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11.
T Someya M Shibasaki T Noguchi S Takahashi T Inaba 《Journal of clinical psychopharmacology》1992,12(3):169-174
In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism. 相似文献
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The effect of single or combined coaxial exposure by Nd: YAG and CO2 (pulse wave) laser on the brain at the subacute stage was examined in experimental animals. Soft X-ray microangiography and histological examination of the brain were performed 48 hours after laser exposure. The lasers in this study were pulse wave form CO2 of 2, 4 and 8 watts and YAG lasers of 10, 20 and 40 watts, employed separately or simultaneously using 130 YZ of Nihon Infrared Industries Company. Japanese white rabbits were anesthetized with pentobarbital. Bilateral fronto-parietal craniectomy were made, and the dura was removed. After intravenous injection of Evans blue, the lasers were employed to the cerebral cortex using a micromanipulator attached to the operation microscope. The spot size was 0.7 mm in diameter for CO2 laser and 1.2 mm for Nd: YAG laser. Forty-eight hours after exposure, microangiography was performed and brains were prepared for the histological examination. Histological examination and microangiogram of the brain after CO2 laser exposure revealed semilunar avascular area in the edematous layer surrounded with dilated vessels. Histological examination and microangiogram of the brain after Nd: YAG laser exposure revealed broad avascular or oligovascular zones in the surrounding edematous tissue, in which the surviving vessels were narrowed. Edematous zones were also shown in the subcortical portion. The histological examination and microangiogram after combined coaxial exposure of CO2 and Nd: YAG lasers revealed triangular avascular or oligovascular zones in the edematous tissue, in which the surviving vessels were narrowed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new antiinflammatory agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs. 相似文献
16.
Hiromitsu Matsuzaki Hiroyuki Hata Norio Asou Minoru Yoshida Fumihiko Matsuno Motohiro Takeya Kazunari Yamaguchi Isao Sanada Kiyoshi Takatsuki 《Cancer science》1992,83(5):450-457
A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-l. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC. 相似文献
17.
Norihiro Ishida Koji Hayashi Asuka Hattori Keiichiro Yogo Toru Kimura Tatsuo Takeya 《Journal of bone and mineral research》2006,21(1):48-57
We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts. 相似文献
18.
F Ichida A Yoshikawa M Mizokami M Yamamoto N Inaba H Takamizawa T Ohmura A Ohmizu J Ohata Y Uemura 《The Journal of international medical research》1988,16(3):231-236
The efficacy and safety of a recombinant yeast-derived hepatitis B vaccine were evaluated in 209 subjects after three administrations at 0, 4 and 20 weeks. Subjects were divided into four groups given 5 micrograms vaccine subcutaneously, 10 micrograms subcutaneously, 10 micrograms intramuscularly and 20 micrograms subcutaneously to define the effective dose and to compare the effect of administration. Seroconversion of the antibody to hepatitis B surface antigen after the third vaccination reached 96.6% in the group given 5 micrograms vaccine subcutaneously and 100% in the other groups. The final geometric mean antibody titres were 700 IU/l in subjects given 5 micrograms subcutaneously, 2004 IU/l in those given 10 micrograms subcutaneously, 4674 IU/l in those given 10 micrograms intramuscularly and 3342 IU/l in those given 20 micrograms subcutaneously. In the groups given 10 micrograms, the early seroconversion rate of the antibody to hepatitis B surface antigen and the geometric mean antibody titres after the third vaccination were significantly higher in subjects administered intramuscularly than subcutaneously (P less than 0.05). No major adverse effects were observed and minor reactions were the same as, or less than, those reported for the plasma-derived vaccine. Before and after administration, no significant fluctuation in the yeast antibody titre was observed. These results demonstrate the efficacy and safety of the yeast-derived vaccine, and show that 10 micrograms was the effective dose. 相似文献
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Analyses of T-cell differentiation from hemopoietic stem cells in the G0 phase by an in vitro method. 总被引:1,自引:0,他引:1 下载免费PDF全文
J Toki T Kumamoto H Ogata M Kawamura M Fukumoto Cherry Y Yamamoto S Than M Inaba Y Himeno et al. 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(17):7548-7551
Using differential radiation sensitivity of components of mouse embryonal thymus, an in vitro method for studying T-cell differentiation from hemopoietic stem cells (HSCs) in the G0 phase was established. Intrathymic T-cell precursors present in embryonal thymus were found to be quite radioresistant (up to 20 Gy), and consequently 25-Gy-irradiated embryonal thymic lobes were used. Thymic lobes (25-Gy irradiated) taken from mouse fetuses (gestation day 15) were placed in Millipore-HA culture plates supported on squares of gelatin foam sponge in 24-well culture plates in which neonatal thymus stromal cells were cultured. HSCs (10(5) cells per well) in the G0 phase were added to these thymic lobes and cocultured at 37 degrees C in a 5% CO2/95% air incubator. Half the culture medium was changed every week. After 3 weeks, a large number of colonies had formed. Immunohistochemical studies and fluorescence-activated cell sorter analyses revealed that the colonizing cells regularly develop and exhibit surface markers characteristic of T cells (Thy-1, IL-2R, L3T4, Lyt-2, etc.). In situ hybridization analyses revealed that mRNA expression for T-cell receptor (TCR) beta chains occurred within colonizing cells. Using a monoclonal antibody (F23.1), expression of TCR beta-chain variable domain (V beta 8) on the surface of these developing T cells was demonstrated. These cells responded to interleukin 2 and/or anti-CD3 monoclonal antibody, indicating functional T cells. This method will be useful in studying T-cell differentiation pathways from pluripotent HSCs and in clarifying the mechanisms involved in negative and positive selection of T cells within the thymus. 相似文献