Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerogen-specific alloreactivity, in the form of mixed lymphocyte responses and cell mediated lympholysis, was measured in vitro using lymphocytes from mice that received neonatal inoculations of H-2 semiallogeneic hematopoietic cells. It was found that depletion of specific alloreactivity, as detected by these assays, was discernable within the thymus glands within 24 to 48 hr of injection. Reduced in vitro alloreactivity was also apparent among spleen cells obtained from neonatally injected mice that had matured immunologically (8 weeks of life). In mice that accepted their test skin allografts (in vivo evidence of tolerance), tolerogen-specific activity was essentially undetectable in vitro. Unexpectedly, markedly attenuated MLR and CML activity was the characteristic finding in neonatally injected mice that rejected their test grafts (in vivo evidence of lack of tolerance). Thus, in vitro assays failed to be predictive of the in vivo tolerant state. These results indicate that clonal reduction of tolerogen-reactive cells is an expected and persistent consequence of the injection of tolerance conferring inocula into neonatal mice. Moreover, we believe that the state of tolerance is maintained in adult tolerant mice by mechanisms that cannot easily be studied or predicted by the results of in vitro assays.
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PMID:Failure of in vitro assays to predict accurately the existence of neonatally induced H-2 tolerance. 252 80

Investigating HLA-A, HLA-B, HLA-C, and HLA-DR antigens, MLR, CML, and PLT reactivity in two unrelated persons it was found that despite their HLA-D/DR identity cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the necessary proliferative impetus for the generation of CTL.
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PMID:HLA-D/DR identity results in a positive CML reaction. 265 91

In vivo administration of an anti-interleukin-2 (anti-IL-2) receptor monoclonal antibody is a potential new therapy for prevention of allograft rejection of a freshly transplanted organ. Such an approach is more selective than targeting all T cells, or even the CD4 or CD8 major subsets, because only the very recently activated cells should be affected. A clinical trial of anti-Tac monoclonal antibody is in progress in which 20 mg of the immunoglobulin G 2a (lgG2a) antibody is administered intravenously daily for 10 days after cadaveric renal transplantation. Combinations with and without azathioprine, and with varying doses of cyclosporine with prednisone, are being evaluated in a randomized trial. Results to date show a significant immunosuppressive effect of anti-Tac, as measured by a reduced incidence and later onset of acute rejection episodes compared with cyclosporine plus prednisone or cyclosporine plus azathioprine plus prednisone. Removal or cytodestruction of IL-2-receptor positive cells from the peripheral blood does not occur to any major degree, even though serum levels of the antibody are always detectable. In addition, functional studies of MLR, CML, and suppressor cell generation 4 days after cessation of anti-Tac administration show no significant difference between treated and control groups The effect of anti-Tac seems, therefore, to be limited to inhibition of IL-2-mediated T-cell growth during the period of administration, with recovery after a few days' lag period.
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PMID:Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation. 268 58

Cianidanol (Ci) [(+)-catechin] is a lipophilic compound which interacts with membrane lipids and affects responsiveness and function of immunocompetent cells. We therefore studied the immunomodulating properties of Ci on the proliferative response of human peripheral T-cells in one-way mixed lymphocyte reaction (1-MLR) and autologous mixed lymphocyte reaction (AMLR); on the generation of cytotoxic T-cells (Tc-cells), suppressor T-cells (Ts-cells, comprising radiosensitive as well as radioresistant suppressor T-cells) and radioresistant suppressor T-cells (rrTs) in 1-MLC; and on the cytolytic activity of Tc-cells and K-cells. In 1-MLR we observed a small stimulation of cell proliferation at Ci concentrations up to 108 microM whereas higher concentrations led to a marked suppression (100% at 435 microM). The generation of Ts-cells and rrTs-cells in 1-MLR was clearly suppressed at Ci-concentrations above 435 microM and 108 microM, respectively. The timing of Ts-cell formation was not influenced. The Tc-cell generation in 1-MLR was inhibited at high doses, and at 870 microM 59% suppression was observed. A similar dose-dependent suppressive effect of Ci was seen by testing for the cytolytic activity of ADCC-reactive K-cells and of CML-reactive Tc-cells generated in 1-MLR in the absence of Ci. At the highest concentration used (870 microM) the CML was suppressed by 45% and the ADCC by 46%. Our investigation on Ci's influence on the efferent and afferent part of immune responses in vitro demonstrated both stimulatory and inhibitory effects usually occurring at low and high concentrations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunomodulating properties of cianidanol on responsiveness and function of human peripheral blood T-cells and K-cells. 297 31

We report here the results of a phase I clinical trial using counterflow centrifugal elutriation (CCE) for the removal of donor T lymphocytes before allogeneic bone marrow transplantation (BMT). Thirty-eight patients received lymphocyte-depleted allografts from HLA-identical, MLR-nonreactive sibling donors. The patients entered onto the study were either at high risk on the basis of age (median, 39 years) or disease status (acute leukemia in early relapse [ER], chronic myelogenous leukemia [CML] in accelerated phase [AP], or therapy resistant [RES] lymphoma). All patients received a standard lymphocyte dose of 1 x 10(6) morphologic lymphocytes per kilogram ideal body weight (BW) and were maintained on cyclosporine A (CsA) for 170 days after BMT. Prompt engraftment occurred in 37 of 38 patients with a median time to absolute neutrophil count (ANC) greater than 500/microL of 18 days. Although acute graft-v-host disease (GVHD; clinical stage I or greater) was observed in 45%, it was limited to the skin in all but five patients. Survival was related to disease status at the time of BMT. Among patients with acute leukemia in first or second remission, CML in chronic phase (CP) or lymphoma in partial remission (PR), 64% are currently alive, in contrast to 31% of patients with acute leukemia in third remission or early relapse, CML in second CP or AP, or RES lymphoma. Median follow-up for all patients was 351 days (range, 105 to 711 days). We conclude that this procedure is safe and warrants further evaluation in a randomized efficacy trial.
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PMID:Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial. 304 36

There is now overwhelming evidence that preoperative donor specific blood transfusions (DST) improve kidney graft survival remarkably. However, the exact mechanism is as yet unknown. In this study, we compared a DST group with a non-DST and investigate the mechanism of the beneficial effect of DST by using MLR, CML, and the MLR inhibition test. In the DST group, the severity of acute rejection and MLR reactivity was decreased after DST in most cases, but there was no such tendency in CML reaction. In the MLR inhibition test, the MLR serum inhibitory factor was induced in 70% of the cases (7 out of 10) received 3 times of DST. All of them were directed against recipient cell (auto-lymphocyte) and not to the blood donor cell and its activity was found in IgG fraction. The specificity to the stimulator cell was also found in 43% (3 out of 7). The results of MLR inhibition tests were well correlated with clinical findings and changes of MLR and CML. In positive cases of MLR inhibition tests, acute rejection occurred in 14% (1 out of 7), CML decreased in all (3 out of 3) and MLR decreased in 83% (5 out of 6) after DST. On the contrary, in negative cases, acute rejection occurred in 67% (2 out of 3), CML increased in all (3 out of 3) and MLR increased in 67% (2 out of 3). These results suggested that antibodies directed against recognition sites on auto-lymphocytes, so called anti-idiotypic antibodies, will be induced by 3 DST and play an important role in the prolongation of graft survival.
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PMID:[Immunological analysis of mixed lymphocyte culture reaction inhibitory factor induced by donor specific blood transfusions in potential kidney transplant patients]. 315 45

Investigating HLA-A, -B, -C, -DR and -Dw antigens and MLR, CML, and PLT reactivity in two unrelated persons, it was found that, despite their HLA-D/DR identity, cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the proliferative impetus for the generation of CTL.
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PMID:HLA-DP antigens provide the proliferative impetus for the generation of cytotoxic T lymphocytes. 326 48

RNA was extracted from placentae of synpregnant C3H mice (day 14 of gestation) and from A6B9IC5 teratocarcinoma. After isolation of poly-(A)+ RNA on an oligo d(T) cellulose column, putative messenger RNA was injected into Xenopus laevi oocytes. Supernatants and homogenates from the oocytes were assayed for immunoregulatory activity in MLR, CML, and NK assays and found to be immunosuppressive. These data indicate that immunomodulators could be obtained from the placenta by molecular biology technology in sufficient quantities for eventual clinical applications.
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PMID:Immunoactive products of placenta: VIII. Translation products of messenger RNA extracted from murine placenta or A6B9IC5 teratocarcinoma are immunosuppressive in vitro. 406 27

A quantitative serological difference was found between strains Hz1 and M505 carrying mutant H-2 haplotypes ba and bd, respectively, and the original strain B6(H-2(b)). The finding suggests that the mutations occurred in the H-2K(b) gene, and together with data on MLR and CML challenges the current concept of H-2 regions' involvement in immune reactions.
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PMID:Serological distinction of mutants B6.CH(zl) and B6.M505 from strain C57BL-6. 413 24

Human NK activity is radiosensitive under the control of X-linked genes. We have evaluated the expression of these genes in other forms of cellular cytotoxicity. The NK radioresistant and radiosensitive phenotype is expressed in ADCC. Specific cellular cytotoxicity, generated in a MLC with a radiosensitive donor as responder, was radioresistant. NK-like activity recruited from nonadherent cells of radiosensitive subjects stimulated with allogenic cells, mitogens (PHA, Con A or PWM), or recall antigens (TT or PPD) was radioresistant. The acquisition of radioresistance was relatively rapid, beginning within 24 hr after exposure to PHA, prior to detectable proliferation. Radioresistance of MLR augmented NK-like activity was maximal 3 days after initiation of the culture. MLR augmented NK-like activity was spared by the immunosuppressive polypeptide antibiotic CsA at doses up to 1 micrometer/ml. CsA did, however, reduce acquisition of radioresistance by the NK-like activity at doses above 0.01 mu gm/ml, a concentration which does not inhibit uptake of 3H-thymidine but does reduce the level of specific CML. These data suggest that mitogens and antigens, including allogeneic cells, are recruiting radioresistant NK-like activity which can be distinguished from the radiosensitive spontaneous NK activity of the cell donor. Further, in the MLR, both radiosensitive and radioresistant NK-like activity may be recruited.
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PMID:Radioresistance of culture-induced augmented natural killer-like activity. 619 19


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