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141.
R.S.K. Chaganti Roller B. Bailey Suresh C. Jhanwar Zalmen A. Arlin Bayard D. Clarkson 《Cancer Genetics and Cytogenetics》1982,5(3):215-221
Malignancy in patients with constitutional chromosome abnormality is of interest not only because it permits insights into the relationship between chromosome abnormality and cancer, but also because it provides opportunities to address such questions as the clonality and evolution of tumors. We report Ph1-positive chronic myelogenous leukemia (CML) in a 50-year-old mosaic (45,X/46,XX) Turner syndrome patient whose leukemia was restricted to the monosomic cell line. Our extensive cytogenetic studies of this patient demonstrated that non-leukemic normal cells persisted in the marrow and were able to proliferate during a period of temporary suppression of the leukemic clone following aggressive treatment. 相似文献
142.
Tarner IH Nakajima A Seroogy CM Ermann J Levicnik A Contag CH Fathman CG 《Clinical immunology (Orlando, Fla.)》2002,105(3):304-314
Rheumatoid arthritis (RA) is an autoimmune arthritis, for which treatment options remain limited. This study investigated the potential role of adoptive cellular gene therapy as a novel means for treating the RA animal model collagen-induced arthritis (CIA). Adoptive transfer of antigen-specific T-cell hybridomas retrovirally transduced to express IL-4 1 day before booster immunization significantly reduced the number of inflamed joints. Cell transfer after clinical onset of disease had no therapeutic effect. Bioluminescence imaging showed that the hybridomas migrated to the inflamed joints, thus delivering the regulatory protein locally at the site of inflammation. The homing was, at least in part, due to chemotaxis in response to proinflammatory chemokines that are expressed in inflamed joints. There were no significant changes in the cytokine milieu of the draining lymph nodes, nor in the systemic levels of anti-collagen antibodies in treated mice. We conclude that the beneficial clinical effects observed in our model were most likely based on the local action(s) of IL-4 in the inflamed joints and that the local delivery (and effects) of regulatory cytokines, like IL-4, constitutes a novel and effective method of preventing organ-specific autoimmune disease and of minimizing systemic adverse effects. 相似文献
143.
Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment. 总被引:12,自引:2,他引:12 下载免费PDF全文
W B van den Berg L A Joosten M Helsen F A van de Loo 《Clinical and experimental immunology》1994,95(2):237-243
Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis. To validate a key role for IL-1 in arthritic processes we have studied the protective effect of neutralizing antimurine IL-1 antibodies in the murine collagen-induced arthritis (CIA) model. Combination of anti-IL-1 alpha and anti-IL-1 beta given before onset of arthritis was shown to prevent disease completely. Remarkably, a single treatment was also highly effective in the established phase of arthritis, reducing both inflammation as well as cartilage destruction. Suppression was most pronounced with the combination, but anti-IL-1 beta alone also induced significant relief. Finally, we studied the protective effect of IL-1 neutralization on cartilage metabolism in a unilateral expression model of collagen arthritis. To this end zymosan was injected in one knee joint before onset of disease, resulting in accelerated expression in that particular joint and the draining paw. Anti-IL-1 treatment started after accelerated expression of arthritis was able to fully normalize chondrocyte synthetic function, which was highly suppressed in the control group. It is concluded that IL-1 is an important determinant in both inflammation and cartilage destruction in collagen arthritis, and this may have implications for therapy in human arthritis. 相似文献
144.
Functional mapping of the activity of the R region in the human T-cell leukemia virus type I long terminal repeat to increase gene expression 总被引:3,自引:0,他引:3
We previously demonstrated the activity of the R fragment in the long terminal repeat of human T-cell leukemia virus type I for elevation of the level of gene expression. In this study, the fragment was deleted with BAL31 nuclease to determine its functional domain. Series of the shortened R fragments were linked to the simian virus 40 promoter unit, which regulated expression of a reporter gene. Examination with the R fragments deleted from the 5 and 3 ends showed that borders of the functional domain were mapped within nucleotide positions 458 to 473 for the 5 end and nucleotide positions 559 to 594 for the 3 end, respectively. Thus we conclude that a 136-base-pair fragment corresponding to the second half of the R region was sufficient to allow elevation of the level of gene expression. 相似文献
145.
采用半固体一步单层琼脂培养法和单克隆荧光抗体技术分别观察重症肝炎外周血TL-CFU和mIL-2R,发现重症肝炎患者TL-CFU(104.4±32.6)及mIL-2R(35.6±8.6)较正常人明显降低。在培养体系中加胎肝细胞质液后,无论在重症肝炎组还是在正常组均不能明显地提高TL-CFU,说明胎肝细胞质液不含具生物佐的促TL-CFU因子。但对mIL-2R表达的影响,在重症肝炎组病人,只有在PHA存在条件下才能促进mIL-2R的表达,说明胎肝细胞质波含有某种(些)物质能协同PHA促进重症肝炎患者外周血淋巴细胞mIL-2R表达。 相似文献
146.
147.
In the present study, we describe the potential role of melatonin, a pineal hormone, in regulating the activation of the antigen-specific T cell response. Melatonin encouraged the proliferation of Th cells and improved their ability to secrete IL-4, but down-regulated the levels of IL-2 and interferon-gamma (IFN-γ). Melatonin, however, could not exert any influence on the T cells of unprimed mice. On studying the regulation of subclass of IgG isotype, melatonin specifically enhanced the secretion of antigen-specific IgG1 antibodies and decreased the yield of IgG2a isotype. The results suggest that melatonin possibly acts by selectively activating a Th2-like immune response. 相似文献
148.
Nelson K. S. Khoo Francis P. H. Chan Mary Nel Saarloos Peeyush K. Lala 《Clinical & experimental metastasis》1992,10(4):239-252
In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E2 (PGE2)mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 ,g/ml of water) or Indo (CIT; 10 g/ml) 5 days after s.c. transplantation of 5 × 105 metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 g/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1+, Thy-1–, Lyt-2– phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20–23, 31–34) of IL-2 (15 000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1+, Thy-1–, Lyt-2–); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1+, Thy-1+ and Lyt-2+ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu + IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE2 synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT. Thus, Ibu proved to be an excellent substitute for Indo in preventing metastasis and NK cell activation when given alone, and also in ameliorating established metastasis and activating lymphokine-activated killer cells when combined with IL-2. 相似文献
149.
Chemically induced mutants of an I-Ak,d expressing antigen-presenting B-cell--B-lymphoma hybridoma have recently been generated by immunoselection in vitro and were found to possess alterations in some of their serologically and functionally defined I-Ak region dependent functions. In order to identify at the structural level the origin of the differences in serological and functional properties of these mutants, I-Ak molecules from several of these mutant hybridomas were compared biochemically to wild-type I-Ak polypeptides by two-dimensional gel electrophoresis and high-pressure liquid chromatographic tryptic peptide analyses. Two-dimensional gel electrophoresis indicated that no major structural alterations, resulting in changes in mol. wt or charge, had occurred in the Ak alpha or Ak beta polypeptides from the mutant cells. Likewise, Ak alpha peptide maps of the mutants were indistinguishable from the normal Ak alpha peptide maps. However, two of the three mutants studied did exhibit one additional peptide in their Ak beta peptide maps. These results suggest that the major deficiencies in T-cell-activating functions of these mutants are a result of a limited alteration in the Ak beta polypeptide primary structure. 相似文献
150.
Increased c-Fos/activator protein-1 confers resistance against anergy induction on antigen-specific T cell 总被引:1,自引:0,他引:1
Kawasaki H Nakata Y Suzuki G Chihara K Tokuhisa T Shiozawa S 《International immunology》1999,11(12):1873-1880
We have studied the contribution of c-Fos/activator protein-1 (AP-1) to antigen-specific T cell response with reference to T cell anergy by increasing c-Fos/AP-1 in vivo and in vitro. First, after injection of a high dose of staphylococcus enterotoxin B (SEB), clonal deletion of SEB-reactive V(beta)8(+) CD4 T cells occurred both in control B6 and H2-c-fos transgenic (fos) mice, whereas proliferation of T cells against SEB was profoundly depressed in B6 but not in fos mice. Second, the keyhole limpet hemocyanin-specific CD4 T(h)1 cell clone produced decreasing amounts of IL-2 in response to increasing amounts of concanavalin A (Con A) in vitro, whereas the decrease was less significant in the T(h)1 clones stably transfected with c-fos gene. Electrophoretic mobility shift assay with nuclear protein from the transformants showed that overexpression of the c-fos gene compensated the amounts of AP-1 in the nuclei of Con A-treated T(h)1 clones. Thus, increased c-Fos/AP-1 confers resistance against anergy induction on antigen-specific T cells. 相似文献