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Factors affecting patency of venous allografts in miniature swine.

In immunologically defined National Institutes of Health miniswine, a segment of internal jugular vein was anastomosed to the carotid artery as an interposition graft. Patency of swine major histocompatibility complex matched, one haplotype mismatched, and complete mismatched veins was 9.8, 6.3, and 3.0 weeks respectively (p = 0.009). More than 90% of mismatched and 20% of matched allografts developed a positive crossmatch before occlusion (p = 0.006). The mixed lymphocyte response did not predict graft occlusion. Treatment of 10 swine with cyclosporine (10 mg/kg/day) did not significantly improve patency for one haplotype mismatched grafts. In haplotype mismatched veins, cryopreserved grafts occluded more rapidly than noncryopreserved grafts: mean 2.4 versus 6.3 weeks, respectively (p = 0.002). In all cryopreserved vein grafts, alloantibody appeared at or after graft occlusion rather than before occlusion as seen with fresh allografts (p = 0.046). The mean patency of cryopreserved versus fresh autografts was 3.3 and greater than 32 weeks, respectively (p = 0.004). In summary, these results indicate that (1) allograft patency is related to the degree of swine major histocompatibility complex match and development of cytotoxic alloantibodies; (2) moderate-dose cyclosporine does not prolong allograft patency nor suppress development of antibody; (3) cryopreservation may accelerate graft occlusion through nonimmunologic mechanisms.

Animals↗

[Relation of the effect of human complement in the cytotoxic test to the origin of the HLA serum].

The use of human complement in HLA typing produced strongly positive results only in examinations with polyspecific sera from pregnant women, while with mono- or bispecific sera positive results were obtained only in some instances and the results were usually weaker. With polyspecific sera from patients after multiple transfusions negative results were obtained. The action of complement did not depend on the titre of HLA cytotoxins. The results confirm the hitherto held view that it is not suitable to use human complement for HLA typing.

Animals↗

Analysis of anti-lymphocyte antibodies by flow cytometry or microlymphocytotoxicity in women with recurrent spontaneous abortions immunized with paternal leukocytes.

The identification of anti-lymphocyte antibodies was investigated in women with a history of recurrent spontaneous abortions who received leukocyte immunization treatment. The antibodies were detected by two-color flow cytometric analysis (FCMX) and by microlymphocytotoxicity (MCX). Twice the number of positive patients (women who had been immunized with paternal leukocytes and produced antilymphocyte antibodies) could be identified by flow cytometry versus a standard microcytotoxicity assay (66 versus 33%). In addition, when mixed lymphocyte culture assays were performed to determine if serum blocking factors had been induced, those couples who were positive by FCMX showed inhibition of the mixed lymphocyte culture responses in contrast to most FCMX negative patients who did not. Thus, the sensitivity of the FCMX and its rapidity makes it an alternative to the mixed lymphocyte culture assay for assessing immunotherapy in women with recurrent spontaneous abortions.

Abortion, Habitual↗

[Study of the antibody-dependent lymphocytotoxicity test as a function of the nature of the antibodies].

It is well known that IgM antibodies are inactive for the LDA test. Moreover, this work showed 7 S IgM to be just as inactive as 19 S IgM. With HLA antibodies, usually IgG, this work showed that the LDA test was not inhibited by a temperature of + 15 instead of + 37 degrees C. With cold lymphocytotoxic antibodies 19 S and 7 S IgM the LDA test was negative even at + 15 degrees C (optimum temperature for these complement dependant lymphocytotoxic antibodies) with or without prolonged incubation. Under these same conditions, a negative result was obtained using auto-lymphocytes as a target. Finally, our results confirmed that IgM antibodies with anti-HLA activity could not act as mediators even for targets with corresponding HLA activity.

Antilymphocyte Serum↗

Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests.

Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.

Blood Donors↗

Donor-specific blood transfusions versus cyclosporine--the DST story.

DST provides excellent graft survival in one- and zero-haplotype-matched donor-recipient pairs as well as a trend towards improving graft survival in HLA-identical matches; serum creatinine levels are good in functioning grafts; Imuran coverage does appear to decrease DST sensitization to the blood donor in nonsensitized patients undergoing a first transplant, which encourages early DST and transplantation in this group; flow cytometry has been extremely helpful in excluding subliminal anti-class 1 antigen activity in patients with positive B warm crossmatches alone; DST, in itself, does not appear to preclude subsequent cadaveric transplantation in patients sensitized to their blood donor; and the family history of the blood donor is known, with essentially no risk to the recipients of hepatitis, AIDS, etc. In regards to the issue of whether DST or Cs is better, both have merits, and one must be aware of the circumstances that relate to the optimum application of each therapy. Only a prospective study of DST- and Cs-treated patients with a long-term follow-up will probably resolve the issue of the optimum regimen for one-haplotype-matched living related donor-recipient pairs. The ultimate strategy may involve the selective use of each regimen for the most appropriate circumstances.

Adolescent↗