284 research outputs found

    Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

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    <p>Abstract</p> <p>Background</p> <p>Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases.</p> <p>Patients and Methods</p> <p>We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (<it>EGFR</it>) and <it>KRAS </it>mutations.</p> <p>Results</p> <p>SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (<it>p </it>= 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed <it>EGFR </it>mutations, and none of them showed <it>KRAS </it>mutations.</p> <p>Conclusions</p> <p>SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/9433341526290040</url>.</p

    Surgical load in major fractures - results of a survey on the optimal quantification and timing of surgery in polytraumatized patients

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    PURPOSE It is known that the magnitude of surgery and timing of surgical procedures represents a crucial step of care in polytraumatized patients. In contrast, it is not clear which specific factors are most critical when evaluating the surgical load (physiologic burden to the patient incurred by surgical procedures). Additionally, there is a dearth of evidence for which body region and surgical procedures are associated with high surgical burden. The aim of this study was to identify key factors and quantify the surgical load for different types of fracture fixation in multiple anatomic regions. METHODS A standardized questionnaire was developed by experts from Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT)-Trauma committee. Questions included relevance and composition of the surgical load, operational staging criteria, and stratification of operation procedures in different anatomic regions. Quantitative values according to a five-point Likert scale were chosen by the correspondents to determine the surgical load value based on their expertise. The surgical load for different surgical procedures in different body regions could be chosen in a range between "1," defined as the surgical load equivalent to external (monolateral) fixator application, and "5," defined as the maximal surgical load possible in that specific anatomic region. RESULTS This questionnaire was completed online by 196 trauma surgeons from 61 countries in between Jun 26, 2022, and July 16, 2022 that are members of SICOT. The surgical load (SL) overall was considered very important by 77.0% of correspondents and important by 20.9% correspondents. Intraoperative blood loss (43.2%) and soft tissue damage (29.6%) were chosen as the most significant factors by participating surgeons. The decision for staged procedures was dictated by involved body region (56.1%), followed by bleeding risk (18.9%) and fracture complexity (9.2%). Percutaneous or intramedullary procedures as well as fractures in distal anatomic regions, such as hands, ankles, and feet, were consistently ranked lower in their surgical load. CONCLUSION This study demonstrates a consensus in the trauma community about the crucial relevance of the surgical load in polytrauma care. The surgical load is ranked higher with increased intraoperative bleeding and greater soft tissue damage/extent of surgical approach and depends relevantly on the anatomic region and kind of operative procedure. The experts especially consider anatomic regions and the risk of intraoperative bleeding as well as fracture complexity to guide staging protocols. Specialized guidance and teaching is required to assess both the patient's physiological status and the estimated surgical load reliably in the preoperative decision-making and operative staging

    Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis.

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    Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab.This is an electronic version of an article published in Free Radical Research, 42(11-12), 957-965: 2008 November. Free Radical Research is available online at: http://informahealthcare.com/doi/abs/10.1080/0891693080240630

    Efficacy of AiiM, an N-Acylhomoserine Lactonase, against Pseudomonas aeruginosa in a Mouse Model of Acute Pneumonia

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    Quorum sensing (QS) in Pseudomonas aeruginosa regulates the production of many virulence factors and plays an important role in the pathogenesis of P. aeruginosa infection. N-acyl homoserine lactones (AHL) are major QS signal molecules. Recently, a novel AHL-lactonase enzyme, AiiM, has been identified. The aim of this study was to evaluate the effect of AiiM on the virulence of P. aeruginosa in a mouse model of acute pneumonia. We developed a P. aeruginosa PAO1 strain harboring an AiiM-expressing plasmid. The production of several virulence factors by the AiiM-expressing strain was examined. Mice were intratracheally infected with an AiiM-expressing PAO1 strain. Lung histopathology, bacterial burden, and bronchoalveolar lavage (BAL) fluid were assessed at 24 h postinfection. AiiM expression in PAO1 reduced production of AHL-mediated virulence factors and attenuated cytotoxicity against human lung epithelial cells. In a mouse model of acute pneumonia, AiiM expression reduced lung injury and greatly improved the survival rates. The levels of proinflammatory cytokines and myeloperoxidase activity in BAL fluid were significantly lower in mice infected with AiiM-expressing PAO1. Thus, AiiM can strongly attenuate P. aeruginosa virulence in a mammalian model and is a potential candidate for use as a therapeutic agent against P. aeruginosa infection

    Tsunami run-up heights of the 2003 Tokachi-oki earthquake

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    Tsunami height survey was conducted immediately after the 2003 Tokachi-oki earthquake. Results of the survey show that the largest tsunami height was 4 m to the east of Cape Erimo, around Bansei-onsen, and locally at Mabiro. The results also show that the tsunami height distribution of the 2003 Tokachi-oki earthquake is clearly different from that of the 1952 Tokachi-oki earthquake, suggesting the different source areas of the 1952 and 2003 Tokachioki earthquakes. Numerical simulation of tsunami is carried out using the slip distribution estimated by Yamanaka and Kikuchi (2003). The overall pattern of the observed tsunami height distribution along the coast is explained by the computed ones although the observed tsunami heights are slightly smaller. Large later phase observed at the tide gauge in Urakawa is the edge wave propagating from Cape Erimo along the west coast of the Hidaka area.The 2003 Tokachi-oki earthquak
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