Lung findings on high-resolution computed tomography in idiopathic ankylosing spondylitis--correlation with clinical findings, pulmonary function testing and plain radiography

Previous studies on the association of ankylosing spondylitis and abnormalities of the lung parenchyma have been based largely on plain radiography and pulmonary function testing. This study, although uncontrolled, is the first to use high-resolution computed tomography to examine the entire lung parenchyma in ankylosing spondylitis patients, and to correlate the findings with clinical assessment, plain radiography and pulmonary function testing. The study population comprised 26 patients meeting the New York criteria for idiopathic ankylosing spondylitis who attended the out-patient department at our institution. High-resolution computed tomography examination revealed abnormalities in 19 patients (70%): these included interstitial lung disease (n = 4), bronchiectasis (n = 6), emphysema (n = 4), apical fibrosis (n = 2), mycetoma (n = 1) and non-specific interstitial lung disease (n = 12). Plain radiography was abnormal in only four patients and failed to identify any patient with interstitial lung disease. All patients with interstitial lung disease on high-resolution computed tomography had respiratory symptoms and three of the four had evidence of a restrictive process on pulmonary function testing. This study raises, for the first time, the possible association between interstitial lung disease and ankylosing spondylitis, and highlights the use of high-resolution computed tomography in detecting such disease in ankylosing spondylitis patients.      

一叶萩的化学成分

目的：对一叶萩枝叶的化学成分进行研究。方法：应用各种色谱技术从一叶萩总碱部位中分离化合物，根据理化常数和波谱（NMR及MS等）分析方法对化合物的结构进行鉴定。结果：自一叶萩枝叶的总碱部位中分离得到11个化合物。分别鉴定为：（-）-15β-ethoxy-14，15-dihvdroviroallosecurinine（1），一叶萩碱（securinine，2），二氢一叶萩碱（14，15-dihydrosecurinine，3），4-epiph），llanthine（4），securitinine（5），右旋别一叶萩碱（viroallosecurinine，6），一叶萩醇A（securinol A，7），secu’amamineA（8），ent-phyllanthidine（9），（＋）-aquilegiohde（10）和（＋）-menisdaurilide（11）。结论：1为新化合物，4，8，10和11为首次从一叶萩中分离得到。     

Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis‐related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well‐established cancer gene lysine (K)‐specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome‐sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D‐mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G- CSF-mediated activation of signaling complexes of the p21ras route

Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p21ras route through interaction with its specific receptor (G-CSF-R). The cytoplasmic membrane-proximal region of G-CSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAK2. In contrast, activation of Shc and Syp, signaling molecules implicated in the p21ras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSF-induced activation of signaling complexes of the p21ras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G- CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R). In contrast to BAF3 cell transfectants expressing wild-type G-CSF-R, BAF/W650-R cells did not proliferate and did not show activation of JAK2, STAT1, or STAT3 in response to G-CSF. Immunoprecipitations with anti-Shc and anti-Grb2 antisera showed that mutant W650R also failed to activate Syp and Shc. These data indicate that the membrane-proximal cytoplasmic domain of G- CSF-R is not only crucial for proliferative signaling and activation of JAK2 and STATs, but is also required for activation of the p21ras route, which occurs via the membrane-distal region of G-CSF-R.     

Intraperitoneal chemotherapy for patients with advanced ovarian cancer: a review of the evidence and standards for the delivery of care

OBJECTIVES: To evaluate the role of intraperitoneal (IP) chemotherapy as part of primary treatment in patients with advanced ovarian cancer and to develop standards of care within the context of current clinical practice. METHODS: A multidisciplinary expert panel, convened to develop standards on the use of IP chemotherapy, searched the MEDLINE, EMBASE, and Cochrane Library databases up to December 2006 for randomized trials or published standards on the efficacy and/or delivery of IP chemotherapy. RESULTS: Eight randomized trials comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified. Three trials reported statistically significant improvements in median survival of 8.0, 11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9-month improvement in median overall survival (RR=0.75, 95% CI=0.58-0.97) represented a 25% reduction in the risk of death with IP chemotherapy. Severe adverse events and catheter-related complications were often dose limiting with IP chemotherapy. Using a consensus-based approach with a nationally representative panel, multidisciplinary care standards were developed to review medical and surgical criteria, the practice setting, volume requirements, and the institutional criteria required to safely deliver IP chemotherapy. CONCLUSION: The survival benefits with cisplatin-based IP chemotherapy may represent a significant improvement in the outlook for select patients with advanced ovarian cancer. The delivery of IP chemotherapy is more challenging than the IV route; however, severe adverse events and catheter-related complications may be offset through research defining the optimum treatment regimen, and the standardization of care. System-wide standards for the delivery of IP chemotherapy in Canada for patients with optimally debulked stage III ovarian cancer are offered.     

p38 MAPK对嗜酸性粒细胞和支气管上皮细胞共培养时细胞因子释放的调控作用

目的 了解嗜酸性粒细胞和支气管上皮细胞相互作用诱导细胞因子释放的p38 MAPK信号转导通路.方法 用CD16磁珠抗体分离外周血中嗜酸性粒细胞,以嗜酸性粒细胞和支气管上皮细胞(BEAS-2B)接触共培养为实验模型,观察SB 203580对细胞培养上清液中细胞因子浓度的影响.细胞因子浓度采用ELISA和流式细胞微珠方法测定.结果 SB 203580能够有效抑制BEAS-2B细胞释放IL-6、IL-8(P＜0.05)和嗜酸性粒细胞释放IL-8(P＜0.01).SB 203580对嗜酸性粒细胞与BEAS-2B细胞接触共培养诱导的IL-6、IL-8和IP-10释放具有显著抑制作用(P＜0.001).结论 嗜酸性粒细胞、BEAS-2B细胞单独或相互作用时均通过p38 MAPK信号转导通路释放细胞因子.