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Biomedical subjects

Y Tokudome

Publications and source records attributed to Y Tokudome.

At least 19 recordsLinked to original sources

Soybean products and reduction of breast cancer risk: a case-control study in Japan.

Components of the Japanese diet, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Since soybean products are widely consumed in Japan, a case-control study taking account of the menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167 breast cancer cases were included and 854 women confirmed as free of cancer were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. There were reductions in risk of breast cancer associated with high intake of soybean products among premenopausal women. Compared with women in the lowest tertile, the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI, 0.25-0.95). A significant decrease in premenopausal breast cancer risk was also observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89 for highest vs lowest tertile; P for trend=0.02). The present study found a statistically inverse association between tofu or isoflavone intake and risk of breast cancer in Japanese premenopausal women, while no statistically significant association was evident with the risk among postmenopausal women.

Adult↗

Discrepancies in dietary intakes and plasma concentrations of fatty acids according to age among Japanese female dietitians.

OBJECTIVE: To clarify the influences of age on dietary intakes and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. SUBJECTS AND METHODS: In autumn 1996, we estimated dietary FA intakes based on 7 day weighed diet records and analyzed plasma FA concentrations in 79 healthy Japanese female dietitians, and investigated their relationships with age, dividing into three age groups (young (32-42 y), middle-aged (43-50 y) and elderly (51-66 y)). RESULTS: Dietary intakes of total FA, saturated FAs, monounsaturated FAs, n-3 polyunsaturated FAs (PUFAs) and alpha-linolenic acid (18:3n-3) were significantly highest in the middle-aged group, and lowest in the elderly. Similar trends were observed for dietary intakes of n-6 PUFAs and linoleic acid (18:2n-6), but there were no differences with regard to eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and n-3 highly unsaturated FAs (HUFAs=EPA+22:5n-3+DHA). On the other hand, plasma concentrations of all FAs except for arachidonic acid (20:4n-6) demonstrated positive correlations with age. Moreover, plasma concentrations of EPA in all age groups, DHA in the elderly and n-3 HUFAs in the middle-aged and the elderly were all positively correlated with dietary intakes. CONCLUSIONS: We should take into account the influence of age on dietary habit and lipid metabolism when interpreting associations between dietary FA intakes and plasma FA concentrations.

Adult↗

Relative validity of a semi-quantitative food frequency questionnaire versus 28 day weighed diet records in Japanese female dietitians.

OBJECTIVE: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). SUBJECTS AND METHODS: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996-1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. RESULTS: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum-median-maximum) ranged from 0.17 (beverages)-0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)-0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)-0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)-0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. CONCLUSIONS: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. SPONSORSHIP: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242).

Adult↗

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↗

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↗

Development of data-based semi-quantitative food frequency questionnaire for dietary studies in middle-aged Japanese.

BACKGROUND: We designed a data-based semi-quantitative food frequency questionnaire to clarify the relationship between food intake and lifestyle-related diseases among middle-aged Japanese. METHODS: A total of 351 middle-aged individuals were recruited to a one-day weighed diet record survey in 1994. In all, 586 foods were consumed. Intake of 31 nutrients including energy, protein, fat, carbohydrate, vitamins, minerals and dietary fiber by food was computed by multiplying the weight of food consumed by its nutrient content. First, 252 foods with up to 90 cumulative % contribution to nutrient intake were selected. Of these, foods having apparently the same/similar nutrient content were combined into 206 foods by research dietitians. Next, 183 foods with up to 0.90 cumulative multiple regression coefficient and 90 cumulative % contribution were chosen. At this stage an additional food grouping was made. RESULTS: Finally, 102 foods/recipes were included in the questionnaire: rice (2 items), bread and noodles (11), eggs, milk and dairy products (10), soybean, soybean products and other beans (7), meat including beef, pork and chicken (12), fish (5), other fish, shellfish and fish products (10), green-yellow vegetables (8), other vegetables and mushrooms (7), edible roots (2), seaweeds (3), seeds (2), fruits (8), beverages (7) and confectioneries (8). The frequencies were classified into eight categories. Portion size was calculated for the respective foods largely from the one-day weighed diet record. CONCLUSIONS: The developed semi-quantitative food frequency questionnaire substantially covered the intake of 31 nutrients and may be competent to rank middle-aged Japanese efficiently.

Databases as Topic↗

Effect of serum protein binding on real-time trafficking of liposomes with different charges analyzed by positron emission tomography.

Liposomes have been used as carriers of various materials and as tools for gene transfer: for the latter purpose, positively charged liposomes are usually used. To evaluate the stability in the presence of serum and the in vivo behavior of such liposomes as well as those aspects of neutral and negatively charged liposomes, we investigated liposomal agglutinability in the presence of serum, serum protein binding to these liposomes, and real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol without or with charged lipid were prepared in the presence of mannitol, and the turbidity change in the presence of serum was determined. Turbidity increase was not observed for so-called long-circulating liposomes, i.e., liposomes modified with glucuronic acid or with poly(ethylene glycol), or for negatively charged liposomes containing dicetyl phosphate (DCP), phosphatidylglycerol, or phosphatidylserine. On the contrary, a significant turbidity increase was observed when positively charged liposomes modified with stearylamine, stearyltrimethylammonium chloride or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as a component of liposomes for gene transfer, were used. These liposomes were found to have bound a high amount of serum proteins after separation of unbound serum proteins by use of a spin column. The liposomal trafficking in vivo was determined for three kinds of liposomes, i.e., liposomes with DMRIE, those with DCP, and those without charged lipids. These liposomes were prepared in the presence of 2-[18F]fluoro-2-deoxy-D-glucose ([2-18F]FDG), and the [2-18F]FDG-labeled liposomes were administered to mice to perform PET scans. Positively charged liposomes containing DMRIE showed high accumulation in the liver compared with neutral and negatively charged liposomes. Since DMRIE-liposomes tended to aggregate in the presence of serum, and to be associated with serum protein, these characteristics may lead to the high uptake of DMRIE-liposomes by the liver.

1,2-Dipalmitoylphosphatidylcholine↗

Antitumor activity of vincristine encapsulated in glucuronide-modified long-circulating liposomes in mice bearing Meth A sarcoma.

Liposomes modified with the uronic acid derivative palmityl-D-glucuronide (PGlcUA) have a long circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method, and then free or liposomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose administration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppressed tumor growth, and prolonged the survival time (T/C = 1.37). Furthermore, two-dose administration of the liposomes cured one third of the animals. The therapeutic effect of PGlcUA-liposomes was greater than that of control liposomes containing dipalmitoylphosphatidylglycerol instead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for delivering antitumor agents to tumor tissues.

Animals↗

In vivo trafficking of long-circulating liposomes in tumour-bearing mice determined by positron emission tomography.

Various kinds of long-circulating liposome, such as ganglioside GM1-, polyethyleneglycol- (PEG-), and glucuronide-modified liposomes, have been developed for passive targeting of liposomal drugs to tumours. To evaluate the in vivo behaviour of such long-circulating liposomes, we investigated the liposomal trafficking, especially early trafficking just after injection of liposomes, by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and modifier, namely, GM1, distearoylphosphatidylethanolamine (DSPE)-PEG or palmityl-D-glucuronide (PGlcUA), were labelled with [2-18F]-2-fluoro-2-deoxy-D-glucose ([2-18F]FDG), and administered to mice bearing Meth A sarcoma after having been sized to 100 nm. A PET scan was started immediately after injection of liposomes and continued for 120 min. PET images and time-activity curves indicated that PEG liposomes and PGlcUA liposomes were efficiently accumulated in tumour tissues time dependently from immediately after injection. In contrast, GM1 liposomes accumulated less in the tumour as was also the case for control liposomes that contained dipalmitoylphosphatidylglycerol (DPPG) instead of a modifier. Long-circulating liposomes including GM1 liposomes, however, remained in the blood circulation and avoided liver trapping compared with control DPPG liposomes. These data suggest that PGlcUA and PEG liposomes start to accumulate in the tumour just after injection, whereas GM1 liposomes may accumulate in the tumour after a longer period of circulation.

1,2-Dipalmitoylphosphatidylcholine↗

Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs.

Analogs of a synthetic peptide having the L-arginine-L-glycine-L-aspartic acid (RGD) sequence have been found to decrease metastatic colonization. To enhance the metastasis-suppressing efficacy of these analogs, we sought to stabilize these analogs and to prolong their circulation time by incorporating them into a liposomal formulation. Various structures of RGD analogs grafted to hydrophobic groups were synthesized and then incorporated into liposomes. Liposomes composed of distearoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol and appropriate RGD analogs were injected intravenously along with B16BL6 murine melanoma cells into mice. Liposomal RGD (0.6 mumol of the analog equivalent to ca. 200 micrograms RGD peptides) inhibited lung colonization up to 76%. This dose is an order of magnitude lower than that for comparable inhibition reported for free RGD. Multi-dose administration of liposomal RGD (0.15 mumol of the analog) also inhibited the spontaneous lung metastasis of cells from a primary tumor site of B16BL6 cells subcutaneously implanted into the footpad of mice. Taken together, our data indicate that liposomal RGD may serve as a useful anti-metastatic agent.

Amino Acid Sequence↗

Real-time analysis of liposomal trafficking in tumor-bearing mice by use of positron emission tomography.

Long-circulating liposomes are known to accumulate passively in tumor tissues of tumor-bearing animals. To evaluate the in vivo behavior of such liposomes, we investigated the real-time liposomal trafficking by a non-invasive method using position emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and palmityl-D-glucuronide (PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[18F]fluoro-2-deoxyglucose ([2-18F]FDG). [2-18F]FDG-labeled liposomes sized by extrusion through a filter with various-sized pores were administered to mice bearing Meth A sarcoma, and a PET scan was performed for 120 min. Small-sized, long-circulating liposomes (100 nm in diameter) constructed with PGlcUA tended to accumulate in the tumor tissues. On the contrary, control liposomes (100 nm in diameter) containing dipalmitoylphosphatidylglycerol instead of PGlcUA accumulated in the liver. Large-sized PGlcUA-containing liposomes (> 300 nm) also accumulated in the liver, as well as in the spleen. Time-activity curves indicated that the small long-circulating liposomes (< 200 nm) transiently accumulated in the liver right after the injection but that the accumulation there decreased time-dependently. These data suggest that, although the majority of small long-circulating liposomes remain in the bloodstream, some extravasate once into the interstitial spaces in the liver re-enter the bloodstream again, and finally accumulate in the tumor tissues. This PET technique might be useful for studying real-time liposomal trafficking and for tumor imaging.

Animals↗

Induction of coenzyme A-dependent transacylation activity in rat liver microsomes by administration of clofibrate.

The effect of administration of clofibrate on the activity of coenzyme A-dependent (CoA-dependent) transacylation of 1-acyl-glycerophosphocholine (1-acyl-GPC) was examined in rat liver microsomes. Administration of clofibrate to rats increased the activity of Co-A-dependent transacylation of 1-[14C]acyl-GPC and the activity reached a value (8.37 nmol/min per mg protein) twice that in control rats (3.95 nmol/min per mg protein) without any changes in apparent Km values for CoA (1.2 microM in control and 1.0 microM in clofibrate-treated) and 1-acyl-GPC (33.4 microM in control and 27.8 microM in clofibrate-treated). The rate of CoA-dependent transfer of [14C]arachidonic acid (20:4) from 1-acyl-2-[14C]20:4-glycerophosphoethanolamine (GPE) or 1-acyl-2-[14C]20:4-glycerophosphoinositol (GPI) to 1-acyl-GPC (synthesis of 1-acyl-2-[14C]20:4-GPC) was also increased by treatment with clofibrate (1.9-fold and 1.5-fold increases, respectively). These results suggest that a CoA-dependent transacylation system of 1-acyl-GPC was induced by treatment with clofibrate.

Acyltransferases↗

[The effect of long-term group education for obese women in a public health center].

In order to improve maintenance of weight reduction, a long-term (5 month) weight reduction class for obese women consisting of repeated group learning three times a month in areas of dietary regimen and practice of physical exercise, and self-help group activities was conducted at a health center. Maintenance of achieved weight reduction was studied six months and one year after completion of the class. The results are as follows. 1) Among 30 alumni, percentages of rebound, regaining weight of more than half of reduction during the class, were 18% at six months and 48% at one year after the class. These results appear to indicate the difficulty in maintaining weight loss. 2) However, when changes were studied in terms of fat mass and lean body mass, rebound of fat mass, regaining fat mass of more than half of reduction, was very small--only 5%, through the follow-up periods--while lean body mass increased gradually. These results indicate very good maintenance of fat mass reduction, and from the view point of the objective of weight reduction which is principally fat mass reduction, this objective was supported. 3) The attendees were divided into two groups, diet group and exercise group. There were almost no differences in the follow-up results for weight maintenance between the two groups. This can be attributed to the fact that since the combination of dieting and exercise was emphasized in both groups, with moderate energy restriction and balanced food intake in the dietary regimen and aerobic walking for exercise in addition to the classroom learning, instructions for lifestyle changes were rather similar for both groups.

Adult↗

[A dietary method for epidemiological study of cancer].

A semiquantitative frequency questionnaire was developed to estimate the average intake of foods and nutrients of individuals with the aim of utilization in cancer epidemiology. Validity of the questionnaire was evaluated in comparison with four 7-day dietary records carried on 25 spouses over one year. Absolute mean intakes estimated by the questionnaire and by the records were roughly comparable at the group level. However, the individual's estimated intakes generally showed poor agreements between the two methods in terms of rank correlation, except for a few foods such as fish and milk and for alcoholic beverages. Further efforts should be exercised to develop a more accurate dietary method.

Age Factors↗