Dietary intake of antioxidant vitamins and risk of stroke: the Japan Public Health Center-based Prospective Study.

BACKGROUND/OBJECTIVES: Epidemiologic evidence on the relationship between antioxidant vitamin intake and stroke is limited. We aimed to investigate the association between dietary intake of antioxidant vitamins and the incidence of total stroke and ischemic stroke. SUBJECTS/METHODS: The subjects were 82 044 Japanese men and women aged 45-74 years under the Japan Public Health Center-based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was done using a food frequency questionnaire. During 983 857 person-years of follow-up until the end of 2009 we documented 3541 incident total strokes and 2138 ischemic strokes. RESULTS: Dietary intakes of α-carotene, ß-carotene, α-tocopherol and vitamin C were not inversely associated with the incidence of total stroke and ischemic stroke adjustment for cardiovascular risk factors and selected lifestyle variables. When stratified by current smoking status, the inverse association between dietary vitamin C intake and incidence of total stroke observed among non-smokers but not smokers, with respective multivariable hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95% confidence interval (CI), 0.68-0.96; P-trend=0.03) among non-smokers; and 1.03 (0.84-1.25; P-trend=0.55) among smokers. As for ischemic stroke, the corresponding multivariable hazard ratios were 0.76 (0.60-0.96; P-trend=0.02) among non-smokers; and 1.00 (0.78-1.28; P-trend=0.61) among smokers. CONCLUSIONS: Dietary vitamin C intake was inversely associated with the incidence of total stroke and ischemic stroke among non-smokers.

Seasonal differences in total antioxidant capacity intake from foods consumed by a Japanese population.

BACKGROUND/OBJECTIVES: This cross-sectional study aimed to estimate total antioxidant capacity (TAC) intake from food and beverages in a Japanese population from 7-day seasonal dietary records. SUBJECTS/METHODS: The 7-day weighed dietary records of 390 subjects over four seasons between 1996 and 1998 were used. The TAC values (µmol trolox equivalents (µmol TE)/g) of various foods and beverages were defined, as reported in previous studies for weighed dietary records, using several different methods. TAC values of foods were estimated in 242 food and beverage items: 86.5% of vegetables, 99.1% of fruits, 71.5% of potatoes, 96.7% of beans, and 100% of chocolates. Differences in TAC intake per day and intake (g) per day among seasons in each of the food and beverage group were compared using a general linear model for repeated measures. The TAC intake/day were calculated for each food and beverage item in the four seasons. RESULTS: TAC intake/day (µmol TE/day) varied from 10 189 (summer) to 12 292 (winter). TAC intake/day from fruits (2696) and potatoes (395) was highest in autumn, from vegetables (2827) it was highest in summer and from beans (4151) and tea (2331) it was highest in winter. CONCLUSIONS: The dietary habits of the studied Japanese population showed the highest antioxidant capacity in winter and the lowest in summer.

Rice, bread, noodle and cereal intake and colorectal cancer in Japanese men and women: the Japan Public Health Center-based prospective Study (JPHC Study).

BACKGROUND: Colorectal cancer (CRC) incidence rate increased rapidly in Japan between the 1950s and 1990s. We examined the association between rice intake and CRC risk in comparison with bread, noodles and cereal among Japanese adults enrolled in the Japan Public Health Center-based prospective Study. METHODS: A total of 73,501 Japanese men and women were followed-up from 1995 to 1999 until the end of 2008 for an average of 11 years. During 801,937 person-years of follow-up, we identified 1276 incident cases of CRC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC for rice, noodle, bread and cereal intake were calculated by Cox proportional hazards model. RESULTS: Overall, no significant association was observed for the highest quartile of rice intake compared with the lowest and the risk of CRC and its subsites in men (HR, 0.77; 95% CI, 0.56-1.07) and women (HR, 1.10; 95% CI, 0.71-1.68). However, a non-significant inverse trend was observed between rice intake and rectal cancer in men. No clear patterns of association were observed in bread, noodle and cereal intake. CONCLUSION: Our findings suggest that the consumption of rice does not have a substantial impact on the risk of CRC in the Japanese population.

Requirement of integrin ß3 for iron transportation during enamel formation.

Rodent incisors exhibit pigmentation on their labial surfaces. Although previous studies have shown that this pigment is composed of iron, the existence of other elements has not been investigated. This study found that the lower incisors of CD61, also known as integrin ß3, null mice (CD61(-/-)) lacked pigmentation. Although ameloblasts differentiated and formed enamel normally, no ferric ion accumulation was observed in maturation-stage ameloblasts in CD61(-/-) mice. Surface elements of control and CD61-/- lower incisors were compared by x-ray photoelectron spectroscopy (XPS). XPS analysis detected C, Ca, N, O, and P on the labial surfaces of lower incisors of both mice, whereas Fe was detected only in control samples. No peak of non-ferrous metal or other element was detected in either group. Quantitative RT-PCR analysis of 18 iron-transportation-related genes with mRNA from maturation-stage ameloblasts and ALC, a pre-ameloblastic cell line, was performed. The results suggested that CD61 regulates the expressions of Slc11a2 and Slc40a1, both of which are involved in iron transportation in epithelial tissues. These results suggested that the pigment on the labial surface of mouse incisors is composed of Fe and that both anemia and reduction of iron-transporting proteins may cause the loss of pigmentation in CD61(-/-) mice.

Dietary fiber intake and risk of cardiovascular disease in the Japanese population: the Japan Public Health Center-based study cohort.

BACKGROUND/OBJECTIVES: There has been no study with regard to the association between dietary fibers and the incidence of stroke and coronary heart disease (CHD) in Asia. We investigated the association between dietary fiber and the risk of cardiovascular disease (CVD), which we defined as stroke or CHD, in a Japanese population. SUBJECTS/METHODS: We studied 86 387 Japanese subjects (age 45-65 years, without CVD or cancer in 1995 as Cohort I and in 1998 as Cohort II) and used a self-administered questionnaire to follow-up the participants until the end of 2004. Dietary fiber intake was estimated from food-frequency questionnaires comprising 138 food items. RESULTS: After 899 141 person-years of follow-up, we documented the incidence of 2553 strokes and 684 cases of CHD. Multivariable-adjusted hazard ratios (95% confidence intervals (CIs)) of CVD for the third to fifth quintiles of total fiber were 0.79 (0.63-0.99), 0.70 (0.54-0.89) and 0.65 (0.48-0.87) in women, respectively, compared with the lowest quintile. Total fiber intake was inversely associated with the incidence of stroke, either cerebral infarction or intracerebral hemorrhage in women. The results for insoluble fiber in women were similar to those for total fiber, whereas those for soluble fiber were weak. An inverse association of total fiber with CVD was observed primarily in non-smokers (P for trend=0.045 and 0.001) and not in smokers (probability values for interaction between total fiber and smoking were 0.06 and 0.01 in men and women, respectively). CONCLUSIONS: Higher total dietary fiber was associated with reduced risk of CVD in Japanese non-smokers.

Analysis of estrogenic activity of foodstuffs and cigarette smoke condensates using a yeast estrogen screening method.

Hormone mimics present in our environment are of concern because such agents could potentially reduce fertility and increase sexual dysfunction in wildlife and increase the risk of breast and reproductive organ cancers in man. Therefore, monitoring of the levels of estrogenic compounds in environmental materials is essential in order to prevent their exposure to man and to discover potential harmful effects on human health. In the present study, we analyzed estrogenic activity in 23 foodstuffs and cigarette smoke condensate samples extracted with an organic solvent, using the yeast estrogen screening (YES) system. Three soybean-related foodstuffs (soy sauce, tofu, miso), beer, coffee and cigarette smoke condensates showed clear estrogenic activity in the YES system. HPLC fractionations followed by the YES of these YES-positive samples revealed the presence of many estrogenic compounds in cigarette smoke condensates, whereas the other samples exerted estrogenic activities in only one or two fractions. Genistein was able to be isolated as the major active principle in soy sauce, tofu and miso, its concentration in these three foodstuffs ranging from 0.1 to 394 microg/g or ml. 8-Prenylnaringenin was also isolated from beer extracts as a major compound with estrogenic activity present at 0.22-4.0 ng/ml. Estrogenic activity of 8-prenylnaringenin with YES was 10-times as high as that of genistein, although it was 100-times less than that of 17beta-estradiol. Based on our results in vitro, 10 mg miso and 10 ml beer can be calculated to have similar estrogenic activity to 1 pmole 17beta-estradiol. It is very important that the effects of genistein and 8-prenylnaringenin on human health are elucidated.

Testicular toxicity in F344 rats by aminophenylnorharman, formed from norharman and aniline.

9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman (APNH)] is a novel mutagenic heterocyclic amine, produced by the reaction of norharman with aniline in the presence of S9 mix. In the present study, the acute toxicity of this compound was investigated in male F344 rats. Ten-week-old animals were treated with a single intragastric injection of APNH at doses of 45 or 90 mg/kg body wt and euthanized 1, 3, or 6 days afterward. When APNH was administered at a dose of 90 mg/kg, vacuolation of Sertoli cells in the testis was seen at 1 day after treatment. The testicular damage had markedly progressed by day 6, with multinucleated giant cells and loss of round spermatids in the seminiferous tubules observed in groups 1 and 2 of the four histological categories of spermatogenesis. Numbers of spermatogonia were also decreased by APNH treatment. No toxic changes were observed in Leydig cells under these conditions and serum follicle-stimulating hormone and luteinizing hormone concentrations were also unchanged from control values. Such severe testicular damage was not observed at any time point at the 45 mg/kg dose level of APNH. Moreover, neither norharman nor aniline alone exerted acute testicular toxicity at doses equivalent to 90 mg/kg of APNH. In addition to the testicular lesions, erosive changes of urinary bladder, thymic atrophy, and panmyelophthisis were evident in rats given APNH at 90 mg/kg.

Validity and reproducibility of a self-administered questionnaire to determine dietary supplement users among Japanese.

OBJECTIVE: To evaluate reproducibility and validity of a self-administered food frequency questionnaire (FFQ) to determine the dietary supplement use. DESIGN: Questionnaire data were compared with dietary records (DR) in four 7 day periods for validity. FFQ1 and FFQ2 administered at an interval of approximately one year were compared for reproducibility. SETTING AND SUBJECTS: A total of 361 samples were selected for a validation study of a questionnaire from the subgroup of the Japan Public Health Center-based prospective Study on cancer and cardiovascular disease (JPHC Study) cohort II. Categories of dietary supplements in the FFQ were 'multivitamins', 'beta-carotene', 'vitamin C', 'vitamin E', and 'other supplements'. For each category, inquiries were made as to the brand name, frequency and duration of use. A dietary supplement user was defined as a subject who used a dietary supplement one or more times a week for a year or longer. RESULTS: Prevalence of overall supplement use was 10.9%. Percentage agreement between FFQ1 and FFQ2 was 91.7%. Sensitivity and specificity of supplement use by FFQ were 80.6% and 89.2%, respectively. Sensitivity was high for 'vitamin C'. When the self-reported categories were corrected, sensitivity for 'multivitamins' and 'vitamin E' improved. CONCLUSIONS: The FFQ on dietary supplements used for the JPHC 5 y follow-up survey was valid to determine overall use and well-defined dietary supplement use such as vitamin C. Categories must be corrected when determining multivitamin and 'vitamin E'.

Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats.

9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman, APNH), produced by the reaction of norharman with aniline in the presence of S9 mix, is a novel heterocyclic amine (HCA), with mutagenicity to Salmonella typhimurium TA 98 and YG 1024 comparable to that of other HCAs such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). This experiment was designed to investigate its potential to induce glutathione S-transferase placental form (GST-P) positive foci in the liver. Male F344 rats, 7 weeks old, were fed diet containing 0, 10, 20, or 50 ppm APNH for 4 weeks, killed by ether euthanasia and performed complete necropsy. Numbers of GST-P positive foci larger than 0.1 mm in diameter induced by APNH at the dose of 10, 20, and 50 ppm were increased in a dose dependent manner to 0.52, 1.3, and 21 foci/cm2, respectively, with areas of 0.006, 0.01, and 2.3 mm2/cm2. No such GST-P positive foci were observed in rats fed control diet. These findings suggest that APNH has hepatocarcinogenic potential in male F344 rats.

Evaluation of gamma thalamotomy for parkinsonian and other tremors: survival of neurons adjacent to the thalamic lesion after gamma thalamotomy.

OBJECT: The effects of gamma thalamotomy for parkinsonian and other kinds of tremor were evaluated. METHODS: Thirty-six thalamotomies were performed in 31 patients by using a 4-mm collimator. The maximum dose was 150 Gy in the initial six cases, which was reduced to 130 Gy thereafter. The longest follow-up period was 6 years. The target was determined on T2-weighted and proton magnetic resonance (MR) images. The point chosen was in the lateral-most part of the thalamic ventralis intermedius nucleus. This is in keeping with open thalamotomy as practiced at the authors' institution. In 15 cases, gamma thalamotomy was the first surgical procedure. In other cases, previous therapeutic or vascular lesions were visible to facilitate targeting. Two types of tissue reaction were onserved on MR imaging: a simple oval shape and a complex irregular shape. Neither of these changes affected the clinical course. In the majority of cases, the tremor subsided after a latent interval of approximately 1 year after irradiation. The earliest response was demonstrated at 3 months. In five cases the tremor remained. In four of these cases, a second radiation session was administered. One of these four patients as well as another patient with an unsatisfactory result underwent open thalamotomy with microrecording. In both cases, depth recording adjacent to the necrotic area revealed normal neuronal activity, including the rhythmic discharge of tremor. Minor coagulation was performed and resulted in immediate and complete arrest of the remaining tremor. CONCLUSIONS: Gamma thalamotomy for Parkinson's disease seems to be an alternative useful method in selected cases.

Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods.

Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.

Contribución al estudio de la prevalencia de la infección por clamidia en parejas con infertilidad / Contribution to the study of clamidial onfection in infertility couples

Objetivo: Establecer la prevalencia de la infección por chlamydia trachomatis en una población con problemas de la reproducción. Diseño: estudio descriptivo epidemiológico realizado entre julio de 1997 y junio de 1998. Material: A 140 parejas con problemas de reproducción, atendidas en la Unidad de Reproducción Humana del Hospital Nacional Edgardo Rebagliati Martins de EsSalud, se les tomó muestra endocervical (mujeres) o uretral (hombres) para detección de clamidia. Medidas de estudios: Detección de presencia de chlamydia trachomatis por método de inmunofluorescencia directa, IgG e IgA. Resultados: Al estudio de antígeno de clamidia por inmunofluorescencia directa, 122 (43,6 por ciento) pacientes fueron positivos, en 59,8 por ciento en ambos miembros de la pareja. La mayoría de los pacientes no presentó síntomas, en 23 por ciento no hubo alteración del espermatograma, a pesar de ser positivo a clamidia y, en las mujeres, la mayoría mostró alteraciones tubáricas a la laparoscopia y un 12 por ciento microvesículas en la serosa. Conclusión: La prevalencia de infección por clamidia en parejas con infertilidad en nuestro medio es alta, lo que debe ser considerado en los protocolos de manejo en reproducción, para diagnóstico y tratamiento, así como para tomar medidas adecuadas de prevención.

Pituitary adenomas treated by microsurgery with or without Gamma Knife surgery: experience in 122 cases.

The clinical outcome of 122 patients with pituitary adenomas treated by microsurgery and/or Gamma Knife radiosurgery (GKRS) was analyzed to evaluate patient selection criteria and the role of GKRS. Sixty-six resections were performed in 59 patients. All tumors were macroadenomas, except for 5 ACTH-producing adenomas. Twenty-four of the 31 hypersecreting adenomas showed normal serum hormone values after treatment. Postoperative complications were rhinorrhea, cranial nerve palsies, and a small thalamic infarct. GKRS was performed on 18 of the operated patients because of residual tumors, mostly in the cavernous sinus. Thirty-five of the 63 patients treated by GKRS were followed for more than 2 years. All adenomas except 2 were stable or had decreased in size. Eleven of 17 functioning adenomas showed normal serum hormone values after treatment. It is concluded that tumors that compress the optic pathway should be removed and that residual tumors in the cavernous sinus are good indications for radiosurgery.

Fractionated Gamma Knife radiosurgery for malignant gliomas: neurobiological effects and FDG-PET studies.

Experimental single-dose neural irradiation was performed in rats and monkeys. Acute and 'early' late damage was observed following single high-dose treatments. By contrast, following a single low-dose treatment, neither 'early' nor 'delayed' late damage was noted. Based on these experiments, a clinical trial of fractionated Gamma Knife surgery for malignant gliomas was begun, and patients were followed by FDG-PET studies. An acute response of the tumor was obtained without damage to the surrounding brain. Fractionated Gamma Knife surgery is a potential alternative treatment for malignant gliomas.

Early diagnosis of tuberculosis by fibreoptic bronchoscopy.

We carried out a retrospective study of the methods used to achieve an early diagnosis of 67 patients with pulmonary tuberculosis treated at our institute between 1984 and 1989. Sputum bacteriology was positive in 56 of the 67 patients, 22 were positive on microscopical examination of smears and on culture and 34 on culture alone. The 11 patients with negative sputum bacteriology were all diagnosed by fibreoptic bronchoscopy. In addition, 21 of the 34 smear-negative/culture-positive patients were examined by fibreoptic bronchoscopy and the initial diagnosis was made in 7 of these. Thus the initial diagnosis was made by sputum bacteriology in 49 cases and by fibreoptic bronchoscopy in 18 cases. The median number of days between obtaining a specimen and starting therapy was 7 days for sputum microscopy, 41 days for sputum culture, 7 days for microscopic examination of bronchoscopy specimens, 51 days for culture of the same and 19 days for biopsy. Fibreoptic bronchoscopy is therefore useful for the diagnosis of cases of tuberculosis in which tubercle bacilli are not detected in sputum and, in some instances, for an earlier diagnosis of smear-negative/culture-positive patients.

[Informed consent of the family in the chemotherapy for lung cancer].

In Japan where the question of cancer notification has yet to be resolved, it is difficult to obtain an informed consent from the patient himself in clinical studies of the chemotherapies for cancer. In fact, the chemotherapy is administered while not enough explanation is given to the family let alone the patient. Such is the present situation. For the purpose of finding out the best possible method at present, we carried out a method whereby an informed consent of the family is substituted for a consent of the patient in phase II study of inoperable non-small cell carcinoma of the lung. As a result, the consent was obtained from 21 (91.3%) out of 23 families. This method should be taken into consideration as a feasible one under the present circumstances. It was in only one family (4.3%) that a consent on the notification of diagnosis from the family to the patient was obtained. In order for the informed consent to be established, efforts to form a social consensus on cancer notification are needed.

Human tumor clonogenic assay for carcinoma of the lung. II. Factors that influence colony formation in soft agar.

The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors.

The different effects of recombinant human tumor necrosis factor on rat fibrosarcoma sublines.

The antitumor effect of recombinant human tumor necrosis factor (rH-TNF) on two clones of rat fibrosarcoma with different metastatic potential to lymph nodes was examined. The colony formation of clone A, which has high metastatic potential, was completely inhibited by continuous exposure to rH-TNF at 50 U/ml. In contrast, colony formation of clone G, which has low metastatic potential, was not inhibited by high concentrations of rH-TNF (10,000 U/ml). The inhibitory effect of rH-TNF on colony formation by clone A was also observed with a 1-h exposure to rH-TNF. This effect was time and concentration dependent, as determined by the colony assay, 3H-thymidine uptake assay, and 51Cr-release assay. 3H-thymidine and 3H-uridine uptake per cell of clone A exposed to rH-TNF was not decreased. This suggests that the mechanisms of the antitumor effect of rH-TNF were not due to inhibition of DNA and RNA synthesis of tumor cells. In vivo growth and lymph node metastases of clone A inoculated i.p. to Donryu strain rats were completely suppressed by 14 consecutive i.p. injections of 10(5) or 10(6) U/kg per day of rH-TNF. On the other hand the growth of clone G was not influenced by rH-TNF administration.