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排序方式: 共有260条查询结果,搜索用时 15 毫秒
1.
Yoshikuni Kudo Toru Egashira Fusako Takayama Yasumitsu Yamanaka Tatsuo Shimada 《Archives of toxicology》1993,67(7):502-509
To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum -glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl--d-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion. 相似文献
2.
Yoshinori Naoe Masamichi Inami Ikuo Kawamura Fusako Nishigaki Susumu Tsujimoto Sanae Matsumoto Toshitaka Manda Kyoichi Shimomura 《Cancer science》1998,89(6):666-672
FK317 is a member of a new class of bioreductive agents that exhibit strong cytotoxicity against various human cancer cells. The effect of FK317 was found to be stronger than that of mitomycin C (MMC), adriamycin (ADR) or cisplatin (CDDP). Alkaline elution analysis indicated that FK317 formed interstrand DNA-DNA and DNA-protein cross-links in cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK317. In a cell-free system the deacetylated metabolites produced cross-linked DNA under reductive conditions, though FK317 itself did not form DNA-DNA cross-links. In order to elucidate the metabolic activation mechanisms, we established an FK317-resistant subline from human non-small cell lung cancer cells (Lu99) by stepwise and brief exposure (1 h) to FK317. The resistant subline (Lu99/317) showed cross-resistance to MMC and carboquone (CQ), but not to ADR or CDDP. DT-diaphorase, which is one of the activation enzymes of MMC and CQ, was deficient in Lu99/317 cells as determined by enzyme activity assay. However, the levels of NADPH:cytochrome P450 reductase, which is another activation enzyme for MMC and CQ, were comparable in resistant and parent cell lines. Treatment of the cells with dicumarol, an inhibitor of DT-diaphorase, reduced the cytotoxicity of FK317 to Lu99 cells, but not to Lu99/317 cells. These results indicate that deacetylation of FK317 is necessary for its reductive activation, and deacetylated FK317 is reduced by DT-diaphorase to form an active metabolite, which produces DNA-DNA interstrand and DNA-protein cross-links that lead to cell death. 相似文献
3.
Tomoka Tabata Yuki Kuramoto Tomohito Ohtani Hiroshi Miyawaki Yohei Miyashita Fusako Sera Hidetaka Kioka Shuichiro Higo Yoshihiro Asano Shungo Hikoso Yasushi Sakata 《Internal medicine (Tokyo, Japan)》2022,61(13):1987
Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients. 相似文献
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To examine the role of thyroid hormones in the seasonal breeding cycle in Japanese monkeys (Macaca fuscata fuscata), sexually mature females were thyroidectomized (n=6) in early December, during the midbreeding season, or they received sham operations (n=4). They were housed indoors individually, and blood samples were collected two to three times a week to monitor gonadotropin
and gonadal steroid hormone secretions. Control monkeys exhibited ovulatory cycles during the breeding season. The mean dates
of onset and end of the ovulatory cycles were October 22±13 d and February 25±14 d, respectively. These dates coincided well
with those of our colonies under captivity. By contrast, three of the six thyroidectomized monkeys terminated ovulatory cycles
immediately after operations; the remaining three monkeys ovulated only once or twice after thyroid removal. The mean dates
of onset and end of the ovulatory cycles of thyroidectomized monkeys were October 18±4 d and December 31±4 d, respectively.
This was a significantly earlier termination of the ovulatory cycles than in controls. Mean concentrations of plasma thyroxine
of control monkeys were maintained throughout the experimental period, whereas plasma thyroxine concentrations of thyroidectomized
monkeys decreased abruptly to undetectable levels. Thyroidectomized monkeys exhibited significantly higher levels of plasma
prolactin (PRL) than controls. Moreover, even in control monkeys, plasma PRL increased during the transition out of the breeding
season. These results suggest that thyroid hormones play an important role in the regulation of ovulatory cycles in Japanese
monkeys, directory or indirectly, possibly by mediating the changes of PRL secretion. 相似文献
6.
Kenneth F. Hossack Robert A. Bruce Fusako Kusumi Toshiko Kannagi 《The American journal of cardiology》1983,52(7):721-726
Of 100 patients (89 men, 11 women) studied preoperatively to determine their aerobic and hemodynamic profiles at rest and during upright treadmill exercise. The mean maximal cardiac output (CO), measured using the direct Fick principle, was 57 ± 14% of average normal values. The reduction in maximal heart rate (63 ± 13% of normal) was a greater factor in the reduction in CO than stroke volume (88 ± 16% of normal). Maximal oxygen consumption (V?O2max) was 48 ± 15% of normal and the greater reduction in V?O22max compared with CO was due to lower peripheral extraction in the coronary patients. Variables that correlated with maximal CO in a univariate analysis included angina severity (r = ?0.45), V?O22max (r = 0.67), maximal heart rate (r = ?0.31), left ventricular dysfunction (r = ?0.45), maximal systolic blood pressure (r = ?0.31) and number of vessels with ≥ 50% diameter reduction (r = ?0.3). Resting ejection fraction did not correlate with maximal CO. In a multivariate analysis, 4 variables correlated significantly (r = 0.77) with maximal CO: in order, V?O22max, number of vessels with ≥ 50% stenosis, magnitude of ST depression and sex. 相似文献
7.
Differential effects of FK506 and methotrexate on inflammatory cytokine levels in rat adjuvant-induced arthritis 总被引:4,自引:0,他引:4
Magari K Miyata S Nishigaki F Ohkubo Y Mutoh S Goto T 《The Journal of rheumatology》2003,30(10):2193-2200
OBJECTIVE: To investigate the effects of prophylactic and therapeutic treatments with FK506 (tacrolimus), an immunosuppressive drug that specifically inhibits T cell activation, and methotrexate (MTX) on inflammatory cytokines, tumor necrosis factor (TNF)-a, interleukin (IL)-1beta, and IL-6 levels in rat adjuvant-induced arthritis (AIA). METHODS: AIA was induced in female Lewis rats. Arthritis was assessed by hindpaw swelling. TNF-a, IL-1beta, and IL-6 levels in paw extracts were determined by ELISA. To assess the effects on cytokine levels, rats were treated prophylactically with FK506 (3 mg/kg) or MTX (0.1 mg/kg) from day 1 to day 17, and therapeutically with FK506 (5 mg/kg) or MTX (1 mg/kg) from day 15 to day 17 (3-day treatment) or day 15 to 20 (6-day treatment) by oral administration. RESULTS: TNF-a, IL-1beta, and IL-6 levels in paw tissue were found to significantly increase between day 15 and day 21 after adjuvant injection, when the arthritis was in a developed stage. Prophylactic treatment with FK506 and MTX suppressed arthritis and reduced the levels of those inflammatory cytokines. FK506 caused a marked reduction of TNF-a and IL-1beta levels in paw tissue even in short-term (3-day) therapeutic treatment. It reduced all levels of TNF-a, IL-1beta, and IL-6 in paws in 6-day therapeutic treatment. In contrast, therapeutic treatment with MTX affected neither TNF-a or IL-6 levels in paws. MTX reduced IL-1beta levels only in the 6-day treatment. CONCLUSION: FK506 is more effective than MTX in reducing elevated levels of inflammatory cytokines TNF-a, IL-1beta, and IL-6 in established stages of AIA. Our findings suggest that inhibition of T cell activation results in a rapid reduction of inflammatory cytokine levels even after the arthritis is established in AIA. 相似文献
8.
9.
Niwa F Kawai M Kanazawa H Iwanaga K Matsukura T Hasegawa T Heike T 《Clinical endocrinology》2012,77(2):255-261
Background For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important. Methods To address the above two issues, we performed thyrotropin‐releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less. Results For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10–15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10–15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later. Conclusions Thyrotropin‐releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic–pituitary–thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation. 相似文献
10.