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Y Murakami H Hara T Okada H Hashizume M Kii Y Ishihara M Ishikawa M Shimamura S Mihara G Kato K Hanasaki S Hagishita M Fujimoto 《Journal of medicinal chemistry》1999,42(14):2621-2632
A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors. 相似文献
105.
Fujio Atsuta Kenichi Sato Koscak Maruyama Yutaka Shimada 《Journal of muscle research and cell motility》1993,14(5):511-517
Summary The distribution of connectin (titin), nebulin and -actinin in the areas of myotendinous junctions of chicken pectoralis muscles was examined by immunocytochemical methods. Staining with antibodies against connectin (4C9, SM1 and P1200) and nebulin formed doublets flanking nonterminal Z-bands; near the end of muscle fibres singlets were seen within the terminal sarcomere on the side adjacent to the terminal Z-bands. The apical regions of muscle processes, where no myosin filaments are present although actin filaments exist, were reactive with anti-nebulin but not with anti-connection. Antibodies against pectoralis (skeletal muscle type) -actinin stained non terminal Z-bands and that against gizzard (smooth muscle type) the sarcolemma. Terminal Z-bands were unreactive with both of these antibodies. These findings indicate that, although terminal and nonterminal Z-bands differ in their molecular composition, connectin and nebulin filaments appear to link myosin and actin filaments, respectively, to both Z-band types. 相似文献
106.
To determine the availability and limitations of the detection of ischemic lesions by stress thallium-201 myocardial SPECT as the daily routine procedure, we compared and evaluated the detectability of the quantitative analysis (%uptake and washout rate (WR)) and visual evaluation in 104 patients with effort angina and 17 normal subjects. Visual evaluation combined with WR analysis resulted in significantly higher sensitivity (88.0%) but lower specificity (60.2%) than the other methods. The sensitivity by visual evaluation was quite low in multivessel disease (MVD), and in the regions supplied by mild coronary stenosis or by the left circumflex artery. These were markedly improved by combining visual evaluation and WR analysis, but sensitivity in the MVD group was unsatisfactory even with this analytic method in comparison with the single vessel disease group. One of the causes of low sensitivity in the MVD group might be the "true negative": No induction of the ischemia in the regions of milder stenosis, or the regions supplied by the collateral coronary flow. We therefore conclude that the combination of visual evaluation as a qualitative analysis and WR analysis as a quantitative analysis, is the most useful daily routine procedure as a screening test for detecting ischemia. 相似文献
107.
Shuto T Hirohashi K Ikebe T Mikami S Yamamoto T Kubo S Wakasa K Kinoshita H 《World journal of surgery》2000,24(12):1566-1569
The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic
for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic
resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these
72 patients was significant worse than for the 195 with single nodular HCC (p= 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination
after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p < 0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other
two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest,
there was no significant difference among the three groups assigned according to tumor differentiation (p= 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional
nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during
or after surgery in the presence of cirrhosis was 5.444 (p= 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up
after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed
according to the results of preoperative imaging studies. 相似文献
108.
K Kaneko M Chiba M Hashizume O Kunii S Sasaki T Shimoda Y Yamashiro W Caypil D Dauletbaev 《Archives of disease in childhood》2003,88(11):966-968
BACKGROUND: The Aral Sea region is a natural area seriously polluted by human activities. Recent surveillance revealed the increased prevalence of diverse chronic diseases in children. AIMS: To investigate the function of renal tubules, which are most at risk of damage as a result of heavy metal intoxication, in children of the Aral Sea region. METHODS: A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were examined by means of random urine samples. Both urinary N-acetyl-beta-D-glucosaminidase (NAG; U/mmol Cr) and beta2 microglobulin (BMG; microg/mmol Cr) were calculated for each subject. RESULTS: Mean urinary NAG and BMG were both significantly higher in Kazalinsk than in Zhanakorgan (NAG: 0.77 (0.58) and 0.62 (0.37) U/mmol Cr; BMG: 41.8 (54.8) and 22.5 (20.4) microg/mmol Cr, respectively; mean (SD), p < 0.01). The number of children with abnormal values of NAG (>1.5 U/mmol Cr) was significantly more prevalent in Kazalinsk than in Zhanakorgan (7.9% and 2.6%, respectively, p < 0.05). CONCLUSION: Renal tubular function of children around the Aral Sea region is profoundly impaired. This should be taken into account when considering the health problems of this area. 相似文献
109.
Tanaka Y Hongo K Tada T Takizawa T Kakizawa Y Koyama J Kobayashi S Sakurai A Hashizume K 《No shinkei geka. Neurological surgery》2000,28(12):1087-1092
We analyzed 7 pituitary adenomas in patients with multiple endocrine neoplasia type 1 (MEN1). Their incidence was 1.6% among 450 patients with pituitary adenomas which had been treated surgically in our department between 1978 and 1999. The age, gender, symptoms, type of hormone secretion, pathological and operative findings in the MEN1 patients were not apparently different from those in the non-MEN1 patients. Incidence of non-functioning pituitary adenomas, however, was more frequently encountered in our series than that in previous reports among Caucasian people. One patient who had 5 previous operations for the MEN tumors died following postoperative subarachnoid hemorrhage. Four of the seven patients presented initial symptoms related to pituitary adenomas and increased serum Ca level was retrospectively recognized in three of the four at the time of treatment for the pituitary adenomas. 相似文献
110.
Osamu Kawashima Mitsuru Ohata Kazuhiko Sakamoto Kenichi Hashimoto Hisato Nakajima Masayoshi Yamauchi 《Nihon Arukōru Yakubutsu Igakkai zasshi》2003,38(1):58-68
Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin. 相似文献