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Biomedical subjects

S Tsugane

Publications and source records attributed to S Tsugane.

At least 91 records · Page 5Linked to original sources

A pilot study for a randomized controlled trial to prevent gastric cancer in high-risk Japanese population: study design and feasibility evaluation.

Observational epidemiological studies suggest that some nutrients reduce the risk of gastric cancer and that individuals with atrophic gastritis are at high risk of developing gastric cancer. One possible measure for gastric cancer prevention is therefore nutritional supplementation for the high risk group. Before recommending this strategy for the general public, however, a randomized controlled trial (RCT) is necessary. To evaluate the feasibility of an RCT, the authors conducted a pilot study using recipients of a health check-up program in a general hospital in Japan. The subjects who were asked to participate in the trial had been diagnosed as having atrophic gastritis on the basis of serum pepsinogen I < 70 ng/ml and the ratio of pepsinogen I to II < 3.0. They were requested to ingest double-blinded capsules containing different levels of vitamin C and beta-carotene every day. Out of the 219 subjects (118 males, 101 females) who were eligible for the study and had the required pepsinogen measurement, 90 (41%) met the criteria for atrophic gastritis. Among them, 55 (61%) (35 males, 20 females) gave their informed consent to participate in the RCT. Fifty-four participants completed a 3-month course of supplementation, and all of them agreed to a 5-year supplementation period. The authors concluded that an RCT using double-blinded nutritional supplements and targeting apparently healthy individuals is feasible in an intervention study for cancer prevention in Japan.

Adult↗

A data-based approach for designing a semiquantitative food frequency questionnaire for a population-based prospective study in Japan.

A self-administered food frequency questionnaire (FFQ) has been used commonly in epidemiologic studies of diet and chronic diseases. The analysis of dietary data in the target population is useful for designing a new questionnaire. The authors studied the major food sources of nutrient intakes in the Japanese population in order to develop a FFQ for a population-based prospective study. Subjects were 180 men aged 40-49 years and their 155 spouses who were sampled from four Public Health Center districts. Weighed food records over three consecutive weekdays were collected during the winters of 1989-1991. All foods reported were grouped into 154 items, and the percent contribution of each food to the total population intake of 15 nutrients was computed. Based on these data, a FFQ with 138 items was developed. The food list covered well the population intake of most nutrients (median = 83%, range = 55-91%), except for lipid (70%) and sodium (55%). The questionnaire was applied to the prospective study conducted in the same areas where the dietary data were collected, and an investigation to assess its reproducibility and validity is currently underway.

Adult↗

Temporal change in the reproducibility of a self-administered food frequency questionnaire.

The authors studied temporal change in the reproducibility of a self-administered food frequency questionnaire. During 1988-1994, 492 residents of a rural Japanese town completed five questionnaires including 27 food items, with intervals ranging from 2 weeks through 5.5 years. The reproducibility decreased steadily over time for pairs of the questionnaires administered in the same season (median Spearman's r at 2 weeks and 5 years = 0.62 and 0.28, respectively). The reduction was less marked for those surveyed in different seasons (median r at 5 months and 5.5 years = 0.35 and 0.28, respectively). The short-term, different season correlation at 5 months was lower than the short-term, same season correlation at 1 year. For individual food items, a lower initial reproducibility, infrequent consumption, and a larger difference in seasonal intake were associated with a greater reduction in reproducibility over time. The results indicate that reproducibility studies should deliberately choose the intervals and the seasons for surveys.

Epidemiologic Methods↗

Oxidative DNA damage induced by silica in vivo.

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.

8-Hydroxy-2'-Deoxyguanosine↗

Perceptions of change in diet have limited utility for improving estimates of past food frequency of individuals.

Accuracy of methods to assess past diet in retrospective studies is of concern. Adjustment of current intake for subjects' perceptions of change is one alternative to estimate past intake. The authors studied the potential utility of perceived change in diet in residents of a rural Japanese community who participated in three sequential surveys with self-administered questionnaires. Frequencies of consumption for 27 foods were investigated in the first and second questionnaires administered in 1988 and 1993 (n = 451), and perceived changes in their frequencies during this period were asked in the second and third questionnaires surveyed within two weeks (n = 214). Perceptions of change in diet were highly reproducible. At a group-level analysis, they were consistent with the changes in food frequencies in 21 of the 27 items. Nevertheless, whereas current diet adjusted for perceived change correlated better with past intake than did current intake alone in 17 foods, improvement in Pearson's correlations was only marginal (median = 0.02). Perceptions of change in diet would therefore be of limited utility in improving estimate of past intake among individuals in retrospective studies.

Adult↗

A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis.

Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis. It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis. In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level. The SAA1 gamma [Ala52(GCC), Ala57(GCG)] differed from SAA1 alpha [Val52(GTC), Ala57(GCG)] only at one base, indicating a single point mutation. On the other hand, SAA1 beta [Ala52(GCC), Val57(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes. Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi 2(2) = 11.59, p = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs. 0.37). There was also a notable difference in the distribution of SAA1 genotypes (chi 5(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs. 0.18). Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis.

Adult↗

CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de Janeiro, Brazil.

Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYP1A1, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.

Base Sequence↗

Prognostic value of p53 protein accumulation in cancer cell nuclei in adenocarcinoma of the uterine cervix.

Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing malignancies of the female reproductive system because of its tendency to spread aggressively and to be resistant to radiation and systemic therapies. To clarify the prognostic significance of p53 alteration in CxAd, we immunohistochemically examined the incidence of p53 nuclear accumulation, which is considered to be mostly parallel with p53 gene mutation, and its association with clinicopathological parameters in 26 patients with CxAd. The overall incidence of p53 nuclear accumulation was 46% (12 of 26), being higher in groups with clinically advanced disease, higher degrees of cellular atypia, and deeper myometrial invasion, but significantly lower in patients with integration of human papillomavirus (HPV) type 16 or 18 DNA. Nuclear p53 immunoreactivity as well as lymph node status, depth of invasion and the absence of HPV-DNA integration were significant indicators of a poor prognosis. Examination of p53 nuclear accumulation could be applied to biopsy material, and would be of practical assistance in predicting the prognosis of CxAd both preoperatively and postoperatively.

Adenocarcinoma↗

Prognostic significance of the overexpression of c-erbB-2 protein in adenocarcinoma of the uterine cervix.

BACKGROUND: The overexpression of c-erbB-2 protein is a prognostic marker in patients with breast cancer. Alteration of the c-erbB-2 oncogene in development of adenocarcinoma of the uterine cervix, an unfavorable gynecologic neoplasm, is unknown. METHODS: To clarify the role of the c-erbB-2 oncogene in adenocarcinoma of the uterine cervix, formalin-fixed, paraffin-embedded tissue sections from 44 cases of cervical adenocarcinoma were immunohistochemically examined for expression of c-erbB-2 protein and for c-erbB-2 gene amplification in DNA by slot blot-hybridization analysis. RESULTS: The expression of c-erbB-2 protein was detected in 34 cases (77%). Strong expression on cell membranes was detected in 11 cases (25%). Most cases with strong membrane expression of c-erbB-2 protein also showed amplification of the c-erbB-2 gene by slot blot-hybridization. Expression of the protein on cell membranes was more often seen at clinical Stage II or III (9 of 23 [39%]) than at Stage 0 or 1 (2 of 21 [9%]) (P < 0.05, Fisher's exact test). Expression of the c-erbB-2 protein was also associated with poorer prognosis of patients with cervical adenocarcinoma by comparison of survival curves (P < 0.005) and by the Cox regression model analysis. CONCLUSIONS: Overexpression of c-erbB-2 protein is associated with amplification of c-erbB-2 gene and frequently occurred in cervical adenocarcinomas of the patients with poor prognoses.

Adenocarcinoma↗

Observer disagreement in histological classification of ovarian tumors in Japan.

Histological slides of 789 cases of ovarian tumor registered by the Japanese Gynecologic Oncology Group, sponsored by the Ministry of Health and Welfare, Japan, were reviewed by three certified pathologists in order to evaluate the observer disagreement among the pathologists and the reproducibility of the histological classification. In 53.0% of the cases, all observers agreed upon the diagnosis. At least two of them agreed in 88.4% of the cases. The observer disagreement was highest for low potential malignancy (borderline malignancy) tumors (44.4%), including serous, mucinous, and endometrioid tumors. The results of the study clearly indicate the necessity of establishing a slide review system in order to obtain reliable data for comparative research. Moreover, the histological criteria, especially of tumors of borderline malignancy, should be more clearly defined to obtain high reproducibility of ovarian tumor diagnosis.

Carcinoma↗

Differing effects of vasopressin on regional cerebral blood flow of dogs following intracisternal vs. intra-arterial administration.

We investigated the differential effect of the intracisternal and intraarterial administration of vasopressin on the regional cerebral blood flow (rCBF) in the parietal cortex of dogs. Regional CBF, velocity and blood volume were assayed by laser flowmetry. The intracisternal injection of 1 nmol vasopressin significantly increased the rCBF and velocity, without affecting blood volume. However, the intravertebral arterial injection of 1 nmol vasopressin significantly decreased the rCBF and velocity. This discrepancy can be explained by a difference in the affected vasculature; large blood vessels in the subarachnoid space vs. whole cerebral vascular system. The intracisternal and intraarterial injection of the nitric oxide inhibitor NG-monomethyl-L-arginine reduced the rCBF from the base line, and significantly suppressed the rCBF elevation induced by vasopressin. The effect of vasopressin may be considered as the summation of the increased flow from the dilated large vessels via the release of nitric oxide from the endothelium, and of the decreased flow from the contracted small vessels.

Animals↗

Effects of vasopressin on regional cerebral blood flow in dogs.

Vasopressin may regulate the regional cerebral blood flow (rCBF) via two balancing effects: increased flow from the vessels dilated by nitric oxide from the endothelium, and decreased flow from the vessels contracted by direct stimulation of smooth muscle. The effect on the rCBF in anesthetized dogs following the intracisternal or intraarterial administration of vasopressin was investigated by laser flowmetry with the device placed on the dura over the parietal cortex. The intracisternal injection of 1 nmol vasopressin significantly increased the rCBF to 145.3 +/- 27.3% of base line. In contrast, the intravertebral arterial injection of vasopressin had no significant effect on the rCBF. This can be explained by a difference in the affected vasculature; mainly large vessels in the subarachnoid space vs. whole vascular system supplied by the vertebral artery. The intracisternal injection of 10 mumol of NG-monomethyl-L-arginine (L-NMMA) reduced the rCBF; pretreatment with this agent significantly suppressed the elevation in rCBF induced by vasopressin. The intraarterial injection of L-NMMA reduced the rCBF more than its intracisternal administration. It also suppressed the rCBF induced by vasopressin.

Animals↗

Risk factors for lung cancer in Rio de Janeiro, Brazil: a case-control study.

The association between the risk of lung cancer and tobacco smoking, dietary factors and occupational exposures was examined in a hospital-based case-control study. The study involved 123 consecutive cases and 123 controls, matched by age (+/- 3), sex, and race. In this first study of lung cancer risk in Brazil, we found that tobacco smoking is the strongest risk factor with an odds ratio (OR) for current and former smokers of 22 (CI, 6.5-76) and 7.7 (CI, 2.2-27), respectively. An OR of 2.8 (CI, 1.0-7.7) was found for users of black tobacco in the form of hand-rolled cigarettes) in combination with conventional cigarettes, after adjustment for life-time consumption of any kind of tobacco; users of conventional cigarettes only were considered as a reference group. Cessation of smoking had an important influence in reducing the lung cancer risk, whereas early initiation of smoking increased the risk. Among dietary factors, frequent consumption of meat (P < 0.01) and pasta (P = 0.02) were positively associated with lung cancer risk after adjusting for smoking and income. No association was found with green/yellow vegetables or fruits. We were unable to detect any significant association related to occupational exposures. This study confirmed the association of lung cancer with smoking as the most important predictor of risk. It also indicates the increase in risk associated with the use of black tobacco in combination with conventional cigarettes.

Adult↗

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.

Adolescent↗

Salty food intake and risk of Helicobacter pylori infection.

To clarify the risk factors for Helicobacter pylori infection, which is considered to play an etiologic role in atrophic gastritis, duodenal ulcer and gastric cancer, various parameters including diet and socioeconomic characteristics were compared between H. pylori-infected and non-infected men. In a cross-sectional study of 634 men aged 40 to 49 years selected randomly from five areas with different rates of gastric cancer mortality, 474 of 628 men evaluated were positive for IgG antibody against H. pylori. After logistic regression analysis adjusted for area, the results showed a significant association between frequent intake of pickled vegetables and prevalence of H. pylori antibody (odds ratios against men who consume < 1 day/week 1.19 for 1-2 days/week, 1.92 for 3-4 days/week, 1.90 for 5-7 days/week; P for trend = 0.02). Daily consumption of miso soup was also associated with an increased risk (odds ratio against non-daily consumer = 1.60, 95% confidence interval = 1.03-2.49). Occupation, number of siblings, education, smoking and alcohol drinking, and other dietary habits were not significantly associated with the prevalence of infection in this population. Although there are limitations in a cross-sectional study such as this, consumption of salty foods appears to increase the risk of H. pylori infection, which could be a marker of salty food intake or an intermediate risk factor in the etiologic sequence between salty food intake and gastric cancer.

Adult↗

Cytochrome P-450 lA1 genotype in lung cancer patients and controls in Rio de Janeiro, Brazil.

Mspl restriction fragment length polymorphism in cytochrome P-450 IA1 (CypIA1) gene, which has been associated with lung cancer susceptibility in Japanese, was studied in persons from Rio de Janeiro, in the framework of a hospital-based, age, race (black or nonblack), and gender-matched case-control study (n = 222; 110 cases and 112 controls). Contrary to the hypothesis, there was no difference in the frequency of the C genotype (Mspl site-present homozygous), even after racial breakdown. There were no significant differences between cases and controls when categorized according to tobacco consumption. The lifetime quantity of tobacco smoked was not different among lung cancer patients with three different genotypes (A, Mspl site-absent, homozygous; B, heterozygote; and C). The background frequency of the Mspl polymorphism C genotype is a little less than 10%, similar to that of the Japanese healthy population. The CyplA1 Mspl polymorphism itself does not seem to be related to susceptibility to bronchial carcinogenesis in this area.

Adult↗

Alcohol consumption and risk of esophageal cancer in Japan: a case-control study in seven hospitals.

In a multi-center case-control study, we evaluated the risk of esophageal cancer in the Japanese population. All patients and controls were inpatients in the surgical departments of seven hospitals nationwide. Patients eligible for the study were those newly diagnosed as having primary esophageal cancer. One control per case was selected from among patients admitted to the same hospital, and 141 male pairs were analyzed using logistic regression analysis. The results showed dose-response relation between the risk of esophageal cancer and both the quantity (g/week) and frequency (times/week) of alcohol drinking (P value for trend = 0.0001). Although a statistically significant risk increase was shown among moderate to heavy smokers (15 < or = cigarette/day < 25) (odds ratio, 4.35:95% confidence interval, 1.81-10.49), the dose-response for cigarette smoking was unclear (P value for trend = 0.07). No combined effect of alcohol drinking and cigarette smoking was found. A frequent intake of fruit was associated with a decreased risk (P value for trend = 0.02). After adjustment for alcohol consumption, cigarette smoking and fruit intake were found not to be associated with the risk, whereas a preference for high-temperature food and drink showed a statistically significant positive association (P value for trend = 0.02). Drinkers who consumed shochu most frequently showed a three-fold increased risk over that for beer consumers, although the association disappeared after adjusting for the amount of alcohol consumed. The present results confirm alcohol intake and a preference for high-temperature food to be associated with an increased risk of esophageal cancer and show the amount of alcohol consumed, rather than the type of alcoholic beverage, to be the main risk determinant.

Alcohol Drinking↗

Calvasculin, as a factor affecting the microfilament assemblies in rat fibroblasts transfected by src gene.

Cell transformations accompany alterations in cell morphology and microfilament patterns. Calvasculin encodes mRNA termed pEL-98, 18A2, 42A, p9Ka, or mts1, found to be elevated in several metastatic cell lines. We report the elevation of calvasculin expression in SR-3Y1 cells, which show disappearance of ordered microfilaments, compared to that in 3Y1 cells and that the similar distribution of calvasculin to that of actin filaments. Interestingly, calvasculin co-sediments with F-actin and bundles actin filaments in a Ca(2+)-dependent manner. This activity, along with the elevation of calvasculin following transformation, suggests that the disorganization of filaments in SR-3Y1 cell is due to the cross-linking activity of calvasculin.

Actin Cytoskeleton↗