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Biomedical subjects

Y Kido

Publications and source records attributed to Y Kido.

At least 55 records · Page 3Linked to original sources
PubMed1998

Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue.

Type 2 diabetes is a complex metabolic disorder characterized by peripheral insulin resistance and impaired beta cell function. Insulin resistance is inherited as a non-mendelian trait. In genetically predisposed individuals, resistance of skeletal muscle and adipose tissue to insulin action precedes the onset of clinical diabetes, and is thought to contribute to hyperglycaemia by leading to impaired beta cell function and increased hepatic glucose production. It is not clear whether beta cell and liver defects are also genetically determined. To test the hypothesis that insulin resistance in muscle and fat is sufficient to cause type 2 diabetes in the absence of intrinsic beta cell and liver abnormality, we generated transgenic mice that were insulin-resistant in skeletal muscle and adipose tissue. These mice developed all the prodromal features of type 2 diabetes but, despite the compounded effect of peripheral insulin resistance and a mild impairment of beta cell function, failed to become diabetic. These findings indicate the need for a critical re-examination of the primary site(s) of insulin resistance in diabetes.

Adipose Tissue↗
PubMed1998

Monoclonal-based enzyme-linked immunosorbent assay and immunochromatographic rapid assay for monensin.

Monensin, a member of the ionophoric polyether antibiotics, is used primarily as a coccidiostat. A protein conjugate of monensin was prepared and utilized to produce monoclonal antibodies in the BALB/c-P3X63Ag8U.1 fusion system. Only one hybridoma that produces monoclonal antibody against monensin was isolated from one in 329 wells. The monoclonal antibody was used to develop quantitative assays for monensin by means of an enzyme-linked immunosorbent assay (ELISA). The detection limit was 1 ng ml-1 and the relative standard deviations were 2.1-6.3% intra-assay and 5.9-12.9% inter-assay. All ELISA results for assay of chicken plasma and cattle milk were confirmed using a bioassay to be used as the official method. The ELISA and bioassay results showed close correlations for plasma (r2 = 0.98, n = 25) and milk (r2 = 0.95, n = 25). Using the anti-monensin monoclonal antibodies produced, a rapid test kit based on the immunochromatographic method was developed. Detection limits of monensin for cattle milk, cattle plasma and chicken plasma were about 40, 40 and 160 ppb. respectively.

Animals↗
PubMed1998

Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells.

The adaptor protein Shc contains a phosphotyrosine binding (PTB) domain and a Src homology 2 (SH2) domain, both of which are known to interact with phosphorylated tyrosines. We have shown previously that tyrosine 1148 of the activated epidermal growth factor (EGF) receptor is a major binding site for Shc while tyrosine 1173 is a secondary binding site in intact cells. In the present study, we investigated the interaction between the PTB and SH2 domains of Shc and the activated human EGF receptor. Mutant 52-kDa Shc with an arginine-to-lysine substitution at residue 175 in the PTB domain (Shc R175K) or 397 in the SH2 domain (Shc R397K) was coexpressed in Chinese hamster ovary cells overexpressing the wild-type or mutant EGF receptors that retained only one of the autophosphorylation sites at tyrosine 1148 (QM1148) or 1173 (QM1173). Shc R397K was coprecipitated with the QM1148 and QM1173 receptors, was tyrosine-phosphorylated, and associated with Grb2 and Sos. In contrast, coprecipitation of Shc R175K with the mutant receptors was barely detectable. In cells expressing the QM1173 receptor, Shc R175K was tyrosine-phosphorylated and associated with Grb2, while association of Sos was barely detectable. In cells expressing the QM1148 receptor, tyrosine phosphorylation of Shc R175K was markedly reduced. When both Shc R175K and 46-kDa Shc R397K were coexpressed with the mutant receptors, p46 Shc R397K was dominantly tyrosine-phosphorylated. In cells expressing the wild-type receptor, Shc R397K, but not Shc R175K, translocated to the membrane in an EGF-dependent manner. In addition, Ras activity stimulated by the immunoprecipitates of Shc R397K was significantly higher than that by the immunoprecipitates of Shc R175K. The present results indicate that tyrosine 1148 of the activated EGF receptor mainly interacts with the Shc PTB domain in intact cells. Tyrosine 1173 interacts with both the PTB and SH2 domains, although the interaction with the PTB domain is dominant. In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Topostatin, a novel inhibitor of Topoisomerases I and II produced by Thermomonospora alba strain No. 1520. II. Physico-chemical properties and structure elucidation.

Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of Thermononospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and II, and it has neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The molecular formula of topostatin was determined as C36H58N4O11S based on the FAB-MS analyses, and the structure was elucidated to be a novel 14-membered ring containing peptide and terpenoid by various NMR spectroscopies.

Enzyme Inhibitors↗
PubMed1997

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Adult↗
PubMed1997

A newly isolated family of short interspersed repetitive elements (SINEs) in coregonid fishes (whitefish) with sequences that are almost identical to those of the SmaI family of repeats: possible evidence for the horizontal transfer of SINEs.

The SmaI family of repeats is present only in the chum salmon and the pink salmon, and it is not present in five other species in the same genus or in other species in closely related genera. In the present study, we showed that another short interspersed repetitive elements (SINEs) family, which is almost identical to the SmaI family, is present in all fishes in the subfamily Coregoninae, being regarded as the most primitive salmonids. This new family of SINEs was designated the SmaI-cor family (SmaI family of repeats in coregonids). The consensus sequence of the SmaI-cor family was found to be 98.6% homologous to that of the SmaI family. Accordingly, it is difficult to explain the high degree of homology between these two families of SINEs by any mechanism other than the horizontal transfer of SINEs. The estimates of the rate of neutral mutation of nuclear genes, comparing chum salmon and European whitefish, confirmed this possibility. Our results strongly suggest that a member(s) of the SmaI-cor family might have been transferred horizontally from one coregonid species to a common ancestor of chum and pink salmon or to these two species independently, to allow subsequent amplification of the SmaI family in their respective genomes.

Animals↗
PubMed1997

Enhancement of the mitogenic effect by artificial juxtacrine stimulation using immobilized EGF.

Mouse epidermal growth factor (EGF) was covalently conjugated with the water-soluble polymer, poly(acrylic acid) (EGF-PAA), or with the water-insoluble polymer, surface-hydrolyzed poly(methyl methacrylate) (EGF-PMMA). Immobilized EGF (EGF-PMMA) stimulated DNA synthesis in Chinese hamster ovary cells overexpressing EGF receptors in amounts that were 5 to 10% of those of free EGF required for comparable effects. In addition, the maximal mitogenic effect of EGF-PMMA was greater than that of unconjugated EGF or EGF-PAA. EGF, EGF-PAA, and EGF-PMMA induced the autophosphorylation of EGF receptors and the stimulation of mitogen-activated protein kinase. However, whereas the onset of these effects was delayed with EGF-PMMA, they persisted for much longer than those of EGF and EGF-PAA. Unlike EGF and EGF-PAA, EGF-PMMA was not associated with cells after their removal from culture and did not induce receptor internalization. Culturing cells with PMMA-immobilized EGF thus represents a model system for studying "juxtacrine" stimulation of cells by membrane-bound growth factors.

Acrylic Resins↗
PubMed1997

Recommended daily exercise for Japanese does not increase the protein requirement in sedentary young men.

In a previous study, we reported that protein intake at the level of dietary protein allowance for Japanese adults, i.e. 1.08 g/kg per day, was enough for recommended daily exercise. However, whether or not recommended daily exercise increases the protein requirement for young adults has not been examined. In this study, we investigated the effect of recommended daily exercise on the protein requirement under an isoenergetic state by a nitrogen balance method. After an adaptation period of 3 days, 12 healthy college students exercised for 10 days with a non-exercise control period of 10 days before or after the exercise period. They were given a maintenance level of energy and 0.64 g/kg per day of high-quality mixed proteins, estimated as the average protein requirement for adults by the Ministry of Health and Welfare of Japan, throughout the experimental period. They performed treadmill running during the exercise period at about 65% of VO2 max for 25 or 40 min/d, which expended 200 or 300 kcal of extra energy, respectively. Although the exercise increased the dermal nitrogen loss, a compensatory decrease in urinary nitrogen excretion was observed. Consequently, the exercises (200 and 300 kcal/d) did not significantly affect the nitrogen balance. These findings indicate that the recommended amount of daily exercise does not change the protein requirement.

Adult↗
PubMed1997

Japanese dietary protein allowance is sufficient for moderate physical exercise in young men.

The sufficiency of the dietary protein allowances recommended by the Ministry of Health and Welfare of Japan for various physical exercises has not been examined. We investigated the protein requirement for moderate-intensity physical exercise using nitrogen balance in the isoenergetic state. Seventeen healthy college students exercised for 10 days with an adaptation period of three days and non-exercise control period of 10 days. They were given a maintenance level of energy and 1.08 g/kg per day of high quality mixed proteins recommended by the Ministry of Health and Welfare of Japan throughout the experimental period. They performed treadmill running during the exercise period at about 65% of VO2max for 25, 41 or 48 min/day, which required 200, 300 or 400 kcal of extra energy, respectively. Although the exercise increased dermal nitrogen loss, urinary nitrogen excretion tended to decrease. Consequently, the exercise ranging from 200 to 400 kcal/day did not significantly alter the nitrogen balance. Thiobarbituric acid-reactive substances and glutathione disulfide were not increased after exercise, suggesting that the moderate exercise, recommended for health promotion by the Ministry of Health and Welfare of Japan, does not cause oxidative damage to healthy subjects. These findings demonstrate that a protein intake of 1.08 g/kg per day is enough for moderate exercise.

Adult↗
PubMed1997

A new antiherpetic agent, AH-1763 IIa, produced by Streptomyces cyaneus strain no. 1763.

A new antiherpetic agent, AH-1763 IIa, was isolated from the culture broth of strain No. 1763 identified as Streptomyces cyaneus. It was purified through column chromatographies of Diaion HP-10 and silica gel. The structure was determined to be 11-hydroxy-5-methyl-2-(2-hydroxy-1-methylpropyl)-4H-anthraceno [1,2-b]pyran-4,7,12-trione by several spectroscopic experiments, that is a new antibiotic belonging to pluramycin-group.

Animals↗
PubMed1997

Perforated diverticulum of the transverse colon.

We report a case of perforated diverticulitis of the transverse colon. The preoperative diagnosis of perforated appendicitis was made on the basis of findings of both ultrasonography and CT. At surgery, an inflammatory mass resembling carcinoma was found in the transverse colon, and segmental resection was then performed. Diverticulitis of the transverse colon is rare, and there have been few reports in the English-language medical literature. This report describes a true diverticulum of the transverse colon that presented as acute diverticulitis.

Adult↗
PubMed1996

Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas.

BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) has demonstrated significantly increased response rates in comparison with the use of 5-FU alone in patients with advanced colorectal carcinoma. However, the higher response rate of LV/5-FU may occur at the expense of increased toxicity and side effects such as diarrhea, myelosuppression, and mucositis. During chemotherapy, a high incidence of hypocalcemia associated with this chemotherapy regimen was noted. This study was therefore aimed at assessing the side effects of chemotherapy using low dose LV/5-FU on calcium metabolism. METHODS: Twenty-five patients with advanced gastric or colorectal carcinoma were treated with chemotherapy comprised of low dose LV administered at 20 mg/m2/ day by intravenous bolus, followed by 1-hour intravenous infusion of 5-FU at 425-600 mg/m2/day for 5 consecutive days every 28 days. RESULTS: The toxic effects were generally mild, and included diarrhea, mucositis, leukopenia, and nausea/vomiting. Fifteen patients (65%) experienced hypocalcemia. The plasma 1,25-(OH)2D3 levels were significantly reduced on Day 5 due to the chemotherapy. CONCLUSIONS: The toxic effects of the regimen were generally mild. However, a high percentage of hypocalcemia occurred with the combination of LV/5-FU. It is therefore necessary to examine carefully the serum calcium levels of patients when using this chemotherapeutic modality.

Aged↗
PubMed1996

Interaction of Shc with adaptor protein adaptins.

The role of Shc as a substrate of receptors for growth factors and cytokines is well established. To gain further insight into the function of Shc in signal transduction, we used an affinity method to identify potential Shc-binding proteins. Incubation of bovine brain lysates with a glutathione S-transferase (GST)-Shc fusion protein immobilized on glutathione-Sepharose beads resulted in the binding of cellular proteins of approximately 115, 110, and 100 kDa as well as those of 50 and 17 kDa. Amino acid sequencing of tryptic peptides revealed that the 100-kDa protein was almost identical to beta-adaptin and that the 110- and 115-kDa proteins were almost identical to alphaA-adaptin. Using immunoblot analysis, anti-alpha-adaptin antibody recognized several proteins of 100 approximately 115 kDa, and anti-beta-adaptin antibody recognized a 100-kDa protein, suggesting that alphaA-, alphaC-, and beta-adaptins are bound to the GST-Shc fusion protein. Immunoblot analysis with anti-alpha-adaptin antibody revealed that alpha-adaptin was coimmunoprecipitated with Shc from PC12, KB, and COS cell lysates, suggesting a specific interaction of Shc and adaptins in intact cells. A binding study using mutant GST-Shc fusion proteins revealed that the collagen homologous region (amino acids 233-377) of Shc was required for adaptin binding. Conversely, the collagen homologous region of Shc inhibited the binding of adaptins to GST-Shc. In addition, adaptin was able to bind mutant fusion proteins containing amino acids 233-369, 233-355, 346-369, and 346-355 of Shc, but failed to bind a mutant containing amino acids 233-345, suggesting that amino acids 346-355 (RDLFDMKPFE) in the collagen homologous region of Shc are required for adaptin binding. Thus, this study indicates the specific interaction of Shc with alpha- and beta-adaptin components of plasma membrane adaptor proteins that are thought to be involved in receptor endocytosis.

Adaptor Protein Complex 2↗
PubMed1996

Cystic mesothelioma of the peritoneum.

We report a case of cystic mesothelioma of the peritoneum (CMP), a rare tumor. The magnetic resonance imaging (MRI) findings and the histochemical features were studied. The patient was an 18-year-old women who presented with upper abdominal pain. Abdominal ultrasonography and computed tomography showed a well defined cystic mass with a solid papillary projection in its lumen. MRI of the cyst showed high intensity on T2- and proton weighted images and low intensity on T1-weighted images, and the solid projection showed low intensity on T2- and proton-weighted images and slight low intensity on T1-weighted images, on which it was well enhanced. The lesion was suspected to be a benign cyst, such as a hemangioma, lymphangioma, or a splenic or pancreatic cyst. Complete surgical resection was performed. The resected specimen consisted of a unilocular cystic mass, with a solid projection, weighing 260 g and measuring 10 cm in diameter. The final diagnosis, arrived at by histopathological examination, was low-grade malignant CMP. The tumor cells were strongly positive for keratin, weakly positive for vimentin, and negative for epithelial membranous antigen. The patient is now well and symptom-free with no recurrence 19 months after operation. CMP is a rare tumor; only 12 cases have previously been reported in Japan.

Adolescent↗
PubMed1996

Tryptophan modulates exocrine secretory function in rat pancreatic acini.

We investigated the effect of tryptophan (Trp) on exocrine secretory function, using isolated rat pancreatic acini. Trp inhibited cholecystokinin-octapeptide (CCK-8)-stimulated amylase secretion, causing a downward shift in the dose-response curve. The inhibitory effect of Trp was dose-dependent and was observed only on the sustained secretion, there being no effect on the initial phase of amylase secretion. Trp (10mM) also inhibited amylase secretion in response to carbachol and bombesin, as well as fluoride, a potent activator of guanine-nucleotide binding proteins. Since Ca2+ influx is necessary for sustained secretion, we examined the effect of Trp on Ca2+ influx and efflux. Trp increased the CCK-8-stimulated Ca2+ influx rate without affecting Ca2+ efflux, suggesting that Trp elevates intracellular Ca2+ levels. Increasing intracellular Ca2+ levels with A23187 resulted in the inhibition of CCK-8-stimulated amylase secretion. These results indicate that Trp inhibits CCK-stimulated sustained amylase secretion, in part by increasing Ca2+ influx into acinar cells.

Amylases↗
PubMed1996

Modulation of thermogenic response to parenteral amino acid infusion in surgical stress.

Thermogenic response to parenteral infusion of amino acid mixtures in rats undergoing surgical stress was investigated with the aid of a small animal indirect calorimeter. Male Wistar rats (n = 12) were laparotomized and received intestinal abrasion along with construction of a parenteral route. After 48 h, nutrient-induced thermogenesis (NIT) produced by amino acid mixtures was examined and compared with that of control rats (n = 12) without surgical stress. The NIT values of the leucine-enriched solution were greater than those of the control solution in both rats with and without surgical stress. The NIT generated by the leucine-enriched solution in rats with surgical stress was significantly higher than that in rats without. NIT values for 10 different kinds of single amino acid solutions with identical concentrations was then examined in 60 rats. The NIT values of the leucine and the glycine solutions were relatively higher than those of other solutions. However, when puromycin was injected intraperitoneally into 12 rats just before measurement of the NIT in response to amino acid mixtures, no significant differences were found in NIT values between the mixtures. In summary, surgical stress increased the thermogenic response to the leucine-enriched solution, indicating that utilization of leucine may be augmented under surgical stress. In fact, leucine itself may be a thermogenic amino acid. Inhibition of protein synthesis prevented the increase in thermogenic response induced by the leucine-enriched solution. We conclude that thermogenic responses to parenteral amino acid mixtures may differ depending not only upon the compositions of amino acids but also upon the host conditions.

Amino Acids↗
PubMed1996

A total parenteral nutrition solution supplemented with a nucleoside and nucleotide mixture sustains intestinal integrity, but does not stimulate intestinal function after massive bowel resection in rats.

The effects of supplementing a total parenteral nutrition solution with a nucleoside and nucleotide mixture on mucosal adaptive processes after massive bowel resection were studied. Male Wistar rats (n=30) underwent 80% small intestine resection, were randomized into two groups and received either standard total parenteral nutrition (TPN) or TPN supplemented with a nucleoside and nucleotide mixture (2.5 mL.kg-1.d-1). An additional five rats, fed a nonpurified diet and not resected, were used as controls. After 4 or 7 d, rats were killed and samples were collected for mucosal indices and intestinal enzymatic activities (disaccharidases and diamine oxidase). After massive small bowel resection and TPN, residual jejunal mucosal wet weights, villus heights, protein and RNA contents on d 4 and 7, and total wet weights and DNA contents on d 7 were significantly lower than in the control group. Administration of the nucleoside and nucleotide mixture resulted in significantly higher residual jejunal total and mucosal weights, proteins, DNA, RNA contents, and the ratio of proliferating cell nuclear antigen positive cells per crypt than did the standard TPN solution on d 7. However, disaccharidase and diamine oxidase activities were not affected by supplementation with the nucleoside and nucleotide mixture. Our data suggest the supplementation of a nucleoside and nucleotide mixture to a TPN solution can attenuate the initial mucosal atrophy and improve intestinal cell turnover after massive bowel resection, but the supplementation has little effect on enterocyte enzymatic activities.

Amine Oxidase (Copper-Containing)↗