Gen Kobashi

Dietary risk factors for inflammatory bowel disease A Multicenter Case‐Control Study in Japan

&NA; To evaluate the role of dietary factors in the etiology of inflammatory bowel disease (IBD), we conducted a multicenter hospital‐based case‐control study in a Japanese population. Cases were IBD patients aged 15 to 34 years [ulcerative colitis (UC) 111 patients; Crohns disease (CD) 128 patients] within 3 years after diagnosis in 13 hospitals. One control subject was recruited for each case who was matched for sex, age, and hospital. A semiquantitative food frequency questionnaire was used to estimate preillness intakes of food groups and nutrients. All the available control subjects (n = 219) were pooled, and unconditional logistic models were applied to calculate odds ratios (ORs). In the food groups, a higher consumption of sweets was positively associated with UC risk [OR for the highest versus lowest quartile, 2.86; 95% confidence interval (CI), 1.24 to 6.57], whereas the consumption of sugars and sweeteners (OR, 2.12; 95% CI, 1.08 to 4.17), sweets (OR, 2.83; 95% CI, 1.38 to 5.83), fats and oils (OR, 2.64; 95% CI, 1.29 to 5.39), and fish and shellfish (OR, 2.41; 95% CI, 1.18‐4.89) were positively associated with CD risk. In respect to nutrients, the intake of vitamin C (OR, 0.45; 95% CI, 0.21 to 0.99) was negatively related to UC risk, while the intake of total fat (OR, 2.86; 95% CI, 1.39 to 5.90), monounsaturated fatty acids (OR, 2.49; 95% CI, 1.23 to 5.03) and polyunsaturated fatty acids (OR, 2.31; 95% CI, 1.12 to 4.79), vitamin E (OR, 3.23; 95% CI, 1.45 to 7.17), and n‐3 (OR, 3.24; 95% CI, 1.52 to 6.88) and n‐6 fatty acids (OR, 2.57; 95% CI, 1.24 to 5.32) was positively associated with CD risk. Although this study suffers from the shortcoming of recall bias, which is inherent in most retrospective studies (prospective studies are warranted to confirm the associations between diet and IBD risk), the present findings suggest the importance of dietary factors for IBD prevention.

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester

To assess human exposure to bisphenol A (BPA) over a 10-year period, BPA concentrations in maternal serum (MS) and amniotic fluid (AF) obtained at early second trimester were determined. ELISA was used to measure BPA in 200 MS/AF pairs in women carrying fetuses with normal karyotypes (Group I) and in 48 pairs with abnormal karyotypes (Group II). In Group I, BPA concentrations in AF (median: 0.26 ng/ml) were lower (P<0.01) than in MS (2.24 ng/ml). Over a 10-year period, yearly BPA concentrations in MS decreased from 5.62 to 0.99 ng/ml (P<0.001). Eight of the Group I AF samples had relatively high concentrations of BPA (2.80-5.62 ng/ml). In Group II, BPA concentrations in AF (0 ng/ml) were lower (P<0.01) than in MS (2.97 ng/ml). MS BPA concentrations in Group II were higher (P<0.01) than in Group I.

Pre-conceptional Natural Killer Cell Activity and Percentage as Predictors of Biochemical Pregnancy and Spontaneous Abortion with Normal Chromosome Karyotype

Problem: The aim of the present study was to determine whether pre‐conceptional natural killer (NK) cell activity and percentage are predictive of subsequent spontaneous abortion in women with recurrent spontaneous abortion (RSA).

High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion

PROBLEM: The aim of this study was to assess the role of natural killer (NK) cells in pregnant women with a history of recurrent spontaneous abortion (RSA). 
METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were prospectively assessed for peripheral NK cell activity, percentage of the NK cell subsets, and subsequent pregnancy outcome. 
RESULTS: NK cell activity in women with subsequent live birth (group I) at 4–5 gestational weeks (GW) (mean±SD, 32.5±12.3%) significantly decreased at 6–7 GW (28.1±12.1%) and at 8–9 GW (28.0±11.8%). NK cell activity in women with subsequent abortion with normal chromosomes (group II) at 6–7 GW (41.2±19.0%) was significantly higher than that in group I women, while NK cell activity at 6–7 GW in women with subsequent abortion with abnormal chromosomes (group III) was the same as the level in group I women. 
CONCLUSIONS: High NK cell activity at 6–7 GW correlates with subsequent abortion with normal chromosomes.

Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes

Antiphospholipid antibody (aPL) is associated with thromboembolism. There is scant evidence of a relationship between the aPL profile and serious adverse pregnancy outcome. The aim of this study was to assess whether aPL measurements during early pregnancy were useful in predicting a serious adverse pregnancy outcome. In this prospective study, we measured aPLs, including lupus anticoagulant (LA), IgG, IgM, IgA anticardiolipin antibody (aCL), IgG, IgM phosphatidylserine-dependent antiprothrombin antibody, and IgG kininogen-dependent antiphosphatidylethanolamine antibody (aPE) during the first trimester in a consecutive series of 1155 women. The 99 th percentile cut-off values in each aPL were determined using samples from 105 women who did not exhibit any pregnancy morbidity. We assessed the predictive risk of a serious adverse pregnancy outcome adjusted for confounding factors. We found that IgG aCL was associated with developing pregnancy-induced hypertension (PIH) (odds ratio 11.4, 95% CI 2.7-48); IgG aPE with PIH (8.3, 2.4-29), severe PIH (20.4, 4.5-91), and premature delivery (PD) (12.7, 3.1-50); and LA with PD (11.0, 2.8-44) and low birth weight (8.0, 2.1-31). The combinations of IgG aPE plus IgG aCL (17.5, 4.7-66.7) or IgG aPE plus LA (22.2, 5.4-909) measurements predicted severe PIH with 30.8% sensitivity and 99.2% specificity. We conclude that aPL measurements during early pregnancy may be useful in predicting adverse pregnancy outcome.

Dietary habits and risk of ossification of the posterior longitudinal ligaments of the spine (OPLL); findings from a case-control study in Japan.

The relation between dietary habits and the risk of ossification of the posterior longitudinal ligaments of the spine (OPLL) was investigated in a case-control study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were identified and individually matched by age and sex with community controls (n = 138) randomly selected from the general population in Hokkaido. A self-administered food-frequency questionnaire was used to assess habitual dietary intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated, using conditional logistic regression models to compute the OR adjusted for a history of diabetes mellitus. We found that frequent consumption of pickles (salted products) was significantly associated with an increased risk of OPLL, with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI, 0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our findings suggest that dietary habits may constitute independent risk factors for OPLL. Further studies will be needed to prospectively determine the relationship between dietary habits and OPLL risk.

High body mass index after age 20 and diabetes mellitus are independent risk factors for ossification of the posterior longitudinal ligament of the spine in Japanese subjects: a case-control study in multiple hospitals.

Study Design. A sex- and age-matched case-control study was carried out. Objectives. To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors. Summary of Background Data. The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits. Methods: A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis. Results. A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation ≥25, after adjustment for other possible lifestyle risk factors. Conclusion. Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women

An association between preeclampsia (PE) and a common missense mutation of the methylenetetrahydrofolate reductase gene (MTHFR), a C to T substitution at nucleotide 677 (C677T), which converts an alanine to a valine residue, has been reported in Italian and Japanese populations. We examined 101 cases of hypertension in pregnancy (HP), including 73 cases of PE, and 215 normal pregnancy controls to confirm the association in Japanese women. No significant differences of the frequency of the T677 allele frequency or percentage of T677 homozygotes were detected among the various types of cases: HP (0.38, 12%, respectively), severe HP (0. 40, 12%), PE (0.38, 11%), severe PE (0.41, 11%), primiparous HP (0. 40, 12%), primiparous PE (0.44, 18%), nonelderly HP (0.39, 13%), nonelderly PE (0.40, 14%), nonobese HP (0.38, 12%), nonobese PE (0. 39, 10%), HP without homozygous T235 of the angiotensinogen gene (TT of AGT) (0.38, 15%), PE without TT of AGT (0.38, 15%), and controls (0.38, 15%). The results indicate that T677 of MTHFR may not be a risk factor for PE in Japanese population.

Massive Intravenous Immunoglobulin Treatment in Women with Four or More Recurrent Spontaneous Abortions of Unexplained Etiology: Down-Regulation of NK Cell Activity and Subsets

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets.
 METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies.
 RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre‐infusion NK cell activity (mean±SD, 40.9±17.0%) at 4.4±0.5 weeks of gestation (GW) decreased to 15.0±7.9% at post‐infusion status (5.4±0.5 GW). Pre‐infusion percentages of CD56+CD16− cells (3.5±2.1%) and CD56+CD16− cells (16.8±8.8%) decreased to 3.0±2.2% and 11.1±6.9%, respectively, after MIVIg treatment.
 CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

Association of a variant of the angiotensinogen gene with pure type of hypertension in pregnancy in the Japanese: Implication of a racial difference and significance of an age factor

The contribution of genetic factors to hypertension in pregnancy, including pre-eclampsia, has been well documented. The association with a common molecular variant of the angiotensinogen (AGT) gene, in which methionine (M235) is substituted for threonine (T235) at residue 235, has been reported in both Caucasians and Japanese. In the present study, we examined 115 cases of pure type of hypertension in pregnancy (PHP) and 381 normal pregnant controls in order to look for subgroups in which the AGT gene is the major factor in the PHP pathogenesis. By classification of PHP cases according to the clinical diagnosis, gravidity, and maternal age, we found significantly higher frequencies of T235 in both all PHP patients and preeclampsia/eclampsia patients than in normal controls. These results are discordant with those reported for Caucasian subjects where only a group of preeclamptic primigravidae was associated with the AGT variant, possibly indicating the existence of a racial difference. We also found that the variant frequency was significantly higher in the PHP subgroup with maternal age of 20-34 years (0.93) than in a subgroup of multigravid PHP patients age 35 years or older (0.77, P < 0.05) or in normal controls of age 20-34 years (0.76, P < 0.001). The result indicates that the AGT variant plays a significant role in hypertension in the age group 20-34 years.