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Biomedical subjects

M Kobayashi

Publications and source records attributed to M Kobayashi.

At least 361 records · Page 20Linked to original sources
PubMed2001

Carboplatin calculated with Chatelut's formula plus etoposide for elderly patients with small-cell lung cancer.

OBJECTIVE: This dose escalation was conducted to evaluate the applicability of Chatelut's dosing, and to determine the efficacy and toxicity of carboplatin with etoposide in previously untreated elderly patients (>70 years) with small cell lung cancer. PATIENTS AND METHODS: Seventeen patients were treated with etoposide for 3 days and carboplatin calculated dose using Chatelut's formula on day 1 intravenously. The starting doses of etoposide on days 1 to 3, and carboplatin using the area under the concentration versus time curve (AUC) were 90 mg/m2 and 4 mg/ml x min, respectively. RESULTS: The median age was 77 years (range 71 to 87). Dose-limiting toxicity (DLT) was seen at level 4 (AUC 5 mg/ml x min of carboplatin and etoposide 100 mg/m2). Hematologic toxicity was the primary DLT. Grade 4 thrombocytopenia and Grade 4 leukopenia were observed at level 4. Non-hematologic toxicity was insignificant. The overall response rate was 94%. CONCLUSION: Etoposide at 100 mg/m2 and AUC of carboplatin of 4.5 mg/ml x min as calculated using Chatelut's formula every four weeks is the recommended dose for further phase II trials for elderly patients with small cell lung cancer.

Aged↗
PubMed2001

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features.

OBJECTIVE: The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A population of 735 IgAN patients whom we were able to observe for more than two years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. CONCLUSION: These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.

Adolescent↗
PubMed2001

Dietary habits among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases.

Dietary habit is closely associated with development of cancer and cardiovascular diseases, however little prospective evidence has been published for Japanese, whose dietary habit is substantially different from Western countries. Therefore, frequencies of food consumption, food preference, cooking method and acceptance of dietary advice were investigated at the baseline by two kinds of self-administered food frequency questionnaires. Dietary habits between urban and rural (Tokyo and Osaka vs. others), or between Okinawa and non-Okinawa revealed recognizable differences. The so-called westernized foods such as bread, beef and coffee were more consumed in the urban areas such as Tokyo and Osaka and also in Okinawa. The frequencies of salted food intake such as pickled vegetables and salted seafoods were remarkably low in Okinawa. Cooking methods for meats, seafoods and vegetables were also unique in Okinawa. No distinct geographical difference was shown in food preference and modification of dietary habit by dietary advice.

Adult↗
PubMed2001

Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator--activated receptor-gamma.

Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin resistance associated with obesity, a major risk factor for the development of type 2 diabetes. The insulin resistance induced by TNF-alpha is antagonized by thiazolidinediones (TZDs), a new class of insulin-sensitizing drugs. The aim of the current study was to dissect the mechanism whereby pioglitazone, one of the TZDs, ameliorates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Pioglitazone restored insulin-stimulated 2-deoxyglucose (DOG) uptake, which was reduced by TNF-alpha, with concomitant restorations in tyrosine phosphorylation and protein levels of insulin receptor (IR) and insulin receptor substrate (IRS)-1, as well as association of the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase with IRS-1 and PI 3-kinase activity. Adenovirus-mediated gene transfer of either wild-type human peroxisome proliferator-activated receptor (PPAR)-gamma2 or a mutant carrying a replacement at the consensus mitogen-activated protein kinase phosphorylation site (hPPAR-gamma2-S112A) promoted adipogenesis of 3T3-L1 fibroblasts and restored TNF-alpha-induced decrease of triglyceride in adipocytes as effectively as pioglitazone. Overexpression of the PPAR-gamma proteins in TNF-alpha-treated adipocytes restored protein levels of IR/IRS-1, but did not improve insulin-stimulated tyrosine phosphorylation of IR/IRS-1 or insulin-stimulated 2-DOG uptake. These results indicate that the ability of pioglitazone to restore insulin-stimulated tyrosine phosphorylation of IR/IRS-1, which is necessary for amelioration of TNF-alpha-induced insulin resistance, may be independent of the adipogenic activity of PPAR-gamma that regulates protein levels of IR/IRS-1.

3T3 Cells↗
PubMed2001

Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes.

Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110(CAAX)) or Akt activation stimulated by platelet-derived growth factor. Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. These results indicate that cellular insulin resistance induced by chronic GH treatment in 3T3-L1 adipocytes is caused by uncoupling between activation of PI 3-kinase and its downstream signals, which is specific to the insulin-stimulated PI 3-kinase pathway. This effect of GH might result from the altered subcellular distribution of IRS-1-associated PI 3-kinase.

3T3 Cells↗
PubMed2001

Susceptibility and negative epistatic loci contributing to type 2 diabetes and related phenotypes in a KK/Ta mouse model.

The KK/Ta mouse strain serves as a suitable polygenic model for human type 2 diabetes. Using 93 microsatellite markers in 208 KK/Ta x (BALB/c x KK/Ta)F1 male backcross mice, we carried out a genome-wide linkage analysis of KK/Ta alleles contributing to type 2 diabetes and related phenotypes, such as obesity and dyslipidemia. We identified three major chromosomal intervals significantly contributing to impaired glucose metabolism: one quantitative trait locus for impaired glucose tolerance on chromosome 6 and two loci for fasting blood glucose levels on chromosomes 12 and 15. The latter two loci appeared to act in a complementary fashion. Two intervals showed significant linkages for serum triglyceride levels, one on chromosome 4 and the other on chromosome 8. The KK allele on chromosome 8 acts to promote serum triglyceride levels, whereas the KK allele on chromosome 4 acts to suppress this effect in a recessive fashion. In addition, it is suggested that the chromosome 4 locus also acts to downregulate body weight and that the chromosome 8 locus acts to upregulate serum insulin levels. Our data clearly showed that each disease phenotype of type 2 diabetes and related disorders in KK/Ta mice is under the control of separate genetic mechanisms. However, there appear to be common genes contributing to different disease phenotypes. There are potentially important candidate genes that may be relevant to the disease.

Alleles↗
PubMed2001

Primary central nervous system lymphomas express Vh genes with intermediate to high somatic mutations.

Primary central nervous system lymphoma (PCNSL) is a rare disease, especially among non-AIDS patients. Although almost all PCNSLs belong to the diffuse large B-cell lymphoma (DLBL) category, its clinical course differs from that of other types of DLBL. To elucidate the histogenesis of PCNSL, we analyzed the source of the cells from its variable region (VH) sequences using the polymerase chain reaction (PCR) method to amplify the immunoglobulin heavy chain (IgH) gene of DNA extracted from paraffin sections. Fifteen patients with AIDS-unrelated PCNSL of DLBL type, (7 males and 8 females), were evaluated. Only one case showed positive evidence of EBV infection. The prognosis was very poor with a median survival of 9 months. Analysis of the VH sequences revealed that the VH4 family was used in 4 cases and the VH3 family in 2 cases. The homology with previously published germline sequences was random, ranging from 82.7-93.2%, showing intermediate to high somatic mutations. In 3 of 6 cases, the existence of intraclonal diversity was suspected. These findings suggest that PCNSLs are histogenetically derived from antigen selected B cells in the germinal center (GC) environment.

Adult↗
PubMed2001

[Survey of pesticide residues in baby foods (1996.4-1998.6)].

Between April 1996 to June 1998, 133 samples of 9 food commodities were analyzed for pesticide residues. In 8 samples of 5 commodities, 5 kinds of pesticides residues were detected. The baby foods in which the pesticides were detected were produced from vegetables and fruits. In our investigations, pesticide residues have been frequently detected in the raw materials. For the baby foods containing pesticides, intake amounts of the pesticides calculated from the daily feeding volume and the ADI were compared. Residual pesticide levels in baby food commodities are low, and it was concluded that they are not likely to present any problem in normal usage.

Humans↗
PubMed2001

[Efficacy of lidocaine cream in protecting against thermal stress during hyperthermia].

Hyperthermia is performed in combination with chemotherapy as multimodal treatment for recurrent and advanced cancer. It is generally believed that the temperature cannot be raised higher because of thermal stress. In this study, we examined the efficacy of lidocaine cream in protecting against thermal stress during hyperthermia. We devised a new local anesthetic cream containing 5% lidocaine. The subjects were eighteen patients with stomach cancer, liver cancer, or large intestine cancer. This cream was applied locally to the skin with an occlusive dressing for about one hour before hyperthermia was performed, and was wiped away just before hyperthermia. The pain scores in the treatment group were significantly lower than in the no-treatment group (p < 0.05). The scores for sensation of heat in the treatment group were lower, though not to a significant extent, than those in the no-treatment group. No adverse effects were observed. Plasma concentrations of lidocaine were lower than 0.5 microgram/ml, and percutaneous absorption of lidocaine from the lidocaine cream was minimal.

Anesthetics, Local↗
PubMed2001

Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs.

YM976 is a novel and specific phosphodiesterase 4 inhibitor. In our previous report, we indicated that YM976 has less emetogenicity, a major adverse effect of PDE4 inhibitors, than rolipram. In the present study, we examined the antiasthmatic effects of YM976 in guinea pigs. YM976 orally administered exhibited inhibition of antigen-induced bronchoconstriction, airway plasma leakage, airway eosinophil infiltration, and airway hyperreactivity (AHR), with ED(50) values of 7.3, 5.7, 1.0, and 0.52 mg/kg, respectively. Rolipram also dose dependently suppressed these responses. Prednisolone suppressed eosinophil infiltration and AHR, whereas it failed to inhibit bronchoconstriction and plasma leakage. Theophylline moderately suppressed bronchoconstriction and edema, but neither eosinophil infiltration nor AHR. YM976 suppressed the peroxidase activity in the bronchoalveolar lavage fluid, and elevated the intracellular peroxidase activity and cAMP contents of infiltrated cells, suggesting that YM976 inhibited not only the infiltration but also the activation of leukocytes. In vitro studies revealed that YM976 potently suppressed eosinophil activation (EC(30) = 83 nM), and exerted a little relaxation on LTD(4)-precontracted tracheal smooth muscle (EC(50) = 370 nM). Rolipram exhibited a potent tracheal relaxation activity (EC(50) = 50 nM). In vivo studies indicated that the inhibitory effect of YM976 on LTD(4)-induced bronchospasm was marginal even at 30 mg/kg p.o., although rolipram significantly inhibited the bronchospasm at the same dose. These results suggested that YM976, unlike rolipram, showed the inhibition of antigen-induced airway responses due to anti-inflammatory effects, but not to direct tracheal relaxation. In conclusion, YM976 may have potential therapeutic value in the treatment of asthma through its anti-inflammatory activities.

Animals↗
PubMed2001

[Knowledge, behavior, and attitudes toward sex among adolescent students at a junior/high school in Cote d'Ivoire].

OBJECTIVES: To be able to provide appropriate information about sex to adolescent students in the Cote D'Ivoire, we conducted a study to determine knowledge, behavior, and attitudes toward sex. METHODS: We conducted a cross-sectional study at a junior/high school using a self-administered questionnaire which contained students' characteristics (age, sex, grade, tribe, region), their knowledge about sex, sexual behavior (including experience of sex and contraception), and attitudes toward sex. Knowledge about sex and proportions employing contraception were compared between males and females and between the lower and the upper grades. We also examined associations between attitudes toward sex and contraception. RESULTS: A total of 695 (males: 278, females: 417) students filled in our questionnaire (response rate: 33.1%). The proportion of the students who had experienced sex was 84.2% for males, 46.5% for females, and the average age of the first sex was 14.3 and 15.6 years in males and females, respectively the proportions using contraception was 49.6% and 46.9%. In students of the lower grades, males had greater knowledge than females, but this difference was reduced with progression through the upper grades. The proportion using contraception in the upper grades was also higher and an association between attitude toward sex and contraception was clear. CONCLUSION: Adolescent students' knowledge, behavior, and attitudes toward sex could be relatively easily investigated at a junior/high school of Cote D'Ivoire. The majority of males and half of the females in this setting already had experience of sexual intercourse. The study showed that difference in sexual knowledge between males and females shrunk with increase in school grade. We also showed an association between attitude toward sex and contraception.

Adolescent↗