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Objectives: To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden. Methods: Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry. Results: Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 μg/L, 0.34 μg/L, and 0.96 μg/dL, respectively. Urinary Cd level was 0.34 μg/g creatinine (GM) and hair Hg was 1.31 μg/g (GM). Approximately one-third (35 %) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 μg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 μg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg. Conclusions: Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children. [ABSTRACT FROM AUTHOR]

Elevated matrix metalloproteinase-1 (MMP-1) expression is known to correlate with poor prognosis of pancreatic cancer. We investigated the molecular mechanisms of constitutive expression of MMP-1 in pancreatic cancer cell lines. Expression of MMP-1 mRNA and protein as well as its enzymatic activity were observed in three pancreatic cancer cell lines. Transient transfection assays of two MMP-1 promoter/luciferase constructs (full-length 4.4-kb or proximal 0.6-kb region) showed high levels of transcription in pancreatic cancer cells compared with non-MMP-1 producing cells. The 0.6-kb promoter region of MMP-1 gene contained three activator protein-1 (AP-1) sites and the strong AP-1 activity was detected by electrophoretic mobility shift assays (EMSAs). In these cells, production and phosphorylation of c-Jun were commonly observed. Phosphorylated c-Jun NH2-terminal kinase (p-JNK) and activator transcription factor-2 (p-ATF-2) were also detected in two of the three cell lines. Phosphorylated extracellular signal-regulated kinase (p-ERK) was observed in one. The promoter activity, AP-1-binding activity and MMP-1 production were suppressed by a specific inhibitor of JNK or MEK. K-ras mutation, reported to be present in three cell lines used, is known to activate JNK and ERK pathways. Considering the facts together, our results revealed that activation of JNK/AP-1 or ERK/AP-1 pathway plays crucial roles in constitutive transactivation of MMP-1 in these cancer cells. This study contributes to provide new insights into strategies for inhibiting tumor cell invasion in pancreatic cancer.

Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome.

It is known that prenatal and postnatal exposure to ethanol can result in hyperactive behavior and learning disturbance in offspring. We have previously shown that docosahexaenoic acid (DHA) ameliorated hyperactivity induced by in utero ethanol exposure in rat pups. The present study is designed to clarify the effects of DHA on neurite outgrowth and gene expression of GAP-43 and SCG10, neuron specific growth-associated proteins (GAPs) in PC12 cells treated with ethanol. Ethanol seemed to enhance the neurite outgrowth induced by nerve growth factor (NGF). DHA administration further increased neurite outgrowth in both NGF alone and the combination of NGF and ethanol treated PC12 cells. DHA treatment increased the levels of both GAP-43 and SCG10 mRNAs, and simultaneous administration of ethanol suppressed the elevation of GAP-43 and SCG10 mRNA enhanced by DHA. The present study has demonstrated, for the first time, the effect of ethanol and DHA on GAPs' gene expression. Interaction of ethanol and docosahexaenoic acid in NGF-induced neurite formation, as well as the mechanisms by which DHA ameliorate the hyperactivity induced by in utero ethanol exposure, are to be elucidated.