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PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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DOI： 10.2188/jea.JE20140055

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/dmrr.2406

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3802/jgo.2013.24.3.249

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/eurpub/ckr194

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Access below to see full text; http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2702.2011.04039.x/full
PMID:22642659

DOI： DOI: 10.1111/j.1365-2702.2011.04039.x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Access below to see full text; http://www.medsci.org/v09p0488.htm
PMID:22927774

DOI： doi:10.7150/ijms.4682

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:22228701

DOI： DOI: 10.1002/dmrr.2277

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Access below to see full text; http://eurpub.oxfordjournals.org/content/early/2012/01/11/eurpub.ckr194.long
PMID:22241757

DOI： doi: 10.1093/eurpub/ckr194

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/dmrr.2277

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:21328338

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:21328338
To overcome drug resistance in ovarian carcinoma, novel resistance mechanisms must be elucidated for clinical application. We purified 2 proteins in the 300 kDa range from cisplatin-resistant cells (NOS2CR2) by affinity chromatography with cisplatin-exposed Glutathione Sepharose 4B. The purified proteins were identified as spectrin αII and βII by peptide mass mapping analysis. Western blot analysis detected greater expression of spectrin αII and βII in NOS2CR2 than in wild-type cells (NOS2). The same result was obtained for spectrin βII expression by immunohistochemical staining. To determine whether spectrin αII and βII contribute to resistance, a drug sensitivity test was performed on SKOV3 ovarian cancer cells transfected with small interfering RNA. Sensitivity to platinum drugs was increased in the expression reduced cells. In a clinical study of five ovarian serous adenocarcinoma cases, tumor specimens taken after treatment with carboplatin stained more strongly for spectrin βII expression than untreated specimens. Fifty-two tumor specimens from 46 patients with ovarian serous adenocarcinoma were immunohistochemically stained for spectrin βII and scored. Tumors previously treated by chemotherapy scored higher than those not treated. Of 27 cases with detectable residual tumors at the time of surgery, cases scoring 4-6 had shorter progression-free survival periods after platinum-based chemotherapy than cases scoring 0-3 (p = 0.012). The cytoskeleton proteins Spectrin αII and βII contributed to drug resistance by anchoring the GS-Pt complex to the cell membrane, arresting cisplatin activity. Thus spectrin βII may be a useful predictor of platinum sensitivity in ovarian serous adenocarcinoma.

DOI： 10.1002/ijc.25983

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Several reports have found the onset or activity of inflammatory myopathies to show spatial clustering and seasonal association. We recently detected autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) in more than 20% of patients with dermatomyositis. Anti-MDA-5 antibodies were associated with the presence of rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis (CADM). The present study aims to assess the growing prevalence of CADM and the geographical incidence of anti-MDA-5-positive patients.

METHODS: We reviewed medical charts and examined the presence of anti-MDA-5 antibodies in 95 patients, including 36 CADM patients. Sera were obtained from 1994 through 2011. Statistical analyses were performed to assess whether CADM development and the presence of anti-MDA-5 antibodies were associated with various parameters, including age at disease onset, season of onset, annual positivity, and population of resident city.

RESULTS: Tertiles based on the year when the sera were collected showed increasing tendencies of CADM and anti-MDA-5-positive patients among all of the dermatomyositis patients. From 1994 to 2010, the relative prevalence of CADM and anti-MDA-5 antibody-positive patients significantly increased. Interestingly, the presence of anti-MDA-5 antibodies in 26 patients was inversely associated with the population of their city of residence.

CONCLUSIONS: This is the first study to examine the distribution of anti-MDA-5-positive dermatomyositis phenotypes in Japan. Regional differences in the incidences of these phenotypes would suggest that environmental factors contribute to the production of antibodies against MDA-5, which triggers innate antiviral responses.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 21113028

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:22006230

DOI： 10.1007/s10654-011-9623-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:21535304

DOI： 10.1111/j.1447-0756

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:21220191
BACKGROUND: There are few studies that compare the physiological and biological efficacies between different early skin-to-skin contacts (SSC) post birth.

AIM: To investigate physiologically and biochemically how early SSC with different initiation and duration time influence the stress post birth for full-term infants.

STUDY DESIGN: Non-experimental study.

SUBJECTS: Study I; Thirty-two infants who began SSC 5min or less [birth SSC, mean initiation time (standard deviation): 1.6 (1.1) min] after birth and 36 infants who did so more than 5min [very early SSC, 26.3 (5.0) min] in heart rate (HR) and oxygen saturation (SpO(2)) analysis. Study II; Eighteen infants who underwent SSC for 60min or less [mean initiation time: 7.5 (12.2) min] and 61 infants who did so for more than 60min [15.3 (12.5) min] in salivary cortisol analysis.

OUTCOME MEASURES: HR and SpO(2) measured for 30min post birth. Salivary cortisol concentration measured at 1min, 60min, and 120min post birth.

RESULTS: Birth SSC group reached HR stability of 120-160bpm significantly faster than very early SSC group by Kaplan-Meier analysis (P=0.001 by log-rank test). As for SpO(2) stability of 92% and 96%, no significantly between-group difference was found. Salivary cortisol levels were significantly lower between 60 and 120min after birth in SSC group, continuing for more than 60min compared with SSC group for 60min or less after adjustment for salivary cortisol level at 1min besides the infant stress factors (P=0.046).

CONCLUSIONS: Earlier SSC beginning within 5min post birth and longer SSC continuing for more than 60min within 120min post birth are beneficial for stability of cardiopulmonary dynamics and the reduction of infant stress during the early period post birth.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

近年、成人病胎児期起源仮説、Developmental Origin of Health and Disease(DOHaD)仮説が注目されている。今回、母娘二世代362組の母子健康手帳を用いて、二世代間の妊娠分娩経過の関連を検討した。世代間比較では、二世代目は一世代目に比べ身長が高く、妊娠中の平均収縮期血圧が低く、体重増加量が少なく、出生した児の体重が軽かった。また、分娩時出血量が多く、分娩様式では帝王切開を受けた人が多かった。一方、二世代間の非妊娠時体格、妊娠中期以降の血圧や体重増加量、出生児の出生体重と頭囲は統計学的に有意な正の関連を示した。また、重回帰分析による三世代目の出生体重に関連する因子の分析では、二世代目の出生体重が二世代目の非妊娠時のBMIや妊娠時の体重増加量より強く関連することが示された。本研究の結果により、世代間の妊娠分娩経過には、社会背景の変化や医療水準の向上などによる差異はあるものの、関連がみられた。また、前世代の胎内環境が次世代の胎内環境に影響を与えることが示唆された。以上より、前世代の妊娠分娩経過を知ることは、妊娠早期からの保健指導を可能にし、妊娠中の合併症の予防、さらにはその先に続いてゆく世代の健康につながっていく可能性が示唆された。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID:21791889
The women's own intrauterine environment may influence their own pregnancy and their babies. The aim of our study was to investigate how a woman's birth weight affects the course of her pregnancy later in life as well as the body size of her babies; this study was based on the developmental origins of health and disease (DOHaD) concept. We collected Maternal and Child Health handbooks from 414 women and their biological mothers. They were classified into 3 categories based on the Fetal growth curve of Japan: light-for-date (LFD), which means birth weight is less than the -1.5SD; appropriate-for-date (AFD), which means it lies between the -1.5SD and +1.5SD; and heavy-for-date (HFD), which means it is in the +1.5SD, or higher. In the first trimester, systolic blood pressures (SBPs) were 117.6 (14.4 mmHg), 111.6 (12.4 mmHg), and 105.0 (11.6 mmHg), and diastolic blood pressures (DBP) were 71.0 (8.5 mmHg), 65.7 (9.4 mmHg), and 62.1 (8.7 mmHg) in women born LFD, AFD, and HFD, respectively (SBP: p for trend = 0.018, DBP: p for trend = 0.027). In the second and third trimesters, both SBP and DBP were higher for women born LFD than for those of the other 2 groups. Birth weights of the babies of women born LFD, AFD, and HFD were 2,791.1 (483.0 g), 3,043.4 (361.0 g), and 3,248.0 (431.5 g), respectively (p for trend < 0.01). Our findings support the DOHaD concept and suggest that intrauterine environment in fetal life may be passed down from generation to generation.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20976133

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20631456
BACKGROUND: A number of lifestyle factors, including smoking and drinking, are known to be independently associated with all-cause mortality. However, it might be more effective in motivating the public to adopt a healthier lifestyle if the combined effect of several lifestyle factors on all-cause mortality could be demonstrated in a straightforward manner.

METHODS: We examined the combined effects of 6 healthy lifestyle behaviors on all-cause mortality by estimating life expectancies at 40 and 60 years of age among 62 106 participants in a prospective cohort study with a 14.5-year follow-up. The healthy behaviors selected were current nonsmoking, not heavily drinking, walking 1 hour or more per day, sleeping 6.5 to 7.4 hours per day, eating green leafy vegetables almost daily, and having a BMI between 18.5 to 24.9.

RESULTS: At age 40, we found a 10.3-year increase in life expectancy for men and a 8.3-year increase for women who had all 6 healthy behaviors, as compared with those who had only 0 to 2 healthy behaviors. Increases of 9.6 and 8.2 years were observed for men and women, respectively, at age 60 with all 6 healthy behaviors. When comparing currently nonsmoking individuals with 0 to 1 healthy behaviors, the life expectancy of smokers was shorter in both men and women, even if they maintained all 5 other healthy behaviors.

CONCLUSIONS: Among individuals aged 40 and 60 years, maintaining all 6 healthy lifestyle factors was associated with longer life expectancy. Smokers should be encouraged to quit smoking first and then to maintain or adopt the other 5 lifestyle factors.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20699444

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20451548
OBJECTIVE: To examine a combination of healthy lifestyles on the risk of metabolic syndrome (MetS) to inform future interventions.

METHODS: A total of 1897 men aged 35-60 years participated in an annual health check-up in 2002 and 2005. MetS was defined by AHA/NCEP criteria. Logistic regression analyses were used to estimate age- and BMI-adjusted odds ratios (ORs) of MetS incidence for each healthy lifestyle (regular physical activity, adherence to healthy eating behaviors, not current smoking, and maintaining a stable weight since one's mid-twenties), separately (Model 1) and simultaneously (Model 2). A points system was developed to derive 3-year risk of MetS incidence by assigning a specific point to each healthy lifestyle.

RESULTS: MetS developed in 285 (15.0%) subjects after the follow-up. The ORs of MetS for each healthy lifestyle ranged from 0.42 to 0.64 (Model 2). Three-year risk of MetS incidence was predicted to differ from 1% to 60% according to the individual point total of the points system. The population-attributable fraction of MetS in subjects whose point total was not in the highest quartile was 71%.

CONCLUSION: Adherence to healthy lifestyles was associated with a lower risk of MetS among apparently healthy middle-aged Japanese male workers.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20211645
OBJECTIVE: To investigate the associations between dietary intake of n-3 polyunsaturated fatty acids (plant-derived alpha-linolenic acid: ALA, and marine-derived eicosapentaenoic and docosahexaenoic acid: EPA+DHA) and insulin resistance (IR) in a lean population with high n-3 PUFA intake.

METHOD: We cross-sectionally studied 3383 Japanese local government workers aged 35-66 in 2002. IR was defined as the highest quartile of homeostasis model assessment, and nutrient intake was estimated from a diet history questionnaire. The odds ratios (ORs) of IR taking the lowest quartile of ALA or EPA+DHA intake as the reference were calculated by logistic regression analysis.

RESULTS: Mean age, body mass index (BMI), and dietary ALA, and median of dietary EPA+DHA were 47.9 years, 22.9 kg/m(2), and 1.90 g/day (0.88%E) and 0.77 g/day (0.36%E), respectively. The ORs of IR decreased across the quartiles of ALA intake (multivariate-adjusted OR for Q4 versus Q1=0.74, P for trend=0.01) and the association was observed only in subjects with a BMI of <25 kg/m(2) (P for interaction=0.033). However EPA+DHA showed no such associations consistently.

CONCLUSION: Higher ALA intake was significantly associated with a lower prevalence of IR in normal weight individuals of middle-aged Japanese men and women.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 20351478
OBJECTIVE: The purpose of this study was to investigate the dietary iron intake and associated other dietary factors and clinical characteristics among a representative sample cohort of Japanese population.

METHODS: We obtained data from NIPPON DATA80 and 90 that were conducted with the National Nutrition Surveys in 1980 and in 1990. Then we estimated nutrient and food intakes of individuals in the National Nutrition Survey of 1980 and that of 1990, which were adjusted on the basis of data of the National Nutrition Survey of 1995. Finally, we analyzed data for the 10,422 participants (4585 men and 5837 women) in NIPPON DATA80 and 8342 participants (3488 men and 4854 women) in NIPPON DATA90 having dietary iron intake information.

RESULTS: In NIPPON DATA80 and 90, there was a significant relationship between the dietary iron intake and age for both men and women. Dietary protein intake was associated with iron intake where as dietary fat intake did not show any association. Regarding the minerals, significant relationships were observed between the different minerals and dietary iron intake. Apart from the food group of milk and dairy products, there were significant differences in other food groups according to quintiles of iron intakes for men and women.

CONCLUSIONS: We described the mean dietary iron intake and its relation with other dietary factors and clinical characteristics in Japanese adults as the baseline data in NIPPON DATA80 and in NIPPON DATA90.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PMID: 19543206
The association between BMI and all-cause mortality may vary with gender, age, and ethnic groups. However, few prospective cohort studies have reported the relationship in older Asian populations. We evaluated the association between BMI and all-cause mortality in a cohort comprised 26,747 Japanese subjects aged 65-79 years at baseline (1988-1990). The study participants were followed for an average of 11.2 years. Proportional-hazards regression models were used to estimate mortality hazard ratios (HRs) and 95% confidence intervals. Until 2003, 9,256 deaths occurred. The underweight group was associated with a statistically higher risk of all-cause mortality compared with the mid-normal-range group (BMI: 20.0-22.9); resulting in a 1.78-fold (95% confidence interval: 1.45-2.20) and 2.55-fold (2.13-3.05) increase in mortality risk among severest thin men and women (BMI: <16.0), respectively. Even within the normal-range group, the lower normal-range group (BMI: 18.5-19.9) showed a statistically elevated risk. In contrast, being neither overweight (BMI: 25.0-29.9) nor obese (BMI: > or =30.0) elevated the risk among men; however among women, HR was slightly elevated in the obese group but not in the overweight group compared with the mid-normal-range group. Among Japanese older adults, a low BMI was associated with increased risk of all-cause mortality, even among those with a lower normal BMI range. The wide range of BMI between 20.0 and 29.9 in both older men and women showed the lowest all-cause mortality risk.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To evaluate the influence of menopausal status on the serum adiponectin concentration and investigate whether the contribution of adiponectin to insulin resistance is modified by menopausal status. SUBJECTS: We conducted a population-based, cross-sectional study of 207 premenopausal and 206 postmenopausal Japanese women. MEASUREMENTS: Data on anthropometric characteristics, fasting serum adiponectin, glucose and insulin concentrations were used. Insulin resistance (homeostasis model assessment of insulin resistance: HOMA-IR) was calculated. RESULTS: Postmenopausal women had significantly higher HOMA-IRs than premenopausal women [1.50 (1.42, 1.59) vs 1.18 (1.12, 1.24), geometric mean (1 standard error range), P = 0.005]. Paradoxically, adiponectin levels in postmenopausal women were also significantly higher than those in premenopausal women [10.3 (9.95, 10.7) vs 9.04 (8.71, 9.39), P = 0.028]. Multiple regression analysis showed that body mass index (BMI) was the only significantly independent predictor [standardized partial regression coefficients (sbeta) = 0.319, P < 0.001] for HOMA-IR among premenopausal women, whereas both BMI and adiponectin were the significant predictors among postmenopausal (sbeta = 0.334 and -0.141, P < 0.001 and < 0.05, respectively). When the subjects were restricted to those without metabolic disorders including high blood pressure, hypertriglyceridaemia, hypo-HDL cholesterolaemia and high fasting glucose, adiponectin (sbeta = -0.249, P < 0.05) was the only significant predictor for HOMA-IR among postmenopausal women but BMI was not significant (sbeta = 0.223, P = 0.075). CONCLUSIONS: The transition to menopause increases serum adiponectin concentrations. And the significant and negative association between adiponectin and HOMA-IR was observed only after menopause. Therefore, adiponectin may play a role in the improvement of an incipient insulin-resistant state after, rather than before, menopause.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Few epidemiologic studies have examined the association between the rate of eating and obesity. In this study, we cross-sectionally examined the association of the self-reported rate of eating with current Body Mass Index (BMI), and BMI-change from 20 years of age to the current age. METHODS: Subjects were 3737 male (mean age +/- standard deviation and mean BMI +/- standard deviation: 48.2 +/- 7.1 years and 23.3 +/- 2.7 kg/m(2)) and 1005 female (46.3 +/- 7.0 years and 21.8 +/- 2.8 kg/m(2)) Japanese civil servants. We measured self-reported categorical rate of eating, current BMI, BMI at age 20, and BMI-change from age 20. Energy intake was assessed over a 1-month period with a brief-type diet history questionnaire. RESULTS: The multiple regression analysis in which the current BMI was regressed by categorical rate of eating, energy intake, age, and lifestyle factors showed that current BMI steadily increased by -0.99, -0.67, 0.81, and 1.47 kg/m(2) along with the progress of categorical rate of eating from the 'medium' group to 'very slow', 'relatively slow', 'relatively fast', and 'very fast' groups, respectively, in men. In women, the corresponding values were -1.06, -0.35, 0.50, and 1.34 kg/m(2). When the BMI increment from age 20 to current age was regressed in the same manner, the increment was -0.63, -0.34, 0.57, and 1.05 kg/m(2) in men and -0.71, -0.32, 0.34, and 1.14 kg/m(2) in women, respectively. Additionally, both BMI at age 20 and current height were positively associated with rate of eating. CONCLUSIONS: Our results among middle-aged men and women suggest that eating fast would lead to obesity.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Low birth weight has been associated with adult hypertension in several Western populations. This association needs to be evaluated in Japanese people. METHODS AND RESULTS: A population-based cross-sectional study of 3,107 subjects (2,303 males and 804 females) aged 35-66 years was conducted. The participants responded to a questionnaire about their birth weights, blood pressure, medical history, parental history, and lifestyle factors. Hypertension was defined as systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg and/or under treatment by anti-hypertensives. Multiple logistic regression analysis adjusted for age, sex, body mass index, parental history, and lifestyle revealed the adjusted odds ratios for hypertension were 1.26 (95% confidence interval: 0.88-1.80), 1.00 (reference), 0.89 (0.73-1.08) and 0.70 (0.49-1.00) in subjects in birth weight categories of <2,500 g, 2,500-<3,000 g, 3,000-<3,500 g, 3,500- g, respectively (p-value for trend =0.009). Furthermore, this inverse association was clearly pronounced in normal-weight subjects. CONCLUSION: Low birth weight was independently associated with adult hypertension in the Japanese workplace population. Our results support the inverse association observed previously in Western populations and suggest that intrauterine environmental insults might lead to permanent changes in the metabolism and structure of the fetal organs influencing the regulation of blood pressure.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Low birth weight has been associated with metabolic and vascular diseases, but the precise mechanism is debated. Adiponectin is one of the key molecules in metabolic disease, and a decrease in level precedes the onset of type 2 diabetes and development of atherosclerosis. Our aim is to examine whether low birth weight is associated with adiponectin concentration in adult. METHODS: We conducted a population-based cross-sectional study of 2277 subjects (1661 men and 616 women) aged 35 to 66 years who had their self-reported birth weights and adiponectin concentrations measured as adults. RESULTS: After adjusting for potential confounders, including age, sex, current body mass index (BMI), smoking status, alcohol consumption, and exercise, geometric mean adiponectin levels were 6.63, 6.45, 6.86, 7.05, 6.75, and 7.22 microg/mL for subjects with birth weights less than 2500, 2500 to less than 2800, 2800 to less than 3000, 3000 to less than 3200, 3200 to less than 3500, and greater than 3500 g, respectively. A positive association was found between birth weight and adiponectin concentration (trend p = 0.002). Stratified by current BMI of 25 kg/m2, a positive association was not observed for subjects with a BMI less than 25 kg/m2, but was pronounced in those with a BMI of 25 kg/m2 or greater. CONCLUSION: This study indicates that low birth weight contributes to decreased adiponectin concentrations in adult life independently of current BMI, especially for obese subjects.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The incidence of ovarian cancer in Japan has increased since the 1970s. The many studies that have assessed the relationship between body mass index (BMI) and the risk of ovarian cancer have produced contradictory results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk, which was initiated in 1988. METHODS: A self-administered questionnaire on dietary habits and other risk factors for cancer was completed by 36,456 Japanese women. After 7.6 years of follow up, 38 cases of ovarian cancer were available for analysis. Cox proportional-hazards models were used to compute relative risks and to adjust for confounders. RESULTS: Compared to women with BMI of 18.5-24.9 kg/m2, the relative risk of ovarian cancer was 2.24 (95% CI = 1.10-4.21) for BMI of 25.0-29.9 and 1.78 (95% CI = 0.24-13.34) for BMI of > or = 30 kg/m2. A test for trend revealed that this finding was statistically significant (P = 0.014). CONCLUSION: The results of this study suggest that being overweight is independently associated with a higher risk of developing ovarian cancer in the Japanese population.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidemiologic evidence is lacking for the association between alcohol consumption and the risk of breast cancer in Japanese women. We addressed this association in a prospective cohort study with an average follow-up of 7.6 years. At baseline (1988-1990), cohort participants completed a self-administered questionnaire that included alcohol use, reproductive history and hormone use. The women were followed up for breast cancer incidence through December 31, 1997. Cox proportional hazards models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer incidence and any association with alcohol consumption. During a follow-up of 271,412 person-years, we identified 151 women with breast cancer, of whom 45 were current drinkers and 11 drank > or =15 g of alcohol/day. After adjustment for age and other potential risk factors for breast cancer, the RR for current drinkers was 1.27 (95% CI 0.87-1.84) compared to nondrinkers. Average alcohol intake of <15 g/day did not significantly increase the risk for breast cancer. However, risk was significantly increased for women who consumed > or =15 g/day of alcohol (RR = 2.93, 95% CI 1.55-5.54). Age at starting drinking and frequency of consumption per week were not significantly associated with breast cancer risk. Our cohort study demonstrated that Japanese women who consume at least a moderate amount of alcohol have an increased risk of breast cancer.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To assess the validity of self-reported height and weight in a Japanese workplace population, and to examine factors associated with the validity of self-reported weight. DESIGN: Comparison of self-reported height and weight with independent measurement. SUBJECTS: In total, 4253 men and 1148 women aged 35-64 y (mean measured body mass index (BMI): 23.3 kg/m(2) in men, 21.9 kg/m(2) in women) were included in the study. MEASUREMENTS: Self-reported height and weight were obtained by a self-administered questionnaire. Measured height and weight were based on annual health checkups. Sex, age, measured BMI, and the presence of hypertension, diabetes, and hyperlipidemia were examined as potential factors associated with the accuracy of self-reported weight. RESULTS: Self-reported height and weight were highly correlated with measured height and weight for men and women (Pearson's r for men and women: 0.979 and 0.988 in height, 0.961 and 0.959 in weight, 0.943 and 0.950 in BMI, respectively). For men, mean differences+/-2 s.d. of height and weight were 0.078+/-2.324 cm and -0.034+/-5.012 kg, respectively, and for women 0.029+/-1.652 cm and 0.024+/-4.192 kg, respectively. The prevalence of obesity with BMI > or =25 kg/m(2) based on self-reported data (23.6 and 11.5% for men and women, respectively) was slightly smaller than that based on measured data (24.9 and 12.4%, respectively). Specificity and sensitivity, however, were quite high for both men and women (sensitivity was 85.8 and 85.2%, and specificity was 97.0 and 98.9%, respectively). The subjects with higher measured BMI significantly underestimated their weight compared with those with smaller BMI after adjustments for age in men and women. Furthermore, the presence of diabetes in men and age in women affected self-reported weight. Neither the presence of hypertension nor hyperlipidemia was associated with reporting bias. CONCLUSION: The self-reported height and weight were generally reliable in the middle

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Leptin's hematopoietic or proinflammatory role has been experimentally reported. We investigated whether serum leptin concentrations are associated with white blood cell (WBC) counts in humans. METHODS: Serum leptin concentrations of Japanese civil servants aged 40 to 59 years (1082 men and 200 women) were analyzed in relation to their WBC count. Serum leptin concentrations and WBC counts were measured by radioimmunoassay and automated particle counter respectively, using samples obtained at the time of the participants' annual health checkups. RESULTS: The geometric mean (+/-geometric standard deviation) leptin concentrations were 3.25 +/- 1.82 ng/mL and 6.25 +/- 3.99 ng/mL, and the geometric mean WBC counts, 5770 +/- 1269/mm(3) and 5107 +/- 1228/mm(3), in men and women respectively. The WBC count adjusted for age, body mass index (BMI), physical activity, and drinking and smoking habits increased together with the increase in leptin concentration. Multiple linear regression against WBC count by the leptin concentration and those covariates revealed a significant and independent association with serum leptin concentration especially in women (standardized beta = 0.31, p < 0.001), and also in men (standardized beta = 0.17, p < 0.001). BMI was not significantly associated with WBC counts in the multivariate model adjusting for leptin levels in both sexes. CONCLUSIONS: Our results are in line with leptin's hematopoietic or proinflammatory functions. The increased WBC counts often observed in obese people would be mediated by the increased leptin concentration.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prognosis of stomach cancer with advanced stage remains poor. New biomarkers of the disease that may contribute to establish the potential screening strategy would be of value for the early detection of individuals at high risk of the disease. METHODS: We conducted a prospective, nested case-control analysis among apparently healthy men and women who were followed for up to 8 years in the Japan Collaborative Cohort (JACC) Study, to evaluate serum levels of insulin-like growth factor I, II, and binding protein 3 (IFG-I, IGF-II, and IGFBP-3), transforming growth factorbeta-1 (TGFbeta1), soluble fas (sFas) and superoxide dismutase activity (SOD) in 210 stomach cancer cases diagnosed in the JACC Study in relation to those levels in their 410 controls. RESULTS: Among 6 serum biomarkers tested for case-control differences, only sFas level in female stomach cancer cases was significantly higher than that of controls (2.22 pg/ml vs. 2.04 pg/mL, respectively; P=0.013 by two-way analysis of covariance controlling for matching variable). CONCLUSION: None of the biomarkers consistently predicted future risk of stomach cancer in both men and women in the present analysis. Serum sFas level in women, however, should be studied much more thoroughly whether it provides meaningful refinement of risk stratification, or it elucidate the mechanisms of tumorigenesis in women.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To elucidate whether leptin is involved in the etiology of female colorectal cancer. METHODS: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. RESULTS: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, CI: 0.41-4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29-18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. CONCLUSION: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Host factors expressed by individual past medical history of hypertension, stroke, and myocardial infarction may have a relationship with colorectal cancer. METHODS: As part of the Japan Collaborative Cohort Study (JACC Study) for the Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho), we conducted a follow-up study of 110,792 Japanese inhabitants aged 40-79 years to reveal the relationship of past medical history of hypertension, stroke, and myocardial infarction at the baseline in 1988-1990 with colorectal cancer death for about 10 years up to the end of 1999. RESULTS: Past medical history of hypertension associated with an increased risk of female rectal cancer when analyzing all cancer cases with adjustment for age, body mass index, and exercise (hazard ratio [HR]=1.97, 95% confidence interval [CI]; 1.13-3.43). Past medical history of myocardial infarction was also an increased risk for female rectal cancer (HR=3.05, 95% CI; 1.28-7.28). Females who had a medical history of stroke had increased risk of rectal cancer without statistical significance. CONCLUSION: There was a positive association of past medical history of hypertension and myocardial infarction and an increased risk of rectal cancer in women.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recently, it has been hypothesized that inflammation increases the risk of colorectal cancer. We investigated whether serum levels of C-reactive protein (CRP), a biomarker of inflammation, are associated with colorectal cancer, using serum samples collected in the Japan Collaborative Cohort Study (JACC Study). METHODS: We conducted a nested case-control study in the JACC Study, investigating the relationship between the risk for colorectal cancer and serum levels of CRP determined by a high-sensitivity CRP enzyme immunoassay. The subjects recruited were 141 patients with colorectal cancer (63 males and 78 females) and 327 controls with no history of cancer (148 males and 179 females). Each case of colorectal cancer was matched for sex, age and participating institution to 2 or 3 controls. We used ttest to analyze mean differences in CRP levels between colorectal cancer cases and controls. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a conditional logistic regression model after adjusting for the potential confounding factors. RESULTS: Serum CRP levels were not clearly associated with the risk of colorectal cancer. The OR of the highest serum CRP levels was 1.18 (95% CI: 0.68-2.06) for colorectal cancer and 1.42 (95% CI: 0.73-2.74) for colon cancer, compared to subjects with lowest serum levels. The OR for incidence of colorectal cancer showed a similar trend, but the difference was not significant. Thus, high serum CRP levels did not appear to increase the risk of colorectal cancer. CONCLUSIONS: The present results suggest that high serum CRP levels are not associated with the risk of colorectal cancer in the JACC Study.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Glucose intolerance may increase the risk of developing colorectal cancer. METHODS: In a sero-epidemiological nested case-control study, conducted as part of the Japan Collaborative Cohort Study (JACC Study) for Evaluation of Cancer Risk, we measured serum glycoalbumin in 123 patients with colorectal cancer and 279 controls. Conditional logistic regression was used to evaluate the risk of colorectal cancer. RESULTS: There were trends towards an association between high levels of glycoalbumin and an increased risk of colorectal cancer in men (odds ratio [OR]=2.39; 95% confidence interval [CI]; 0.89- 6.36) and between high levels of glycoalbumin and a decreased risk of colorectal cancer in women (OR=0.41; 95% CI, 0.14-1.04). CONCLUSIONS: A high level of glycoalbumin may increase the risk of colorectal cancer in men. The finding that high levels of glycoalbumin in women decreased their risk of colorectal cancer was inconsistent with previous reports, and may have been the result of limitations in the procedure in selecting samples and statistical power.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Because alcohol drinking is a potential risk factor for colorectal cancer, the trend in alcohol consumption in Japan may partly explain the increase in incidence and mortality rates of this malignancy until 1990-1995. METHODS: We analyzed data from the Japan Collaborative Cohort Study. From 1988 to 1990, 23,708 men and 34,028 women, aged 40-79 years, completed a questionnaire on lifestyle factors including drinking habits. Incidence rate ratios (IRR) were estimated by using proportional hazards models. RESULTS: During the mean follow-up of 7.6 years through December 1997, we documented 418 incidents of colon cancer and 211 of rectal cancer. Male ex- or current drinkers demonstrated a twofold risk for colon cancer compared with nondrinkers: the multivariate-adjusted IRR was 2.01 (95% confidence interval [CI] 1.09-3.68) for ex-drinkers and 1.97 (95% CI: 1.28-3.03) for current drinkers. The doseresponse relationship between alcohol consumption and the risk, however, was not clear. Female exdrinkers were at an increased risk without statistical significance. For rectal cancer, we found a slightly lower risk in light current drinkers who consumed less than 22 g ethanol per day: the multivariate IRR was 0.61 (95% CI: 0.33-1.13) for men and 0.69 (95% CI: 0.27-1.74) for women. Although the IRR for all current drinkers was almost unity in men, an increasing trend in risk was detected with increasing alcohol consumption in current drinkers (trend p=0.027). CONCLUSIONS: Taking the findings from our study and other prospective investigations into consideration, more attention should be paid to alcohol consumption in the prevention of colon cancer in Japan.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The association between social relationships and lower mortality has been well documented in Western countries. This study aims to investigate that association among elderly Japanese in a rural area. METHODS: An analysis was conducted with 1,994 subjects (58.1% women), 78.3% of the total elderly aged 65 and older in a town, who were independent in activities of daily living. A baseline survey was carried out in 1992, and subjects were followed until 1999. Cox proportional hazard models examined the association between social relationships (availability of casual friend/ support provider, group membership, job, living arrangement) and an 88-month mortality. RESULTS: A significant association between social relationships and mortality was observed among the old-old (aged 75 and older). Among men, having a job and group membership were significantly associated with lower mortality with hazard ratios (95% confidence intervals) of 0.62 (0.41-0.94) and 0.60 (0.40-0.90), respectively, after adjustment for age, diagnosed illnesses, self-rated health, other social relationships, annual income, and home ownership. Among women, having a job and living alone were significantly associated with lower mortality with hazard ratios (95% confidence intervals) of 0.67 (0.45-0.99) and 0.35 (0.13-0.97), respectively. CONCLUSIONS: Social relationships such as having a job and group membership were associated with lower mortality among the old-old. In addition, old-old women living alone were better off in terms of mortality after adjustment for possible confounders. This suggests the importance of considering family relationships in terms of quality in areas where multi-generation households prevail.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The many studies into the relation between cigarette smoking and the risk of ovarian cancer have produced inconsistent results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, initiated in 1988. METHODS: A self-administered questionnaire on smoking habits and other risk factors for cancer was completed by 34 639 Japanese women. After 7.6 years of follow up, 39 cases of ovarian cancer were available for analyses. Cox proportional-hazards models were used to compute relative risks (RR) and to adjust for confounders. RESULTS: Relative to those who had never smoked, the RR of ovarian cancer were 1.63 (95% confidence interval [CI] = 0.21-12.50) for former smokers and 2.27 (95% CI = 0.85-6.08) for current smokers. Among current smokers, the RR were 1.48 (95% CI = 0.20-10.92), 5.56 (95% CI = 1.68-19.06), and 1.86 (95% CI = 0.25-14.30) among women who smoked <10, 10-19, and at least 20 pack-years ([number of cigarettes smoked per day/20] x number of years subject has smoked), respectively, relative to those who had never smoked. A test for trend was statistically significant (P = 0.044). CONCLUSIONS: These data indicate that cigarette smoking increases the risk of developing ovarian cancer in the Japanese population.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Alterations in the serum concentration of transforming growth factor beta-1 (TGFbeta1) have been observed in gastric cancer patients. No study, however, has ever examined the association between the serum TGFbeta1 level and stomach cancer prospectively. We conducted a prospective, nested case-control analysis among apparently healthy men and women who were followed for up to 8 years in the JACC Study to assess whether serum level of total TGFbeta1 is associated with a subsequent risk of stomach cancer. The concentration of serum TGFbeta1 in previously collected blood samples was analyzed by ELISA for 209 individuals in whom a diagnosis of stomach cancer was documented, and for 409 controls matched with them for gender, age and study area. Baseline blood levels of TGFbeta1 were not related to the risk of stomach cancer in either men or women, a finding unchanged even after adjustment for potential confounders. The multivariate-adjusted odds ratio of stomach cancer in men and women was 1.10 (95% CI, 0.82 to 1.48) and 1.09 (95% CI, 0.80 to 1.48), respectively, for each increase of 1 SD in the TGFbeta1 value. In conclusion, serum TGFbeta1 levels were not associated with increased risks of subsequent stomach cancer.gene A52C polymorphism related to the metabolism of long-chain fatty acids and oxidized LDL in the etiology of colorectal cancer.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To examine the relation between serum fatty acids and risk of colorectal cancer, the authors conducted a nested case-control study of 169 colorectal cancer cases and 481 controls matched by age and enrollment area as part of the Japan Collaborative Cohort Study. Serum samples were donated by subjects at baseline (between 1988 and 1990) and were stored at -80 degrees C until 2002. Serum fatty acid levels were measured by using gas chromatography and were expressed as the weight percentage of total lipids. Conditional logistic regression analyses adjusted for lifestyle factors revealed that total omega-3 polyunsaturated fatty acids (odds ratio = 0.24, 95% confidence interval: 0.08, 0.76), alpha-linolenic acid (odds ratio = 0.39, 95% confidence interval: 0.16, 0.91), docosapentaenoic acid (odds ratio = 0.30, 95% confidence interval: 0.11, 0.80), and docosahexaenoic acid (odds ratio = 0.23, 95% confidence interval: 0.07, 0.76) all showed a significantly decreased risk for the highest versus the lowest quartile levels for colorectal cancer in men. For women, a weak negative association was observed between docosapentaenoic acid and colorectal cancer risk, although it was not statistically significant. No adverse effects of high serum levels of omega-6 polyunsaturated fatty acids on colorectal cancer risk were detected.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The relation between weight fluctuation and the risk of cardiovascular disease (CVD) is fairly consistent, although the physiologic basis for the relationship is uncertain. In the present study the association between long-term weight fluctuation and the development of metabolic syndrome (MS), a potent CVD risk factor, was investigated. METHODS AND RESULTS: A cross-sectional study of 664 Japanese men aged 40-49 years was conducted. The root mean square error around the slope of weight on age (weight - RMSE) was calculated by a simple linear regression model, in which the subject's actual weights at ages 20, 25, 30 years and 5 years prior to the study, as well as current weight, were dependent variables against the subject's age as the independent variable. Weight-RMSE was significantly and positively associated with the prevalence of each MS components (high blood pressure, hypertriglyceridemia, low-high density lipoprotein-cholesterol, high fasting glucose, and obesity). Such associations, as well as clustering of the MS component together with RMSE increase, were apparent among subjects with body mass index (BMI) <25 kg/m2, although the prevalence of MS or its components was much higher among overweight subjects (BMI >or=25 kg/m2). CONCLUSIONS: Development of MS possibly explains the risk of CVD not only in overweight or obese persons, but also in normal-weight persons with large weight fluctuation.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of this research was to examine the relationship between perceived psychologic stress and colorectal cancer mortality in a prospective large-scale study. METHODS: Between the years 1988 and 1990, 32,153 men and 45,854 women aged 40 to 79 years were enrolled. Participants completed a self-administered questionnaire that addressed demographic, lifestyle, and psychosocial characteristics. Subjects were subsequently followed for mortality until the end of 1999. Perceived psychologic stress was assessed using the question "Do you feel stress during your daily life?" The 4 possible responses, ranging from "little or none" (1) to "extreme" (4), were dichotomized as low (1 or 2) or high (3 or 4) stress. Relative risks (RRs) with 95% confidence intervals (CIs) for colon and rectal cancer according to the perceived level of stress were estimated using Cox's proportional hazard model. RESULTS: During the follow-up period (average, 9.6 years), 193 colon cancer deaths (96 men and 97 women) and 127 rectal cancer deaths (88 men and 39 women) were confirmed within the study group. Women who reported high stress had a 1.64-fold higher risk of colon cancer mortality (multivariate-adjusted RR, 1.64; 95% CI, 1.01-2.66) compared with those reporting low stress. There was no significant association between perceived stress and female rectal cancer or male colon and rectal cancer mortality. CONCLUSIONS: Perceived psychologic stress was weakly associated with increased mortality from colon cancer in women. No positive or inverse association was found in men. Further studies are needed to confirm our results.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To examine associations of serum carotenoids, retinol, and tocopherols with colorectal cancer risk, we conducted a case-control study nested within the Japan Collaborative Cohort Study. These micronutrients were measured in prediagnostic serum samples from 116 men and women who developed colorectal cancer during an 8-yr follow-up period and from 298 matched controls. In men, the higher level of serum total carotenoids was associated with a decreased risk: The multivariate-adjusted odds ratio (OR) for the highest vs. the lowest tertile was 0.34 (95% confidence interval [CI] = 0.11-1.00; trend P over tertiles = 0.040). In women, the higher levels of alpha- and and total carotenoids were instead related to an increased risk: The corresponding ORs were 4.72 (95% CI = 1.29-17.3), 2.00 (0.70-5.73), and 2.47 (0.73-8.34), respectively (trend P = 0.007, 0.040, and 0.064, respectively). We also found a somewhat decreasing risk with increased serum retinol in all subjects and alpha-tocopherol in men: The ORs (95% CI) for the highest tertiles were 0.29 (0.11-0.78; trend P over tertiles = 0.010) and 0.29 (0.07-1.17; trend P = 0.098), respectively. The effects of some carotenoids on colorectal cancer risk may be modified by sex or by factors associated with sex, including smoking and drinking habits.

担当区分：筆頭著者   記述言語：日本語  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oxidative stress plays an important role in carcinogenesis, but few epidemiologic studies have examined associations with risk of colorectal cancer. Relationships between serum levels of oxidized low-density lipoprotein (oxLDL) and oxLDL antibody (oLAB) and colorectal cancer risk were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 161 incidents and deaths from colorectal cancer were identified through 1999, and 395 controls were matched for gender, age, and study area. Measurements were taken of serum oxLDL levels in 119 cases and 316 controls and serum oLAB levels in 153 cases and 376 controls. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, were 1.55 (0.70-3.46), 1.90 (0.84-4.28), and 3.65 (1.50-8.92) for oxLDL (P(trend) = 0.004) and 0.98 (0.54-1.80), 0.75 (0.39-1.48), and 1.68 (0.90-3.13) for oLAB (P(trend) = 0.140). Further adjustment for serum total cholesterol and alpha-tocopherol did not materially change these associations. Odds ratio (95% confidence interval) of the highest quartile of serum oxLDL compared with the lowest quartile was 3.40 (1.09-10.58; P(trend) = 0.045). Analyses restricted to colon cancer cases and corresponding controls yielded similar relationships between serum oxLDL and oLAB levels and risk. In conclusion, higher levels of serum oxLDL may increase risk of colorectal cancer.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The role of inflammation in the genesis of cardiovascular disease has attracted attention and in the present study the association among metabolic syndrome (MS), white blood cell (WBC) count, and insulin concentration was investigated. METHODS AND RESULTS: A cross-sectional study of 3,594 Japanese men aged 34-69 years evaluated the MS components (high blood pressure, hypo-high density lipoprotein (HDL)-cholesterolemia, hypertriglyceridemia, hyperglycemia), as defined by the criteria given in the Third Report of the National Cholesterol Education Program Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults, except for obesity [body mass index (BMI) >/=25 kg/m(2)]. WBC count had a positive correlation with BMI, blood pressure, triglyceride, glucose and insulin, and a negative correlation with HDL-cholesterol. The multi-adjusted means of WBC count and insulin concentration were significantly higher in MS subjects defined as having 3 or more of the components than in non-MS subjects with no more than 2 components. Both means also increased with the number of MS components (p<0.001 for trend). In the multiple linear regression analysis, BMI, HDL-cholesterol, systolic blood pressure, glucose and triglyceride had a significant and independent association with WBC count, but the insulin concentration did not. CONCLUSIONS: The cluster of MS components based on insulin resistance may cause low-grade inflammation.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We used 202 cases of stomach cancer and 394 controls nested within the Japan Collaborative Cohort Study For Evaluation of Cancer Risk (JACC study) to investigate whether family history has an independent effect on the risk of stomach cancer after controlling for the Helicobacter pylori infection. A positive history of stomach cancer in one or more first-degree relatives was associated with an increased risk of the disease in women, but not in men after controlling for H. pylori infection and other confounding variables. Women with both a family history and H. pylori infection were associated with more than five-fold increased risk of the disease (OR 5.10, 95% CI 1.58-16.5) compared to those without these factors. These results suggest the existence of inherited susceptibility to the disease in women, and that measurements of H. pylori infection together with the family history allow meaningful evaluation of risk beyond that provided by either factor alone.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A previous report demonstrated that AP-2alpha favors the survival of ovarian cancer patients by clinical findings. However, the functional roles of AP-2alpha in human ovarian cancers have not been determined. To clarify the roles, we overexpressed AP-2alpha in SKOV3 human ovarian cancer cells, which originally possess little AP-2alpha. AP-2alpha overexpression changed cell morphology from spindle to epithelioid type and suppressed cell proliferation and invasion, which would be partially correlated with decreased phosphorylation levels of the erbB2, Akt and ERK pathways, increased E-cadherin and reduced pro-matrix metalloproteinase-2 levels. Moreover, nude mice intraperitoneally injected with AP-2alpha-overexpressing cells survived longer than those with neo-transfected cells. The present data represent the first direct evidence that AP-2alpha plays a tumor suppressive role in ovarian cancer.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese. DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40-79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated. RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI >/=28 kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44-8.06) compared with those with BMI of 20-<22 kg/m(2). 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29-9.02) compared with those with 20-BMI of <22 and B-BMI of <22 kg/m(2). There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men. CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The relationship between bowel movement (BM) frequency and the risk of colorectal cancer was examined in a large cohort of 25 731 men and 37 198 women living in 24 communities in Japan. At enrolment, each participant completed a self-administrated questionnaire on BM frequency and laxative use. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using Cox's proportional-hazard model. During the follow-up period (average length 7.6 years), 649 cases of colorectal cancer, including 429 cases of colon cancer, were identified. Among women, subjects who reported a BM every 2-3 days had the lowest risk of developing colorectal (IRR=0.71, 95% CI=0.52-0.97) and colon cancer (IRR=0.70, 95% CI=0.49-1.00), whereas those reporting a BM every 6 days or less had an increased risk of developing colorectal (IRR=2.47, 95% CI=1.01-6.01) and colon cancer (IRR=2.52, 95% CI=0.93-6.82) compared with those reporting >or=1 BM per day. A similar, but nonsignificant, association between the frequency of BM and cancer risk was observed in men. There was no association between colorectal or colon cancer risk and laxative use. Regulating BM frequency might therefore have a role in the prevention of colorectal cancer.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

If having children is regarded as an exposure in life, its effect on a host could be considered as being due to female sex hormones associated with pregnancy in women and some lifestyle factors associated with large families in both men and women. To explore the roles of having children in the etiology of colon cancer, we examined 36,629 women and 24,877 men aged 40-79 years who completed a questionnaire on the number of children and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During 291,080 and 200,648 person-years of follow-up, we documented 198 female and 202 male incident colon cancers, respectively. After adjusting for some factors known or suspected to modify the risk of colon cancer, compared with the women with no children, the multivariate-adjusted relative risks of colon cancer were 0.74 (95% confidence interval [CI]: 0.30-1.84) for one child, 1.00 (95% CI: 0.46-2.20) for two, 0.70 (95% CI: 0.31-1.55) for three, and 0.59 (95% CI: 0.26-1.33) for four or more. The risk of colon cancer showed a significantly monotonic decrease with increasing number of children (P value for trend = 0.047). There was no association between the number of children and colon cancer risk among men. From these prospective data, having children may reduce risk of colon cancer among women, but not among men, suggesting that modifications of hormone profiles secondary to pregnancies may influence female colon cancer risk.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Phospholipid transfer protein (PLTP) can generate pre-beta high-density lipoprotein (HDL), an efficient acceptor of peripheral cholesterol, by mediating a process called HDL conversion. The transfer of phospholipids to immature HDL is also essential in maintaining reverse cholesterol transport. The phospholipid transfer activity of PLTP has been associated with various patho-physiological conditions; however, little information is available concerning the relationship between PLTP mass and disease. METHODS AND RESULTS: Using a sandwich enzyme-linked immunosorbent assay, PLTP concentration was measured and related to the risk of developing cardiovascular disease in a worksite-based cohort of Japanese men (n=2,567). Multiple linear regression analysis showed significant associations between PLTP and HDL cholesterol, triglycerides, low-density lipoprotein cholesterol, and body mass index (standardized beta=0.395, -0.191, -0.064, and -0.064, respectively; R(2)=0.31). During the follow-up period, there were 10 cases of coronary heart disease (CHD) and 7 of stroke. The multivariate adjusted relative risk of CHD was 0.46 (95% confidence interval, 0.20-1.07) for an increase of 1 standard deviation in the PLTP value (p=0.071). PLTP concentration was not related to the risk of stroke. CONCLUSIONS: The results of this prospective study indicate that the serum PLTP concentration would serve as a predictor of CHD, independent of HDL cholesterol, triglycerides and other established risk factors.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The relationship between diet and colorectal cancer mortality was analyzed in a prospective study of 45,181 men and 62,643 women aged 40-79 yr enrolled in the Japan Collaborative Cohort Study. Between 1988 and 1990, subjects completed a self-administered questionnaire on their sociodemographic characteristics, diet, and other lifestyle habits. During the follow-up period (average 9.9 yr), 284 colon cancer deaths (138 men and 146 women) and 173 rectal cancer deaths (116 men and 57 women) were confirmed. The only significant association of colorectal cancer mortality with vegetable intake was observed between male rectal cancer mortality and green leafy vegetable consumption [hazard ratio (HR) using Cox proportional hazard models = 0.6; 95% confidence interval (CI) = 0.3-0.9; P for trend = 0.02]. Yogurt intake was also inversely associated with male rectal cancer mortality (HR = 0.5; 95% CI = 0.2-1.0; P for trend = 0.04). Egg consumption was positively associated with male colon cancer mortality (P for trend = 0.04). Women with high fruit consumption had increased colon cancer mortality (HR = 1.6; 95% CI = 1.0-2.6; P for trend = 0.04). It should be noted that this study lacked statistical power due to small sample size and measurement error in the food-frequency questionnaire. Further investigation is therefore necessary to confirm the association between diet and colorectal cancer, especially by subsites and gender.

担当区分：筆頭著者   記述言語：日本語  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To elucidate the effect of long-term weight variability on C-reactive protein (CRP) levels. DESIGN: Cross-sectional study of the circulating CRP. SUBJECTS: A total of 637 Japanese men aged 40-49 y in1997. MEASUREMENTS: Serum CRP levels, body mass index in 1997 (current BMI), the slope of weight on age (weight-slope) representing an individual's weight trend of direction and magnitude, and the root mean square error around the slope of weight on age (weight-RMSE) representing the weight fluctuation magnitude, as calculated by a simple linear regression model in which each value of the subject's five actual weights (aged 20, 25, 30 y, five years ago, and current) was a dependent variable and the subject's ages independent variables. RESULTS: After adjustment for age and confounders, including smoking and health status, the odds ratios of elevated CRP (> or =0.06 mg/dl) were 1.83 (95% CI: 1.25-2.69), 2.63 (1.69-4.11), and 10.31 (2.17-48.98) for upper normal-weight (BMI: 22-<25 kg/m(2)), overweight (25-<30), and obese (> or =30) persons, respectively, compared with lower normal-weight persons (18.5-<22). Adjusting for age, confounders, and current BMI, weight-slope was positively associated with CRP level especially among subjects with BMI> or =25 kg/m(2) (trend P<0.01), and weight-RMSE was positively associated with CRP level particularly among subjects with BMI <25 kg/m(2) (trend P<0.05). CONCLUSION: Our results suggest a state of low-grade systemic inflammation not only in overweight and obese persons, but also in normal-weight persons with large weight fluctuation, possibly explaining in part the positive association between weight fluctuation and CVD.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate whether long-term weight fluctuation is associated with the fasting serum insulin concentration. DESIGN AND SUBJECTS: Weight histories of 1932 male Japanese workers aged 40-59 y were analyzed in relation to their current fasting serum insulin concentration. MEASUREMENTS: Individual weight fluctuation was calculated by root mean square error (RMSE) along the linear regression line of weight measured at five to six different ages. RESULTS: The mean RMSE and fasting insulin concentration were 1.22 kg and 4.5 microU/ml, respectively. The multivariate adjusted insulin level became higher with the increase in weight fluctuation. Subanalysis stratified by current body mass index (BMI) showed that the multivariate adjusted insulin level in individuals in the top quartile of fluctuation was 4.3 microU/ml, against 3.9 microU/ml in those in the bottom quartile (P=0.018, analysis of covariance (ANCOVA)) in the normal weight subgroup with current BMI below 25 kg/m(2). In the overweight subgroup with BMI 25 kg/m(2) or above, the level was 6.9 microU/ml in individuals in the top quartile and 6.2 microU/ml in those in the bottom quartile (P=0.054, ANCOVA). CONCLUSION: The results suggest that weight fluctuation increases the risk of developing hyperinsulinemia. Prospective observations together with measurement of changes in adiposity are needed for confirmation.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we examined the association of circulating CRP in healthy reference range (< or =1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS). DESIGN: Cross-sectional study of circulating CRP in adult men. SUBJECTS: A total of 3692 Japanese men aged 34-69 y. MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI). RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (> or =0.06 mg/dl) and moderately (> or =0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed. CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To examine the influences of recall period, current body weight, weight gain and loss, and weight variability on the accuracy of long-term recall of past weight. DESIGN AND SUBJECTS: Comparison of recalled weights around 25 y old with weights measured at age 25y in health checkup records among 2453 Japanese men (age: 34-61 y). MEASUREMENTS: Deviations between reported and measured weights were examined as to the three indexes: actual error (reported-measured), percent error (actual error/measured x 100), and absolute value of the percent error. Weight variability was defined as (1) the coefficient of variation of weight (CV) and (2) the root mean square error around the slope of weight on age (RMSE). RESULTS: Recalled weight strongly correlated with measured weight (r=0.849). Correlation coefficients decreased as age or the elapsed time since age 25y increased. Recalled weight (mean=58.3 kg) was slightly greater than measured weight at age 25y (mean=57.0 kg, mean actual error=1.28 kg). Subjects with a current body mass index (BMI) of less than 28.6 kg/m(2) overestimated their past weights, whereas those with BM1 of 28.6 kg/m(2) or over underestimated it. Subjects with weight loss since age 25y underestimated their past weights, whereas those with stable weight or gain overestimated it. There were monotonic increases in the three indexes of deviation across the CV quartile categories. Concerning the effect RMSE, a similar trend was observed. CONCLUSION: These results indicate that past body weights over a long period seem to be recalled with good accuracy. However, it should be kept in mind when using recalled weight in an epidemiologic study that accuracy of recall is influenced by age or elapsed time, current BMI, weight gain and loss, and weight variability.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of this study was to explore epidemiological features of malignant ovarian neoplasm in Japan. METHODS: The number of deaths from malignant ovarian neoplasm was obtained from the national vital statistics. Estimated incidence rates, based on several cancer registries, were also used for analyses. We divided the subjects into two age groups (0-29 and 30+ years) and examined secular trends in mortality (1950-1997) and incidence (1975-1993) by age, time, and birth cohort. RESULTS: The age-adjusted mortality rate has increased approximately 4-fold (from 0.9 to 3.6 per 100,000 women) from 1950 to 1997. Age-specific mortality rates showed a rising pattern in the elderly, whereas mortality in the younger people tended to increase in the 1950s and 1960s, but then decreased in the 1970s and afterward. In analyses using a mathematical model, the time effect in the population aged 0-29 years increased with advancing period up to 1970, and then decreased. The cohort effects had positive values, which indicate higher than additive influence from age/time effect, for birth cohorts from 1900 to 1935. The age-adjusted incidence rate increased approximately 1.5-fold (from 3.6 to 5.7) from 1975 to 1993. The rate increased in the early 1980s, but has remained stable since the late 1980s. Age-specific incidence rates in older age groups increased steadily up to 1985, and have remained stable since, while the rates in younger women have remained almost unchanged. CONCLUSION: The major effects on malignant ovarian neoplasm in Japan are supposed to be due to declining parity and therapeutic improvements.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We evaluated the clinical features, treatment, and survival status of the patients with borderline ovarian tumors. METHODS: A retrospective review of the charts of 150 patients with borderline ovarian tumor registered at the Tokai Ovarian Tumor Study Group from January 1, 1980, to December 31, 1994, was conducted to obtain clinical and pathological information. RESULTS: In stage II and III disease, the numbers of patients with no residual tumor, residual tumor of <2 cm, 2-5 cm, and >5 cm were 9, 10, 3, and 3, respectively. The sizes of residual tumors and corresponding clinical response to chemotherapy were as follows: residual tumor of <2 cm, complete response (CR), 6 patients; no change (NC), 2; progressive disease (PD), 2; tumors 2-5 cm, NC, 1 patient, PD, 2; tumors >5 cm, PD, 3 patients. The survival for patients with residual tumor <2 cm was significantly better than for those with residual tumor from 2-5 cm and of >5 cm (P < 0.05). The survival for patients with stage II and III serous tumor was significantly longer than that for patients with stage II and III mucinous tumor (P < 0.05). CONCLUSION: In advanced borderline ovarian tumor, the prognosis of patients with gross residual tumor after initial surgery, and especially with mucinous tumor, was poor.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated hyaluronidase activity in gynaecological normal and malignant tissues. Hyaluronidase activity in culture medium of tissue specimens was detected by hyaluronic acid zymography and quantified by densitometry. Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa) at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P < 0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase activity was not observed in cervical cancer tissues. Hyaluronidase activity was significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer tissues than in cervical cancer tissue and was significantly higher in ovarian cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest that the cancer cells make use of the original characteristic of the organ to invade and metastasize. Moreover, these results reflect the difference in metastatic forms and are suggestive of a strong relationship between hyaluronidase activity and invasion and metastasis of ovarian and endometrial cancers compared with cervical cancer.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Five tumor markers were analyzed clinically in 101 patients with borderline ovarian tumors who were treated by the Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospital, between January 1986 and December 1994. The positive rate of CA125 was 68.2% in serous tumor and 51.9% in mucinous tumor. The positive rate of CA19-9 was 51.5% in serous tumor and 44.7% in mucinous tumor. The positive rates and mean serum levels of CA125 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. The mean serum levels of CA19-9 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. CA125 and CA19-9 were useful for screening of borderline ovarian tumors. The positive rates of CEA and TPA in mucinous tumor were 32.5 and 27.3%, respectively, although none of the patients with serous tumor were positive in CEA and TPA. The positive rates and mean serum levels of CEA in mucinous tumor by stage had rising tendencies with an increase in each stage. The positive rate of CA72-4 was significantly lower than that of CA125 (P < 0.05).

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND. The authors conducted a comparison study of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) activities in clinically different metastatic types of ovarian cancer, cervical cancer, and endometrial cancer tissues. METHODS. Gelatinase activity in culture medium obtained from each cancer tissue was detected by zymography and was quantitated by densitometer. Tissue inhibitor of metalloproteinase-1 activity was measured in culture medium by the human TIMP-1 enzyme immunoassay kit. RESULTS. Six dominant gelatinases were detected in ovarian, cervical, and endometrial cancers: 200-kDa; 130-kDa; 92-kDa (MMP-9); 83-kDa, which is an active form of 92-kDa gelatinase; 72-kDa (MMP-2); and 66-kDa gelatinase, which is an active form of 72-kDa gelatinase. The 92-kDa and 72-kDa gelatinolytic bands were present in all samples. The expression rates of 200-, 130-, and 83-kDa gelatinase in endometrial cancer and cervical cancer tissues were higher than that observed in ovarian cancer tissue. Densitometric analysis showed that the 92-kDa/72-kDa ratio was significantly higher in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.05), and the 66-kDa/72-kDa ratio was significantly higher in endometrial cancer tissue than in ovarian cancer tissue (P < 0.01). Tissue inhibitor of metalloproteinase-1 activity was significantly lower in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.01). CONCLUSIONS. These results reflect the difference of metastatic forms and are indicative of the possibility of the strong relationship to MMP activity in the invasion and metastasis of cervical cancer and endometrial cancer, compared with those of ovarian cancer.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

CA125 II, an improved version of the conventional CA125 was compared with CA125 as to which was more useful in gynecologic disease. In the diagnosis of tumors around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same sensitivity and specificity as CA125. CA125 II also has high simultaneous reproducibility in the low concentration area. The examination by the receiver operating characteristic curve revealed that CA125 II has higher precision than that of CA125 when it is used for the screening test. In conclusion, CA125 II is a better tumor marker than conventional CA125.

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Our purpose was to evaluate type IV collagenase in ovarian and endometrial cancer tissues. STUDY DESIGN: Tissue specimens were obtained from patients with ovarian and endometrial cancer and uterine myoma. Gelatinase activity was detected by zymography and quantitated by densitometer. RESULTS: Four dominant gelatinases were detected in ovarian and endometrial cancer tissues: 200, 130, 92, and 72 kd gelatinase. Other forms observed were 83 kd gelatinase, which is an active form of 92 kd gelatinase, and 66 kd gelatinase, which is an active form of 72 kd gelatinase. Densitometric analysis showed that the 92 kd/72 kd ratio in ovarian cancer tissues was significantly higher than in normal ovarian tissues (p < 0.05) and that the 66 kd/72 kd ratio was higher in ovarian cancer tissues (p = 0.07). Both ratios in endometrial cancer tissues were significantly higher than in normal endometrial tissues (p < 0.05). CONCLUSION: Gelatinase activity was remarkably higher in ovarian and endometrial cancer tissues. Especially, 92, 83, and 66 kd gelatinases were clearly detected in cancer tissues, suggesting that these gelatinases were related to the malignant phenotype, because degradation of the components of the basement membrane such as type IV collagen is necessary for cancer cells to metastasize.

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