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Biomedical subjects

K Sugawara

Publications and source records attributed to K Sugawara.

At least 19 recordsLinked to original sources
PubMed2001

Dietary fiber showed no preventive effect against colon and rectal cancers in Japanese with low fat intake: an analysis from the results of nutrition surveys from 23 Japanese prefectures.

BACKGROUND: Since Fuchs' report in 1999, the reported protective effect of dietary fiber from colorectal carcinogenesis has led many researchers to question its real benefit. The aim of this study is to evaluate the association between diet, especially dietary fiber and fat and colorectal cancer in Japan. METHODS: A multiple regression analysis (using the stepwise variable selection method) was performed using the standardized mortality ratios (SMRs) of colon and rectal cancer in 23 Japanese prefectures as objective variables and dietary fiber, nutrients and food groups as explanatory variables. RESULTS: As for colon cancer, the standardized partial correlation coefficients were positively significant for fat (1,13, P = 0.000), seaweeds (0.41, P = 0.026) and beans (0.45, P = 0.017) and were negatively significant for vitamin A (-0.63, P = 0.003), vitamin C (-0.42, P = 0.019) and yellow-green vegetables (-0.37, P = 0.046). For rectal cancer, the standardized partial correlation coefficient in fat (0.60, P = 0.002) was positively significant. Dietary fiber was not found to have a significant relationship with either colon or rectal cancers. CONCLUSIONS: This study failed to show any protective effect of dietary fiber in subjects with a low fat intake (Japanese) in this analysis, which supports Fuchs' findings in subjects with a high fat intake (US Americans).

Colonic Neoplasms↗
PubMed2001

Relationship between some chemical components of herbage, dietary preference and fresh herbage intake rate by the Japanese serow.

The serow is a native Japanese mammal and has been designated as a special natural treasure. However, it has been a pest of crops since the 1970s. Since the serow is an indigenous and protected species, it must be controlled without endangering the animal itself. To do this, it is necessary to determine if the serow selects particular crops to consume, and if so, what components of the crop plants influence this choice.In Experiment 1, we measured the preference of four serows for two crop plants and three wild plants, using the cafeteria method. The plants were offered to the animals from 09.00 to 15.30. The serows preferred crop plants to wild plants. The crude protein content of crop plants (28.0 and 32.7%) was higher than that of the other plants (P<0.05). Dry matter (DM) intakes per hour correlated positively with crude protein content (P<0.01) and negatively with nitrogen free extract content (NFE) (P<0.05) and acid detergent fibre content (ADF) (P<0.01) in the offered plants. In Experiment 2, the food intakes of 17 plants consisting of 6 crops and 11 wild plants were measured. Individual 300g samples from each plant were offered for 20min. The serows ate the crops and the forbs in preference to the tree leaves. They consumed little of the conifer tree leaves and the grasses. The dry matter intake and the ADF content were negatively correlated (P<0.05). The dry matter intake and the crude protein content were positively correlated (P=0.054). A multiple regression formula was constructed as follows: Y=1.65CP+0.56NFE+0.38DM-57.45,R(2)=0.54,P=0.016The feeding characteristics suggest that crops might be selected and ingested by the serows because of their higher crude protein, NFE and the dry matter contents.

Journal Article↗
PubMed2001

Role of individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of influenza C virus hemagglutinin-esterase protein.

The hemagglutinin-esterase (HE) glycoprotein of influenza C virus is composed of three domains: a stem domain active in membrane fusion (F), an acetylesterase domain (E), and a receptor-binding domain (R). The protein contains eight N-linked glycosylation sites, four (positions 26, 395, 552, and 603) in the F domain, three (positions 61, 131, and 144) in the E domain, and one (position 189) in the R domain. Here, we investigated the role of the individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of the HE protein by eliminating each of the glycosylation sites by site-specific mutagenesis. Comparison of electrophoretic mobility between the wild-type and the mutant proteins showed that while seven of the glycosylation sites are used, one (position 131) is not. Analysis of reactivity of the mutants with anti-HE monoclonal antibodies demonstrated that glycosylation at position 144 is essential for the formation of conformation-dependent epitopes. It was also evident that glycosylation at the two sites in the F domain (positions 26 and 603), in addition to that in the E domain (position 144), is required for the HE molecule to be transported from the endoplasmic reticulum and that mutant HEs lacking one of these three sites failed to undergo the trimer assembly. Removal of an oligosaccharide chain at position 144 or 189 resulted in a decrease in the esterase activity. By contrast, two mutants lacking an oligosaccharide chain at position 26 or 603, which were defective not only in cell surface expression but in trimerization, possessed full-enzyme activity, suggesting that the HE monomers present within the cell have acetylesterase activity. Fusion activity of cells expressing each of mutant HEs was found to be comparable with the ability of the protein to be transported to the cell surface, suggesting that there is no specific oligosaccharide chain that plays a critical role in promoting membrane fusion.

Acetylesterase↗
PubMed2001

UCS15A, a non-kinase inhibitor of Src signal transduction.

Src tyrosine kinase plays key roles in signal transduction following growth factor stimulation and integrin-mediated cell-substrate adhesion. Since src-signal transduction defects are implicated in a multitude of human diseases, we have sought to develop new ways to identify small molecule inhibitors using a yeast-based, activated-src over-expression system. In the present study, we describe the identification of a unique src-signal transduction inhibitor, UCS15A. UCS15A was found to inhibit the src specific tyrosine phosphorylation of numerous proteins in v-src-transformed cells. Two of these phosphoproteins were identified as bona-fide src substrates, cortactin and Sam68. UCS15A differed from conventional src-inhibitors in that it did not inhibit the tyrosine kinase activity of src. In addition, UCS15A appeared to differ from src-destabilizing agents such as herbimycin and radicicol that destabilize src by interfering with Hsp90. Our studies suggest that UCS15A exerted its src-inhibitory effects by a novel mechanism that involved disruption of protein-protein interactions mediated by src. One of the biological consequences of src-inhibition by UCS15A was its ability to inhibit the bone resorption activity of osteoclasts in vitro. These data suggest that UCS15A may inhibit the bone resorption activity of osteoclasts, not by inhibiting src tyrosine kinase activity, but by disrupting the interaction of proteins associated with src, thereby modulating downstream events in the src signal transduction pathway.

3T3 Cells↗
PubMed2001

XANES analysis of sulfur form change during pyrolysis of coals.

Three kinds of coal and their density separated samples were rapidly pyrolyzed in a free-fall reactor under a nitrogen stream at a terminal temperature of 1253 K. X-ray absorption near edge structure analysis was applied to directly determine the sulfur forms in the coal and pyrolysis char. The results showed that the low-density group contained sulfide and sulfoxide, which could contribute to the high extent of organic sulfur removal. Thermally stable thiophenic sulfur was observed in the higher density groups as a major form of organic sulfur.

Journal Article↗
PubMed2001

No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.

OBJECTIVE: The urinary ratio of 6beta-hydroxycortisol to cortisol is known as a possible marker of CYP3A4 activity. We investigated the correlation between this ratio and the disposition of alprazolam, which is a substrate of CYP3A4. METHODS: Twelve healthy volunteers took a single dose (0.8 mg) of alprazolam at 0800 hours. Blood samplings were conducted up to 48 h after the dosing. Urine was collected during the 24 h prior to dosing. Quantification of alprazolam in plasma and that of cortisol and 6beta-hydroxycortisol in urine was performed using high-performance liquid chromatography. RESULTS: Mean (+/-SD) values of peak plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-48)] and elimination half-life (tl/2) of alprazolam were 12.0+/-3.0 ng/ml, 1.5+/-0.9 h, 200+/-41 ng/ml h and 16.0+/-4.3 h, respectively. Mean (+/-SD) urinary ratio of 6beta-hydroxycortisol to cortisol was 3.28+/-0.67. No significant correlations were found between urinary ratio of 6beta-hydroxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (Cmax: rs= -0.06; tmax: r(s)= 0.34; AUC(0-48): rs=0.08; t1/2: r(s)= -0.36). CONCLUSION: This study suggests that the urinary ratio of 6beta-hydroxycortisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.

Adult↗
PubMed2001

Ecabet sodium inhibits the ability of Helicobacter pylori to induce neutrophil production of reactive oxygen species and interleukin-8.

The pathogenic role of human neutrophils has been implicated in Helicobacter pylori-associated gastritis. Ecabet sodium, a locally acting antiulcer drug, has anti-H. pylori actions. The aim of this study was to examine the effects of ecabet on the ability of H. pylori to stimulate human neutrophils. H. pylori were added to 1 x 10(5) neutrophils and incubated for 30 min in the presence of ecabet. Bacterial suspensions which had been incubated with ecabet for 30 min were also used to stimulate neutrophils. The intracellular production of reactive oxygen species was measured with a FACScan. Bacterial suspensions were also added to neutrophils in the presence of ecabet and incubated at 37 degrees C for 12 h to measure interleukin (IL)-8 production by enzyme-linked immunosorbent assay. The mean fluorescence intensity was found to be attenuated dose-dependently by ecabet (P < 0.01). Ecabet also inhibited IL-8 production by neutrophils in a dose-dependent manner (P < 0.001). Bacteria with prior incubation with ecabet induced significantly lower IL-8 production than those without this incubation (P < 0.05). Ecabet sodium has preventive effects on the ability of H. pylori to stimulate human neutrophils. It may lead to reduced gastritis activity and decreased oxidative damage of the gastric mucosa in H. pylori-associated gastritis.

Abietanes↗
PubMed2001

Antigenic and genetic analyses of influenza B viruses isolated in Lusaka, Zambia in 1999.

Previous studies of the hemagglutinin (HA) genes of various influenza B virus isolates demonstrated the existence of two antigenically distinct virus lineages represented by B/Victoria/2/87 and B/Yamagata/16/88, respectively. Here, we investigated the antigenic and genetic characteristics of influenza B viruses isolated from children living in Lusaka, Zambia between January and May 1999. Antigenic analysis with chicken antiviral sera showed that all the Zambian isolates had the HA protein belonging to B/Yamagata/16/88-related lineage. Furthermore, phylogenetic analyses of the eight RNA segments performed by using the total or partial nucleotide sequences of the two representative Zambian strains (B/Lusaka/270/99 and B/Lusaka/432/99) as well as the previously reported sequences suggested that the Zambian viruses are closely related to the recently circulating reassortants represented by B/Shiga/T30/98 and B/Yamanashi/166/98 which acquired the genes coding for three polymerase proteins (PB2, PB1, and PA), HA, nucleoprotein, and matrix protein from a B/Yamagata/16/88-like parent and the gene encoding nonstructural proteins (NS1 and NS2) from a B/Guandong/8/93-like parent.

Animals↗
PubMed2001

Reactive oxygen species uncouple external horizontal cells in the carp retina and glutathione couples them again.

We have investigated the effect of free radicals on the electrical gap junctions between horizontal cells in the carp retina. In our previous study, L-buthionine sulfoximine, an inhibitor of glutathione synthesis, caused uncoupling of horizontal cells four days after injection. In the present study, we have used paraquat, a generator of exogenous reactive oxygen species, to investigate whether it was the depletion of glutathione or an increase in the level of reactive oxygen species which resulted in horizontal cell uncoupling after L-buthionine sulfoximine injection. Intracellular recordings were made from L-type horizontal cells at various time-points after intravitreal injection of paraquat. Injection of 25nmol paraquat caused an increase in response amplitude to central spot light stimuli by two days after injection, which continued for a further two to three days and had almost disappeared by seven days after injection. There was also a sharp increase in reactive oxygen species production, peaking at four days and disappearing by seven days after injection, and an accompanying depletion and a restoration of glutathione levels with a similar time-course. Marking cells with Lucifer Yellow clearly illustrated uncoupling of horizontal cells after paraquat injection. If paraquat and L-buthionine sulfoximine were injected simultaneously, the increase in response to central spots was observed as early as one day after injection. This response amplitude was not more enhanced than that observed after L-buthionine sulfoximine injection alone, although a dramatic increase in the level of reactive oxygen species was observed. From these results, we suggest that reactive oxygen species are involved in uncoupling, while recovery from uncoupling is dependent on glutathione. Furthermore, we conclude that a balance between glutathione and reactive oxygen species levels is the most important factor controlling gap junctional intercellular communication of L-type horizontal cells in the carp retina.

Animals↗
PubMed2001

Differences in carcinogenesis by the length of carcinogen exposure period in rat colon.

To clarify the carcinogenic factors--whether it is the kind of carcinogen or their length of exposure--that determine whether colorectal cancer develops from an adenoma or develops de novo in the absence of an adenoma, we histopathologically analyzed a total of 229 rat colon tumors induced by administration of 1,2-dimethyl-hydrazine (DMH) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for three or 15 weeks. In the three-week-exposure groups, 71% of DMH-induced carcinomas and 82% of MNNG-induced carcinomas coexisted with low-grade dysplasia (adenomatous remnant). However, in the 15-week-exposure groups, lowgrade dysplasia was observed in only 10% of DMH-induced and 27% of MNNG-induced carcinomas. Even in the tumors smaller than 20 mm3, it was observed in only 10% of DMH-induced and 32% of MNNG-induced carcinomas. Furthermore, carcinomas without low-grade dysplasia predominated from the initial period of tumor occurrence. Next, we investigated association of K-ras and APC gene mutations with these carcinogenesis patterns in 80 tumors. K-ras mutations were not detected in any tumors induced by three weeks of exposure. However, in the 15-week-exposure groups, this mutation was observed in 57% of DMH-induced tumors and 13% of MNNG-induced tumors. APC mutations in the region homologous to the human mutation cluster region were observed in only 6% of tumors. Thus, our results suggest that the carcinogenesis patterns in rat colon are dependent on the length of exposure to carcinogen and that K-ras mutations were partly involved in a subset of them.

1,2-Dimethylhydrazine↗
PubMed2001

Changes in intraluminal pressure in rat large intestines with aging and effects of dietary fiber.

Changes in intraluminal pressure in rat colon with aging and with the effects of dietary fiber were measured. A pressure sensor was inserted into the rat large intestine under endoscopic guidance. The intraluminal pressure curve in the colon was recorded, and the motility index was calculated by this curve. The rats were divided into three groups with a fiber-free diet, a cellulose diet (10% w/w), or a pectin diet (10% w/w). Intraluminal pressure was measured in the proximal, middle, and distal colon at 2, 4, 8, 12, and 16 months after birth. Intraluminal pressure in three sites increased with age and decreased in the latter half of the study. The motility index was lower during the course in the fiber groups, especially the pectin group more than the nonfiber group. This result suggests that long-term ingestion of dietary fiber might have a prophylactic effect on the development of diverticula.

Age Factors↗
PubMed2001

BIP, a BRAM-interacting protein involved in TGF-beta signalling, regulates body length in Caenorhabditis elegans.

BACKGROUND: The TGF-beta superfamily has diverse biological activities and is involved in the early development of animals. We previously identified a novel family member, BMP receptor associated molecule (BRAM), which binds to the intracellular domain of BMP type IA receptor and is involved in the BMP signalling pathway. RESULTS: To identify novel molecules involved in TGF-beta signalling pathways, we performed yeast two-hybrid screening using BRAM as bait. From a Xenopus cDNA library, we cloned a cDNA encoding 693 amino acids and containing the motif for an oxysterol binding protein (OSBP), which we designated BRAM interacting protein (BIP). We then isolated a BIP homologue from the Caenorhabditis elegans that encodes 733 amino acids and also contains the OSBP-like motif. Immunoprecipitation and Western blotting studies revealed that C. elegans BIP could interact with the C. elegans BRAM homologues BRA-1 and BRA-2. C. elegans BIP was expressed in pharyngeal muscle, hypodermis and several neuronal cells, an expression pattern overlaps with those of BRA-1 and BRA-2. Finally, we found that inhibition of BIP expression in C. elegans by double stranded RNA interference produces a Sma phenotype. CONCLUSIONS: BIP was isolated using the yeast two-hybrid systems. BIP may function in the TGF-beta pathway and regulate body length in C. elegans.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in extensive and poor metabolizers of S-mephenytoin.

Pantoprazole, a proton pump inhibitor, is administered as a racemic mixture. To determine the role of cytochrome P450 (CYP) 2C19 in the stereoselective metabolism of pantoprazole, we investigated the pharmacokinetic disposition of (+)- and (-)-pantoprazole in 7 extensive metabolizers and 7 poor metabolizers of S-mephenytoin. All of the subjects received an oral 40-mg dose of racemic pantoprazole as the enteric-coated formulation. In the extensive metabolizers, the mean clearance of (-)-pantoprazole was only slightly lower than that of (+)-pantoprazole and no significant differences in the other pharmacokinetic parameters between (+)- and (-)-pantoprazole were observed. The mean (+)/(-) ratios for maximum concentration, area under the plasma concentration-time curve from 0 to infinity, and elimination half-life were 0.94, 0.82, and 0.90, respectively. In contrast, in the poor metabolizers, the clearance values of both enantiomers were significantly lower than those in the extensive metabolizers, and a significant difference in pharmacokinetics between (+)- and (-)-pantoprazole was observed. The mean elimination half-life for (+)-pantoprazole was 3.55-fold longer than that of (-)-pantoprazole, and the mean maximum concentration and area under the plasma concentration-time curve from 0 to infinity for (+)-pantoprazole were 1.31- and 3.59-fold greater, respectively, than those for (-)-pantoprazole. These results indicate that the stereoselective metabolism of pantoprazole depends on S-mephenytoin 4'-hydroxylase (CYP2C19). The metabolism of (+)-pantoprazole was impaired to a greater extent than (-)-pantoprazole in the poor metabolizers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Analysis of lifestyle and behavioral characteristics in Meniere's disease patients and a control population.

A questionnaire was devised to quantify and measure four categories: the behavioral characteristics of Type A, self-restraint and escape; the causes of anxiety; means of relaxation; and symptoms incidental to anxiety. Questionnaire analysis was performed in patients (n = 60) with Meniere's disease and in a control population (n = 936). It was statistically proven that the patient group possessed a stress-causative tendency in behavioral characteristics, felt stronger anxiety and showed more severe symptoms owing to this anxiety. Since the level of anxiety highly correlates with the score of behavioral characteristics and also with severity of symptoms, it seems likely that behavioral characteristics produce the anxiety, which, in turn, results in various symptoms of autonomic nervous disorders. A tendency towards stress-causative behavioral characteristics in Meniere's disease patients may be important in the genesis of endolymphatic hydrops.

Adaptation, Psychological↗