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Y. TAKINAMI H. YUKI A. NISHIDA S. AKUZAWA A. UCHIDA Y. TAKEMOTO M. OHTA M. SATOH G. SEMPLE & K. MIYATA 《Alimentary pharmacology & therapeutics》1997,11(1):113-120
Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [125 I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED 50 value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED 50 values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats. 相似文献
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats. 相似文献
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H. HATA H. MATSUZAKI F. MATSUNO T. SONOKI S. TAKEMOTO N. KURTBAYASHI A. NAGASAKI K. TAKATSUKI 《Clinical and experimental immunology》1994,96(2):370-375
A new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM). established from the pleural of fusion and bone marrow, respectively, of the same patient. Since I2BM expresses CD20, CD38, and PCA-I antigens, while 12PE has lost CD20. 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to 12BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-I expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells. 相似文献
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S. OKA K. OGINO T. HOUBARA S. YOSHIMURA Y. OKAZAKI T. TAKEMOTO N. KATO Y. IIDA T. UDA 《Histopathology》1990,17(3):231-236
The immunohistochemical localization of copper, zinc-superoxide dismutase (Cu,Zn-SOD) in human gastric mucosa and gastric cancer was studied using a monoclonal antibody. In gastric mucosa, parietal cells, pyloric glandular cells and foci of intestinal metaplasia showed positive staining in the cytoplasm and/or nucleus. The wide distribution of Cu, Zn-SOD in the gastric mucosa suggests cell function may be vulnerable to active oxygen species. In gastric cancer, 34 of 70 cases showed a positive reaction for Cu, Zn-SOD. There was a relationship between the grade of Cu,Zn-SOD immunoreactivity and the histological type of gastric cancer, well-differentiated types of gastric cancer being more frequently positive. The positive cases of poorly-differentiated adenocarcinoma were characterized by a pattern of diffusely infiltrative invasion. These results suggest that some types of gastric cancer are resistant to active oxygen species. 相似文献
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Tatsuya FUJINO Makoto NAKAMUTA Yoko AOYAGI Kunitaka FUKUIZUMI Ryosuke TAKEMOTO Tsuyoshi YOSHIMOTO Toshihiko MIYAHARA Naohiko HARADA Hironori SAKAI Manabu NAKASHIMA Munechika ENJOJI 《Journal of digestive diseases》2009,10(1):21-25
OBJECTIVE: Pegylated interferon (PEG‐IFN) plus ribavirin (RBV) combination therapy is now a popular treatment for patients with chronic hepatitis C; however, the reported sustained virologic response (SVR) rate remains at nearly 50% in genotype 1b infected patients. Therefore, it is of clinical benefit to be able to predict the effect of combination therapy on individual patients earlier in the treatment. We estimated the predictive serum HCV core antigen levels for SVR in the early therapeutic stage of combination therapy. METHODS: The HCV core antigen in patients with high‐level HCV viremia, in whom standard PEG‐IFNα2b plus RBV combination therapy had been completed, was measured at baseline and at 3, 7, 14, 28 and 84 days of treatment, and their SVR was determined at 24 weeks after treatment. Sixty genotype 1b‐ and 30 genotype 2‐infected patients were included. RESULTS: Thirty (50%) genotype 1b and 27 (90%) genotype 2 patients achieved a SVR. In genotype 1b patients the decline of HCV core antigen levels was statistically different between the SVR and non‐SVR groups. When we defined a separation level at 500 fmol/L, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for SVR at day 7 was 79.4%, 88.5%, 90%, 76.7%, and 83.3%, respectively. In genotype 2 patients, there was no significant difference in the HCV core antigen values between the SVR and non‐SVR groups. CONCLUSION: In genotype 1b patients, 500 fmol/L of HCV core antigen level at day 7 was the best predictor for therapeutic response in the early stage of treatment. 相似文献
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Prevalence of use of medically prescribed hypnotics among adult Japanese women in urban residential areas 总被引:1,自引:0,他引:1
TAKAYUKI KAGEYAMA MICHINORI KABUTO HIROSHI NITTA YOSHIKA KUROKAWA KAZUHIKO TAIRA SHOSUKE SUZUKI TAI-ICHIRO TAKEMOTO 《Psychiatry and clinical neurosciences》1998,52(1):69-74
Abstract Based on a population survey on insomnia among 3600 adult Japanese women living in urban areas, the prevalence of use of medically prescribed hypnotics is determined. The prevalence of use of medically prescribed hypnotics increases with an increase in age (<1.0% for those aged 49 or younger, while 14.3% for those aged 70 or older), in agreement with the results reported in many Western nations. The current sleep disturbance is mild in nearly half of these hypnotics users. More than one-third of the hypnotic users are receiving health care not for sleep problems but for depression, anxiety, or other reasons. More than one-third of the hypnotic users are found to be receiving hypnotics from non-psychiatrists. The percentage of this group is particularly high among those aged 60 or over, probably reflecting the fact that they are often consulting physicians for physical reasons. On the other hand, more than 80% of insomniacs are suggested to be untreated. Future public health research should focus on the quality of life and health care behaviors of untreated insomniacs and hypnotic users, especially among the elderly people, in order to assess the need for primary health care to prevent accidents, mortality, and psychiatric disorders related to sleep problems. 相似文献
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Antiproliferative effects of 5-fluorouracil and interferon-alpha in combination on a hepatocellular carcinoma cell line in vitro and in vivo 总被引:2,自引:0,他引:2
SAKIKO KOJIRO HIROHISA YANO SACHIKO OGASAWARA SEIYA MOMOSAKI YUMI TAKEMOTO NAOYO NISHIDA MASAMICHI KOJIRO 《Journal of gastroenterology and hepatology》2006,21(1):129-137
Background and Aim: We investigated the antiproliferative effects of interferon‐alpha (IFN‐α) and 5‐fluorouracil (5‐FU) in combination on a hepatocellular carcinoma (HCC) cell line. Method: In the in vitro study, IFN‐α and/or 5‐FU was added to the culture of the poorly differentiated‐type HCC cell line, HAK‐1B, and their antiproliferative effects and additional or synergic effects in combination treatment were examined. In the in vivo study, HAK‐1B cells were transplanted into nude mice and the changes in tumor volume and weight, apoptosis, BrdU and cyclin A positive cells, and artery‐like blood vessels were investigated. Expressions of angiogenesis factors and IFN‐α receptor (IFNAR‐2) were examined in the developed tumors. Results: In vitro growth of HAK‐1B cells was suppressed dose‐dependently to 5‐FU, but the addition of IFN‐α did not induce additional or synergic effects. In vivo growth in terms of tumor diameter and weight was suppressed at most in the IFN‐α + 5‐FU (combination) group, that is, the tumor volume became 29.3% and the tumor weight became 54.7% of the control. In the combination group, numbers of BrdU‐positive S‐phase cells and cyclin A positive cells increased together with the increase in apoptotic cells, but there was no significant relation between the tumor shrinkage effects and angiogenesis factors or artery‐like blood vessels. In the combination group, INFAR‐2 decreased significantly in comparison to the other groups. Conclusion: The synergic growth‐suppression effects in the current in vivo study using the combination treatment are attributable to the enhanced induction of S‐phase arrest and of apoptosis. 相似文献
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Masahito HARA Yusuke NISHIMURA Yasuhiro NAKAJIMA Daisuke UMEBAYASHI Masaya TAKEMOTO Yuu YAMAMOTO Shoichi HAIMOTO 《Neurologia medico-chirurgica》2015,55(7):547-556
Minimally invasive transforaminal lumbar interbody fusion (TLIF) as a short fusion is widely accepted among the spine surgeons. However in the long fusion for degenerative kyphoscoliosis, corrective spinal fixation by an open method is thought to be frequently selected. Our objective is to study whether the mini-open TLIF and corrective TLIF contribute to the improvement of the spinal segmental and global alignment. We divided the patients who performed lumbar fixation surgery into three groups. Group 1 (G1) consisted of mini-open TLIF procedures without complication. Group 2 (G2) consisted of corrective TLIF without complication. Group 3 (G3) consisted of corrective TLIF with instrumentation-related complication postoperatively. In all groups, the lumbar lordosis (LL) highly correlated with developing surgical complications. LL significantly changed postoperatively in all groups, but was not corrected in the normal range in G3. There were statistically significant differences in preoperative and postoperative LL and mean difference between the pelvic incidence (PI) and LL between G3 and other groups. The most important thing not to cause the instrumentation-related failure is proper correction of the sagittal balance. In the cases with minimal sagittal imbalance with or without coronal imbalance, short fusion by mini-open TLIF or long fusion by corrective TLIF contributes to good clinical results if the lesion is short or easily correctable. However, if the patients have apparent sagittal imbalance with or without coronal imbalance, we should perform proper correction of the sagittal spinal alignment introducing various technologies. 相似文献