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Biomedical subjects

G Rook

Publications and source records attributed to G Rook.

25 records · Page 2Linked to original sources
PubMed1989

T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis.

We sought to protect CBA mice against tuberculosis using in vivo transfer of a T-cell line previously shown to be capable of I-A-restricted recognition of peritoneal macrophages infected in vitro with Mycobacterium tuberculosis. This line induces total bacteriostasis in vitro. In mice that received 500 rads of irradiation 48 h before infection, the T-cell line caused significant prolongation of life when given intravenously with a challenge dose of 5 x 10(6) organisms. Similar experiments with two other T-cell lines showed that these lines offered no protection. Bacterial load at the time of death was inversely related to the time of survival. Thus, death occurred at a lower bacterial load in adoptively protected mice, implying the contribution of an immunopathological component in these animals. The protective T-cell line, which was CD4+ CD8-, had no effect on the rate of growth of strain BCG in CBA nu/nu mice or M. tuberculosis in fully T-cell-deprived mice. This could indicate that CD8+ cells play a role in this system or that there is a need for the recruitment of interleukin 2-producing cells in the recipient. Experiments with monoclonal antibodies to selectively deplete T-cell subsets in normal CBA mice showed that depletion of CD4+ cells strikingly shortened survival, whereas depletion of CD8+ cells did not. However, CD8-depleted mice died with a lower bacterial load than those found in nondepleted controls, and the lesions in CD8-depleted mice were histopathologically distinct. These results suggest that the CD8+ cells either down-regulate bacteriostasis or cause immunopathology in this model and that it is the CD4+ cells that are the major protective subset in long-term protection experiments.

Animals↗
PubMed1989

The use of antigen-bearing nitrocellulose particles derived from Western blots to study proliferative responses to 27 antigenic fractions from Mycobacterium leprae in patients and controls.

Antigens present in sonicates of Mycobacterium leprae were separated by SDS-PAGE, blotted electrophoretically on to nitrocellulose, and visualized with a colloidal gold stain. Six bands identified by existing monoclonal antibodies, and a further 21 bands not previously studied, were converted into antigen-bearing nitrocellulose particles for use in vitro lympho-proliferation studies. Controls (putative non-contacts) responded poorly to the antigenic fractions presented in this way. Contacts responded variably to a wide range of the antigens, and most frequently (23%) to the 18,000 MW fraction. Responses to this, and to several other low molecular weight antigens, were not seen in non contacts, and were very rare in all patient groups, which tended to respond to high molecular weight components. The most interesting individual band was at 36,000 MW. This caused significant stimulation of cells from 25% of tuberculoid donors, but never stimulated the cells from lepromatous cases. Indeed this fraction significantly suppressed the background proliferation of the cells from 30% of the lepromatous cases, though the significance of this observation is unclear. Responses to the 65,000 MW heat-shock protein did not differ significantly between the donor groups. Overall the results suggest that the spectrum of clinical leprosy may not be determined by the response to any one antigen. However, this study can not rule out the possibility that the response to one or a few antigens determines the outcome during the first few days after infection.

Antigens, Bacterial↗
PubMed1986

Subdivision of daughter strains of bacille Calmette-Guérin (BCG) according to secreted protein patterns.

In order to identify proteins secreted by live organisms, daughter strains of the Bacillus Calmette-Guérin (BCG) were grown for 4-7 d in a defined medium containing [35S]methionine. Secreted components were then separated by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions, and analysed by autoradiography and in an Ambis beta-scanner. The results indicate that BCG daughter strains can be subdivided into two groups according to their secretion of a 46 kDa protein dimer consisting of two similar 23 kDa subunits. High-producer strains (Japanese, Brazilian and Russian) secrete very large quantities of this material, which constitutes approximately 23% of all secreted protein. These findings correlate with earlier studies in which degradation products of the protein dimer may have been identified, and with the data from patterns of cell wall lipids.

Bacterial Proteins↗
PubMed1981

Autoantibodies to cartilage and type II collagen in relapsing polychondritis and other rheumatic diseases.

Cartilage antibodies were demonstrated by indirect immunofluorescence (IFL) on human fetal cartilage in 6 out of 9 patients with relapsing polychondritis (RPC), in 4 out of 260 patients with rheumatoid arthritis (RA), and in only 1 out of 1016 patients with other disorders. The antibodies were specific for cartilage and evenly stained the whole cartilage matrix. They were predominantly of IgG class and varied in titres from 1:1 to 1:320. Follow-up studies in the RPC patients indicated that higher titres were present during the early acute phase of the disease. Five of the 6 positive cases had developed the disease within the past 12 months, and the 3 negative cases had had the disease for 3 to 7 years when tested. The RA cases showing positive cartilage IFL had no clinical evidence of RPC. Sequential measurements in 2 of the 4 cases showed that these antibodies became detectable some years after the onset of arthritis. Absorption studies with human type II collagen and purified porcine proteoglycan failed to remove the cartilage IFL. Antibodies to human native type II collagen were measured by an enzyme-linked immunosorbent assay. The highest levels were found in the RA sera which also displayed cartilage IFL, but the 2 tests gave discordant results. RPC sera showed the same antibody levels by this method, as did cartilage-IFL-negative RA sera, though both groups had higher mean levels than health controls. The findings that cartilage antibodies are detected in the majority of cases of RPC and only rarely in other diseases suggests these antibodies may play an important role in the pathogenesis of cartilage destruction in RPC.

Acute Disease↗