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Biomedical subjects

K Rubin

Publications and source records attributed to K Rubin.

At least 91 records · Page 5Linked to original sources
PubMed1986

Homologous type II collagen induces chronic and progressive arthritis in mice.

Native mouse type II collagen was used for immunization of DBA/1 mice. Arthritis developed exclusively in male animals and was characterized by a variable and delayed onset, a slow and progressive development, and frequent exacerbations of disease in several joints including those that were previously affected. Titers of anti-type II collagen autoantibodies were found not to correlate well with arthritis development. It appears that experimental arthritis induced with homologous type II collagen resembles rheumatoid arthritis in humans, both in certain clinical features and in the lack of correspondence between anti-type II collagen autoantibody titers and disease symptoms.

Animals↗
PubMed1986

Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies.

Twenty monoclonal antibodies reactive with type II collagen were characterized as to their determinant specificity and their reactivity with cartilage-derived components. The monoclonal antibodies reacted with 7 different epitopes on the native type II collagen triple helical structure. Antibodies defining 3 of these epitopes occurred more frequently in sera from arthritic mice than in sera from nonarthritic mice. In vivo injection of some selected autoreactive antibodies caused synovitis, but in no case did it give rise to full-blown arthritis.

Animals↗
PubMed1986

Reactivity of monoclonal anti-type II collagen antibodies with cartilage and synovial tissue in rheumatoid arthritis and osteoarthritis.

Monoclonal antibodies to 3 different epitopes on native type II collagen were used for immunohistochemical analysis of antigenic determinants that are exposed in the cartilage and synovial tissue obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Two of the monoclonal antibodies reacted with cartilage from both OA and RA joints, but not with that from normal joints. The third monoclonal did not stain any of the cartilage sections. The 2 positive antibodies also reacted with cartilage fragments in the synovial tissue of both RA and OA joints, and in RA pannus tissue, the antibodies showed intracellular staining in many class II transplantation antigen-expressing synovial cells lying close to the damaged cartilage.

Animals↗
PubMed1986

Hepatocyte adhesion to collagen. Isolation of membrane glycoproteins involved in adhesion to collagen.

Adhesion of hepatocytes to collagenous substrates and their spreading have been shown to involve a specific recognition event, possibly mediated by membrane proteins with affinity for collagen. In the present communication, we describe the isolation of membrane components that are involved in the adhesion of rat hepatocytes to collagen. These components could be solubilized from liver microsomal membranes by treatment with detergents or papain--but not by treatment with EDTA, urea or high salt. The purification of detergent-solubilized components was monitored by an assay determining the ability of membrane components to neutralize antibody-mediated inhibition of hepatocyte adhesion to collagen. By affinity chromatography on lentil lectin-Sepharose it was found that the neutralizing activity resided within the glycoprotein fraction. These glycoproteins were purified further by affinity-chromatography on collagen type I linked to Sepharose. Antibodies raised against the glycoproteins with affinity for immobilized collagen, effectively inhibited hepatocyte adhesion to collagen. The bulk of the neutralizing activity migrated with an apparent molecular weight of 120 000-140 000 in preparative SDS-PAGE.

Animals↗
PubMed1986

Suppressors of SNF2 mutations restore invertase derepression and cause temperature-sensitive lethality in yeast.

Mutations in the SNF2 gene of Saccharomyces cerevisiae prevent derepression of the SUC2 (invertase) gene, and other glucose-repressible genes, in response to glucose deprivation. We have isolated 25 partial phenotypic revertants of a snf2 mutant that are able to derepress secreted invertase. These revertants all carried suppressor mutations at a single locus, designated SSN20 (suppressor of snf2). Alleles with dominant, partially dominant and recessive suppressor phenotypes were recovered, but all were only partial suppressors of snf2, reversing the defect in invertase synthesis but not other defects. All alleles also caused recessive, temperature-sensitive lethality and a recessive defect in galactose utilization, regardless of the SNF2 genotype. No significant effect on SUC2 expression was detected in a wild-type (SNF2) genetic background. The ssn20 mutations also suppressed the defects in invertase derepression caused by snf5 and snf6 mutations, and selection for invertase-producing revertants of snf5 mutants yielded only additional ssn20 alleles. These findings suggest that the roles of the SNF2, SNF5 and SNF6 genes in regulation of SUC2 are functionally related and that SSN20 plays a role in expression of a variety of yeast genes.

Enzyme Repression↗
PubMed1986

Generation of monoclonal rheumatoid factors after immunization with collagen II-anti-collagen II immune complexes. An anti-idiotypic antibody to anti-collagen II is also a rheumatoid factor.

Two monoclonal IgG rheumatoid factors were obtained after hybridization of spleen cells from DBA/1 mice immunized with immune complexes containing native collagen type II and a monoclonal anti-collagen II antibody. One of these rheumatoid factors reacted not only with purified murine Fc fragments, but also with Fab fragments of the anti-collagen II antibody used for immunization, whereas no reactivity was seen with Fab fragments from normal mouse IgG. The findings demonstrate the ability of immune complexes encompassing native collagen type II to induce production of IgG rheumatoid factors, and suggest that an idiotypic relationship may exist between certain rheumatoid factors and anti-collagen II antibodies.

Animals↗
PubMed1986

Binding of collagen type II to rheumatoid synovial cells.

Binding of biotin-labelled native and denatured collagen type II and of aggregated IgG to frozen sections of synovial tissue from patients with rheumatoid arthritis (RA) or juvenile chronic arthritis (JCA) was investigated with the help of an avidin-biotin-peroxidase (ABC) technique. A large number of lymphocyte-like and plasma cell-like cells within the investigated biopsies aggregated IgG, and can be assumed to produce rheumatoid factors. In five out of six cases a smaller number of lymphocyte-like and plasma cell-like cells bound native collagen type II. Denatured collagen type II bound mainly to cells within the synovial lining and to endothelial cells within the inflamed synovial tissues. Binding of denatured but not of native collagen II was abolished by preincubation with rabbit antibodies towards human fibronectin. It is suggested that the method described here, using biotinylated antigens, may be of value for the study of local antibody production via investigations on frozen tissue sections, and that local antibody production against native collagen type II occurs within the inflamed synovial tissues at least in some cases of rheumatoid arthritis and juvenile chronic arthritis.

Animals↗
PubMed1986

Specific attachment of Staphylococcus aureus to immobilized fibronectin.

Staphylococcus aureus cells have been shown to possess surface-associated proteins with affinity for soluble fibronectin. We have investigated the ability of these surface proteins to mediate attachment to immobilized fibronectin and collagen. Attachment was quantified by determination of bacterial ATP in a bioluminescence assay. The ability to attach to fibronectin- or collagen-coated plastic surfaces was investigated for four S. aureus strains: Cowan 1, Newman, SA113(83A), and Wood 46. Cells from the different strains varied in their attachment properties, but all cells except those of strain Wood 46 attached readily to substrates coated with fibronectin. Only cells from strain Cowan 1 attached reproducibly to collagen-coated substrates in the absence of fibronectin. The attachment of cells from strain SA113(83A) to fibronectin-coated surfaces was shown to be dependent on time, fibronectin concentration, and bacterial growth phase. Soluble fibronectin or NH2-terminal fibronectin fragment (Mr, 29,000) disturbed the attachment to surfaces coated with fibronectin bound to denatured collagen type I. The attachment process to such substrates was also effectively inhibited by preincubating the substrate with fibronectin-binding proteins isolated from S. aureus Newman and SA113 (83A) and purified with affinity chromatography.

Amino Acid Sequence↗
PubMed1986

Patterns of autoreactivity to collagen type II in autoimmune MRL/l mice.

The kinetics and mechanisms for secretion of antibodies against native and denatured collagen type II have been studied in spontaneously arthritic MRL/l mice. Circulating antibodies were quantified by an ELISA assay and frequencies of specific antibody secreting spleen cells by an ELISPOT assay. The degree of humoral immunity to collagen type II increased at late stages of the disease (6 months of age) whereas severe synovitis was seen earlier (5 months of age). Both the appearance of anti-collagen II producing cells and development of synovitis was preceded by and not correlated with a general state of polyclonal B cell activation. In MRL/l mice, collagen II specific antibodies appeared spontaneously and titres were largely unaffected by collagen II immunization. The levels of circulating anti-collagen II antibodies in MRL/l mice were lower, and the antibodies displayed lower avidities and different specificities as compared with the antibodies generated in collagen II high responder DBA/l mice after immunization with collagen II. It is suggested that the antibody response in MRL/l mice against collagen type II does not need MHC-restricted T cell help and that induction of antibody production to collagen II in MRL/l mice is triggered by joint cartilage destruction and subsequent collagen II release.

Aging↗
PubMed1985

Different populations of rheumatoid adherent cells mediate activation versus suppression of T lymphocyte proliferation.

Adherent cells from synovial tissue of rheumatoid arthritis patients were fractionated on Percoll density gradients and analyzed to determine phenotypes, effects on allogeneic T lymphocyte proliferation, and production of prostaglandin E2 (PGE2). Cells expressing HLA-DR predominated in all fractions, and esterase-positive cells were enriched in light fractions. Heavy cells were potent stimulators in the mixed lymphocyte reaction and produced little PGE2, whereas light cells suppressed the mixed lymphocyte reaction and produced a large quantity of PGE2. These results suggest that macrophage-like synovial cells that suppress T helper lymphocyte activity are generated secondary to synovial lymphocyte activation in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1985

Appearance of different lymphoid cells in synovial tissue and in peripheral blood during the course of collagen II-induced arthritis in rats.

The involvement of different sets of lymphoid cells in the development of collagen II-induced arthritis in rats was studied by means of immunohistochemical analyses on frozen sections of tissue from joint biopsy specimens taken at different phases of arthritis development. Particular attention was paid to cells involved in early pannus formation. Accumulation of anti-Ia-reactive cells close to the cartilage surface was seen early in the development of pannus, and the anti-Ia reactive cells could in later phases be seen infiltrating cartilage and crowding bone surfaces at sites of marginal erosion. With the help of monoclonal anti-T-cell subset antibodies and rabbit anti-rat immunoglobulin antiserum, it was demonstrated that synovial infiltration of T lymphocytes, particularly W3/25-reactive T "helper" cells, occurs very early in the development of arthritis, whereas a moderate increase of Ox 8-positive 'suppressor/cytotoxic' T cells and a small number of B cells and plasma cells are seen later in the course of the disease. Levels of Ia-expressing cells and of T cells belonging to different subsets were recorded in peripheral blood by means of immunocytochemical analyses on cell smears; no significant deviations from normal levels were seen during the development of arthritis.

Animals↗
PubMed1985

T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific T-cell lines and clones.

Collagen type II-specific long-term cultured T helper cells, derived from the DBA/1 mouse, have been established and characterized. Clones from these T-cell lines could be shown to recognize either species-specific or species-nonspecific determinants on the collagen type II molecule, including determinants on autologous mouse collagen. Induction of arthritis via transfer to both irradiated and normal syngeneic recipient mice was obtained with both collagen type II-specific T-cell lines and an autoreactive and collagen type II-specific T-cell clone. Fewer cells were needed to evoke arthritis in normal than in irradiated recipients. Cells from lines and the clone used for transfer were by immunocytochemistry shown to have T helper phenotype.

Animals↗