INFLUENCE OF LATERAL TRUNK TILT ON THROWING ARM KINETICS DURING BASEBALL PITCHING

The purpose of this study was to investigate the relationship between lateral trunk tilt angle and several injury-related kinetic parameters during pitching. Based on kinematic data of 12 overhand and three-quarter-hand pitchers, several pitching motions with different lateral trunk tilt angles from the original were simulated. Joint kinetics among the simulated motions was compared. As a result, elbow medial force and elbow varus torque were generally increased as the lateral trunk tilt increased, that is the greater contra-lateral side-bending to the throwing arm side. On the other hand, the shoulder shear force was decreased as the lateral trunk tilt increased. Data from the study demonstrated that the shoulder proximal force was irrelevant to the trunk tilt angle

Thioredoxin/Txnip: Redoxisome, as a Redox Switch for the Pathogenesis of Diseases

During the past few decades, it has been widely recognized that Reduction-Oxidation (redox) responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin1 (Trx1) and Thioredoxin2 (Trx2), mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/thioredoxin binding protein-2/vitamin D3 upregulated protein) directly binds to Trx1 and Trx2 (Trx) and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP-3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named “Redoxisome,” consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes

Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

BACKGROUND: Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated associations between the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We carried out polymerase chain reaction-restriction fragment length polymorphism analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies were assessed in 78 patients with T1DM. RESULTS: We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively). CONCLUSIONS: Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies

ヒト大腸癌肝転移におけるHVEM発現の重要性について

Background: Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM). Methods: This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO. Results: High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM. Conclusions: Tumor HVEM expression might play a critical role in CRLM.博士（医学）・乙第1447号・令和元年12月5日© Society of Surgical Oncology 2019This is a post-peer-review, pre-copyedit version of an article published in Annals of surgical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1245/s10434-019-07625-

The role of Kupffer cells in complement activation in D-Galactosamine/lipopolysaccharide-induced hepatic injury of rats.

To investigate the role of Kupffer cells in complement activation, we used a rat model of acute hepatic injury induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). In in vivo study, minimal histological changes were observed after i.p. GalN (200 mg/kg) single administration. Complement hemolytic activity (CH 50) decreased to 70% of its initial value 2-3 h after i.p. LPS (1.5 mg/kg) single administration. Massive hepatic necrosis was induced by simultaneous administration of GalN and LPS. After 2-3 h, CH 50 decreased to 70% of its initial value, and deposition of C3 fluorescence (C3) was observed in Kupffer cells. After 4 h, GPT was greatly increased (1286 +/- 240 IU/l), CH 50 was further reduced, and C3 was observed on hepatocyte membranes and in the cytosol. In in vitro study, we used hepatocyte cultures and co-cultures of hepatocytes and Kupffer cells to investigate the participation of GalN, LPS, complement, and Kupffer cells in hepatic cell necrosis. We found no increase of LDH (% leakage) when LPS and complement were added to the medium (22.7 +/- 5.7%). A moderate increase was observed with the addition of GalN (33.2 +/- 2.6%). A remarkable increase was observed only with the addition of GalN, LPS, and complement to the co-culture (50.0 +/- 8.8%). These results suggest that Kupffer cells activated by LPS are very important in promoting acute hepatic injury by complement.</p

Fecal microbiota transplantation prevents Candida albicans from colonizing the gastrointestinal tract

Gut microbes symbiotically colonize the gastrointestinal (GI) tract, interacting with each other and their host to maintain GI tract homeostasis. Recent reports have shown that gut microbes help protect the gut from colonization by pathogenic microbes. Here, we report that commensal microbes prevent colonization of the GI tract by the pathogenic fungus, Candida albicans. Wild‐type specific pathogen‐free (SPF) mice are resistant to C. albicans colonization of the GI tract. However, administering certain antibiotics to SPF mice enables C. albicans colonization. Quantitative kinetics of commensal bacteria are inversely correlated with the number of C. albicans in the gut. Here, we provide further evidence that transplantation of fecal microbiota is effective in preventing Candida colonization of the GI tract. These data demonstrate the importance of commensal bacteria as a barrier for the GI tract surface and highlight the potential clinical applications of commensal bacteria in preventing pathogenic fungal infections.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149500/1/mim12680_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149500/2/mim12680.pd

The antioxidant N-acetyl cysteine suppresses lidocaine-induced intracellular reactive oxygen species production and cell death in neuronal SH-SY5Y cells

Analysis of cell apoptosis by FACS. Levels of cell apoptosis were measured using an Annexin V-FITC Apoptosis Detection Kit (BioVision, Milpitas, CA, USA), according to the manufacturer’s instructions. For these analyses, SH-SY5Y cells were seeded into 6-well plates (3 × 105 cells/well) and incubated overnight. The following day, cells were treated with the indicated concentrations of the appropriate drug(s) for varying lengths of time and harvested by centrifugation at 1200 rpm for 3 min. The culture supernatants were discharged, and the resulting pellets were resuspended in a mixture comprised of 500 μl binding buffer, 5 μl Annexing V-FITC, and 5 μl propidium iodide (PI; 50 μg/ml) for 5 min at room temperature in the dark and analyzed using a FACSCalibur flow cytometer (BD Biosciences, San Jose, CA, USA). (PDF 2009 kb