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Humans ; Token Economy*

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Drinking*

No abstract available.
Acetaldehyde* ; Disulfiram* ; Ethanol* ; Patch Tests*

T cell activation is a critical event for initiation and regulation of immune responses and inhibitors of such signaling pathways are clinically useful for the treatment of patients received allogratt and autoimmune disease. In the course of screening soil microorganisms from the forest of Cheju island in Korea for new immunosuppressive agent, one of Streptomyces species (CK-95441) was found to produce a new immunosuppressant, tautomycetin which also had antifungal activity. Tautomycetin showed the inhibition of T cell proliferation in murine mixed lymphocyte reaction (MLR) and T cell activation induced by concanavalin A. Tautomycetin also blocked the induction of IL-2 gene expression which was examined in Jurkat TAg cell line in which multiple NFAT-binding sites and minimal IL-2 promoter drive the production of B-galactosidase. Also, the level of inhibition in activation-induced IL-2 receptor expression by tautomycetin was greater than those by cyclosporin A measured by flow cytometry. But, Fas ligand-induced apoptosis in Jurkat cells was unaffected by tautomycetin which was measured by DNA fragmentation assay. These results suggested that tautomycetin will be able to be used as a potent immunosuppressive drug following organ transplantation.

The T cell antigen receptor (TcR) in combination with costimulatory signals triggered by accessory molecules present on the surface of the antigen-presenting cells (APC) regulates the activation and growth of T lymphocytes. Calyculin A and Okadaic acid is known to be an inhibitor of serine/threonine phosphatase and RK-682 specifically blocks functions of tyrosine phosphatase. To investigate roles of these inhibitors in TcR-mediated signaling cascade, chimeric molecule CD8-5 which contains the extracellular and transmembrane domains of the human CD8a molecule and the cytoplasmic tail of TcR 5 chain were stably expressed in Jurkat cell line. CD8-5 chimeric protein induced tyrosine phosphorylation of various cytoplasmic substrates and IL-2 gene expression in a NFAT dependent manner by stimulation with anti-CD8 mAb OKT8 as seen in TcR stimulation. When CD8-5 transfectants were preincubated with Okadaic acid, Calyculin or RK682, they differentially affected tyrosine phosphorylation of signaling mediators including CD8-5 molecule. When Jurkat Tag cell line was used where SV40 T antigen is stably expressed and the expression of p-galactosidase is driven by the multiple NFAT binding sites plus minimal IL-2 promoter, these phosphatase inhibitors -RK682, Calyculin A, Okadaic acid- effectively inhibited IL-2 gene expression at the concentration of 1.2832 x 10 ' M, 3.9924 x 10 M, 7.2707 x 10 M respectively. These results suggested that Okadaic acid, Calyculin or RK682 modulate TcR-proximal as well as TcR-distal signaling events during T cell activation.
Antigen-Presenting Cells ; Antigens, Viral, Tumor ; Binding Sites ; Cell Line ; Cytoplasm ; Gene Expression ; Humans ; Interleukin-2 ; Jurkat Cells ; Okadaic Acid* ; Phosphorylation ; Receptors, Antigen, T-Cell ; T-Lymphocytes ; Tyrosine

No abstract available.
Animals ; Antibiotics, Antifungal/*therapeutic use ; Humans ; Immunosuppression/*methods ; Protein Structure, Tertiary ; T-Lymphocytes/*immunology ; *Transduction, Genetic

The systematic study of products from bacteria and fungi has led to the development of two immunosuppressive drugs, cyclosporin A and FK 506 (tacrolimus) which are useful to suppress adaptive immune responses to the grafted tissue. However, they affect all immune responses indiscriminately and are both toxic to kidneys and other organs. To facilitate the development of immunosuppressor to block the T cell receptor (TcR)-mediated signaling cascade specifically, a novel Jurkat T cell transfectants, JK NFAT-SEAP were generated in which the expression of the secreted alkaline phosphatase (SEAP) is driven by the multiple NFAT binding sites plus minimal IL-2 promoter. Upon stimulation with ionomycin or anti-TcR mAb OKT3 in the presence of PMA, these transfectants secreted high level of SEAP into the medium, which was conveniently analyzed by SEAP analysis. The secretion of SEAP was effectively inhibited by cyclosporin A or FK 506 at the concentration of [10 ' ug/ml], [10 ug/ml] respectively. JK NFAT-SEAP transfectants will provide two major advantages for the development of a novel immunosuppressor. First, analysis of SEAP secreted into the culture medium by SEAP analysis enables us to test a large number of samples within a short period of time. Second, Usage of IL-2 promoter for the expression of SEAP makes us identify bioproducts to target specifically on TcR-mediated signaling pathway.
Alkaline Phosphatase ; Bacteria ; Binding Sites ; Cell Line* ; Cyclosporine ; Fungi ; Interleukin-2 ; Ionomycin ; Kidney ; Mass Screening* ; Muromonab-CD3 ; Receptors, Antigen, T-Cell ; T-Lymphocytes* ; Tacrolimus ; Transplants

OBJECTIVE: Multiple typologies of alcoholics have been studied, such as Jellineck's disease concept classification, Cloninger's neurobiological learning model, Bucker's developmental model, DSM III-B and DSM IV classification, and Babor's multidimensional typology. To study if Babor's typology modification could be used to classify Korean alcoholics, we grouped 95 male inpatient alcoholics into Babor's typology modification. METHODS: This study employed cluster analysis of measures representing several dimensions premorbid risk and vulnerability dependence severity and alcohol-related problems, chronicity and alcohol-related consequences, and comorbid psychopathology. We compared demographic and clinical characteristics among Babor's type A and type B alcoholics and normal control group. RESULTS: Type B alcoholics showed more characteristic symptoms in family history, more childhood behavior problems, earlier onset, more drinking amount, and more dependence severity, more medical, social, physical problems, more life time severity, more depressive, anxiety, hostility, compared with type A alcoholics. The statistically significant variables differentiating three groups(type A, type B, normal control group) were drinking days, dependence severity, lifetime severity, medical, social consequence. Alcohol Use Inventory to Babor s typology of alcoholism was very useful scale differentiating three groups. CONCLUSION: Babor's typology of alcoholism was useful for classification of inpatient alcoholics of Korea. It can be helpful and applicable to clinical diagnosis and research in Korean alcoholic patients.
Alcoholics ; Alcoholism ; Anxiety ; Classification ; Diagnosis ; Drinking ; Hostility ; Humans ; Inpatients ; Korea ; Learning ; Male ; Psychopathology