新規人口鰓システムによる水中からの高効率な酸素の取り込み

制度:新 ; 文部省報告番号:甲1995号 ; 学位の種類:博士(工学) ; 授与年月日:2005/3/15 ; 早大学位記番号:新392

Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome.

We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.</p

Association Between SLFN11 and Antitumor Activity of Trabectedin

Background/Aim: Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. Materials and Methods: The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models. Results: SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model. Conclusion: SLFN11 expression might be a key factor in the antitumor activity of trabectedin

Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney

Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy. We examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and alpha-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro. The number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of alpha-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1 beta and tumor necrosis factor-alpha but not with IL-4, transforming growth factor-beta and high glucose in cultured human macrophages. The present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy

Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J) : a study protocol

The BIM deletion polymorphism is reported to be associated with poor outcomes of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR-TKIs, including gefitinib. We have shown that a histone deacetylase inhibitor, vorinostat, can epigenetically restore BIM function and apoptosis sensitivity to EGFR-TKIs in EGFR-mutant NSCLC cells with BIM deletion polymorphisms. The purpose of this study is to determine the feasibility of combined treatment of vorinostat with gefitinib in BIM deletion polymorphism positive EGFR-mutant NSCLC patients. BIM deletion polymorphism positive EGFR mutant NSCLC patients treated with at least one EGFR-TKI and one regimen of chemotherapy are being recruited to this study. Vorinostat (200-400mg) will be administered orally once daily on days 1-7, and gefitinib 250 mg orally once daily on days 1-14. With a fixed dose of gefitinib, the dose of vorinostat will be escalated following a conventional 3+3 design. The primary endpoint is to define the maximum tolerated dose (MTD) of vorinostat combined with 250 mg of gefitinib. This is the first phase I study of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism

Phase I/II study of alectinib in lung cancer with RET fusion gene : study protocol

Background : The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC. Methods/Design : RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design. The primary endpoint is safety. In step 2, alectinib will be administered at the recommended dose (RD) defined by step 1. The primary endpoint is the response rate of RET inhibitor treatment-naïve patients. Conclusion : This is the first study to investigate the safety and preliminary efficacy of alectinib in RET fusion-positive NSCLC patients. If successful, alectinib treatment may lead to substantial and important changes in the management of NSCLC with RET fusion genes

Meckel憩室内に発生した小腸カルチノイドの一例

京都府立医科大学附属北部医療センター　外科京都府立医科大学　消化器外科Department of Surgery, North Medical Center Kyoto Prefectural University of MedicineDivision of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine症例は69歳男性。某年1月に右下腹部痛を主訴に当院救急を受診し感染性腸炎の診断で入院となった。精査で炎症を伴う小腸腫瘍を指摘され、異所性膵による膵炎の診断で腹腔鏡補助下小腸部分切除術を施行した。術中、回腸末端から55cm 口側の回腸漿膜下に突出した腫瘍を認めた。病理組織学的検査の結果、Meckel憩室内カルチノイド（NET G1）と診断した。小腸腫瘍はMeckel憩室も鑑別にあがるが、今回我々はMeckel憩室内カルチノイドを合併する稀な症例を経験したので報告する

胆嚢十二指腸瘻による胆石性イレウスの一例

京都府立医科大学附属北部医療センター　外科京都府立医科大学　消化器外科Department of Surgery, North Medical Center Kyoto Prefectual University of MedicineDivision of Digestive Surgery, Department of Surgery, Kyoto Prefectual University of Medicine症例は60歳、男性。腹痛・嘔気を主訴に近医から当院受診となった。CTでは小腸内に結石を認めており、その口側腸管の拡張を認めていたことから胆石性イレウスの診断となった。イレウス管留置を行い保存的加療を継続していたが嘔吐、腹痛ともに改善せず、当院外科で腸閉塞解除術を施行した。術中所見では腸管壊死は認めなかったため結石摘出術のみを施行し閉腹した。高度肥満に対する減量指導を行いながら外来で経過観察し、胆嚢十二指腸瘻閉鎖術を二期的に行う方針となっている