p53遺伝子転写活性化に対するbc1-2の影響についての基礎的研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1215号, 学位授与年月日：平成8年3月25日,学位授与年：199

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm.

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation, 'nephron-like' features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity to the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialized filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly (Drosophila melanogaster) orthologues of the major constituents of the slit diaphragm, including nephrin, NEPH1 (also known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find that the nephrocyte diaphragm is completely lost in flies lacking the orthologues of nephrin or NEPH1-a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in human congenital nephrotic syndrome of the Finnish type, NPHS1) or NEPH1. These changes markedly impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting that the two cell types are evolutionarily related, and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases.This work was supported by Wellcome Trust grants awarded to H.S. (072441 and 079221, H.W., B.D., H.S.); Deutsche Forschungsgemeinschaft (SFB 590) awarded to Elisabeth Knust (F.G.), ARC 1242 (H.W., B.D., H.S., F.G.); MEC grant awarded to M.R-G. (BFU2007-62201, S.P-S., M.R-G.); Fundación Ramón Areces grant to the CBMSO (M.R-G.); EC grant LSHG-CT-2004-511978 to MYORES (M.R-G.); an FPU fellowship from the MEC awarded to A.G-L.Peer reviewe

自験例における肺癌に対する気管分岐部形成術

金沢大学医薬保健研究域医学系The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory

肺癌の手術成績からみた新病期分類, とくにIIIA期, IIIB期の妥当性と問題点

金沢大学医薬保健研究域医学系The purpose of this study was to evaluate the results of new TNM staging system for lung cancer in 1997, especially T3N0M0, stage IIIA, stage IIIB, and pm. Five-year survival rates of the patients with stage IIIA and stage IIIB were 16% and 18% respectively (NS). Five-year survival rates of patients with T3N1M0, T1N2M0, T2N2M0, and T3N2M0 were 40%, 28%, 15%, and 3%, respectively. The prognosis of T3N2M0 was significantly worse than that of T3N1M0, T1N2M0, and T2N2M0. Five-year survival rates of the patients excluding pm 1 with T4N0M0, T4N1M0, T4N2M0, and T4N3M0 were 21%, 10%, 10%, and 0%, respectively. The prognosis of the patients with T4N0 was significantly better than that of T4N2 and T4N3. In the patients with pm, 5-year survival rates of the patients with pm 1 and pm 2 were 26% and 7%, respectively (p < 0.01). In the patients with pm 1, 5-year survival rates of the patients with N0 + N1 and N1 + N2 were 53% and 16%, respectively (p < 0.01). From our these results, we supported the new TNM system as putting T3N0M0 to stage IIB, putting pm 2 into stage IV. We proposed; 1) chest wall invasion with bone destruction stay in stage IIIA or is T4, 2) T3N1M0 is classified with stage IIB, 3) main stem bronchus invasion is classified with T2, 4) pm 1 is subdivide by N status. Furthermore, stage III seemed to be reasonably subdivided into T1-2N3M0, T4N0-1M0 as stage IIIA and T3-4N2, T1-4N3 as stage IIIB

胸壁再建術症例の再建法とその成績の検討

金沢大学医薬保健研究域医学系Twenty-three patients underwent chest wall reconstruction in our department. The underlying disease was bronchial carcinoma in 14, urachus tumor in 2, breast cancer in 1, renal cancer in 1, thymic Hodgkin\u27s lymphoma in 1, tuberculosis in 1, fibrosarcoma in 1, and pseudoaneurysm of the aortic arch caused by reconstructed material in 1. An average of 3.4 ribs were resected in 18 patients and sternectomies were performed in 5. Chest wall reconstruction was performed with Marlex mesh in 14, Marlex mesh with methyl methacrylate in 5, Marlex mesh with steel wire in 1, Marlex mesh with omentopexy in 1, Marlex mesh with A-O plate in 1, and net formation with catgut in 1. There was no operative death. Postoperative wound infection occurred in only 1 patient with Marlex mesh cleaned by irrigation and administration of antibiotics. Three patients with Marlex mesh and metyl methacrylate required removal of the prosthetic material postoperatively because of wound infection in 1, seroma in 1, and dislocation of the former reconstructed material in 1. One patient with Marlex mesh and steel wire had protrusion of the wire under the skin and the wire was removed. Eleven patients of lung cancer died at 2-17 months after surgery. In conclusion, chest wall reconstruction with Marlex mesh had excellent results, and chest wall resection and reconstruction for malignancy could be good palliation

原発性肺癌胸腔内再発および重複肺癌に対する再切除の意義

金沢大学医薬保健研究域医学系Thirty patients have undergone multiple resections for non-small cell lung cancer from 1973 to July 1994, constituting 2.6% of 1,153 who had undergone pulmonary resection for such tumor. In the 22 patients for recurrent cancer, 15 resections of the ipsilateral lung and 9 of the contralateral lung were performed with no operative death. The survival rate following second resection in 22 patients was 33.8% at 3 years and 13.5% at 5 years. Survival rate was poor in patients with DNA aneuploid primary tumor and there was not a patients of 5 years survival. Three out of the 5 patients which had a diploid pattern in the primary tumor, showed an aneuploid pattern in the recurrent tumor. Long survival patients were founded only in the patients which had a diploid primary tumor. In the 8 patients for second primary lung cancer, 4 resections of the ipsilateral lung and 4 of the contralateral lung were performed, including two bronchoplastic surgery for early hilar squamous cell carcinoma. The survival rate following second resection in 8 patients was 64.2% at 5 years with good result. We concluded that an aggressive surgical approach is safe and warranted in patients with second primary lung cancer