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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 1,027 records · Page 57Linked to original sources
PubMedDate not supplied

Effect of gonadal steroids on gonadotropin-releasing hormones stimulated human chorionic gonadotropin release by trophoblast cells.

The effect of gonadal steroids on basal and GnRH-stimulated hCG release was studied using collagenase-dispersed trophoblast cells from early pregnancy. Both GnRH and a GnRH superagonist, Buserelin, stimulated hCG release with a similar dose dependency. Progesterone (0.1 to 10 micrograms/ml) inhibited GnRH-stimulated hCG release in a dose dependent manner as well as basal hCG release. Relatively high concentrations of estradiol (10 micrograms/ml) stimulated both basal and GnRH-mediated hCG release and antagonized the inhibitory effect of progesterone on hCG release at 1 micrograms/ml as well as RU486 (1 microgram/ml). These results indicate that progesterone has an important role in both basal and GnRH-mediated hCG regulatory system in the placenta.

Buserelin↗
PubMedDate not supplied

Effects of diacylglycerol and gonadotropin-releasing hormone on human chorionic gonadotropin release by cultured trophoblast cells.

The effect of activation of calcium- and phospholipid-dependent protein kinase (protein kinase C) on human chorionic gonadotropin (hCG) release by cultured trophoblast cells was studied and a role of protein kinase C in the GnRH-mediated hCG release was also evaluated. Both GnRH and 1-oleoyl-2-acetylglycerol (OAG), a protein kinase C activator, stimulated hCG release after 3 h incubation in a dose-dependent manner with ED50 of 55 nmol/l and 4.0 nmol/l, respectively. A tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) also stimulated hCG release while two non-tumor-promoting compounds, phorbol and 4 alpha-phorbol, failed to stimulate hCG release. hCG release by maximal effective dose of GnRH (10 mumol/l) or OAG (1 mumol/l) was further stimulated when cells were incubated with same concentrations of GnRH and OAG. OAG-stimulated hCG release was completely inhibited by a protein kinase C inhibitor, H-7, with ID50 of 23 nmol/l while H-7 did not affect GnRH-mediated hCG release. These results indicate that GnRH-stimulated hCG release is not mediated by protein kinase C pathway, however, the secretion of hCG is also regulated by the mechanism that involves protein kinase C activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

Feto-maternal interaction of IGF-I and its binding proteins in fetal growth.

Elevated levels of maternal IGF-I and IGF-binding proteins IGFBP-1 are regulated by placental hormones rather than pituitary control during pregnancy. Maternal IGF-I promotes fetal growth by stimulating nutrient transfer to fetus through placenta and IGFBP-1 suppresses fetal growth by inhibiting IGF-I binding to receptors in placenta. Since IGF-I and IGFBP-1 are produced in placenta and decidua, respectively, fetal growth is regulated by these substances in the locally formed paracrine system.

Carrier Proteins↗
PubMedDate not supplied

Ethical problems in neonatal intensive care unit--medical decision making on the neonate with poor prognosis.

In current NICU (neonatal intensive care units), it is inevitable that ethical decisions on neonates with a poor prognosis will have to be made. At Tokyo Women's Medical College, we have been applying our own policy of medical decision making, which is somewhat different to those of most western countries. Most families are not asked to make final decisions, and the ethical committee is not actively involved. Staff in the NICU make the decision after plenary discussions. The position after decision making is not to discontinue the life supporting system but to observe, with no additional treatments and with routine care (class C). From October 1984 to September 1989, 58 out of 1589 neonates admitted to the NICU at Tokyo Women's Medical College died and 32 (55%) of them were classified as class C. The main causes of medical decision making were; non-viable (4/4, 100%), lethal malformations (13/20, 65%) and birth asphyxia (15/19, 79%).

Decision Making↗
PubMedDate not supplied

Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats.

Keishi-bukuryo-gan (TJ-25) is a traditional Chinese herbal remedy containing five components: bark of Cinnamomum cassia, root of Paeonia lactiflora, seed of Prunus persica or P. persiba var. davidiana, carpophores of Poria cocos and root bark of Paeonia suffruticosa. This preparation has been used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and infertility. In the present study, the effects of TJ-25 on plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2), and on uterine wet weight and thymidine kinase (TK) activity were documented in immature rats. Long-term daily oral administration of TJ-25 (300 mg/kg) for 14 days decreased plasma levels of LH, FSH and E2 by 94%, 67% and 50%, respectively, compared to controls. Uterine wet weight and TK activity were reduced to 65% and 64% that of controls, respectively. Short-term effects of TJ-25 on E2 were also examined. Thirty hours after administration of E2 (1.0 micrograms/kg) alone, uterine wet weight and TK activity were elevated 2.4- and 21-fold, respectively, over controls. However, simultaneous administration of TJ-25 (three consecutive doses, every 12 h) with E2 reduced E2-induced increases in uterine wet weight and TK activity by 29% and 39%, respectively. Treatment with TJ-25 also enhanced LH-RH-induced increases in plasma LH and FSH levels 1.2- and 2.5-fold, respectively, as compared with controls. The results obtained in the present study indicate that TJ-25 may act as a LH-RH antagonist and/or as a weak anti-estrogen.

Administration, Oral↗
PubMedDate not supplied

Correlates of problem drinking among young Japanese women: personality and early experiences.

Problem drinking patterns were measured by the CAGE questionnaire among 90 currently drinking young Japanese women who were recently recruited by a Japanese company. Problem drinking was examined in terms of personality (temperament and character as defined by Cloninger) and early life experiences (perceived parental behavior, parental abusive behavior, being bullied at school, and positive and negative life events experienced before the age of 16). Multiple regression analysis revealed that problem drinking could be predicted by a set of personality scores, early death of a close friend, and the interaction of the death of a close friend and low explorative excitability (novelty-seeking component 1). This suggests that problem drinking in young women is partly determined by both personality and negative life events during childhood.

Adult↗
PubMedDate not supplied

Dilatation of coronary stenosis as the salutary effect of nitroglycerin in relief of myocardial ischemia in the dog.

To clarify the role of coronary responses to nitroglycerin (NTG) in relieving myocardial ischemia, we examined the effects of NTG in canine models of dynamic and fixed coronary stenoses. Application of coronary stenosis in the proximal left circumflex artery decreased resting coronary blood flow by approximately 40% and caused a significant depression of left ventricular (LV) dP/dt. During fixed coronary stenosis created with an externally applied constrictor device, intravenous NTG, 5 micrograms/kg, reduced mean aortic pressure by 12 +/- 1.1 mm Hg (mean +/- SEM, p less than 0.01) and coronary blood flow by 9 +/- 1.0% (p less than 0.01) but did not affect stenosis resistance and LV dP/dt. During dynamic coronary stenosis produced with an intraluminal microballoon occluder, intravenous NTG caused a marked increase in coronary blood flow by 40 +/- 8.3% (p less than 0.01) and a decrease in stenosis resistance by 62 +/- 9.3% (p less than 0.01), as compared with postocclusion values, concomitant with a significant improvement in LV dP/dt. Intracoronary infusion of NTG, 1.0 microgram/kg/min, had few systemic and coronary hemodynamic effects during fixed coronary stenosis, whereas intracoronary NTG increased coronary blood flow and reduced stenosis resistance, depending on its dose, during dynamic coronary stenosis. These results indicate that NTG is capable of increasing coronary blood flow and alleviating myocardial ischemia due to direct stenosis-dilating effects related to the vasomobility of the coronary stenosis.

Administration, Oral↗
PubMedDate not supplied

Clinical significance of the serum levels of the 7S domain of type IV collagen in patients with primary biliary cirrhosis.

The serum levels of the 7S domain of type IV collagen were measured with a radio-immunoassay in 42 patients with primary biliary cirrhosis (asymptomatic: n = 28; symptomatic: n = 14), 10 patients with chronic active hepatitis, 10 patients with liver cirrhosis and 10 healthy female controls. Serum levels of the 7S domain of type IV collagen were: 4.28 ng/mL (3.88-4.72 ng/mL; mean and range of mean +/- s.d.) in healthy controls; 5.97 ng/mL (5.07-7.02 ng/mL) in patients with chronic active hepatitis; 8.23 ng/mL (6.40-10.58 ng/mL) in patients with liver cirrhosis; and 6.79 ng/mL (4.76-9.67 ng/mL) in patients with primary biliary cirrhosis. Patients with liver cirrhosis and primary biliary cirrhosis had higher levels of serum 7S domain of type IV collagen than healthy controls (P < 0.001, respectively). Serum levels of the 7S domain of type IV collagen in patients with asymptomatic primary biliary cirrhosis, 5.83 ng/mL (4.55-7.48 ng/mL) were significantly lower than those in symptomatic primary biliary cirrhosis, 9.18 ng/mL (6.53-12.91 ng/mL; P < 0.001). Serum levels of the 7S domain of type IV collagen increased significantly along with advancement of the histological stages of primary biliary cirrhosis. Serum levels of the 7S domain of type IV collagen in the paired sera of eight patients with asymptomatic primary biliary cirrhosis (mean interval 30 months, range 12-48 months) showed significant rises during the intervals (P < 0.05), while serum levels of albumin and total bilirubin did not change significantly during these intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMedDate not supplied

Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s.

The prognosis of 174 patients with cirrhosis during the 1980s (1981-89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow-up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971-80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased (P < 0.01), and non-liver-related mortality significantly increased (P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary.

Adult↗
PubMedDate not supplied

Decreased variation of electrocardiographic R-R interval in patients with liver cirrhosis.

Electrocardiographic R-R interval variations were assessed to determine the functional integrity of the cardiac vagal nervous system in 20 normal controls and 71 cirrhotic patients. The ratio of the coefficient of variation to standard prediction value was used as an index. The cirrhotic patients showed significant reductions in the ratio of the coefficient compared with controls (0.71 +/- 0.27 vs 0.91 +/- 0.14; P < 0.01). There was a significant relationship between decreased R-R interval variation and the liver function tests. The ratio of the coefficient increased with improvement in encephalopathy, and decreased with the development of encephalopathy. These results show that there is dysfunction of the cardiac vagal nervous system in patients with liver cirrhosis, and that this abnormality is partially reversible and might be related to liver dysfunction.

Adult↗
PubMedDate not supplied

Relatively preserved hippocampal glucose metabolism in mild Alzheimer's disease.

The purpose of this study was to clarify the changes in hippocampal glucose metabolism in mild Alzheimer's disease (AD) using positron emission tomography (PET) and 2-(18F)fluoro-2-deoxy-D-glucose (FDG). Forty-one patients with probable mild AD (age: 69.0 +/- 8.0 years; MMSE: 22.6 +/- 2.1) and 22 normal volunteers (age: 67.7 +/- 7.1 years) were studied. The regional cerebral metabolic rate for glucose (CMRglc) was measured using FDG and PET. Although the mean CMRglc in the parietal region was significantly lower in the AD group (right: 6.35 +/- 1.26 mg/100 g/min; left: 6.37 +/- 1.21 mg/100 g/min) than in the control group (right: 7.73 +/- 1.02 mg/100 g/min; left: 7.63 +/- 0.95 mg/100 g/min), the mean CMRglc in the hippocampus did not show a significant difference between the AD group (right: 4.58 +/- 0.70 mg/100 g/min; left: 4.63 +/- 0.67 mg/100 g/min) and the control group (right: 5.22 +/- 0.65 mg/100 g/min; left: 5.22 +/- 0.67 mg/100 g/min) by analysis of variance and post-hoc Tukey's test. The magnitude of the hippocampal CMRglc reduction was not as large as that of parietal CMRglc reduction. Statistical parametric maps (SPM) analysis also did not significantly demonstrate reduced hippocampal CMRglc in AD patients, although it did show a significant reduction in parietal CMRglc in AD patients. Hippocampal CMRglc was not significantly decreased in mild AD. This was unexpected in view of previous studies that have shown atrophy and clinical dysfunction concerning hippocampus in AD, and suggests that the pathophysiology of the hippocampus in AD may be more complex than was previously thought.

Aged↗
PubMedDate not supplied

Intratumoural thymidylate synthase and dihydropyrimidine dehydrogenase activities are good predictors of 5-fluorouracil sensitivity in colorectal cancer.

To identify factors that influence the clinical response to 5-fluorouracil (5-FU), we studied the correlation between in vitro sensitivity to 5-FU and the expression of seven biological markers. The markers, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), pyrimidine nucleoside phosphorylase, p53 (wild/mutant), p21, cyclo-oxygenase-2, and inducible nitric oxide synthase were measured in tumour tissues from 32 colorectal cancer patients. The activities of TS and DPD were significantly lower in the tumours sensitive to 5-FU compared with those that were not sensitive to 5-FU. In tumours with TS < 3.7 pmol/min per mg protein and DPD < 98 pmol/min per mg protein, the percentage of cases sensitive to 5-FU (67%) and the mean percentage inhibition of tumour cells by 5-FU (42.8%) were significantly higher than in the other tumours (0% and 13.1%, respectively). The other biological markers did not correlate with in vitro sensitivity to 5-FU. Tumour sensitivity to 5-FU can be more precisely predicted by taking the activities of both TS and DPD into consideration than by using either alone.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Protective effects of an antiulcer agent, ecabet sodium on colorectal carcinogenesis in rodents.

A new antiulcer agent, ecabet sodium is one of dehydroabietic acid derivatives prepared from pine resin. The effects of ecabet sodium on colorectal carcinogenesis were investigated in azoxymethane-pretreated mice with chronic ulcerative colitis induced by 3 repeated administration of 3% dextran sulfate sodium and in 1, 2-dimethylhydrazine-treated rats. Although daily treatment with ecabet sodium did not affect the colorectal DNA-synthesizing enzyme activities and bromodeoxyuridine-immunoreactive S-phase cells, high-grade dysplasia in ecabet sodium-treated mice was less frequent than in untreated mice. In rats, ecabet sodium administration reduced the elevated activity of thymidylate synthetase in colorectal tumors.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Correlation between histological differentiation and DNA-synthesizing enzymes in rat colorectal tumors induced with 1, 2-dimethylhydrazine.

Thymidylate synthase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Colorectal carcinogenesis induced with 1,2-dimethylhydrazine in rats enhanced mRNA expression levels of both enzymes, resulting in the increase of both enzyme activities and bromodeoxyuridine-immunoreactive S-phase cells. Poorly and well differentiated adenocarcinomas of the colorectum showed the relative elevation of activities of thymidylate synthase and thymidine kinase, respectively. These results indicate that the relationship between de novo and salvage pathways for pyrimidine nucleotide synthesis may depend on the histopathological grades of cell differentiation.

Animals↗
PubMedDate not supplied

Effects of lentinan on colorectal carcinogenesis in mice with ulcerative colitis.

Lentinan; i.e., polysaccharides extracted from a kind of black mushroom shiitake, has been clinically applied as an antitumor and antimetastatic drug, and has been reported to prevent both chemical and viral carcinogenesis. It is known that lentinan affects the tumorous vascular system resulting in the induction of hemorrhagic necrosis which is dependent on T-cells in the tumor. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. In the present study, the additive treatment with lentinan in the azoxymethane-dextran sulfate sodium treated mice enhanced the colorectal high-grade dysplasia, though not significantly, and the splenic weight. This may show the proliferation of pathogenic splenic T cells resulting in a change for the worse of ulcerative colitis, anemia induced with hemorrhage and colorectal carcinogenesis; i.e., high-grade dysplasia of the mucosa and/or invasive adenocarcinomas of the colorectum. The present results may recommend chemoimmunotherapy while using lentinan, but not immunotherapy using lentinan alone, is indicated for the management of cancer patients.

Animals↗