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Several genes were found closely associated with major histocompatibility class I and class II beta-chain genes in chicken genomic DNA clusters by hybridizing tissue-specific cDNA probes to cosmid clones. A cDNA probe for one of these genes, probe C12.3 isolated from a chicken liver cDNA library, was used to clone the homologous sequence H12.3 from a human B-lymphoblastoid cell line cDNA library. C12.3 and H12.3 encode exactly the same 317-residue-long protein. The sequence of 12.3 shows significant homology with the two known guanine nucleotide-binding protein beta subunits (GP beta 1 and GP beta 2) and other proteins that all share the same segmented structure with seven internal homologous repeats about 45 residues in length. Unlike the chicken gene, the human H12.3 gene and its mouse counterpart are not located on the same chromosome as the major histocompatibility complex. A possible involvement of the C12.3 gene product in major histocompatibility complex-linked control of lymphocyte proliferation in chickens is discussed.

Components of the coagulation and fibrinolytic systems were determined in patients undergoing open heart surgery with cardiopulmonary bypass. The variables studied included prothrombin, antithrombin-III, spontaneous plasmin activity, plasminogen and functional antiplasmin activity. The variables were measured using chromogenic peptide substrate assays. A marked, transitory, increase in spontaneous plasmin activity prior to cardiopulmonary bypass, but after heparin injection was found. A decrease in antiplasmin activity during bypass was observed, while actual plasminogen level, when correcting for hemodilution, was unchanged. Both prothrombin and antithrombin-III paralleled the decrease in hemoglobin concentration during bypass. These findings suggest that the injection of heparin induced a transient activation of the fibrinolytic system, whereas no detectable consumption of the measured coagulation variables was observed.

Two nifA-like genes, designated anfA and vnfA, have been identified in Azotobacter vinelandii. The anfA gene is located upstream from the nitrogenase-3 structural gene cluster (anfHDGK) and is preceded by a sequence that is potentially part of a ntrA-dependent promoter. The product of anfA appears to be required for expression of nitrogenase-3, since cells of the anfA deletion strain CA66 were unable to synthesize this nitrogenase when derepressed in N-free, Mo- and V-deficient medium. The vnfA gene was identified after determination of the nucleotide sequence of DNA flanking the Tn5 insertion in mutant strain CA46. Two open reading frames (ORF1 and ORF2) were found located upstream from the vnfA gene, and a nifE-like ORF, preceded by a possible ntrA-dependent promoter, was found downstream from this gene. It is not known whether vnfA is expressed only under N2-fixing conditions. However, potential ntrA-dependent promoters were found immediately upstream from vnfA (within the 3' end of ORF2) and immediately downstream from ORF1. The region spanning ORF1 and ORF2 contained an A + T-rich sequence that was also found immediately upstream from the potential ntrA-dependent promoter of anfA. The product of vnfA appears to be required for the synthesis of nitrogenase-2, since cells of strain CA46 synthesized only nitrogenase-1 and -3 but not nitrogenase-2 when grown in the presence of vanadium. The product of nifA, which is required for synthesis of nitrogenase-1, is not required for synthesis of either nitrogenase-2 or nitrogenase-3. However, growth data indicate that nifA is required for a factor (or factors) necessary for maximal diazotrophic growth under Mo- and V-deficient conditions.

Short-term pure cultures and long-term cocultures of adult rat hepatocytes with rat liver epithelial cells, presumably derived from primitive biliary cells, were used to define in vitro models of iron overloaded hepatocytes in order to understand the molecular mechanism responsible for liver damage occurring in patients with hemochromatosis. In vitro iron overload was obtained by daily addition of ferric nitrilotriacetate to the culture medium. A concentration of 20 microM ferric salt induced hepatocyte iron overload with minimal cytotoxicity as evaluated by cell viability, morphological changes of treated cells and cytosolic enzyme leakage into the culture medium. The effects of iron overload on protein biosynthesis and secretion were studied in both short-term pure cultures and long-term cocultures of hepatocytes. The amounts of intracellular and newly synthesized proteins were never modified by the iron treatment. Furthermore, neither the relative amounts of transferrin and albumin mRNAs nor their translational products were altered by iron overload. Moreover, no change in the transferrin isomeric forms were observed in treated cells. In contrast, a prolonged exposure of cocultured hepatocytes to 20 microM ferric salt led to a significant decrease in the amount of proteins secreted in the medium. This decrease included the two major secreted proteins, namely albumin and transferrin, and probably all other secreted proteins. These results demonstrate that iron loading alters neither the total nor the liver specific protein synthesis activity of cultured hepatocytes. They suggest that chronic overload may impede the protein secretion process.

Disseminated intravascular coagulation (DIC) most often manifests itself through hemorrhagic episodes following thrombotic consumption of platelets and coagulation factors in the microvasculature. Rarely patients suffer major arterial thrombosis in the setting of disseminated intravascular coagulation. We treated such a patient, whose thrombotic diathesis was refractory to traditional heparin and fresh frozen plasma therapy, with infusion of anti-thrombin III concentrate. The response was a prompt improvement in both clinical and laboratory parameters followed by recurrent thrombosis when concentrate therapy was discontinued. This is the first reported case where DIC complicated by major arterial thrombosis was treated with antithrombin III concentrate. Our findings demonstrate that antithrombin III concentrates are useful in treating patients with DIC complicated by major arterial thrombosis.

A convenient route of synthesis of amphibian bombesin and bombesin-like peptide alytesin was found. These tetradecapeptides were obtained by assembling the 1-5 and 6-14 fragments by means of DCC-HONB or mixed anhydrides methods. Structure of the tetradecapeptides was confirmed by high resolution NMR spectroscopy data. The bombesin and alytesin synthesized potently decrease body temperature and stimulate pancreatic juice secretion.