Pulmonary resection for patients with lung cancer with interstitial lung diseases may provoke acute exacerbation at a substantially high rate and has high associated mortality. Surgical procedures that proved to be a risk factor for acute exacerbation should be chosen cautiously for these high-risk patients.

Abstract-We recently reported that angiotensin II (Ang II) induced IL-6 mRNA expression in cardiac fibroblasts, which played an important role in Ang II-induced cardiac hypertrophy in paracrine fashion. The present study investigated the regulatory mechanism of Ang II-induced IL-6 gene expression, focusing especially on reactive oxygen species (ROS)-mediated signaling in cardiac fibroblasts. Ang II increased intracellular ROS in cardiac fibroblasts, and the increase was completely inhibited by the AT-1 blocker candesartan and the NADH/NADPH oxidase inhibitor diphenyleneiodonium (DPI). We first confirmed that antioxidant N-acetylcysteine, superoxide scavenger Tiron, and DPI suppressed Ang II-induced IL-6 expression. Because we observed that exogenous H 2 O 2 also increased IL-6 mRNA, the signaling pathways downstream of Ang II and exogenous H 2 O 2 were compared. Ang II, as well as exogenous H 2 O 2 , activated ERK, p38 MAPK, and JNK, which were significantly inhibited by N-acetylcysteine and DPI. In contrast with exogenous H 2 O 2 , however, Ang II did not influence phosphorylation and degradation of IB-␣/␤ or nuclear translocation of p65, nor did it increase NF-B promoter activity. PD98059 and SB203580 inhibited Ang II-induced IL-6 expression. Truncation and mutational analysis of the IL-6 gene promoter showed that CRE was an important cis-element in Ang II-induced IL-6 gene expression. NF-B-binding site was important for the basal expression of IL-6, but was not activated by Ang II. Ang II phosphorylated CREB through the ERK and p38 MAPK pathway in a ROS-sensitive manner. Collectively, these data indicated that Ang II stimulated ROS production via the AT1 receptor and NADH/NADPH oxidase, and that these ROS mediated activation of MAPKs, which culminated in IL-6 gene expression through a CRE-dependent, but not NF-B-dependent, pathway in cardiac fibroblasts. Key Words: angiotensin II Ⅲ interleukin-6 Ⅲ reactive oxygen species Ⅲ mitogen-activated protein kinase Ⅲ cardiac fibroblast C linical, experimental, and genetic data have demonstrated that the renin angiotensin system is linked to the pathogenesis of a variety of cardiac diseases. Expression of angiotensin II (Ang II), the key effector molecule of the renin angiotensin system, is increased under various pathophysiological conditions and stimulates cardiomyocyte hypertrophy and interstitial fibrosis coinciding with accumulation of extracellular matrix. Recent reports had shown that Ang II stimulates membrane-bound NAD(P)H oxidase, which generates reactive oxygen species (ROS) in a variety of nonphagocytic cells. 1 ROS may act as a second messenger that regulates various intracellular signal transduction cascades and the activity of various transcription factors. NF-B and AP-1 are the best characterized transcription factors to be influenced by the cellular oxidation-reduction (redox) state. 2,3 The primary target of activation of NF-B by ROS appears to be the phosphorylation and subsequent degradation of IB. 4 Another well-characterized redox sensitive signali...

BackgroundHealth insurance claims (ie, receipts) record patient health care treatments and expenses and, although created for the health care payment system, are potentially useful for research. Combining different types of receipts generated for the same patient would dramatically increase the utility of these receipts. However, technical problems, including standardization of disease names and classifications, and anonymous linkage of individual receipts, must be addressed.MethodsIn collaboration with health insurance societies, all information from receipts (inpatient, outpatient, and pharmacy) was collected. To standardize disease names and classifications, we developed a computer-aided post-entry standardization method using a disease name dictionary based on International Classification of Diseases (ICD)-10 classifications. We also developed an anonymous linkage system by using an encryption code generated from a combination of hash values and stream ciphers. Using different sets of the original data (data set 1: insurance certificate number, name, and sex; data set 2: insurance certificate number, date of birth, and relationship status), we compared the percentage of successful record matches obtained by using data set 1 to generate key codes with the percentage obtained when both data sets were used.ResultsThe dictionary’s automatic conversion of disease names successfully standardized 98.1% of approximately 2 million new receipts entered into the database. The percentage of anonymous matches was higher for the combined data sets (98.0%) than for data set 1 (88.5%).ConclusionsThe use of standardized disease classifications and anonymous record linkage substantially contributed to the construction of a large, chronologically organized database of receipts. This database is expected to aid in epidemiologic and health services research using receipt information.

Gene transfer of dopamine-synthesizing enzymes into the striatal neurons has led to behavioral recovery in animal models of Parkinson's disease (PD). We evaluated the safety, tolerability, and potential efficacy of adeno-associated virus (AAV) vector-mediated gene delivery of aromatic L-amino acid decarboxylase (AADC) into the putamen of PD patients. Six PD patients were evaluated at baseline and at 6 months, using multiple measures, including the Unified Parkinson's Disease Rating Scale (UPDRS), motor state diaries, and positron emission tomography (PET) with 6-[(18)F]fluoro-L-m-tyrosine (FMT), a tracer for AADC. The short-duration response to levodopa was measured in three patients. The procedure was well tolerated. Six months after surgery, motor functions in the OFF-medication state improved an average of 46% based on the UPDRS scores, without apparent changes in the short-duration response to levodopa. PET revealed a 56% increase in FMT activity, which persisted up to 96 weeks. Our findings provide class IV evidence regarding the safety and efficacy of AADC gene therapy and warrant further evaluation in a randomized, controlled, phase 2 setting.