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Nomenclature for factors of the HLA system--1977.

A Nomenclature Committee composed of geneticists and immunologists, including specialists in tissue typing, has met after each of the Histocompatibility Testing Workshops beginning with the 3rd Workshop in 1967. The Committee met again, in part under the auspices of the World Health Organisation and for report to the International Union of Immunological Societies, after the 7th Workshop in Oxford in September 1977, with the aim of updating the nomenclature for specificities of the HLA-A, B, C and D loci and establishing a nomenclature for the new specificities identified by serological techniques on B lymphocytes.

B-Lymphocytes↗

AeiB: A family study.

This reports the first example of Aei in conjunction with an apparently normal B antigen. Fortunately family studies clearly outlined the genetic transmission.

ABO Blood-Group System↗

Kidney transplantation in children.

Over the past decade, the success rate of pediatric kidney transplantation has dramatically increased, based on improvements in histocompatibility testing, immunosuppressive management, and diagnosis and treatment of rejection. The 1-year graft survival rate now approaches 90%. The optimal age for recipients as well as for donor organs is greater than six years. Recurrence of primary disease in the graft accounts for approximately 5% graft loss in children. Sequential immunosuppressive protocols have been particularly successful in children, and maintenance immunosuppression routinely includes corticosteroids, azathioprine, and cyclosporin A. Posttransplantation complications include rejection, infection, hypertension, growth retardation, and noncompliance.

Adolescent↗

Unrelated donor and autologous marrow transplant therapy of chronic myelogenous leukemia (CML).

Marrow transplant from an HLA-matched sibling donor can cure CML. Best results are observed when patients are transplanted early in chronic phase. T-lymphocyte depletion of donor marrow can effectively prevent chronic graft versus host disease, but is associated with a high incidence of relapse. Hematologic relapse after marrow transplantation can be treated successfully with alpha-interferon, donor buffy coat cells or second transplant. HLA phenotypically matched and, in some cases, 1 HLA antigen mismatched unrelated donors can also be used successfully for marrow transplantation therapy of CML. Complications include an increased incidence of graft failure and graft vs. host disease. Chronic phase patients transplanted early in the disease course have the best outcome. The development of the National Marrow Donor Program in the United States and a network of donor registries throughout the world as well as the establishment of new techniques for histocompatibility testing will increase the availability of unrelated donors and expedite the donor search process. Autologous marrow transplantation can induce complete hematologic and cytogenetic remissions and may prolong survival when compared with results expected from conventional therapy for CML. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection techniques and to develop further post-transplant anti-leukemia cell therapy to use as an adjunct to autologous marrow transplantation for CML.

Bone Marrow Transplantation↗

The quest for living-related kidney donors for children with end-stage renal disease.

In a pediatric renal transplant program that actively seeks living-related kidney donors, we achieved a living donor rate of 55% in 119 children. This approximates the national average but is less than an idealized goal. For black children, the living-donor transplant rate was 41%, a disconcertingly low rate. In an attempt to define factors that negatively affected living-related donor availability, we analyzed our evaluation process by distinct phases (interview, histocompatibility testing and medical evaluation). We classified our families on the basis of locale (urban, suburban and rural), family unit (two or less parents, adult sibs or other relatives presenting at interview) and economic status (designating only economic-disadvantaged and other). While histoincompatibility is predictably a negative factor, the negative impacts of medical illness in the donor pool, economic disadvantage and single parent family are striking and cumulative. Our data validate the relative success of an aggressive recruitment policy in a patient population that includes many economically disadvantaged families. For pediatric renal transplant programs with low living-related donor rates, our data should encourage review and possible modification of the donor recruitment process.

Adult↗

[Association between hepatitis B surface antigenemia and HLA histocompatibility phenotypes].

To test whether HLA histocompatibility phenotypes might be associated with circulating hepatitis B surface antigen (HBsAg), we performed chi-square test with Yate's correction and Fisher's exact test on findings in 315 normal healthy hospital staffs with known HLA types and HBsAg status. A significant relation between locus A of HLA types and HBs antigenemia was demonstrated, with negative association suggested between A1, AW23, A26, A29, +AW30 +AW31 and AW32 types and HBs antigenemia. Another significant relation between locus B of HLA types and HBs antigenemia was shown, with negative association suggested between B7, B8, BW21, BW44 and BW49 and HBs antigenemia. There was no significant relation between locus C of HLA type and HBs antigenemia, but type CW4 was revealed to have a relative risk of 2.11. Therefore, previous suggestion that both susceptability and resistance to hepatitis B virus infection may be in part genetically determined and previous observation of population differences in HBsAg prevalences could be interpreted by these findings.

Adolescent↗

Requirement of major histocompatibility complex-compatible microenvironment for spleen colony formation (CFU-S on day 12 but not on day 8).

To clarify major histocompatibility complex (MHC) restriction between hematopoietic stem cells (HSCs) and microenvironments, T cell-depleted bone marrow cells (BMCs) were transplanted into MHC-compatible and MHC-incompatible recipients. A significantly larger number of spleen colony-forming units (CFU-S) on day 12 were noted in MHC-compatible recipients, while only a small number were observed in MHC-incompatible recipients. There was, however, no significant difference in CFU-S counts on day 8 between the two groups. A large number of CFU-S counts on day 12 were also observed in F1 hybrid recipients, as seen in syngeneic recipients. The decrease in CFU-S counts on day 12 in MHC-incompatible recipients was also observed even after in vivo abrogation of T and NK cells. The difference in CFU-S counts on day 12 became more prominent when HSC-enriched cells were transferred. These results suggest that an MHC restriction exists between pluripotent HSCs (P-HSCs) and spleen microenvironments. Furthermore, experiments using B10. A recombinant strains revealed that H-2D and S loci play a crucial role in the MHC restriction. The experiments of serial transplantation suggest that the differentiation and proliferation of P-HSCs are inhibited in MHC-incompatible microenvironments. It is therefore likely that the MHC-compatible microenvironment is essential to the differentiation and proliferation of P-HSCs.

Animals↗

Augmentation of cell mediated lysis (CML) by THF.

The in-vitro model of cell mediated lysis (CML) was used to study whether a thymic hormone (THF) participates in the processes which lead to generation of effector cells. It was found that THF increases the capacity of effector cells from spleens of intact mice in the CML assay. This effect of THF on generation of effector cells was manifested when THF was present during the mixed lymphocyte culture. On the other hand, addition of THF to the effector (CML) phase did not elevate the lytic capacity of killer cells. Moreover, THF compensated the impaired lytic capacity of effector cells from adult thymectomized mice and raised it to the level of intact mice. The results are compatible with the hypothesis that THF acts on the generation of CML effector cells of both intact and adult thymectomized mice.

Animals↗

Gene order in the major histocompatibility complex of the rat.

The loci in the major histocompatibility complex (MHC) of the rat which code for class I and class II antigens--RT1.A and RT1.B, respectively--have previously been separated by laboratory-derived recombinants and by observations in inbred and wild rats. Closely linked to the MHC is the growth and reproduction complex (Grc) which contains genes influencing body size (dw3) and fertility (ft). These phenotypic markers were used in this study to orient the A and B loci of the MHC. Two recombinants were used for mapping. The BIL(R1) animal is a recombinant between the MHC and Grc, and it carries the haplotype RT1.AlBlGrc+. The r10 animal is an intra-MHC recombinant, and it has the haplotype RT1.AnB1Grc. These recombinants were characterized serologically, by mixed lymphocyte reactivity, by immune responsiveness to poly (Glu52Lys33Tyr15) and by the presence of the dw-3 gene. The data demonstrate that the gene order of the loci is: dw-3--RT1.B--RT1.A.

Animals↗

Cross-reactivity between RSV-induced tumor antigen and B5 MHC alloantigen in the chicken.

Lymphocytes from chickens homozygous (B2B2) at the major histocompatibility complex (MHC) were tested for cytotoxic against five types of target chicken embryo fibroblasts (CEF). Lymphocytes from B2B2 chickens bearing RSV-induced tumors lysed in vitro targets of B2B2 and B5B5 RSV-infected CEF and B5B5 normal CEF, but did not lyse B2B2 and B24B24 normal CEF. Lymphocytes from normal B2B2 chickens did not lyse any of the five types of CEF targets. Alloantisera absorption studies showed that both RSV-infected and uninfected CEF shared alloantigens, in particular B-F alloantigens, with syngeneic erythrocytes. Absorption with B2B2 RSV-infected CEF significantly lowered the titer of B2B2 anti-B5B5 alloantisera. Cross-reactivity between B5 antigen(s) and tumor-associated antigen was suggested and the nature of the cross-reactivity was discussed. It is hypothesized that this cross-reactivity prevents B5B5 chickens from recognizing the RSV-induced tumors as foreign, enhances tumor growth and leads to death of the host.

Animals↗

Intrathymic delivery of plasmid-encoding endoplasmic reticulum signal-sequence-deleted MHC class I alloantigen can induce long-term allograft survival.

Intrathymic (IT) delivery of donor alloantigen is a potent strategy to induce operational tolerance. In this study we determined whether this effect was dependent on direct allorecognition of the tolerogen. Ten microgrammes of plasmid, encoding either the wildtype major histocompatibility complex (MHC) class I molecule K(b) or a truncated form in which the signal sequence for translocation into the endoplasmic reticulum was deleted, preventing cell surface expression and direct allorecognition of the tolerogen, was administered intrathymically to CBA.Ca (H2(k)) recipients. In addition, recipients were treated with anti-CD4 antibody (YTA3.1) at the time of IT injection and underwent transplantation 28 days later with a fully mismatched C57BL/10 (H2(b)) cardiac allograft. Wildtype, as well as truncated K(b) genes, were able to induce long-term survival of the cardiac allografts, in contrast to empty control plasmid. Reverse-transcriptase PCR showed expression of the K(b) genes for up to 28 days in thymus and spleen of pretreated recipients. These data show that direct allorecognition of the tolerogen was not required for the induction of long-term allograft survival following the introduction of plasmid-encoded MHC alloantigen into the thymus.

Animals↗