Repeated Stressing and Crystalline State of Annealed Steel

The action of repeated loading, especially of repeated compression for the crystalline state of 0.41% carbon steel was investigated by X-ray. As a result it was established that the crystal fragmentation occurs when the maximum stress exceeds the lower yield point of that material but has no direct relation with fatigue failure. In the case of alternate tension and compression with equal amplitude (mean stress equals zero), the specimens break down far below the yield point, of course, but is not necessarily preceeded by the crystal fragmentation. Then, what is the true nature of fatigue of metals is our problem. According to the authors' view, failure begins when the accumulation of crystal distorsion exceeds a certain limit proper to the individual grain

Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy

Role of Matrix Metalloproteinase-2 in Eosinophil-Mediated Airway Remodeling

Airway remodeling is responsible for the progressive decline of lung function in bronchial asthma. Matrix metalloproteinase-2 and fibroblast-to-myofibroblast transition are involved in tissue remodeling. Here we evaluated whether eosinophils play a role in fibroblasts-to-myofibroblasts transition and in the expression of matrix metalloproteinase-2. We co-cultured human eosinophils with human fetal lung fibroblast-1 cells, assessed the expression of remodeling-associated molecules by immunoassays and polymerase-chain reaction, and eosinophils-mediated migration of human fetal lung fibroblast-1 cells using a Boyden chamber. To clarify the participation of matrix metalloproteinase-2 in airway remodeling we administered bone marrow-derived eosinophils by intra-tracheal route to transgenic mice overexpressing the human matrix metalloproteinase-2. The expression of α-smooth muscle actin significantly increased in human fetal lung fibroblast-1 cells co-cultured with human eosinophils compared to controls. There was enhanced expression of matrix metalloproteinase-2 during fibroblast-to-myofibroblast transition. An inhibitor of matrix metalloproteinases blocked eosinophils-associated fibroblast-to-myofibroblast transition and increased migration of fibroblasts. The human matrix metalloproteinase-2 transgenic mice receiving adoptive transfer of mouse eosinophils exhibited increased inflammation and advanced airway remodeling compared to wild type mice. This study demonstrated that eosinophils induce fibroblast-to-myofibroblast transition, secretion of matrix metalloproteinase-2, accelerated migration of fibroblasts, and promote matrix metalloproteinase-2-related airway remodeling. These findings provide a novel mechanistic pathway for eosinophil-associated airway remodeling in bronchial asthma

Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy

<p>Abstract</p> <p>Purpose</p> <p>To determine the risk factors of severe radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for primary or secondary lung tumors.</p> <p>Materials and methods</p> <p>From January 2003 to March 2009, SBRT was performed on 117 patients (32 patients before 2005 and 85 patients after 2006) with lung tumors (primary = 74 patients and metastatic/recurrent = 43 patients) in our institution. In the current study, the results on cases with severe RP (grades 4-5) were evaluated. Serum Krebs von den Lungen-6 (KL-6) and serum Surfactant protein-D (SP-D) were used to predict the incidence of RP. A shadow of interstitial pneumonitis (IP) on the CT image before performing SBRT was also used as an indicator for RP. Since 2006, patients have been prescreened for biological markers (KL-6 & SP-D) as well as checking for an IP-shadow in CT.</p> <p>Results</p> <p>Grades 4-5 RP was observed in nine patients (7.7%) after SBRT and seven of these cases (6.0%) were grade 5 in our institution. A correlation was found between the incidence of RP and higher serum KL-6 & SP-D levels. IP-shadow in patient's CT was also found to correlate well with the severe RP. Severe RP was reduced from 18.8% before 2005 to 3.5% after 2006 (<it>p </it>= 0.042). There was no correlation between the dose volume histogram parameters and these severe RP patients.</p> <p>Conclusion</p> <p>Patients presenting with an IP shadow in the CT and a high value of the serum KL-6 & SP-D before SBRT treatment developed severe radiation pneumonitis at a high rate. The reduction of RP incidence in patients treated after 2006 may have been attributed to prescreening of the patients. Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors.</p

Systematic protein-protein interaction mapping for clinically relevant human GPCRs

G‐protein‐coupled receptors (GPCRs) are the largest family of integral membrane receptors with key roles in regulating signaling pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR‐mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two‐hybrid (MYTH) approach and identified interacting partners for 48 selected full‐length human ligand‐unoccupied GPCRs in their native membrane environment. The resulting GPCR interactome connects 686 proteins by 987 unique interactions, including 299 membrane proteins involved in a diverse range of cellular functions. To demonstrate the biological relevance of the GPCR interactome, we validated novel interactions of the GPR37, serotonin 5‐HT4d, and adenosine ADORA2A receptors. Our data represent the first large‐scale interactome mapping for human GPCRs and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins

A case of cytomegalovirus colitis initially misdiagnosed as colonic ischemia in an immunocompetent Japanese woman

Cytomegalovirus colitis should be considered in a patient presenting with bloody stool even among immunocompetent patients

Effects of Drying Temperature for Cryptomeria japonica on the Permeability of Wood Preservative. II: The Permeability of Dried, Split Log Pieces

Poor impregnation of sapwood from Cryptomeria japonica kiln-dried logs is a problem for preservative treatment in Japan. The permeability of copper azole (CuAz) into sapwood was reported to decrease with an increase in the drying temperature of logs, due in part to the presence of bordered pits. However, damaged and aspirated bordered pits appeared abundantly at 100 °C and 120 °C, although the difference in permeability was very little. To investigate this phenomenon, two types of smaller split log pieces, one containing both heartwood and sapwood, and the other containing sapwood without heartwood, were dried at 20 °C to 120 °C to test higher drying conditions. Results were similar to those of the dried logs. However, the impregnation and penetration at 80 °C were the lowest, and those at 100 °C and 120 °C were greater than the dried logs. Additionally, the number of damaged bordered pits on dried, split samples was generally higher than that of dried logs, as observed with scanning electron microscopy

MK2206 potentiates cisplatin-induced cytotoxicity and apoptosis through an interaction of inactivated Akt signaling pathway

[Objectives]To improve conventional chemotherapeutic efficacy, it is important to detect new molecular markers for chemosensitivity and possible accelerating cell-killing mechanisms. In this study, we investigated how MK2206, an allosteric Akt inhibitor, enhances the cisplatin (CDDP)-induced cytotoxicity and apoptosis in urothelial cancer cells. [Materials and methods]We examined bladder cancer cell lines for the expression of phospho(p)-Akt and its downstream targets by Western blot. The potential antitumor effects were analyzed by MTT assay in vitro and by subcutaneous xenograft models in vivo. The cell invasion was examined by transwell invasion assay, and the activities of the Akt signaling pathway and expression of apoptosis-related proteins were measured by Western blot. [Results]The expression of p-Akt and its downstream targets was increased in invasive bladder cancer cell lines vs. in noninvasive bladder cancer cell lines. MK2206 (500 nM) inhibited cell invasion in UMUC3 cell line and significantly increased the susceptibility of bladder cancer cell lines to CDDP. When used in combination with CDDP, MK2206 (500 nM) enhanced CDDP-induced cytotoxicity and apoptosis, with suppressed expression of p-Akt and its downstream targets. In vivo MK2206 combined with CDDP effectively suppressed tumor growth in subcutaneous xenograft models. [Conclusions]These results suggest that concomitant use of MK2206 could promote the CDDP-induced cytotoxicity and apoptosis in urothelial cancer cell lines through the inhibited expression of the Akt pathway. This combined treatment may provide a new therapeutic option to enhance chemosensitivity in bladder cancer