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Biomedical subjects

H V Bashir

Publications and source records attributed to H V Bashir.

32 records · Page 2Linked to original sources

HLA family studies and multiple sclerosis: A common gene, dominantly expressed.

All available Australian families with more than one member suffering multiple sclerosis (MS) were HLA typed. As with all other individual published studies, convincing evidence for linkage between the HLA system and disease was not obtained. An analysis of 100 published affected sib-pairs and 17 cousin-pairs, however, established the existence of an HLA-linked disease susceptibility gene for MS, which is likely to be dominantly expressed. Dominance was also supported by the finding of only three HLA-DR2 (Dw2) homozygous individuals out of 60 unrelated patients which enabled rejection of a recessive gene hypothesis (p less than 0.02). Analysis of the sib-pair data strongly suggested that this MS gene is not rare in the normal population and may be as common as DR2.

Australia↗

The distribution of a specific HLA-B27-associated cell surface component on the tissues of patients with ankylosing spondylitis.

In this paper, we report the presence on Epstein-Barr virus-transformed lymphoblastoid cell lines on platelets and on fibroblasts of an HLA-B27-associated cell surface complex (antigenically related to some antigens of Klebsiella K43 and K21) which is identical to or cross-reactive with the determinant present on the peripheral blood lymphocytes (PBL) of B27-positive patients with ankylosing spondylitis (AS). By contrast, no Klebsiella K43 markers could be demonstrated on the spermatozoa of B27+ AS+ individuals even though these cells expressed the HLA-B27 alloantigen. No B27-associated K43 antigen was detected on the erythrocytes of patients or of normal controls. The B27-associated membrane marker is still detectable on lymphoblastoid cell lines after 20 generations and on fibroblasts after about 10 generations. This finding implies that the continued expression of Klebsiella-modified B27 structure is generally determined and does not require the repeated exposure of the cell surface to Klebsiella antigen. These data suggest that certain non-lymphoid as well as lymphoid cells may be involved in the complex sequence of events leading to the clinical manifestation of AS.

Blood Platelets↗

Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component.

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.

Antigens, Bacterial↗

The role of Klebsiella in the pathogenesis of ankylosing spondylitis. II Evidence for a specific B27-associated marker on the lymphocytes of patients with ankylosing spondylitis.

Although the strong association of HLA-B27 with ankylosing spondylitis (AS) is well documented, the significance of this association is largely unknown. It has recently been reported that Klebsiella pneumoniae was present in the faeces of patients with AS more frequently than in healthy individuals, and that there appeared to be some cross-reactivity between HLA-B27 and Klebsiella. We have therefore attempted to gain an insight into the possible role of Klebsiella in the pathogenesis of AS. The results presented here indicate that HLA-B27 positive individuals with AS have a significantly lower in vitro lymphocyte responsiveness to Klebsiella antigens, as compared with B27 positive and B27 negative healthy controls. By contrast, B27 positive patients with AS as well as B27 positive and negative controls respond equally well to phytohaemagglutinin, Staphylococcus, Streptococcus, Yersinia and Shigella. To investigate a possible cross-reactivity between Klebsiella and HLA-B27, antisera were raised in rabbits against various isolates of Klebsiella. An antiserum to one isolate (427) of Klebsiella lysed the lymphocytes of B27 positive AS patients but not of B27 positive or B27 negative controls. These observations strongly suggest that some Klebsiella antigens cross-react with a gene product closely associated with HLA-B27 or possibly with a modified B27 antigen in patients with AS.

Animals↗

Response of HL-A identical unrelated individuals in the mixed lymphocyte culture test.

The immunological responsiveness as measured in the mixed lymphocyte culture test has been studied in 13 pairs of HL-A identical unrelated individuals. In all combinations stimulation occurred and it was frequently of a similar magnitude to that observed against non-HL-A identical subjects.It is postulated that another locus, adjacent to the HL-A locus, is also responsible for the non-stimulation observed between HL-A identical siblings, and that observations made in the related situation should not be transposed to the unrelated situation without some reservation.

Cytotoxicity Tests, Immunologic↗