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PubMed1986

Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.

The monokine, cachectin/tumor necrosis factor (TNF) differs from interleukin 1 (IL-1) in primary structure and in recognition by a distinct cellular receptor. It does, however, encode effector functions that are similar to those of IL-1 and characteristic of the host response to inflammation or tissue injury. Accordingly, we examined the possibility that recombinant-generated human TNF regulates hepatic acute-phase gene expression. In picomolar concentrations, TNF mediated reversible, dose- and time-dependent increases in biosynthesis of complement proteins factor B and C3, alpha 1 antichymotrypsin, and decreases in biosynthesis of albumin and transferrin in human hepatoma cell lines (Hep G2, Hep 3B). Biosynthesis of complement proteins C2 and C4, and alpha 1 proteinase inhibitor were not affected by TNF. TNF also increased factor B gene expression, but had no effect on C2 gene expression, in murine fibroblasts transfected with cosmid DNA bearing the human C2 and factor B genes. The effect of TNF on acute-phase protein expression (C3, factor B, albumin) was pre-translational as shown by changes in specific messenger RNA content.

Acute-Phase Proteins↗
PubMed1979

HLA and disease.

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Adrenal Hyperplasia, Congenital↗
PubMed1986

Contrasting evolutionary histories among tightly linked HLA loci.

Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom association of alleles-make the system of particular interest from the perspective of population genetics. Information on the dynamic evolutionary forces that have acted on a locus can be inferred from the number and distribution of alleles that it carries. Ten loci from the HLA region of the human MHC, each sampled from several different populations, have been examined for departures from the expected value of homozygosity under the condition of selective neutrality. The homozygosities of five class I and II loci that code for membrane glycoproteins, HLA-A, -B, -C, -DR, and -DQ, and of glyoxylase I (GLO) were significantly less than the neutrality expectations. This suggests the presence of some form of balancing selection. In spite of being closely linked, in fact, located between the class I and class II histocompatibility loci, the homozygosities of the four class III or complement loci C2, Bf, C4A, and C4B, which are detected by electrophoresis, were indistinguishable from, or exceeded, that expected under neutrality. Although this conforms to the suggestion that, in general, electrophoretic variants are neutral, because of the tight linkage to loci demonstrating a history of selection, it is possible that the mechanism for generating variation in the class III loci may be different from that of the class I and class II loci.

Alleles↗
PubMed1977

Opsonic requirements for staphylococcal phagocytosis. Heterogeneity among strains.

Efficient phagocytosis of staphylococci by human neutrophilis is dependent on bacterial opsonization by serum factors. These factors include specific antibodies as well as components of the classical and alternative complement systems. In this study the opsonic requirements of three strains of S. aureus and three strains of S. epidermidis were investigated by incubating [3H]thymidine-labelled bacteria in sera with different opsonic activities and measuring rates of phagocytosis by human neutrophils. Opsonization of S. aureus Cowan I and 502 A depended primarily on activation of the classical complement pathway. Effective opsonization occurred in the absence of immunoglobulin but not in the absence of complement. A protein A deficient mutant of S. aureus Cowan I was poorly opsonized in the absence of IgG, however. S. aureus Wood 46 and two strains of S. epidermidis were opsonized primarily through the alternative complement pathway and depended on the presence of serum IgG. A third S. epidermidis strain was efficiently opsonized in heat-inactivated serum without complement activity. Thus, a heterogeneity of opsonic requirements was found among staphylococcal strains. It is proposed that cell wall protein A may be an important determinant of this heterogeneity.

Complement C2↗
PubMedDate not supplied

Temporal arteritis in polymyalgia rheumatica: immune complex deposits and the role of the leukocyte elastase in the pathogenesis.

Immunohistochemical studies were performed on the temporal artery of 34 patients with clinically established polymyalgia rheumatica (PR) or temporal arteritis, 6 patients with vasculitis, and 25 patients with various diseases. The combined immunofluorescence and peroxidase-anti-Peroxidase Methode zeigte Immunoglobulin- und C3-Ablagerunin histologically affected and to some degree also in unaffected arteries of patients with PR and in all patients with temporal arteritis. The deposits were found both inter- and intracellularly, and contained IgA and to a lesser extend IgG, IgM, and C3. Linear deposits of leukocyte elastase were found along the fragmented internal lamina, and decaying polymorphonuclear (PMN) leukocytes surrounded by elastase-containing inclusions were found in the neighborhood of zones rich in elastic material. These findings suggest that immune complex deposition is a prominent feature of temporal arteritis and that the PMN elastase is probably involved in the destruction of elastic fibers. The combined immunohistochemical investigation appears to increase the diagnostic value of temporal artery biopsy.

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