The prevalence of psychological distress during pregnancy in Miyagi Prefecture for 3 years after the Great Eas t Japan Earthquake.

BACKGROUND: To examine changes in psychological distress prevalence among pregnant women in Miyagi Prefecture, which was directly affected by the Great East Japan Earthquake and tsunami, and compare it with the other, less damaged areas of Japan. METHODS: This study was conducted in conjunction with the Japan Environment and Children`s Study. We examined 76,152 pregnant women including 8270 in Miyagi Regional Center and 67,882 in 13 other regional centers from the all-birth fixed data of the Japan Environment and Children's Study. We then compared the prevalence and risk of distress in women in Miyagi Regional Center and women in the 13 regional centers for 3 years after the disaster. RESULTS: Women in the Miyagi Regional Center suffered more psychological distress than those in the 13 regional centers: OR 1.38 (95% CI, 1.03-1.87) to 1.92 (95% CI, 1.42-2.60). Additionally, women in the inland area had a consistently higher prevalence of psychological distress compared to those from the 13 regional centers: OR 1.67 (95% CI, 1.18-2.38) to 2.19 (95% CI, 1.60-2.99). CONCLUSIONS: The lack of pre-disaster data in the Japan Environment and Children's Study made it impossible to compare the incidence of psychological distress before and after the March 2011 Great East Japan Earthquake. However, 3 years after the Great East Japan Earthquake, the prevalence of pregnant women with psychological distress did not improve in Miyagi Regional Center. Further, the prevalence of mental illness in inland areas was consistently higher than that in the 13 regional centers after the disaster.

Effects of aluminum hinged shoes on the structure of contracted feet in Thoroughbred yearlings.

We applied aluminum hinged shoes (AHSs) to the club foot-associated contracted feet of 11 Thoroughbred yearlings to examine the effects of the shoes on the shape of the hoof and third phalanx (P III). After 3 months of AHS use, the size of the affected hooves increased significantly, reaching the approximate size of the healthy contralateral hooves with respect to the maximum lateral width of the foot, the mean ratio of the bearing border width to the coronary band width, and the mean ratio of the solar surface width to the articular surface width. These results suggest that the AHSs corrected the contracted feet in these yearling horses.

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells.

Mitochondria utilize diverse cytoskeleton-based mechanisms to control their functions and morphology. Here, we report a role for kinesin-like protein KLP6, a newly identified member of the kinesin family, in mitochondrial morphology and dynamics. An RNA interference screen using Caenorhabditis elegans led us to identify a C. elegans KLP-6 involved in maintaining mitochondrial morphology. We cloned a cDNA coding for a rat homolog of C. elegans KLP-6, which is an uncharacterized kinesin in vertebrates. A rat KLP6 mutant protein lacking the motor domain induced changes in mitochondrial morphology and significantly decreased mitochondrial motility in HeLa cells, but did not affect the morphology of other organelles. In addition, the KLP6 mutant inhibited transport of mitochondria during anterograde movement in differentiated neuro 2a cells. To date, two kinesins, KIF1Bα and kinesin heavy chain (KHC; also known as KIF5) have been shown to be involved in the distribution of mitochondria in neurons. Expression of the kinesin heavy chain/KIF5 mutant prevented mitochondria from entering into neurites, whereas both the KLP6 and KIF1Bα mutants decreased mitochondrial transport in axonal neurites. Furthermore, both KLP6 and KIF1Bα bind to KBP, a KIF1-binding protein required for axonal outgrowth and mitochondrial distribution. Thus, KLP6 is a newly identified kinesin family member that regulates mitochondrial morphology and transport.

Combining a peptide vaccine with oral ingestion of Lentinula edodes mycelia extract enhances anti-tumor activity in B16 melanoma-bearing mice.

New anticancer vaccines must overcome regulatory T cell (Treg)-mediated immunosuppression. We previously reported that oral ingestion of Lentinula edodes mycelia (L.E.M.) extract restores melanoma-reactive T cells in melanoma-bearing mice via a mitigation of Treg-mediated immunosuppression. In this study, we investigated the effect of oral ingestion of the extract on peptide vaccine-induced anti-tumor activity. The day after subcutaneous inoculation in the footpad with B16 melanoma, mice were freely fed the extract and were vaccinated with a tyrosinase-related protein 2(180-188) peptide. The peptide vaccine was repeated thrice weekly. Melanoma growth was significantly suppressed in mice treated with both the peptide vaccine and L.E.M. extract compared with mice treated with vaccine or extract alone, and the effect was CD8(+) T cell-dependent. The combination therapy increased H-2K(b)-restricted and B16 melanoma-reactive T cells in the draining lymph nodes and spleen. Flow cytometric and immunohistological analyses revealed that the combination therapy significantly decreased the percentage of Tregs in the draining lymph nodes and spleen of melanoma-bearing mice compared to treatment with vaccine or extract alone. Kinetic analyses of peptide-specific T cells and Tregs revealed that induction of peptide-specific T cells by the peptide vaccine alone was transient, but when combined with L.E.M. extract, it efficiently prolonged the duration of peptide-specific T cell induction without increasing the percentage of Tregs. These results indicate that combination therapy enhances peptide vaccine-induced anti-tumor activity due to attenuation of the increase in the percentage of Tregs in tumor-bearing hosts.

Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo.

Extrahepatic manifestations of hepatitis C virus (HCV) infection occur in 40%-70% of HCV-infected patients. B-cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with HCV infection. The mechanism by which HCV infection of B cells leads to lymphoma remains unclear. Here we established HCV transgenic mice that express the full HCV genome in B cells (RzCD19Cre mice) and observed a 25.0% incidence of diffuse large B-cell non-Hodgkin lymphomas (22.2% in males and 29.6% in females) within 600 days after birth. Expression levels of aspartate aminotransferase and alanine aminotransferase, as well as 32 different cytokines, chemokines and growth factors, were examined. The incidence of B-cell lymphoma was significantly correlated with only the level of soluble interleukin-2 receptor α subunit (sIL-2Rα) in RzCD19Cre mouse serum. All RzCD19Cre mice with substantially elevated serum sIL-2Rα levels (> 1000 pg/mL) developed B-cell lymphomas. Moreover, compared with tissues from control animals, the B-cell lymphoma tissues of RzCD19Cre mice expressed significantly higher levels of IL-2Rα. We show that the expression of HCV in B cells promotes non-Hodgkin-type diffuse B-cell lymphoma, and therefore, the RzCD19Cre mouse is a powerful model to study the mechanisms related to the development of HCV-associated B-cell lymphoma.

Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell-mediated immunosuppression.

Mitigation of regulatory T cell-mediated immunosuppression is crucial for optimal in vivo anti-tumor immune responses. In this study, we examined the anti-tumor effect induced by oral ingestion of an immunomodulating diet comprised of Lentinula edodes mycelia (L.E.M.) extract. C57BL/6 mice were inoculated subcutaneously in the footpad with B16 melanoma and fed L.E.M. extract. Ingestion of L.E.M. extract significantly inhibited tumor growth, and this in vivo anti-tumor effect was not observed in nude mice, suggesting a T cell-dependent mechanism. In addition, ingestion of L.E.M. extract led to significant restoration of H-2K(b) -restricted and melanoma-reactive T cells in the spleen and draining lymph nodes of melanoma-bearing mice. Flow cytometry analysis revealed that the percentage of Foxp3(+) CD4(+) T cells increased in spleen and draining lymph nodes in melanoma-bearing mice, but decreased significantly with ingestion of L.E.M. extract. Importantly, selective depletion of CD8(+) T cells abolished the L.E.M.-induced anti-tumor effect, whereas that of CD4(+) T cells or CD25(+) cells showed no additive influence on the effect. Real-time PCR analysis revealed that ingestion of L.E.M. extract by melanoma-bearing mice decreased the level of Foxp3 mRNA within the tumor tissues, and lowered plasma transforming growth factor (TGF)-ß. Furthermore, an in vitro assay revealed that an immunosuppressive activity of CD4(+) T cells from melanoma-bearing mice was canceled by ingestion of L.E.M. extract. Our results indicate that oral ingestion of L.E.M. extract restores immune responses of class I-restricted and melanoma-reactive CD8(+) T cells in melanoma-bearing mice, presumably by a mitigation of regulatory T cells-mediated immunosuppression.

An RNAi screen for mitochondrial proteins required to maintain the morphology of the organelle in Caenorhabditis elegans.

Mitochondria are dynamic organelles that frequently divide and fuse together, resulting in the formation of intracellular tubular networks. In yeast and mammals, several factors including Drp1/Dnm1 and Mfn/Fzo1 are known to regulate mitochondrial morphology by controlling membrane fission or fusion. Here, we report the systematic screening of Caenorhabditis elegans mitochondrial proteins required to maintain the morphology of the organelle using an RNA interference feeding library. In C. elegans body wall muscle cells, mitochondria usually formed tubular structures and were severely fragmented by the mutation in fzo-1 gene, indicating that the body wall muscle cells are suitable for monitoring changes in mitochondrial morphology due to gene silencing. Of 719 genes predicted to code for most of mitochondrial proteins, knockdown of >80% of them caused abnormal mitochondrial morphology, including fragmentation and elongation. These findings indicate that most fundamental mitochondrial functions, including metabolism and oxidative phosphorylation, are necessary for maintenance of the tubular networks as well as membrane fission and fusion. This is the first evidence that known mitochondrial activities are prerequisite for regulating the morphology of the organelle. Furthermore, 88 uncharacterized or poorly characterized genes were found in the screening to be implicated in mitochondrial morphology.

Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum.

We previously reported that oral ingestion of Lentinula edodes mycelia (L.E.M.) extract can inhibit the growth of a subcutaneously established melanoma in a T cell-dependent manner via mitigation of regulatory T cell (Treg)-mediated immunosuppression. In this study, we tested the antitumor effect and mechanism of oral ingestion of L.E.M. extract following inoculation of murine colon carcinoma colon-26 (C26) cells into the subserosal space of the cecum (i.c.) of syngeneic mice. In this model, the primary site of the immune response was gut-associated lymphoid tissue (GALT), which is known to be an immunological tolerance-inducing site for numerous dietary antigens. Oral ingestion of the L.E.M. extract suppressed the growth of i.c.-inoculated C26 cells in a T cell-dependent manner and restored the T cell response of the mesenteric lymph nodes and the spleen, not only to a tumor antigen-derived peptide, presented on H-2Ld molecules, but also to C26 cells. I.c. inoculation of C26 cells increased the potential of CD4+ T cells of the mesenteric lymph nodes to produce transforming growth factor (TGF)-ß, but ingestion of the L.E.M. extract decreased the ability of both CD4+ and CD8+ T cells in the mesenteric lymph nodes to produce this immunosuppressive cytokine. Although ingestion of L.E.M. showed only a marginal effect on Tregs in this model, this treatment significantly reduced the plasma levels of TGF-ß and IL-6, both of which were increased in the i.c. C26-inoculated mice. In summary, our results indicate that oral ingestion of L.E.M. extract can restore antitumor T cell responses of mice even when the primary antitumor immune response is elicited in GALT, and provide important implications for anticancer immunotherapy of human colon cancer.