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 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

To acquire good image quality and to minimize unnecessary radiation dose to patients, it is important to ensure that the radiopharmaceutical administered is accurately measured. Quality control of radionuclide calibrators should be performed to achieve these goals. The purpose of this study is to support the quality control of radionuclide calibrators in nuclear medicine centers and to investigate the level of measurement accuracy of the radionuclide calibrators. 58 radionuclide calibrators from 45 nuclear medicine centers, 74 radionuclide calibrators from 58 nuclear medicine centers, and 60 radionuclide calibrators from 45 nuclear medicine centers were tested with I-131, Tc-99m and I-123, respectively. The results showed that 81% of calibrators for I-131, 61% of calibrators for Tc-99m and 67% of calibrators for I-123 were within +/-5%. 17% of calibrators for I-131, 20% of calibrators for Tc-99m and 15% of calibrators for I-123 had a deviation in the range 5%<|delta|< or =10%. 2% of calibrators for I-131, 19% of calibrators for Tc-99m and 18% of calibrators for I-123 had a deviation of |delta|>10%. Follow-up measurements were performed on the calibrators whose error exceeded the +/-10% limit. As a result, some of the calibrator showed an improvement and their deviation decreased below the +/-10% limit. The results have shown that such comparisons are necessary to improve the accuracy of the measurement and to identify malfunctioning radionuclide calibrators.
Dietary Sucrose ; Follow-Up Studies ; Humans ; Nuclear Medicine ; Quality Control ; Radioactivity

OBJECTIVE: To examine the correlation between bone mineral density and intervertebral disc degeneration through retrospective study. METHOD: Bone mineral density (BMD) and Magnetic resonance (MR) image of lumbar spine from 61 postmenopausal women were assessed to examine the correlation between bone mineral density and intervertebral disc degeneration. We determined BMD of lumbar spine using the dual energy X-ray absorptiometry (DEXA). And we evaluated signal intensity of intervertebral disc, disc height and disc herniation at each lumbar disc level using the MR image. The correlation between BMD (mean value of 2nd, 3rd and 4th lumbar spine BMD) and the sum of grading scores of intervertebral disc degeneration was assessed in all the patients. RESULTS: There was a positive correlation between BMD of lumbar spine and the sum of grading scores of intervertebral disc degeneration (r=0.415, p value=0.00087). CONCLUSION: Bone mineral density has an inverse correlation to intervertebral disc degeneration and which is important when considering degenerative spinal disease and osteoporosis.
Absorptiometry, Photon ; Bone Density* ; Female ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration* ; Osteoporosis ; Retrospective Studies ; Spinal Diseases ; Spine