Genetic Association between Akt1 Polymorphisms and Alzheimer's Disease in a Japanese Population

A recent paper reported that Aβ oligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)-Akt-mTOR signaling pathway. Intraneuronal Aβ, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD

Defect of oral tolerance in NC/Nga mice

The NC/Nga mouse is a model animal for human atopic dermatitis. In this study, we investigated oral tolerance induction in NC/Nga mice. In BALB/c mice, oral administration of ovalbumin (OVA) resulted in suppression of both OVA-specific T and B cell responses induced by OVA immunization. In NC/Nga mice, OVA-induced antigen (Ag) -specific T and B cell responses were significantly less than those in BALB/c mice. Furthermore, oral administration of OVA did not suppress OVA-specific immunoresponses in NC/Nga mice. We further examined antibody (Ab) response against food Ag by feeding mice an experimental diet that contained OVA or casein as a protein source. The level of serum OVA or casein-specific IgG was significantly higher in NC/Nga mice than in BALB/c mice. These results indicate that NC/Nga mice have a defect in the induction of oral tolerance. NC/Nga mice can therefore be used as a model for investigating the mechanism of oral tolerance

Oolong tea increases energy metabolism in Japanese females

Oolong tea is a traditional Chinese tea that has long been believed to be beneficial to health such as decreasing body fat. We were interested in this assertion and tried to evaluate the effect of oolong tea on energy expenditure (EE) in comparison with green tea. The subjects were eleven healthy Japanese females (age 20±1 y body mass index(BMI) 21.2±2.5kg/m2)who each consumed of three treatments in a crossover design : 1) water, 2) oolong tea, 3) green tea. Resting energy expenditure (REE) and EE after the consumption of the test beverage for 120 min were measured using an indirect calorimeter. The cumulative increases of EE for 120 min were significantly increased 10% and 4% after the consumption of oolong tea and green tea, respectively. EE at 60 and 90 min were significantly higher after the consumption of oolong tea than that of water (Plt0.05). In comparison with green tea, oolong tea contained approximately half the caffeine and epigallocatechin galate, while polymerized polyphenols were double. These results suggest that oolong tea increases EE by its polymerized polyphenols

High Level Expression of Platelet-derived Endothelial Cell Growth Factor predicts Good Prognosis in Colorectal Cancer Patients

Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. PD-ECGF expression is elevated in colorectal carcinoma, but its prognostic value does not reach a consensus. The aim of this study is to clarify the prognostic value of the PD-ECGF expression in colorectal carcinomas. PD-ECGF expression was measured by enzyme- linked immunosorbent assay in frozen materials from 71 colorectal cancer patients who had recived curative resection. Patients were divided into high expression and low expression groups based on cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of 71 tumors were stained for PD-ECGF and CD68. PD-ECGF expression in normal mucosa was 34.4 ﾂｱ 15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for high PD-ECGF expression group was significantly longer than that of low expression group (P=0.006). A multivariate Cox\u27s regression analysis revealed a high PD-ECGF expression as an independent factor for better outcome. In immunohistochemical study, almost all tumor cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. In conclusion, the PD-ECGF expression measured in this study was derived from stromal macrophages. High PD-ECGF expression was a predictor for favorable outcome after curative resection for colorectal cancer

Expressions of Vascular Endothelial Growth Factor (VEGF)-D and VEGF Receptor-3 in Colorectal Cancer: Relationship to Lymph Node Metastasis

Angiogenic factors play a major role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)- D is a ligand for VEGF receptor-3 (VEGFR-3/Flt-4), which mainly expressed on the lymphatic endothelium. Recent experimental studies have shown that VEGF-D induces tumor lymphangiogenesis and promote metastatic spread of tumor cells via lymphatic vessels. However, the contribution of VEGFD to lymph node metastasis in human colorectal cancer is less understood. We therefore examined VEGF-D and VEGFR-3 expression in patients with colorectal cancer. Sections of formalin-fixed and paraffin-embedded specimens from 76 colorectal cancers were immunohistochemically stained for VEGF-D and VEGFR-3. Staining for VEGF-D was positive in the cytoplasm of tumor cells in 43 of 76 examined tumors (56.6%). Staining for VEGFR-3 was positive in endothelial cells in 38 (50.0%) tumors. Univariate analysis showed that both VEGF-D and VEGFR-3 expressions correlated significantly with lymph node metastasis, histological type and depth of tumor invasion. However, logistic regression analysis indicated that VEGF-D expression, but not that of VEGFR-3, was an independent predictor for lymph node metastasis. Our data suggest that VEGF-D plays an important role in lymph node metastasis in colorectal cancer

Elevated Expression of Poly(ADP-Ribose) Polymerase-1 is Associated with Liver Metastasis in Colorectal Cancer.

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) and its subsequent cleavage are early markers of apoptosis. PARP-1 is associated with DNA repair and so chromosome stability, cell cycle regulation, as well as tumorigenesis. To investigate the role of PARP-1 expression in colorectal carcinoma and its metastasis of liver, we compared the expression of PARP-1 in primary colorectal cancers with (n=15) and without liver metastasis (n=17) using a semi-quantitative reverse transcription - polymerase chain reaction. We also examined the expressions of poly(ADP-ribose) (PAR) and p53 in these tumors by immunohistochemistry. A significantly higher PARP-1 mRNA expression was noted in tumors with liver metastasis than those without liver metastasis (p<0.01). Colorectal cancers positively stained for p53 exhibited significantly higher PARP-1 mRNA expression than p53-negative tumors (p<0.01). The PAR labeling index (LI) of tumors with metastasis (0.33 ﾂｱ 0.33) was not significantly different (p=0.35) from that of tumors without liver metastasis (0.38 ﾂｱ 0.19). p53-positive tumors tended to have higher PAR LI levels than p53-negative tumors (p=0.08). Our findings suggest that PARP-1 may contribute to liver metastasis due to its DNA repair activity, resulting in survival of the tumor cells with accumulation of metastaticrelated gene\u27s damages. Detailed analysis of PARP-1 may be useful in cancer research and/or cancer therapy

Carcinoembryonic Antigen (CEA) in Colorectal Cancer - Prognostic Significance of Portal Blood Level -

The prognostic significance of carcinoembryonic antigen (CEA) values in the drainage vein of the tumor (portal blood levels of CEA) of colorectal cancer patients were evaluated by examining the correlation with the peripheral blood levels of CEA and histopathologic findings of the tumor. 1) Portal blood levels of CEA were significantly increased by the operative procedure. Mean values of CEA in portal blood were higher than those in peripheral blood. Portal blood CEA was correlated with Dukes\u27 staging, and revealed higher positive rates than CEA in peripheral blood in each stage. Elevated CEA levels were noted in those who had cancer infiltration extending through the proper muscle layer. There was a close correlation between portal CEA and CEA content in cancerous tissue (ng/g, wet weight) (p<0.05), but no significant correlation between peripheral CEA level and cancerous tissue CEA (r = 0.372). The mean values of portal CEA in aneuploidy were significantly higher than those in diploidy. These findings indicate that circulating CEA in peripheral blood might be influenced by the metabolic process of CEA in the liver as well as cancer progression rather than CEA production of the tumor. 2) The 5 year survival rate of the patient\u27s group with a negative rate of portal CEA (93%) was far better than that with a positive rate (57%). This study suggested that the portal blood level of CEA in colorectal carcinoma may be very useful for assessment of the patient\u27s survival

Seismicity controlled by resistivity structure : the 2016 Kumamoto earthquakes, Kyushu Island, Japan

The M JMA 7.3 Kumamoto earthquake that occurred at 1:25 JST on April 16, 2016, not only triggered aftershocks in the vicinity of the epicenter, but also triggered earthquakes that were 50–100 km away from the epicenter of the main shock. The active seismicity can be divided into three regions: (1) the vicinity of the main faults, (2) the northern region of Aso volcano (50 km northeast of the mainshock epicenter), and (3) the regions around three volcanoes, Yufu, Tsurumi, and Garan (100 km northeast of the mainshock epicenter). Notably, the zones between these regions are distinctively seismically inactive. The electric resistivity structure estimated from one-dimensional analysis of the 247 broadband (0.005–3000 s) magnetotelluric and telluric observation sites clearly shows that the earthquakes occurred in resistive regions adjacent to conductive zones or resistive-conductive transition zones. In contrast, seismicity is quite low in electrically conductive zones, which are interpreted as regions of connected fluids. We suggest that the series of the earthquakes was induced by a local accumulated stress and/or fluid supply from conductive zones. Because the relationship between the earthquakes and the resistivity structure is consistent with previous studies, seismic hazard assessment generally can be improved by taking into account the resistivity structure. Following on from the 2016 Kumamoto earthquake series, we suggest that there are two zones that have a relatively high potential of earthquake generation along the western extension of the MTL