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D Jezek

Publications and source records attributed to D Jezek.

5 recordsLinked to original sources

Treatment of acute cellular rejection with T10B9.1A-31 or OKT3 in renal allograft recipients.

T10B9.1A-31, a nonmitogenic immunoglobulin Mk monoclonal antibody that detects an epitope on the alpha/beta chains of the T cell antigen receptor (TCR alpha/beta), or OKT3, an anti-CD3 mAb, was employed in a randomized double-blind phase II clinical trial to treat biopsy-proven acute cellular renal allograft rejection. Two of the 40 patients initially selected for the protocol were considered to be nonevaluable. Analysis of the remaining 38 patients receiving both living related and cadaveric donor allografts revealed a patient survival of 100% and a graft survival of 97%. Primary rejection reversal was achieved in 18/19 (95%) patients treated with T10B9.1A-31 and in 20/21 (95%) of patients receiving OKT3. The two patients who did not respond to the first mAb responded to the crossover mAb. Rerejection occurred in 3/18 (17%) of patients treated with T10B9.1A-31 and in 3/20 (15%) treated with OKT3. The mean day of rejection reversal was 1.9 +/- 0.7 with T10B9.1A-31 and 3.37 +/- 1.21 with OKT3 treatment. The rise in mean serum creatinine after mAb administration and the mean creatinine on days 1 through 6 were significantly less in patients treated with T10B9.1A-31. Biopsy specimens analyzed for rejection revealed no significant difference between the T10B9.1A-31 and OKT3 cohorts. The mean serum creatinines at 30, 60, 180, and 360 days posttransplantation were the same for both groups. Significantly fewer febrile, respiratory, and untoward effects followed the first dose (day 0) and fewer febrile, gastrointestinal, and neurological side effects occurred with subsequent doses (days 1-9) in patients treated with T10B9.1A-31. Infectious complications occurred in 3/13 patients treated only with T10B9.1A-31, in 9/17 OKT3-treated patients, and in 4/8 patients treated with both mAb. Analysis of human antimouse antibody (HAMA) revealed that the development of HAMA with T10B9.1A-31 was similar to that of OKT3.

Adult

T10B9.1A-31 anti-T-cell monoclonal antibody: preclinical studies and clinical treatment of solid organ allograft rejection.

T10B9.1A-31 is an immunoglobulin Mk (lgMk), CD3b class, murine monoclonal antibody. It is not itself mitogenic, but it partially blocks mitogenesis produced by concanavilin-A, phytohemagglutinin, and a soluble antigen cocktail and is lytic for human peripheral blood T lymphocytes (PB-T) in the presence of fresh autologous human complement and rabbit complement. It reacts with a monomorphic epitope found on all mature PB-Ts that modulates in vitro and in vivo with the CD3/T-cell antigen receptor (TCR) complex, but unlike OKT3, which reacts with CD3 proteins, T10B9.1A-31 reacts with an epitope of the TCR alpha/beta heterodimer. Immunoprecipitation of HPB-ALL with T10B9.1A-31 or OKT3 revealed that T10B9.1A-31 does not react with the 20-to 26-kd polypeptides that compose CD3, and T10B9.1A-31 failed to bind to the PEER cell, which is CD3 gamma/delta positive, TCR alpha/beta negative. Phase 1 clinical trials demonstrated that T10B9.1A-31 caused a rapid decrease in PB-Ts and no toxic effects other than fever, chills, rigors, and transient hypotension. These side effects were absent in methylprednisolone (MP)-pretreated patients. Phase II studies revealed that T10B9.1A-31 reversed steroid refractory acute rejection in three of five renal allografts treated with cyclosporine (CyA) and prednisone (P) maintenance immunosuppression, reversed steroid and polyclonal antisera refractory rejection in three cardiac allograft recipients receiving CyA/P, and attenuated acute rejection in three of three renal patients receiving baseline azathioprine/prednisone (AZA/P) when used as primary therapy. Rerejection was not seen when patients received CyA baseline immunosuppression but was seen in patients maintained on AZA/P OKT3 was efficacious in treating rejection following T10B9.1A-31 therapy. Side effects of T10B9.1A-31 appears to reverse acute rejection crisis effectively in renal and cardiac transplantation with a low incidence of rerejection in CyA-maintained patients and with fewer, milder side effects. Sequential therapy with OKT3 is possible because OKT3 and T10B9.1A-31 are of different isotypes and idiotypes.

Animals

[Sertoli cell secretion].

The article deals with the secretion of Sertoli cells. Different substances they secrete and their role in the testis are described. These cells release a number of factors in their environment, thus creating a local "milieu" and exerting a local control of spermatogenesis in the seminiferous tubules. As target cells for FSH and testosterone, Sertoli cells are also included in a systemic control of spermatogenesis, and because of that, they are necessary for the normal function of the male sex gland.

Animals