Biomedical subjects

D J Gash

Publications and source records attributed to D J Gash.

4 recordsLinked to original sources

PubMed1986

Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells.

We have isolated the bovine and human genes for Müllerian inhibiting substance (MIS), a testicular glycoprotein that causes regression of the Müllerian duct during development of the male embryo. The mRNA sequence of bovine MIS, determined from an analysis of cDNA and genomic clones, codes for a protein of 575 amino acids containing a 24 amino acid leader peptide. The human gene has five exons that code for a protein of 560 amino acids. A comparison of the bovine and human MIS proteins reveals a highly conserved C-terminal domain that shows marked homology with human transforming growth factor-beta and the beta chain of porcine inhibin. Animal cells transfected with the human gene secrete biologically active MIS, which causes regression of the rat Müllerian duct in vitro.

Amino Acid Sequence↗

PubMed1983

Complement biosynthesis by human bronchoalveolar macrophages.

Complement production by bronchoalveolar macrophages recovered from 8 normal volunteers and 15 patients with a variety of lung diseases was measured functionally and immunochemically. While macrophages from all eight normals demonstrated the capacity to secrete hemolytically active C2 and factor B within 48 hr of culture at consistent rates, bronchoalveolar macrophages from patients secreted C2 and factor B in widely differing amounts, and in some cases, not at all. No functional, secreted C3 was detected from normal macrophage monolayers, although apparently native C3 protein was synthesized and secreted. In contrast, functional C3 was produced by macrophage monolayers from 3 of 15 patients. These findings suggest that complement production by the normal human bronchoalveolar macrophage differs from its progenitor cell, the blood monocyte, and that complement production by bronchoalveolar macrophages may be altered in different pulmonary diseases.

Adult↗

PubMed1982

Complement proteins C2, C4 and factor B. Effect of glycosylation on their secretion and catabolism.

Tunicamycin, an inhibitor of N-acetylglucosaminylpyrophosphopolyisoprenol-dependent glycosylation, was used to study the effect of glycosylation on the synthesis, post-translational modification, secretion and function of the complement proteins that are associated with the major histocompatibility complex in humans, mice and guinea pigs. Tunicamycin blocked glycosylation of pro-C4, C2 and factor B and inhibited secretion of the corresponding native complement proteins synthesized by guinea-pig peritoneal macrophages in tissue culture. In addition, underglycosylated pro-C4 was more rapidly catabolized intracellularly than the corresponding fully glycosylated pro-complement protein. C4 protein secreted by cells incubated with tunicamycin had approximately the same specific biological activity as the protein obtained from control culture media, suggesting that carbohydrate is not required for its activity in immune haemolysis. Direct studies of carbohydrate incorporation and the tunicamycin effect suggested an unequal distribution of sugar among the C4 subunits, with maximal incorporation of carbohydrate into alpha-, and less into the beta-chain of the native protein.

Animals↗

PubMed1980

Control of complement synthesis and secretion in bronchoalveolar and peritoneal macrophages.

The effect of inflammation on C (C2 and C4) biosynthesis by bronchoalveolar and peritoneal cells was studied with methods that detect changes in synthesis rates and qualitative changes in cell populations. Adherent bronchoalveolar macrophages produced less C2 and C4 than adherent peritoneal macrophages. However, the subset of cells capable of producing C was more than 20-fold greater in the peritoneal cell population than in the population of bronchoalveolar cells. The rate of synthesis per C producing bronchoalveolar macrophage was 5 to 10 times the rate by C producing peritoneal macrophages. In contrast, the effect of an inflammatory stimulus on C production was the result of a change in rate of synthesis per cell, not a change in the proportion of C producing cells. This stimulatory effect was exerted locally, not on a cell population harvested from a distant site. At least two mechanisms for local control of C levels in tissues have been identified--that is, a change in synthesis rate and a qualitative change in macrophage cell population. The capacity to alter C levels at a site of inflammation may be important for C dependent functions in host defenses.

Animals↗