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Biomedical subjects

N Iwamoto

Publications and source records attributed to N Iwamoto.

At least 19 recordsLinked to original sources

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial.

A multi-institutional phase II trial was conducted to evaluate the efficacy and toxicity of combination chemotherapy consisting of gemcitabine and UFT, which is composed of tegafur and uracil, for non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC received an oral administration of UFT (tegafur 200 mg m(-2)) b.i.d. from days 1 to 14 and intravenous injection of gemcitabine 900 mg m(-2) on days 8 and 15. This treatment was repeated every 4 weeks. A total of 44 patients were enrolled into this trial. The median age of all patients was 74 years, with 23 patients younger than 75 years and 21 patients with 75 years of age or older. A total of 18 patients (41%) achieved a partial response. The median survival time was 13.2 months and the 1-year survival rate was 59%. The most common grade 3-4 toxicity was neutropenia (57%). The frequency of grade 3 nonhaematologic toxicities was less than 5%. In addition, no significant difference in the response, survival or toxicities was observed between the patients younger than and those older than 75 years of age. This combination chemotherapy demonstrated a promising effectiveness and acceptable toxicity in patients with advanced NSCLC, even in patients older than 75 years. .

Aged↗

Evidence for nucleosynthesis in the supernova gamma process: universal scaling for p nuclei.

Analyzing the solar system abundance, we find two universal scaling laws concerning the p and s nuclei. They indicate that the gamma process in supernova (SN) explosions is the most probable origin of the p nuclei that has been discussed with many possible nuclear reactions and sites in about 50 years. In addition, the scalings lead to new concepts: a universality of the gamma process and a new nuclear cosmochronometer. We carry out gamma-process nucleosynthesis calculations for typical core-collapse SN explosion models, and the results satisfy the observed scalings.

Journal Article↗

[Thoracoscopic repair of diaphragmatic thinning for pleuroperitoneal communication; report of a case].

A 53-year-old man presented with massive right hydrothorax just after introduction of continuous ambulatory peritoneal dialysis (CAPD). Because the glucose concentration of pleural fluid was markedly high compared with that of serum, we diagnosed pleuroperitoneal communication. Thoracoscopic surgery was performed and thinning of the diaphragm was found. We sutured the diaphragm to repair the thin portion and performed pleurodesis with 50% glucose solution. He restarted CAPD 1 month post-operatively and continued at home without pleural effusion. Eight months post-operatively, he experienced dyspnea again and chest X-ray showed right hydrothorax. Although the cause of recurrent hydrothorax is unknown, it may be that not only surgical repair but also more intense pleurodesis is needed.

Diaphragm↗

Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis.

In order to evaluate the erectile function in male renal failure patients treated with hemodialysis (HD), we investigated the International Index of Erectile Function (IIEF) in patients and healthy controls. The subjects were 174 male patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining 131 patients did not have DM. The controls were 1133 healthy males. We evaluated the prevalence of erectile dysfunction (ED) using the erectile function (EF) score, which is one of the five domains of the IIEF, in each age group (upto 39 y old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified into five categories using EF in each age group. The univariate logistic regression analysis and multiple variate analysis of IIEF in HD patients were performed. The prevalence of ED in HD patients was significantly higher than that in the controls in each age group. The severity of ED in HD patients was also significantly higher than that in the controls in each age group. In the logistic regression analysis and multiple variate analysis of IIEF in HD patients, DM and age were significant risk factors on sexual dysfunction. ED was more prevalent in male renal failure patients treated with HD than in the controls. In the patient group, ED was more prevalent in older DM patients.

Adult↗

Erythrocyte aldose reductase correlates with erectile dysfunction in diabetic patients.

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Erythrocyte aldose reductase (AR) has been implicated in a variety of diabetic complications. The subjects were 62 diabetic patients, of whom 25 were treated with hemodialysis (chronic renal failure CRF group) and the remaining 37 did not have chronic renal failure (DM group). The controls were 20 healthy volunteers age-matched to the patients. The level of AR was measured by the quantitative determination kit for AR in all patients and controls. In this study, ED was diagnosed by 5-item version of the International Index of Erectile Function (IIEF-5). The average level of AR in the CRF group was significantly higher than that in the DM group and controls (P<0.001). The average level of AR in the DM group without ED was significantly lower than that in the DM group with ED and controls (P<0.005). These results suggest that the level of AR may be a useful modality for prediction of ED in diabetic patients.

Aged↗

Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS: To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS: The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol. CONCLUSIONS: These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.

Adult↗

Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.

BACKGROUND: CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. METHODS: We examined 831 adults undergoing health screening. The majority (780) was Pro90 homozygous for the CD36 gene product, but 51 displayed a CD36 mutation (2 homozygous and 49 heterozygous for Ser90). This is the major mutation site involved in CD36 deficiency in Japanese. RESULTS: Among parameters related to insulin resistance, there were no differences in body mass index (BMI), HDL cholesterol, total cholesterol, triglycerides, insulin and insulin resistance index (HOMA IR), or blood pressure between 91 normal subjects (45 male and 46 female) randomly selected from the 780 Pro90 homozygotes and the 51 (29 male and 22 females) CD36-deficient subjects (Ser90 homozygote and Pro90Ser heterozygote). Free fatty acid concentrations, however, were higher in Ser90 CD36 subjects than in Pro90 control subjects. CONCLUSIONS: The CD36Pro90Ser mutation is not necessarily related to the insulin resistance syndrome, but is associated with high free fatty acid concentrations in Japanese.

Adult↗

Antidiabetic activity of a xanthone compound, mangiferin.

Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes. MF lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration (p < 0.01). However, no effect on the blood glucose level in normal mice was seen, indicating that MF could be useful in treating type-2 diabetes. In addition, MF improved hyperinsulinemia and, on insulin tolerance test, reduced blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF exerts its antidiabetic activity by decreasing insulin resistance.

Administration, Oral↗

Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.

The antidiabetic activity of the rhizoma of Anemarrhena asphodeloides was investigated in KK-Ay mice, an animal model of genetic type 2 diabetes. The water extract of the rhizoma (AA) (90 mg/kg) reduced blood glucose levels from 570 +/- 29 to 401 +/- 59 mg/dl 7 h after oral administration (p<0.05) and also tended to reduce serum insulin levels in KK-Ay mice. AA-treated KK-Ay mice had significantly reduced blood glucose levels in an insulin tolerance test. Based on these results, the antidiabetic mechanism of AA may be due to decreased insulin resistance. In addition, the active components of AA were confirmed to be mangiferin and its glucoside.

Animals↗

The suppressive effect of mangiferin with exercise on blood lipids in type 2 diabetes.

The effect of mangiferin (MF) with exercise on bood lipids was studied in KK-Ay mice, an animal model of type 2 diabetes. MF (30 mg/kg) reduced the blood cholesterol (p<0.05) and triglyceride level (p<0.01) of KK-Ay mice with exercise 2 weeks after oral administration when compared with the control group. Diabetes also often has elevated lipid levels. Therefore, it may be that MF has beneficial effects on hyperlipidemia in type 2 diabetes.

Animals↗

Effects of soy protein on levels of remnant-like particles cholesterol and vitamin E in healthy men.

We determined the effects of soy protein isolate (SPI) intake on remnant-like particles (RLP), lipolytic enzymes, lipid transfer protein, transaminases, sex hormones, iron, calcium, and vitamin E in healthy men. In the first randomized, crossover experiment, 14 men were given either 20 g per day of SPI or nothing (control) for each 4-week segment. After 3 weeks of SPI intake, TG and RLP cholesterol levels were significantly lower than the baseline by 13.4% (p<0.05) and 9.8% (p<0.05), respectively. However, no significant change was found in total and low-density lipoprotein (LDL) cholesterol levels or the activities of lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase. Although the levels of transaminases. testosterone, iron, and calcium did not change, the vitamin E level was reduced from the baseline by 9.7%, a significant decrease (p<0.01). In the second study, we attempted to determine the effect of vitamin E supplement taken with SPI. For each 3-week segment, 12 men were given 20 g per day of SPI, either with or without 200 mg per day of vitamin E, in a randomized crossover design. The vitamin E level was reduced by 9.2%, a significant decrease (p<0.05), after SPI intake for 3 weeks, and vitamin E supplement increased vitamin E level significantly (p<0.05). These results demonstrate that SPI intake reduces remnant lipoproteins, TG, and the plasma level of vitamin E, although vitamin E supplementation compensates for the reduction of vitamin E. Therefore the supplementation of vitamin E may be required in subjects with long-term and abundant intake of soy protein.

Adult↗

Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice.

The antidiabetic activity of Momordica charantia L. (Cucurbitaceae) was investigated in KK-Ay mice, an animal model with type 2 diabetes with hyperinsulinemia. The water extract of the fruit of Momordica charantia L. (MC) reduced the blood glucose of KK-Ay mice 3 weeks after oral administration (p<0.01) and also significantly lowered the serum insulin of KK-Ay mice under similar conditions (p<0.01). However, MC did not affect the blood glucose in normal mice. MC-treated KK-Ay mice blood glucose significantly decreased in an insulin tolerance test. Moreover, the muscle content of facilitative glucose transporter isoform 4 (GLUT4) protein content in the plasma membrane fraction from muscle significantly increased in the orally MC-treated mice when compared with that of the controls (p<0.01). These results suggest that the antidiabetic effect of MC is derived, at least in part, from a decrease in insulin resistance because of the increase of GLUT4 protein content in the plasma membrane of the muscle.

Administration, Oral↗

Acetyl-seryl-aspartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells.

A natural tetrapeptide, acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological negative regulator of hematopoiesis. The precursor of AcSDKP, thymocin beta 4, is expressed in many tissues including kidney. The present study examined the antiproliferative effect of AcSDKP in two renal cell lines, namely, renal interstitial fibloblasts cell line (NRK 49F) and renal proximal tubular epitherial cells (LLC-PK1). An addition of AcSDKP for 48 hours in theses cells resulted in a concentration-dependent attenuation in the proliferation rate (significant difference to non-treated cells was observed at 10(-9) to 10(-5) M AcSDKP) determined by a colorimetry of alamer blue oxidation. The cell cycle analysis of NRK 49F cells treated with AcSDKP showed that AcSDKP significantly reduced the ratio of S-phase to G2/M-phases. Thus, physiological concentrations of AcSDKP is capable of altering cell cycle to inhibit the proliferation of renal cells.

Animals↗

Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells.

1. Carvedilol, an adrenoceptor blocker with antioxidant activity, was studied for its ability to interact with NO in a cell-free condition and in an endothelial cell line (ECV304). 2. In a cell-free system, carvedilol attenuated NO-dependent reduction of carboxy-2-phenyl-4,4, 5,5-tetramethyl-imidazoline-1-oxyl-3-oxide induced by a NO donor, 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene (NOC5), which was determined by electron paramagnetic resonance (EPR) spectrometry. The EPR study also showed that nitrosylhaemoglobin formation in rat red blood cells by the addition of NO-saturated solution was attenuated by prior incubation with 0.1 - 10 microM carvedilol. 3. NO-induced fluorescence in 4,5-diaminofluorescein-2 diacethyl (DAF-2DA)-loaded ECV304 cells was attenuated by carvedilol but not by labetalol. The IC(50) of carvedilol for NOC5 or sodium nitroprusside-induced fluorescence of DAF-2DA in ECV304 cells was 1. 0x10(-7) M, which was similar to the reported IC(50) of carvedilol for the antioxidant effect. 4. Cell toxicity induced by a NO donor determined by the number of viable cells after 24 h treatment with 2-2'(hydroxynitrosohydrazino)bis-ethanamine was significantly attenuated by pretreatment with 1 microM carvedilol. 5. Both free and cell-associated carvedilol quenched NO. Because NO mediates both physiological and pathophysiological processes, NO quenching by the drug may have diverse clinical implications depending upon specific functions of local NO in tissues where carvedilol is distributed.

Animals↗

Effect of epinephrine on GLUT2 protein content in mouse liver.

The intraperitoneal administration of epinephrine (EP) to mice caused a significant increase in the blood glucose level and a significant decrease in the liver glycogen content 1 h after its administration at 0.6 mg/kg (blood glucose; p < 0.01, liver glycogen; p < 0.01). The liver type glucose transporter (GLUT2) mRNA expression and protein content from mouse liver significantly increased in the intraperitoneally EP-treated mice when compared to that in normal mice (mRNA; p < 0.01, protein; p < 0.01). These results suggest that the hyperglycemic effect of EP is due, at least in part, to the increase of GLUT2 protein synthesis.

Animals↗

Biosynthesis of Vicia graminea lectin- and Vicia unijuga lectin-binding glycoproteins in human tumor and nontumor cells and an estimation of its epitope structure.

We investigated biosynthesis of Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding (Vgu) glycoproteins, which are human malignant tumor-associated antigens, in cultured human tumor and non-tumor cells by pulse-labeling experiments with [35S]-methionine, followed by immunoprecipitation using immobilized VUA, SDS-PAGE and autofluorography. It was shown that Vgu glycoproteins synthesized by tumor cells were 15-30 times greater than those of non-tumor cells. It was also shown that about 40-70% of Vgu glycoproteins synthesized by non-tumor cells were secreted from the cells while more than 80% of the antigen synthesized by tumor cells was not secreted, and that Vgu glycoproteins consisted of multiple molecular species with the same epitope. To estimate the epitope structure of Vgu glycoproteins, in preliminary experiments we prepared sialoglycoproteins and/or sialoglycopeptides from purified human glycophorin A. Human glycophorins A(M) and A(N) (GPs-A(M) and A(N)) were treated with Clostridium perfringens neuraminidase to remove all sialic acid residues linked to carbohydrate chains, with Newcastle disease virus (NDV) to remove alpha2-3 linked sialic acid residues, and by Edman's degradation to eliminate N-terminal amino acid of GP-As. Partial or complete desialylation reactions resulted in disappearance of the reactivity of GP-A(M) and GP-A(N) with corresponding antisera and in appearance of reactivities with VUA and VGA. Elimination of N-terminal amino acid of GP-As also resulted in appearance of reactivities with VUA. These results show that sialoglycoproteins with similar serological properties of Vgu glycoprotein could be prepared from GP-As, and suggest that the epitope structure of Vgu glycoprotein may be related to the MN blood type-epitope structure and its sialic acid residues at N-terminal moiety of GP-As.

Amnion↗

Assessment of cerebrospinal fluid levels of serum amyloid P component in patients with Alzheimer's disease.

Serum amyloid P component (SAP) is a normal plasma constituent that is observed both in senile plaque and in neurofibrillary tangle in brains of patients with Alzheimer's disease (AD). In this study, we evaluated the SAP levels in cerebrospinal fluid (CSF) of 72 patients with AD, 11 frontotemporal dementia and nine normal control subjects. There was no significant difference in the SAP levels between the AD group and other groups. However, among AD patients, cognitive function was rated using the Mini-Mental State Examination and was correlated with the SAP level (R = 0.38, P < 0.05). Our results suggest that measurement of the SAP levels in CSF can be useful for assessing the degree of cognitive impairment in AD patients.

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