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Biomedical subjects

J R Batchelor

Publications and source records attributed to J R Batchelor.

At least 109 records · Page 6Linked to original sources

Gold-induced thrombocytopenia: detection of anti-platelet antibody.

We describe a patient with rheumatoid arthritis who developed a sudden, severe thrombocytopenia during the early stages of treatment with sodium aurothiomalate. There were no haemorrhagic manifestations and the thrombocytopenia was rapidly corrected by corticosteroid treatment. The presence of anti-platelet IgG was demonstrated in serial serum specimens by an enzyme-linked immunosorbent assay (ELISA). Although most of this reactivity proved to be directed against allogeneic antigens on donor platelets, IgG reactive with autologous platelets was detected in the first serum sample obtained.

Adult↗

Immunogenicity of retransplanted rat kidney allografts. Effect of inducing chimerism in the first recipient and quantitative studies on immunosuppression of the second recipient.

It has been previously shown that long surviving, enhanced (AS X AUG)F1 rat kidneys residing in a primary AS recipient are not acutely rejected if transferred into a second AS recipient. The reduced immunogenicity of the retransplanted graft was attributed to a depletion of incompatible passenger cells. It is shown here that if the primary AS recipient is made chimeric by x irradiation and injection of (AS X AUG)F1 bone marrow cells, transfer of the long surviving, enhanced graft into a second AS recipient provokes acute graft rejection comparable to that observed when normal (AS X AUG)F1 kidneys are transplanted into untreated AS recipients. Transplantation of passenger cell-depleted AUG kidneys into AS recipients leads to graft rejection, with a median survival time of 22 d. Treatment of these recipients with as little as 1.5 mg/kg cyclophosphamide for 14 d induces prolonged graft survival. By contrast, five times as much cyclophosphamide treatment is required to induce prolonged survival of normal AUG kidneys (i.e., containing incompatible passenger cells) transplanted to AS recipients. These results confirm that the major alloimmunogenic stimulus of rat kidney grafts is provided by the incompatible passenger cells.

Animals↗

Bone-marrow transplantation for severe aplastic anaemia using histocompatible unrelated volunteer donors.

Two patients with severe aplastic anaemia received bone-marrow transplants from unrelated donors selected for HLA compatibility. Graft-versus-host disease occurred in both patients but responded to treatment. Both patients had stormy courses after grafting, but subsequently their conditions improved, and one was not receiving any treatment at follow-up after day 330 while the other had mild chronic graft-versus-host disease at day 150. These results show that unrelated, histocompatible volunteers may successfully donate marrow for the treatment of severe aplastic anaemia, though many problems remain to be solved.

Adult↗

Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia.

In 1979 two patients with Philadelphia (Ph1)-chromosome-positive chronic granulocytic leukaemia (CGL) were treated with chemoradiotherapy and transplantation of bone marrow from their respective identical twins. Subsequently twelve patients with Ph1-positive CGL in chronic phase were treated with chemoradiotherapy followed by transplantation of bone marrow from their HLA-identical sibs. Two of the fourteen patients have died of complications of the transplant procedure; twelve patients are alive and well. All the survivors have normal or nearly normal blood counts; there is no evidence of recurrent leukaemia or Ph1-positive cells in any patient after follow-up periods ranging from 97 to 1112 days. Bone-marrow transplantation should be considered in the management of any young patient with CGL who has a suitable marrow donor.

Adolescent↗

Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

Adolescent↗

Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells.

The immunogenicity of long-surviving, enhanced (AS X AUG)F1 renal allografts retransplanted into secondary AS recipients was restored by the injection of small numbers of donor strain dendritic cells derived from afferent lymph. Whereas 1 X 10(4) to 5 X 10(4) dendritic cells were able to trigger an acute rejection response, neither the passenger volume of donor strain blood nor 5 X 10(6) T or B lymphocytes were able to do so, thereby demonstrating more than a 100-fold difference in immunogenic potency. It is concluded that intrarenal dendritic cells provide the major immunogenic stimulus of a kidney allograft. These results suggest that the antigenic strength of major histocompatibility complex-incompatible tissue correlates with the content of donor strain dendritic cells. They also provide further evidence that antigens of the major histocompatibility complex behave like conventional antigens unless they are on the surface of allogeneic dendritic cells.

Animals↗

HLA antigens and Bf allotypes in SLE: evidence for the association being with specific haplotypes.

The clinical features and HLA types of 67 unrelated patients with Systemic Lupus Erythematosus (SLE) were analyzed. The results showed: 1. An increase in frequencies of A1, B8, and DR3. These antigens are in close linkage disequilibrium and our data show that susceptibility to SLE is associated with the presence of all three antigens, implicating the specific haplotype which bears these antigens. 2. An increase in frequency of DR2, but not A3 or B7, these latter two antigens being in linkage disequilibrium with DR2. 3. 73.3% of the 54 Caucasoid SLE group were either B8 and/or DR2. This is in comparison with 37.5% in the controls and the difference is significant (p less than 0.001). 4. There was no association apparent between extent of disease, particular organ involvement and level of circulating antibodies to double stranded DNA with any HLA region product.

Adolescent↗

The relationship of HLA-B and DR phenotypes to Behcet's syndrome, recurrent oral ulceration and the class of immune complexes.

A series of eighty Caucasian patients was divided into four groups with the mucocutaneous, arthritic, neurological and ocular types of Behcet's syndrome (BS) and a fifth group of patients with recurrent oral ulcers. The immunogenetic basis of the four types of BS was extended from HLA-B locus to the DR locus. Whereas B5 and more precisely the Bw51 split is the most discriminating marker of the ocular type of BS, DR7 also shows a significant increase in the ocular and neurological types. Indeed, most if not all patients with the ocular type have B5 and/or DR7. B12 and/or DR2 is significantly increased at the less severe end of the spectrum, the mucocutaneous and arthritic types. Patients with recurrent oral ulcers also show an increase in B12 and/or DR2. However, B12 and/or DR7 shows an increase in the relative risk in all four types of BS. These results suggest that HLA-B12, B5, DR7 and DR2 might in some way be associated with tissue localization of disease. Alternatively, since patients with HLA-B12 show a significantly greater ratio of IgG:IgA circulating immune complexes than those with B5/DR7/DR2, tissue localization might be influenced by the immune complex isotype. A significant relationship was also found between the MT2 and MT3 B cell alloantigen system and BS, with particular reference to MT2 and the neurological type and MT3 and the ocular type of BS.

Antigen-Antibody Complex↗

Do alleles in linkage disequilibrium compensate for each other's disadvantageous effects?

When alleles from two different loci behave as independent factors it is possible to calculate the expected frequency of their joint occurrence. In the HLA system significant departures from expected haplotype frequencies occur. Thus antigen B8 occurs together with A1 or/and DR3 in about 95 cases out of 100 (the figure expected by chance is about 45 out of 100). In a similar manner the antigens A3, B7 and DR2 are found associated very much more often than expected by chance alone. The reasons for these observations are obscure, but Fischer (1930) and more recently Bodmer (Bodmer & Bodmer 1978) have argued that some form of natural selection is a major factor in the occurrence and maintenance of linkage disequilibrium. In the present study we show that individual alleles of the common haplotype A1-B8-DR3 can exert different effects as regards IgE levels. This may provide evidence that one of the contributory mechanisms leading to linkage disequilibrium involves selection against individuals having a harmful allele unless it is in association with another conferring compensatory effects.

Alleles↗

Relationship of HLA phenotype to immunoglobulin class present in immune complexes from patients with Behçet's syndrome.

The immunoglobulin class of circulating immune complexes (IC) was examined in 35 patients with Behçet's syndrome (BS) according to the HLA phenotype of these patients. Cold precipitable complexes were separated and assayed by laser nephelometry and polyethylene glycol precipitable complexes were assayed by rocker immuno-electrophoresis for IgG, IgA and C3. The results suggest that in patients with BS, HLA-B12 is associated with an increased proportion of IgG and a decreased proportion of IgA and C3 in their immune complexes, whilst the converse was found with HLA-B5 or DRw2. The ratio of IgA:IgG in immune complexes was therefore low in patients with HLA-B12 but high in those with HLA-B5 or DRw2. We suggest that a linkage may exist between HLA and gene(s) determining the immunoglobulin class, in response to antigenic stimulation or the site of antigen localization.

Antigen-Antibody Complex↗

Lymphocytotoxins in rheumatoid arthritis: prevalence, lymphocyte specificity, and HLA-DR antigens.

37% (57/155) of sera from patients with rheumatoid arthritis contain cold-reacting lymphocytotoxic antibodies. Lymphocytotoxins were predominantly of the weakly reactive type and were more likely to be present in patients who were HLA-DR4 positive. By contrast, patients who were HLA-DR3 positive were more likely to have strongly reactive lymphocytotoxins. The lymphocyte subclass reactivity of the lymphocytotoxins was: 67% versus B lymphocytes, 27% against both T and B cells, and 7% for T cells.

Antibody Specificity↗