Efficacy of a School-Based Universal Program for Bullying Prevention: Considering the Extended Effects Associated with Achievement of the Direct Purposes of the Program

We have developed a group of universal prevention programs for children’s health and adjustment. The programs are characterized by new theories such as the somatic-marker hypothesis and enjoyable methods that utilize animated stories and games. This study adopted one of the programs, a universal program for bullying prevention in third-grade students, and evaluated its efficacy. Participants were third-grade students in two public elementary schools in Japan. Homeroom classes in the schools were randomly divided into intervention and control groups. The final intervention group included 99 children (58 boys, 41 girls) and the final control group included 96 children (45 boys, 51 girls). The program was implemented weekly in one regular 45-minute class over eight weeks for all homeroom class members. Participants completed two questionnaires both before and after the program. Similar assessment periods were used for the control group. The questionnaires assessed the main purposes of the program (to enhance the understanding of bullying, to cultivate empathetic feelings for bullying victims, and to cultivate behavioral capabilities that stop bullying), and measured the adaptive status of children in homeroom class and at school. Results indicated that all of the main program purposes were achieved in the intervention group compared to the control group. Moreover, the level of the children’s adjustment in homeroom class and at school significantly increased with the program, except for motivation for learning, which did not change. The necessity of future research that examines the sustainability of the efficacy of the program with randomized controlled trials is discussed, along with the study limitations

The Effect of Gefitinib on B-RAF Mutant Non-small Cell Lung Cancer and Transfectants

Abstract:We previously reported one patient with squamous cell carcinoma of the lung that showed the long-term effect to gefitinib with complete response. In the present report, we examine the epidermal growth factor receptor (EGFR) and K-RAS, HER2, and B-RAF mutations in this patient to find a B-RAF exon11 mutation, resulting in a substitution of valine by phenylalanine at codon 470 (V470F) as a novel type of B-RAF mutation in human cancers. In addition, the fluorescence in situ hybridization analysis for EGFR showed the high polysomy status. B-RAF is a nonreceptor serine/threonine kinase whose kinase domain has a structure similar to other protein kinases, including EGFR members. Of interest, the B-RAF V470F mutation corresponds to a position similar to the EGFR G719X mutation located on the phosphate binding (P)-loop of EGFR that clamps ATP into the catalytic cleft. This observation suggests that gefitinib may have an anti-cancer effect on B-RAF mutant tumors. Indeed, previous reports demonstrated that H1666 cells harboring B-RAF G465V mutations showed sensitivity to gefitinib, inhibiting phosphorylation of ERK1/2. We examined the effect of gefitinib on transient transfectants of the B-RAF mutant, but no drastic inhibition of ERK1/2 phosphorylation that was one of the downstream molecules of B-RAF was induced by gefitinib.In summary, we found a novel B-RAF V470F mutation in lung squamous cell carcinoma that showed response to gefitinib. However, our in vitro investigation did not explain the response observed in this particular patient. Further investigation is necessary to elucidate the mechanism of tumor sensitivity to EGFR tyrosine kinase inhibitors

地域住民によるまちづくり活動の継続性に関する研究

昭和女子大学201

Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis

The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity

Anti-Atherogenic Effect of Eztimibe in Apo-E Knockout Mice

Apo-E KO マウス( ApoE-/-) を用いて,コレステロール吸収阻害薬のezetimibe( EZ) とHMG-CoAreductase 阻害薬のfluvastatin( Fluva) の動脈硬化形成に与える影響について検討した.高脂肪食負荷ApoE-/- マウスではEZ の投与により,総コレステロールおよびLDL コレステロールをそれぞれ63%,74%減少させ,胸部大動脈のプラーク形成を明らかに抑制するとともに,内皮依存性の血管弛緩反応を有意に改善した.一方,Fluva 投与ではその効果が認められなかった.また,EZ 投与はmonocyte chemoattractantprotein-1,vascular cell adhesion molecule-1,intercellular adhesion molecule-1 などの白血球走化・接着因子やNADPH oxidase コンポーネントの肺組織中mRNA 発現を有意に抑制した.高脂肪食負荷ApoE-/- マウスにおいて,EZ は明らかな抗動脈硬化作用を示した.The aim of present study was to investigate the effects ofezetimibe, a cholesterol absorption inhibitor, on athrosclerosisin apolipoprotein E knockout (ApoE-KO) mice. Tretmentwith ezetimibe, but not fluvastatin, significantly Decreased serum total and low density lipoprotein (LDL)Cholesterol and lesions of atherosclerotic plaque of aorta Inwastern diet-fed ApoE-KO mice. Ezetimibe also restorednitric oxide-mediated vascular relaxation in isolated aorticrings.Moreover, ezetimibe treatment significantly decreased the mRNA expression of a chemoattractant, adhesion molecules,and several subunits of NADPH oxidase in lung tissues.These results suggest that ezetimibe may inhibit athrosclerosis by ameliorating vascular inflammation and oxidative stress in ApoE-KO mice independently of lowering serum cholesterol level.原著journal articl

Living Donor Liver Transplantation with Renoportal Anastomosis for a Patient with Congenital Absence of the Portal Vein

A congenital absence of the portal vein (CAPV) is a rare disorder that may lead to an intrapulmonary shunt. A 14-year-old male with CAPV underwent living donor liver transplantation with a left lobe graft from his father. The portal vein reconstruction was achieved with a renoportal anastomosis using an interpositional graft from the native collateral vein, because portal venous system directly drains to the left renal vein without constructing the confluence of superior mesenteric vein and splenic vein. The patient is doing well with a normal liver function and mild hypoxemia

Successful Treatment of Infectious Endocarditis Associated Glomerulonephritis Mimicking C3 Glomerulonephritis in a Case with No Previous Cardiac Disease

We report a 42-year-old man with subacute infectious endocarditis (IE) with septic pulmonary embolism, presenting rapidly progressive glomerulonephritis and positive proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA). He had no previous history of heart disease. Renal histology revealed diffuse endocapillary proliferative glomerulonephritis with complement 3- (C3-) dominant staining and subendothelial electron dense deposit, mimicking C3 glomerulonephritis. Successful treatment of IE with valve plastic surgery gradually ameliorated hypocomplementemia and renal failure; thus C3 glomerulonephritis-like lesion in this case was classified as postinfectious glomerulonephritis. IE associated glomerulonephritis is relatively rare, especially in cases with no previous history of valvular disease of the heart like our case. This case also reemphasizes the broad differential diagnosis of renal involvement in IE

Counseling for hemodialysis outpatients.

Maintenance hemodialysis outpatients must limit salt and water intake to maintain electrolyte balance and blood pressure. In Kawashima Hospital, nationally registered dietitians provide hemodialysis patients with monthly nutritional counseling. We investigated whether nutritional counseling affects interdialytic weight gain (IDWG) and blood pressure. We investigated 48 hemodialysis patients whose monthly average IDWG ratio to dry weight exceeded 5.1% and who had not had a long-term hospital admittance of ＞1 month. After the 48-month nutritional counseling period, the IDWG ratio had improved in 37 of the patients (77.1%), significantly decreasing from 6.0±0.7 to 5.3±0.9%. Estimated salt and water intake decreased significantly from 13.3±2.7 to 11.8±2.4 g/day and 2528±455 to 2332±410 ml/day, respectively. During the intervention period, normalized protein catabolic rate and body mass index did not change substantially. Pre-hemodialysis systolic and diastolic blood pressures had significantly decreased from 149±19 to 134±18 mmHg, and 82±13 to 75±10 mmHg for 48 months after study initiation, respectively. The dosage of antihypertensive drugs had significantly decreased in the group that experienced improvement in the IDWG ratio. Long-term nutritional counseling by nationally registered dietitians may improve the IDWG ratio and blood pressure of hemodialysis patients by decreasing their salt and water intake

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE

BRAF V600 mutations in Langerhans cell histiocytosis with a simple and unique assay

BACKGROUND: BRAF (V-raf murine sarcoma viral oncogene homolog B1) is a serine-threonine protein kinase involved in cell survival, proliferation, and differentiation. The most common missense mutation of BRAF (mainly V600E) contributes to the incidence of various cancers, including Langerhans cell histiocytosis (LCH). BRAF inhibitors molecularly targeting the V600E mutation have been developed to counteract the effect of the mutation. To ensure the administration of effective pharmacotherapy, it is therefore imperative to develop an effective assay to screen LCH patients for the V600E mutation. However, tumor tissues of LCH typically contain many inflammatory cells which make a correct judgement of the mutation status difficult in the DNA sequence analysis. RESULTS: In this study, we present a new, highly sensitive analyzing method combining PCR, restriction enzyme digestion, and a sequencing assay using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens. TspRI is a restriction enzyme that cleaves the sequence encompassing the wild-type BRAF codon 600 into two fragments, which cannot be used as a template for subsequent BRAF PCR amplification. We therefore evaluated the sensitivity of BRAF V600 mutation detection by amplifying the primary PCR product digested with TspRI and sequencing the secondary PCR products. The V600E mutation was detected in FFPE tissue samples from 32 LCH patients; our assay was able to identify mutations in four samples that gave inconclusive results, and ten that were negative, according to standard PCR and sequencing. CONCLUSIONS: We presented a new and highly sensitive method to detect BRAF V600 mutations. This screening method is expected to play an important role to select the most effective therapies