Heterogeneous distribution of the determinants defined by monoclonal antibodies on HLA-A and B antigens bearing molecules.
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Biomedical subjects
Publications and source records attributed to C Russo.
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Rabbits were immunized with hybrids constructed with human and murine cells. Serological and immunochemical studies showed that xenoantiserum 1595 is operationally specific for HLA-A2, xenoantisera 0806 and 0746 for HLA-A3 and xenoantiserum 0745 for HLA-B27. The Fab2 blocking assay suggests a spatial relationship between allotypic determinants recognized by the xenoantisera and those reacting with the HLA-A, B-specific monoclonal antibodies (MoAb) Q1/28, 6/31, Q6/64, and CR-1 and the anti-beta 2-microglobulin (beta 2-mu) MoAb NAMB-1.
Human T lymphocytes activated with PHA express Ia-like antigens and acquire the ability to stimulate autologous T lymphocytes in mixed lymphocyte reaction. This reaction is immunological in nature since it has specificity and memory. Ia-like antigens play a role in the stimulation of T lymphocytes by autologous PHA-T lymphocytes since monoclonal antibodies to Ia-like antigens can significantly, although not completely, inhibit the stimulation.
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Human null cells were isolated from peripheral blood lymphocytes (PBL) by differential centrifugation on a Ficoll-Hypaque gradient of the PBL following simultaneous rosetting with erythrocyte indicators specific for B and T lymphocytes. Specifically, the T lymphocytes were rosetted with 2-aminoethylisothiuronium bromide-treated sheep erythrocytes (ShE), whereas the B lymphocytes were either rosetted with ShE coated with xenoantibodies against human gamma globulin or first sensitized with monoclonal antibodies to human Ig-like antigens and then rosetted with ShE coated with xenoantibodies against mouse gamma globulin. Approximately 90% of the lymphocytes isolated were null cells that did not bear detectable B-cell markers-that is, surface immunoglobulin and/or Ia-like antigens-or T-cell markers-that is, ShE receptors. The large majority of the null cells expressed receptors for the IgG Fc fragment (53-93%), C3 component (65-92%) and monkey erythrocytes (60-91%) but lacked receptors for the IgM Fc fragment and murine erythrocytes. The null cells exhibited high natural killer cell activity and antibody-dependent cellular cytotoxicity and were two- to four-fold active than the total PBL and the T-enriched cell fractions. The null cells, however, did not respond to stimulation with phytohaemagglutinin and failed to function as either stimulators or responders in an unidirectional mixed lymphocyte reaction.
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The purpose of this study is to see if immunotherapy with C. parvum and prevention of central nervous system relapse with intrathecal methotrexate can prolong duration of complete remission and survival as well as avoid central nervous system relapse. For induction, three weekly I.V. injections of vincristine and Daunorubicin were given with daily prednisone orally, followed by 5-day courses of Cytosine Arabinoside and 6-mercaptopurine. The patients were randomized to chemotherapy or chemoimmunotherapy. Maintenance consisted of vincristine, Daunorubicin, and prednisone one week every odd month, and a 5-day course of Cytosine Arabinoside and 6-mercaptopurine every even month. Every week, the chemoimmunotherapy group also received, without chemotherapy, one injection of C. parvum 4 mg, subcutaneously. All patients received five weekly injections of intrathecal methotrexate 13 mg/m2 right after complete remission was achieved. Out of 181 evaluable cases, 80 (44%) achieved complete remission, 45 were randomized to chemotherapy, and 35 to chemoimmunotherapy. In the chemoimmunotherapy group 32/35 relapsed, and in the chemotherapy group 36/45. Median duration of complete remission and survival were: for group chemotherapy, 8 and 15 months; for group chemoimmunotherapy, 5 and 10 months. This difference is not significant. Intrathecal methotrexate was given to all patients. Six patients (7%) had central nervous system leukemia at the time of the first injection. None had central nervous system relapse after prevention with intrathecal methotrexate. This method seems useful in preventing central nervous system relapse in patients with acute myeloblastic leukemia, but does not seem to prolong complete remission.
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Serological and immunochemical studies showed that monoclonal antibody Q2/70 (MoAb Q2/70), produced by the hybridoma technique, is specific for human Ia-like antigens. This antibody recognizes an antigenic determinant which is different from those defining the serologic polymorphism of Ia-like antigens, and is expressed on subsets of human Ia-like molecules and on lymphoid cells from other species. MoAb Q2/70 inhibits unidirectional MLRs* between allogenic human lymphocytes, but not between murine and human lymphocytes. In ADCC* assays. MoAb Q2/70 mediates lysis of cultured human B lymphoid cells RPMI 4098, effected by murine splenocytes. The antibody is suitable to isolate immunologically functional B lymphocytes from human peripheral blood.
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