Histophotometric characteristics of structural-metabolic heterogeneity of hepatocytes in acute hemorrhage and pulmonary artery thromboembolism]

Basing on the data obtained at early autopsies, we compared the structure and metabolism of liver acini in acute blood loss and pulmonary artery thromboembolism. Morpho- and pathogenetic impairment of hepatocytes of various acinic zones was correlated and studied histo-enzymatically.     

Characteristics of the interaction between 2-alkylmalonates and the substrate-binding site of the dicarboxylate carrier of rat liver mitochondria

The effect of thirteen synthetic 2-n-alkyl derivatives of malonic acid on the rate of the mitochondrial succinate oxidase reaction controlled by the dicarboxylate carrier, was studied. These compounds were shown to act as competitive inhibitors of succinate transport and could interact with the carrier according to the 1:1 stoichiometry. The affinity of the inhibitor for the carrier increased in parallel with the increase in the alkyl residue length. This dependence was impaired only in the case of pentyl-, hexyl- and heptylmalonates having close values of inhibition constants. The data obtained suggest that the polar site and two hydrophobic regions are located in the vicinity of the carrier active site. The possible organization of the carrier substrate-binding site is discussed.     

Protein factors that bind to the murine 2',5'-oligoadenylate synthetase ME-12 gene 5' upstream regulatory region

The murine 2',5'-oligoadenylate synthetase ME-12 gene regulatory region AB forms six complexes with protein factors in murine BALB/c 3T3 cells as demonstrated by the mobility shift electrophoresis assay under the reaction conditions used. The complexes, designated C1-C6 in order of their decreasing electrophoretic mobility, showed three distinctive specificities with regulatory region AB, element A, and element B as probes or competing DNA: 1) C1 is region AB-specific (this complex did not form with either element A or B used alone or as a mixture); 2) C5 formed both with element A and element B; 3) C2, C3, C4, and C6 formed with element B, but not A. The protein factors that give rise to these complexes show differential DNA binding activities in various buffer solutions at different pH values. The C4-forming protein factor is the interferon (IFN)-alpha/beta-stimulated response factor (ISRF) which shows element B specificity. It preexists in the cytoplasm. ISRF appears to be complexed to an inhibitor (ISRFI) in the cytoplasm and to dissociate from the inhibitor and to translocate into the nucleus upon treatment of cells with IFN-alpha/beta. We propose that IFN-alpha/beta treatment of BALB/c 3T3 can trigger at least two events: 1) loosening of a tight inhibitor-ISRF complex with the release of free ISRF; this may be mediated via phosphorylation of ISRF or ISRFI; 2) translocation of ISRF into the nucleus and binding to the enhancer element B, which results in the activation of 2',5'-oligoadenylate synthetase gene expression.     

The quantitative analysis of lipopolysaccharide antigen in the blood serum of patients with salmonellosis by using complement-bound liposome lysis]

Titration of group B Salmonella O-antigen in the blood sera of patients and donors was carried out by means of the complement-dependent lysis of liposomes sensitized with S. typhimurium LPS. Good correlation (r = 0.95) of the levels of S. typhimurium somatic O-antigen in the patients' sera determined by liposomal immunoassay and aggregate hemagglutination test was established. The concentration of the antigens in the tested samples was within 0.5-50 micrograms/ml. Statistical analysis of the results obtained by liposomal immunoassay techniques demonstrated differences in the distribution functions for the blood sera of patients with different diseases and of donors.     

Hepatotrophic growth factor in blood of mice treated with carbon tetrachloride

The presence of a human hepatocyte growth factor (hHGF)-like DNA-synthesis promoter in platelet-poor serum of mice with liver injury was examined. Activity of the serum for stimulating DNA synthesis in cultured rat hepatocytes was low in untreated or vehicle-treated mice, but markedly increased 24 h after carbon tetrachloride administration and then dropped to normal levels prior to the peak of liver DNA synthesis. The effect of the serum was additive with the maximal effects of mouse and human epidermal growth factors, but not with that of hHGF. The growth-stimulating factor in the mouse serum, like hHGF, had affinity for heparin and was heat-labile. These results indicate that the level of a serum hHGF-like hepatocyte growth factor increased in mice treated with carbon tetrachloride prior to liver regeneration.     

Reactive oxygen species facilitate the in vitro and in vivo lipopolysaccharide-induced release of tumor necrosis factor

Secretion of TNF from mouse peritoneal macrophages exposed to LPS in vitro was enhanced in the presence of H2O2 or sodium periodate. Neither of these agents induced release of TNF in the absence of LPS. Both iron chelators and free radical scavengers inhibited this enhanced secretion of TNF, implying the involvement of free radicals via a Fenton-type reaction. Oxidant stress, in the form of alloxan or divicine, also enhanced serum levels of TNF in mice made sensitive to LPS by low-level infection with malaria, and then given i.v. LPS. Pretreatment with the iron chelator, desferal, or the free radical scavenger, BHA, inhibited TNF release in these animals. Less TNF was also detected in mice given desferal before LPS in the absence of exogenous radical generator. These results could have implications for understanding the details of the MLR, the adherence of neutrophils to the walls of pulmonary vessels in free radical-induced lung pathology, and the side effects of bleomycin.