Machiko Minatoya

Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk.

BACKGROUND The age-adjusted incidence rate of prostate cancer (PCa) has been reported to be lower among Asians than Western populations. A traditional Japanese meal, high in soybean products or isoflavones, may be associated with a decreased risk of PCa. Equol, which is converted from daidzein by human intestinal flora, is biologically more active than any other isoflavone aglycone. MATERIALS AND METHODS We reviewed not only recent epidemiological studies on association of isoflavones with PCa risk, but also recent research on human intestinal bacteria responsible for converting daidzein into equol. Studies were systematically searched from the database published within the last 5 years of from 2008-2012. RESULTS Five out of 6 articles showed significant association of isoflavones with a decreased risk of PCa, and two of them consistently showed that equol-producers carry a significantly reduced risk of PCa. Furthermore, 5 human intestinal bacteria that can convert daidzein into equol were identified in the last 5 years. CONCLUSIONS If equol can reduce risk of PCa, a possible strategy for reducing the risk of PCa may be to increase the proportion of equol-producers by changing the intestinal flora to carrying an equol-producing bacterium with dietary alteration or probiotic technology.

The Hokkaido Birth Cohort Study on Environment and Children's Health : cohort profile -- updated 2017

The Hokkaido Study on Environment and Children’s Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Equol, Adiponectin, Insulin Levels and Risk of Breast Cancer

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death among women. Soy isoflavones have been widely studied and among all isoflavones equol has been gaining interest with regard to its relationship with breast cancer risk. Obesity has been revealed as one of the breast cancer risk factors, known to be associated with high levels of circulating insulin and decreased levels of adiponectin. Hence there have been many studies investigating relationships between insulin and adiponectin levels and breast cancer risk. Additionally recent findings have suggested that insulin and adiponectin themselves may have influence on breast cancer development, independent of obesity. In the present review, we discuss the relationships between breast cancer risk and equol, insulin and adiponectin levels, which are three important factors in our ongoing hospital-based case-control study. Herein these factors are reviewed not only from the clinical viewpoint but also from possible chemical and biological points of view which may explain clinical observations.

Design and synthesis of medium-ring lactam libraries inspired by octalactin a. A convergent-divergent approach.

Small molecule compound libraries based on medium rings1 are virtually unknown.2 This critical gap in the literature is probably caused by two main factors. First, medium ring natural products are themselves uncommon and therefore less likely to be the object of total synthesis efforts.3 Second, there is a widely held view that medium rings remain the most challenging and difficult systems to synthesize.4 As part of a program to identify interesting chemotypes for library development, we examined several medium-ring natural products. One system in particular, namely, octalactin A (1) (Figure 1),5 continues to attract intense interest because of its fascinating architecture and potent antitumor profile.6

Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary.

Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health.

Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates. Metabolites of DEHP are detectable in majority of the population. Findings on adverse health outcomes, particularly birth weight in association with prenatal exposure to DEHP remain equivocal. Besides, there is insufficient evidence to address influence on metabolic function from epidemiological studies. Thus, our objective was to investigate cord blood adipokine levels and birth size in association with prenatal DEHP exposure in prospective birth cohort study. Mono-2-methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin levels in cord blood were measured as markers of metabolic function. Birth weight and length were obtained from birth record. Association between maternal MEHP levels and cord blood adiponectin and leptin levels, birth weight and ponderal index (PI) were examined for 167 mother-child pairs who had both MEHP and cord blood adipokine measurements. The median MEHP level was 8.81ng/ml and the detection rate was 100%. There was no sex difference in MEHP levels. Both leptin and adiponectin levels were higher in girls than in boys. MEHP level was positively associated with adiponectin level among boys and was negatively associated with leptin level among girls. MEHP level were negatively associated with PI only in girls and this could be due to decreased leptin level. This study suggested that prenatal DEHP exposure may be associated with cord blood adipokine and birth size. The influence potentially be sex-specific and could be more significant in girls.

Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children’s Health

Background: Bisphenol A (BPA) is widely used and BPA exposure is nearly ubiquitous in developed countries. While animal studies have indicated adverse health effects of prenatal BPA exposure including reproductive dysfunction and thyroid function disruption possibly in a sex-specific manner, findings from epidemiologic studies have not been enough to prove these adverse effects. Given very limited research on human, the aim of this study was to investigate associations between cord blood BPA levels and reproductive and thyroid hormone levels of neonates and whether associations differed by neonate sex. Methods: The study population included 514 participants of the Hokkaido study recruited from 2002 to 2005 at one hospital in Sapporo, Japan. The BPA level in cord blood was determined by ID-LC/MS/MS, and the limit of quantification was 0.040 ng/ml. We measured nine types of reproductive hormone levels in cord blood, and thyroid hormone levels were obtained from neonate mass screening test data. There were 283 subjects, who had both BPA and hormone levels measurements, included for the final analyses. Results: The geometric mean of cord blood BPA was 0.051 ng/ml. After adjustment, BPA level was negatively associated with prolactin (PRL) (&bgr; = −0.38). There was an interaction between infant sex and BPA levels on PRL; a weak negative association was found in boys (&bgr; = −0.12), whereas a weak positive association was found in girls (&bgr; = 0.14). BPA level showed weak positive association with testosterone, estradiol, and progesterone levels in boys. No association was found between BPA and thyroid hormone levels. Conclusions: Our findings suggested that fetal BPA levels might be associated with changes in certain reproductive hormone levels of neonates in a sex-specific manner, though further investigations are necessary.

Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines and birth size: The Hokkaido Study on environment and children's health

ABSTRACT Perfluoroalkyl substances (PFASs) are synthetic chemicals that persist in the environment and in humans. There is a possible association between prenatal PFASs exposure and both neonate adipokines and birth size, yet epidemiological studies are very limited. The objective of this study was to examine associations of prenatal exposure to PFASs with cord blood adipokines and birth size. We conducted birth cohort study, the Hokkaido Study. In this study, 168 mother‐child pairs were included. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in maternal blood were determined by liquid chromatography tandem mass spectrometry. Cord blood adiponectin and leptin levels were measured by ELISA and RIA, respectively. Birth weight and ponderal index (PI) were obtained from birth record. The median maternal PFOS and PFOA were 5.1 and 1.4 ng/mL, respectively. The median total adiponectin and leptin levels were 19.4 &mgr;g/mL and 6.2 ng/mL, respectively. Adjusted linear regression analyses found that PFOS level was positively associated with total adiponectin levels (&bgr;=0.12, 95% CI:0.01, 0.22), contrary was negatively associated with PI (&bgr;=−2.25, 95% CI: −4.01, −0.50). PFOA level was negatively associated with birth weight (&bgr;=−197, 95% CI: −391, −3). Leptin levels were not associated with PFASs levels. PFOS and adiponectin levels showed marginal dose‐response relationship and both PFOS and PFOA and birth size showed significant dose‐response relationships. Results from this study suggested that prenatal PFASs exposure may alter cord blood adiponectin levels and may decrease birth size. HighlightsAssociation between maternal PFOS and PFOA and cord adipokines were investigated.The median maternal PFOS and PFOA were 5.1 and 1.4 ng/mL, respectively.Maternal PFOS was positively associated with cord blood total adiponectin levels.PFOS and adiponectin levels showed marginal dose‐response relationship.

Relation of Serum Adiponectin Levels and Obesity with Breast Cancer: A Japanese Case-Control Study

BACKGROUND It is known that obesity is one of the risk factors for breast cancer although the association may differ between ethnic groups and with the menopausal status. Recently obesity-related risk factors including serum adiponectin and insulin levels have been analyzed together with BMI in association with breast cancer risk. MATERIALS AND METHODS We measured serum high molecular weight (HMW) adiponectin and insulin levels in a hospital based case-control study, including 66 sets of Japanese female breast cancer cases and age and menopausal status matched controls. Serum levels of HMW adiponectin, insulin levels and body mass index (BMI) were examined in association with breast cancer risk with adjustment for the various known risk factors by menopausal status. RESULTS Women in the highest HMW adiponectin levels showed significant reduced risk of breast cancer in both pre and postmenopausal women (odds ratio (OR), 0.01; 95% confidence interval (CI), 0.00-0.26 and 0.13; 0.03-0.57, respectively). Lower BMI showed decreased breast cancer risk in both pre and postmenopausal women (OR, 0.04; 95% CI, 0.00-0.69, OR, 0.28; 95% CI, 0.07-1.11, respectively). CONCLUSIONS These results indicated that higher serum HMW adiponectin levels and lower BMI are associated with a decreased breast cancer risk in both pre and postmenopausal women in Japan, adding evidence for the obesity link.

Cord blood BPA level and child neurodevelopment and behavioral problems: The Hokkaido Study on Environment and Children's Health

Abstract Background Bisphenol A (BPA) is a ubiquitous environmental chemical which has been detected in various populations. There have been concerns that endocrine disrupting property of BPA may cause adverse health effects on neurodevelopmental and behavioral problems. Yet findings from prospective cohort studies to assess influence of prenatal exposure to BPA on child neural development were not conclusive. Especially, with relatively lower levels of exposure and its influence was not examined. Thus, the aim of this study was to evaluate child mental, psychomotor and behavioral problems at different ages in association with prenatal BPA exposures in the prospective birth cohort study. Method BPA level in cord blood was determined by ID-LC/MS/MS. Bayley Scales of Infant Development 2nd Edition was used to assess mental and motor development at 6 and 18 month of age. Kaufman Assessment Battery for Children to assess intelligence and Child Behavior Checklist (CBCL) to assess behavioral problems were used at 42 month of age. Out of 514 subjects in Sapporo cohort, 285 mother-child pairs with BPA measurement and child developmental assessments were included in this study. Results The median level of cord blood BPA was 0.051ng/ml. No association was found between BPA level and either mental or psychomotor development at 6 and 18 month of age. BPA level was positively associated with total, internalizing and externalizing problem scores of CBCL, respectively (β=4.77, 95% CI: -0.28, 9.82, β=4.35, 95% CI: -0.48, 9.18, β=4.33, 95% CI: -0.86, 9.25) with marginal significance. Cord blood BPA concentration was positively associated with development problems score (β=2.60, 95% CI: 0.15, 5.06) with significance. Conclusion Our findings suggested no association between cord blood BPA level and child mental, psychomotor, however, cord blood BPA level may be associated with child behavioral problems at early age.