Combined effects of AHR, CYP1A1, and XRCC1 genotypes and prenatal maternal smoking on infant birth size : Biomarker assessment in the Hokkaido Study

Objectives: We investigated the individual and combined effects of maternal polymorphisms encoding the aromatic hydrocarbon receptor (AHR; rs2066853), cytochrome P450 (CYP) 1A1 (rs1048963), and the X-ray-complementing gene 1 (XRCC1; rs1799782) and prenatal smoking in relation to infant birth size. Methods: Totally, 3263 participants (1998 non-smokers and 1265 smokers) were included in the study between 2003 and 2007. Two groups of mothers were distinguished by plasma cotinine levels by ELISA measured during the third trimester (cut-off = 11.48 ng/mL). We conducted data analysis using multiple linear regression models. Results: Infants whose mothers smoked and had AHR-GG, CYP1A1-AG/GG, and XRCC1-CT/TT genotypes weighed, -145 g less than those born of mothers who did not smoke and had the AHR-GA/AA, CYP1A1-AA, and XRCC1-CC genotypes (95% CI: -241, -50). Conclusions: We demonstrated that infants whose mothers smoked during pregnancy with the combination of AHR, CYP1A1, and XRCC1 polymorphisms had lower birth size

Successful Treatment of Cardiac Diffuse Large B-cell Lymphoma : A Report of Two Cases

Cardiac lymphoma is a rare neoplasm of the heart,defined as an extranodal lymphoma exclusively located in the heart and/or pericardium. Multiple imaging modalities may help to diagnose cardiac tumors ; however, pathological diagnosis is difficult because of the limited approaches for obtaining tissue samples. This report describes two cases of prompt histological diagnosis of cardiac lymphoma as diffuse large B-cell type and their successful treatment with chemotherapy. Immunohistochemical analyses revealed one case as CD5-positive and the other as CD5-negative lymphoma. This report highlights the necessity of histological diagnosis and the importance of clinicopathological characterization of cardiac lymphoma. Shinshu Med J 59 : 177―183, 2011 (Received for publication January 7, 2011; accepted in revised form February 16, 2011)Article信州医学雑誌 59(3): 177-183(2011)departmental bulletin pape

Respiratory Failure after Open Descending Aortic Aneurysm Repair: Risk Factors and Outcomes.

Purpose:This study was conducted to identify predictors of respiratory failure after open repair of descending thoracic aortic aneurysm (DTAA), and to identify any relationship between respiratory failure and long-term survival.Methods:A total of 75 patients undergoing elective open DTAA repair at the Shiga University of Medical Science Hospital were included in the study. Univariate and multivariate logistic regression analyses were performed to assess the odds ratios for incident postoperative respiratory failure after open DTAA repair. Survival over time was estimated by the Kaplan-Meier method.Results:Respiratory failure, defined as ventilation dependence for longer than 48 hours, occurred in 11 patients (14.7%). Independent predictors of respiratory failure after DTAA included prolonged operation time and reduced preoperative forced expiratory volume in 1 second/forced vital capacity × 100 (FEV1%). In-hospital mortality was higher (p = 0.020) among patients with respiratory failure (18.2% of those who suffered respiratory failure) than among those without (0%). The survival rates at 8 years were significantly lower (p = 0.010) in the respiratory failure group (at 44.2%) than in the group without respiratory failure (at 89.0%).Conclusion:Lower FEV1% and longer operation time were risk factors of postoperative respiratory failure after open repair of DTAA, which in turn is associated with significantly reduced long-term survival

Surgical treatment for secondary aortoesophageal fistula after prosthetic aortic replacement: A report of four cases.

Introduction:With the increase of thoracic aortic aneurysm surgery and thoracic endovascular aortic repair, secondary aortoesophageal fistula (AEF) has been reported. However, the treatment strategy for AEF remains controversial.Presentation of cases:Four patients who had undergone prosthetic aortic replacement for thoracic aortic aneurysm 4-36 months previously, were hospitalized with sepsis-like symptoms. They were diagnosed with aortic prosthetic graft infection after computed tomography revealed ectopic gas around the prosthesis. After that, esophagogastroduodenoscopy revealed an esophageal perforation, so we diagnosed AEF. They received medication and stepwise surgery; 1 patient was discharged, 2 remain hospitalized, and 1 died.Discussion:Some reports have suggested that combined surgery provides better outcomes for AEF. Infection may be controlled by esophagectomy and antibiotic treatment, so prosthesis replacement is not always necessary. However, we should note that infection between a prosthetic graft and the native aorta brings a danger of pseudoaneurysm of the anastomosis.With the increase of thoracic aortic aneurysm surgery and thoracic endovascular aortic repair, secondary aortoesophageal fistula (AEF) has been reported. However, the treatment strategy for AEF remains controversial.Four patients who had undergone prosthetic aortic replacement for thoracic aortic aneurysm 4-36 months previously, were hospitalized with sepsis-like symptoms. They were diagnosed with aortic prosthetic graft infection after computed tomography revealed ectopic gas around the prosthesis. After that, esophagogastroduodenoscopy revealed an esophageal perforation, so we diagnosed AEF. They received medication and stepwise surgery; 1 patient was discharged, 2 remain hospitalized, and 1 died.Some reports have suggested that combined surgery provides better outcomes for AEF. Infection may be controlled by esophagectomy and antibiotic treatment, so prosthesis replacement is not always necessary. However, we should note that infection between a prosthetic graft and the native aorta brings a danger of pseudoaneurysm of the anastomosis.Conclusion:Based on our experience we conclude that surgery performed stepwise along with infection control and general health improvement is a valid treatment strategy for secondary AEF after prosthetic aortic replacement

Associations between maternal mono-(2-ethylhexyl) phthalate levels, nuclear receptor gene polymorphisms, and fatty acid levels in pregnant Japanese women in the Hokkaido study

We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log(10)-transformed MEHP levels and maternal genotypes on log(10)-transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (p(int) = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A

Indirect positive effects of agricultural modernization on the abundance of Japanese tree frog tadpoles in rice fields through the release from predators

In Japan, the density of Japanese tree frogs (Hyla japonica) may not be necessary high in traditional rice fields compared to modern fields because the modernization of drainage systems from shallow earthen ditches to deep concrete-line ones reduces the abundance of predators/competitors for tadpoles, such as dojo loach (Misgurnus anguillicaudatus). This hypothesis was tested using two approaches. First, laboratory experiments revealed that the presence of the loach significantly reduced the survival of tree frog eggs and tadpoles. Second, observational studies in rice fields showed that the direct effect of modernization on tadpoles was not significant but the indirect (and thus total) effects were weakly positive due to the reduction in the density of dojo loach. Our study suggests that recent agricultural intensification in rice fields does not negatively impact all aquatic species but that some species may not be affected or can even flourish by having tolerance for the changes and release from potential predators or competitors

Dioxin-metabolizing genes in relation to effects of prenatal dioxin levels and reduced birth size : The Hokkaido study

Objectives: We investigated the effects of maternal polymorphisms in 3 genes encoding dioxin metabolizing enzymes in relation to prenatal dioxin levels on infant birth size in Japan. Methods: We examined the relationship between dioxin exposure and birth size in relation to the polymorphisms in the genes encoding aromatic hydrocarbon receptor (AHR [G >A, Arg554Lys]), cytochrome P450 (CYP) 1A1 (T6235C), and glutathione S-transferase mu I (GSTM1; Non-null/null) in 421 participants using multiple linear regression models. Results: In mothers carrying the GSTM1 null genotype, a ten-fold increase in total dioxin toxic equivalency was correlated with a decrease in birth weight of -345g (95% confidence interval: -584, -105). Conclusions: We observed adverse effects of maternal GSTM1 null genotype on birth weight in the presence of dioxins exposure during pregnancy

Association between maternal passive smoking and increased risk of delivering small-for-gestational-age infants at full-term using plasma cotinine levels from The Hokkaido Study : a prospective birth cohort

Objectives: To investigate the association between plasma cotinine level measured at the 8th gestational month and the delivery of small-for-gestational-age (SGA) infants, using a highly sensitive ELISA method. Design: Prospective birth cohort study from The Hokkaido Study on Environment and Children's Health. Setting: Hokkaido, Japan. Participants: Our sample included 15 198 mother-infant pairs enrolled in 2003-2012. Main outcome measures: SGA, defined as a gestational age-specific weight Z-score below -2. Results: The number of SGA infants was 192 (1.3%). The cotinine cut-off level that differentiated SGA infants from other infants was 3.03 ng/mL for both the total population and the full-term births subgroup (sensitivity 0.307; positive predictive value 2.3%). Compared with infants of mothers with a plasma cotinine level of <3.03 ng/mL, infants of mothers with a plasma cotinine level of ≥3.03 ng/mL showed an increased OR for SGA in the total population and the full-term infant group (2.02(95% CI 1.45 to 2.83) and 2.44(95% CI 1.73 to 3.44), respectively). Conclusion: A plasma cotinine level of ≥3.03 ng/mL, which included both passive and active smokers, was associated with an increased risk of SGA. This finding is of important relevance when educating pregnant women about avoiding prenatal passive and active smoking due to the adverse effects on their infants, even those born at full-term

Relationships between maternal perfluoroalkyl substance levels, polymorphisms of receptor genes, and adverse birth outcomes in the Hokkaido birth cohort study, Japan

We assessed the associations between perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) levels in third trimester maternal serum, the maternal genotypes of genes encoding nuclear receptors, and birth outcomes. We studied a prospective birth cohort of healthy pregnant Japanese women (n = 372) recruited in Sapporo between July 2002 and October 2005. We analyzed PFOS and PFOA levels using liquid chromatography-tandem mass spectrometry and analyzed 13 single nucleotide polymorphisms (SNPs) of proliferator-activated receptor alpha, gamma, gamma coactivator 1A, delta, constitutive androstane receptor, liver X receptor alpha, and beta (LXRB) using real-time polymerase reaction (PCR). We employed multiple linear regression models to establish the influences of log10-transformed PFOS and PFOA levels and maternal genotypes on birth size. In female infants, we identified interactions between PFOS levels, the maternal genotype of LXRB (rs1405655), and birth weight. The estimated mean changes in birth weight in response to PFOS levels, the maternal genotype LXRB (rs1405655)-TC/CC (compared to TT), and their interactions were -502.9 g (95 % confidence interval [CI] = -247.3, -758.5 g), -526.3 g (95 % CI = -200.7, -852.0 g), and 662.1 g (95 % CI = 221.0, 1,103.2 g; pint = 0.003), respectively. Interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) also significantly affected birth chest circumference and the Ponderal index (pint = 0.037 and 0.005, respectively). Thus, interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) affects birth sizes in female infants. We found that certain SNPs modify the effects of PFOS levels on birth size

Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women

Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women. Differences in dioxin exposure concentrations in maternal blood among the genotypes were investigated. Comparisons among the GG, GA, and AA genotypes of AHR showed a significant difference (genotype model: P = 0.016 for the mono-ortho polychlorinated biphenyl concentrations and toxicity equivalence quantities [TEQs]). Second, we found a significant association with the dominant genotype model ([TT + TC] vs. CC: P = 0.048 for the polychlorinated dibenzo-p-dioxin TEQs; P = 0.035 for polychlorinated dibenzofuran TEQs) of CYP1A1 (rs4646903). No significant differences were found among blood dioxin concentrations and polymorphisms in AHRR, CYP1A1 (rs1048963), CYP1A2, and CYP1B1. Thus, polymorphisms in AHR and CYP1A1 (rs4646903) were associated with maternal dioxin concentrations. However, differences in blood dioxin concentrations were relatively low