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Biomedical subjects

H Itakura

Publications and source records attributed to H Itakura.

At least 19 recordsLinked to original sources
PubMed2001

Temporal changes in liver cancer incidence rates in Japan: accounting for death certificate inaccuracies and improving diagnostic techniques.

Primary liver cancer (PLC) rates have risen dramatically during the past few decades in some regions, particularly in Japan, where PLC is now the third major cause of cancer death. PLC is one of the most difficult tumors to diagnose correctly, because (i) the liver is a frequent site of cancer metastasis and (ii) death from PLC is often attributed to cirrhosis or chronic hepatitis. Also, because the disease is often rapidly fatal, a large proportion of liver cancer cases are identified based on death certificates alone without confirmation by clinical records. Thus, worldwide differences in published incidence rates for this disease reflect regional or national differences in both the accuracy of death certificates and the sensitivity of diagnostic methods. By comparing death certificate causes of death with those based on pathology review, we were able to adjust 1958--1994 incidence rates for a large Japanese cohort for these errors. Although the death certificate false-positive error rate declined, the false-negative error rate remained high throughout the study. The introduction of improved liver cancer diagnostic methods in Japan in the early 1980s was associated with a sharp increase in PLC incidence. We conclude that errors in death certificate causes of death and changes in liver cancer diagnostic techniques have had an important impact on the reported incidence of this disease. Taking these factors into account, rates of hepatocellular carcinoma rose between 2.4- and 4.3-fold in our Japanese cohort from 1960 to 1985, peaked about 1993 and declined thereafter. Incidence rates of cholangiocarcinoma remained stable through 1987.

Carcinoma, Hepatocellular↗
PubMed2001

Generation and characterization of a fairly stable triplet carbene.

Most molecules are held together by covalent bonds-electron pairs jointly shared by the two atoms that are linked by the bond. Free radicals, in contrast, have at least one unpaired electron. In the case of carbon-based radicals, the carbon atom at the radical centre no longer makes four bonds with other atoms as it would do in its normal, tetravalent state. The presence of unpaired electrons renders such radicals highly reactive, so they normally occur only as transient intermediates during chemical reactions. But the discovery by Gomberg in 1900 of triphenylmethyl, the first relatively stable free radical containing a central trivalent carbon atom, illustrated that radicals with suitable geometrical and electronic structures can be stable. Compounds containing a divalent carbon atom that uses only two of its four valence electrons for bonding are usually less stable than Gomberg-type radicals with trivalent carbon. Although the role of these so-called carbenes in chemical reactions has long been postulated, they were unambiguously identified only in the 1950s. More recently, stable carbenes have been prepared, but the singlet state of these molecules, with the two nonbonding valence electrons paired, means that they are not radicals. Carbenes in the second possible electronic state, the triplet state, are radicals: the two nonbonding electrons have parallel spins and occupy different orbitals. Here we report the preparation and characterization of a triplet carbene, whose half-life of 19 minutes at room temperature shows it to be significantly more stable than previously observed triplet carbenes.

Journal Article↗
PubMed2001

Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.

We investigated the protective effects of the traditional Japanese herbal medicine Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) (SRBT) against hypercholesterolemia and atherosclerotic lesions. We focused on atherosclerosis using female heterozygous Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. The total plasma cholesterol levels increased for up to 12 weeks after beginning a diet containing 0.1% cholesterol and then reached a plateau of about 600 mg dl(-1). When SRBT was administered at a dose of 1.0 g kg(-1)per day for 24 weeks, total plasma cholesterol levels were significantly decreased after 20-24 weeks. On the other hand, pravastatin at a dose of 10 mg kg(-1)per day produced a significant decrease in total plasma cholesterol levels from 4 to 24 weeks (about 105-130 mg dl(-1)). Moreover, 1.0 g kg(-1)per day of SRBT significantly decreased plasma low density lipoprotein (LDL) cholesterol levels but did not change either very low density lipoprotein (VLDL), or high density lipoprotein (HDL) cholesterol levels. Animals that received pravastatin had significantly decreased LDL cholesterol levels and VLDL cholesterol levels after 8 weeks and at 24 weeks. We also examined the expression of apoB, E and LDL receptor mRNA levels in the liver at 24 weeks after beginning the administration of 1.0 g kg(-1)per day of SRBT. Both apoE and LDL receptor mRNA levels were significantly increased compared with those in rabbits receiving the 0.1% cholesterol diet. SRBT at a dose of 1.0 g kg(-1)per day significantly depressed the intimal surface area of the thoracic aortae involved with atheromatous plaques. The present results suggest that SRBT may protect against hypercholesterolemia and atheromatous lesions by affecting apoE and LDL receptor mRNA gene expression in the liver.

Animals↗
PubMed2001

Energy value and digestibility of dietary oil containing mainly 1,3-diacylglycerol are similar to those of triacylglycerol.

Diacylglycerol (DAG) is a component of various vegetable oils. Approximately 70% of the DAG in edible oils are in the configuration of 1,3-DAG. We recently showed that long-term ingestion of dietary oil containing mainly 1,3-DAG reduces body fat accumulation in humans as compared to triacylglycerol (TAG) oil with a similar fatty acid composition. As the first step to elucidate the mechanism for this result, we examined the difference in the bioavailabilities of both oils by measuring food energy values and digestibilities in rats. Energy values of the DAG oil and the TAG oil, measured by bomb calorimeter, were 38.9 and 39.6 kJ/g, respectively. Apparent digestibility expressed according to the formula: (absorbed) x (ingested)(-1) x 100 = (ingested - excreted in feces) x (ingested)(-1) x 100 for the DAG oil and the TAG oil were 96.3+/-0.4 and 96.3+/-0.3% (mean +/- SEM), respectively. The similarity in the bioavailabilities of both oils supports the hypothesis that the reduced fat accumulation by dietary DAG is caused by the different metabolic fates after the absorption into the gastrointestinal epithelial cells.

Absorption↗
PubMed2001

Regulation by long-chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells.

Cholesteryl ester transfer protein (CETP) is an important determinant of lipoprotein function, especially high density lipoprotein (HDL) metabolism, and contributes to the regulation of plasma HDL levels. Since saturated and polyunsaturated fatty acids (FA) appear to influence the CETP activity differently, we decided to investigate the effects of FA on the expression of CETP mRNA in HepG2 cells using an RNA blot hybridization analysis. Long-chain FA (>18 carbons) at a 0.5 mM concentration were added to the medium and incubated with cells for 48 h at 37 degrees C under 5% CO2. After treatment with 0.5 mM arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA), the levels of CETP mRNA were less than 50% of the control levels (AA, P = 0.0005; EPA, P < 0.01; DHA, P < 0.0001), with a corresponding significant decrease in the CETP mass. These results suggest that FA regulate the gene expression of CETP in HepG2 and this effect is dependent upon the degree of unsaturation of the acyl carbon chain in FA.

Arachidonic Acid↗
PubMed2001

Solubilization of phytosterols in diacylglycerol versus triacylglycerol improves the serum cholesterol-lowering effect.

OBJECTIVE: This study was performed to investigate the difference in the serum-cholesterol- and triglyceride-lowering activities between phytosterols dissolved in diacylglycerol (PS/DG) and dispersed in triacylglycerol (PS/TG). The effects of the solvent on the concentrations of serum beta-sitosterol and campesterol were examined. DESIGN: The study had a randomised crossover design. SUBJECTS: Twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged 29-50 y participated in this study. INTERVENTIONS: For 2 weeks before the test period (designated as the control period), all subjects consumed control mayonnaise (PS free) daily with supper and were randomly assigned to two groups for the 2 week test period; one group was given mayonnaise containing PS (500 mg/day) dissolved in DG (10 g/day), and the other mayonnaise containing PS (500 mg/day) dispersed in TG (10 g/day). After a wash out period consuming control PS-free mayonnaise for 4 weeks, the groups were reversed for 2 weeks. RESULTS: PS/TG feeding had no effect on the serum cholesterol level. In contrast, PS/DG feeding significantly reduced the total and LDL cholesterol levels from the initial value of 5.57 to 5.31 mmol/l (4.7%; P<0.05) and from 3.69 to 3.39 mmol/l (7.6%; P<0.05), respectively. Moreover, the degree of total cholesterol reduction induced by PS/DG feeding in the test period was significantly greater than that induced by PS/TG feeding (P<0.05). In addition, the serum beta-sitosterol and campesterol concentrations did not change during the PS/TG or PS/DG feeding periods. CONCLUSIONS: Dissolution of PS in DG had a better serum cholesterol lowering effect than dissolution in TG. SPONSORSHIP: Kao Corporation.

Adult↗
PubMed2001

Daily cocoa intake reduces the susceptibility of low-density lipoprotein to oxidation as demonstrated in healthy human volunteers.

Nine male volunteers were given 36 g of cocoa powder (containing 2610 mg of polyphenols) per day with sugar and 6 volunteers received an equivalent amount of sugar for 2 weeks. Conjugated diene production in LDL induced by 2-2' azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) and copper ion were evaluated. The lag time was significantly prolonged at 1 and 2 weeks in V-70 and at 2 weeks in copper ion after cocoa powder consumption. The level of excretion of epicatechin in urine was significantly higher in the cocoa group than that in the control group. In conclusion, the antioxidants in cocoa powder might be absorbed and increase the resistance of human LDL to oxidation.

Adult↗
PubMed2001

Suppressive mechanisms of EPA on human T cell proliferation.

In vivo and in vitro experiments show that polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) inhibit mitogen- or antigen-stimulated proliferation of T cells in rodents and humans. However, the exact manner and mechanisms by which PUFA inhibits T cell proliferation is not clear. In the present study, we investigated the suppressive effects of EPA, an n-3 PUFA, on PHA stimulated human peripheral blood T cells. Our results showed that EPA suppresses mitogen- or antigen-stimulated human T cell proliferation by at least 2 steps; step 1) EPA suppresses T cell proliferation by inhibiting IL-2R alpha expression and IL-2 production; step 2) EPA induces cell death of blast T cells without reducing the expression of IL-2R alpha. We also showed that EPA selectively stimulates the cell death of blast T cells but not resting T cells. The suppressive effect of EPA was mediated via the production of reactive oxygen products, because EPA-stimulated H2O2 production and the suppressive effect of EPA was restored by addition of catalase or NAC. These results taken together suggest that such immunosuppressive effects of EPA may explain the apparent benefits of EPA-enriched diets for patients with inflammatory disorders.

Cell Death↗
PubMed2001

Fat-soluble vitamin status is not affected by diacylglycerol consumption.

OBJECTIVE: The objective of this study was to examine the effect of dietary diacylglycerol (DAG) on the bioavailability of fat-soluble vitamins in comparison with triacylglycerol (TAG). METHODS: We conducted a long-term administration test of DAG and TAG in 27 healthy men aged 27-47 years. After measuring baseline values, subjects were randomized into two groups, one group (n = 15) was given DAG and the other (n = 12) was given TAG. Subjects ingested 20 g of DAG or TAG either in mayonnaise or an emulsion drink of their own choice at meals once a day for 12 weeks. At 4, 8 and 12 weeks, fasting blood samples were drawn and serum levels of vitamin A, E, and D were measured. RESULTS: There were no significant changes in vitamin A levels throughout the study period. Compared to the initial values (using a Student's t test for paired values), significant differences of vitamin E and D were seen at some points during the experiment. According to a two-way repeated measures analysis of variance, however, DAG and TAG (lipid) and time had no effect on fat-soluble vitamin levels. CONCLUSIONS: Our results indicate that DAG does not affect the absorption of the fat-soluble vitamins in diets.

Adult↗
PubMed2001

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

Aged↗
PubMed2001

[Effects of aging on oxidisability of low density lipoprotein].

Oxidised LDL is taken up by macrophages via scavenger receptors, leading to foam cell formation and is thus considered to contribute to atherogenesis. Aging results in the increase of lipids and the decrease of antioxidant enzyme activity in serum. In this study, we investigated the effects of aging on LDL oxidisability. We measured LDL oxidation lag time, plasma lipids, albumin and uric acid were examined in 306 Japanese (169 men, 137 women). The mean +/- SE of LDL oxidation-lag time in subjects was 58.9 +/- 1.0 min. The lag time (80.3 +/- 4.8 min) was longest in subjects in their 20 s and shortest in those in their 40 s (58.9 +/- 1.0 min). The longest lag time was in second-decade men (88.9 +/- 6.2 min) and shortest in fourth-decade women (50.7 +/- 2.2 min), and these results were similar even excluding subjects with abnormal biochemical data (total cholesterol, triglyceride, GOT, GPT, gamma GTP, creatinine and glucose). We analyzed the effects of various factors on lag time using multiple linear regression. Aging, uric acid and LDL-cholesterol significantly influenced lag time. Our results suggest that LDL oxidisability might been regulated by aging, changes in LDL-cholesterol with aging and variations in physical antioxidant function.

Adult↗
PubMed2001

Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation.

Flavonoids, a group of polyphenolic compounds, exist naturally and serve as antioxidants in vegetables, fruits, and so on. The inhibition of low density lipoprotein (LDL) oxidation may be an effective way to prevent or delay the progression of atherosclerosis. In the present study, we analyzed the radical scavenging capacity of 10 flavonoids (catechin, epicatechin [EC], epigallocatechin [EGC], epicatechin gallate [ECg], epigallocatechin gallate [EGCg], myricetin, quercetin, apigenin, kaempferol, and luteolin) toward 1,1-diphenyl-2-picryl-hydrazyl [DPPH]. After 20 min of incubation, EGCg was the most effective DPPH radical scavenger, luteolin being the least active of this flavonoid group. The mutual antioxidant effect of flavonoids with alpha-tocopherol (alpha-toc) on LDL oxidizability was investigated by using the lipophilic azo radical initiator 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) [AMVN-CH3O]. An inhibitory effect of flavonoids on LDL oxidation was observed in the order of luteolin>ECg>EC>quercetin>catechin>EGCg>EGC>myricetin>kaempferol> apigenin. The shortened lag time induced by higher doses of alpha-toc (6 mg/100 mL) was restored by flavonoids. These results suggest that 1) radical trapping effects of flavonoids differ according to their structure, and 2) flavonoids act as hydrogen donors to alpha-toc radical; furthermore, by interaction with alpha-toc, they have a greater potential to delay the oxidation of LDL.

Antioxidants↗
PubMed2001

Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids.

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.

Chylomicrons↗