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Biomedical subjects

S Tokudome

Publications and source records attributed to S Tokudome.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of lifestyle and risk factors among Japanese with and without gastric cancer family history.

To find specific risk factors of gastric cancer (GC) independent of GC family history (GCFH), 2 studies were conducted using the database of the Hospital-based Epidemiological Research Program at Aichi Cancer Center: (i) a comparison of lifestyles between non-cancer cases with positive and negative GCFH status and (ii) a case-reference investigation of subjects with and without GCFH, treated separately. The first showed no significant variation of GCFH status with regard to smoking, drinking and most food habits. Multivariate analyses in the case-referent studies revealed odds ratios (ORs) for GC associated with habitual smoking of 2.78 (95% CI 1.22-6.28) for those with and 2.74 (95% CI 1.76-4.26) for those without GCFH. In individuals with GCFH, an independently lowered OR (0.52, 95% CI 0.27-0.99) was evident for frequent consumption of raw vegetables, whereas the opposite was noted for pickled vegetables (2. 39, 95% CI 1.28-4.45). No statistically significant interaction was found between GCFH and selected lifestyle items. In conclusion, our results suggest a limited influence of GCFH on risk factors for GC.

Adult↗
PubMed2000

Additive effects of estrogen deficiency and diabetes on bone mineral density in rats.

We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive.

Alkaline Phosphatase↗
PubMed2000

Validity of brief intelligence tests for patients with Alzheimer's disease.

The validity of two kinds of brief intelligence tests for patients with Alzheimer's disease (AD) was investigated. In study 1, five short forms of the Japanese Wechsler Adult Intelligence Scale-Revised (JWAIS-R) were administered to 102 AD patients. The results showed that the intra-class correlation coefficients (ICC) between IQ estimated with the short forms and those obtained by administration of the full JWAIS-R were satisfactory, ranging from 0.82 to 0.98, and that the abbreviated forms took a shorter time to execute. In study 2, the Raven's Coloured Progressive Matrices (RCPM) and the Mini-Mental State Examination (MMSE) were administered to 67 AD patients. The ICC between the IQ estimated with these tests and the full-scale IQ of the JWAIS-R were both acceptable at 0.57, and each test could be carried out in a very short time. It was concluded that these brief tests, particularly the WAIS-R short forms, are highly practical for quick measurement of intelligence in AD patients, although they have their respective limitations.

Aged↗
PubMed2000

Interpretation and enantiomer analysis of methamphetamine abusers' urine and illegally brewed methamphetamine crystals.

This study deals with the high-performance liquid chromatographic identification of methamphetamine (MAMP) and amphetamine (AMP) enantiomers (d- and l-forms) in five illicit MAMP crystals and in urine specimens from 30 Japanese MAMP abusers. The analysis revealed that two of the types of crystals have a different optical purity ratio (l/d) and the other three have a single crystal of either the d- or l-enantiomer. The l/d ratios of two types of crystals were 0.04 and 49.4, and no racemic form (l/d = 1.00) was found. The urinary analysis showed that nonmetabolized MAMP and its demethylated metabolite, AMP, were present in urine specimens of all addicts. The stereoisomeric profiles in urine can be classified roughly into five groups according to the detected amount and the l/d ratio of MAMP and AMP enantiomers collected at one time point. In the first group, only d-MAMP and d-AMP were detected (in 16 cases). In the second group, only l-MAMP and l-AMP were detected (in one case). In the third group, the amount of the l-enantiomer detected, for both MAMP and AMP, was less than that of the d-enantiomer, and the l/d ratio was between 0.004 and 0.54 for MAMP and between 0.01 and 0.07 for AMP (in five cases). In the fourth group, the l-enantiomer of MAMP and AMP was found to be more abundant than the d-enantiomer, and the l/d ratio was between 2.63 and 30.11 for MAMP and between 1.23 and 31.30 for AMP (in four cases). In the fifth group, the amount of l-MAMP detected was greater than that of d-MAMP, and less l-AMP than d-AMP was detected. The l/d ratios were between 1.13 and 8.82 for MAMP and between 0.17 and 0.82 for AMP (in four cases). These results might be suitable for identification and the forensic toxicological investigation of AMP analogues.

Adolescent↗
PubMed2000

A simple method for detecting plasma propofol.

IMPLICATIONS: We measured plasma propofol levels by head space-gas chromatography analysis using solid-phase microextraction. This method saves time, and does not require elimination of interfering substances in the plasma. The coefficient variation was +/-5% to +/-30%. The detection limit was 10 ng/mL.

Anesthetics, Intravenous↗
PubMed2000

Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer.

Although it has been clarified that dietary, drinking, and smoking habits contribute to the onset of gastric cancer, little is known about their impact on prognosis of gastric cancer. To examine this question, a prognostic analysis was conducted using data from Aichi Cancer Center Research Institute and Hospital. From January 1988 to December 1994, information on 877 gastric cancer patients (578 men and 299 women) regarding habitual smoking and drinking, food consumption, histological grade, and clinical stage of tumor as well as follow-up results were collected. Survival status of all patients was followed up until December 1998, and the survival function was estimated by the Kaplan-Meier method. Proportional hazard analysis was used to test the effect of each lifestyle item on gastric cancer death. After controlling for age, gender, histological grade, and stage of disease, hazard ratios (HR) were calculated. Values for consumption of raw vegetables [HR = 0.74, 95% confidence interval (CI) = 0.56-0.98], tofu (HR = 0.65, 95% CI = 0.42-0.99), and chicken meat (HR = 0.61, 95% CI = 0.39-0.95) more than three times per week demonstrated significantly decreased risk. However, the risk ratio was 2.53 (95% CI = 1.22-5.29) for habitual smokers, and an inverse dose-response relationship was also found between ever smoking and gastric cancer patient survival. Therefore, this study suggested that frequent intake of raw vegetables and tofu is favorable, whereas habitual smoking is an adverse prognostic factor for gastric cancer. Our study implies that an improvement of survival of Japanese gastric cancer might be achieved by lifestyle improvement.

Adenocarcinoma↗
PubMed2000

Elevated risk of tuberculosis by occupation with special reference to health care workers.

We conducted a study to evaluate tuberculosis (TB) risk in Japan by work performed, either paid or unpaid. We collated information on sex, age, employment category, occupation, and family history from 1120 registration cards of new TB cases at two wards in Nagoya City over seven years (1989-1995). We used census data and data from the Survey of Physicians, Dentists and Pharmacists conducted in 1990 to estimate the population at risk by employment category and occupation. Elevated TB incidence rates were observed for female nurses (SIR: 3.81; 95% CI: 1.97-6.65), clinical laboratory technicians (SIR: 25.00; 6.81-63.99), and males without a paid job (SIR: 1.35; 1.20-1.53). A work environment conducive to transmission may have increased the TB risk in female nurses and clinical laboratory technicians. Male jobless people and institutionalized elderly residents may have enhanced the TB risk for males without a paid job.

Adolescent↗
PubMed1999

Rapid quantification of HTLV-I provirus load: detection of monoclonal proliferation of HTLV-I-infected cells among blood donors.

In this report, we quantified HTLV-I provirus load using the AmpliSensor system, which utilizes fluorescence to measure PCR products. With this method, provirus loads could be measured within 6 hr, and the results obtained correlated well with those obtained by other methods. Samples from 256 blood donors, who were positive for antibodies against HTLV-I, were analyzed, showing that provirus load ranged from less than 0.1% to 56% among carriers. We analyzed the association between provirus load and the biomarkers age and sex and found that it was not influenced by either. Provirus load was better correlated with soluble interleukin-2 receptor (sIL-2R) levels than with antibody titer against the virus. Among 18 blood donors with high provirus load (more than 10%), Southern blotting detected monoclonal integration of HTLV-I in infected cells in 2 cases, both of them showing high sIL-2R levels (more than 900 U/ml). Sequential analyses of provirus load showed stable levels of provirus in the same carriers, suggesting that some factors other than age or sex determined provirus load in infected individuals. Thus, this rapid method is a useful tool for the early detection of adult T-cell leukemia and other HTLV-I-associated diseases.

Adolescent↗
PubMed1999

Effect of body size on breast-cancer risk among Japanese women.

With the use of data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC), the effect of body size on the risk of breast cancer was evaluated among Japanese women, who are generally leaner than white women. In total, 1,359 breast-cancer cases were included, and 24,207 women, confirmed as free of cancer, were recruited as a reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple-logistic regression analysis. Separate analyses were performed for pre- and post-menopausal women. Furthermore, stratification by decade of age was done to evaluate the effect of body size on the development of breast cancer. The results obtained from the present study were as follows. (1) Current body-mass index (BMI) was positively associated with postmenopausal breast cancer (OR 2.08, 95% CI 1.49-2.92 for highest quintile vs. lowest), although higher BMI did not affect the risk in pre-menopausal women. (2) Estimates of risk were below unity for BMI at around age 20 in post-menopausal women. (3) After stratifying BMI at around age 20, gaining BMI in later life was positively associated with increased risk, regardless of BMI in early life. These findings suggest that avoidance of marked weight gain during adult life, especially after natural menopause and/or after age 60, may reduce the risk of breast cancer.

Adult↗
PubMed1999

Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes.

1. The roles of different human cytochrome P450s (CYP) in phenacetin O-deethylation were investigated using human liver microsomes and recombinant proteins. Phenacetin O-deethylase (POD) activities in human liver microsomes at substrate concentrations of 10 and 500 microM were inhibited by 0.1 and 1 microM alpha-naphthoflavone and activated by 10 and 100 microM alpha-naphthoflavone. The activation of POD activity in human liver microsomes by alphanaphthoflavone was inhibited by 100 microM aniline, anti-CYP2E1 antibody, 1 microM ketoconazole and anti-CYP3A4 antibody. 2. In recombinant CYP from human B-lymphoblast cells, POD activities at a phenacetin concentration of 500 microM were detected for CYP2E1 and CYP3A4, as well as CYP1A2, CYP1A1, CYP2C19, CYP2C9 and CYP2A6. In recombinant CYP from human B-lymphoblast cells or baculovirus-infected insect cells and in reconstituted systems, a requirement of cytochrome b5 (b5) for POD activities catalysed by CYP2E1 and CYP3A4 was observed. The activation of POD activity by alpha-naphthoflavone was observed for CYP3A4, but not for CYP2E1. Co-expression of b5 with CYP3A4 enhanced the activation of POD activity by alpha-naphthoflavone. 3. In the absence of alpha-naphthoflavone, the POD activity in pooled human liver microsomes at 500 microM phenacetin was significantly inhibited (p<0.0001) by 10 microM fluvoxamine, but not by 1 microM ketoconazole. In the presence of alpha-naphthoflavone, the activity was significantly inhibited (p<0.0001) by 1 microM ketoconazole, but not by 10 microM fluvoxamine. 4. Inter-individual differences in the effects of alpha-naphthoflavone on POD activity in human liver microsomes were observed, and the involvement of CYP3A4 as well as CYP1A2 in POD activity in human liver was identified even at a low substrate concentration.

Aniline Compounds↗
PubMed1999

Comparative case-referent study of risk factors among hormone-related female cancers in Japan.

To assess the impact of reproductive and anthropometric factors as a risk indicator for female cancers in hormone-related organs, i.e., the breast, endometrium and ovary, we conducted a comparative case-referent study using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The case group consisted of 1,465, 133 and 99 women who had first been diagnosed as having breast, endometrial and ovarian cancer, respectively. The referents were 25,488 female first-visit outpatients who had not previously been diagnosed with any type of cancer. The odds ratios (ORs) and their 95% confidence intervals (95%CI) were estimated using an unconditional logistic regression model. An inverse association with experience of delivery and a positive association with body mass index (BMI) and with change of BMI after 20 years of age, were observed consistently for all three cancer sites. We observed similar risk and protective factors for breast and endometrial cancer, but the effect of reproduction and overweight condition (BMI> or =25) were more prominent in endometrial cancer. Although the present study failed to find site-specific risk factors for ovarian cancer, the results provided evidence that being overweight and/or weight gain in adult life is a common risk factor for all three cancer sites. The results obtained from this study suggested that avoidance of weight gain may reduce the risk of female hormone-related cancers.

Adult↗
PubMed1999

Effect of life styles on the risk of subsite-specific gastric cancer in those with and without family history.

To evaluate a combined effect of gastric cancer family history (GCFH) and selected living habits on the subsite-specific of gastric cancer, a hospital-based case-referent study was conducted in Tokai area of Japan. The study subjects were 850 newly diagnosed gastric cancer (GC) patients and 28,619 cancer-free first-visit outpatients. Odds ratios (ORs) of all subsites of GC in subjects with both GCFH and habitual smoking were significantly higher (OR = 4.22) compared with those with merely GCFH (OR = 1.81) or habitual smoking (OR = 2.83). When positive GCFH subjects frequently consumed raw vegetable, the risk of GC decreased in cardia (OR = 0.68), antrum (OR = 0.43) and all subsites (OR = 0.74). Our findings provided evidence that GCFH and habitual smoking increased the risk of GC with family history, while frequent intake of raw vegetable decreased the risk and it was modified by other environmental factors.

Adult↗
PubMed1999

Foods contributing to absolute intake and variance in intake of fat, fatty acids and cholesterol in middle-aged Japanese.

On the basis of 351 one-day weighed diet records, we selected foods/recipes contributing to nutrients of interest for a data-based food frequency questionnaire by contribution analysis and multiple regression analysis. Total fat was largely of animal and vegetable origin, irrespective of analytic methods. Saturated fatty acid was mostly from animal and vegetable sources according to contribution analysis, and that of animal origin was the main contributor by multiple regression analysis. Mono-unsaturated fatty acid was substantially supplied by animal and vegetable products by either analytic method. Poly-unsaturated fatty acid, n-6 poly-unsaturated fatty acid and linoleic acid were found to be of vegetable origin and chicken egg according to contribution analysis; while vegetable oil and mayonnaise were the major contributors to variance in intake. Arachidonic acid was, however, mostly provided by animal sources including chicken egg and fish, irrespective of analytic methods. N-3 poly-unsaturated fatty acids and alpha-linolenic acid were of vegetable and marine origin. Eicosapentaenoic and docosahexaenoic acids were particularly from marine products, irrespective of analytic methods, except for chicken egg in docosahexaenoic acid by contribution analysis. Cholesterol was of animal and marine origin by either analytic method. Thus, foods contributing to absolute intake and variance in intake of fat, fatty acids and cholesterol differed considerably.

Animals↗
PubMed1999

Foods contributing to absolute intake and variance in intake of selected vitamins, minerals and dietary fiber in middle-aged Japanese.

Using 351 one-day weighted diet records, we selected foods providing vitamins, minerals and dietary fiber according to contribution analysis (CA) and multiple regression analysis (MRA). Vitamin C was supplied by various vegetables and fruits, and carotene was specifically derived from green-yellow vegetables based on MRA as well as CA. Vitamin A was provided by green-yellow vegetables, fruits, chicken egg and milk (whole) according to CA; whereas chicken liver and pork liver were major sources according to MRA. Vitamin E was mainly of vegetable origin as determined by CA, and largely of spinach, safflower oil and pumpkin as determined by MRA. Vitamin D was mainly derived from chicken egg, fish and mushroom based on CA, and particularly from fish based on MRA. Calcium was supplied by milk (whole), soy products and chicken egg as determined by CA; while milk, tofu and various small fishes were the main contributors to variance. Magnesium was provided by soy products, well-milled rice and spinach according to both analyses, and iron by chicken egg, spinach and soy products. Zinc was largely derived from well-milled rice, followed by chicken egg and milk (whole) as determined by CA, and copper was provided by well-milled rice, soy and wheat products. Dietary fiber was supplied by vegetable sources, whether water soluble or insoluble, based on both analytic methods.

Animals↗
PubMed1999

Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be mainly N-demethylated to desmethylazelastine in humans. In the present study, Eadie-Hofstee plots of azelastine N-demethylation in human liver microsomes were biphasic. In microsomes from human B-lymphoblast cells, recombinant cytochrome P-450 (CYP)2D6 and CYP1A1 exhibited higher azelastine N-demethylase activity than did other CYP enzymes. On the other hand, recombinant CYP3A4 and CYP1A2 as well as CYP1A1 and CYP2D6 in microsomes from baculovirus-infected insect cells were active in azelastine N-demethylation. The K(M) value of the recombinant CYP2D6 (2.1 microM) from baculovirus-infected insect cells was similar to the K(M) value of the high-affinity (2.4+/-1.3 microM) component in human liver microsomes. On the other hand, the K(M) values of the recombinant CYP3A4 (51.1 microM) and CYP1A2 (125.4 microM) from baculovirus-infected insect cells were similar to the K(M) value of the low-affinity (79.7+/-12.8 microM) component in human liver microsomes. Bufuralol inhibited the high-affinity component, making the Eadie-Hofstee plot in human liver microsomes monophasic. Azelastine N-demethylase activity in human liver microsomes (5 microM azelastine) was inhibited by ketoconazole, erythromycin, and fluvoxamine (IC(50) = 0.08, 18.2, and 17.2 microM, respectively). Azelastine N-demethylase activity in microsomes from twelve human livers was significantly correlated with testosterone 6beta-hydroxylase activity (r = 0.849, p<.0005). The percent contributions of CYP1A2, CYP2D6, and CYP3A4 in human livers were predicted using several approaches based on the concept of correction with CYP contents or relative activity factors (RAFs). Our data suggested that the approach using RAF(CL) (RAF as the ratio of clearance) is most predictive of the N-demethylation clearance of azelastine because it best reflects the observed N-demethylation clearance in human liver microsomes. Summarizing the results, azelastine N-demethylation in humans liver microsomes is catalyzed mainly by CYP3A4 and CYP2D6, and CYP1A2 to a small extent (in average, 76.6, 21.8, and 3.9%, respectively), although the percent contribution of each isoform varied among individuals.

Animals↗
PubMed1998

Involvement of CYP1A2 in mexiletine metabolism.

AIMS: Mexiletine has been reported to be hydroxylated by cytochrome P450 2D6 (CYP2D6) in humans. However, the involvement of CYP1A2 in the metabolism of mexiletine has been proposed based on the interaction with theophylline which is mainly metabolized by CYP1A2. The aim of this study was to clarify the role of human CYP1A2 in mexiletine metabolism. METHODS: Human CYP isoforms involved in mexiletine metabolism were investigated using microsomes from human liver and B-lymphoblastoid cells expressing human CYPs. The contributions of CYP1A2 and CYP2D6 to mexiletine metabolism were estimated by the relative activity factor (RAF). RESULTS: Mexiletine p- and 2-hydroxylase activities in human liver microsomes were inhibited by ethoxyresorufin and furafylline as well as quinidine. Mexiletine p- and 2-hydroxylase activities in microsomes from nine human livers correlated significantly with bufuralol 1'-hydroxylase activity (r = 0.907, P < 0.001 and r = 0.886, P < 0.01, respectively). Microsomes of B-lymphoblastoid cells expressing human CYP1A2 exhibited lower mexiletine p- and 2-hydroxylase activities than those expressing human CYP2D6. It was estimated by RAF that the major isoform involved in mexiletine metabolism was CYP2D6, and the contribution of CYPIA2 to both mexiletine p- and 2-hydroxylase activities was 7-30% in human liver microsomes. However, the Km values of the expressed CYP1A2 (approximately 15 microM) were almost identical with those of the expressed CYP2D6 (approximately 22 microM) and human liver microsomes. CONCLUSIONS: Mexiletine is a substrate of CYP1A2. The data obtained in this study suggest that the interaction of mexiletine with theophylline might be due to competitive inhibition of CYP1A2.

Anti-Arrhythmia Agents↗