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Biomedical subjects

T Hirohata

Publications and source records attributed to T Hirohata.

At least 19 recordsLinked to original sources

Activity-dependent neural tissue oxidation emits intrinsic ultraweak photons.

Living organisms have been known to spontaneously emit ultraweak photons in vivo and in vitro. Origin of the photon emission remains unclear, especially in the nervous system. The spontaneous ultraweak photon emission was detected here from cultured rat cerebellar granule neurons using a photomultiplier tube which was highly sensitive to visible light. The photon emission was facilitated by the membrane depolarization of neurons by a high concentration of K+ and was attenuated by application of tetrodotoxin or removal of extracellular Ca2+, indicating the photon emission depending on the neuronal activity and likely on the cellular metabolism. Furthermore, almost all the photon emission was arrested by 2,4-dinitrophenylhydrazine, indicating that the photon emission would be derived from oxidized molecules. Detection of the spontaneous ultraweak photon emission will realize noninvasive and real-time monitoring of the redox state of neural tissue corresponding to the neuronal activity and metabolism.

Animals↗

Serum testosterone:estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients.

The reason for the large male predominance in the occurrence of hepatocellular carcinoma (HCC) remains unknown, and sex hormones may contribute to this phenomenon. We examined possible associations of serum levels of testosterone, free testosterone, estradiol, sex hormone binding globulin, and testosterone:estradiol ratio (T:E2 ratio) with HCC development in a follow-up study of 46 Japanese male patients with liver cirrhosis predominantly of hepatitis C virus origin (76%). Serum samples were collected between December 1985 and December 1987, and the patients were completely followed until the end of 1995 for an average of 5.1 years. During the follow-up period, 20 patients (43%) developed HCC. Univariate analysis demonstrated that serum T:E2 ratio and testosterone were significant predictors of HCC; the hazard ratios (and 95% confidence intervals) in the middle and upper tertiles relative to the lower tertile were 2.0 (0.5-7.6) and 4.0 (1.1-14.6; P trend = 0.03) for T:E2 ratio and 0.8 (0.2-3.1) and 2.9 (1.0-8.5; P trend = 0.05) for testosterone. Adjustment for age, serum albumin, hepatitis virus markers, and other clinicobiological variables substantially increased the corresponding hazard ratios. In multivariate analysis, serum free testosterone appeared to be associated with increased risk, yet independent associations with estradiol and sex hormone binding globulin were not evident. These results indicate that elevated serum testosterone, together with decreased serum estrogens, may promote the development of HCC in cirrhosis.

Adult↗

Ulcerative colitis and colorectal cancer: a follow-up study in Fukuoka, Japan.

BACKGROUND: Our goal was to study the higher death rate and the causes of such deaths among ulcerative colitis (UC) patients in the Japanese population, and to compare our findings in such cases with those for Crohn's disease (CD). METHODS: In all, 174 UC (male/female: 54/120) and 66 CD (34/32) patients who were registered for the research promotion programme in Fukuoka prefecture (1971-1981) were traced up to the end of 1994. The standardized mortality ratios (SMR) were calculated based on the death rates of the Japanese population by age, sex and calendar year. RESULTS: The overall follow-up rate was 96.7%. Among the UC patients, the SMR for all causes were 0.84 (95% CI: 0.11-4.31) for men; 1.05 (95% CI: 0.08-4.69) for women; and 0.94 (95% CI :0.09-4.50) for both sexes combined. When excluding deaths due to colorectal cancer, the SMR for the same groups were 0.43, 0.94 and 0.67, respectively. The SMR for both sexes were 1.82 (95% CI: 0.17-5.96) for malignant neoplasms and 9.93 (95% CI: 4.67-17.3) for colorectal cancer. Patients who died from colorectal cancer showed onset at a younger age (mean: 25.5 years) as well as a longer disease course of UC (mean: 17.0 years). Regarding the CD patients, the SMR for all causes were 1.75 (95% CI: 0.15-5.75) for both sexes. Most deaths were caused by gastrointestinal complications. CONCLUSIONS: An excess mortality from colorectal cancers was indicated in the UC patients, especially in males. The overall SMR in male UC patients decreased by 50% when the deaths from colorectal cancer were excluded. The excess mortality in those with CD over UC patients was attributed to gastrointestinal complications rather than malignant diseases. Some carcinogenic factors therefore seem most likely to exist in the pathogenesis of UC.

Adolescent↗

[Disease prevention by vitamins based on epidemiological investigations in humans].

Epidemiological studies in humans clearly indicate that higher consumption of vegetables and fruits, or a plant based diet, reduce the risk of cancer and coronary heart disease. Antioxidant vitamins or micro-nutrients contained in vegetables and fruits seem to be active components in the prevention of cancer and coronary heart disease. Intervention studies, however, failed to demonstrate protective effects. Further intervention studies with different study design are needed to clarify the role of supplemental vitamins or micro-nutrients in the prevention of cancer and coronary heart disease. The results of a few cohort and intervention studies have provided a good evidence that vitamin E supplement is protective against coronary heart disease.

Coronary Disease↗

The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/10(6) cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < < or = 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate with the susceptibility to lung carcinogenesis.

Adult↗

A long-term follow-up study on risk factors for hepatocellular carcinoma among Japanese patients with liver cirrhosis.

To identify virological parameters (serostatus of hepatitis B surface antigen [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(-) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio [HR] = 5.85, 95% confidence interval [CI] 1.65-20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21-1.99). For genotype 1 HCV infection, patients with HCV-RNA levels < 1 Meq/ml tended to present lower risk than patients with > or = 1 Meq/ml (P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and alpha-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.

Adult↗

[Surgical management of pulmonary metastases].

The results of surgical resection for pulmonary metastases from colorectal, breast, and renal cell carcinomas, soft tissue sarcoma, and osteosarcoma are reviewed. The number of pulmonary metastases, the presence of hilar or mediastinal involvement, and extrapulmonary foci are discussed in terms of surgical treatment. The size of pulmonary tumors or tumor doubling time has no significant effect on survival, while the number of metastatic foci does. Although a slight survival advantage has been noted for patients without hepatic metastases from colorectal cancer before pulmonary metastases occur, the difference in survival rates among patients with and without hepatic metastases is not significant. The role of surgery is less clear in breast cancer patients, and therefore further prospective study is considered essential. Higher relapse rates have been reported in patients with soft tissue sarcoma and osteosarcoma, although patients with these metastases can achieve long-term survival after a second metastasectomy. VATS is not be recommended for metastatic cancer surgery, because intraoperative identification of metastatic foci is often difficult.

Breast Neoplasms↗

Relationship of hepatitis C virus genotypes and viremia levels with development of hepatocellular carcinoma among Japanese.

The roles of hepatitis C virus (HCV) genotypes and viremia levels in the pathogenesis of hepatocellular carcinoma (HCC) were examined in case-control analyses of 69 patients with HCC, 55 patients with liver cirrhosis (LC) without HCC, and 30 controls undergoing health examinations. Major HCV genotypes (genotypes 1 and 2) were determined by both reverse transcription-polymerase chain reaction (RT-PCR)-based and serological assays, and the HCV-RNA level by a branched DNA assay. Genotype 1 was detected in 68-82% of HCCs, 71-73% of LCs, and 50-72% of controls. Based on RT-RCR, the relative risk for genotype 1 vs. 2 contrasting either HCC or LC patients with controls was estimated at 3.6 (95% confidence interval: 1.1-12.5) for HCC and 4.8 (1.1-20.4) for LC, whereas no risk excess was evident for the occurrence of HCC in LC (relative risk: 0.7). The corresponding association based on the serological assay was somewhat weaker and statistically insignificant. No significant difference in age or time lapse after blood transfusion was observed according to the genotype. The HCV-RNA titer for genotype 1 was significantly lower among HCC patients than among LC patients or controls. Genotype 1 HCV may be associated with HCC through affecting relatively early stages of liver diseases progression prior to the establishment of LC.

Adult↗

Heterosexual transmission of hepatitis C virus among married couples in southwestern Japan.

The heterosexual transmission of hepatitis C virus (HCV) remains controversial, and data from general populations are scanty. In this cross-sectional study, we assessed the seroprevalence of antibodies to hepatitis C virus (anti-HCV) and the presence and genotype of HCV-RNA among 109 married couples within an endemic, community-based Japanese population. Overall, 25% of the husbands and 32% of the wives had anti-HCV. Spouses with anti-HCV-positive partners were around 2 times more likely to have anti-HCV than spouses with anti-HCV-negative partners (p = 0.01). Of 6 couples in which both spouses had HCV-RNA, however, 3 presented discordant HCV genotypes (type 1b vs. 2b). The couples' anti-HCV concordance status was not significantly influenced by the presence or absence of HCV-RNA among anti-HCV-positive partners (odds ratio [OR]: 0.8 for wives, 0.6 for husbands), nor by the length of marriage, the number of pregnancies or the use of contraceptives. No significant associations with anti-HCV were observed for serum markers of sexually transmitted agents, including human T-lymphotropic virus (OR = 1.1, 95% confidence interval [CI] 0.5-2.3), Treponema pallidum (OR = 0.7; CI 0.1-6.1) and hepatitis B virus (OR = 1.6; CI 0.9-3.0). Our results suggest that the clustering of HCV infection among specific couples within this endemic population may not be attributable to heterosexual transmission. Follow-up studies are necessary to determine the risk of heterosexual transmission of HCV in endemic areas.

Adult↗

Diet/nutrition and stomach cancer in Japan.

Incidence rates of stomach cancer in Japan are much higher than in other countries, but have shown a large decline in the past 20 years. Incidence rates among the Japanese in Hawaii are only one third or less of the indigenous Japanese in Japan. Epidemiologic studies indicate that consumption of salt or salty foods is associated with increased risk of stomach cancer, in concert with the results of experimental studies in rodents. In contrast, consumption of vegetables and fruit is associated with decreased risk. Accumulated evidence is strong that a reduction in salty food intake and an increase in vegetable and fruit intake is important to primary prevention of stomach cancer. Possible protective roles of tea and allium vegetables and supplemental use of micronutrients, interaction between salty food intake and H. pylori infection and other factors need further investigation. Occurrence of stomach cancer in Japan may be reduced by two thirds or more via dietary changes, as seen in the population of Japanese ancestry in Hawaii.

Antibodies, Bacterial↗

Relationship of alcohol use, physical activity and dietary habits with serum carotenoids, retinol and alpha-tocopherol among male Japanese smokers.

BACKGROUND: Despite considerable interest in the anticarcinogenic and anti-atherosclerotic effects of carotenoids and alpha-tocopherol, little is known about determinants of these serum micronutrients. METHODS: The association of lifestyle factors including alcohol use, physical activity and dietary habits with serum levels of carotenoids (lycopene, lutein, cryptoxanthin and beta-carotene), retinol and alpha-tocopherol were studied in 194 healthy men aged 24-60 years who smoked > 15 cigarettes/day. A self-administered questionnaire ascertained consumption frequency of 12 food items, alcohol consumption, levels of physical activity and the number of cigarettes smoked per day. RESULTS: Of the dietary items studied, total vegetable intake was significantly, positively associated with beta-carotene levels, as was fruit intake with serum levels of each carotenoid. Tofu intake was unexpectedly, but strongly related to decreased levels of cryptoxanthin and beta-carotene. None of the food items was materially related to serum levels of retinol and alpha-tocopherol. Alcohol consumption was most strongly and inversely associated with levels of all the carotenoids except lutein, whereas was positively associated with retinol level but not with alpha-tocopherol level. Frequency of participation in sports was significantly and positively associated with both retinol and alpha-tocopherol levels. The amount of cigarettes smoked per day was unrelated to each micronutrient level in this study of moderate or heavy smokers. CONCLUSIONS: The consumption of vegetables and fruits is an important determinant of serum carotenoid levels even in smokers. Alcohol consumption is inversely associated with carotenoid levels, although the mechanism for this is not clear. Tofu and physical activity influence serum levels of antioxidative micronutrients, and these relationships need further studies.

Adult↗

Environmental factors and aryl hydrocarbon hydroxylase activity (CYP1A1 phenotype) in human lymphocytes.

Since aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene (BP) and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine AHH activity in the determination of susceptibility to lung cancer. Lymphocytes from healthy male adults (239) of non-smokers and smokers were cultured in vitro and assayed for non-induced and 3-methylcholanthrene (MC)-induced AHH activity and AHH inducibility (MC-induced AHH activity/non-induced AHH activity). A day-to-day variation in AHH activity was not observed while a seasonal variation was apparent. Very wide differences in non-induced AHH and MC-induced AHH activities were observed. The association of some selected environmental factors and AHH activity was studied. Age was related to non-induced AHH activity (Spearman's rank correlation coefficients (r), r = 0.185, p < 0.005) and AHH inducibility (r = -0.329, p < 0.001). Coffee consumption was associated with non-induced (age-adjusted r = 0.138, p < 0.05) and MC-induced AHH activity (age-adjusted r = 0.173, p < 0.01). Cigarette smoking was correlated with non-induced AHH activity (age-adjusted r = 0.191, p < 0.005) and AHH inducibility (age-adjusted r = -0.191, p < 0.005). No significant association was observed for any other selected factors, including alcohol intake or broiled food consumption. In conclusion, AHH activity might be affected by cigarette smoking and coffee consumption, and was dependent on the age of the donor. Day-to-day and seasonal variation analyses showed that this assay method was reproducible and reliable and AHH inducibility might be a useful biomarker in cancer epidemiology. As those factors may affect the AHH activity, a careful control of those factors to AHH activity is necessary in epidemiological studies on the association between AHH inducibility in human lymphocytes and lung cancer.

Adult↗

Mutagenicity of 24-hour duplicate of Japanese diet.

In order to elucidate the genotoxicological characteristics of the Japanese diet, the mutagenicity of 24-h duplicate of the diet samples were investigated. The mutagenicity of blue rayon extract was examined in the Ames Salmonella/microsome assay. Thirty-two (91.4%) of 35 samples revealed mutagenicity toward Salmonella typhimurium TA98 in the presence of S9 mix. The mutagenic activities showed significant correlations with the consumption rates of broiled fish (r = 0.517, p = 0.0021) and broiled meat (r = 0.494, p = 0.0036). In other test conditions, 6 (17.1%), 5 (14.3%) and 8 (22.9%) samples were mutagenic to Salmonella typhimurium TA98 without S9 mix, TA100 with S9 mix and TA100 without S9 mix, respectively. Findings in the present study suggest that high consumption of broiled fish and broiled meat are important as the source of mutagens/carcinogens in the Japanese diet. In the present study, however, biological inference of these findings could not be made in relation to the occurrence of cancers, especially of the gastric cancer, which is the most prevalent form of cancer in Japan.

Aged↗

Hepatitis C virus infection and risk of hepatocellular carcinoma among Japanese: possible role of type 1b (II) infection.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important risk factor for hepatocellular carcinoma HCC), the strength of this association has been inconsistent. In addition, the role of specific HCV genotypes in HCC progression has not yet been determined. PURPOSE: We conducted a case-control study to estimate the relative risk (RR) of HCC in relation to HCV infection among residents of the Fukuoka Prefecture, where HCC risk is among the highest in Japan, and to examine whether the risk differs according to HCV genotypes and/or HCV RNA titers. METHODS: Stored serum samples obtained from 91 patients with HCC and 410 healthy control subjects, who had been frequency matched to the patients with regard to sex and age, were tested for antibodies to HCV by use of second-generation immunoradiometric and immunoblot assays. The presence of serum HCV RNA and of specific HCV genotypes was determined by use of polymerase chain reaction-based assays, and HCV RNA titers were measured by use of a branched DNA assay. RESULTS: Antibodies to HCV were detected in 71 patients (78.0%) and in 30 control subjects (7.3%), of whom 57 patients and 25 control subjects had serum HCV RNA. One patient was positive for HCV RNA but not for antibodies to HCV. The sex- and age-adjusted RR of HCC among individuals positive for antibodies to HCV was estimated to be 53.7 (95% confidence interval [CI] = 27.1-106.2). Antibodies to HCV were much more prevalent among patients negative for serum, hepatitis B surface antigen (HBsAg) (69 of 72, 95.8 %) than among HBsAg-positive patients (two of 19, 10.5%); the RR increased to 339.6 (95% CI = 96.5-1195.8) in the separate analysis of HBsAg-negative subjects. The most frequent genotype among HCV RNA-positive subjects was type lb (also called type II) (found in 49 [86.0%] of 57 patients and in 15 [60.0%] of 25 control subjects); individuals with type 1b infection experienced a significantly elevated risk (RR = 3.8; 95% CI = 1.0-13.9) compared with the risk observed for individuals with type 2a (also called type III) infection. No statistically significant association between HCV RNA titers and HCC was evident. CONCLUSIONS: HCV infection, particularly type 1b infection, plays an important role in the development of HCC among the study population. We estimated that approximately 78% (95% CI = 69%-86%) of the HCCs that occur in this high-risk area are attributable to HCV infection, if we assume that the patients in this study were representative population samples. IMPLICATIONS: Further studies are needed to clarify potential risk factors, including specific HCV genotypes, for progression to HCC among HCV carriers.

Adult↗

Nutrition and stomach cancer.

Epidemiologic evidence on the relation between nutrition and stomach cancer is reviewed. Stomach cancer shows a distinct international variation and dramatic worldwide decline. These descriptive features suggest that dietary factors are important in determining the risk of stomach cancer. The authors assessed relevant data regarding specific dietary hypotheses in the etiology of stomach cancer. A negative association with fresh vegetables and fruits is highly consistent in numerous case-control studies in different populations. Both epidemiologic and experimental data suggest that vitamins C and carotenoids lower risk of stomach cancer. Evidence is sparse and inconsistent as to protective effects of vitamin E and selenium. Epidemiologic studies have not lent, and will not provide, supportive evidence for an etiologic role of nitrate intake. High salt intake has been associated with an increased risk in many case-control studies and limited cohort studies. Taken together with animal data, it is considered that high salt intake is a risk factor for stomach cancer. Both epidemiologic and experimental data are inconclusive as to whether high-starch diets confer an increased risk. Cohort studies using quantitative dietary assessment and biologic measurement of micronutrients are needed for further understanding of etiologic roles of dietary factors in the causation of stomach cancer.

Animals↗

Type IV collagenase activity and cavernous sinus invasion in human pituitary adenomas.

Pituitary adenomas are regarded generally as benign tumours, but some of them can invade the cavernous sinus. On the other hand, matrix metalloproteinase-9 (MMP-9), which is a type IV collagenase, recently has been found to be expressed in matastases and to be related to the invasiveness of various malignant tumours including brain tumours. In order to investigate some characteristic features of pituitary adenomas which invade the cavernous sinus, we examined immunohistological studies for MMP-9 in seven pituitary adenomas for type IV collagen in a dura mater and assayed for type IV collagenase activity in seven adenomas using type IV collagen labelled with fluorescein isothiocyaniate (FITC). We found immunopositive adenoma cells for MMP-9 in all invasive adenoma and immunopositive spindle like cells for type IV collagen in the dura mater. All three invasive adenomas had high levels of type IV collagenase activity (0.57-0.72 U/ml), but the four adenomas which did not invade the cavernous sinus had low levels of type IV collagenase activity (0.0-0.10 U/ml). These results suggest that the level of type IV collagenase activity in a pituitary adenoma may be related to its ability to invade the cavernous sinus.

Adenoma↗

Endoscopic resection of intraventricular ependymal cyst presenting with psychosis.

BACKGROUND: Intracranial ependymal cysts are rare lesions generally located in the cerebral parenchyma, juxtraventricular region, or subarachnoid space; but no case of a purely intraventricular ependymal cyst has been reported. CASE REPORT: A case of intraventricular ependymal cyst presenting with symptoms of psychosis is reported. The patient's symptoms resolved almost completely following endoscopic resection of the cyst. The embryologic basis of the development of an ependymal cyst inside the ventricle and its histologic characteristics are discussed. Possible mechanism of psychosis in this case is also discussed. CONCLUSION: Minimally invasive techniques, as in this case, may be useful in refractory psychotic cases with cystic lesions.

Adult↗