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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 199 records · Page 11Linked to original sources
PubMed1998

Effects of endoscopic variceal ligation on portal hypertensive gastropathy and gastric mucosal blood flow.

OBJECTIVE: Portal hypertensive gastropathy (PHG) has been recognized recently as a potential cause of upper gastrointestinal tract bleeding and is associated with a change in gastric hemodynamic indices in cirrhotic patients with portal hypertension. Endoscopic variceal ligation (EVL) is the treatment of choice for esophageal varices. We investigated the early effect of EVL on PHG and gastric mucosal blood flow (GMBF). METHODS: We examined 35 cirrhotic patients who were treated by EVL. PHG was evaluated endoscopically and GMBF was measured by laser Doppler flowmetry before and 1 or 2 wk after EVL. RESULTS: After EVL, only two patients (5.7%) developed severe PHG, 6 (17.1%) developed mild PHG, and 27 (77.1%) showed no change in endoscopic appearance of PHG. In those patients who developed PHG, EVL significantly decreased GMBF at the corpus (p < .05). However, no significant changes of GMBF at the corpus were noted after EVL in those patients who had no worsening of endoscopic features. EVL had no effect on GMBF at the antrum in any patients. CONCLUSIONS: Endoscopic variceal ligation is safe and does not lead, at least within 1-2 wk, to worsening of gastropathy in most cases. Our finding that gastropathy developed in the presence of reduced GMBF may suggest that PHG develops as a result of congestion caused by blockade of gastric blood drainage rather than by hyperemia.

Adult↗
PubMed1998

Hypertension due to coexisting pheochromocytoma and aldosterone-producing adrenal cortical adenoma.

A 49-year-old male was diagnosed as having primary aldosteronism at age 39, and he was treated with antihypertensive drugs. In 1995, a computed tomogram revealed a mass in the right adrenal gland. Radiological examinations and endocrinological data revealed the presence of a pheochromocytoma in the right and an adrenocortical tumor in the left adrenal gland. Right adrenalectomy and left partial adrenalectomy were performed. Histologically, the right adrenal mass was compatible with pheochromocytoma, and the left adrenal mass was an adrenocortical adenoma. Endocrinological data as well as blood pressure returned to normal after operation.

Adrenal Cortex Neoplasms↗
PubMed1998

Efficacy of coronary artery bypass grafting in patients with a dilated left ventricle due to myocardial infarction.

This study was designed to clarify the efficacy of coronary artery bypass grafting (CABG) on left ventricular (LV) function in 16 patients with a dilated LV due to myocardial infarction (LV end-systolic volume index: LVESVI >60 ml/m2). All had attained complete revascularization. To estimate the LV wall motion quantitatively using echocardiography, a wall motion score (WMS) was used (LV was divided into 17 segments with a four-point scale: akinesis=3, severe hypokinesis=2, hypokinesis=1, normal=0 and then summed). Exercise stress tests were performed after surgery, revealing that anginal symptoms had vanished in all the patients. In 5 patients with a preoperative end-systolic volume index (ESVI) >100 ml/m2, the ejection fraction (EF) did not change, and both were under 30% (before to after: 26+/-4 to 26+/-4%). Neither the ESVI (148+/-50 to 133+/-39 ml/m2) nor the end-diastolic volume index (end-diastolic volume index (EDVI): 198+/-62 to 180+/-37 ml/m2) changed; the WMS did not change (33+/-2 to 33+/-3). During exercise, in spite of the increase in heart rate (HR) (at rest, 81+/-20; HR during exercise, 111+/-21 beats/min, p<0.005) and LV end-diastolic pressure (EDP) (22+/-9; 35+/-13 mmHg, p<0.02), both cardiac index (CI) (2.4+/-0.3; 2.6+/-0.4 L/min x m2) and minute work (MW: 4.0+/-1.1; 4.1+/-0.4 kg x M/min) did not increase. In 11 patients with a preoperative ESVI <100 ml/m2, EF was extremely increased in 5 patients (more than 10%, 35+/-4 to 60+/-6%, p<0.005=improved subgroup) in whom the EDVI (130+/-16 to 120+/-13 ml/m2) did not change whereas the ESVI (82+/-14 to 48+/-7 ml/m2) was reduced. However, in the 6 remaining patients (ie nonimproved subgroup), neither ESVI (78+/-8 to 74+/-12 ml/m2), EDVI (115+/-10 to 115+/-20 ml/m2) nor EF (31+/-7 to 35+/-3%) changed. During exercise, HR (at rest, 88+/-13; during exercise, 108+/-11 beats/min, p<0.005), LVEDP (20+/-6; 29+/-7 mmHg, p<0.01), CI (2.5+/-0.6; 3.3+/-0.5 L/min x m2, p<0.05), MW (4.6+/-1.0; 6.5+/-1.5 kg x M/min, p<0.05) increased. The WMS in the nonimproved subgroup did not change (29+/-6 to 27+/-2), but in the improved subgroup it reduced after surgery (27+/-3 to 19+/-4, p<0.01). These data suggested that CABG in patients with a dilated LV was effective against anginal symptoms, but was restricted to left ventricular function. It may be possible to estimate postoperative LV function, including exercise tolerance, from the preoperative LVESVI.

Aged↗
PubMed1998

Cepharanthine inhibits proliferation of cancer cells by inducing apoptosis.

Cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata was examined for a possible apoptosis-inducing effect in murine P388 doxorubicin-sensitive (P388/S) and -resistant (P388/DOX) cells. A significant increase in LDH release from cells was observed after P388/S and P388/DOX cells had been exposed to cepharanthine for 24 h. Cepharanthine (10 micrograms/ml) markedly induced apoptosis in resistant cells after 6 h and 24 h. By the means of agarose electrophoresis the DNA ladder was detected in cell lines treated with cepharanthine for 24 h. Cepharanthine (1-10 micrograms/ml) also induced the production of reactive oxygen species in P388/DOX cells, while no such cepharanthine-induced increase in reactive oxygen species was observed in P388/S cells. Flow cytometry analysis showed a high level of Fas-antigen expression in P388/DOX cells treated with cepharanthine. Furthermore, we found that the inhibitition of DNA and protein synthesis caused by cepharanthine (10 micrograms/ml) was more significant in resistant cells than in sensitive cells. Cepharanthine had no effect on the GSH content of P388/S and P388/DOX cells. Our experimental results suggest that cepharanthin can induce apoptosis both in P388/S and P388/DOX cells, especially in the latter. Apoptosis induced by cepharanthine may be implicated in the production of reactive oxygen species and Fas-antigen expression in tumor cells.

Alkaloids↗
PubMed1998

Effects of certain resorcinol derivatives on the tyrosinase activity and the growth of melanoma cells.

Effects of certain resorcinol derivatives on tyrosinase activity, melanin formation and some other biological activities were studied in order to develop a new, potent depigmentor and/or antimelanoma drug. NKO-09, having isopentyl group in position 6 of resorcinal, exhibited a more potent effect than the compounds which have methyl (NKO-10), ethyl (NKO-11), hexyl (KOM-14), octyl (NKO-14), decyl (NKO-19), dodecyl (NKO-15) and tetradecyl (NKO-16) group in inhibiting the tyrosinase activities (both tyrosine hydroxylation and dopa oxidation). NKO-09 was more potent than hydroquinone in inhibiting the tyrosine hydroxylation; furthermore, NKO-09 inhibited the dopa oxidation different from hydroquinone. In the studies on melanin formation, protein synthesis and the growth of the melanoma cells, NKO-09 caused the most potent effect among the test compounds, except for the growth of the melanoma cells. KOM-14 was more potent than NKO-09 in the antimelanoma activity, and its effect was superior than that of 5-fluorouracil. From these findings, it is suggested that NKO-09 and KOM-14 can be used as an efficacious depigmentor and antimelanoma drug, respectively.

Animals↗
PubMed1998

Mitochondrial DNA point mutation at nucleotide pair 3316 in a Japanese family with heterogeneous phenotypes of diabetes.

A mitochondrial DNA (mtDNA) point mutation at nucleotide pair (np) 3316 has been reported in relation to diabetes. We recently encountered a non-obese family with this type of mutation. The proband in the affected family, a 49-year-old woman who had been previously diagnosed as having an insulin-requiring non-insulin-dependent diabetes mellitus (NIDDM), was referred to our hospital for treatment of diabetic gangrene in her left foot. Her insulin secretory capacity was markedly reduced, but the insulin sensitivity evaluated by the euglycemic hyperinsulinemic clamp technique was normal. In addition, her serum lactate level was markedly increased after a 5 min ambulation, although her serum pyruvate and ketones remained within the normal range. Twenty-year-old twin sons had been treated with insulin since the age of 7, when both were diagnosed with insulin-dependent diabetes mellitus (IDDM). The proband's mother, a 68-year-old, was nondiabetic at this time. MtDNA analysis revealed a point mutation at np 3316 in all family members, which was homoplasmic for the mutation on a photograph of agarose gel electrophoresis containing ethidium bromide under ultraviolet light. This mutation seemed to be maternally transmitted in the family, and the onset of diabetes was occurring earlier and the insulin secretory capacity was declining from generation to generation, so that these findings suggest that the point mutation at np 3316 is associated with various phenotypes of diabetes.

DNA, Mitochondrial↗
PubMed1998

Reversed circadian blood pressure rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects.

To assess the significance of reversed circadian blood pressure (BP) rhythms as a predictive factor of vascular events in NIDDM, vital status after an average 4-year follow-up was determined in 325 NIDDM subjects in whom the circadian BP profile had been monitored between 1988 and 1996. Circadian BP rhythm was analyzed by the COSINOR (a compound word for cosine and vector) method, as previously described. After exclusion of 37 dropped-out subjects, 288 were recruited to the further analysis, of which 201 had a normal circadian BP rhythm (group N) and the remaining 87 had a reversed one (group R). There was no difference in sex, HbA1c, the prevalence of smokers, serum lipids, or serum electrolytes between groups N and R at baseline, whereas age, the prevalence of hypertension, serum creatinine, and diabetic complications were more pronounced in group R than in group N. During the follow-up period (which averaged 52 months in group N and 36 months in group R), fatal and nonfatal vascular (cerebrovascular, cardiovascular, peripheral vascular arteries, and retinal artery) events occurred in 20 subjects in group N and 56 in group R. Unadjusted survival times and event-free times were estimated by the Kaplan-Meier product-limit method, and there was a significant difference in both unadjusted survival and event-free survival rates between groups N and R (P < 0.001 each; log-rank test). The Cox proportional-hazards model adjusted for age, sex, circadian BP pattern, duration of diabetes, therapy for diabetes, various diabetic complications, and hypertension demonstrated that circadian BP pattern and age exhibited significant, high adjusted relative risks for fatal events, and that diabetic nephropathy, postural hypotension, and hypertension as well as circadian BP pattern exhibited significant, high adjusted relative risks with respect to the occurrence of various nonfatal vascular events. These results suggest that reversed circadian BP rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects.

Blood Pressure↗
PubMed1998

Liver transferase activity in healthy Japanese employees aged 18-39 years.

The aims of the present study were to identify correlates of alanine aminotransferase (ALT or GPT) and aspartate aminotransferase (AST or GOT) activities among a healthy working population aged 18-39, and to discuss liver transferase abnormalities. Subjects included 1,009 employees of a company in Fukushima, Japan. Pregnant women, employees exposed to organic solvents, and employees with a history of liver diseases were excluded. Serum ALT and AST levels were measured by an enzymatic method. Other information including BMI, job type and lifestyles was recorded. Mean ALT and AST levels were significantly higher for males than females (P < 0.001). Multiple linear regression analysis revealed that sex and BMI explained 45% and 31% of the variability in ALT and AST, respectively. The prevalence of abnormal ALT levels (> 40 IU) was 16.3% for males and 0.4% for females. Sex, BMI, and shift work were independently associated with abnormal ALT levels by logistic regression analysis. It is concluded that ALT and AST levels are well-correlated with sex and BMI, and that abnormal liver transferase activity is prevalent in male employees but rare in females, suggesting that liver function tests should be introduced for male employees under 40 years of age.

Adolescent↗
PubMed1998

Dose-dependent effects of dichloropropanol on liver histology and lipid peroxidation in rats.

A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols (DCPs) was reported recently. The purpose of the present study is to examine the effects of DCPs on various organs, the dose dependency and the pathogenetic potential of DCP hepatotoxicity. A single intraperitoneal injection was given to six groups of rats with 0.2 ml of 20% ethanol (control), or 1/8 x, 1/4 x, 1/2 x, 1 x, and 2 x LD50 (0.11 ml/kg) of 1,3-dichloro, 2-propanol (DC2P) diluted in 20% ethanol. After blood samplings, all organs were subjected to histologic examinations with light and electron microscopes. Fresh liver tissues from further 4 control and 4 experimental rats sacrificed 6 hours after the injection of 20% ethanol and 1 x LD50 of DC2P were homogenized and subjected to evaluate lipid peroxidation, glutathione S-transferase activity and reduced glutathione contents in the liver. The rats administered with only ethanol or 1/8 and 1/4 LD50 of DC2P showed no serological or histopathological abnormalities. Marked elevation of serum glutamate pyruvate transaminase (SGPT) with a diffuse massive necrosis of the liver cells were noted in all rats of both the 1 x and 2 x LD50 groups, and irregular zonal necroses were found in 3 of 4 rats injected with 1/2 LD50. There were no serious toxic changes in other organs. Hepatic malondialdehyde level was significantly increased, associated with decreases of liver glutathione S-transferase activity and reduced glutathione content. It was concluded that the serious DC2P-toxicity was mainly found in the livers, dose dependently, and one of the causative mechanisms of this hepatotoxicity might be the lipid peroxidation.

Alanine Transaminase↗
PubMed1998

Resistance to growth inhibition by transforming growth factor-beta in malignant glioma cells with functional receptors.

OBJECT: The aim of this study was to investigate the mechanism by which malignant glioma cells escape from growth inhibition mediated by transforming growth factor-beta (TGF-beta), a ubiquitous cytokine that inhibits cell proliferation by causing growth arrest in the G1 phase of the cell cycle. METHODS: The authors measured the response of eight malignant glioma cell lines to the growth-inhibiting activity of TGF-beta in vitro and the expression of TGF-beta Types I and II receptors in malignant glioma cells. The effect of TGF-beta on the expression of a p27Kip1 cyclin-dependent kinase inhibitor was also investigated to assess the downstream signal transmission from TGF-beta receptors. All malignant glioma cell lines were insensitive to growth inhibition by TGF-beta1 and TGF-beta2. Analyses of TGF-beta receptors by means of affinity labeling in which 125I-TGF-beta1 was used showed that six glioma lines had both TGF-beta Types I and II receptors on their cell surfaces, whereas two lines had very small amounts of TGF-beta Type I and/or Type II receptors. Northern blot analysis showed that all tumor lines expressed variable levels of messenger RNAs for both TGF-beta Types I and II receptors. Flow cytometric analyses revealed that treatment of malignant glioma cells with TGF-beta1 significantly downregulated the expression of p27Kip1 protein in all malignant glioma cell lines except one. CONCLUSIONS: The authors suggest that most malignant glioma cells express TGF-beta Types I and II receptors, which can transmit some signals downstream and that the loss of response to TGF-beta growth inhibition may not be caused by an abnormality of the TGF-beta receptors.

Adenocarcinoma↗
PubMed1998

[Development of an anticancer drug in Japan based on a new clinical trial system].

According to the revision of Pharmaceutical Affairs Law in 1996, the GCP has been enacted into the law. Next year the new GCP was established based on the ICH-GCP and it has been active since April, 1997. Though the new GCP makes it possible for the regulatory authorities (Japan, the United States and European Union) to accept clinical trial data mutually, the circumstances of clinical trial in Japan have been required big changes. But considerable investigators/institutions in Japan which carry out clinical trials seem to have not still adapted their usual clinical trial system to a new one yet. At the first time, in this article are described the process of both the revision of Japanese pharmaceutical law and the establishment of the new Japanese GCP. The second, the characteristics of the new Japanese GCP especially about the roles and responsibilities of investigators are discussed. Furthermore approaches of the US FDA for new anticancer drugs development are also described.

Antineoplastic Agents↗
PubMed1998

Quasispecies nature of hepatitis C virus (HCV) in patients with chronic hepatitis C with mixed HCV subtypes.

The quasispecies nature of hepatitis C virus (HCV) in patients with mixed HCV subtype infection was compared with that in patients with single HCV subtype infection. The number of HCV quasispecies was compared between 35 patients with mixed HCV subtype infection and 83 patients with single subtype infection. Subtype was determined by primers deduced from the core region and by line probe assay respectively. The number of quasispecies was evaluated by polymerase chain reaction amplification of hypervariable region 1 and by fluorescence single-strand conformation polymorphism analysis. There was no difference in clinical background between patients with mixed subtype infection and patients with single subtype infection. The number of quasispecies in patients with multiple subtype HCV infection was larger than in patients with single subtype HCV infection. The immunologic environments which allow the coexistence of more HCV quasispecies in patients with multiple HCV subtype infection differs from that in patients with single HCV subtype infection.

Adult↗
PubMed1998

Chronopharmacology of granulocyte colony-stimulating factor in mice.

The role of the sensitivity of bone marrow cells to, and the pharmacokinetics of granulocyte colony-stimulating factor (G-CSF) on the rhythm of leukocyte-increasing effect was investigated in ICR male mice housed under a standardized light-dark cycle (lights on at 0700, off at 1900). A significant circadian rhythm was demonstrated for leukocyte counts at 24 hr after G-CSF (250 microg/kg, s.c.) injection at six different circadian times (P < .01). The leukocyte counts of mice given G-CSF at 0500, 0900, 1300 or 1700 were significantly higher than those of mice given G-CSF at 2100 (P < .01, respectively). The rhythmic pattern resembled overall the rhythm occurring after saline injection. In the comparison between leukocyte counts after G-CSF injection at 0700 and 1900, the time when leukocyte counts are equal in nondrugged state, the leukocyte counts at 24 hr after G-CSF (250 microg/kg, i.v.) injection were approximately 50% higher in mice injected with the drug at 0700 than at 1900 (P < .01). Bone marrow cultures obtained at two times of day resulted in different numbers of myeloid colonies even when treated with the same concentrations of G-CSF in vitro. The colony-forming activity of G-CSF was significantly more potent at 0700 than at 1900 (P < .01). The plasma G-CSF concentrations after G-CSF (250 or 5 microg/kg, i.v.) injection were significantly higher in mice receiving injections with the drug at 0700 than at 1900 (P < .05, respectively). The area under the curve and mean residence time were significantly larger in mice injected with the drug at 0700 than at 1900 (P < .01, P < .05, respectively). Our suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to, and the pharmacokinetics of the drug.

Animals↗
PubMed1998

Direct percutaneous transluminal angioplasty for acute middle cerebral artery occlusion.

PURPOSE: We review our initial experience with direct percutaneous transluminal angioplasty (PTA) as a reperfusion treatment for acute occlusion of the middle cerebral artery. METHODS: Ten patients in whom successful thrombolysis might not be expected because of the risk of hemorrhagic complications or reocclusion were treated with direct PTA. When early ischemic findings were present on the initial CT scans and/or when lenticulostriate arteries were involved, we performed direct PTA rather than thrombolytic therapy. Direct PTA was also performed when superselective local angiography via a Tracker catheter advanced just distal to the occlusion site showed the presence of a large embolus or high-grade stenosis suggestive of thrombosis. Angioplasty was performed with a Stealth balloon catheter with a maximum diameter of 2.0 to 2.5 mm. The balloon catheter was advanced into the site of occlusion and inflated to 2 atm initially, and subsequently up to 3 atm. Two to six inflations, each of 30 seconds' duration, were performed. RESULTS: Although the rate of initial recanalization was 100% (10 of 10), reocclusion occurred in two patients with atherothrombotic M2 occlusion. The final angiographic success rate of direct PTA was 80% (8 of 10). There were no hemorrhagic or technical complications, and five of 10 patients showed marked clinical improvement. In two of seven patients with cardioembolic M1 trunk occlusion, crushed fragments of the embolus obstructed M2 portions after direct PTA, necessitating local thrombolysis. CONCLUSION: Direct PTA may be performed safely as an alternative to thrombolytic therapy in patients with acute occlusion of the middle cerebral artery when early CT findings and/or lenticulostriate artery involvement are present or when superselective local angiography shows the presence of a large embolus or high-grade stenosis.

Acute Disease↗
PubMed1998

[The usefulness of percutaneous ethanol injection therapy under guidance with carbon dioxide contrast enhanced ultrasound sonography].

We evaluated the usefulness of percutaneous ethanol injection therapy (PEIT) under Carbon dioxide (CO2) contrast enhanced ultrasound sonography (CEUS) guidance during digital subtraction angiography (DSA) in 21 cases of hepatocellular carcinoma (HCC) with 28 nodules that could not be detected by plain (non-contrast enhanced) US (PUS). In all cases of HCC that could not be visualized by PUS, PEIT could be performed successfully under CEUS guidance. Tumor size was below 10 mm in most cases, in 2 cases tumor size was more than 20 mm. Tumor location was roughly divided into 5 areas: just below the diaphragm and it's vicinity, liver surface, edge of the liver, around the portal and hepatic vein, and around the inferior vena cave. The detection rate of the nodules that could not be visualized with PUS was 35.7% for CT and 32.1% for DSA. PEIT was performed 1-9 times for each lesion, 3.32 times on an average. The effectiveness of PEIT was judged by CT. All cases were confirmed as LDA. We concluded that the range of indication of PEIT can be expanded by this method.

Carbon Dioxide↗