decrease in most of the studied materials in hypothyroidism.

Effect of irradiation on glycosaminoglycans content in rat tissue.

Glycosaminoglycan (GAGs) fractions were determined in tissues (skin, liver, lungs, aortic wall) and blood serum of rats irradiated with a single dose of 500 R. An increase of total GAGs as well as changes in the fractions were found in the tissues and urine of exposed rats.

Increased lipid peroxidation and antioxidant activity in methionine-induced hepatitis in rabbits.

The liver is especially susceptible to the toxic effects of methionine due to its role in sulfur amino acid metabolism. Therefore, the excessive amounts of this amino acid may induce liver damage. To test the mechanisms of methionine-related hepatotoxicity, liver thiobarbituric acid reactive substances (TBARS), and activities of superoxide dismutase, catalase and selenium-dependent glutathione peroxidase were measured in rabbits fed a methionine-enriched diet for 6 or 9 mo. Morphological studies of livers were also made. Feeding rabbits the methionine-enriched diet for 9 mo resulted in a significant increase in liver TBARS levels and antioxidant enzyme activities. Moreover, an inflammatory infiltration of portal triads in the treated rabbits were observed. These results indicate that methionine may induce hepatitis by increasing free radical processes.

Lipid peroxidation in the nuclear fraction of rat lungs induced by hydralazine.

Hydralazine (1-hydrazinophthalazine) was administered in drinking water as a 0.0312% solution to randomly bred female Wistar rats during 3 weeks. The average daily intake of this compound was 6.74 mg for a rat. The treatment resulted in lipid peroxidation in the nuclear fraction of the lungs. This lipid peroxidation was detected spectrophotometrically by the appearance of a peak at 233-235 nm in the spectrum of chloroform-methanol extract. The close proximity of DNA may make it a possible target for attack by free radicals.

Collagenolytic activity in leukocytes isolated from patients with leukemias and Hodgkin's disease.

Collagenolytic activity in leukocytes and plasma concentration of hydroxyproline were estimated in 80 patients with leukemias and Hodgkin's disease and in 20 healthy individuals. An increase of both studied parameters was found in chronic myelocytic leukemia and Hodgkin's disease, and a decrease was shown in acute myelocytic leukemia and acute lymphatic leukemia. The results obtained imply that metabolic changes occur in leukemia leukocytes, and indicate the presence of disturbances in the metabolism of connective tissue in the studied disorders.

Enhancement of neutral metalloproteinase in the dermis after one topical application of tumor-promoting phorbol ester.

The effect of a tumor-promoting skin mitogen, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of matrix degradation in the dermis of mouse skin has been examined. Dermis specimens were analyzed for proteoglycan content and neutral proteoglycan degrading activity. Total neutral metalloproteinase activity (latent plus active forms), determined by direct tissue assay, was significantly elevated in TPA-treated dermis than in control dermis. The active form of neutral metalloproteinase was significantly higher in TPA-treated dermis than in control dermis. Serine protease activity on proteoglycans was much lower than that of metalloproteinase. The increase in the total and active neutral metalloproteinase supports the hypothesis that these enzymes are involved in matrix degradation which is related to tumor promotion.

Copper and zinc concentrations, and superoxide dismutase activities in malignant and nonmalignant tissues of female reproductive organs.

The copper and zinc concentrations in 44 malignant and 48 nonmalignant women tissue samples of reproductive organs in women were measured. In malignant samples, the mean copper concentrations were 110%, 76%, and 38% higher for cervix, endometrium and ovary than the nonmalignant ones. The zinc concentrations in the analysed malignant tissues were lower than that in the corresponding nonmalignant tissues. The results of superoxide dismutase activities determinations demonstrate a considerable lowering of the enzymatic capacities to remove free oxygen radical in malignant tissues. A hypothesis for possible mechanism involving elevated copper concentrations, and decreased zinc concentrations, which may be responsible for malignant processes, are presented.

Plasma selenium concentration in patients with stomach and colon cancer in the Upper Silesia.

Plasma selenium concentration was assessed in 44 patients with cancer of the gastrointestinal tract (19 subjects with stomach cancer and 25 with colon cancer) and 25 age-matched healthy control subjects. Selenium concentration was determined by the fluorometric method. The observed plasma selenium concentrations in gastrointestinal cancer patients (37.0 +/- 11.05 ng Se/ml or 38.4 +/- 12.6 ng Se/ml in stomach or colon cancer patients, respectively) were significantly lower as compared to the healthy age-matched control group (51.4 +/- 14.4 ng Se/ml). The diagnosed low selenium status may be considered as a high risk for cancer development.