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Biomedical subjects

H Bashir

Publications and source records attributed to H Bashir.

At least 19 recordsLinked to original sources

HLA and nonspecific polyarthritis in the highlands of Papua New Guinea.

We have studied the HLA profile of a series of 49 patients (32 men, 17 women) presenting with asymmetric polyarthritis to the Goroka Base Hospital, Papua New Guinea. Antigens A11 and B27 were found to be significantly increased in patients when compared with a control sample of 100 healthy Papua New Guinean highlanders. Significant negative associations were also recorded with A24[A9] and Bw22. None of the patients studied presented with the complete triad of Reiter's disease although 6 patients, all men, had some extraarticular symptoms. On the basis of these additional symptoms, the 6 patients were diagnosed to have an incomplete form of Reiter's disease and were excluded from further comparisons. In the remaining 43 patients, who fit the nonspecific category that has been called tropical polyarthritis, B27 was present in 20.9% of the cases, which was not significantly different from the control frequency of 11.0%. But the positive association with A11 was still found in the nonspecific arthritis cases. Our data do not support the concept that the patients included in this study constitute a single diagnostic category which is related to Reiter's disease. It is suggested that these patients be regarded as suffering from nonspecific polyarthritis of unknown, probably multiple, aetiology, until further more specific diagnostic entities can be determined.

Adolescent

HLA studies of Highland and Coastal New Guineans.

The HLA profile of three New Guinean populations, two Highland (Asaro, Watut), and one Coastal is presented. The Highland populations are characterized by a low average number of alleles segregating at the HLA loci and also by a low mean value of heterozygosity at these loci. The genetic affinities of the two Highland groups with other Melanesian populations in the Pacific are remote. The Coastal group, on the other hand, shows strong similarities in its antigenic diversity and haplotypic combinations with other Melanesian populations. Nonetheless, the two Highland groups show significant divergence from each other in terms of allelic and haplotypic frequencies. Two different waves of migration settled in the Highlands of New Guinea between 10,000 and 15,000 years ago, and it is possible that the Watut, an Angan speaking group, represents the remnants of the first migration into the interior, whereas the Asaro, members of the Eastern Central family of the Trans-New Guinea phylum, arrived at a later date.

Adult

Bone marrow transplantation in 33 patients with malignant blood diseases and severe aplastic anaemia.

Allogeneic bone marrow transplantation using HLA-identical sibling donors was performed in 29 patients with malignant blood diseases and in four patients with severe aplastic anaemia. Twenty-five patients received immunosuppressive therapy with cyclosporin A to minimize graft-versus-host disease (GVHD) and eight received methotrexate. Twenty-one of 29 patients (72%) with malignant blood diseases and three of the four patients with severe aplastic anaemia remained alive and disease-free from 0.5 to 16 (median, seven) months after transplantation. Acute GVHD, predominantly of the skin, occurred in 25 of 28 evaluable cyclosporin A recipients (of whom two died), and in all five evaluable methotrexate recipients. Mild chronic GVHD occurred in 10 of 16 evaluable patients. Interstitial pneumonitis occurred in five patients, of whom two died. HLA-identical sibling marrow transplantation is associated with a mortality similar to that of induction chemotherapy for acute leukaemia, and should be considered in adults with acute leukaemia in remission or relapse, chronic myelogenous leukaemia in metamorphosis or blastic transformation, lymphoma unresponsive to conventional therapy, and in severe aplastic anaemia.

Adolescent

Evidence for the involvement of HLA-DR antigens in restricted cytotoxicity by fetal calf serum-specific human T cells.

Fetal calf serum (FCS) generated at least two distinct populations of human cytotoxic cells in vitro. One population expressed natural killer (NK) cell-like activity and lysed K562 and HSB-2 targets more effectively than autologous or allogeneic lymphoblastoid cell lines (LCLs). The other population contained FCS-specific cytotoxic T cells which preferentially lysed the autologous LCLs and showed minimal lysis of K562. E-rosette separation and cold target competition experiments clearly established that NK cells were not involved in the self-reactive lysis. Moreover, the lytic activity of the E-rosetted T cells was reduced by up to 95% when autologous target cells were grown in human AB serum rather than FCS, showing that FCS-associated determinants on targets were essential in the cytolytic phase. Autologous LCLs grown in FCS were also considerably stronger competitors than human serum-grown LCLs. The consistent self-preferred lysis suggested that HLA antigen-related restriction was involved, but the patterns of lysis did not implicate HLA-A or B antigens, and monoclonal antibody (W6/32) to an A, B, and C monomorphic determinant failed to block FCS-specific lysis. In contrast, monoclonal antibody (DA.2) to a monomorphic determinant of DR effectively blocked FCS-specific lysis. Cytotoxicity tests with a small panel of DR-typed donors indicated that strong cross-reactions were invariably associated with sharing of DR antigens, particularly DR2, and to a lesser but significant extent DR7. Although DR antigen sharing did not always result in lysis of allogeneic targets, the overall evidence strongly suggests that FCS-specific T-cell cytotoxicity in humans is restricted by products encoded by or associated with the DR genes.

Animals

HLA antigens in Bali (Indonesia) with a special reference to an isolated community.

One hundred eighty-two Balinese were typed for HLA-A and -B locus antigens. From these, 103 were also typed for HLA-C, 51 for HLA-DR, 172 for Bf and 173 for GLO. These results and the significant phenotypic associations are situated with respect to other South-East Asian populations. In addition to this first study, 175 individuals from an isolated Balinese village typed for HLA-A, -B, -DR, Bf and GLO are presented. The effect of isolation on haplotype (HLA-A/-B/Bf/-DR) variability is discussed.

Asia, Southeastern

Modification of the platelet suspension immunofluorescence test.

This study reports two modifications of the Platelet Suspension Immunofluorescence Test which make it more convenient to use for the rapid identification of platelet-specific antibodies and for screening individuals if platelet donors of a particular type are urgently required. Platelets frozen both before and after paraformaldehyde (PFA) fixation were compared with fresh PFA-fixed platelets using anti-PLA1 and anti-HLA antisera. Further, a comparison was made between the results of the test when performed in tissue culture trays or in tubes as originally described. Platelets, prefixed with PFA and then frozen appeared similar in all respects to fresh PFA-fixed platelets with no loss of antigenicity and no non-specific fluorescence. Although platelets fixed after frozen storage were also satisfactory, they were less convenient to use and lost some brilliance in staining. When the test was performed in tissue culture trays, there was no loss in sensitivity, and the volume of antiserum used was halved. However, the main advantage was the efficiency and ease with which the test could be performed, especially when handling large numbers of samples.

Antibodies

Search for Klebsiella cell wall components cross-reactive with lymphocytes of B27+ AS+ individuals.

It has been suggested that some Klebsiella sp may cross-react with a cell surface determinant on the lymphocytes of B27+AS+ individuals. Studies were undertaken to identify culture filtrates capable of rendering the lymphocytes of B27-positive healthy controls susceptible to lysis by the anti-Klebsiella antiserum. Polyacrylamide gel electrophoresis of cell wall material of Klebsiella K43 prepared by sonication, high-speed centrifugation, and nonidet solubilization, demonstrated the presence of four major protein bands. When antisera raised in rabbits to each of these were tested for their cytotoxic effect on the lymphocytes of B27+AS+ individuals, an antiserum to one component only, of 40-52 K daltons molecular weight, reproduced the activity of the whole serum. Studies on the K43 filtrate indicated that the 'modifying' factor appeared to reside in a 25-50 K dalton component. Immunoelectrophoresis against anti-K43 serum demonstrated overlapping bands in the culture filtrate and the 40-52 K dalton cell wall fraction and these appeared to be identical on immunodiffusion. Antibody to the cell wall component removed both the 'modifying' activity and the appropriate protein band from the filtrate. The results suggest that a 40-52 K dalton component of the Klebsiella K43 cell wall is cross-reactive with a determinant on the lymphocytes of B27+AS+ individuals and is similar to or identical with a modifying factor in K43 culture filtrate which renders the lymphocytes of B27-positive healthy controls susceptible to lysis by anti-Klebsiella antiserum.

Cell Wall

Adverse reactions due to leucocyte and platelet antibodies.

Each blood transfusion exposes the recipient to the hazards of immunisation to histocompatibility antigens as well as white cell and platelet antigens. As the number of transfusions received by a patient increases so too does the likelihood of the development of antibodies which may by their multispecific character effectively prevent lifesaving therapy in the future. Special steps can and should be taken to minimise the risks of immunisation in the group of patients who will be dependent on long term transfusion therapy. An extension of knowledge about the antigenic systems of leucocytes and platelets, including HLA, and the introduction of more specific tests for the detection of antibodies directed against them should assist in the provision of more appropriately matched blood components.

Antigen-Antibody Reactions

HLA-DRw7 and steroid-responsive nephrotic syndrome of childhood.

We searched for possible immunogenetic markers in steroid-responsive nephrotic syndrome of childhood (SRNS). The incidence of HLA-DRw7 was significantly greater in SRNS patients than in controls (71% in patients, 29.8% in controls, P < 0.005). The HLA-A and -B locus antigens occurred in normal frequencies. The relative risk factor for HLA-DRw7 in SRNS was 5.9. This report failed to show a relationship between HLA-DRw7 and atopy, use of alkylating agents or occurrence of relapse after remission induced by these agents. We believe that SRNS may be an immunologic disorder whose pathogenesis is related to an MHC-linked Ir gene.

Cyclophosphamide

Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing.

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.

Adolescent

Thirteen cases of leukemia in a family.

Thirteen cases of leukemia, 12 of them acute, occurred in 3 generations of a family comprising 293 members. Individual cases could not be linked to the possession of any of a range of genetic markers. Cytogenetic studies showed no constitutional chromosome abnormalities. Preliminary results of virologic studies suggested the presence of oncornaviruses in at least 1 leukemic individual in this family. This aggregation of leukemia cases likely resulted from a genetic, probably polygenic, predisposition, in association with the activity of leukemogenic factors whose nature remains to be clearly defined.

Adolescent