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Sample records for c-met causing juxtamembrane

  1. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

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    Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

    2014-01-01

    c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  2. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

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    Peyda Korhan

    Full Text Available c-Met, the receptor for Hepatocyte Growth Factor (HGF, overexpressed and deregulated in Hepatocellular Carcinoma (HCC. Caveolin 1 (CAV1, a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  3. Research progress in c-Met and hepatocellular carcinoma

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    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  4. C-MET overexpression and amplification in gliomas.

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    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  5. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

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    Birgit Piater

    Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

  6. Efficacy of c-Met inhibitor for advanced prostate cancer

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    Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

    2010-01-01

    Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  7. Anomalous inhibition of c-Met by the kinesin inhibitor aurintricarboxylic acid.

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    Milanovic, Mina; Radtke, Simone; Peel, Nick; Howell, Michael; Carrière, Virginie; Joffre, Carine; Kermorgant, Stéphanie; Parker, Peter J

    2012-03-01

    c-Met [the hepatocyte growth factor (HGF) receptor] is a receptor tyrosine kinase playing a role in various biological events. Overexpression of the receptor has been observed in a number of cancers, correlating with increased metastatic tendency and poor prognosis. Additionally, activating mutations in c-Met kinase domain have been reported in a subset of familial cancers causing resistance to treatment. Receptor trafficking, relying on the integrity of the microtubule network, plays an important role in activation of downstream targets and initiation of signalling events. Aurintricarboxylic acid (ATA) is a triphenylmethane derivative that has been reported to inhibit microtubule motor proteins kinesins. Additional reported properties of this inhibitor include inhibition of protein tyrosine phosphatases, nucleases and members of the Jak family. Here we demonstrate that ATA prevents HGF-induced c-Met phosphorylation, internalisation, subsequent receptor trafficking and degradation. In addition, ATA prevented HGF-induced downstream signalling which also affected cellular function, as assayed by collective cell migration of A549 cells. Surprisingly, the inhibitory effect of ATA on HGF-induced phosphorylation and signalling in vivo was associated with an increase in basal c-Met kinase activity in vitro. It is concluded that the inhibitory effects of ATA on c-Met in vivo is an allosteric effect mediated through the kinase domain of the receptor. As the currently tested adenosine triphosphate competitive tyrosine kinase inhibitors (TKIs) may lead to tumor resistance (McDermott U, et al., Cancer Res 2010;70:1625-34), our findings suggest that novel anti-c-Met therapies could be developed in the future for cancer treatment. Copyright © 2011 UICC.

  8. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

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    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  9. PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

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    Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

    2009-01-01

    c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

  10. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

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    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  11. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  12. A cytosolic juxtamembrane interface modulates plexin A3 oligomerization and signal transduction.

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    Rachael Barton

    Full Text Available Plexins (plxns are transmembrane (TM receptors involved in the guidance of vascular, lymphatic vessel, and neuron growth as well as cancer metastasis. Plxn signaling results in cytosolic GTPase-activating protein activity, and previous research implicates dimerization as important for activation of plxn signaling. Purified, soluble plxn extracellular and cytosolic domains exhibit only weak homomeric interactions, suggesting a role for the plxn TM and juxtamembrane regions in homooligomerization. In this study, we consider a heptad repeat in the Danio rerio PlxnA3 cytosolic juxtamembrane domain (JM for its ability to influence PlxnA3 homooligomerization in TM-domain containing constructs. Site-directed mutagenesis in conjunction with the AraTM assay and bioluminescent energy transfer (BRET² suggest an interface involving a JM heptad repeat, in particular residue M1281, regulates PlxnA3 homomeric interactions when examined in constructs containing an ectodomain, TM and JM domain. In the presence of a neuropilin-2a co-receptor and semaphorin 3F ligand, disruption to PlxnA3 homodimerization caused by an M1281F mutation is eliminated, suggesting destabilization of the PlxnA3 homodimer in the JM is not sufficient to disrupt co-receptor complex formation. In contrast, enhanced homodimerization of PlxnA3 caused by mutation M1281L remains even in the presence of ligand semaphorin 3F and co-receptor neuropilin-2a. Consistent with this pattern of PlxnA3 dimerization in the presence of ligand and co-receptor, destabilizing mutations to PlxnA3 homodimerization (M1281F are able to rescue motor patterning defects in sidetracked zebrafish embryos, whereas mutations that enhance PlxnA3 homodimerization (M1281L are not. Collectively, our results indicate the JM heptad repeat, in particular residue M1281, forms a switchable interface that modulates both PlxnA3 homomeric interactions and signal transduction.

  13. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

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    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-01-01

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  14. In vivo detection of c-Met expression in a rat C6 glioma model.

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    Towner, R A; Smith, N; Doblas, S; Tesiram, Y; Garteiser, P; Saunders, D; Cranford, R; Silasi-Mansat, R; Herlea, O; Ivanciu, L; Wu, D; Lupu, F

    2008-01-01

    The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T(1) relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal'brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas.

  15. HGF and c-Met Interaction Promotes Migration in Human Chondrosarcoma Cells

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    Tsou, Hsi-Kai; Chen, Hsien-Te; Hung, Ya-Huey; Chang, Chia-Hao; Li, Te-Mao; Fong, Yi-Chin; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway. PMID:23320110

  16. HGF and c-Met interaction promotes migration in human chondrosarcoma cells.

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    Hsi-Kai Tsou

    Full Text Available Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3'-kinase (PI3K/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway.

  17. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.

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    Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade

    2013-11-01

    c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

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    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  19. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

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    Bozkaya Giray

    2012-09-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  20. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

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    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

    c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

  1. Recent advances in the discovery of small molecule c-Met Kinase inhibitors.

    Science.gov (United States)

    Parikh, Palak K; Ghate, Manjunath D

    2018-01-01

    c-Met is a prototype member of a subfamily of heterodimeric receptor tyrosine kinases (RTKs) and is the receptor for hepatocyte growth factor (HGF). Binding of HGF to its receptor c-Met, initiates a wide range of cellular signalling, including those involved in proliferation, motility, migration and invasion. Importantly, dysregulated HGF/c-Met signalling is a driving factor for numerous malignancies and promotes tumour growth, invasion, dissemination and/or angiogenesis. Dysregulated HGF/c-Met signalling has also been associated with poor clinical outcomes and resistance acquisition to some approved targeted therapies. Thus, c-Met kinase has emerged as a promising target for cancer drug development. Different therapeutic approaches targeting the HGF/c-Met signalling pathway are under development for targeted cancer therapy, among which small molecule inhibitors of c-Met kinase constitute the largest effort within the pharmaceutical industry. The review is an effort to summarize recent advancements in medicinal chemistry development of small molecule c-Met kinase inhibitors as potential anti-cancer agents which would certainly help future researchers to bring further developments in the discovery of small molecule c-Met kinase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Husmann, Knut, E-mail: khusmann@research.balgrist.ch [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Ducommun, Pascal [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Division of Plastic Surgery and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich (Switzerland); Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland)

    2015-09-04

    The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

  3. {sup 89}Zr-Onartuzumab PET imaging of c-MET receptor dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Pool, Martin; Kol, Arjan; Giesen, Danique; Vries, Elisabeth G.E. de [University of Groningen, Department of Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Terwisscha van Scheltinga, Anton G.T. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); Lub-de Hooge, Marjolijn N. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands)

    2017-08-15

    c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of {sup 89}Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent {sup 89}Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent {sup 89}Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, {sup 89}Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that {sup 89}Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. (orig.)

  4. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Granito A

    2015-04-01

    Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

  5. c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

    Science.gov (United States)

    Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2018-03-02

    Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

    Science.gov (United States)

    Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

    2018-06-01

    Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

  7. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  8. Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

    Science.gov (United States)

    Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

    2014-06-14

    A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

  9. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  10. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J. (Merck)

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

  11. Activated HGF-c-Met Axis in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Levi Arnold

    2017-12-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a highly morbid disease. Recent developments including Food and Drug Administration (FDA approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met and its ligand hepatocyte growth factor (HGF are overexpressed in head and neck squamous cell carcinoma (HNSCC; and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ, cellular Src kinase (c-Src, phosphotidylinsitol-3-OH kinase (PI3K alpha serine/threonine-protein kinase (Akt, mitogen activate protein kinase (MAPK, and wingless-related integration site (Wnt pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes.

  12. Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies.

    Science.gov (United States)

    Qamsari, Elmira Safaie; Sharifzadeh, Zahra; Bagheri, Salman; Riazi-Rad, Farhad; Younesi, Vahid; Abolhassani, Mohsen; Ghaderi, Sepideh Safaei; Baradaran, Behzad; Somi, Mohammad Hossein; Yousefi, Mehdi

    2017-12-01

    The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers.

  13. Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

    Science.gov (United States)

    Kwon, Youngjoo; Godwin, Andrew K

    2017-04-01

    Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

  14. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    Science.gov (United States)

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  15. 11C-MET PET/MRI for detection of recurrent glioma.

    Science.gov (United States)

    Deuschl, C; Kirchner, J; Poeppel, T D; Schaarschmidt, B; Kebir, S; El Hindy, N; Hense, J; Quick, H H; Glas, M; Herrmann, K; Umutlu, L; Moenninghoff, C; Radbruch, A; Forsting, M; Schlamann, M

    2018-04-01

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11 C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11 C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11 C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid 11 C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11 C-MET PET (96.77% and 73.68%), and for hybrid 11 C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11 C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11 C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid PET/MRI might strengthen

  16. {sup 11}C-MET PET/MRI for detection of recurrent glioma

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, C. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Kirchner, J.; Schaarschmidt, B. [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Poeppel, T.D.; Herrmann, K. [University Hospital Essen, Clinic for Nuclear Medicine, Essen (Germany); Kebir, S.; Glas, M. [University Hospital Essen, Division of Clinical Neurooncology, Department of Neurology, Essen (Germany); El Hindy, N. [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Hense, J. [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Quick, H.H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Umutlu, L.; Moenninghoff, C.; Radbruch, A.; Forsting, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schlamann, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Cologne, Department of Diagnostic and Interventional Radiology, Cologne (Germany)

    2018-04-15

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid {sup 11}C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid {sup 11}C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid {sup 11}C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid {sup 11}C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for {sup 11}C-MET PET (96.77% and 73.68%), and for hybrid {sup 11}C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid {sup 11}C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing {sup 11}C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid

  17. Salvianolic acid A reverses cisplatin resistance in lung cancer A549 cells by targeting c-met and attenuating Akt/mTOR pathway.

    Science.gov (United States)

    Tang, Xia-Li; Yan, Li; Zhu, Ling; Jiao, De-Min; Chen, Jun; Chen, Qing-Yong

    2017-09-01

    Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC) treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin. Moreover, we revealed that SAA enhanced sensitivity to cisplatin in A549/DDP cells mainly through suppression of the c-met/AKT/mTOR signaling pathway. Knockdown of c-met revealed similar effects as that of SAA in A549/DDP cells. In addition, SAA effectively prevented multidrug resistance associated protein1 (MDR1) up-regulation in A549/DDP cells. Taken together, our results indicated that SAA suppressed c-met expression and enhanced the sensitivity of lung adenocarcinoma A549 cells to cisplatin through AKT/mTOR signaling pathway. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  18. Salvianolic acid A reverses cisplatin resistance in lung cancer A549 cells by targeting c-met and attenuating Akt/mTOR pathway

    Directory of Open Access Journals (Sweden)

    Xia-li Tang

    2017-09-01

    Full Text Available Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP and the reversal mechanism of salvianolic acid A (SAA, a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin. Moreover, we revealed that SAA enhanced sensitivity to cisplatin in A549/DDP cells mainly through suppression of the c-met/AKT/mTOR signaling pathway. Knockdown of c-met revealed similar effects as that of SAA in A549/DDP cells. In addition, SAA effectively prevented multidrug resistance associated protein1 (MDR1 up-regulation in A549/DDP cells. Taken together, our results indicated that SAA suppressed c-met expression and enhanced the sensitivity of lung adenocarcinoma A549 cells to cisplatin through AKT/mTOR signaling pathway.

  19. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Science.gov (United States)

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  20. The applications of 11C-MET PET in brain tumor

    International Nuclear Information System (INIS)

    Hua Fengchun

    2002-01-01

    11 C-methionine (MET), an amino acid, is the most widely used radio pharmaceutics which can reflect transport metabolism of amino acid in vivo, and synthesis of protein in tumor. 11 C-MET PET can be used for evaluation of brain tumor: detection of tumor, differential diagnosis between recurrence and radiation necrosis and early evaluation of response to treatment. Especially, for the definition of tumor margin and detection of low-grade tumors, PET with 11 C-MET is better than PET with 18 F-FDG or other modalities such as CT and MRI

  1. Activation of c-MET induces a stem-like phenotype in human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Geert J L H van Leenders

    Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

  2. De interactie van SiC met Fe, Ni en hun legeringen

    NARCIS (Netherlands)

    Schiepers, R.C.J.

    1991-01-01

    De interactie tussen SiC en metalen gebaseerd op Fe en Ni is bestudeerd in het temperatuurtraject 700-1035°C door middel van vaste-stof-diffusiekoppels. In de koppels van SiC met Fe, Ni en hun legeringen treden hevige reakties op, die de vorming van een goede verbinding verhinderen. Door het grate

  3. Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

    Science.gov (United States)

    Yang, Yifei; Zhang, Yuan; Yang, LingYun; Zhao, Leilei; Si, Lianghui; Zhang, Huibin; Liu, Qingsong; Zhou, Jinpei

    2017-02-01

    Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC 50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment. Copyright © 2016. Published by Elsevier Inc.

  4. A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions.

    Directory of Open Access Journals (Sweden)

    Haguy Wolfenson

    Full Text Available Focal adhesions (FAs are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization.

  5. ADAM10/17-Dependent Release of Soluble c-Met Correlates with Hepatocellular Damage

    Czech Academy of Sciences Publication Activity Database

    Chalupský, Karel; Kanchev, Ivan; Žbodáková, Olga; Buryová, Halka; Jiroušková, Markéta; Kořínek, Vladimír; Gregor, Martin; Sedláček, Radislav

    2013-01-01

    Roč. 59, č. 2 (2013), s. 76-78 ISSN 0015-5500 R&D Projects: GA ČR GAP305/10/2143; GA ČR GAP303/10/2044; GA AV ČR IAA500520812 Institutional support: RVO:68378050 Keywords : c-Met * HGF * shedding * ADAM metalloproteinase * liver Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.778, year: 2013

  6. Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

    Science.gov (United States)

    Xu, Chuanhui; Plattel, Wouter; van den Berg, Anke; Rüther, Nele; Huang, Xin; Wang, Miao; de Jong, Debora; Vos, Hans; van Imhoff, Gustaaf; Viardot, Andreas; Möller, Peter; Poppema, Sibrand; Diepstra, Arjan; Visser, Lydia

    2012-04-01

    The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte growth factor protein expression in patients with classical Hodgkin's lymphoma. Expression of c-Met and its ligand, hepatocyte growth factor, were determined by immunohistochemistry. Prognostic values were defined in cohorts of German and Dutch patients with classical Hodgkin's lymphoma. Functional studies were performed on Hodgkin's lymphoma cell lines. Expression of c-Met was detected in the tumor cells of 52% (80/153) of the patients and expression of its ligand, hepatocyte growth factor, in 8% (10/121) of the patients. c-Met expression correlated with a 5-year freedom from tumor progression of 94%, whereas lack of expression correlated with a 5-year freedom from tumor progression of 73% (Pfreedom from tumor progression. In functional studies activation with hepatocyte growth factor did not affect cell growth, while the c-Met inhibitor SU11274 suppressed cell growth by inducing G2/M cell cycle arrest. Although functional studies showed an oncogenic role of the hepatocyte growth factor/c-Met signaling pathway in cell cycle progression, expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts.

  7. Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer.

    Science.gov (United States)

    Duan, Jianchun; Yang, Xiaodan; Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; An, Tongtong; Bai, Hua; Wang, Jie

    2018-01-05

    The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive. Among patients with IHC 2+ staining, 35.5% was FISH positive, while cases with IHC 3+ staining,64% was FISH positive. Both protein expression and copy number of c-MET did not significantly correlate with clinical prognosis in these patients treated with EGFR-TKIs. IHC could be used as a preliminary screening method for c-MET copy number amplification and should be confirmed by FISH only in IHC positive case which facilitate selection of ALK or MET inhibitor therapy. c-MET gene copy number, protein expression and somatic mutation for exon 14 were detected by fluorescent- In-Situ -Hybridization (FISH), Immunohistochemistry (IHC), and Denaturing-High-Performance-Liquid-Chromatography (DHPLC), respectively, in 196 NSCLC patients. The relationship between c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar's test.

  8. Phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin.

    Science.gov (United States)

    Miyata, Yasuyoshi; Sagara, Yuji; Kanda, Shigeru; Hayashi, Tomayoshi; Kanetake, Hiroshi

    2009-04-01

    Hepatocyte growth factor receptor/c-Met is associated with malignant aggressiveness and survival in various cancers including bladder cancer. Although phosphorylation of hepatocyte growth factor receptor/c-Met is essential for its function, the pathologic significance of phosphorylated hepatocyte growth factor receptor/c-Met in bladder cancer remains elusive. We investigated the clinical significance of its expression, and its correlation with cancer cell progression-related molecules. The expression levels of 2 tyrosine residues of hepatocyte growth factor receptor/c-Met (pY1234/1235 and pY1349) were examined immunohistochemically in 133 specimens with nonmetastatic bladder cancer. We also investigated their correlation with matrix metalloproteinase-1, -2, -7, and -14; urokinase-type plasminogen activator; E-cadherin; CD44 standard, variant 3, and variant 6; and vascular endothelial growth factor. Expression of phosphorylated hepatocyte growth factor receptor/c-Met was detected in cancer cells, but was rare in normal urothelial cells. Although hepatocyte growth factor receptor/c-Met, pY1234/1235 hepatocyte growth factor receptor/c-Met, and pY1349 hepatocyte growth factor receptor/c-Met were associated with pT stage, multivariate analysis identified pY1349 hepatocyte growth factor receptor/c-met expression only as a significant factor for high pT stage. Expression of pY1349 hepatocyte growth factor receptor/c-Met was a marker of metastasis and (P = .001) and cause-specific survival (P = .003). Expressions of matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin correlated with pY1349 hepatocyte growth factor receptor/c-Met expression. Our results demonstrated that pY1349 hepatocyte growth factor receptor/c-Met plays an important role in tumor development, and its expression is a significant predictor of metastasis and survival of patients with bladder cancer. The results suggest that these activities are mediated, at least in part, by matrix

  9. In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.

    Science.gov (United States)

    Towner, Rheal A; Smith, Nataliya; Tesiram, Yasvir A; Abbott, Andrew; Saunders, Debbie; Blindauer, Rebecca; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

    2007-01-01

    The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  10. In Vivo Detection of c-MET Expression in a Rat Hepatocarcinogenesis Model Using Molecularly Targeted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Rheal A. Towner

    2007-01-01

    Full Text Available The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO–anti-c-MET molecularly targeted magnetic resonance imaging (MRI contrast agent. SPIO–anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T2 values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3 cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO–anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  11. Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma

    NARCIS (Netherlands)

    Fieten, H; Spee, B; Ijzer, J; Kik, M J; Penning, L C; Kirpensteijn, J

    Hepatocyte growth factor (HGF) and the proto-oncogenic receptor c-Met are implicated in growth, invasion, and metastasis in human cancer. Little information is available on the expression and role of both gene products in canine osteosarcoma. We hypothesized that the expression of c-Met is

  12. Development of antibody-based c-Met inhibitors for targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Lee D

    2015-02-01

    Full Text Available Dongheon Lee, Eun-Sil Sung, Jin-Hyung Ahn, Sungwon An, Jiwon Huh, Weon-Kyoo You Hanwha Chemical R&D Center, Biologics Business Unit, Daejeon, Republic of Korea Abstract: Signaling pathways mediated by receptor tyrosine kinases (RTKs and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics. Keywords: hepatocyte growth factor, ligands, receptor tyrosine kinase, signaling pathway, therapeutic agent

  13. Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression.

    Science.gov (United States)

    Walter, Beatriz A; Begnami, Maria; Valera, Vladimir A; Santi, Mariarita; Rushing, Elisabeth J; Quezado, Martha

    2011-01-01

    Chordomas are low to intermediate grade malignancies that arise from remnants of embryonic notochord. They often recur after surgery and are highly resistant to conventional adjuvant therapies. Recently, the development of effective targeted molecular therapy has been investigated in chordomas that show receptors for tyrosine kinase (RTKs) activation. Expression of specific RTKs such as Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial transition factor (c-MET) in chordomas may offer valuable therapeutic options. We investigated changes in copy number of chromosome 7 and correlated it with EGFR gene status and EGFR and c-MET protein expression in 22 chordoma samples. Chromosome 7 copy number was evaluated by chromogenic in situ hybridization (CISH) and protein expression of EGFR and c-MET by immunohistochemistry. Tumors mostly showed conventional histopathologic features and were found mainly in sacral (41%) and cranial sites (54.5%). Aneusomy of chromosome 7 was seen in 73% of the samples, 62% of primary tumors and in all recurrent chordomas. EGFR and c-MET were both expressed, but only c-MET protein expression was significantly correlated with chromosome 7 aneusomy (P ≤ 0.001). c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis. c-MET overexpression shows promise as a molecular marker of response to targeted molecular therapy in the treatment of chordomas.

  14. Combination Therapy with c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells.

    Science.gov (United States)

    Fuse, Marisa A; Plati, Stephani Klingeman; Burns, Sarah S; Dinh, Christine T; Bracho, Olena; Yan, Denise; Mittal, Rahul; Shen, Rulong; Soulakova, Julia N; Copik, Alicja J; Liu, Xue Zhong; Telischi, Fred F; Chang, Long-Sheng; Franco, Maria Clara; Fernandez-Valle, Cristina

    2017-11-01

    Neurofibromatosis type 2 (NF2) is a nervous system tumor disorder caused by inactivation of the merlin tumor suppressor encoded by the NF2 gene. Bilateral vestibular schwannomas are a diagnostic hallmark of NF2. Mainstream treatment options for NF2-associated tumors have been limited to surgery and radiotherapy; however, off-label uses of targeted molecular therapies are becoming increasingly common. Here, we investigated drugs targeting two kinases activated in NF2-associated schwannomas, c-Met and Src. We demonstrated that merlin-deficient mouse Schwann cells (MD-MSC) treated with the c-Met inhibitor, cabozantinib, or the Src kinase inhibitors, dasatinib and saracatinib, underwent a G 1 cell-cycle arrest. However, when MD-MSCs were treated with a combination of cabozantinib and saracatinib, they exhibited caspase-dependent apoptosis. The combination therapy also significantly reduced growth of MD-MSCs in an orthotopic allograft mouse model by greater than 80% of vehicle. Moreover, human vestibular schwannoma cells with NF2 mutations had a 40% decrease in cell viability when treated with cabozantinib and saracatinib together compared with the vehicle control. This study demonstrates that simultaneous inhibition of c-Met and Src signaling in MD-MSCs triggers apoptosis and reveals vulnerable pathways that could be exploited to develop NF2 therapies. Mol Cancer Ther; 16(11); 2387-98. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. cMET in NSCLC: Can We Cut off the Head of the Hydra? From the Pathway to the Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Steen, Nele [Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, Wilrijk 2610 (Belgium); Pauwels, Patrick [Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, Wilrijk 2610 (Belgium); Molecular Pathology Unit, Pathology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650 (Belgium); Gil-Bazo, Ignacio [Department of Oncology, Clínica Universidad de Navarra, Pamplona 31008 (Spain); Castañon, Eduardo [Department of Oncology, Clínica Universidad de Navarra, Pamplona 31008 (Spain); Phase I-Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650 (Belgium); Raez, Luis [Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, FL 33024 (United States); Cappuzzo, Federico [4Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, FL 33024 (United States); Rolfo, Christian, E-mail: Christian.Rolfo@uza.be [Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, Wilrijk 2610 (Belgium); Phase I-Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650 (Belgium)

    2015-03-25

    In the last decade, the tyrosine kinase receptor cMET, together with its ligand hepatocyte growth factor (HGF), has become a target in non-small cell lung cancer (NSCLC). Signalization via cMET stimulates several oncological processes amongst which are cell motility, invasion and metastasis. It also confers resistance against several currently used targeted therapies, e.g., epidermal growth factor receptor (EGFR) inhibitors. In this review, we will discuss the basic structure of cMET and the most important signaling pathways. We will also look into aberrations in the signaling and the effects thereof in cancer growth, with the focus on NSCLC. Finally, we will discuss the role of cMET as resistance mechanism.

  16. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

    Science.gov (United States)

    Sotoudeh, Kambiz; Hashemi, Forough; Madjd, Zahra; Sadeghipour, Alireza; Molanaei, Saadat; Kalantary, Elham

    2012-05-28

    c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

  17. A basic peptide within the juxtamembrane region is required for EGF receptor dimerization.

    Science.gov (United States)

    Aifa, Sami; Aydin, Jan; Nordvall, Gunnar; Lundström, Ingemar; Svensson, Samuel P S; Hermanson, Ola

    2005-01-01

    The epidermal growth factor receptor (EGFR) is fundamental for normal cell growth and organ development, but has also been implicated in various pathologies, notably tumors of epithelial origin. We have previously shown that the initial 13 amino acids (P13) within the intracellular juxtamembrane region (R645-R657) are involved in the interaction with calmodulin, thus indicating an important role for this region in EGFR function. Here we show that P13 is required for proper dimerization of the receptor. We expressed either the intracellular domain of EGFR (TKJM) or the intracellular domain lacking P13 (DeltaTKJM) in COS-7 cells that express endogenous EGFR. Only TKJM was immunoprecipitated with an antibody directed against the extracellular part of EGFR, and only TKJM was tyrosine phosphorylated by endogenous EGFR. Using SK-N-MC cells, which do not express endogenous EGFR, that were stably transfected with either wild-type EGFR or recombinant full-length EGFR lacking P13 demonstrated that P13 is required for appropriate receptor dimerization. Furthermore, mutant EGFR lacking P13 failed to be autophosphorylated. P13 is rich in basic amino acids and in silico modeling of the EGFR in conjunction with our results suggests a novel role for the juxtamembrane domain (JM) of EGFR in mediating intracellular dimerization and thus receptor kinase activation and function.

  18. Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

    Science.gov (United States)

    Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

    2007-02-01

    Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

  19. The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Luis J. Herrera

    2005-01-01

    Full Text Available The hepatocyte growth factor (HGF receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE, and normal esophagus (NE using immunohistochemistry (IHC and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100% EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.

  20. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Science.gov (United States)

    Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

    2013-01-01

    We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  1. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Directory of Open Access Journals (Sweden)

    Peizhen Hu

    Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  2. Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent.

    Science.gov (United States)

    Kim, Eun-Mi; Joung, Min-Hee; Lee, Chang-Moon; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Kim, Dong Wook

    2010-07-15

    The mesenchymal-epithelial transition factor (c-Met), which is related to tumor cell growth, angiogenesis and metastases, is known to be overexpressed in several tumor types. In this study, we synthesized technetium-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP) derivatives, prepared by solid phase peptide synthesis and the 'click-to-chelate' protocol for the introduction of tricarbonyl technetium-99m, as a potential c-Met receptor kinase positive tumor imaging agent, and evaluated their in vitro c-Met binding affinity, cellular uptake, and stability. The (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12, [(99m)Tc(CO)(3)]13, and [(99m)Tc(CO)(3)]14) were prepared in 85-90% radiochemical yields. The cold surrogate cMBP derivatives, [Re(CO)(3)]12, [Re(CO)(3)]13, and [Re(CO)(3)]14, were shown to have high binding affinities (0.13 microM, 0.06 microM, and 0.16 microM, respectively) to a purified cMet/Fc chimeric recombinant protein. In addition, the in vitro cellular uptake and inhibition studies demonstrated the high specific binding of these (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12-14) to c-Met receptor positive U87MG cells. 2010 Elsevier Ltd. All rights reserved.

  3. Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and human hepatocarcinogenesis.

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    Lee, Susie A; Ladu, Sara; Evert, Matthias; Dombrowski, Frank; De Murtas, Valentina; Chen, Xin; Calvisi, Diego F

    2010-08-01

    Sprouty2 (Spry2), a negative feedback regulator of the Ras/mitogen-activated protein kinase (MAPK) pathway, is frequently down-regulated in human hepatocellular carcinoma (HCC). We tested the hypothesis that loss of Spry2 cooperates with unconstrained activation of the c-Met protooncogene to induce hepatocarcinogenesis via in vitro and in vivo approaches. We found coordinated down-regulation of Spry2 protein expression and activation of c-Met as well as its downstream effectors extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) in a subset of human HCC samples with poor outcome. Mechanistic studies revealed that Spry2 function is disrupted in human HCC via multiple mechanisms at both transcriptional and post-transcriptional level, including promoter hypermethylation, loss of heterozygosity, and proteosomal degradation by neural precursor cell expressed, developmentally down-regulated 4 (NEDD4). In HCC cell lines, Spry2 overexpression inhibits c-Met-induced cell proliferation as well as ERK and AKT activation, whereas loss of Spry2 potentiates c-Met signaling. Most importantly, we show that blocking Spry2 activity via a dominant negative form of Spry2 cooperates with c-Met to promote hepatocarcinogenesis in the mouse liver by sustaining proliferation and angiogenesis. The tumors exhibited high levels of activated ERK and AKT, recapitulating the subgroup of human HCC with a clinically aggressive phenotype. The occurrence of frequent genetic, epigenetic, and biochemical events leading to Spry2 inactivation provides solid evidence that Spry2 functions as a tumor suppressor gene in liver cancer. Coordinated deregulation of Spry2 and c-Met signaling may be a pivotal oncogenic mechanism responsible for unrestrained activation of ERK and AKT pathways in human hepatocarcinogenesis.

  4. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

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    Sotoudeh Kambiz

    2012-05-01

    Full Text Available Abstract Background c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. Methods In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Results Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124 of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04, deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014, neural invasion (P = 0.002 and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044. The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065 and vascular invasion (P = 0.078 were observed. Conclusions c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429

  5. MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met.

    Science.gov (United States)

    Korhan, Peyda; Erdal, Esra; Atabey, Neşe

    2014-08-08

    c-Met receptor tyrosine kinase has been regarded as a promising therapeutic target for hepatocellular carcinoma (HCC). Recently, microRNAs (miRNAs) have been shown as a novel mechanism to control c-Met expression in cancer. In this study, we investigate the potential contribution of miR-181a-5p dysregulation to the biology of c-Met overexpression in HCC. Herein, we found an inverse expression pattern between miR-181a-5p and c-Met expression in normal, cirrhotic and HCC liver tissues. Luciferase assay confirmed that miR-181a-5p binding to the 3'-UTR of c-Met downregulated the expression of c-Met in HCC cells. Overexpression of miR-181a-5p suppressed both HGF-independent and -dependent activation of c-Met and consequently diminished branching-morphogenesis and invasion. Combined treatment with miR-181a-5p and c-Met inhibitor led to a further inhibition of c-Met-driven cellular activities. Knockdown of miR-181a-5p promoted HGF-independent/-dependent signaling of c-Met and accelerated migration, invasion and branching-morphogenesis. In conclusion, our results demonstrated for the first time that c-Met is a functional target gene of miR-181a-5p and the loss of miR-181a-5p expression led to the activation of c-Met-mediated oncogenic signaling in hepatocarcinogenesis. These findings display a novel molecular mechanism of c-Met regulation in HCC and strategies to increase miR-181a5p level might be an alternative approach for the enhancement of the inhibitory effects of c-Met inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Comparative evaluation of 11C-MET PET-CT and MRI for GTV delineation in precision radiotherapy for gliomas

    International Nuclear Information System (INIS)

    Wang Ru; Qian Liting; Wang Shicun; Liu Wei; Luo Wenguang; Zhang Hongbo; Li Guanghu; Hu Zhigang; Liu Lei

    2014-01-01

    Objective: To evaluate the difference between MRI and 11 C-MET PET-CT for gross tumor volume (GTV) delineation in the precision radiotherapy for gliomas. Methods: Six patients with a pathologically confirmed diagnosis of gliomas were selected for target delineation. Five physicians in our department were called to delineate the GTV based on the preoperative MRI and 11 C-MET PET-CT images of these patients. The GTVs based on the two methods were compared. Results: There was no significant difference between the GTVs based on MRI and 11 C-MET PET-CT (P=0.917), and their coefficients of variation were also similar (P=0.600). The coincidences of GTVs were different among the patients, with a maximum value of 73.0% and a minimum value of 51.8%. GTV showed no significant difference when defined by different physicians on MRI and PET-CT (P=0.709); the biggest difference was 27.66 cm 3 on PET-CT and 40.37 cm 3 on MRI. Conclusions: The boundaries of gliomas defined on MRI and PET-CT are different. The GTVs delineated by different physicians on MRI and PET-CT are similar, and the biggest difference on PET-CT is smaller than that on MRI, which suggests that 11 C-MET PET-CT is a more direct way for displaying GTV. (authors)

  7. Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies.

    Science.gov (United States)

    Aliebrahimi, Shima; Montasser Kouhsari, Shideh; Ostad, Seyed Nasser; Arab, Seyed Shahriar; Karami, Leila

    2018-06-01

    c-Met receptor tyrosine kinase is a proto-oncogene whose aberrant activation is attributed to a lower rate of survival in most cancers. Natural product-derived inhibitors known as "fourth generation inhibitors" constitute more than 60% of anticancer drugs. Furthermore, consensus docking approach has recently been introduced to augment docking accuracy and reduce false positives during a virtual screening. In order to obtain novel small-molecule Met inhibitors, consensus docking approach was performed using Autodock Vina and Autodock 4.2 to virtual screen Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database against active and inactive conformation of c-Met kinase domain structure. Two hit molecules that were in line with drug-likeness criteria, desired docking score, and binding pose were subjected to molecular dynamics simulations to elucidate intermolecular contacts in protein-ligand complexes. Analysis of molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area studies showed that ZINC08234189 is a plausible inhibitor for the active state of c-Met, whereas ZINC03871891 may be more effective toward active c-Met kinase domain compared to the inactive form due to higher binding energy. Our analysis showed that both the hit molecules formed hydrogen bonds with key residues of the hinge region (P1158, M1160) in the active form, which is a hallmark of kinase domain inhibitors. Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to surmount Met-dependent cancers.

  8. Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress

    International Nuclear Information System (INIS)

    Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gaiser, Timo; Gillen, Matthew; Lee, Seung-Bum; Gutierrez-Ruiz, Ma Concepcion; Conner, Elizabeth A.; Factor, Valentina M; Thorgeirsson, Snorri S.; Marquardt, Jens U.

    2016-01-01

    Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity.

  9. The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

    International Nuclear Information System (INIS)

    Vu, Hoang Anh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2009-01-01

    We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.

  10. Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

    Science.gov (United States)

    Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

    2017-11-28

    In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

  11. RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements

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    Iván Plaza-Menacho

    2016-12-01

    Full Text Available Receptor tyrosine kinases exhibit a variety of activation mechanisms despite highly homologous catalytic domains. Such diversity arises through coupling of extracellular ligand-binding portions with highly variable intracellular sequences flanking the tyrosine kinase domain and specific patterns of autophosphorylation sites. Here, we show that the juxtamembrane (JM segment enhances RET catalytic domain activity through Y687. This phospho-site is also required by the JM region to rescue an otherwise catalytically deficient RET activation-loop mutant lacking tyrosines. Structure-function analyses identified interactions between the JM hinge, αC helix, and an unconventional activation-loop serine phosphorylation site that engages the HRD motif and promotes phospho-tyrosine conformational accessibility and regulatory spine assembly. We demonstrate that this phospho-S909 arises from an intrinsic RET dual-specificity kinase activity and show that an equivalent serine is required for RET signaling in Drosophila. Our findings reveal dual-specificity and allosteric components for the mechanism of RET activation and signaling with direct implications for drug discovery.

  12. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

    Science.gov (United States)

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-07-22

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.

  13. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

    Science.gov (United States)

    Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

    2017-08-01

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

  14. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    Science.gov (United States)

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  15. Hepatocyte Growth Factor-c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing.

    Science.gov (United States)

    Shibata, Shumei; Miwa, Toru; Wu, Hsiao-Huei; Levitt, Pat; Ohyama, Takahiro

    2016-08-03

    The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies. We found the roles of hepatocyte growth factor (HGF) signaling in stria vascularis development for the first time and that lack of HGF signaling in the inner ear leads to profound hearing loss in the mouse. Our findings reveal a novel mechanism that may underlie human deafness DFNB39 and DFNB97. Our findings reveal an additional example of context-dependent c-MET signaling diversity, required here for proper cellular invasion developmentally that is essential for specific aspects of auditory-related organogenesis. Copyright © 2016 the authors 0270-6474/16/368200-10$15.00/0.

  16. Hepatocyte Growth Factor–c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing

    Science.gov (United States)

    Shibata, Shumei; Miwa, Toru; Wu, Hsiao-Huei; Levitt, Pat

    2016-01-01

    The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies. SIGNIFICANCE STATEMENT We found the roles of hepatocyte growth factor (HGF) signaling in stria vascularis development for the first time and that lack of HGF signaling in the inner ear leads to profound hearing loss in the mouse. Our findings reveal a novel mechanism that may underlie human deafness DFNB39 and DFNB97. Our findings reveal an additional example of context-dependent c-MET signaling diversity, required here for proper cellular invasion developmentally that is essential for specific aspects of auditory-related organogenesis. PMID:27488639

  17. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, Cornelius [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); Moenninghoff, Christoph; Goericke, Sophia; Forsting, Michael; Umutlu, Lale [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kirchner, Julian [University Hospital Duesseldorf, Institute of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Koeppen, Susanne [University Hospital Essen, Department of Neurology, Essen (Germany); Binse, Ina; Poeppel, Thorsten D.; Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Hense, Joerg [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Schlamann, Marc [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Giessen, Department of Neuroradiology, Essen (Germany)

    2017-08-15

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM. (orig.)

  18. Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives as potential c-met inhibitors.

    Science.gov (United States)

    Zhao, Sijia; Zhang, Yu; Zhou, Hongyang; Xi, Shuancheng; Zou, Bin; Bao, Guanglong; Wang, Limei; Wang, Jiao; Zeng, Tianfang; Gong, Ping; Zhai, Xin

    2016-09-14

    Six series of novel 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c-Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c-Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure.

    Science.gov (United States)

    Wang, Kun; Li, Yuwen; Zhu, Tiantian; Zhang, Yongting; Li, Wenting; Lin, Wenyu; Li, Jun; Zhu, Chuanlong

    2017-07-05

    Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF. Overexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs). After cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs. Overexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.

  20. Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz

    2014-09-01

    Full Text Available Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor-targeted therapy has been used in the treatment of LC (lung cancer, mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(PH:quinone oxidoreductase, also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin in 108 patients with non-small cell lung carcinoma (NSCLC. NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1 oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2 selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3 since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke.

  1. Mechanism of c-Met and EGFR tyrosine kinase inhibitor resistance through epithelial mesenchymal transition in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Ichwaku; Rajanna, Supriya; Webb, Andrew; Chhabra, Gagan; Foster, Brad [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Illinois (United States); Webb, Brian [Thermo Fisher Scientific, Rockford, Illinois (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Illinois (United States)

    2016-09-02

    According to currently available estimates from Cancer Research UK, 14.1 million new lung cancer cases were diagnosed and a staggering 8.2 million people worldwide died from lung cancer in 2012. EGFR and c-Met are two tyrosine kinase receptors most commonly overexpressed or mutated in Non-small Cell Lung Cancer (NSCLC) resulting in increased proliferation and survival of lung cancer cells. Tyrosine kinase inhibitors (TKIs), such as erlotinib, approved by the FDA as first/second line therapy for NSCLC patients have limited clinical efficacy due to acquired resistance. In this manuscript, we investigate and discuss the role of epithelial mesenchymal transition (EMT) in the development of resistance against EGFR and c-Met TKIs in NSCLC. Our findings show that Zeb-1, a transcriptional repressor of E-Cadherin, is upregulated in TKI-resistant cells causing EMT. We observed that TKI-resistant cells have increased gene and protein expression of EMT related proteins such as Vimentin, N-Cadherin, β-Catenin and Zeb-1, while expression of E-Cadherin, an important cell adhesion molecule, was suppressed. We also confirmed that TKI-resistant cells display mesenchymal cell type morphology, and have upregulation of β-Catenin which may regulate expression of Zeb-1, a transcriptional repressor of E-Cadherin in TKI-resistant NSCLC cells. Finally, we show that down-regulating Zeb-1 by inducing miR-200a or β-Catenin siRNA can increase drug sensitivity of TKI-resistant cells. - Highlights: • Resistance to TKIs in NSCLC cells is mediated via modulation in EMT related proteins. • EMT may induce c-Met mediated TKI resistance, similar to EGFR TKI resistance. • Role of β-catenin and cadherins in TKI resistance was validated by FACS and qPCR. • Knockdown of β-catenin or Zeb-1 can increase TKI sensitivity in TKI-resistant cells. • Targeting key EMT related proteins may overcome TKI resistance in NSCLC.

  2. Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

    Science.gov (United States)

    Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

    2018-06-01

    Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

    Science.gov (United States)

    Kumar, Gaurav; Moussa, Marwan; Wang, Yuanguo; Rozenblum, Nir; Galun, Eithan; Goldberg, S. Nahum

    2016-01-01

    Purpose To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Materials and Methods Rats were used in this institutional animal care and use committee–approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met–negative R3230 tumors for comparison with the native c-Met–positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. Results After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor

  4. YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

    Science.gov (United States)

    Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

    2015-01-01

    Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, prectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

  5. A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

    Science.gov (United States)

    2018-01-29

    Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

  6. Development of a Novel SPECT Tracer to Image c-Met Expression in Non-Small Cell Lung Cancer in a Human Tumor Xenograft.

    Science.gov (United States)

    Han, Zhaoguo; Xiao, Yadi; Wang, Kai; Yan, Ji; Xiao, Zunyu; Fang, Fang; Jin, Zhongnan; Liu, Yang; Sun, Xilin; Shen, Baozhong

    2018-05-18

    Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99m Tc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging. Cell uptake assays were performed on two NSCLC cell lines with different c-Met expression: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2 and 4 h after injection of the probe. Blocking assays, biodistribution and autoradiography were also conducted to determine probe specificity. Results: 99m Tc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than H1299 cells. Biodistribution and autoradiography also showed significantly higher accumulation of 99m Tc-HYNIC-cMBP in H1993 tumors than H1299 (H1993: 4.74±1.43 %ID/g and H1299: 1.00±0.37 %ID/g at 0.5h, pc-Met was demonstrated by competitive block with excess un-radiolabeled peptide. Conclusion: We developed a novel SPECT tracer, 99m Tc-HYNIC-cMBP, for c-Met-targeted imaging in NSCLC that specifically bound to c-Met with favorable pharmacokinetics in vitro and in vivo. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  7. Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

    International Nuclear Information System (INIS)

    Yeh, Chen-Yun; Tseng, Vincent S; Lee, Yuan-Chii G; Shen, Cheng-Huang; Chow, Nan-Haw; Liu, Hsiao-Sheng; Shin, Shin-Mei; Yeh, Hsuan-Heng; Wu, Tsung-Jung; Shin, Jyh-Wei; Chang, Tsuey-Yu; Raghavaraju, Giri; Lee, Chung-Ta; Chiang, Jung-Hsien

    2011-01-01

    A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers. Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p < 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p < 0.01). In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy

  8. Genetic Nrf2 Overactivation Inhibits the Deleterious Effects Induced by Hepatocyte-Specific c-met Deletion during the Progression of NASH

    Directory of Open Access Journals (Sweden)

    Pierluigi Ramadori

    2017-01-01

    Full Text Available We have recently shown that hepatocyte-specific c-met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting in augmented production of reactive oxygen species and accelerated development of fibrosis. The aim of this study focuses on the elucidation of the underlying cellular mechanisms driven by Nrf2 overactivation in hepatocytes lacking c-met receptor characterized by a severe unbalance between pro-oxidant and antioxidant functions. Control mice (c-metfx/fx, single c-met knockouts (c-metΔhepa, and double c-met/Keap1 knockouts (met/Keap1Δhepa were then fed a chow or a methionine-choline-deficient (MCD diet, respectively, for 4 weeks to reproduce the features of nonalcoholic steatohepatitis. Upon MCD feeding, met/Keap1Δhepa mice displayed increased liver mass albeit decreased triglyceride accumulation. The marked increase of oxidative stress observed in c-metΔhepa was restored in the double mutants as assessed by 4-HNE immunostaining and by the expression of genes responsible for the generation of free radicals. Moreover, double knockout mice presented a reduced amount of liver-infiltrating cells and the exacerbation of fibrosis progression observed in c-metΔhepa livers was significantly inhibited in met/Keap1Δhepa. Therefore, genetic activation of the antioxidant transcription factor Nrf2 improves liver damage and repair in hepatocyte-specific c-met-deficient mice mainly through restoring a balance in the cellular redox homeostasis.

  9. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

    Science.gov (United States)

    Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

    2012-04-01

    Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

  10. Design and optimization of a series of 1-sulfonylpyrazolo[4,3-b]pyridines as selective c-Met inhibitors.

    Science.gov (United States)

    Ma, Yuchi; Sun, Guangqiang; Chen, Danqi; Peng, Xia; Chen, Yue-Lei; Su, Yi; Ji, Yinchun; Liang, Jin; Wang, Xin; Chen, Lin; Ding, Jian; Xiong, Bing; Ai, Jing; Geng, Meiyu; Shen, Jingkang

    2015-03-12

    c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of π-π stacking interactions and solvent accessible polar moieties led to a series of highly potent and selective type I c-Met inhibitors. On the basis of in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development.

  11. Study of expression of genes cIAP and cMET, in liver tissue with and without neoplasia of Rattus norvegicus

    International Nuclear Information System (INIS)

    Coto Valverde, Daniel Esteban

    2010-01-01

    The expression levels of cIAP genes and cMET were determined in liver tissues with and without neoplasm of the organism Rattus norvegicus, for prevention, diagnosis and treatment of hepatocellular carcinoma. The technique of reaction Polymerase Chain in real time (qPCR), is used to obtain the expression, of both genes cIAP and cMET, and this has decreased in neoplastic samples compared to samples not affected. The expression of these genes has been analyzed in samples with neoplastic formations, but treated with an anti-tumor agent. The expression has presented an increase of the cMET gene, unlike the cIAP gene, which has decreased its expression. Perform statistical analysis has been impossible because the number of samples used has been reduced. The results obtained differ with those expected theoretically. (author) [es

  12. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  13. Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

    Directory of Open Access Journals (Sweden)

    Tseng Vincent S

    2011-04-01

    Full Text Available Abstract Background A cross-talk between different receptor tyrosine kinases (RTKs plays an important role in the pathogenesis of human cancers. Methods Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. Results A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p p Conclusions In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.

  14. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

    2014-01-01

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

  15. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

    Science.gov (United States)

    Ito, Yoko; Correll, Kelly; Schiel, John A; Finigan, Jay H; Prekeris, Rytis; Mason, Robert J

    2014-07-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. Copyright © 2014 the American Physiological Society.

  16. Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways

    Directory of Open Access Journals (Sweden)

    Weibo Chen

    2014-01-01

    Full Text Available Purpose. Tumor microenvironment confers drug resistance to kinase inhibitors by increasing RKT ligand levels that result in the activation of cell-survival signaling including PI3K and MAPK signals. We assessed whether HSC-LX2 coculture conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the drug resistance. Experimental Design. The effect of LX2 on sorafenib resistance was determined by coculture system with Huh7 cells. The rescue function of LX2 supernatants was assessed by MTT assay and fluorescence microscopy. The underlying mechanism was tested by administration of pathway inhibitors and manifested by Western blotting. Results. LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK. LX2 secreted HGF into the culture medium that triggered drug resistance, and exogenous HGF could also induce sorafenib resistance. The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture. Increased phosphorylation of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells. The Jak inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3 activation. The combined administration of sorafenib and p-Stat3 inhibitor S3I-201 augmented induced apoptosis even in the presence of sorafenib resistance. Conclusions. HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. A combined administration of sorafenib and S3I-201 was able to augment sorafenib-induced apoptosis even in the presence of LX2 coculture.

  17. Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization.

    Science.gov (United States)

    An, Xiao-De; Liu, Hongyan; Xu, Zhong-Liang; Jin, Yi; Peng, Xia; Yao, Ying-Ming; Geng, Meiyu; Long, Ya-Qiu

    2015-02-01

    Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two imidazonaphthyridinone frameworks with 1,8- and 3,5-disubstitution pattern as class I and class II c-Met kinase inhibitors, respectively. Further structural optimization on type II inhibitors by truncation of the imidazonaphthyridinone core and incorporation of an N-phenyl cyclopropane-1,1-dicarboxamide pharmacophore led to the discovery of novel imidazopyridine-based c-Met kinase inhibitors, displaying nanomolar enzyme inhibitory activity and improved Met kinase selectivity. More significantly, the new chemotype c-Met kinase inhibitors effectively inhibited Met phosphorylation and its downstream signaling as well as the proliferation of Met-dependent EBC-1 human lung cancer cells at submicromolar concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Involvement of c-Met- and phosphatidylinositol 3-kinase dependent pathways in arsenite-induced downregulation of catalase in hepatoma cells.

    Science.gov (United States)

    Kim, Soohee; Lee, Seung Heon; Kang, Sukmo; Lee, Lyon; Park, Jung-Duck; Ryu, Doug-Young

    2011-01-01

    Catalase protects cells from reactive oxygen species-induced damage by catalyzing the breakdown of hydrogen peroxide to oxygen and water. Arsenite decreases catalase activity; it activates phosphatidylinositol 3-kinase (PI3K) and its key downstream effector Akt in a variety of cells. The PI3K pathway is known to inhibit catalase expression. c-Met, an upstream regulator of PI3K and Akt, is also involved in the regulation of catalase expression. To examine the involvement of c-Met and PI3K pathways in the arsenite-induced downregulation of catalase, catalase mRNA and protein expression were analyzed in the human hepatoma cell line HepG2 treated with arsenite and either an inhibitor of c-Met (PHA665752 (PHA)) or of PI3K (LY294002 (LY)). Arsenite treatment markedly activated Akt and decreased the levels of both catalase mRNA and protein. Both PHA and LY attenuated arsenite-induced activation of Akt. PHA and LY treatment also prevented the inhibitory effect of arsenite on catalase protein expression but did not affect the level of catalase mRNA. These findings suggest that arsenite-induced inhibition of catalase expression is regulated at the mRNA and post-transcriptional levels in HepG2 cells, and that the post-transcriptional regulation is mediated via c-Met- and PI3K-dependent mechanisms.

  19. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.

    Science.gov (United States)

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-10-28

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique C-terminal tail of c-Met (supersite). There is a strong link between aberrant c-Met activity and oncogenesis, which makes this kinase an important cancer drug target. The furanosylated indolocarbazole K-252a belongs to a family of microbial alkaloids that also includes staurosporine. It was recently shown to be a potent inhibitor of c-Met. Here we report the crystal structures of an unphosphorylated c-Met kinase domain harboring a human cancer mutation and its complex with K-252a at 1.8-A resolution. The structure follows the well established architecture of protein kinases. It adopts a unique, inhibitory conformation of the activation loop, a catalytically noncompetent orientation of helix alphaC, and reveals the complete C-terminal docking site. The first SH2-binding motif (1349YVHV) adopts an extended conformation, whereas the second motif (1356YVNV), a binding site for Grb2-SH2, folds as a type II Beta-turn. The intermediate portion of the supersite (1353NATY) assumes a type I Beta-turn conformation as in an Shc-phosphotyrosine binding domain peptide complex. K-252a is bound in the adenosine pocket with an analogous binding mode to those observed in previously reported structures of protein kinases in complex with staurosporine.

  20. Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer

    Directory of Open Access Journals (Sweden)

    Demin Jiao

    2016-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT and angiogenesis have emerged as two pivotal events in cancer progression. Curcumin has been extensively studied in preclinical models and clinical trials of cancer prevention due to its favorable toxicity profile. However, the possible involvement of curcumin in the EMT and angiogenesis in lung cancer remains unclear. This study found that curcumin inhibited hepatocyte growth factor (HGF-induced migration and EMT-related morphological changes in A549 and PC-9 cells. Moreover, pretreatment with curcumin blocked HGF-induced c-Met phosphorylation and downstream activation of Akt, mTOR, and S6. These effects mimicked that of c-Met inhibitor SU11274 or PI3 kinase inhibitor LY294002 or mTOR inhibitor rapamycin treatment. c-Met gene overexpression analysis further demonstrated that curcumin suppressed lung cancer cell EMT by inhibiting c-Met/Akt/mTOR signaling pathways. In human umbilical vein endothelial cells (HUVECs, we found that curcumin also significantly inhibited PI3K/Akt/mTOR signaling and induced apoptosis and reduced migration and tube formation of HGF-treated HUVEC. Finally, in the experimental mouse model, we showed that curcumin inhibited HGF-stimulated tumor growth and induced an increase in E-cadherin expression and a decrease in vimentin, CD34, and vascular endothelial growth factor (VEGF expression. Collectively, these findings indicated that curcumin could inhibit HGF-promoted EMT and angiogenesis by targeting c-Met and blocking PI3K/Akt/mTOR pathways.

  1. Negative control of the HGF/c-MET pathway by TGF-β: a new look at the regulation of stemness in glioblastoma.

    Science.gov (United States)

    Papa, Eleanna; Weller, Michael; Weiss, Tobias; Ventura, Elisa; Burghardt, Isabel; Szabó, Emese

    2017-12-13

    Multiple target inhibition has gained considerable interest in combating drug resistance in glioblastoma, however, understanding the molecular mechanisms of crosstalk between signaling pathways and predicting responses of cancer cells to targeted interventions has remained challenging. Despite the significant role attributed to transforming growth factor (TGF)-β family and hepatocyte growth factor (HGF)/c-MET signaling in glioblastoma pathogenesis, their functional interactions have not been well characterized. Using genetic and pharmacological approaches to stimulate or antagonize the TGF-β pathway in human glioma-initiating cells (GIC), we observed that TGF-β exerts an inhibitory effect on c-MET phosphorylation. Inhibition of either mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway attenuated this effect. A comparison of c-MET-driven and c-MET independent GIC models revealed that TGF-β inhibits stemness in GIC at least in part via its negative regulation of c-MET activity, suggesting that stem cell (SC) maintenance may be controlled by the balance between these two oncogenic pathways. Importantly, immunohistochemical analyses of human glioblastoma and ex vivo single-cell gene expression profiling of TGF-β and HGF confirm the negative interaction between both pathways. These novel insights into the crosstalk of two major pathogenic pathways in glioblastoma may explain some of the disappointing results when targeting either pathway alone in human glioblastoma patients and inform on potential future designs on targeted pharmacological or genetic intervention.

  2. Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis.

    Science.gov (United States)

    Wang, Fang; Li, Shanshan; Zhao, Yueguang; Yang, Kunxian; Chen, Minju; Niu, Heng; Yang, Jingyu; Luo, Ying; Tang, Wenru; Sheng, Miaomiao

    2016-08-01

    The overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients. PubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided. A total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34-4.91, P = 0.005; and HR = 1.63 95% CI = 1.20-2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52-4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69-1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64-1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43-1.33, P = 0.333]. Our meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a

    OpenAIRE

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M.; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-01-01

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique...

  4. Evaluation of clinial usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging

    International Nuclear Information System (INIS)

    Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi

    1994-01-01

    We studied 11 C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11 C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3 H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of 11 C-MET, the increase in rate of radioactivity of 11 C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11 C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author)

  5. Hepatocyte growth factor/c-MET axis-mediated tropism of cord blood-derived unrestricted somatic stem cells for neuronal injury.

    Science.gov (United States)

    Trapp, Thorsten; Kögler, Gesine; El-Khattouti, Abdelouahid; Sorg, Rüdiger V; Besselmann, Michael; Föcking, Melanie; Bührle, Christian P; Trompeter, Ingo; Fischer, Johannes C; Wernet, Peter

    2008-11-21

    An under-agarose chemotaxis assay was used to investigate whether unrestricted somatic stem cells (USSC) that were recently characterized in human cord blood are attracted by neuronal injury in vitro. USSC migrated toward extracts of post-ischemic brain tissue of mice in which stroke had been induced. Moreover, apoptotic neurons secrete factors that strongly attracted USSC, whereas necrotic and healthy neurons did not. Investigating the expression of growth factors and chemokines in lesioned brain tissue and neurons and of their respective receptors in USSC revealed expression of hepatocyte growth factor (HGF) in post-ischemic brain and in apoptotic but not in necrotic neurons and of the HGF receptor c-MET in USSC. Neuronal lesion-triggered migration was observed in vitro and in vivo only when c-MET was expressed at a high level in USSC. Neutralization of the bioactivity of HGF with an antibody inhibited migration of USSC toward neuronal injury. This, together with the finding that human recombinant HGF attracts USSC, document that HGF signaling is necessary for the tropism of USSC for neuronal injury. Our data demonstrate that USSC have the capacity to migrate toward apoptotic neurons and injured brain. Together with their neural differentiation potential, this suggests a neuroregenerative potential of USSC. Moreover, we provide evidence for a hitherto unrecognized pivotal role of the HGF/c-MET axis in guiding stem cells toward brain injury, which may partly account for the capability of HGF to improve function in the diseased central nervous system.

  6. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies.

    Directory of Open Access Journals (Sweden)

    Anna Olivieri

    2011-12-01

    Full Text Available The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1 is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1, and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  7. Alternative signaling pathways as potential therapeutic targets for overcoming EGFR and c-Met inhibitor resistance in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Jason T Fong

    Full Text Available The use of tyrosine kinase inhibitors (TKIs against EGFR/c-Met in non-small cell lung cancer (NSCLC has been shown to be effective in increasing patient progression free survival (PFS, but their efficacy is limited due to the development of resistance and tumor recurrence. Therefore, understanding the molecular mechanisms underlying development of drug resistance in NSCLC is necessary for developing novel and effective therapeutic approaches to improve patient outcome. This study aims to understand the mechanism of EGFR/c-Met tyrosine kinase inhibitor (TKI resistance in NSCLC. H2170 and H358 cell lines were made resistant to SU11274, a c-Met inhibitor, and erlotinib, an EGFR inhibitor, through step-wise increases in TKI exposure. The IC50 concentrations of resistant lines exhibited a 4-5 and 11-22-fold increase for SU11274 and erlotinib, respectively, when compared to parental lines. Furthermore, mTOR and Wnt signaling was studied in both cell lines to determine their roles in mediating TKI resistance. We observed a 2-4-fold upregulation of mTOR signaling proteins and a 2- to 8-fold upregulation of Wnt signaling proteins in H2170 erlotinib and SU11274 resistant cells. H2170 and H358 cells were further treated with the mTOR inhibitor everolimus and the Wnt inhibitor XAV939. H358 resistant cells were inhibited by 95% by a triple combination of everolimus, erlotinib and SU11274 in comparison to 34% by a double combination of these drugs. Parental H2170 cells displayed no sensitivity to XAV939, while resistant cells were significantly inhibited (39% by XAV939 as a single agent, as well as in combination with SU11274 and erlotinib. Similar results were obtained with H358 resistant cells. This study suggests a novel molecular mechanism of drug resistance in lung cancer.

  8. Integration of an In Situ MALDI-Based High-Throughput Screening Process: A Case Study with Receptor Tyrosine Kinase c-MET.

    Science.gov (United States)

    Beeman, Katrin; Baumgärtner, Jens; Laubenheimer, Manuel; Hergesell, Karlheinz; Hoffmann, Martin; Pehl, Ulrich; Fischer, Frank; Pieck, Jan-Carsten

    2017-12-01

    Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated "in-line reader" for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components. Here we adapt our c-MET kinase assay to optimize for MALDI-MS compatibility and test its feasibility for compound screening. The pros and cons of the Echo (Labcyte) as a transfer system for in situ MALDI-MS sample preparation are discussed. We demonstrate that this method generates robust data in a 1536-grid format. We use the MALDI-MS to directly measure the ratio of c-MET substrate and phosphorylated product to acquire IC50 curves and demonstrate that the pharmacology is unaffected. The resulting IC50 values correlate well between the common label-based capillary electrophoresis and the label-free MALDI-MS detection method. We predict that label-free MALDI-MS-based high-throughput screening will become increasingly important and more widely used for drug discovery.

  9. Synthesis of Pyridine and Spiropyridine Derivatives Derived from 2-aminoprop- 1-ene-1,1,3-tricarbonitrile Together with their c-Met Kinase and Antiproliferative Evaluations.

    Science.gov (United States)

    Mohareb, Rafat M; Abouzied, Amr S; Abbas, Nermeen S

    2018-02-07

    Among a wide range of pyridines, 3-cyanopyridines acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the pyridine nucleus were known in the market. The aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of 3-cyanopyridine derivatives using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) as the key starting material for many heterocyclization reactions. Muticoponent reactions were adopted using compound 1 to get different pyridine derivatives that were capable for different heterocyclization reactions. Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform where some compounds gave high activities. Compounds that showed high antiprolifeative activity were tested gor c-Met-independent and the results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than foretinib. The Pim-1 kinase inhibition activity of some selected compounds showed that compounds 5e and 16c were high potent to inhibit Pim-1 activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Comparative evaluation of 11C-MET PET-CT and MRI for GTV delineation in precision radiotherapy for gliomas%基于11C-MET PET-CT与MRI对脑胶质瘤精确放疗GTV勾画的比较研究

    Institute of Scientific and Technical Information of China (English)

    王如; 钱立庭; 汪世存; 刘伟; 罗文广; 张洪波; 李广虎; 胡智刚; 刘磊

    2014-01-01

    目的 探讨11C-MET PET-CT和MRI图像对脑胶质瘤GTV确定的差异.方法 选取6例经病理证实为胶质瘤患者的术前MRI及11C-MET PET-CT图像,分别由我科5位医师在两种图像资料上勾画GTV,比较两者差异.结果 在MRI11C-MET PET-CT上勾画的GTV体积相似(P=0.917),GTV变异系数也相似(P =0.600).勾画的GTV重合度最大为73.0%、最小为51.8%.方差分析显示不同勾画者之间在两种图像资料上勾画的GTV相似(P =0.709),但PET-CT组GTV最大差值为27.66 cm3,而MRI组的为40.37 cm3.结论 MRI与PET-CT显示的肿瘤边界存在差异,不同勾画者勾画的GTV相似,PET-CT组的GTV最大差值较MRI组的小,11C-MET PET-CT显示GTV较为直观.%Objective To evaluate the difference between MRI and 11C-MET PET-CT for gross tumor volume (GTV) delineation in the precision radiotherapy for gliomas.Methods Six patients with a pathologically confirmed diagnosis of gliomas were selected for target delineation.Five physicians in our department were called to delineate the GTV based on the preoperative MRI and 11C-MET PET-CT images of these patients.The GTVs based on the two methods were compared.Results There was no significant difference between the GTVs based on MRI and 11C-MET PET-CT (P =0.917),and their coefficients of variation were also similar (P =0.600).The coincidences of GTVs were different among the patients,with a maximum value of 73.0% and a minimum value of 51.8%.GTV showed no significant difference when defined by different physicians on MRI and PET-CT (P =0.709) ; the biggest difference was 27.66 cm3 on PET-CT and 40.37 cm3 on MRI.Conclusions The boundaries of gliomas defined on MRI and PET-CT are different.The GTVs delineated by different physicians on MRI and PET-CT are similar,and the biggest difference on PET-CT is smaller than that on MRI,which suggests that 11C-MET PET-CT is a more direct way for displaying GTV.

  11. Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

    Directory of Open Access Journals (Sweden)

    Eunice Yuen Ting Lau

    2016-05-01

    Full Text Available Like normal stem cells, tumor-initiating cells (T-ICs are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs would regulate liver T-ICs. We found that the presence of α-SMA(+ CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC.

  12. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases.

    Science.gov (United States)

    Son, Bo-Ra; Marquez-Curtis, Leah A; Kucia, Magda; Wysoczynski, Marcin; Turner, A Robert; Ratajczak, Janina; Ratajczak, Mariusz Z; Janowska-Wieczorek, Anna

    2006-05-01

    Human mesenchymal stem cells (MSCs) are increasingly being considered in cell-based therapeutic strategies for regeneration of various organs/tissues. However, the signals required for their homing and recruitment to injured sites are not yet fully understood. Because stromal-derived factor (SDF)-1 and hepatocyte growth factor (HGF) become up-regulated during tissue/organ damage, in this study we examined whether these factors chemoattract ex vivo-expanded MSCs derived from bone marrow (BM) and umbilical cord blood (CB). Specifically, we investigated the expression by MSCs of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF, and their functionality after early and late passages of MSCs. We also determined whether MSCs express matrix metalloproteinases (MMPs), including membrane type 1 (MT1)-MMP, matrix-degrading enzymes that facilitate the trafficking of hematopoietic stem cells. We maintained expanded BM- or CB-derived MSCs for up to 15-18 passages with monitoring of the expression of 1) various tissue markers (cardiac and skeletal muscle, neural, liver, and endothelial cells), 2) functional CXCR4 and c-met, and 3) MMPs. We found that for up to 15-18 passages, both BM- and CB-derived MSCs 1) express mRNA for cardiac, muscle, neural, and liver markers, as well as the vascular endothelial (VE) marker VE-cadherin; 2) express CXCR4 and c-met receptors and are strongly attracted by SDF-1 and HGF gradients; 3) express MMP-2 and MT1-MMP transcripts and proteins; and 4) are chemo-invasive across the reconstituted basement membrane Matrigel. These in vitro results suggest that the SDF-1-CXCR4 and HGF-c-met axes, along with MMPs, may be involved in recruitment of expanded MSCs to damaged tissues.

  13. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

    OpenAIRE

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-01-01

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

  14. Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis.

    Science.gov (United States)

    Ji, Ting-Ting; Huang, Xuan; Jin, Jie; Pan, Sheng-Hua; Zhuge, Xiao-Ju

    2016-05-01

    To discuss the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lncRNA-TUG1 in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between lncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after lncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western-blot test. The expression level of lncRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (P TUG1 specific siRNA (P TUG1 was silenced (P TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lncRNA-TUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  15. Enhanced Prediction of Src Homology 2 (SH2) Domain Binding Potentials Using a Fluorescence Polarization-derived c-Met, c-Kit, ErbB, and Androgen Receptor Interactome*

    Science.gov (United States)

    Leung, Kin K.; Hause, Ronald J.; Barkinge, John L.; Ciaccio, Mark F.; Chuu, Chih-Pin; Jones, Richard B.

    2014-01-01

    Many human diseases are associated with aberrant regulation of phosphoprotein signaling networks. Src homology 2 (SH2) domains represent the major class of protein domains in metazoans that interact with proteins phosphorylated on the amino acid residue tyrosine. Although current SH2 domain prediction algorithms perform well at predicting the sequences of phosphorylated peptides that are likely to result in the highest possible interaction affinity in the context of random peptide library screens, these algorithms do poorly at predicting the interaction potential of SH2 domains with physiologically derived protein sequences. We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. The resulting interaction experiments revealed over 1000 novel peptide-protein interactions and provided a glimpse into the common and specific interaction potentials of c-Met, c-Kit, GAB1, and the human androgen receptor. We used these data to build a permutation-based logistic regression classifier that performed considerably better than existing algorithms for predicting the interaction potential of several SH2 domains. PMID:24728074

  16. c-Met Overexpression Contributes to the Acquired Apoptotic Resistance of Nonadherent Ovarian Cancer Cells through a Cross Talk Mediated by Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase 1/2

    Directory of Open Access Journals (Sweden)

    Maggie K.S. Tang

    2010-02-01

    Full Text Available Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis, which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in three-dimensional not in two-dimensional cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K/Akt and extracellular signal-regulated kinase (ERK 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified a central role of Ras as a mechanism of this cross talk. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of nonadherent ovarian cancer ascites cells and may have important clinical implications.

  17. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

    Science.gov (United States)

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-10-03

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest

  18. HGF/c-MET Pathway in AIDS-Related Lymphoma

    Science.gov (United States)

    2016-09-01

    of Pediatrics, East Hospital, Tongji University School of Medicine, Shanghai, China 5 William Carey University College of Osteopathic Medicine...12845. 32. Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U and Cullen BR. A viral microRNA...relevance to the accumulation of versican. Prostate. 2005; 63:269–275. 17. Ricciardelli C, Frewin KM, Tan Ide A, Williams ED, Opeskin K, Pritchard MA

  19. Role of cMET in the Development and Progression of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ilaria Bossi

    2013-09-01

    Full Text Available Mesenchymal-epithelial transition (MET is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF. Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC, by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.

  20. Fatty Acid Synthase Activity as a Target for c-Met Driven Prostate Cancer

    Science.gov (United States)

    2013-07-01

    cancer potentially due to increased fecal fat excretion. In addition, several families of plant-derived flavonoid compounds including...Apoptosis by Flavonoids Is Associated with Their Ability to Inhibit Fatty Acid Synthase Activity. J. Biol. Chem., 2005. 280(7): p. 5636-5645. 156... flavonoids , represent a source of relatively nontoxic, orally available and affordable compounds that are known to affect a number of different

  1. Do Allergies Cause Asthma?

    Science.gov (United States)

    ... for Educators Search English Español Do Allergies Cause Asthma? KidsHealth / For Parents / Do Allergies Cause Asthma? Print ... son la causa del asma? Do Allergies Cause Asthma? Allergies don't cause asthma. But kids who ...

  2. What Causes SIDS?

    Science.gov (United States)

    ... Environment Look Like? How Can Caregivers Create a Safe Sleep Environment? Babies Need Tummy ... exactly what causes SIDS at this time. Scientists and health care providers are working very hard to find the cause or causes ...

  3. What Causes Cushing's Syndrome?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print What causes Cushing syndrome? Cushing syndrome can develop for two reasons: Medication ... uhs ), thyroid, or thymus How Tumors Can Cause Cushing Syndrome Normally, the pituitary gland in the brain controls ...

  4. What Causes COPD?

    Science.gov (United States)

    ... please turn JavaScript on. Feature: The Challenge of COPD What Causes COPD? Past Issues / Fall 2014 Table of Contents Long- ... and the airways usually is the cause of COPD. In the United States, the most common irritant ...

  5. The Cause of Gravity

    OpenAIRE

    Byrne, Michael

    1999-01-01

    Einstein said that gravity is an acceleration like any other acceleration. But gravity causes relativistic effects at non-relativistic speeds; so gravity could have relativistic origins. And since the strong force is thought to cause most of mass, and mass is proportional to gravity; the strong force is therefore also proportional to gravity. The strong force could thus cause relativistic increases of mass through the creation of virtual gluons; along with a comparable contraction of space ar...

  6. What causes education?

    DEFF Research Database (Denmark)

    Hyldgaard, Kirsten

    2017-01-01

    Why do universities not give priority to education? The article suggests a formal answer on the basis of Lacan’s four discourses. Why education? Why do we learn? Is it caused by a natural curiosity or is it caused by anxiety? Is it at all possible to control the influence that we undoubtedly have...

  7. What Causes Bad Breath?

    Science.gov (United States)

    ... Videos for Educators Search English Español What Causes Bad Breath? KidsHealth / For Teens / What Causes Bad Breath? Print en español ¿Qué es lo que provoca el mal aliento? Bad breath, or halitosis , can be a major problem, ...

  8. CAUSES OF OCCUPATIONAL INJURIES

    NARCIS (Netherlands)

    KINGMA, J

    1994-01-01

    The causes of occupational injuries (N = 2,365) were investigated. Accidents with machinery and hand tools were the two main causes (49.9%). 89% of the patients with occupational injuries were male. The highest risk group were in the age category of 19 years or less (51.9%). This age group also

  9. Childhood Obesity Causes & Consequences

    Science.gov (United States)

    ... and Local Programs Related Topics Diabetes Nutrition Childhood Obesity Causes & Consequences Recommend on Facebook Tweet Share Compartir ... determine how a community is designed. Consequences of Obesity More Immediate Health Risks Obesity during childhood can ...

  10. What Causes a Toothache?

    Science.gov (United States)

    ... See a Dentist? What is Dental Amalgam (Silver Filling)? Temporomandibular Joint Disorder Men: Looking for a Better ... sinus or ear infections and tension in the facial muscles can cause discomfort that resembles a toothache, ...

  11. Causes of Paralysis

    Science.gov (United States)

    ... and often disabling disease of the central nervous system. > Muscular dystrophy MD is characterized by the degeneration of skeletal muscles. > Neurofibromatosis Progressive disorder of the nervous system that causes tumors on the nerves. > Post-polio ...

  12. What causes IBD?

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. What causes IBD? An overly aggressive cell-mediated immune response to luminal commensal bacteria in genetically susceptible individuals. Sartor, Gastroenterology 2004.

  13. Cancer-causing radiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.; Holland, J.M.; Storer, J.B.

    1977-01-01

    Radiation causes cancer. That simple fact was known by the early 1900s. Further, radiation can induce cancer in almost any tissue in animals and humans. But the cancer-causing dose may vary by 20-fold for different tissues in animals. Such variation is also seen in people who are exposed, typically, to low radiation doses. Hence, the minimum dose that causes human cancer is not known. Thus, the crucial question becomes what factors, including amount of exposure, trigger cancer. Radiation is divided into two types, ionizing and nonionizing. Of the two, ionizing radiation involves higher energies. Thus by ejecting electrons from molecules, charged particles called ion pairs are formed. They are short-lived, and often break down to form highly reactive free radicals, which are molecular fragments containing unpaired electrons. Nonionizing radiation, which involves ultraviolet light and micro- and radiowaves, causes molecular excitations such as vibrations and electron movement, but produces no ions. And though ultraviolet light causes skin cancer, ionizing radiation is, by far, the more potent carcinogen

  14. Vulvovaginitis: causes and management.

    Science.gov (United States)

    Pierce, A M; Hart, C A

    1992-01-01

    Over a period of 33 months in a paediatric accident and emergency department, the clinical pattern and possible causes of vulvovaginitis were studied prospectively in 200 girls presenting with genital discharge, irritation, pain, or redness. The major causes were poor hygiene and threadworms. The suspicion of sexual abuse arose in a few girls but no organisms of sexually transmitted disease were found. Urinary symptoms were common but only 20 patients had a significant bacteriuria and 40 had sterile pyuria. Specific skin problems occurred in 28 cases. Simple measures to improve hygiene and treatment of threadworms gave effective relief. Genital irritation caused urinary symptoms with no clinical evidence of infection, and it is advised that antibiotic treatment should await urine culture. Specific skin problems require help from a dermatologist. The possibility of sexual abuse must be considered especially if the vulvovaginitis is persistent or recurrent after adequate treatment. PMID:1580682

  15. Landslides - Cause and effect

    Science.gov (United States)

    Radbruch-Hall, D. H.; Varnes, D.J.

    1976-01-01

    Landslides can cause seismic disturbances; landslides can also result from seismic disturbances, and earthquake-induced slides have caused loss of life in many countries. Slides can cause disastrous flooding, particularly when landslide dams across streams are breached, and flooding may trigger slides. Slope movement in general is a major process of the geologic environment that places constraints on engineering development. In order to understand and foresee both the causes and effects of slope movement, studies must be made on a regional scale, at individual sites, and in the laboratory. Areal studies - some embracing entire countries - have shown that certain geologic conditions on slopes facilitate landsliding; these conditions include intensely sheared rocks; poorly consolidated, fine-grained clastic rocks; hard fractured rocks underlain by less resistant rocks; or loose accumulations of fine-grained surface debris. Field investigations as well as mathematical- and physical-model studies are increasing our understanding of the mechanism of slope movement in fractured rock, and assist in arriving at practical solutions to landslide problems related to all kinds of land development for human use. Progressive failure of slopes has been studied in both soil and rock mechanics. New procedures have been developed to evaluate earthquake response of embankments and slopes. The finite element method of analysis is being extensively used in the calculation of slope stability in rock broken by joints, faults, and other discontinuities. ?? 1976 International Association of Engineering Geology.

  16. Leading Causes of Blindness

    Science.gov (United States)

    ... have cataracts. They are the leading cause of blindness in the world. By age 80, more than half of all people in the United States either will have a cataract or have had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to ...

  17. Aliteracy : causes and solutions

    NARCIS (Netherlands)

    Nielen, Thijs Martinus Johannes

    2016-01-01

    The reading motivation of the majority of students declines in the upper half of primary school, which implies a risk for aliteracy: Students can read but, due to lack of practice, their skills remain underdeveloped (Chapter 2). In this thesis we have explored causes and solutions for this important

  18. Does intuition cause cooperation?

    NARCIS (Netherlands)

    P.P.J.L. Verkoeijen (Peter); S. Bouwmeester (Samantha)

    2014-01-01

    textabstractRecently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more

  19. Infestation caused by acanthocephala

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2009-03-01

    Full Text Available An on-line case of infestation caused by M. moniliformis is descripted. This rodents’ worm, belonging to acanthocephala, can be rarely responsible of human intestinal pathology. The case is the pretext for a brief revision on this parasitosis. So, biological, epidemiological, clinical and diagnostical findings are reported.

  20. Fighting a lost cause

    NARCIS (Netherlands)

    Mario Haaf

    2015-01-01

    This essay claims that the declared war on drugs has failed, it has caused more harm than good, and that a new approach is necessary. The focus of analysis lays especially on the implemented drug policies of Mexico and the United States. The goal is to point out the flaws of the current policy based

  1. Not without cause

    Science.gov (United States)

    Burdette, Dara L.; Yarbrough, Melanie L.; Orth, Kim

    2009-01-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is a gram-negative halophillic bacterium that causes worldwide seafood-borne gastroenteritis. The prevalence of V. parahaemolyticus in the environment and incidence of infection have been linked to rising water temperatures caused by global warming. Among its virulence factors, V. parahaemolyticus harbors two type III secretion systems (T3SS). Recently, we have shown that T3SS1 induces rapid cellular death that initiates with acute autophagy, as measured by LC3 lipidation and accumulation of early autophagosomal vesicles. While not the first characterized pathogen to usurp autophagy, this is the first example of an extracellular pathogen that exploits this pathway for its own benefit. Here we discuss possible roles for the induction of autophagy during infection and discuss how V. parahaemolyticus-induced autophagy provides insight into key regulatory steps that govern the decision between apoptosis and autophagy. PMID:19011375

  2. Labor Informality: General Causes

    Directory of Open Access Journals (Sweden)

    Gustavo Sandoval Betancour

    2016-04-01

    Full Text Available The article examines the main causes of labor informality in order to verify the validity of classical theories that explain unemployment in market economies and its relationship to informality. Methodologically, the project was based, in the empirical part, on international statistics, comparing the evolution of labor market structure in a combined sample of highly industrialized countries and other less industrialized ones. Empirical evidence supports the conclusion that the classical economic theory of Marxist origin is inefficient to explain the causes of unemployment in contemporary market economies, as well as it fails to satisfactorily explain informality. On the contrary, we conclude that the theory in question is more relevant to explain informality in centrally planned economies where this phenomenon has been present even more significantly than in free market economies.

  3. Hypothalamic demyelination causing panhypopituitarism.

    Science.gov (United States)

    Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

    2018-05-01

    Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

  4. Tracing Actual Causes

    Science.gov (United States)

    2016-08-08

    produce a full explanation. While related, this problem dif- fers from the problem of determining actual causes where the focus is on identifying...1987]. We prove that the decision problem for causal slices is DP1 - complete. DP1 is the class of computational problems that can be solved using an NP ...machine and a co- NP machine simultaneously. Based on this result, we further show that the decision problem for causal histories is in ΠP2 . Closely

  5. Anaerobic Digestion Foaming Causes

    OpenAIRE

    Ganidi, Nafsika

    2008-01-01

    Anaerobic digestion foaming has been encountered in several sewage treatment plants in the UK. Foaming has raised major concerns for the water utilities due to significant impacts on process efficiency and operational costs. Several foaming causes have been suggested over the past few years by researchers. However, the supporting experimental information is limited and in some cases site specific. The present report aimed to provide a better understanding of the anaerobic di...

  6. Hacking for a cause

    OpenAIRE

    Still, Brian

    2005-01-01

    This paper explores the concept of hacktivism, which is hacking for a political or social cause on the Internet. Generally hackers, even those hacking government–sponsored sites, have been negatively stereotyped as malicious thrill seekers or, worse yet, cyberterrorists. But increasingly there are more politically motivated hackers distancing themselves from cyberterrorism by engaging in hacktivism that is intent more upon disruption than disobedience. Certain hacktivists, in fact, have creat...

  7. Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

    Directory of Open Access Journals (Sweden)

    Su M

    2017-11-01

    Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET

  8. Darwin's Sacred Cause

    DEFF Research Database (Denmark)

    Kjærgaard, Peter C.

    2009-01-01

    As we are being flooded by Darwin lollipops, t-shirts, quills and stamps it is becoming increasingly difficult to be heard or seen in the commercialised celebration in 2009. Some are in the business for the science, but a lot are in it for profit. Accordingly, the Darwin industry has left the hands...... of scholarly specialists and been appropriated by money makers. One could not help thinking about this as, in the autumn of 2008, the publisher began hyping Darwin's Sacred Cause as ‘one of the major contributions to the worldwide Darwin anniversary celebrations in 2009' Udgivelsesdato: February...

  9. Fighting a lost cause

    OpenAIRE

    Haaf, Mario

    2015-01-01

    This essay claims that the declared war on drugs has failed, it has caused more harm than good, and that a new approach is necessary. The focus of analysis lays especially on the implemented drug policies of Mexico and the United States. The goal is to point out the flaws of the current policy based on prohibition and persecution by analyzing its origins and comparing the current approach with the failures of the alcohol prohibition in the 1920s in the United States. One of the main points th...

  10. [Epistaxis: causes and management].

    Science.gov (United States)

    Siwiec, H; Szymański, M; Szymańska, A; Klatka, J

    2001-01-01

    Evaluation of 265 patients treated in hospital due to nasal bleeding revealed that almost half of them suffered from hypertension and in about 30% of cases it was impossible to establish the cause of epistaxis. The most frequent way to stop the bleeding was anterior nasal packing and in case of failure posterior nasal packing together with anterior one. Posterior nasal packing with Foley's catheter is relatively simple and effective procedure. Introduction of superselective embolization of maxillary artery and dermoplasty in Rendu-Osler disease was very helpful.

  11. What causes cancer?

    International Nuclear Information System (INIS)

    Trichopoulos, D.; Li, F.P.; Hunter, D.J.

    1996-01-01

    Cancer, a major killer throughout human history, changed its grasp as humankind advanced industrially and technologically. Although the risk of a few types of cancer has declined dramatically in developed countries in this century, the incidence of the most significant forms of the disease has increased. Cancers of the lung, breast, prostate and colon and rectum have all become more frequent in countries where risk factors such as cigarette smoking, unhealthful dietary habits and exposure to dangerous chemicals at work or in the environment are now more common. As industrialization has proliferated, so, too, have the suspected causes of cancer. In recent years, news accounts have been full of warnings about all manner of modern conveniences, from pharmaceuticals to cellular telephones. Meanwhile the pace of technological advance makes it more vital than ever to single out definitive causes of cancer from an ever expanding array of possibilities. For this daunting task, researchers rely heavily on epidemiology. Epidemiologists identify factors that are common to cancer victims’ history and way of life and evaluate them in the context of current biological understanding. Ultimately, the evidence may persuade researchers that one or more of these factors or characteristics “cause” the disease— that is to say, exposure to them significantly increases the odds of the illness developing

  12. Genetic Causes of Rickets

    Science.gov (United States)

    Acar, Sezer; Demir, Korcan; Shi, Yufei

    2017-01-01

    Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Nutritional rickets remains a significant child health problem in developing countries. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D-dependent rickets type 1A (VDDR1A), vitamin D-dependent rickets type 1B (VDDR1B), vitamin D-dependent rickets type 2A (VDDR2A), and vitamin D-dependent rickets type 2B (VDDR2B). The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets) due to impairment in renal tubular phosphate reabsorption as a result of FGF23-related or FGF23-independent causes. In this review, we focus on clinical, laboratory and genetic characteristics of various types of hereditary rickets as well as differential diagnosis and treatment approaches. PMID:29280738

  13. [Tropical causes of epilepsy].

    Science.gov (United States)

    Carod-Artal, F J

    Eighty-five percent of all epileptics live in tropical regions. Prenatal risk factors, traumatic brain injuries and different parasitic infestations of the central nervous system (CNS) are the reasons behind the high prevalence of epilepsy. This work reviews the main parasitic infestations causing epilepsy in the tropics. Neurocysticercosis is the main cause of focal epilepsy in early adulthood in endemic areas (30-50%). All the phases of cysticerci (viable, transitional and calcified) are associated with epileptic seizures. Anti-cysticercus treatment helps get rid of cysticerci faster and reduces the risk of recurrence of seizures in patients with viable cysts. Symptomatic epilepsy can be the first manifestation of neuroschistosomiasis in patients without any systemic symptoms. The pseudotumoral form can trigger seizures secondary to the presence of granulomas and oedemas in the cerebral cortex. The eggs of Schistosoma japonicum are smaller, reach the CNS more easily and trigger epileptic seizures more frequently. Toxocariasis and sparganosis are other parasitic infestations that can give rise to symptomatic seizures. The risk factors for suffering chronic epilepsy after cerebral malaria are a positive familial history of epilepsy and a history of episodes of fever and cerebral malaria that began with coma or which progressed with multiple, prolonged epileptic seizures. About 20% of patients with cerebral infarction secondary to Chagas disease present late vascular epilepsy as a complication. Very few studies have been conducted to examine the prognosis, risk of recurrence and modification of the natural course of seizures associated with tropical parasitic infestations, except for the case of neurocysticercosis.

  14. Green certificates causing inconvenience?

    International Nuclear Information System (INIS)

    Torgersen, Lasse

    2002-01-01

    From early 2002, producers of green energy in selected countries have been able to benefit from generous financial support in the Netherlands. Thus, there has been increased sale of green certificates from Norway and Sweden. But the condition that physical energy delivery should accompany the certificates has caused a marked rise in the price of energy in transit through Germany to the Netherlands. This article discusses the green certificate concept and the experience gained from the Netherlands. One conclusion is that if large-scale trade with green certificates is introduced in Europe without the condition of accompanying energy delivery, then producers of hydro-electric power in Norway and Sweden may be the losers

  15. Infective Causes of Epilepsy.

    Science.gov (United States)

    Bonello, M; Michael, B D; Solomon, T

    2015-06-01

    A wide range of infections of the central nervous system are responsible for both acute seizures and epilepsy. The pathogenesis and clinical semiology of the seizure disorders vary widely between the infective pathogens. The exact mechanisms underlying this are poorly understood, but appear, at least in part, to relate to the pathogen; the degree of cortical involvement; delays in treatment; and the host inflammatory response. The treatment of infective causes of seizures involves both symptomatic treatment with antiepileptic drugs and direct treatment of the underlying condition. In many cases, early treatment of the infection may affect the prognosis of the epilepsy syndrome. The greatest burden of acute and long-term infection-related seizures occurs in resource-poor settings, where both clinical and research facilities are often lacking to manage such patients adequately. Nevertheless, education programs may go a long way toward addressing the stigma, leading to improved diagnosis, management, and ultimately to better quality of life. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. [Relapse: causes and consequences].

    Science.gov (United States)

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  17. Does intuition cause cooperation?

    Science.gov (United States)

    Verkoeijen, Peter P J L; Bouwmeester, Samantha

    2014-01-01

    Recently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more money to a common project when they had to decide quickly (i.e., a decision based on intuition) than when they were instructed to reflect and decide slowly. This intuitive-cooperation effect is of high scientific and practical importance because it argues against a central assumption of traditional economic and evolutionary models. The first experiment of present study was set up to examine the generality of the intuitive-cooperation effect and to further validate the experimental task producing the effect. In Experiment 1, we investigated Amazon Mechanical Turk (AMT) workers' contributions to a 4-player public goods game with a marginal return of 0.5 while we manipulated the knowledge about the other players' contribution to the public goods game (contribution known vs. contribution unknown), the identity of the other players (humans vs. computers randomly generating contributions) and the time constraint (time pressure/intuition vs. forced delay/reflection). However, the results of Experiment 1 failed to reveal an intuitive-cooperation effect. Furthermore, four subsequent direct replications attempts with AMT workers (Experiments 2a, 2b, 2c and Experiment 3, which was conducted with naïve/inexperienced participants) also failed to demonstrate intuitive-cooperation effects. Taken together, the results of the present study could not corroborate the idea that people are intuitively cooperative, hence suggesting that the theoretical relationship between intuition and cooperation should be further scrutinized.

  18. Does intuition cause cooperation?

    Directory of Open Access Journals (Sweden)

    Peter P J L Verkoeijen

    Full Text Available Recently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more money to a common project when they had to decide quickly (i.e., a decision based on intuition than when they were instructed to reflect and decide slowly. This intuitive-cooperation effect is of high scientific and practical importance because it argues against a central assumption of traditional economic and evolutionary models. The first experiment of present study was set up to examine the generality of the intuitive-cooperation effect and to further validate the experimental task producing the effect. In Experiment 1, we investigated Amazon Mechanical Turk (AMT workers' contributions to a 4-player public goods game with a marginal return of 0.5 while we manipulated the knowledge about the other players' contribution to the public goods game (contribution known vs. contribution unknown, the identity of the other players (humans vs. computers randomly generating contributions and the time constraint (time pressure/intuition vs. forced delay/reflection. However, the results of Experiment 1 failed to reveal an intuitive-cooperation effect. Furthermore, four subsequent direct replications attempts with AMT workers (Experiments 2a, 2b, 2c and Experiment 3, which was conducted with naïve/inexperienced participants also failed to demonstrate intuitive-cooperation effects. Taken together, the results of the present study could not corroborate the idea that people are intuitively cooperative, hence suggesting that the theoretical relationship between intuition and cooperation should be further scrutinized.

  19. Environmental Pollution, Causes and Consequences

    OpenAIRE

    Pham van Huong; , Huynh Thanh Dat; Nguyen Quoc Hung

    2017-01-01

    Pollution induces harmful effects on environment and health security. Main deep causes will be analyzed including natural disasters like volcanoes eruption, climate change as well as and men-caused disasters which are nuclear explosions and dioxin sprays.

  20. Drugs that may cause impotence

    Science.gov (United States)

    Impotence caused by medications; Drug-induced erectile dysfunction; Prescription medicines and impotence ... Many medicines and recreational drugs can affect a man's sexual arousal and sexual performance. What causes impotence in one ...

  1. Targeting oncoprotein stability overcomes drug resistance caused by FLT3 kinase domain mutations.

    Directory of Open Access Journals (Sweden)

    Chuanjiang Yu

    Full Text Available FLT3 is the most frequently mutated kinase in acute myeloid leukemia (AML. Internal tandem duplications (ITDs in the juxta-membrane region constitute the majority of activating FLT3 mutations. Several FLT3 kinase inhibitors were developed and tested in the clinic with significant success. However, recent studies have reported the development of secondary drug resistance in patients treated with FLT3 inhibitors. Since FLT3-ITD is an HSP90 client kinase, we here explored if targeting the stability of drug-resistant FLT3 mutant protein could be a potential therapeutic option. We observed that HSP90 inhibitor treatment resulted in the degradation of inhibitor-resistant FLT3-ITD mutants and selectively induced toxicity in cells expressing FLT3-ITD mutants. Thus, HSP90 inhibitors provide a potential therapeutic choice to overcome secondary drug resistance following TKI treatment in FLT3-ITD positive AML.

  2. Applications of root cause analysis

    International Nuclear Information System (INIS)

    Satterwhite, D.G.; Meale, B.M.; Krantz, E.A.

    1986-01-01

    The underlying causes for the failure of components, the root causes, can be obtained from operational data sources. This information is of value in focusing attention of the industry on the actual causes of component unavailability and, therefore, on the important contributors to plant risk. An application of this methodology to an actual plant system, and the results of this study, are presented in this paper

  3. Does excessive pronation cause pain?

    DEFF Research Database (Denmark)

    Olesen, C G; Nielsen, Rasmus Gottschalk N; Rathleff, Michael Skovdal

    2008-01-01

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist of ...

  4. On the Causes of Effects

    Science.gov (United States)

    Dawid, A. Philip; Faigman, David L.; Fienberg, Stephen E.

    2015-01-01

    We welcome Professor Pearl's comment on our original article, Dawid et al. Our focus there on the distinction between the "Effects of Causes" (EoC) and the "Causes of Effects" (CoE) concerned two fundamental problems, one a theoretical challenge in statistics and the other a practical challenge for trial courts. In this…

  5. When Telomerase Causes Telomere Loss.

    Science.gov (United States)

    Glousker, Galina; Lingner, Joachim

    2018-02-05

    Telomerase counteracts telomere shortening, preventing cellular senescence. Telomerase deficiency causes telomere syndromes because of premature telomere exhaustion in highly proliferative cells. Paradoxically, in a recent issue of Cell, Margalef et al. (2018) demonstrate that telomerase causes telomere loss in cells lacking the RTEL1 helicase, which is defective in Hoyeraal-Hreidarsson syndrome (HHS). Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Deaths: leading causes for 2010.

    Science.gov (United States)

    Heron, Melonie

    2013-12-20

    This report presents final 2010 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2010. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2010, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Nephritis, nephrotic syndrome and nephrosis; Influenza and pneumonia; and Intentional self-harm (suicide). These 10 causes accounted for 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2010 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and post-neonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source

  7. Deaths: Leading Causes for 2012.

    Science.gov (United States)

    Heron, Melonie

    2015-08-31

    This report presents final 2012 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2012," the National Center for Health Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2012. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2012, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2012 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  8. Deaths: Leading Causes for 2011.

    Science.gov (United States)

    Heron, Melonie

    2015-07-27

    This report presents final 2011 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements ‘‘Deaths: Final Data for 2011,’’ the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2011. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2011, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2011 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission

  9. Deaths: Leading Causes for 2015.

    Science.gov (United States)

    Heron, Melonie

    2017-11-01

    Objectives-This report presents final 2015 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2015," the National Center for Health Statistics' annual report of final mortality statistics. Methods-Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2015. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. Results-In 2015, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2015 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without

  10. Deaths: Leading Causes for 2013.

    Science.gov (United States)

    Heron, Melonie

    2016-02-16

    This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as

  11. Governing of common cause failures

    International Nuclear Information System (INIS)

    Bock, H.W.

    1998-01-01

    Agreed strategy is to govern common cause failures by the application of diversity, to assure that the overall plant safety objectives are met even in the case that a common cause failure of a system with all redundant trains is assumed. The presented strategy aims on the application of functional diversity without the implementation of equipment diversity. In the focus are the design criteria which have to be met for the design of independent systems in such a way that the time-correlated failure of such independent systems according a common cause can be excluded deterministically. (author)

  12. Research Areas: Causes of Cancer

    Science.gov (United States)

    Understanding the exposures and risk factors that cause cancer, as well as the genetic abnormalities associated with the disease, has helped us to reduce certain exposures and to ameliorate their harmful effects.

  13. Causes of secondary headache (image)

    Science.gov (United States)

    Temporomandibular joint, or TMJ, dysfunction, can be a cause of secondary headache. Secondary headaches result from underlying disorders which produce pain as a symptom. The TMJ may become painful and dysfunctional as a result ...

  14. Noonan Syndrome: Symptoms and Causes

    Science.gov (United States)

    ... be delayed. But because this disorder causes bone maturity to be delayed, growth sometimes continues into the ... mild intellectual disability A wide range of mental, emotional and behavioral issues that are usually mild Hearing ...

  15. THE FUNDAMENTS OF EXPLANATORY CAUSES

    Directory of Open Access Journals (Sweden)

    Lavinia Mihaela VLĂDILĂ

    2015-07-01

    Full Text Available The new Criminal Code in the specter of the legal life the division of causes removing the criminal feature of the offence in explanatory causes and non-attributable causes. This dichotomy is not without legal and factual fundaments and has been subjected to doctrinaire debates even since the period when the Criminal Code of 1969 was still in force. From our perspective, one of the possible legal fundaments of the explanatory causes results from that the offence committed is based on the protection of a right at least equal with the one prejudiced by the action of aggression, salvation, by the legal obligation imposed or by the victim’s consent.

  16. Statins: Do They Cause ALS?

    Science.gov (United States)

    ... muscles needed to move, speak, eat and breathe. Statins are medications prescribed for the treatment of high cholesterol. These medications can sometimes cause muscle pain (myalgia), muscle weakness or, very rarely, severe muscle ...

  17. Endometriosis: Does It Cause Infertility?

    Science.gov (United States)

    ... Website of the American Society for Reproductive Medicine Endometriosis: Does It Cause Infertility? This fact sheet was ... with The Society of Reproductive Surgeons What is endometriosis? Endometriosis is when tissue is found outside the ...

  18. An Unusual Cause of Hydronephroureter

    International Nuclear Information System (INIS)

    Malik, T.; Khan, S.

    2014-01-01

    Intrauterine contraceptive device (IUCD) is a common method of contraception among women because of its low cost and high efficacy. Perforations are possible resulting in multiple complications including urinary complications. Obstructive hydronephrosis and hydroureter is one of the main clinical concerns in genitourinary practice leading to radiological investigations for determination of the cause. Determination of the cause leads to early treatment, hence saving the renal function. In this case report, we describe hydronephrosis and hydroureter secondary to a migrated/displaced IUCD. (author)

  19. Hepatopulmonary syndrome causing severe hypoxaemia

    DEFF Research Database (Denmark)

    Lyngsøe, Bente Kjær; Andersen, Mette Winther; Eriksen, Jan

    2014-01-01

    Dyspnoea is a common complaint in patients with chronic liver disease. Hepatopulmonary syndrome (HPS) is an important cause to be aware of in the setting of liver disease, dyspnoea and hypoxaemia. HPS causes microvascular dilatation, angiogenesis and arteriovenous bypassing. The patients suffer f...... from hypoxaemia in upright position and even during minimal psychical activity. Contrast echocardiography, using micro-bubbles as the contrast, is required to establish the diagnosis. No medical therapy is available, only liver transplantation can cure the disease....

  20. Science 101: What Causes Wind?

    Science.gov (United States)

    Robertson, William C.

    2010-01-01

    There's a quick and easy answer to this question. The Sun causes wind. Exactly how the Sun causes wind takes a bit to explain. We'll begin with what wind is. You've no doubt heard that wind is the motion of air molecules, which is true. Putting aside the huge leap of faith it takes for us to believe that we are experiencing the motion of millions…

  1. [Noroviruses: leading cause of gastroenteritis].

    Science.gov (United States)

    Delacour, H; Dubrous, P; Koeck, J L

    2010-04-01

    Although noroviruses were the first viral agents to be linked to gastrointestinal disease, they were long considered a secondary cause far behind rotaviruses. Development of molecular-based diagnostic techniques has provided clearer insight into the epidemiological impact of noroviruses that are now recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks but also as an important cause of sporadic gastroenteritis in both children and adults. Norovirus infection is generally characterized by mild acute vomiting and diarrhea usually lasting for only a few days, but it can lead to more severe and potentially life-threatening symptoms in high-risk groups such as young children, elderly, and immunodeficient persons. It has been demonstrated that they are present in tropical countries. Molecular epidemiological studies have documented the great genetic diversity of noroviruses with regular emergence of variants. Since no vaccine is available, prevention on norovirus infection depends mainly on strict personal and community hygiene measures.

  2. WELLBORE INSTABILITY: CAUSES AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    Borivoje Pašić

    2007-12-01

    Full Text Available Wellbore instability is one of the main problems that engineers meet during drilling. The causes of wellbore instability are often classified into either mechanical (for example, failure of the rock around the hole because of high stresses, low rock strength, or inappropriate drilling practice or chemical effects which arise from damaging interaction between the rock, generally shale, and the drilling fluid. Often, field instances of instability are a result of a combination of both chemical and mechanical. This problem might cause serious complication in well and in some case can lead to expensive operational problems. The increasing demand for wellbore stability analyses during the planning stage of a field arise from economic considerations and the increasing use of deviated, extended reach and horizontal wells. This paper presents causes, indicators and diagnosing of wellbore instability as well as the wellbore stresses model.

  3. Muscle Deoxygenation Causes Muscle Fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  4. Causes of death in Vanuatu.

    Science.gov (United States)

    Carter, Karen; Tovu, Viran; Langati, Jeffrey Tila; Buttsworth, Michael; Dingley, Lester; Calo, Andy; Harrison, Griffith; Rao, Chalapati; Lopez, Alan D; Taylor, Richard

    2016-01-01

    The population of the Pacific Melanesian country of Vanuatu was 234,000 at the 2009 census. Apart from subsistence activities, economic activity includes tourism and agriculture. Current completeness of vital registration is considered too low to be usable for national statistics; mortality and life expectancy (LE) are derived from indirect demographic estimates from censuses/surveys. Some cause of death (CoD) data are available to provide information on major causes of premature death. Deaths 2001-2007 were coded for cause (ICDv10) for ages 0-59 years from: hospital separations (HS) (n = 636), hospital medical certificates (MC) of death (n = 1,169), and monthly reports from community health facilities (CHF) (n = 1,212). Ill-defined causes were 3 % for hospital deaths and 20 % from CHF. Proportional mortality was calculated by cause (excluding ill-defined) and age group (0-4, 5-14 years), and also by sex for 15-59 years. From total deaths by broad age group and sex from 1999 and 2009 census analyses, community deaths were estimated by deduction of hospital deaths MC. National proportional mortality by cause was estimated by a weighted average of MC and CHF deaths. National estimates indicate main causes of deaths <5 years were: perinatal disorders (45 %) and malaria, diarrhea, and pneumonia (27 %). For 15-59 years, main causes of male deaths were: circulatory disease 27 %, neoplasms 13 %, injury 13 %, liver disease 10 %, infection 10 %, diabetes 7 %, and chronic respiratory disease 7 %; and for females: neoplasms 29 %, circulatory disease 15 %, diabetes 10 %, infection 9 %, and maternal deaths 8 %. Infection included tuberculosis, malaria, and viral hepatitis. Liver disease (including hepatitis and cancer) accounted for 18 % of deaths in adult males and 9 % in females. Non-communicable disease (NCD), including circulatory disease, diabetes, neoplasm, and chronic respiratory disease, accounted for 52 % of premature deaths in adult

  5. Causes of Hypersomnia – Narcolepsy

    Directory of Open Access Journals (Sweden)

    M V Padma Srivastav

    2014-03-01

    Full Text Available The causes of hypersomnia or excessive daytime sleepiness (EDS besides volitionalsleep deprivation and obstructive sleep apnea are principally due to primary centralnervous system abnormalities. Most common amongst these is Narcolepsy, a primarydisorder of the neural control of wakefulness and sleep. The recent discovery ofhypocretin/orexin deficiency as the main cause of narcolepsy will lead to importanttherapeutic advances for patients with narcolepsy and further to understanding of thecontrol of sleep and wakefulness in general. Importantly, the excessive daytimesleepiness is not due to psychiatric conditions, but rather is always due to sleepdeprivation or an underlying diagnosable and treatable sleep disorder.Key words : EDS, Sleep, Narcolepsy

  6. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Mølgaard, Carsten Møller; Olesen Gammelgaard, Christian; Nielsen, R. G.

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...... of antipronation shoes or insoles, which latest was studied by Kulce DG., et al (2007). So far there have been no randomized controlled studies showing methods that the effect of this treatment has not been documented. Therefore the authors can measure the effect of treatments with insoles. Some of the excessive...

  7. Science 101: What Causes Friction?

    Science.gov (United States)

    Robertson, Bill

    2014-01-01

    Defining friction and asking what causes it might seem like a trivial question. Friction seems simple enough to understand. Friction is a force between surfaces that pushes against things that are moving or tending to move, and the rougher the surfaces, the greater the friction. Bill Robertson answers this by saying, "Well, not exactly".…

  8. Water Pollution (Causes, Mechanisms, Solution).

    Science.gov (United States)

    Strandberg, Carl

    Written for the general public, this book illustrates the causes, status, problem areas, and prediction and control of water pollution. Water pollution is one of the most pressing issues of our time and the author communicates the complexities of this problem to the reader in common language. The purpose of the introductory chapter is to show what…

  9. Unusual cause of mechanical ileus

    Energy Technology Data Exchange (ETDEWEB)

    Strobel, E S; Beck, A H

    1987-07-01

    A patient with the signs of mechanic ileus is reported. Past history of dilative cardiomyopathy with atrial fibrillation and the recent occlusion of the left renal artery suggested arterial mesenteric embolism. Celiacography ruled out mesenteric thromboembolism and vigorous enemas resulted in the delivery of the foreign bodies causing the mechanic ileus: 2 '10-Pfennig' coins.

  10. Dislocated Shoulder: Symptoms and Causes

    Science.gov (United States)

    ... caused by: Sports injuries. Shoulder dislocation is a common injury in contact sports, such as football and hockey, and in sports that may involve falls, such as downhill skiing, gymnastics and volleyball. ... is a common source of dislocation. Falls. You may dislocate your ...

  11. Selective Mutism: Causes and Interventions.

    Science.gov (United States)

    Hultquist, Alan M.

    1995-01-01

    This article reviews the literature regarding the diagnostic criteria, causes, assessment, and treatment of selective mutism in school-age children. The most successful treatments have included various forms or combinations of behavior modification, though these may not address the underlying problem. (Author/DB)

  12. Root cause - A regulatory perspective

    International Nuclear Information System (INIS)

    Huey, F.R.

    1990-01-01

    During the past 3 yr, US Nuclear Regulatory Commission (NRC) region V has been pursuing an initiative with region V power reactor licensees to provide improved and more consistent performance in event evaluation. The objectives of the initiative have been to encourage licensees to (a) develop improved skills within the plant organization for events evaluation, with particular emphasis on formal root-cause analysis, and (b) to increase the number of events subjected to root-cause analysis. The NRC's continuing effort now focuses on the need for more consistent quality of event evaluation by licensees. As current licensee programs continue to develop, the NRC will be paying additional attention to how well licensees maintain these programs as an effective and useful tool. Now that licensees have taken the initial steps to establish these programs, licensee management will need to provide continuing attention to ensure that the process does not become overly cumbersome. It is important that the final format for the root-cause programs be easy to use and recognized as being a valuable tool by all licensee personnel involved in the event evaluation process. This will become increasingly important as licensees expand the population of events requiring root-cause analysis and place additional responsibility on the line organization for the implementation of these programs

  13. Endocarditis Caused by Rhodotorula Infection

    OpenAIRE

    Simon, Matthew S.; Somersan, Selin; Singh, Harjot K.; Hartman, Barry; Wickes, Brian L.; Jenkins, Stephen G.; Walsh, Thomas J.; Schuetz, Audrey N.

    2014-01-01

    Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.

  14. Endocarditis caused by Rhodotorula infection.

    Science.gov (United States)

    Simon, Matthew S; Somersan, Selin; Singh, Harjot K; Hartman, Barry; Wickes, Brian L; Jenkins, Stephen G; Walsh, Thomas J; Schuetz, Audrey N

    2014-01-01

    Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.

  15. What Caused the Great Depression?

    Science.gov (United States)

    Caldwell, Jean; O'Driscoll, Timothy G.

    2007-01-01

    Economists and historians have struggled for almost 80 years to account for the American Great Depression, which began in 1929 and lasted until the early years of World War II. In this article, the authors discuss three major schools of thought on the causes of the Great Depression and the long failure of the American economy to return to full…

  16. Mycetoma caused by Nocardia brasiliensis

    Directory of Open Access Journals (Sweden)

    Kar P

    1990-01-01

    Full Text Available One case of actinomycetoma caused by Nocardia brasiliensis presented with a swelling on the right ankle with multiple sinuses discharging sero-sanguinous material without any granules. He was treated successfully with dapsone followed by surgical excision of the swelling and skin graft.

  17. [Gastroduodenal intussusception causing gastric retention.

    DEFF Research Database (Denmark)

    Alamili, M.; Berg, J.O.; Lindstrom, C.

    2008-01-01

    A case of gastroduodenal intussusception caused by a duodenal lipoma is presented. The condition was characterized by severe upper gastrointestinal retention, epigastric pain and weight loss. The mass was diagnosed by CT scan. The diagnosis was confirmed by operation. The patient was treated succ...

  18. Complex Odontome Causing Facial Asymmetry

    Directory of Open Access Journals (Sweden)

    Karthikeya Patil

    2006-01-01

    Full Text Available Odontomas are the most common non-cystic odontogenic lesions representing 70% of all odontogenic tumors. Often small and asymptomatic, they are detected on routine radiographs. Occasionally they become large and produce expansion of bone with consequent facial asymmetry. We report a case of such a lesion causing expansion of the mandible in an otherwise asymptomatic patient.

  19. Other Causes of Leg Pain

    Science.gov (United States)

    ... are visible just under the surface of the skin Spinal stenosis —narrowing in the spine, causing pressure on the nerves and spine, with resulting numbness and pain Lumbar disease Osteoarthritis QUESTIONS TO ASK YOUR HEALTH CARE PROVIDER Does my medical history raise my risk for P.A.D.? Do ...

  20. [Gastroduodenal intussusception causing gastric retention.

    DEFF Research Database (Denmark)

    Alamili, M.; Berg, J.O.; Lindstrom, C.

    2008-01-01

    A case of gastroduodenal intussusception caused by a duodenal lipoma is presented. The condition was characterized by severe upper gastrointestinal retention, epigastric pain and weight loss. The mass was diagnosed by CT scan. The diagnosis was confirmed by operation. The patient was treated...

  1. Unusual Cause of Knee Locking

    Directory of Open Access Journals (Sweden)

    Gazi Huri

    2013-01-01

    Full Text Available We report a case of partial intrasubstance tear of popliteus tendon as an unusual cause of pseudolocking of the knee. A 13-year-old semiprofessional soccer player applied to our clinic with a locked right knee in spite of the therapy applied (cold pack, NSAID, and immobilization in another institution 20 days after the injury. Significant extension loss was observed in his right knee with 30∘–90∘ ROM. Magnetic resonance imaging (MRI and arthroscopy confirmed the intrasubstance tear of popliteus tendon and synovitis. The ruptured part of the tendon was debrided, and the inflammatory tissue around the tendon, which may lead to pseudolocking, was gently removed with a shaver in order to regain the normal ROM. The patient was discharged with full ROM and weight bearing first day after the surgery. To our knowledge, this is the first case demonstrating intrasubstance tear of popliteus tendon causing pseudolocking of the knee.

  2. Toxic agents causing cerebellar ataxias.

    Science.gov (United States)

    Manto, Mario

    2012-01-01

    The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

  3. When exercise causes exertional rhabdomyolysis.

    Science.gov (United States)

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  4. The Causes of Preference Reversal.

    OpenAIRE

    Tversky, Amos; Slovic, Paul; Kahneman, Daniel

    1990-01-01

    Observed preference reversal cannot be adequately explained by violations of independence, the reduction axiom, or transitivity. The primary cause of preference reversal is the failure of procedure invariance, especially the overpricing of low-probability, high-payoff bets. This result violates regret theory and generalized (nonindependent) utility models. Preference reversal and a new reversal involving time preferences are explained by scale compatibility, which implies that payoffs are wei...

  5. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose

    2012-01-01

    on the efficient equilibrium, we consider sunspots as a potential reason for coordination failure. We conduct an experiment with a three player 2x2x2 game in which coordination on the efficient equilibrium is easy and should normally occur. In the control session, we find almost perfect coordination on the payoff......-dominant equilibrium, but in the sunspot treatment, dis-coordination is frequent. Sunspots lead to significant inefficiency, and we conclude that sunspots can indeed cause coordination failure....

  6. Women trafficking: causes, concerns, care!

    Science.gov (United States)

    Khowaja, Shaneela Sadaruddin; Tharani, Ambreen Jawed; Agha, Ajmal; Karamaliani, Rozina Sherali

    2012-08-01

    Pakistan is both a country of origin and destination as far as women trafficking is concerned. Poverty, gender discrimination, lack of education, and ignorance about legal rights are some of the underlying causes. Available data suggest several areas of concern, like, for instance: direct health effects, maladaptive coping leading to the use of illicit drugs, and inaccessibility to healthcare facilities. Therefore, numerous interventions would be required at three levels: the prevention of trafficking, the protection of victims and the prosecution of the traffickers.

  7. A rare cause of osteonecrosis

    Directory of Open Access Journals (Sweden)

    Paolo Agostinis

    2012-01-01

    Full Text Available IntroductionHereditary hemochromatosis (HH is an autosomal recessive disorder caused by mutations in the HFE gene, which increase intestinal iron absorption. The prevalence of C282Y homozygosity, which causes the disorder, is 0.5% in Caucasian populations. The clinical manifestations are related to excess iron in the tissues, especially the liver, heart, pancreas, pituitary, and skin. They include fatigue, loss of libido or impotence in males, liver disease, skin pigmentation, diabetes mellitus, cardiac enlargement—with or without heart failure, and conduction defects. The classic triad of cirrhosis, diabetes mellitus, and skin pigmentation (“bronze diabetes” results from a combination of iron deposits and melanin. It occurs late in the disease, when the total body iron content is more than five times the normal value, about 20 grams. Left untreated, approximately half of all patients with HH eventually develop arthralgia or arthropathy. Chondrocalcinosis, chronic pseudo-osteoarthritis, and osteoporosis are the major rheumatic manifestations of HH. The cause of the arthropathy is still unknown. Iron deposits within joints may trigger a number of pathologic events, such as free radical generation and crystal deposition, which stimulate immune complex formation and inflammation.Materials and methodsWe describe the case of a 48-year-old male suffering from chronic bilateral ankle pain.ResultsThe work-up revealed osteonecrosis of ankle. The patient also presented high plasma ferritin levels and homozygosity for the C282Y mutation. Other than HH, which was confirmed by liver biopsy, the patient had no other risk factors for osteonecrosis.DiscussionHH represents a rare cause of osteonecrosis, and there are no prior reports of aseptic osteonecrosis of the ankle in a patient with this disease. The pathogenetic mechanism remains unknown.

  8. Adrenal Mass Causing Secondary Hypertension.

    Science.gov (United States)

    Robinson, Darlene Y

    2015-11-01

    Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Tyrosine phosphorylation of the BRI1 receptor kinase occurs via a posttranslational modification and is activated by the juxtamembrane domain

    Science.gov (United States)

    In metazoans, receptor kinases control many essential processes related to growth and development and response to the environment. The receptor kinases in plants and animals are structurally similar but evolutionarily distinct from one another, and thus while most animal receptor kinases are tyrosin...

  10. Endocarditis caused by anaerobic bacteria.

    Science.gov (United States)

    Kestler, M; Muñoz, P; Marín, M; Goenaga, M A; Idígoras Viedma, P; de Alarcón, A; Lepe, J A; Sousa Regueiro, D; Bravo-Ferrer, J M; Pajarón, M; Costas, C; García-López, M V; Hidalgo-Tenorio, C; Moreno, M; Bouza, E

    2017-10-01

    Infective endocarditis (IE) caused by anaerobic bacteria is a rare and poorly characterized disease. Most data reported in the literature are from case reports [1-3]. Therefore, we assessed the situation of anaerobic IE (AIE) in Spain using the database of the Spanish Collaboration on Endocarditis (GAMES). We performed a prospective study from 2008 to 2016 in 26 Spanish centers. We included 2491 consecutive cases of definite IE (Duke criteria). Anaerobic bacteria caused 22 cases (0.9%) of definite IE. Median age was 66 years (IQR, 56-73), and 19 (86.4%) patients were men. Most patients (14 [63.6%]) had prosthetic valve IE and all episodes were left-sided: aortic valves, 12 (54.5%); and mitral valves, 8 (36.4%). The most common pathogens were Propionibacterium acnes (14 [63.6%]), Lactobacillus spp (3 [13.63%]), and Clostridium spp. (2 [9.0%]), and the infection was mainly odontogenic. Fifteen of the 22 patients (68.2%) underwent cardiac surgery. Mortality was 18.2% during admission and 5.5% after 1 year of follow-up. When patients with AIE were compared with the rest of the cohort, we found that although those with AIE had a similar age and Charlson comorbidity index, they were more likely to have community-acquired IE (86.4% vs. 60.9%, p = 0.01), have undergone cardiac surgery (68.2% vs 48.7% p = 0.06), and have had lower mortality rates during admission (18.2% vs. 27.3%). IE due to anaerobic bacteria is an uncommon disease that affects mainly prosthetic valves and frequently requires surgery. Otherwise, there are no major differences between AIE and IE caused by other microorganisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Cause of pitting in beryllium

    International Nuclear Information System (INIS)

    Kershaw, R.P.

    1982-01-01

    Light microscopy, bare-film radiography, secondary ion mass spectroscopy, electron microprobe and physical testing were used to examine beryllium specimens exhibiting a stratified, pitted, pattern after chemical milling. The objective was to find the cause of this pattern. Specimens were found to have voids in excess of density specification allowances. These voids are attributed, at least in part, to the sublimation of beryllium fluoride during the vacuum hot pressing operation. The origin of the pattern is attributed to these voids and etching out of fines and associated impurities. Hot isostatic pressing with a subsequent heat treatment close residual porosity and dispersed impurities enough to correct the problem

  13. Onycholysis caused by Candida Krusei

    Directory of Open Access Journals (Sweden)

    Rao S

    2004-01-01

    Full Text Available Onycholysis caused by Candida krusei is rare. A 21 years old male patient presented with grayish discolouration and elevation of all fingernails since one year. Patient was refractory to treatment with fluconazole. Potassium hydroxide preparation of subungual debris revealed fungal elements. Growth on Sabouraud dextrose agar was identified by cultural characteristics, morphotyping, microscopy and biochemical tests as Candida krusei. The isolate was resistant to fluconazole and amphotericin-B but susceptible to nystatin and clotrimazole. Patient responded well to clotrimazole and terbinafine.

  14. NEW TOURISM: CAUSES AND CHARACTERISTICS

    OpenAIRE

    Alberto JonayRodriguez Darias; Agustín Santana Talavera; Pablo Diaz Rodriguez

    2011-01-01

    International tourism has been through major changes, one of them by the 1950s which resulted in conventional forms of tourism. Nevertheless, in the past two decades changes seem to go faster. The upsurge of what was labeled as “new forms of tourism” in the 1990s changed the rules in several ways, turning the planet into a tourist destination and consolidating that “anything can be sold for a tourist”. This paper intends to determine which caused these changes and begin a debate related to th...

  15. NEW TOURISM: CAUSES AND CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Alberto JonayRodriguez Darias

    2011-01-01

    Full Text Available International tourism has been through major changes, one of them by the 1950s which resulted in conventional forms of tourism. Nevertheless, in the past two decades changes seem to go faster. The upsurge of what was labeled as “new forms of tourism” in the 1990s changed the rules in several ways, turning the planet into a tourist destination and consolidating that “anything can be sold for a tourist”. This paper intends to determine which caused these changes and begin a debate related to those (old new forms of tourism and contemporary new forms of tourism.

  16. Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.

    Science.gov (United States)

    Saito, Shinta; Kurosawa, Aya; Adachi, Noritaka

    2016-08-01

    In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V(D)J recombination.

  17. Systemic causes of hair loss.

    Science.gov (United States)

    Lin, Richard L; Garibyan, Lilit; Kimball, Alexandra B; Drake, Lynn A

    2016-09-01

    Hair loss is both a common chief complaint by patients and a clinical challenge for physicians, especially general practitioners, yet few dermatological problems yield as much patient satisfaction when resolved as hair loss. The diagnosis is often attributed to androgen-related hair loss, while other causes, some of which are life-threatening but treatable, are overlooked. We searched for relevant literature on hair loss and supported these findings with our clinical experience to identify seven major systemic etiologies of hair loss, ranging from infectious agents to consumption of unsafe supplements. Many causes are only described in the literature through case studies, though some original articles and meta-analyses are available. Careful history taking, proper examination techniques, and judicious use of laboratory tests are essential to reach at the correct diagnosis in a cost-effective manner when performing patient work-up. Such methodical evaluation of hair loss can result in the appropriate treatment plan and provide significant patient satisfaction. Key messages Hair loss is a common chief complaint and a difficult challenge for both general practitioners and dermatology consultants. We identified seven major categories of systemic hair loss etiology and present a framework for their clinical evaluation. A methodical approach to hair loss can result in the appropriate treatment plan and provide significant patient satisfaction.

  18. Neoplastic causes of abnormal puberty.

    Science.gov (United States)

    Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

    2014-04-01

    Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

  19. 5-HT causes splanchnic venodilation.

    Science.gov (United States)

    Seitz, Bridget M; Orer, Hakan S; Krieger-Burke, Teresa; Darios, Emma S; Thompson, Janice M; Fink, Gregory D; Watts, Stephanie W

    2017-09-01

    Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT 7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT 7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT 1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT 7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT 7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT 7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg -1 ·min -1 ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT 7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT 7 receptor, an in vitro observation (venorelaxation) with in vivo events

  20. Can rain cause volcanic eruptions?

    Science.gov (United States)

    Mastin, Larry G.

    1993-01-01

    Volcanic eruptions are renowned for their violence and destructive power. This power comes ultimately from the heat and pressure of molten rock and its contained gases. Therefore we rarely consider the possibility that meteoric phenomena, like rainfall, could promote or inhibit their occurrence. Yet from time to time observers have suggested that weather may affect volcanic activity. In the late 1800's, for example, one of the first geologists to visit the island of Hawaii, J.D. Dana, speculated that rainfall influenced the occurrence of eruptions there. In the early 1900's, volcanologists suggested that some eruptions from Mount Lassen, Calif., were caused by the infiltration of snowmelt into the volcano's hot summit. Most such associations have not been provable because of lack of information; others have been dismissed after careful evaluation of the evidence.

  1. Adolescent Sleepiness: Causes and Consequences.

    Science.gov (United States)

    Hansen, Shana L; Capener, Dale; Daly, Christopher

    2017-09-01

    Insufficient sleep duration and poor sleep quality are common among adolescents. The multidimensional causes of insufficient sleep duration and poor sleep quality include biological, health-related, environmental, and lifestyle factors. The most common direct consequence of insufficient and/or poor sleep quality is excessive daytime sleepiness, which may contribute to poor academic performance, behavioral health problems, substance use, and drowsy driving. Evaluation of sleepiness includes a detailed sleep history and sleep diary, with polysomnography only required for the assessment of specific sleep disorders. Management involves encouraging healthy sleep practices such as having consistent bed and wake times, limiting caffeine and electronics at night before bed, and eliminating napping, in addition to treating any existing sleep or medical disorders. [Pediatr Ann. 2017;46(9):e340-e344.]. Copyright 2017, SLACK Incorporated.

  2. Cholestasis caused by Fasciola gigantica.

    Science.gov (United States)

    Beştaş, Remzi; Yalçin, Kendal; Çiçek, Muttalip

    2014-01-01

    Fascioliasis is an infectious disease caused by the hepatic trematodes Fasciola hepatica and Fasciola gigantica. Here, we report the case of Fasciola gigantica presenting with biliary obstruction and abdominal pain that was diagnosed and treated by endoscopic retrograde cholangiography (ERCP). A 46-year-old woman presented with right upper quadrant abdominal pain and jaundice. Physical examination revealed icterus and hepatomegaly. Laboratory findings revealed an increase in liver transaminases and bilirubin. Abdominal ultrasonography showed extrahepatic and intrahepatic bile duct dilatation. The patient underwent ERCP. One live Fasciola gigantica was removed from the common bile duct by ERCP. In conclusion, fascioliasis should be considered in the differential diagnosis of obstructive jaundice, especially in endemic regions, and it should be kept in mind that ERCP plays an important role in the diagnosis and treatment of these patients. To our knowledge, this is the second case report of Fasciola gigantica treated by ERCP in Turkey.

  3. A rare cause of hemoptysis

    Directory of Open Access Journals (Sweden)

    Meghan Aversa

    2014-01-01

    Full Text Available Angiosarcomas are rare, malignant, endothelial-cell tumors of vascular origin that can arise at any body site. They frequently metastasize to the lung, heralded by dyspnea, hemoptysis, chest pain, pneumothoraces, and diffuse pulmonary hemorrhage. However, in most cases lung metastases are discovered after the diagnosis of a primary angiosarcoma has already been established. Very rarely will an undiagnosed metastatic angiosarcoma present as diffuse pulmonary hemorrhage. We describe the case of a 59-year-old male who presented to hospital with dyspnea and hemoptysis. CT chest revealed rapidly progressing nodular changes and broncho-alveolar lavage returns were progressively bloody. Open lung wedge biopsy ultimately revealed metastatic angiosarcoma and extensive pulmonary hemorrhage. Our case highlights the key clinical, radiological, and pathological features of this rare malignancy that frequently metastasizes to the lung and reminds clinicians to consider it as a cause of hemoptysis and pulmonary hemorrhage.

  4. Does Corruption Cause Aid Fatigue?

    DEFF Research Database (Denmark)

    Bauhr, Monika; Charron, Nicholas; Nasiritousi, Naghmeh

    2013-01-01

    Does perceived corruption in recipient countries reduce support for foreign aid in donor countries? This under-explored yet salient question is examined using the 2009 Eurobarometer survey for the 27 EU countries. We suggest that perceived corruption can cause aid fatigue but that this relationship...... is highly contextualized. The results show that perceptions about corruption in developing countries reduce overall support for aid among respondents in donor countries. However, this effect is mitigated by country and contextual-level effects and different understandings of what we call the “aid-corruption...... paradox,” namely that the need for foreign aid is often the greatest in corrupt environments. Three different dynamics of the aid-corruption paradox influence support for aid: moral, pragmatic, and strategic understandings. In EU-15 countries, the effect of perceived corruption in recipient states on aid...

  5. Codfish may cause acute abdomen☆

    Science.gov (United States)

    Costa Almeida, Carlos E.; Rainho, Rui; Gouveia, António

    2013-01-01

    INTRODUCTION Foreign bodies ingestion is frequent and can cause several complications. Perforation is rare but can occur in any segment of the gastrointestinal tract. Fish bones are one of the most frequent objects responsible. PRESENTATION OF CASE A 77-year-old patient resorted to emergency room for severe abdominal pain with 5 days of evolution. A CT scan showed an undefined liquid collection involving a linear image with 25 mm, suggestive of a foreign body. On laparotomy an abscess was resected with a fish bone inside. DISCUSSION Bowel perforation by foreign bodies can mimic other abdominal emergency conditions. Since fish bone ingestion is usually not remembered, diagnosis can be late. Surgery is the treatment of choice and is most commonly performed by laparotomy. CONCLUSION A low threshold of suspicion along with a good clinical history and radiological studies is extremely important in order to make a correct diagnosis. PMID:24055920

  6. Contact dermatitis caused by preservatives.

    Science.gov (United States)

    Yim, Elizabeth; Baquerizo Nole, Katherine L; Tosti, Antonella

    2014-01-01

    Preservatives are biocidal chemicals added to food, cosmetics, and industrial products to prevent the growth of microorganisms. They are usually nontoxic and inexpensive and have a long shelf life. Unfortunately, they commonly cause contact dermatitis. This article reviews the most important classes of preservatives physicians are most likely to encounter in their daily practice, specifically isothiazolinones, formaldehyde and formaldehyde-releasers, iodopropynyl butylcarbamate, methyldibromoglutaronitrile, and parabens. For each preservative mentioned, the prevalence of sensitization, clinical presentation of contact dermatitis, patch testing concentrations, cross reactions, and related legislation will be discussed. Mandatory labeling of preservatives is required in some countries, but not required in others. Until policies are made, physicians and patients must be proactive in identifying potential sensitizers and removing their use. We hope that this article will serve as a guide for policy makers in creating legislation and future regulations on the use and concentration of certain preservatives in cosmetics and industrial products.

  7. [Epilepsy: incidens, prevalens and causes].

    Science.gov (United States)

    Forsgren, Lars; Sundelin, Heléne; Sveinsson, Olafur

    2018-05-21

    Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.

  8. Copper disinfection ban causes storm.

    Science.gov (United States)

    Lester, Alan

    2013-05-01

    Since 1 February this year, under the EU's Biocidal Products Directive, it has been illegal to sell or use water treatment systems that use elemental copper, a practice employed historically by a significant number of UK healthcare facilities to combat Legionella. Alan Lester, managing director of specialist supplier of 'environmentally-friendly' water treatment systems, Advanced Hydro, says the ban has caused 'a storm of giant proportion,' with advocates of copper ion-based treatment systems arguing that this disinfection method dates back 3,000 years to Egyptian times, making it an 'undoubtedly proven' technology. Here he explains why the ban came into force, considers why the UK's Health and Safety Executive (HSE) is seeking a derogation, looks at the ban's likely impact, and gives a personal viewpoint on the 'pros and cons' of some of the alternative treatment technologies, including a titanium dioxide-based system marketed by Advanced Hydro itself in the UK.

  9. Hyperprolactinemia: causes, diagnosis, and treatment

    International Nuclear Information System (INIS)

    Karasek, M.; Pawlikowski, M.; Lewinski, A.

    2006-01-01

    The basic data on hyperprolactinemia (i.e. an excess of PRL above a reference laboratory's upper limits), the most common endocrine disorder of the hypothalamic-pituitary axis are given in this review. The following issues are discussed: regulation of prolactin (Prl) secretion, definition of hyperprolactinemia, its etiology and pathogenesis as well as its symptoms, diagnosis, and treatment (including medical and surgical therapy). It should be stressed that finding of elevated PRL serum concentrations constitute the beginning of diagnostic procedure and, after exclusion of physiologic, pharmacologic, and other organic causes of increased PRL levels, should be followed by detailed diagnosis including MRI. In patients in whom hyperprolactinemia has been confirmed the treatment with dopamine agonists (with prevalence of cabergoline, followed by quinagoline) is currently considered first-choice therapy. Surgery should be performed only in the patients resistant or intolerant to these agents, or in patients who refuse long-term therapy. (author)

  10. Rash caused by Oryctes nasicornis.

    Science.gov (United States)

    Veraldi, Stefano; Fanoni, Daniele; Nazzaro, Gianluca

    2016-02-01

    We report a case of rash caused by crushing of a male of Oryctes nasicornis (Linnaeus 1758) (Coleoptera, "http:// it. wikipedia. org/ wiki/ Scarabaeidae" \\o "Scarabaeidae" Scarabaeidae), popularly known as "European rhinoceros beetle", on the skin of an Italian tourist who developed the reaction during a trip to Turkey. The rash appeared one hour after the crushing of the insect on the skin. The patient was observed one day later, when she returned to Italy. To our knowledge, no similar cases have been reported in the literature. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

  11. Can cardiac surgery cause hypopituitarism?

    Science.gov (United States)

    Francis, Flverly; Burger, Ines; Poll, Eva Maria; Reineke, Andrea; Strasburger, Christian J; Dohmen, Guido; Gilsbach, Joachim M; Kreitschmann-Andermahr, Ilonka

    2012-03-01

    Apoplexy of pituitary adenomas with subsequent hypopituitarism is a rare but well recognized complication following cardiac surgery. The nature of cardiac on-pump surgery provides a risk of damage to the pituitary because the vascular supply of the pituitary is not included in the cerebral autoregulation. Thus, pituitary tissue may exhibit an increased susceptibility to hypoperfusion, ischemia or intraoperative embolism. After on-pump procedures, patients often present with physical and psychosocial impairments which resemble symptoms of hypopituitarism. Therefore, we analyzed whether on-pump cardiac surgery may cause pituitary dysfunction also in the absence of pre-existing pituitary disease. Twenty-five patients were examined 3-12 months after on-pump cardiac surgery. Basal hormone levels for all four anterior pituitary hormone axes were measured and a short synacthen test and a growth hormone releasing hormone plus arginine (GHRH-ARG)-test were performed. Quality of life (QoL), depression, subjective distress for a specific life event, sleep quality and fatigue were assessed by means of self-rating questionnaires. Hormonal alterations were only slight and no signs of anterior hypopituitarism were found except for an insufficient growth hormone rise in two overweight patients in the GHRH-ARG-test. Psychosocial impairment was pronounced, including symptoms of moderate to severe depression in 9, reduced mental QoL in 8, dysfunctional coping in 6 and pronounced sleep disturbances in 16 patients. Hormone levels did not correlate with psychosocial impairment. On-pump cardiac surgery did not cause relevant hypopituitarism in our sample of patients and does not serve to explain the psychosocial symptoms of these patients.

  12. Epidermoid Causing Ischemic Stroke in the Brainstem

    Directory of Open Access Journals (Sweden)

    Raghvendra Ramdasi

    2014-01-01

    Full Text Available Intracranial tumors may rarely cause stroke. We report an epidermoid cyst causing stroke in a pediatric patient. We have also reviewed the literature and pathogenesis of stroke caused by intracranial tumors.

  13. Ten Leading Causes of Death and Injury

    Science.gov (United States)

    ... Overdose Traumatic Brain Injury Violence Prevention Ten Leading Causes of Death and Injury Recommend on Facebook Tweet Share Compartir ... in Hospital Emergency Departments, United States – 2014 Leading Causes of Death Charts Causes of Death by Age Group 2016 [ ...

  14. Anxiety: A Cause of High Blood Pressure?

    Science.gov (United States)

    ... of high blood pressure? Can anxiety cause high blood pressure? Answers from Sheldon G. Sheps, M.D. Anxiety doesn't cause long-term high blood pressure (hypertension). But episodes of anxiety can cause dramatic, ...

  15. Can ureteral stones cause pain without causing hydronephrosis?

    Science.gov (United States)

    Song, Yan; Hernandez, Natalia; Gee, Michael S; Noble, Vicki E; Eisner, Brian H

    2016-09-01

    While computerized tomography (CT) is the gold standard for diagnosis of ureterolithiasis, ultrasound is a less costly and radiation-free alternative which is commonly used to evaluate patients with ureteral colic. The purpose of this study was to evaluate the frequency with which patients with ureteral stones and renal colic demonstrate hydronephrosis in order to better understand the evaluation of these patients. Two hundred and forty-eight consecutive patients presenting with ureteral colic and diagnosed with a single unilateral ureteral stone on CT scan in an urban tertiary care emergency department were retrospectively reviewed. Radiology reports were reviewed for stone size, diagnosis, and degree of hydronephrosis. Of the 248 patients evaluated for suspected ureteral stone, 221 (89.1 %) demonstrated any hydronephrosis, while 27 (10.9 %) did not. Hydronephrosis grade, available in 194 patients, was as follows: mild-70.6 %, moderate-27.8 %, and severe-1.5 %. Mean patient age was 47.0 years (SD 15.5), gender distribution was 35.9 % female and 64.1 % male, and mean stone axial diameter was 4.1 mm (SD 2.4). Stone location was as follows: ureteropelvic junction-4.1 %, proximal ureter-21 %, distal ureter-24.9 %, and ureterovesical junction-47.1 %. Axial stone diameter and coronal length (craniocaudal) were both significant predictors of degree of hydronephrosis (ANOVA, p hydronephrosis. In patients with ureteral stones and colic, nearly 11 % do not demonstrate any hydronephrosis and a majority (nearly 71 %) will demonstrate only mild hydronephrosis. Stone diameter appears to be related to degree of hydronephrosis, whereas age, gender, and stone location are not. The lower incidence of hydronephrosis for small stones causing renal colic may explain the lower diagnostic accuracy of ultrasound when compared to CT for detecting ureteral stones.

  16. Infection caused by Mycobacterium tuberculosis.

    Science.gov (United States)

    Peloquin, C A; Berning, S E

    1994-01-01

    To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future. The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts. Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis. Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented. The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control

  17. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    multiple causes of carcinogenesis and shifts the risk-assessment logic to considerations of "what dose does?" in contrast to the current process of the substance-specific question of "what dose is?" Whether reactive oxygen is the proximate or contributing cause of disease or simply a better estimate of biologically effective dose, it has enormous advantages for improved risk- and policy-based decisions. Various estimates of immune system modulation will be given based on radiobiology.

  18. Childhood obesity: causes and consequences.

    Science.gov (United States)

    Sahoo, Krushnapriya; Sahoo, Bishnupriya; Choudhury, Ashok Kumar; Sofi, Nighat Yasin; Kumar, Raman; Bhadoria, Ajeet Singh

    2015-01-01

    Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Childhood obesity can profoundly affect children's physical health, social, and emotional well-being, and self esteem. It is also associated with poor academic performance and a lower quality of life experienced by the child. Many co-morbid conditions like metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and renal disorders are also seen in association with childhood obesity.

  19. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  20. Childhood obesity: causes and consequences

    Directory of Open Access Journals (Sweden)

    Krushnapriya Sahoo

    2015-01-01

    Full Text Available Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Childhood obesity can profoundly affect children′s physical health, social, and emotional well-being, and self esteem. It is also associated with poor academic performance and a lower quality of life experienced by the child. Many co-morbid conditions like metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and renal disorders are also seen in association with childhood obesity.

  1. Environmental Degradation: Causes and Consequences

    Directory of Open Access Journals (Sweden)

    Swati Tyagi

    2014-08-01

    Full Text Available The subject of environmental economics is at the forefront of the green debate: the environment can no longer be viewed as an entity separate from the economy. Environmental degradation is of many types and have many consequences. To address this challenge a number of studies have been conducted in both developing and developed countries applying different methods to capture health benefits from improved environmental quality. Minimizing exposure to environmental risk factors by enhancing air quality and access to improved sources of drinking and bathing water, sanitation and clean energy is found to be associated with significant health benefits and can contribute significantly to the achievement of the Millennium Development Goals of environmental sustainability, health and development. In this paper, I describe the national and global causes and consequences of environmental degradation and social injustice. This paper provides a review of the literature on studies associated with reduced environmental risk and in particular focusing on reduced air pollution, enhanced water quality and climate change mitigation.

  2. INTERCULTURAL MISUNDERSTANDINGS: CAUSES AND SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Майкл Б Хиннер

    2017-12-01

    Full Text Available Intercultural misunderstandings involve a number of complex causes which can easily escalate into conflicts. Since conflicts are also complex, it is not easy to find solutions because there is no one solution for all problems. Systems Theory, transdisciplinarity, and the social ecological model take a holistic approach in investigating complex phenomena. They permit the creation of a theoretical framework based on previous empirical research and theories across scientific disciplines to identify the relevant elements of complex phenomena and to understand the interrelationship of these elements. Intercultural misunderstandings and conflicts are very complex phenomena because they include culture, perception, identity, ethnocentrism, relationships, trust building and conflict management as well as intercultural commu-nication competence which entails cognition, metacognition, and social metacognition. Since most em-pirical studies focus on isolated, individual elements in specific contexts, this article describes the theoretical framework of how the various findings and theories developed in different scientific disciplines can be used to form a cohesive framework to help circumvent intercultural misunderstandings and conflicts. In so doing, it follows the general principles of Systems Theory, transdisciplinarity, and the social ecological model.

  3. Dyscalculia: Characteristics, Causes, and Treatments

    Directory of Open Access Journals (Sweden)

    Gavin R. Price

    2013-01-01

    Full Text Available Developmental Dyscalculia (DD is a learning disorder affecting the ability to acquire school-level arithmetic skills, affecting approximately 3-6% of individuals. Progress in understanding the root causes of DD and how best to treat it have been impeded by lack of widespread research and variation in characterizations of the disorder across studies. However, recent years have witnessed significant growth in the field, and a growing body of behavioral and neuroimaging evidence now points to an underlying deficit in the representation and processing of numerical magnitude information as a potential core deficit in DD. An additional product of the recent progress in understanding DD is the resurgence of a distinction between ‘primary’ and ‘secondary’ developmental dyscalculia. The first appears related to impaired development of brain mechanisms for processing numerical magnitude information, while the latter refers to mathematical deficits stemming from external factors such as poor teaching, low socio-economic status, and behavioral attention problems or domain-general cognitive deficits. Increased awareness of this distinction going forward, in combination with longitudinal empirical research, offers great potential for deepening our understanding of the disorder and developing effective educational interventions.

  4. Evolution caused by extreme events.

    Science.gov (United States)

    Grant, Peter R; Grant, B Rosemary; Huey, Raymond B; Johnson, Marc T J; Knoll, Andrew H; Schmitt, Johanna

    2017-06-19

    Extreme events can be a major driver of evolutionary change over geological and contemporary timescales. Outstanding examples are evolutionary diversification following mass extinctions caused by extreme volcanism or asteroid impact. The evolution of organisms in contemporary time is typically viewed as a gradual and incremental process that results from genetic change, environmental perturbation or both. However, contemporary environments occasionally experience strong perturbations such as heat waves, floods, hurricanes, droughts and pest outbreaks. These extreme events set up strong selection pressures on organisms, and are small-scale analogues of the dramatic changes documented in the fossil record. Because extreme events are rare, almost by definition, they are difficult to study. So far most attention has been given to their ecological rather than to their evolutionary consequences. We review several case studies of contemporary evolution in response to two types of extreme environmental perturbations, episodic (pulse) or prolonged (press). Evolution is most likely to occur when extreme events alter community composition. We encourage investigators to be prepared for evolutionary change in response to rare events during long-term field studies.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

  5. Offshore Blowouts, Causes and Trends

    Energy Technology Data Exchange (ETDEWEB)

    Holand, P

    1996-02-01

    The main objective of this doctoral thesis was to establish an improved design basis for offshore installations with respect to blowout risk analyses. The following sub objectives are defined: (1) Establish an offshore blowout database suitable for risk analyses, (2) Compare the blowout risk related to loss of lives with the total offshore risk and risk in other industries, (3) Analyse blowouts with respect to parameters that are important to describe and quantify blowout risk that has been experienced to be able to answer several questions such as under what operations have blowouts occurred, direct causes, frequency of occurrence etc., (4) Analyse blowouts with respect to trends. The research strategy applied includes elements from both survey strategy and case study strategy. The data are systematized in the form of a new database developed from the MARINTEK database. Most blowouts in the analysed period occurred during drilling operations. Shallow gas blowouts were more frequent than deep blowouts and workover blowouts occurred more often than deep development drilling blowouts. Relatively few blowouts occurred during completion, wireline and normal production activities. No significant trend in blowout occurrences as a function of time could be observed, except for completion blowouts that showed a significantly decreasing trend. But there were trends regarding some important parameters for risk analyses, e.g. the ignition probability has decreased and diverter systems have improved. Only 3.5% of the fatalities occurred because of blowouts. 106 refs., 51 figs., 55 tabs.

  6. The HGF/c-MET Axis as a Critical Driver of Resistance to Androgen Suppression in Metastatic Castrate-Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    signaling inhibition in AR-positive CRPC models increased MET expression and resulted in susceptibility to ligand (HGF) activation. Likewise, our work...positive CRPC models , as detailed in the initial proposal, we found that combined MET inhibition and enzalutamide (AR antagonist) treatment was more...wide analyses, we will be able to better test the study hypothesis with increased patient accrual. Figure: Waterfall plots showing association

  7. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways

    DEFF Research Database (Denmark)

    Bosse, Tanja; Ehinger, Julia; Czuchra, Aleksandra

    2007-01-01

    -WASP. Instead, actin polymerization was driven by Arp2/3 complex activation through the WAVE complex downstream of Rac. Together, our data establish an intricate signaling network comprising as key molecules Cdc42 and PI3-kinase, which converge on Rac-mediated actin reorganization essential for Listeria...

  8. Hypocalcaemia: Causes, diagnostics and treatment

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2014-01-01

    Full Text Available Hypocalcaemia is a state with total calcium serum level below 2.25 mM/l. From the total serum calcium content, 50% is free and ionized, 40% is protein-bound and 10% is bound for organic anions. The most frequent causes of hypocalcaemia are iatrogenic hypoparathyroidism, magnesium deficit, disorders of vitamin D metabolism and chronic renal failure. Iatrogenic hypoparathyroidism is associated with low serum ionized calcium and low serum parathormone levels. There are two important clinical signs of hypocalcemia: Chvostek's sign (twitches of upper lip after percussion on facial nerve over mandible and Trousseau's sign (carpal spasm after increasing pressure in blood pressure cuff placed about the upper arm for 20 milimeters above systolic pressure for 3-5 minutes. The following lab analyses should be performed when hypocalcaemia is an option: serum levels of creatinine, calcium, magnesium, 25 - hydroxyvitamin, parathormone, potassium, sodium, chloride and bicarbonates. If hypocalcaemia is mild, it could be treated with oral calcium preparations, usually calcium carbonate, in a dose of 1 to 2 grams of elemental calcium daily. In more severe hypocalcaemia intravenous calcium-gluconate or calcium-chloride should be administered, as 10% solutions. These parenteral preparations of calcium should be diluted prior to the intravenous administration, and the administration should be longer than 20 minutes in order to avoid adverse effects on heart. If administration of calcium does not correct hypocalcaemia, oral vitamin D should be also prescribed. If this does not regulate calcaemia, from 0.25 to 1 micrograms of 1,25-dihydroxyvitamin D (clacitriol daily should be prescribed. Calcium serum levels should be kept within the lower part of normal serum concentration range.

  9. Mechanics of integrating root causes into PRAs

    International Nuclear Information System (INIS)

    Bruske, S.Z.; Cadwallader, L.C.; Stepina, P.L.; Vesely, W.E.

    1985-01-01

    This paper presents a derivation of root cause importance, root cause data for selected components of a pressurized water reactor auxiliary feedwater system, an Accident Sequence Evaluation Program (ASEP) auxiliary feedwater system model, and the results of root cause importance calculations. The methodology shown herein is straightforward and is easily applied to existing probabilistic risk assessments. Root cause importance can greatly benefit the areas of design, maintenance, and inspection. Root cause importance for various components and circumstances can be evaluated

  10. Root cause and how to find it

    International Nuclear Information System (INIS)

    Gano, D.L.

    1987-01-01

    This paper provides an in-depth discussion of the definition of root cause, the use of the cause-and-effect process to find the root cause, and the use of proper cause categorization as a means to better understand the nuances of root cause. It also provides a detailed statistical breakdown of reactor trips at boiling water reactors for 1986 as compiled from Boiling Water Reactor Owners' Group Scram Frequency Reduction Commitee (BWROGSFRC) data

  11. Sucrose ingestion causes opioid analgesia

    Directory of Open Access Journals (Sweden)

    F.N. Segato

    1997-08-01

    Full Text Available The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12 for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47 = 9.521, P<0.001 and the Tukey multiple comparison test (P<0.05 showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7 receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7 had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03. This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

  12. Esophageal hypermotility: cause or effect?

    Science.gov (United States)

    Crespin, O M; Tatum, R P; Yates, R B; Sahin, M; Coskun, K; Martin, A V; Wright, A; Oelschlager, B K; Pellegrini, C A

    2016-07-01

    Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients' symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring

  13. HERBAL SUPPLEMENTS: CAUSE FOR CONCERN?

    Directory of Open Access Journals (Sweden)

    Paolo Borrione

    2008-12-01

    effects. Also, some herbs are safe in modest amounts but they may become toxic at higher doses. For example, liquorice root can be used safely for treating duodenal and gastric ulcers, but large amounts of liquorice can cause serious side effects such as hypokalemia, high blood pressure, and heart failure. Finally, other herbs, toxic by themselves: for example, germander, an herb used in some weight-loss programs, can cause fatal hepatitis. Other herbs may be toxic because of possible contaminants: the Chinese herbs caowu and chuanwu used for the management of rheumatism, arthritis, bruises, and fractures may contain highly toxic potentially fatal alkaloids such as aconitine.Therefore, despite the increased tendency to seek natural therapies, athletes have to be aware that "natural" does not equal to "safe." Herbs should not be touted as miraculous side effects-free substances, but rather as compounds that work through simple biochemistry. The effects of most herbal supplements have not been studied using rigorous scientific methodology, and the hyperbolic advertising and advocacy literature surrounding herbal products often contains untested claims, and under-reports side effects.All the preparations mentioned above exhibit hormone-like activity. Evidence in animals of reproductive disturbances associated with ingestion of feed rich in oestrogenic substances includes a lower conception rate in sheep after prolonged isoflavones consumption, infertility in cattle after consuming feed containing coumestrol, decreased fertility in captive cheetahs fed with dietary oestrogens, hyperoestrogenism in pigs fed with diets containing zearalenone, uterotropic effects in mice fed with soybean, reduced fecundity in adult males rats fed a high phytoestrogen diet for 3 days (Glover and Assinder, 2006; Srilatha, 2004 Also, in a population-based cohort study in the United Kingdom, a vegetarian diet during pregnancy was associated with a 5-fold higher risk of hypospadias, and consumption

  14. Common-cause analysis using sets

    International Nuclear Information System (INIS)

    Worrell, R.B.; Stack, D.W.

    1977-12-01

    Common-cause analysis was developed at the Aerojet Nuclear Company for studying the behavior of a system that is affected by special conditions and secondary causes. Common-cause analysis is related to fault tree analysis. Common-cause candidates are minimal cut sets whose primary events are closely linked by a special condition or are susceptible to the same secondary cause. It is shown that common-cause candidates can be identified using the Set Equation Transformation System (SETS). A Boolean equation is used to establish the special conditions and secondary cause susceptibilities for each primary event in the fault tree. A transformation of variables (substituting equals for equals), executed on a minimal cut set equation, results in replacing each primary event by the right side of its special condition/secondary cause equation and leads to the identification of the common-cause candidates

  15. A Rare Cause of Postprandial Abdominal Pain

    African Journals Online (AJOL)

    causes abdominal symptoms. Median ... compression of the coeliac artery by the median arcuate ligament. ... existing symptoms might cause frustration to patient and relatives. ... disease, chest pathology, etc., were excluded from the study.

  16. Symptoms and Causes of Peptic Ulcer Disease

    Science.gov (United States)

    ... ulcer. How do H. pylori cause a peptic ulcer and peptic ulcer disease? H. pylori are spiral-shaped bacteria that ... peptic ulcer. How do tumors from ZES cause peptic ulcers? Zollinger-Ellison syndrome is a rare disorder that ...

  17. Restless Legs Syndrome -- Causes and Symptoms

    Science.gov (United States)

    ... miles): 10 25 50 Share: Essentials in Sleep Insomnia Overview & Facts Symptoms & Causes Diagnosis & Self Tests Treatment Sleep Apnea Overview & Facts ... Self Test & Diagnosis Treatment Snoring Overview and Facts Causes and Symptoms Self Tests & ... Insomnia Short Sleeper Hypersomnias Narcolepsy Insufficient ...

  18. Mesenteric lipoma causing recurrent intestinal obstruction

    African Journals Online (AJOL)

    2013-01-12

    Jan 12, 2013 ... vomiting, constipation, and central abdominal mass. ... Mesenteric lipoma may cause abdominal pain by complete intestinal .... Kaniklides C, Frykberg T, Lundkvist K. Pediatric mesenteric lipoma: An unusual cause of repeated ...

  19. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    Science.gov (United States)

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  20. Sjogren's Syndrome: Can It Cause Recurrent UTIs?

    Science.gov (United States)

    ... Sjogren's syndrome last year, I've had three urinary tract infections. Is there any evidence that Sjogren's syndrome causes ... cause symptoms that you might mistake for a urinary tract infection (UTI). Sjogren's syndrome is an autoimmune disorder in ...

  1. Urinary infection caused by Micrococcus subgroup 3

    Science.gov (United States)

    Kerr, Helen

    1973-01-01

    The laboratory findings and clinical presentations in urinary infections in 23 nurses, 10 caused by Micrococcus subgroup 3 and 13 by Escherichia coli, were studied, and the symptoms and possible predisposing factors compared. There were no important differences between the two groups. The infections caused by Micrococcus subgroup 3 were symptomatically severe, as were those caused by Escherichia coli. PMID:4593863

  2. Ventriculoperitoneal shunt infection caused by Bifidobacterium breve.

    Science.gov (United States)

    Suwantarat, Nuntra; Romagnoli, Mark; Wakefield, Teresa; Carroll, Karen C

    2014-08-01

    Bifidobacterium breve is a rare cause of human infections. Previously, bacteremia and meningitis caused by this organism linked to probiotic use have been reported in a neonate. We report the first case of a ventriculoperitoneal shunt infection caused by B. breve in an adult without a history of probiotic use. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Data needs for common cause failure analysis

    International Nuclear Information System (INIS)

    Parry, G.W.; Paula, H.M.; Rasmuson, D.; Whitehead, D.

    1990-01-01

    The procedures guide for common cause failure analysis published jointly by USNRC and EPRI requires a detailed historical event analysis. Recent work on the further development of the cause-defense picture of common cause failures introduced in that guide identified the information that is necessary to perform the detailed analysis in an objective manner. This paper summarizes these information needs

  4. Common cause failures of reactor pressure components

    International Nuclear Information System (INIS)

    Mankamo, T.

    1978-01-01

    The common cause failure is defined as a multiple failure event due to a common cause. The existence of common failure causes may ruin the potential advantages of applying redundancy for reliability improvement. Examples relevant to large mechanical components are presented. Preventive measures against common cause failures, such as physical separation, equipment diversity, quality assurance, and feedback from experience are discussed. Despite the large number of potential interdependencies, the analysis of common cause failures can be done within the framework of conventional reliability analysis, utilizing, for example, the method of deriving minimal cut sets from a system fault tree. Tools for the description and evaluation of dependencies between components are discussed: these include the model of conditional failure causes that are common to many components, and evaluation of the reliability of redundant components subjected to a common load. (author)

  5. Unusual causes of spinal foraminal widening

    Energy Technology Data Exchange (ETDEWEB)

    Zibis, A.H.; Markonis, A.; Karantanas, A.H. [Dept. of CT and MRI, Larissa General Hospital (Greece)

    2000-01-01

    Spinal neural foraminal widening is usually caused by benign lesions, most commonly neurofibromas. Rare lesions can also cause spinal neural foraminal widening. Computed tomography and/or MRI are the modalities of choice for studying the spinal foraminal widening. The present pictorial review describes six rare lesions, namely a lateral thoracic meningocele, a malignant fibrous histiocytoma, a tuberculous abscess, an osteoblastoma, a chondrosarcoma and a malignant tumour of the lung which caused spinal neural foraminal widening. (orig.)

  6. Oral Habits That Cause Malocclusion Problems

    OpenAIRE

    Joelijanto, Rudy

    2012-01-01

    Oral habits that place pressure on the teeth may slowly move the teeth out of place. The aim of this study was to review the literature for articles referring the most common oral habits that cause malocclusion. The oral bad habits that cause malocclussion problems include: Thumb sucking, It is a normal habit for babies, but causes serious orthodontic problems if it continues long after the eruption of permanent teeth. Prolonged thumb sucking can create crowded, crooked teeth, or bite problem...

  7. An unusual cause of anemia and encephalopathy

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar Sharma

    2015-04-01

    Full Text Available The authors present here an interesting case of recent onset anemia that was associated with an encephalopathy of the unusual cause.Although severe anemia can theoretically result in anemic hypoxia and can then lead to hypoxic encephalopathy, it is not a primary cause of encephalopathy. More frequently anemia can contribute together with other multiple causes of encephalopathy, such as infections, metabolic abnormalities, trauma, hepatic dysfunction, hypertension, toxins.

  8. Breakdown Cause and Effect Analysis. Case Study

    Science.gov (United States)

    Biały, Witold; Ružbarský, Juraj

    2018-06-01

    Every company must ensure that the production process proceeds without interferences. Within this article, the author uses the term "interferences" in reference to unplanned stoppages caused by breakdowns. Unfortunately, usually due to machine operators' mistakes, machines break, which causes stoppages thus generating additional costs for the company. This article shows a cause and effect analysis of a breakdown in a production process. The FMEA as well as quality management tools: the Ishikawa diagram and Pareto chart were used for the analysis. Correction measures were presented which allowed for a significant reduction in the number of stoppages caused by breakdowns.

  9. Psychic trauma as cause of death.

    Science.gov (United States)

    Terranova, C; Snenghi, R; Thiene, G; Ferrara, S D

    2011-01-01

    of study Psychic trauma is described as the action of 'an emotionally overwhelming factor' capable of causing neurovegetative alterations leading to transitory or persisting bodily changes. The medico-legal concept of psychic trauma and its definition as a cause in penal cases is debated. The authors present three cases of death after psychic trauma, and discuss the definition of cause within the penal ambit of identified 'emotionally overwhelming factors'. The methodological approach to ascertainment and criterion-based assessment in each case involved the following phases: (1) examination of circumstantial evidence, clinical records and documentation; (2) autopsy; (3) ascertainment of cause of death; and (4) ascertainment of psychic trauma, and its coexisting relationship with the cause of death. The results and assessment of each of the three cases are discussed from the viewpoint of the causal connotation of psychic trauma. In the cases presented, psychic trauma caused death, as deduced from assessment of the type of externally caused emotional insult, the subjects' personal characteristics and the circumstances of the event causing death. In cases of death due to psychic trauma, careful methodological ascertainment is essential, with the double aim of defining 'emotionally overwhelming factors' as a significant cause of death from the penal point of view, and of identifying the responsibility of third parties involved in the death event and associated dynamics of homicide.

  10. Competing causes of death: an analysis using multiple-cause-of-death data from The Netherlands

    NARCIS (Netherlands)

    Mackenbach, J. P.; Kunst, A. E.; Lautenbach, H.; Bijlsma, F.; Oei, Y. B.

    1995-01-01

    The standard methodology for cause-elimination life tables assumes that the various causes of death are statistically unrelated to one another, so that the mortality risks of those who are saved from an eliminated cause equal the risks of dying from other causes which are observed for the general

  11. Causes of permanent childhood hearing impairment.

    Science.gov (United States)

    Korver, Anna M H; Admiraal, Ronald J C; Kant, Sarina G; Dekker, Friedo W; Wever, Capi C; Kunst, Henricus P M; Frijns, Johan H M; Oudesluys-Murphy, Anne Marie

    2011-02-01

    The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the reported distribution of these causes. Population-based study and a systematic review. Inclusion criteria for population-based study: children born between 2003 and 2005, resident in The Netherlands at birth, known at an Audiology Center with PCHI at the age of 3-5 years. The causes of PCHI were determined prospectively by detection of congenital cytomegalovirus on dried blood spots and/or genetic diagnostic investigations in addition to reviewing data from medical records. A systematic review was carried out using three terms (hearing loss, infant, and etiology) and limited to articles published between January 1997 and July 2009. Main outcome measures were: the (weighted) proportions of the various causes of PCHI following diagnostic investigations. In the study-population (n = 185) a hereditary cause was found in 38.9%, acquired cause in 29.7%, miscellaneous cause in 7.1%, and the cause remained unknown in 24.3%. The systematic review of the literature (n = 9 articles) resulted in a weighted mean of 30.4% hereditary, 19.2% acquired, and 48.3% unknown causes of PCHI. The systematic review and the results of the population-based study provided little support for the generally accepted distribution of causes of PCHI. Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.

  12. FastStats: Leading Causes of Death

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Leading Causes of Death Recommend on Facebook Tweet Share Compartir Data are for the U.S. Number of deaths for leading causes of death Heart disease: 633,842 • Cancer: 595,930 • Chronic ...

  13. Model of transition between causes of death.

    Science.gov (United States)

    Damiani, P; Aubenque, M

    1975-06-01

    This paper describes an attempt to estimate the probabilities of transition between various major causes of death during the period 1954-1962. The regression coefficients have been estimated from French département death rates for ten main or typical causes of death, assessed by sex for the age group 45-64 years.

  14. How does climate change cause extinction?

    Science.gov (United States)

    Cahill, Abigail E; Aiello-Lammens, Matthew E; Fisher-Reid, M Caitlin; Hua, Xia; Karanewsky, Caitlin J; Ryu, Hae Yeong; Sbeglia, Gena C; Spagnolo, Fabrizio; Waldron, John B; Warsi, Omar; Wiens, John J

    2013-01-07

    Anthropogenic climate change is predicted to be a major cause of species extinctions in the next 100 years. But what will actually cause these extinctions? For example, will it be limited physiological tolerance to high temperatures, changing biotic interactions or other factors? Here, we systematically review the proximate causes of climate-change related extinctions and their empirical support. We find 136 case studies of climatic impacts that are potentially relevant to this topic. However, only seven identified proximate causes of demonstrated local extinctions due to anthropogenic climate change. Among these seven studies, the proximate causes vary widely. Surprisingly, none show a straightforward relationship between local extinction and limited tolerances to high temperature. Instead, many studies implicate species interactions as an important proximate cause, especially decreases in food availability. We find very similar patterns in studies showing decreases in abundance associated with climate change, and in those studies showing impacts of climatic oscillations. Collectively, these results highlight our disturbingly limited knowledge of this crucial issue but also support the idea that changing species interactions are an important cause of documented population declines and extinctions related to climate change. Finally, we briefly outline general research strategies for identifying these proximate causes in future studies.

  15. A rare cause of Cushing's syndrome

    DEFF Research Database (Denmark)

    Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg

    2014-01-01

    Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH...

  16. Ecthyma gangrenosum caused by Stenotrophomonas maltophilia in ...

    African Journals Online (AJOL)

    Ecthyma gangrenosum caused by Stenotrophomonas maltophilia in a neutropenic leukaemic infant: A case report. D K Das, S Shukla. Abstract. Ecthyma gangrenosum (EG) is a cutaneous lesion, mostly caused by pseudomonas in immunocompromised patients. Other bacterial and fungal pathogens have also been ...

  17. The Good Cause. Theoretical Perspectives on Corruption

    NARCIS (Netherlands)

    de Graaf, G.; von Maravić, P.; Wagenaar, F.P.

    2010-01-01

    From conceptualization to ideas on practical policy recommendations, The Good Cause presents a state-of-the-art study on the causes of corruption. A cohort of internationally-recognized researchers from the various academic fields that study corruption come together to explain their different

  18. Determinants of all cause mortality in Poland.

    Science.gov (United States)

    Genowska, Agnieszka; Jamiołkowski, Jacek; Szpak, Andrzej; Pajak, Andrzej

    2012-01-01

    The study objective was to evaluate quantitatively the relationship between demographic characteristics, socio-economic status and medical care resources with all cause mortality in Poland. Ecological study was performed using data for the population of 66 subregions of Poland, obtained from the Central Statistical Office of Poland. The information on the determinants of health and all cause mortality covered the period from 1st January 2005 to 31st December 2010. Results for the repeated measures were analyzed using Generalized Estimating Equations GEE model. In the model 16 independent variables describing health determinants were used, including 6 demographic variables, 6 socio-economic variables, 4 medical care variables. The dependent variable, was age standardized all cause mortality rate. There was a large variation in all cause mortality, demographic features, socio-economic characteristics, and medical care resources by subregion. All cause mortality showed weak associations with demographic features, among which only the increased divorce rate was associated with higher mortality rate. Increased education level, salaries, gross domestic product (GDP) per capita, local government expenditures per capita and the number of non-governmental organizations per 10 thousand population was associated with decrease in all cause mortality. The increase of unemployment rate was related with a decrease of all cause mortality. Beneficial relationship between employment of medical staff and mortality was observed. Variation in mortality from all causes in Poland was explained partly by variation in socio-economic determinants and health care resources.

  19. Intestinal perforation caused by multiple magnet ingestion

    Directory of Open Access Journals (Sweden)

    Nergul Corduk

    2014-01-01

    Full Text Available Multiple magnet ingestion is rare, but can cause serious gastrointestinal complications. We report a case of 7-year-old girl with multiple intestinal perforations caused by multiple magnet ingestion. The aim of this report is to draw attention to magnetic toys, results of magnet ingestion and the importance of timing of operation.

  20. Systemic causes of heavy menstrual bleeding

    NARCIS (Netherlands)

    Verschueren, Sophie

    2017-01-01

    Heavy menstrual bleeding (HMB) is a common problem in fertile women. In addition to local factors, such as a polyp or a uterine fibroid, systemic causes may lead to HMB. These systemic causes are discussed in this thesis. For years, women with HMB were tested underlying thyroid disorder, but our

  1. Causes of permanent childhood hearing impairment

    NARCIS (Netherlands)

    Korver, Anna M. H.; Admiraal, Ronald J. C.; Kant, Sarina G.; Dekker, Friedo W.; Wever, Capi C.; Kunst, Henricus P. M.; Frijns, Johan H. M.; Oudesluys-Murphy, Anne Marie; Oudesluys-Murphy, A. M.; Korver, A. M. H.; Frijns, J. H. M.; Wever, C. C.; Konings, S.; Beers, W.; Dekker, F. W.; de Vries, J. J. C.; Vossen, A. C. T. M.; Kant, S. G.; van den Akker-van Marle, M. E.; Rieffe, C.; Ens-Dokkum, M. H.; van Straaten, H. L. M.; Uilenburg, N. N.; Elvers, B.; Loeber, G.; Meuwese-Jongejeugd, J.; Maré, M. J.; Van Zanten, G. A.; Goedegebure, A.; Coster, F.; Goverts, S. T.; Admiraal, R. J. C.; Cremers, C. W. R. J.; Kunst, H. P. M.; de Leeuw, M.; Dijkhuizen, J.; Scharloo, M.; Hoeben, D.; Rijpma, G.; Graef, W.; Linschoten, D.; Kuijper, J.; Hof, N. J.; Pans, D.; Jorritsma, F.; van Beurden, M.; ter Huurne, C. T.; Brienesse, P.; Koldewijn, G. J.; Letourneur, K. G.

    2011-01-01

    The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the reported

  2. Causes of permanent childhood hearing impairment

    NARCIS (Netherlands)

    Korver, A.M.; Admiraal, R.J.C.; Kant, S.G.; Dekker, F.W.; Wever, C.; Kunst, H.P.M.; Frijns, J.H.; Oudesluys-Murphy, A.M.

    2011-01-01

    INTRODUCTION: The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the

  3. Can Beta Blockers Cause Weight Gain?

    Science.gov (United States)

    ... cause weight gain? Can beta blockers cause weight gain? Answers from Sheldon G. Sheps, M.D. Yes. Weight gain can occur as a side effect of some ... and metoprolol (Lopressor, Toprol-XL). The average weight gain is about 2.6 pounds (about 1.2 ...

  4. Irreversible brain damage caused by methamphetamine

    Directory of Open Access Journals (Sweden)

    Sebastian Moeller

    2016-03-01

    Full Text Available Methamphetamine is an addictive scene substance usage of which is increasing rapidly. While methamphetamine often causes neuropsychiatric symptoms like anxiety, psychosis and hallucinations, reports of structural ongoing cerebral alterations are rare. We here report a case of this kind of damage caused through methamphetamine use.

  5. Root cause analysis with enriched process logs

    NARCIS (Netherlands)

    Suriadi, S.; Ouyang, C.; Aalst, van der W.M.P.; Hofstede, ter A.H.M.; La Rosa, M.; Soffer, P.

    2013-01-01

    n the field of process mining, the use of event logs for the purpose of root cause analysis is increasingly studied. In such an analysis, the availability of attributes/features that may explain the root cause of some phenomena is crucial. Currently, the process of obtaining these attributes from

  6. The cause multiplicity and the multiple cause style of adverse events in Japanese nuclear power plants

    International Nuclear Information System (INIS)

    Miyazaki, Takamasa

    2008-01-01

    An adverse event in a nuclear power plant occurs due to either one cause or multiple causes. To consider ways of preventing adverse events, it is useful to clarify whether events are caused by single or multiple causes. In this study, the multiple causes is expressed using the cause multiplicity and the multiple cause style. Classified causes of adverse events in Japanese nuclear power plants were analyzed, with the following results: the cause multiplicity of serious adverse events is higher than that of minor adverse events, and the multiple cause style can be expressed by combining two styles: series type and parallel type. Also, for a multiple cause event, a new method of displaying the event is presented as a cause-chain chart where the cause items are arranged in a sequential way and are connected considering the mutual relations among the causes. This new display method shows the whole flow of issues concerning the event more simply than the conventional display method of the chain of phenomena, and would be useful for considering the terminating point of the chain of causes. (author)

  7. The causes of the Chernobyl event

    International Nuclear Information System (INIS)

    Frot, J.

    2000-11-01

    The Chernobylsk event has two components, the explosion of the RBMK type nuclear reactor number 4 and the sanitary damages that resulted. The causes of the explosion are of three kinds: conception error, management fault, exploitation personnel mistakes and political causes. For the sanitary damages there are the immediate causes and the deep causes. No emergency planning to answer to a such disaster and no iodinated tablets delivery to protect the thyroid for the direct causes. The secret culture made that the knowledge developed by the Soviet researchers was not diffused to the medical and nuclear communities of USSR. The civil authorities were not aware of it or they neglected it. (N.C.)

  8. CAUSES OF RESPIRATORY DISTRESS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    M M Karambin

    2008-11-01

    Full Text Available "nThere is a lack of large, prospective epidemiologic studies concerning acute lung injury (ALI and acute respiratory distress syndrome (ARDS in pediatric population. To determine the different causes of respiratory distress in children, we prepared a retrospective study and included the whole 567 children with respiratory distress referred to 17-Shahrivar Hospital, Rasht, Guilan. Using their medical files, data including age, sex, and causes of respiratory distress were collected. SPSS 13.0 (statistical software applied for statistical analysis. Pneumonia, asthma, and croup were the major causes of ARDS in children with a rate of 38.4, 19.04, and 16.5 percent, respectively. It seems that infectious factors are at the top of the list of ARDS causing factors which can be helpful to approach and manage such patients. We suggest vaccinating these at risk groups against common infectious factors such as H. Influenza and RSV which can cause either pneumonia or inducing asthma.

  9. Ruling out secondary causes of hypertension.

    Science.gov (United States)

    Ott, Christian; Schneider, Markus P; Schmieder, Roland E

    2013-05-01

    In the majority of hypertensive patients, no particular cause for abnormal blood pressure is evident (primary or essential hypertension). In contrast, in the minority of patients with secondary hypertension a specific underlying cause is responsible for the elevated blood pressure. The prevalence of secondary hypertension is higher in patients with resistant hypertension than in the general hypertensive population and increases with age. The list of secondary forms of hypertension is long and prevalence of the individual causes of secondary hypertension varies. Hence, this review divides them into two categories: common causes and rare causes. If appropriately diagnosed and treated, patients with a secondary form of hypertension might be cured, or at least show an improvement in their blood pressure control. Consequently, screening for secondary causes of hypertension plays an essential part in the care of patients with arterial hypertension. If the basal work-up raises the suspicion of a secondary cause of hypertension, specific diagnostic procedures become necessary, some of which can be performed by primary care physicians, while others require specialist input.

  10. Analyzing delay causes in Egyptian construction projects

    Directory of Open Access Journals (Sweden)

    Mohamed M. Marzouk

    2014-01-01

    Full Text Available Construction delays are common problems in civil engineering projects in Egypt. These problems occur frequently during project life-time leading to disputes and litigation. Therefore, it is essential to study and analyze causes of construction delays. This research presents a list of construction delay causes retrieved from literature. The feedback of construction experts was obtained through interviews. Subsequently, a questionnaire survey was prepared. The questionnaire survey was distributed to thirty-three construction experts who represent owners, consultants, and contractor’s organizations. Frequency Index, Severity Index, and Importance Index are calculated and according to the highest values of them the top ten delay causes of construction projects in Egypt are determined. A case study is analyzed and compared to the most important delay causes in the research. Statistical analysis is carried out using analysis of variance ANOVA method to test delay causes, obtained from the survey. The test results reveal good correlation between groups while there is significant difference between them for some delay causes and finally roadmap for prioritizing delay causes groups is presented.

  11. Treatment of the pain caused by cancer

    International Nuclear Information System (INIS)

    Nakano, Masao

    1979-01-01

    Relief of pain caused by cancerous invasion is one of the most important role of radiotherapy. Telecobalt has improved the palliative effects for cancer pain, because of its sufficient depth dose. Supervoltage x-ray generated from Linac has expanded indications of treatment for cancer pain by the shortening of treatment time due to high dose rate. Intraoperative electron beam therapy is useful in the case of carcinoma of the pancreas suffering severe pain. Fast neutron therapy is clearly more effective than supervoltage x-ray for pain caused by the invasion of radioresistant cancer. Pelvic angiography is useful for diagnosis of pain focus caused by illiac lymph node metastasis. (author)

  12. Lightning-caused fires in Central Spain

    DEFF Research Database (Denmark)

    Nieto Solana, Hector; Aguado, Inmaculada; García, Mariano

    2012-01-01

    Lightning-caused fire occurrence has been modelled for two different Spanish regions, Madrid andAragon, based on meteorological, terrain, and vegetation variables. The model was built on two very contrasting regions, one presenting low number of lightning-caused fires whereas the other presented...... in the model, where an increasing number of thunderstorms leads to a higher probability of occurrence. Validation was assessed through the Receiver Operator Characteristic, showing a good agreement between the modelled probabilities and the reported lightning-caused fires, with an Area Under the Curve around 0...

  13. Causes and treatment of periorbital hyperchromia

    OpenAIRE

    Glauber Alcântara Oliveira; Andres Raimundo Paiva

    2016-01-01

    The periorbital region is one of the first areas to demonstrate signs of aging such as wrinkling, skin laxity and periorbital hyperpigmentation (HPO). The HPO interferes in the facial appearance resulting on a tired, sadness or hangover aspects. It has a complex etiopathogenesis with factors that could be by primary or secondary cause. The genetic factors are stated as a primary cause and the environmental factors are stated as a secondary cause. In that way, there are many examples of enviro...

  14. Adult Intussusception Caused by Heterotopic Pancreas

    Directory of Open Access Journals (Sweden)

    Va-Kei Kok

    2007-05-01

    Full Text Available Heterotopic pancreas causing small bowel intussusception is rare. We report the case of a 24-year-old woman who presented with intermittent episodes of abdominal cramping and pain that had persisted for 10 days. A target-shaped lesion consisting of multiple concentric rings was found on the left side on contrast-enhanced computed tomography. Surgical intervention demonstrated jejunal intussusception caused by a jejunal heterotopic pancreas. Microscopically, several nesidioblastoses of pancreas were identified. Although very rare, small intestinal pancreatic rests may cause subacute bowel obstruction.

  15. CDC WONDER: Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979. Data...

  16. Neuroendocrine causes of amenorrhea--an update.

    Science.gov (United States)

    Fourman, Lindsay T; Fazeli, Pouneh K

    2015-03-01

    Secondary amenorrhea--the absence of menses for three consecutive cycles--affects approximately 3-4% of reproductive age women, and infertility--the failure to conceive after 12 months of regular intercourse--affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception.

  17. Neuroendocrine Causes of Amenorrhea—An Update

    Science.gov (United States)

    Fourman, Lindsay T.

    2015-01-01

    Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

  18. 92 INSULIN RESISTANCE: CAUSES AND METABOLIC ...

    African Journals Online (AJOL)

    drclement

    2009-12-01

    Dec 1, 2009 ... Edo State Institute of Technology and Management. Usen, Edo State ... type 2 diabetes mellitus. The cause of the vast ... Insulin (molecular mass 6000D) consists of 51 amino acids .... Experimental Biology and. Medicine 2004 ...

  19. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

  20. Liquorice: a root cause of secondary hypertension

    OpenAIRE

    Varma, Ravi; Ross, Calum N.

    2017-01-01

    We describe a patient presenting with hypertension and hypokalaemia who was ultimately diagnosed with liquorice- induced pseudohyperaldosteronism. This rare cause of secondary hypertension illustrates the importance of a methodical approach to the assessment of hypertension.

  1. Symptoms and Causes of Celiac Disease

    Science.gov (United States)

    ... Symptoms & Causes of Celiac Disease What are the symptoms of celiac disease? Most people with celiac disease have one or ... the rash and no other symptoms. Why are celiac disease symptoms so varied? Symptoms of celiac disease vary from ...

  2. [A lung abscess caused by bad teeth].

    Science.gov (United States)

    van Brummelen, S E; Melles, D; van der Eerden, M

    2017-01-01

    An odontogenic cause of a lung abscess can easily be overlooked. A 61-year-old man presented at the emergency department with a productive cough and dyspnoea. He was admitted to the pulmonary ward with a suspected odontogenic lung abscess. A thorax CT scan confirmed the diagnosis 'lung abscess', following which the dental surgeon confirmed that the lung abscess probably had an odontogenic cause. The patient made a full recovery following a 6-week course of antibiotics, and he received extensive dental treatment. Poor oral hygiene can be a cause of a lung abscess. A patient with a lung abscess can be treated successfully with a 6-week course of antibiotics; however, if the odontogenic cause is not recognised the abscess can recur.

  3. NCHS - Leading Causes of Death: United States

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset presents the age-adjusted death rates for the 10 leading causes of death in the United States beginning in 1999. Data are based on information from all...

  4. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  5. Electromagnetic radiation-2450 MHz exposure causes cognition ...

    Indian Academy of Sciences (India)

    83

    Electromagnetic radiation-2450 MHz exposure causes cognition deficit with mitochondrial. 1 ... decrease in levels of acetylcholine, and increase in activity of acetyl ...... neuronal apoptosis and cognitive disturbances in sevoflurane or propofol ...

  6. IMPROVING CAUSE DETECTION SYSTEMS WITH ACTIVE LEARNING

    Data.gov (United States)

    National Aeronautics and Space Administration — IMPROVING CAUSE DETECTION SYSTEMS WITH ACTIVE LEARNING ISAAC PERSING AND VINCENT NG Abstract. Active learning has been successfully applied to many natural language...

  7. Malabsorption: causes, consequences, diagnosis and treatment

    African Journals Online (AJOL)

    2011-06-06

    Jun 6, 2011 ... Review Article: Malabsorption: causes, consequences, diagnosis and treatment. 2011;24(3) ... and osteopenia (malabsorption of calcium, vitamin D, phosphate and magnesium .... A lipase dosage in excess of 75 000 IU per.

  8. Recurrent LDL-receptor mutation causes familial ...

    African Journals Online (AJOL)

    1995-05-05

    May 5, 1995 ... 3. eaudet . New. Recurrent LDL-receptor mutation causes familial hypercholesterolaemia in ... amplification refractory mutation system (ARMS)" and single- strand conformation .... Location. Afrikaner. Mixed race. ApaLl.

  9. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

  10. USFA NFIRS 2013 Fire Incident & Cause Data

    Data.gov (United States)

    Department of Homeland Security — The 2013 Fire Causes & Incident data was provided by the U.S. Fire Administration’s (USFA) National Fire Data Center’s (NFDC’s) National Fire Incident Reporting...

  11. CASE REPORT Uncommon Pathogen Bacillus Cereus Causing ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... Causing Subdural Empyema in a Child. Ethiop J ... 1Department of Child Health,. Airlangga ... secondary to middle ear infection, meningitis, brain surgery, ... classic clinical syndrome is an acute febrile illness punctuated by.

  12. Causes of road traffic accidents in Juba

    African Journals Online (AJOL)

    2017-05-02

    May 2, 2017 ... Introduction: Road traffic accidents (RTAs) are a major cause of death and disability in ... death in many parts of the world resulting in economic ... The long civil war ... the second highest number compared to private cars. In.

  13. Thoracic empyema caused by Campylobacter rectus.

    Science.gov (United States)

    Ogata, Tomoyuki; Urata, Teruo; Nemoto, Daisuke; Hitomi, Shigemi

    2017-03-01

    We report a case of thoracic empyema caused by Campylobacter rectus, an organism considered as a periodontal pathogen but rarely recovered from extraoral specimens. The patient fully recovered through drainage of purulent pleural fluid and administration of antibiotics. The present case illustrates that C. rectus can be a cause of not only periodontal disease but also pulmonary infection. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Lost Cause: an interactive movie project

    OpenAIRE

    Johnson, Kirsten

    2008-01-01

    One of the challenges in designing an interactive cinematic experience is to offer interactive choices which do not distract from immersion into the story. The interactive movie project, Lost Cause focuses on the life of the main character explored through the inter-related perspectives of three other characters. Lost Cause supports an immersive interactive story experience through its correlated design of an interface, narrative content and narrative structure. The movie project is examined ...

  15. Causes of Red Eye-Uveitis

    OpenAIRE

    Selçuk Sızmaz

    2012-01-01

    Uveitis, being an important cause of ocular morbidity, must be taken into consideration in the differential diagnosis and the management of patients with red eye. Uveitis entities can demonstrate variable clinical features. Patients presenting with uveitis must undergo careful systemic evaluation for exact diagnosis and treatment. Studies for standardization of uveitis with variable clinical pictures are emerging. Acute anterior uveitis and panuveitis can cause red eye. The purpose o...

  16. A rare cause of wheezing in infancy.

    Science.gov (United States)

    Indinnimeo, Luciana; Pulicati, Patrizio; Della Rocca, Carlo; Barbato, Angelo

    2006-06-01

    We describe an infant with recurrent wheezing and cough caused by an oropharyngeal cyst. Mucosal oropharyngeal cysts arise from obstruction or traumatic severance of a duct in a minor salivary gland, which leads to retention of mucous secretion . The mucosal cyst of the oropharynx is a rare cause of respiratory distress in the infants. The clinical symptoms depend on the size, shape, and location of the cyst.

  17. The causes of the Chernobyl accident

    International Nuclear Information System (INIS)

    Frot, J.

    2001-01-01

    For the man in the street Chernobyl epitomizes the danger of nuclear energy but when we examine the causes of this accident we see that this drama is not intrinsically linked to the production of electricity from nuclear fission. The author sees 2 components in the Chernobyl event: the accident itself and its sanitary consequences. The author considers 3 main causes to the accident: -) a design that makes the reactor difficult to control, -) a series of 6 humane failures or breaking of operating rules, and -) political reasons: the largest possible budget was dedicated to plutonium production so any improvement for safety was considered as costly and secondary, moreover the religion of secrecy which was well spread in the ancient Soviet Union, prevented any scientific from knowing all the information concerning this type of reactor. As for the sanitary consequences, the author considers direct causes and underlying causes. The lack of information for the local population, the delay taken for iodine distribution or for the interdiction of farm products consumption are included in the direct causes. The slowness of Soviet bureaucracy, tight budgets and politico-scientific disputes are quoted among the underlying causes. (A.C.)

  18. Facial Pores: Definition, Causes, and Treatment Options.

    Science.gov (United States)

    Lee, Sang Ju; Seok, Joon; Jeong, Se Yeong; Park, Kui Young; Li, Kapsok; Seo, Seong Jun

    2016-03-01

    Enlarged skin pores refer to conditions that present with visible topographic changes of skin surfaces. Although not a medical concern, enlarged pores are a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes of enlarged pores have not been elucidated. To review the possible causes and treatment options for skin pores. This article is based on a review of the medical literature and the authors' clinical experience in investigating and treating skin pores. There are 3 major clinical causes of enlarged facial pores, namely high sebum excretion, decreased elasticity around pores, and increased hair follicle volume. In addition, chronic recurrent acne, sex hormones, and skin care regimen can affect pore size. Given the different possible causes for enlarged pores, therapeutic modalities must be individualized for each patient. Potential factors that contribute to enlarged skin pores include excessive sebum, decreased elasticity around pores, and increased hair follicle volume. Because various factors cause enlarged facial pores, it might be useful to identify the underlying causes to be able to select the appropriate treatment.

  19. Historical review of the causes of cancer.

    Science.gov (United States)

    Blackadar, Clarke Brian

    2016-02-10

    In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer.

  20. Unusual causes of mechanical small bowel obstruction

    International Nuclear Information System (INIS)

    Shatnawi, Nawaf J.; Bani-Hani, Kamal E.

    2005-01-01

    We herein report our experience regarding unusual causes of bowel obstruction to increase the awareness of surgeons regarding this disease. From 1991 to 2003, we had experience at the University affiliated hospitals, northern Jordan with 24 patients with small bowel obstruction resulting from unusual causes. We retrospectively reviewed the medical records of these patients with regards to the mode of presentation, cause of obstruction, radiological and operative findings, management and outcome. We recorded 15 patients who underwent previous abdominal surgery. Preoperative diagnosis was correct in only one patient with an internal hernia, but the abdominal CT scan suggested the diagnosis in 5 of the 9 patients who had the scan. The final diagnosis was internal hernias in 11 patients, foreign bodies in 5, ischemic strictures in 3, carcinoid tumors in 2, endometriosis in 2, and metastatic deposit from interstitial bladder carcinoma in one patient. Nine of the 12 patients with recurrent obstruction had either short course or recurrence obstruction during the same hospital admission. W carried out bowel resections in 15 patients (5 resections were due to bowel strangulation). Post operative death occurred in 4 patients. Awareness of these rare causes of intestinal obstruction even in patients with previous abdominal operation might improve the outcome. The tentative diagnosis of adhesion obstruction in patients with unusual obstructive etiology might lead to a higher rate of gangrenous complications. Rigorous preoperative evaluation including careful history and early abdominal CT may show the obstructive cause. (author)

  1. Diabetic Ketoacidosis: Pattern of Precipitating Causes

    Directory of Open Access Journals (Sweden)

    Ashraf Uddin Ahmed

    2014-05-01

    Full Text Available Background: Diabetic ketoacidosis (DKA is one of the most common acute complications of diabetes mellitus (DM. DKA is a recognised presenting feature of type 1 DM, but it commonly complicates previously diagnosed diabetic patients of all types, specially if they get infection or discontinue treatment. Objective: To describe the precipitating causes of DKA. Materials and Methods: This cross-sectional study was done from September to November, 2010 in Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM. Diagnosed DKA cases were evaluated clinically and by laboratory investigations for identification of precipitating causes. Results: Out of 50 patients, 28 were female. Mean age was 38.3 years. Forty patients (80% were known diabetics and 10 (20% were detected diabetic first time during this admission. Severe DKA cases were less common. Infection (20, 40% was the commonest precipitating cause followed by noncompliance (14, 28%. In 7 (14% cases no cause could be identified. Other less common causes included acute myocardial infarction, acute pancreatitis, stroke and surgery. Conclusion: Infection and noncompliance were the major precipitants of DKA. So, it is assumed that many DKA cases might be prevented by proper counselling regarding adherence to medication and sick days’ management.

  2. Cell vacuolation caused by Vibrio cholerae hemolysin.

    Science.gov (United States)

    Figueroa-Arredondo, P; Heuser, J E; Akopyants, N S; Morisaki, J H; Giono-Cerezo, S; Enríquez-Rincón, F; Berg, D E

    2001-03-01

    Non-O1 strains of Vibrio cholerae implicated in gastroenteritis and diarrhea generally lack virulence determinants such as cholera toxin that are characteristic of epidemic strains; the factors that contribute to their virulence are not understood. Here we report that at least one-third of diarrhea-associated nonepidemic V. cholerae strains from Mexico cause vacuolation of cultured Vero cells. Detailed analyses indicated that this vacuolation was related to that caused by aerolysin, a pore-forming toxin of Aeromonas; it involved primarily the endoplasmic reticulum at early times (approximately 1 to 4 h after exposure), and resulted in formation of large, acidic, endosome-like multivesicular vacuoles (probably autophagosomes) only at late times (approximately 16 h). In contrast to vacuolation caused by Helicobacter pylori VacA protein, that induced by V. cholerae was exacerbated by agents that block vacuolar proton pumping but not by endosome-targeted weak bases. It caused centripetal redistribution of endosomes, reflecting cytoplasmic alkalinization. The gene for V. cholerae vacuolating activity was cloned and was found to correspond to hlyA, the structural gene for hemolysin. HlyA protein is a pore-forming toxin that causes ion leakage and, ultimately, eukaryotic cell lysis. Thus, a distinct form of cell vacuolation precedes cytolysis at low doses of hemolysin. We propose that this vacuolation, in itself, contributes to the virulence of V. cholerae strains, perhaps by perturbing intracellular membrane trafficking or ion exchange in target cells and thereby affecting local intestinal inflammatory or other defense responses.

  3. Diagnosis of reversible causes of coma.

    Science.gov (United States)

    Edlow, Jonathan A; Rabinstein, Alejandro; Traub, Stephen J; Wijdicks, Eelco F M

    2014-12-06

    Because coma has many causes, physicians must develop a structured, algorithmic approach to diagnose and treat reversible causes rapidly. The three main mechanisms of coma are structural brain lesions, diffuse neuronal dysfunction, and, rarely, psychiatric causes. The first priority is to stabilise the patient by treatment of life-threatening conditions, then to use the history, physical examination, and laboratory findings to identify structural causes and diagnose treatable disorders. Some patients have a clear diagnosis. In those who do not, the first decision is whether brain imaging is needed. Imaging should be done in post-traumatic coma or when structural brain lesions are probable or possible causes. Patients who do not undergo imaging should be reassessed regularly. If CT is non-diagnostic, a checklist should be used use to indicate whether advanced imaging is needed or evidence is present of a treatable poisoning or infection, seizures including non-convulsive status epilepticus, endocrinopathy, or thiamine deficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Survey of disruption causes at JET

    International Nuclear Information System (INIS)

    De Vries, P.C.; Johnson, M.F.; Alper, B.; Hender, T.C.; Riccardo, V.; Buratti, P.; Koslowski, H.R.

    2011-01-01

    A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the effort to avoid or prevent JET disruptions to be more efficient and effective. As expected, a highly complex pattern of chain of events that led to disruptions emerged. It was found that the majority of disruptions had a technical root cause, for example due to control errors, or operator mistakes. These bring a random, non-physics, factor into the occurrence of disruptions and the disruption rate or disruptivity of a scenario may depend more on technical performance than on physics stability issues. The main root cause of JET disruptions was nevertheless due to neo-classical tearing modes that locked, closely followed in second place by disruptions due to human error. The development of more robust operational scenarios has reduced the JET disruption rate over the last decade from about 15% to below 4%. A fraction of all disruptions was caused by very fast, precursorless unpredictable events. The occurrence of these disruptions may set a lower limit of 0.4% to the disruption rate of JET. If one considers on top of that human error and all unforeseen failures of heating or control systems this lower limit may rise to 1.0% or 1.6%, respectively.

  5. Causes and treatment of periorbital hyperchromia

    Directory of Open Access Journals (Sweden)

    Glauber Alcântara Oliveira

    2016-11-01

    Full Text Available The periorbital region is one of the first areas to demonstrate signs of aging such as wrinkling, skin laxity and periorbital hyperpigmentation (HPO. The HPO interferes in the facial appearance resulting on a tired, sadness or hangover aspects. It has a complex etiopathogenesis with factors that could be by primary or secondary cause. The genetic factors are stated as a primary cause and the environmental factors are stated as a secondary cause. In that way, there are many examples of environmental factors such as excess of sun exposition, post inflammatory hyper pigmentation, excess of subcutaneous vascularization, hyper transparency of the skin, periorbital edema, and fat herniation eyelid. The clinical severity of the condition varies and normally the hyper pigmentation is present bilaterally and symmetrically around the eye region. The main objective of this study was to develop and evaluate the causes and etiological factors, and to describe the possible treatments available in the current literature. It was utilized 26 scientific papers on the following subjects: anatomy, etiology, causes and treatments. Owing to the information scarcity about its etiology, as well as its consensual treatment, it is necessary an adequate clinical examination in order to provide directions to the conduct. There are several suggestions for HPO treatment described: peeling, fillers, autologous fat fillers, cosmetic use, injection of platelet rich plasma (PRP, and carboxytherapy.

  6. Savannah River experience using a Cause Coding Tree to identify the root cause of an incident

    International Nuclear Information System (INIS)

    Paradies, M.W.; Busch, D.A.

    1986-01-01

    Incidents (or near misses) provide important information about plant performance and ways to improve that performance. Any particular incident may have several ''root causes'' that need to be addressed to prevent recurrence of the incident and thereby improve the safety of the plant. Also, by reviewing a large number of these incidents, one can identify trends in the root causes and generic concerns. A method has been developed at Savannah River Plant to systematically evaluate incidents, identify their root causes, record these root causes, and analyze the trends of these causes. By providing a systematic method to identify correctable root causes, the system helps the incident investigator to ask the right questions during the investigation. It also provides the independent safety analysis group and management with statistics that indicate existing and developing trouble sports. This paper describes the Savannah River Plant (SRP) Cause Coding Tree, and the differences between the SRP Tree and other systems used to analyze incidents. 2 refs., 14 figs

  7. Quantifying cause-related mortality by weighting multiple causes of death

    Science.gov (United States)

    Moreno-Betancur, Margarita; Lamarche-Vadel, Agathe; Rey, Grégoire

    2016-01-01

    Abstract Objective To investigate a new approach to calculating cause-related standardized mortality rates that involves assigning weights to each cause of death reported on death certificates. Methods We derived cause-related standardized mortality rates from death certificate data for France in 2010 using: (i) the classic method, which considered only the underlying cause of death; and (ii) three novel multiple-cause-of-death weighting methods, which assigned weights to multiple causes of death mentioned on death certificates: the first two multiple-cause-of-death methods assigned non-zero weights to all causes mentioned and the third assigned non-zero weights to only the underlying cause and other contributing causes that were not part of the main morbid process. As the sum of the weights for each death certificate was 1, each death had an equal influence on mortality estimates and the total number of deaths was unchanged. Mortality rates derived using the different methods were compared. Findings On average, 3.4 causes per death were listed on each certificate. The standardized mortality rate calculated using the third multiple-cause-of-death weighting method was more than 20% higher than that calculated using the classic method for five disease categories: skin diseases, mental disorders, endocrine and nutritional diseases, blood diseases and genitourinary diseases. Moreover, this method highlighted the mortality burden associated with certain diseases in specific age groups. Conclusion A multiple-cause-of-death weighting approach to calculating cause-related standardized mortality rates from death certificate data identified conditions that contributed more to mortality than indicated by the classic method. This new approach holds promise for identifying underrecognized contributors to mortality. PMID:27994280

  8. A rare cause of hypophysitis: tuberculosis

    Directory of Open Access Journals (Sweden)

    Ates Ihsan

    2017-10-01

    Full Text Available Objectives. Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it causes headache and visual defects, it mimics sellar tumors in clinical and radiological aspects. It may occur due to primary or secondary causes. Tuberculosis is one of the rare secondary causes of the hypophysitis. Subject and Results. A 30-year-old male patient presented with fatigue and headache. Panhypopituitarism was considered due to the results and the diagnostic magnetic resonance (MR imaging revealed sagittal section diamater of pituitary gland higher than normal. Biopsy of the pituitary gland was concordant with the granulomatous hypophysitis. Other possible diagnosis was excluded. Conclusion. The tubercular hypophysitis, as a result of performed tests, is discussed hereby, in the case report.

  9. Acute compartment syndrome caused by uncontrolled hypothyroidism.

    Science.gov (United States)

    Modi, Anar; Amin, Hari; Salzman, Matthew; Morgan, Farah

    2017-06-01

    Acute compartment syndrome is increased tissue pressure exceeding perfusion pressure in a closed compartment resulting in nerve and muscle ischemia. Common precipitating causes are crush injuries, burns, substance abuse, osseous or vascular limb trauma. This is a case of 42year old female with history of hypothyroidism who presented to emergency room with acute onset of severe pain and swelling in right lower extremity. Physical examination was concerning for acute compartment syndrome of right leg which was confirmed by demonstration of elevated compartmental pressures. No precipitating causes were readily identified. Further laboratory testing revealed uncontrolled hypothyroidism. Management included emergent fasciotomy and initiating thyroid hormone replacement. This case represents a rare association between acute compartment syndrome and uncontrolled hypothyroidism. We also discuss the pathogenesis of compartment syndrome in hypothyroid patients and emphasize the importance of evaluating for less common causes, particularly in setting of non-traumatic compartment syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. An uncommon cause of anaemia: Sheehan's syndrome.

    Science.gov (United States)

    Melchardt, Thomas; Namberger, Konrad; Weiss, Lukas; Egle, Alexander; Faber, Viktoria; Greil, Richard

    2010-12-01

    Ischemic pituitary necrosis due to severe postpartum haemorrhage called Sheehan's syndrome is a rare cause of hypopituitarism in the western world, but much more common in developing countries. A 45-year-old female patient being a war refugee from Chechnya with severe anaemia and fatigue was diagnosed at our outpatient department with Sheehan's syndrome after severe postpartum haemorrhage and emergency hysterectomy 15 years ago. Panhypopituitarism was adequately treated with substitution of hydrocortisone, thyroxine and transdermal oestrogen which resulted in haemoglobin increase to nearly normal levels and symptoms improved immediately. Severe anaemia caused by panhypopituitarism shows the importance of the hormonal system for erythropoiesis. Clinical and basic scientific evidence indicates thyroidal hormones to be the main cause.

  11. Prosperity as a cause of death.

    Science.gov (United States)

    Eyer, J

    1977-01-01

    The general death rate rises during business booms and falls during depressions. The causes of death involved in this variation range from infectious diseases through accidents to heart disease, cancer, and cirrhosis of the liver, and include the great majority of all causes of death. Less than 2 percent of the death rate-that for suicide and homicide-varies directly with unemployment. In the older historical data, deterioration of housing and rise of alcohol consumption on the boom may account for part of this variation. In twentieth-century cycles, the role of social stress is probably predominant. Overwork and fragmentation of community through migration are two important sources of stress which rise with the boom, and they are demonstrably related to the causes of death which show this variation.

  12. Structures for common-cause failure analysis

    International Nuclear Information System (INIS)

    Vaurio, J.K.

    1981-01-01

    Common-cause failure methodology and terminology have been reviewed and structured to provide a systematical basis for addressing and developing models and methods for quantification. The structure is based on (1) a specific set of definitions, (2) categories based on the way faults are attributable to a common cause, and (3) classes based on the time of entry and the time of elimination of the faults. The failure events are then characterized by their likelihood or frequency and the average residence time. The structure provides a basis for selecting computational models, collecting and evaluating data and assessing the importance of various failure types, and for developing effective defences against common-cause failure. The relationships of this and several other structures are described

  13. A rare cause of hypophysitis: tuberculosis.

    Science.gov (United States)

    Ates, Ihsan; Katipoglu, B; Copur, B; Yilmaz, N

    2017-10-26

    Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it causes headache and visual defects, it mimics sellar tumors in clinical and radiological aspects. It may occur due to primary or secondary causes. Tuberculosis is one of the rare secondary causes of the hypophysitis. Subject and Results. A 30-year-old male patient presented with fatigue and headache. Panhypopituitarism was considered due to the results and the diagnostic magnetic resonance (MR) imaging revealed sagittal section diamater of pituitary gland higher than normal. Biopsy of the pituitary gland was concordant with the granulomatous hypophysitis. Other possible diagnosis was excluded. The tubercular hypophysitis, as a result of performed tests, is discussed hereby, in the case report.

  14. Sudden unexpected death caused by stroke

    DEFF Research Database (Denmark)

    Ågesen, Frederik Nybye; Risgaard, Bjarke; Zachariasardóttir, Sára

    2017-01-01

    Background Stroke is the fifth leading cause of death in young individuals globally. Data on the burden of sudden death by stroke are sparse in the young. Aims The aim of this study was to report mortality rates, cause of death, stroke subtype, and symptoms in children and young adults who suffered....... There was a male predominance (56%) and the median age was 33 years. The incidence of sudden death by stroke in individuals aged 1-49 years was 0.19 deaths per 100,000 person-years. Stroke was hemorrhagic in 94% of cases, whereof subarachnoid hemorrhage was the cause of death in 63% of cases. Seventeen (33%) cases...... contacted the healthcare system because of neurological symptoms, whereof one was suspected of having a stroke (6%). Conclusions Sudden death by stroke in children and young adults occurs primarily due to hemorrhagic stroke. We report a high frequency of neurological symptoms prior to sudden death by stroke...

  15. Organizational root causes for human factor accidents

    International Nuclear Information System (INIS)

    Dougherty, D.T.

    1997-01-01

    Accident prevention techniques and technologies have evolved significantly throughout this century from the earliest establishment of standards and procedures to the safety engineering improvements the fruits of which we enjoy today. Most of the recent prevention efforts focused on humans and defining human factor causes of accidents. This paper builds upon the remarkable successes of the past by looking beyond the human's action in accident causation to the organizational factors that put the human in the position to cause the accident. This organizational approach crosses all functions and all career fields

  16. [Problems caused by poisonous tropical marine animals].

    Science.gov (United States)

    Lääveri, Tinja; Räisänen-Sokolowski, Anne; Jama, Timo

    2014-01-01

    A Finnish physician encounters problems caused by tropical marine animals either during her/his own travelling or while treating travelers who have returned home. Certain species of medusae and cone shells as well as the stings by some fish species are life-threateningly poisonous. A person stung or bitten by any of the most dangerous species must immediately be admitted to the hospital. Foreign material remaining in tissues after stings by echinoderms and spiky fish may cause problems months after the actual injury. The injuries become easily infected, and antimicrobial drug therapy must thus cover gram-negative rod-shaped bacteria as well.

  17. Causes of Red Eye-Uveitis

    Directory of Open Access Journals (Sweden)

    Selçuk Sızmaz

    2012-12-01

    Full Text Available Uveitis, being an important cause of ocular morbidity, must be taken into consideration in the differential diagnosis and the management of patients with red eye. Uveitis entities can demonstrate variable clinical features. Patients presenting with uveitis must undergo careful systemic evaluation for exact diagnosis and treatment. Studies for standardization of uveitis with variable clinical pictures are emerging. Acute anterior uveitis and panuveitis can cause red eye. The purpose of this current study is to summarize the clinical features and laboratory investigations that could help the differential diagnosis of acute anterior uveitis and panuveitis cases. (Turk J Ophthalmol 2012; 42: Supplement 57-62

  18. Subcutaneous phaeohyphomycosis caused by cladophialophora boppii

    Directory of Open Access Journals (Sweden)

    Pereira Rickson

    2010-01-01

    Full Text Available Subcutaneous phaeohyphomycosis is an infection of the skin and subcutaneous tissue, caused by dematiaceous fungi. An adult male presented with a history of multiple reddish nodules over the face and hands. Histopathological examination of the skin biopsies showed a dense granulomatous infiltrate of macrophages, containing intracytoplasmic basophilic bodies throughout the dermis. Gomori methenamine-silver stained sections revealed yeast cells within macrophages. Multiple cultures on Sabouraud′s dextrose agar grew Cladophialophora boppii. The patient was treated with oral itraconazole for a year and the response monitored with dermal ultrasound. This is the first case report of subcutaneous phaeohyphomycosis caused by Cl. boppii in India.

  19. Image processing in diabetic related causes

    CERN Document Server

    Kumar, Amit

    2016-01-01

    This book is a collection of all the experimental results and analysis carried out on medical images of diabetic related causes. The experimental investigations have been carried out on images starting from very basic image processing techniques such as image enhancement to sophisticated image segmentation methods. This book is intended to create an awareness on diabetes and its related causes and image processing methods used to detect and forecast in a very simple way. This book is useful to researchers, Engineers, Medical Doctors and Bioinformatics researchers.

  20. Auricular hematoma cases caused by mobile phones

    Directory of Open Access Journals (Sweden)

    Halil E. Özel, MD

    2015-12-01

    Full Text Available We report auricular hematoma cases caused by mobile phones. A 32-year-old male and a 23-year-old female presented with auricular hematoma, having no significant histories of trauma. The patients underwent simple hematoma aspiration. Hematoma re-accumulated in the first case. Incision and drainage were performed, and then auricular skin was stabilized by suturing a gauze pad over the area. Both patients recovered without sequelae after treatment. Judging from these cases, we want to postulate that prolonged mobile phone use may cause auricular hematoma.

  1. Unusual causes of obstructive jaundice. Computed tomography

    International Nuclear Information System (INIS)

    Rodriguez, E.; Pombo, F.; Cao, I.; Fernandez, R.; Riba da, M.

    1998-01-01

    The purpose of this study is to present selected computed tomography (CT) images showing unusual causes of obstructive jaundice. We reviewed retrospectively the Ct findings of obstructive jaundice in 227 patients. The most common causes of biliary obstruction were adenocarcinoma of the pancreatic head (n=77) and cholangiocarcinoma (n=65). In 13 cases (5.7%), the etiology of obstructive jaundice was unusual or exceptional: tuberculous adenitis (n=3), obstruction of afferent loop (n=2)signet ring cell adenocarcinoma (n=3); in duodenum, gallbladder and papilla of Water), Mirizzi syndrome (n=1), adenocarcinoma of the hepatic flexure (n=1), choledochal cyst (n=1) and pancreatic lymphoma (n=1). (Author) 13 refs

  2. Social Causes and Consequences of Rejection Sensitivity

    Science.gov (United States)

    London, Bonita; Downey, Geraldine; Bonica, Cheryl; Paltin, Iris

    2007-01-01

    Predictions from the Rejection Sensitivity (RS) model concerning the social causes and consequences of RS were examined in a longitudinal study of 150 middle school students. Peer nominations of rejection, self-report measures of anxious and angry rejection expectations, and social anxiety, social withdrawal, and loneliness were assessed at two…

  3. A breast abscess caused by Actinomyces radingae

    Directory of Open Access Journals (Sweden)

    Martine Hoogewerf, Gwen M.P. Diepenhorst, Hannah Visser, Edgar J. Peters, Karin van Dijk

    2016-06-01

    Full Text Available Actinomyces radingae is a rare isolate in clinical specimens. We describe a case of a postmenopausal woman presenting with a breast abscess caused by A. radingae. To our knowledge, this is the second description of a case of a breast infection due to this pathogen. J Microbiol Infect Dis 2016;6(2: 84-86

  4. Homocysteinemia: A rare cause of priapism

    Directory of Open Access Journals (Sweden)

    Jaisukh Kalathia

    2016-01-01

    Full Text Available Priaprism is a persistent painful erection that continuous beyond or is unrelated to sexual stimulation. Majority of cases are idiopathic (46%, alcohol and drug related (21%, perineal trauma (12%, sickle cell anemia and hypercoagualable state related (11%. We report case of priapism caused by hyperhomocysteinemia with favorable outcome with only few cases so far reported in the literature to the best of our knowledge. A 31 year-old male referred to our institution with non resolving priaprism for the last 6 days. Immediate distal shunt (Al-ghorab was created but it could not achieve the detumescence. The penile Doppler showed no flow into the corpora, so a proximal shunt (Quackels was made which achieved satisfactory detumescence. On thorough evaluation for the cause of priaprism, only homocysteine level was found to be significantly raised (40.46 µmol/L, being the unusual and rare cause for priaprism. The patient was discharged on homocheck. In the follow-up the patient is on vacuum assisted device for the erectile dysfunction and has been advised for the penile implant. Priaprism being a urological emergency should be thoroughly evaluated even for the rare causes and should be timely intervened to avoid the unavoidable consequences of permanent erectile dysfunction.

  5. Pulmonary fibrosis caused by histiocytosis X

    International Nuclear Information System (INIS)

    Reinbold, W.D.; Seemann, W.R.; Ruehle, K.H.

    1984-01-01

    This paper reports on a 23-year-old man suffering from pulmonary fibrosis caused by localised histiocytosis X. Although chest film examination shows diffuse pulmonary involvement the patient is asymptomatic. No other organ systems are involved. The different forms and prognosis of histiocytosis X are discussed. (orig.)

  6. Eliminating Problems Caused by Multicollinearity: A Warning.

    Science.gov (United States)

    Kennedy, Peter E.

    1982-01-01

    Explains why an econometric practice introduced by J.C. Soper cannot eliminate the problems caused by multicollinearity. The author suggests that it can be a useful technique in that it forces researchers to pay more attention to the specifications of their models. (AM)

  7. Dysphagia Caused by Chronic Laryngeal Edema.

    Science.gov (United States)

    Delides, Alexander; Sakagiannis, George; Maragoudakis, Pavlos; Gouloumi, Αlina-Roxani; Katsimbri, Pelagia; Giotakis, Ioannis; Panayiotides, John G

    2015-10-01

    A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

  8. Hair Loss: Common Causes and Treatment.

    Science.gov (United States)

    Phillips, T Grant; Slomiany, W Paul; Allison, Robert

    2017-09-15

    Hair loss is often distressing and can have a significant effect on the patient's quality of life. Patients may present to their family physician first with diffuse or patchy hair loss. Scarring alopecia is best evaluated by a dermatologist. Nonscarring alopecias can be readily diagnosed and treated in the family physician's office. Androgenetic alopecia can be diagnosed clinically and treated with minoxidil. Alopecia areata is diagnosed by typical patches of hair loss and is self-limited. Tinea capitis causes patches of alopecia that may be erythematous and scaly and must be treated systemically. Telogen effluvium is a nonscarring, noninflammatory alopecia of relatively sudden onset caused by physiologic or emotional stress. Once the precipitating cause is removed, the hair typically will regrow. Trichotillomania is an impulse-control disorder; treatment is aimed at controlling the underlying psychiatric condition. Trichorrhexis nodosa occurs when hairs break secondary to trauma and is often a result of hair styling or overuse of hair products. Anagen effluvium is the abnormal diffuse loss of hair during the growth phase caused by an event that impairs the mitotic activity of the hair follicle, most commonly chemotherapy. Physician support is especially important for patients in this situation.

  9. Prevention of pulsations caused by flexible risers

    NARCIS (Netherlands)

    Belfroid S.P.C; Golliard, J.; Korst, H.J.C.

    2013-01-01

    In the last few decades, flexible risers have increasingly been used in the offshore oil and gas industry. In gas applications these risers can generate high amplitude tonal pressure fluctuations when the gas velocity reaches a threshold value. The resulting pressure fluctuations can then cause high

  10. Germline KRAS mutations cause Noonan syndrome.

    NARCIS (Netherlands)

    Schubbert, S.; Zenker, M.; Rowe, S.L.; Boll, S.; Klein, C.; Bollag, G.; Burgt, I. van der; Musante, L.; Kalscheuer, V.M.M.; Wehner, L.E.; Nguyen, H.; West, B.; Zhang, K.Y.; Sistermans, E.A.; Rauch, A.; Niemeyer, C.M.; Shannon, K.; Kratz, C.P.

    2006-01-01

    Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream

  11. State of the environment - causes and consequences

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In this chapter the economic development and technologies, gross domestic product, industry, mineral resources exploitation, power plant engineering, gas engineering, heat production, forestry, agriculture, and transport and their environmental impact are reviewed. Selected indicators of the public health and basic factors influencing the death-rate of the Slovak population as well as causes of death in 1997 are presented

  12. Causes of road traffic accidents in Juba

    Directory of Open Access Journals (Sweden)

    Akway M. Cham

    2017-05-01

    Full Text Available Introduction: Road traffic accidents (RTAs are a major cause of death and disability in South Sudan. The purpose of this study was to investigate whether violation of traffic rules is the main cause of RTAs. Method: A cross sectional study design was used with quantitative data covering January – December 2014. The main objective of the research was to understand the epidemiology of RTAs in order to develop preventive measures. A total of 1725cases from road RTAs data were extracted from the directorate of traffic police Central Equatoria state Juba and Juba teaching hospital. Results: Most (99.5% of the RTA drivers were not under the influence of alcohol. Most accidents were caused by male drivers (99%. The highest number of RTAs took place in August (11%. Drivers of private vehicles caused most accidents (37%. Most drivers (46% were aged 20-30 years. RTAs occurred most often on city roads (89.83%. Conclusion: This leads us to conclude that a comprehensive safety system is needed that are premised on the idea of community-based awareness of traffic rules and safety regulations. Resources are limited so there is a need to harness local resources including the local community. More efforts are needed to improve road safety education among the youth/integrate safety into road design.

  13. Causes of Student Absenteeism and School Dropouts

    Science.gov (United States)

    Sahin, Seyma; Arseven, Zeynep; Kiliç, Abdurrahman

    2016-01-01

    The aim of the study is to investigate the causes of student absenteeism and school dropouts at primary, secondary and high school level in Düzce Province and to develop suggestions for solving these problems. A "case study" design, which is one of the qualitative research approaches, was used in this study. The study group consisted of…

  14. Youth Unemployment. The Causes and Consequences.

    Science.gov (United States)

    Organisation for Economic Cooperation and Development, Paris (France).

    This report examines the causes and consequences of youth unemployment in Organisation for Economic Cooperation and Development (OECD) member countries. Summarized first is the youth unemployment situation since the 1974/1975 recession. In a section on recent developments in youth labor markets a series of tables and graphs provide data on youth…

  15. Coin exposure may cause allergic nickel dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Gawkrodger, David J; White, Ian R

    2012-01-01

    Nickel is used in coins because the metal has beneficial properties, including price, colour, weight, and corrosion resistance, and also because it is easy to stamp. It has often been claimed that the duration of skin contact with coins is too short to cause nickel release and dermatitis. However...

  16. Genetically caused congenital anomalies of reproductive system

    Directory of Open Access Journals (Sweden)

    L. F. Kurilo

    2013-01-01

    Full Text Available Classification of congenital disorders, their frequency of occurrence in populations, and some terminology questions discussed in the review. Genetically caused congenital anomalies of reproductive system are outlined. Full information about genetic syndromes is stated in the book: Kozlova S.I., Demikova N.S. Hereditary syndromes and genetic counseling. M., 2007.

  17. Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic ...

    African Journals Online (AJOL)

    Two patients with haematopoietic stem cell transplant who developed pneumonia caused by M. catarrhalis at King Faisal Specialist Hospital and Research Centre in Riyadh are reported and the literature is reviewed. To our knowledge, these are the first case reports of M. catarrhalis pneumonia in haematopoietic stem cell ...

  18. Multiple lung abscesses caused by Streptococcus constellatus

    Directory of Open Access Journals (Sweden)

    Vanina Rognoni

    2018-02-01

    Full Text Available Despite numerous descriptions of body abscesses produced by Streptococcus milleri group bacteria, lung abscesses caused by this group remain under-reported and the clinical and laboratory features have yet to be fully characterised. We present the case of a patient admitted with lung multiple abscesses produced by Streptococcus constellatus.

  19. Secondary Hypertension: Discovering the Underlying Cause.

    Science.gov (United States)

    Charles, Lesley; Triscott, Jean; Dobbs, Bonnie

    2017-10-01

    Most patients with hypertension have no clear etiology and are classified as having primary hypertension. However, 5% to 10% of these patients may have secondary hypertension, which indicates an underlying and potentially reversible cause. The prevalence and potential etiologies of secondary hypertension vary by age. The most common causes in children are renal parenchymal disease and coarctation of the aorta. In adults 65 years and older, atherosclerotic renal artery stenosis, renal failure, and hypothyroidism are common causes. Secondary hypertension should be considered in the presence of suggestive symptoms and signs, such as severe or resistant hypertension, age of onset younger than 30 years (especially before puberty), malignant or accelerated hypertension, and an acute rise in blood pressure from previously stable readings. Additionally, renovascular hypertension should be considered in patients with an increase in serum creatinine of at least 50% occurring within one week of initiating angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy; severe hypertension and a unilateral smaller kidney or difference in kidney size greater than 1.5 cm; or recurrent flash pulmonary edema. Other underlying causes of secondary hypertension include hyperaldosteronism, obstructive sleep apnea, pheochromocytoma, Cushing syndrome, thyroid disease, coarctation of the aorta, and use of certain medications.

  20. Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic ...

    African Journals Online (AJOL)

    Moraxella catarrhalis is a gram negative diplococcus that causes a variety of upper and lower respiratory tract infections. Patients with malignant, hematological disorders treated with intensive cytotoxic chemotherapy, and recipients of various forms of haematopoietic stem cell transplant receiving immunosuppressive ...

  1. Causes and management of postoperative enterocutaneous fistulas

    International Nuclear Information System (INIS)

    Memon, A.S.; Siddiqui, F.G

    2004-01-01

    Objective: To identify the causes of postoperative enterocutaneous fistulas and to evaluate the results of conservative and operative treatment including the effectiveness of octreotide in the management of these fistulas. Subjects and Methods: Forty patients with postoperative fistula were studied. Demographic variables, causes and management outcome was observed and recorded. Results: There were 25 males and 15 females with 50% of the patients being in age group of 21-30 years. Emergency surgery for typhoid perforation(45%) and intestinal tuberculosis (30%) were the commonest causes. Ileum and jejunum were the commonest sites of fistulation found in 85% cases. Twenty-one patients were started on conservative treatment with spontaneous closure occurring in 15 (71.4%) patients. Nineteen patients were operated within three days of admission due to generalized peritonitis (73.7%) and local intra-abdominal collections (26.3%). Wound infection was the commonest complication in the operative group. The mortality rate in this series was 7.5%. All the deaths occurred following surgery. Conclusion: Postoperative enterocutaneous fistula has a high morbidity and a significant mortality. Sepsis in the peritoneal cavity is the major cause of mortality. Conservative treatment has a good outcome for these fistulas. The use of octreotide is highly recommended as it definitely converts high output fistulas to low output fistulas. (author)

  2. Prions: Protein Rebels with a Cause!

    Science.gov (United States)

    Marshall, Karen E.; Serpell, Louise C.

    2017-01-01

    Traditionally we consider infection to arise from viruses, bacteria and parasites. Prions are infectious proteins without any nucleic acids, and therefore do not represent living things. Despite this, they have the ability to replicate themselves and cause diseases such as mad cow disease (bovine spongiform encepthalopathy) and human…

  3. Cancer caused by radioactive gold rings

    International Nuclear Information System (INIS)

    Callary, E.M.

    1989-01-01

    Two recent cases of skin cancer caused by radioactive gold rings are described. The gold was contaminated with radon daughters from hollow goldseeds used to hold radon, back in the 1930s or possibly later. Other radioactive gold rings are probably being worn. The Canadian AECB offers free testing

  4. Liver Hypertension: Causes, Consequences and Prevention

    Indian Academy of Sciences (India)

    Table of contents. Liver Hypertension: Causes, Consequences and Prevention · Heart Pressure : Blood Pressure · Slide 3 · If you continue to have high BP · Doctor Measures Blood Pressure (BP): Medicines to Decrease BP · LIVER ~ ~ LIFE Rightists vs. Leftists · Slide 7 · Slide 8 · Slide 9 · Liver Spleen - Splanchnic ...

  5. Teacher Burnout: Causes, Cures and Prevention

    Science.gov (United States)

    Bousquet, Sarah

    2012-01-01

    In a review of the literature, this study defines teacher burnout, explains the physiological and environmental causes of teacher burnout, and provides suggestions regarding how educators can prevent and recover from teacher burnout. The essay addresses the uniquely stressful experience of teaching and the psychological effects of the profession.

  6. Systemic allergic dermatitis caused by sesquiterpene lactones

    DEFF Research Database (Denmark)

    Paulsen, Evy

    2017-01-01

    Patients with Compositae sensitization are routinely warned against the ingestion of vegetables, spices, teas and herbal remedies from this family of plants. The evidence for the occurrence of systemic allergic dermatitis caused by sesquiterpene lactone-containing plants is mostly anecdotal...

  7. Facial Baroparesis Caused by Scuba Diving

    Directory of Open Access Journals (Sweden)

    Daisuke Kamide

    2012-01-01

    tympanic membrane and right facial palsy without other neurological findings. But facial palsy was disappeared immediately after myringotomy. We considered that the etiology of this case was neuropraxia of facial nerve in middle ear caused by over pressure of middle ear.

  8. Paravertebral Abscess Caused by Bukholderia Pseudomallei in

    Directory of Open Access Journals (Sweden)

    S Ahmad

    2009-05-01

    Full Text Available A 53-year-old Malay man was admitted with intestinal obstruction, fever and lower limb weakness. Initial clinical impression was myelitis causing paralytic ilues and paraperesis. Blood culture showed Burkholderia pseudomallei infection and subsequent MRI showed paravertebral abscess. This case highlights a rare manifestation of melioidosis involving the spine and difficulties in establishing the diagnosis.

  9. IDENTIFYING THE CRITICAL CAUSES OF CONFLICT IN ...

    African Journals Online (AJOL)

    Completing construction projects entails inputs from various professional disciplines; this makes projects prone to conflicts. It has been acknowledged that management of conflict is crucial to improving project performance. Thus, understanding the causes of conflicts in construction project will ease the process of conflict ...

  10. Is It True That Smoking Causes Wrinkles?

    Science.gov (United States)

    Healthy Lifestyle Quit smoking Is it true that smoking causes wrinkles? Answers from J. Taylor Hays, M.D. Yes. So if you need another reason to motivate ... elastin, which are fibers that give your skin its strength and elasticity. As a result, skin begins ...

  11. Social causes of low birth weight.

    OpenAIRE

    Kogan, M D

    1995-01-01

    The manifest importance of reducing the incidence of low birth weight is most obvious for the first year of life: low birth weight is the single most important factor affecting infant morbidity and mortality. However, there is growing evidence that the adverse consequences of low birth weight continue throughout the life cycle. This review deals primarily with social causes of low birth weight.

  12. Common Variable Immunodeficiency Caused by FANC Mutations.

    Science.gov (United States)

    Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

    2017-07-01

    Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

  13. Prevalence and causes of abnormal PSA recovery.

    Science.gov (United States)

    Lautenbach, Noémie; Müntener, Michael; Zanoni, Paolo; Saleh, Lanja; Saba, Karim; Umbehr, Martin; Velagapudi, Srividya; Hof, Danielle; Sulser, Tullio; Wild, Peter J; von Eckardstein, Arnold; Poyet, Cédric

    2018-01-26

    Prostate-specific antigen (PSA) test is of paramount importance as a diagnostic tool for the detection and monitoring of patients with prostate cancer. In the presence of interfering factors such as heterophilic antibodies or anti-PSA antibodies the PSA test can yield significantly falsified results. The prevalence of these factors is unknown. We determined the recovery of PSA concentrations diluting patient samples with a standard serum of known PSA concentration. Based on the frequency distribution of recoveries in a pre-study on 268 samples, samples with recoveries 120% were defined as suspect, re-tested and further characterized to identify the cause of interference. A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%) showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three samples heterophilic antibodies were identified as the probable cause, in the fourth anti-PSA-autoantibodies. The very low recovery caused by the latter interference was confirmed in serum, as well as heparin- and EDTA plasma of blood samples obtained 6 months later. Analysis by eight different immunoassays showed recoveries ranging between PSA which however did not show any disturbed PSA recovery. About 0.3% of PSA determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare, these interferences can cause relevant misinterpretations of a PSA test result.

  14. Research in Review: What Causes Cruelty?

    Science.gov (United States)

    DeRosa, Bill

    1985-01-01

    Addresses the problem of cruelty to animals from a research perspective. Studies of possible causes of childhood cruelty to animals are reviewed and common contributing environmental factors are identified. Implications for educators are discussed and directives for detection and prevention of cruelty are suggested. (ML)

  15. Causes and Treatment of Insomnia among Adolescents.

    Science.gov (United States)

    Morrison, Jack R.; And Others

    1985-01-01

    As much as 13 percent of the adolescent population may suffer from chronic insomnia, which can impair the victim's daily existence and affect personal life, school performance, and school attendance. The prevalence of adolescent insomnia, and its cause, diagnosis, and treatment are examined. (Author/CB)

  16. Economic Loss Caused by GMOs in Denmark

    DEFF Research Database (Denmark)

    Ulfbeck, Vibe Garf

    2008-01-01

    This book presents how European jurisdictions currently respond to economic losses caused by the admixture of gentically modified crops with conventional or organic crops and what alternatives there are from a comparative perspective. Country reports from most European countries are complemented ...

  17. Mycobacterium fortuitum causing surgical site wound infection

    International Nuclear Information System (INIS)

    Kaleem, F.; Usman, J.; Omair, M.; Din, R.U.; Hassan, A.

    2010-01-01

    Mycobacterium fortuitum, a rapidly growing mycobacterium, is ubiquitous in nature. The organism was considered to be a harmless saprophyte but now there have been several reports from different parts of the world wherein it has been incriminated in a variety of human infections. We report a culture positive case of surgical site infection caused by Mycobacterium fortuitum, who responded well to the treatment. (author)

  18. Unusual cause of neonatal intestinal obstruction | Zikavska ...

    African Journals Online (AJOL)

    There are many causes of intestinal obstruction in the neonatal age. The most common types are mechanical and result from congenital malformations of the gastrointestinal tract. However, functional disorders also occur. In some cases, diagnosis can be made prenatally but in others manifestation occurs after birth. The aim ...

  19. Stress in College Athletics: Causes, Consequences, Coping.

    Science.gov (United States)

    Humphrey, James H.; Yow, Deborah A.; Bowden, William W.

    This book addresses the causes and consequences of stress in college sports and offers effective coping mechanisms to help individuals understand and control stressors and emotions in their environment. The chapters are: (1) "Understanding Stress"; (2) "Perceptions of Stress in College Athletics"; (3) "Stress among College Athletes"; (4) "Stress…

  20. Causes, effects and therapy of radiophobie syndrome

    International Nuclear Information System (INIS)

    Becker, K.

    2005-01-01

    The basic symptoms and causes of the origination of radiophobie in Germany and other developed countries are considered. The economic and ecological consequences of the ideological antinuclear politics and the struggle against NPP are analyzed. The measures on overcoming radiophobie among population of developed countries are proposed. The particular attention for this problem solving is given to the position of mass media [ru

  1. Lymphogranuloma venereum causing a persistent genital ulcer.

    Science.gov (United States)

    Marcotte, Terrence; Lee, Yer; Pandori, Mark; Jain, Vivek; Cohen, Stephanie Elise

    2014-04-01

    Lymphogranuloma venereum (LGV) is a sexually transmitted cause of inguinal lymphadenopathy and proctocolitis. We report a patient with a persistent genital ulcer due to LGV (serovar L2b), an unusual presentation among US men who have sex with men. Lymphogranuloma venereum should be considered when evaluating persistent genital ulcers, and LGV-specific testing should be sought.

  2. Invasive Disease Caused by Nontypeable Haemophilus Influenzae

    Centers for Disease Control (CDC) Podcasts

    2015-11-12

    Dr. Elizabeth Briere discusses Nontypeable Haemophilus influenzae which causes a variety of infections in children and adults.  Created: 11/12/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/17/2015.

  3. The Young Drinking Driver: Cause or Effect?

    Science.gov (United States)

    Waller, Patricia F.; Waller, Marcus B.

    Drunk driving is a major public health problem and young people suffer disproportionately high rates of morbidity and mortality as a result of drinking and driving. Motor vehicle injuries are the leading cause of death for persons aged 15-24 in this country, and alcohol is implicated in many of these deaths. Countermeasures to drinking and driving…

  4. Causes of Sexual Promiscuity Among Female Undergraduate ...

    African Journals Online (AJOL)

    This study investigated causes of sexual promiscuity among female undergraduate students in university of Lagos. The sample comprised 150 female undergraduate students randomly selected from all the five female hostels in University of Lagos. A researcher-constructed questionnaire was administered to test the three ...

  5. Identifying Foods causing Allergies/ Intolerances among Diabetic ...

    African Journals Online (AJOL)

    Objective: This study was designed to identify the foods that caused allergies / intolerances and symptoms of reaction experienced by diabetic patients attending State Specialist Hospital, Akure. Materials and Methods: Ninety-eight diabetics aged 30-80 years (30 males and 68 females) were included in the study.

  6. Cell Vacuolation Caused by Vibrio cholerae Hemolysin

    Science.gov (United States)

    Figueroa-Arredondo, Paula; Heuser, John E.; Akopyants, Natalia S.; Morisaki, J. Hiroshi; Giono-Cerezo, Silvia; Enríquez-Rincón, Fernando; Berg, Douglas E.

    2001-01-01

    Non-O1 strains of Vibrio cholerae implicated in gastroenteritis and diarrhea generally lack virulence determinants such as cholera toxin that are characteristic of epidemic strains; the factors that contribute to their virulence are not understood. Here we report that at least one-third of diarrhea-associated nonepidemic V. cholerae strains from Mexico cause vacuolation of cultured Vero cells. Detailed analyses indicated that this vacuolation was related to that caused by aerolysin, a pore-forming toxin of Aeromonas; it involved primarily the endoplasmic reticulum at early times (∼1 to 4 h after exposure), and resulted in formation of large, acidic, endosome-like multivesicular vacuoles (probably autophagosomes) only at late times (∼16 h). In contrast to vacuolation caused by Helicobacter pylori VacA protein, that induced by V. cholerae was exacerbated by agents that block vacuolar proton pumping but not by endosome-targeted weak bases. It caused centripetal redistribution of endosomes, reflecting cytoplasmic alkalinization. The gene for V. cholerae vacuolating activity was cloned and was found to correspond to hlyA, the structural gene for hemolysin. HlyA protein is a pore-forming toxin that causes ion leakage and, ultimately, eukaryotic cell lysis. Thus, a distinct form of cell vacuolation precedes cytolysis at low doses of hemolysin. We propose that this vacuolation, in itself, contributes to the virulence of V. cholerae strains, perhaps by perturbing intracellular membrane trafficking or ion exchange in target cells and thereby affecting local intestinal inflammatory or other defense responses. PMID:11179335

  7. [Causes of emergency dizziness stratified by etiology].

    Science.gov (United States)

    Qiao, Wenying; Liu, Jianguo; Zeng, Hong; Liu, Yugeng; Jia, Weihua; Wang, Honghong; Liu, Bo; Tan, Jing; Li, Changqing

    2014-06-03

    To explore the causes of emergency dizziness stratified to improve the diagnostic efficiency. A total of 1 857 cases of dizziness at our emergency department were collected and their etiologies stratified by age and gender. The top three diagnoses were benign paroxysmal positional vertigo (BPPV, 31.7%), hypertension (24.0%) and posterior circulation ischemia (PCI, 20.5%). Stratified by age, the main causes of dizziness included BPPV (n = 6), migraine-associated vertigo (n = 2), unknown cause (n = 1) for the group of vertigo (14.5%) and neurosis (7.3%) for 18-44 years; BPPV (36.8%), hypertension (22.4%) and migraine-associated vertigo (11.2%) for 45-59 years; hypertension (30.8%), PCI (29.8%) and BPPV (22.9%) for 60-74 years; PCI (30.7%), hypertension (28.6%) and BPPV (25.5%) for 75-92 years. BPPV, migraine and neurosis were more common in females while hypertension and PCI predominated in males (all P hypertension, neurosis and migraine showed the following significant demographic features: BPPV, PCI, hypertension, neurosis and migraine may be the main causes of dizziness. BPPV should be considered initially when vertigo was triggered repeatedly by positional change, especially for young and middle-aged women. And the other common causes of dizziness were migraine-associated vertigo, neurosis and Meniere's disease.Hypertension should be screened firstly in middle-aged and elderly patients presenting mainly with head heaviness and stretching. In elders with dizziness, BPPV is second in constituent ratio to PCI and hypertension.In middle-aged and elderly patients with dizziness, psychological factors should be considered and diagnosis and treatment should be offered timely.

  8. EPRI root cause advisory workstation 'ERCAWS'

    International Nuclear Information System (INIS)

    Singh, A.; Chiu, C.; Hackman, R.B.

    1993-01-01

    EPRI and its contractor FPI International are developing Personal Computer (PC), Microsoft Windows based software to assist power plant engineers and maintenance personnel to diagnose and correct root causes of power plant equipment failures. The EPRI Root Cause Advisory Workstation (ERCAWS) is easy to use and able to handle knowledge bases and diagnostic tools for an unlimited number of equipment types. Knowledge base data is based on power industry experience and root cause analysis from many sources - Utilities, EPRI, US government, FPI, and International sources. The approach used in the knowledge base handling portion of the software is case-study oriented with the engineer selecting the equipment type and symptom identification using a combination of text, photographs, and animation, displaying dynamic physical phenomena involved. Root causes, means for confirmation, and corrective actions are then suggested in a simple, user friendly format. The first knowledge base being released with ERCAWS is the Valve Diagnostic Advisor module; covering six common valve types and some motor operator and air operator items. More modules are under development with Heat Exchanger, Bolt, and Piping modules currently in the beta testing stage. A wide variety of diagnostic tools are easily incorporated into ERCAWS and accessed through the main screen interface. ERCAWS is designed to fulfill the industry need for user-friendly tools to perform power plant equipment failure root cause analysis, and training for engineering, operations and maintenance personnel on how components can fail and how to reduce failure rates or prevent failure from occurring. In addition, ERCAWS serves as a vehicle to capture lessons learned from industry wide experience. (author)

  9. Cross-sectional study on prevalence, causes and avoidable causes of visual impairment in Maori children.

    Science.gov (United States)

    Chong, Cheefoong; Dai, Shuan

    2013-08-02

    To provide information and comparison pertaining to visual impairment of Maori children with other children in New Zealand in particular: prevalence of blindness, causes of visual impairment, and avoidable causes of visual impairment. Retrospective data collection utilising the WHO/PBL eye examination record for children with blindness and low vision at Blind and Low Vision Education Network New Zealand (BLENNZ), Homai. Individuals not of Maori ethnicity or over the age of 16 were excluded from the study. 106 blind and 64 low-vision Maori children were studied. The main cause of blindness in Maori children is cortical visual impairment. Twenty-eight percent of causes of blindness in this population are potentially avoidable with non-accidental injury as the main cause. The prevalence of blindness and low vision in children amounts to 0.05% and 0.03%, respectively. The prevalence and causes of childhood blindness are comparable to the other ethnic groups in New Zealand. The main difference lies in avoidable causes of blindness, which appeared to be much higher in the Maori population. The leading cause of avoidable blindness in Maori children is caused by non-accidental injuries.

  10. Prevalence of Mycoplasma pneumoniae: A cause for community ...

    African Journals Online (AJOL)

    Background: Atypical pneumonia caused by Mycoplasma pneumoniae is a leading cause of ... causing bronchial asthma and chronic obstructive pulmonary ..... Mycoplasma pneumoniae is a frequent cause of exacerbation of bronchial asthma ...

  11. Piriformis syndrome: a cause of nondiscogenic sciatica.

    Science.gov (United States)

    Cass, Shane P

    2015-01-01

    Piriformis syndrome is a nondiscogenic cause of sciatica from compression of the sciatic nerve through or around the piriformis muscle. Patients typically have sciatica, buttocks pain, and worse pain with sitting. They usually have normal neurological examination results and negative straight leg raising test results. Flexion, adduction, and internal rotation of the hip, Freiberg sign, Pace sign, and direct palpation of the piriformis cause pain and may reproduce symptoms. Imaging and neurodiagnostic studies are typically normal and are used to rule out other etiologies for sciatica. Conservative treatment, including medication and physiotherapy, is usually helpful for the majority of patients. For recalcitrant cases, corticosteroid and botulinum toxin injections may be attempted. Ultrasound and other imaging modalities likely improve accuracy of injections. Piriformis tenotomy and decompression of the sciatic nerve can be done for those who do not respond.

  12. Sciatica caused by lumbar epidural gas.

    Science.gov (United States)

    Belfquih, Hatim; El Mostarchid, Brahim; Akhaddar, Ali; gazzaz, Miloudi; Boucetta, Mohammed

    2014-01-01

    Gas production as a part of disc degeneration can occur but rarely causes nerve compression syndromes. The clinical features are similar to those of common sciatica. CT is very useful in the detection of epidural gas accumulation and nerve root compression. We report a case of symptomatic epidural gas accumulation originating from vacuum phenomenon in the intervertebral disc, causing lumbo-sacral radiculopathy. A 45-year-old woman suffered from sciatica for 9 months. The condition worsened in recent days. Computed tomography (CT) demonstrated intradiscal vacuum phenomenon, and accumulation of gas in the lumbar epidural space compressing the dural sac and S1 nerve root. After evacuation of the gas, her pain resolved without recurrence.

  13. Nerve injury caused by mandibular block analgesia

    DEFF Research Database (Denmark)

    Hillerup, S; Jensen, Rigmor H

    2006-01-01

    Fifty-four injection injuries in 52 patients were caused by mandibular block analgesia affecting the lingual nerve (n=42) and/or the inferior alveolar nerve (n=12). All patients were examined with a standardized test of neurosensory functions. The perception of the following stimuli was assessed......: feather light touch, pinprick, sharp/dull discrimination, warm, cold, point location, brush stroke direction, 2-point discrimination and pain perception. Gustation was tested for recognition of sweet, salt, sour and bitter. Mandibular block analgesia causes lingual nerve injury more frequently than...... inferior alveolar nerve injury. All grades of loss of neurosensory and gustatory functions were found, and a range of persisting neurogenic malfunctions was reported. Subjective complaints and neurosensory function tests indicate that lingual nerve lesions are more incapacitating than inferior alveolar...

  14. Cerebral hemorrhage caused by amyloid angiopathy

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Tomonaga, Masanori; Yoshimura, Masahiro; Yamanouchi, Hiroshi; Shimada, Hiroyuki.

    1985-01-01

    Cerebral hemorrhage caused by amyloid angiopathy was studied clinicopathologically, with special attention given to the CT images. Cerebral hemorrhage caused by amyloid angiopathy is characterized, by a lobar-type hemorrhage involving the cortex, with direct extension into the subarachnoid space. Multiple hemorrhages are frequent, and cortical infarctions are present as complications in elderly patients without risk factors. CT scans taken in 5 cases demonstrated lobar hemorrhages in superficial locations, frequently in multiple sites or recurrently, with surrounding edema and mass effect. A subarachnoid extension of the hemorrhage through the superficial cortex, proven pathologically in all cases, was noted by CT in 4 of the 5 cases. However, cortical infarction was not detected by CT in any case. Therefore, CT is of value in the diagnosis of cerebral hemorrhage due to amyloid angiopathy based on distinctive findings such as a lobar hemorrhage in superficial regions, with extension into the subarachnoid space, frequently in multiple sites or recurrently. (author)

  15. Acute Hemolysis Caused by Incidental Trichlorfon Exposure

    Directory of Open Access Journals (Sweden)

    Ming-Ling Wu

    2009-04-01

    Full Text Available Trichlorfon (o-o-dimethyl-2,2,2-trichloro-hydroxyethylphosphate, an organophosphate, has a moderately potent anti-cholinesterase activity. Organophosphate poisoning is well known for its characteristic symptoms and signs, but acute hemolysis caused by trichlorfon is rarely reported. We present a patient who developed acute hemolysis and renal function impairment after percutaneous trichlorfon exposure. A 54-year-old man applied trichlorfon powder to his dog to kill its parasites. Half an hour later, the dog was suspected to die of cholinergic crisis and the patient felt abdominal cramping pain. Later, he developed severe nausea, vomiting, chills, high fever, and cold sweat. Laboratory work-up disclosed a picture of acute hemolysis, jaundice, renal function impairment and leukocytosis. However, there were no clinical features of acute cholinergic syndrome except gastrointestinal symptoms, and blood cholinesterase activities were also normal. He eventually had a full recovery. Trichlorfon should be added to the toxins known to cause acute hemolysis.

  16. Can atorvastatin calcium cause asymptomatic hypercalcemia?

    Science.gov (United States)

    Ipekçi, Süleyman Hilmi; Baldane, Süleyman; Sözen, Mehmet; Kebapçılar, Levent

    2014-10-01

    The use of statins may have unnatural effects. A 54-year-old woman was admitted to the hospital with an incidental finding of hypercalcemia (10.8 mg/dL). There was no disease other than hyperlipidemia, and the patient had been on a course of atorvastatin calcium 10 mg for 1.5 years. A workup investigation to diagnose the cause of hypercalcemia was completed. The investigation did not reveal any pathological diseases that may have caused the hypercalcemia. The hypercalcemia resolved after atorvastatin-calcium was stopped, and the patient developed hypercalcemia shortly after the initiation of the atorvastatin calcium. Here, we report a clinical case of recurrent hypercalcemia possibly induced by atorvastatin calcium administration.

  17. Annular pancreas causing extrahepatic biliary obstruction

    International Nuclear Information System (INIS)

    Ogulin, M.; Jamar, B.

    2004-01-01

    Background. Annular pancreas is an uncommon congenital abnormality, consisting of a flat band of pancreatic tissue, which encircles duodenum or extrahepatic biliary duct. We present a case of obstructive jaundice, caused by annular pancreas. Case report. A 46 years old female was admitted because of a sudden onset of abdominal pain, vomiting and jaundice. For the last six years she occasionally noticed her skin was light yellow, in the last year she felt distension in the upper abdomen, especially after fatty meals. Conclusions. Two US examinations, the first one six months before the admission, showed dilated hepatic ducts. The reason of dilatation was unclear, even after the endoscopic US examination. At operation an almost complete obstruction of the common hepatic duct was found, caused by a narrow band of pancreatic tissue. (author)

  18. Cellulitis and Bacteremia Caused by Bergeyella zoohelcum

    Directory of Open Access Journals (Sweden)

    Wei-Ru Lin

    2007-01-01

    Full Text Available Bergeyella zoohelcum is a rod-shaped, aerobic, Gram-negative, non-motile and non-saccharolytic bacterium. It is frequently isolated from the upper respiratory tract of dogs, cats and other mammals. Clinically, B. zoohelcum has been known to cause cellulitis, leg abscess, tenosynovitis, septicemia, pneumonia and meningitis, and is associated with animal bites. In addition, food-borne transmission was considered in a recent case report. We report a 73-year-old man with liver cirrhosis who had no history of dog bite but had dog exposure, who developed cellulitis of the left lower leg and B. zoohelcum was isolated from blood culture. This patient, without evidence of polymicrobial infection, was treated with cefazolin and gentamicin with a good outcome. B. zoohelcum is a zoonotic pathogen that may cause bacteremia in patients with underlying disease such as liver cirrhosis; it can be treated with a beta-lactam or quinolone.

  19. Psychological consequences caused by nuclear terrorism

    International Nuclear Information System (INIS)

    Peyankov, I.

    2009-01-01

    The psychological consequences caused by eventual nuclear terrorist act are believed to be some of the most: serious. in this article are presented the issues concerning psychological effects as psychological suffering, alteration of risk estimation, changes of individual and social behavior, etc. The most common psychological consequences as a result of the most popular large-scale nuclear accidents in Chernobyl, TMI (USA), Goiania (Brazil) are described. Some of the main factors, such as sex, age, health status, social status and etc, are analyzed. These factors determine the expression of psychological reactions provoked by nuclear accidents or eventual act of nuclear terrorism. In addition, the main precautions to cope with psychological consequences caused by nuclear terrorism are listed

  20. Term stillbirth caused by oral Fusobacterium nucleatum.

    Science.gov (United States)

    Han, Yiping W; Fardini, Yann; Chen, Casey; Iacampo, Karla G; Peraino, Victoria A; Shamonki, Jaime M; Redline, Raymond W

    2010-02-01

    Intrauterine infection is a recognized cause of adverse pregnancy outcome, but the source of infection is often undetermined. We report a case of stillbirth caused by Fusobacterium nucleatum that originated in the mother's mouth. A woman with pregnancy-associated gingivitis experienced an upper respiratory tract infection at term, followed by stillbirth a few days later. F. nucleatum was isolated from the placenta and the fetus. Examination of different microbial floras from the mother identified the same clone in her subgingival plaque but not in the supragingival plaque, vagina, or rectum. F. nucleatum may have translocated from the mother's mouth to the uterus when the immune system was weakened during the respiratory infection. This case sheds light on patient management for those with pregnancy-associated gingivitis.

  1. Proctalgia fugax: caused by pudendal neuropathy?

    Science.gov (United States)

    Takano, Masahiro

    2005-01-01

    There is a strange disease called proctalgia fugax in which rather uncomfortable pain appears suddenly mostly at night without any particular warning and disappears completely without any objective traces. It also is categorized as a functional anorectal pain under the Rome II (diagnostic criteria for the functional gastrointestinal disorders). For the causes, many theories have been advocated but not decisive and therefore were not linked to the definite treatment. The author experienced 68 patients with proctalgia fugax, among which 55 patients had tenderness along the pudendal nerve. The location, character, and degree of pain caused by digital examination were confirmed by all of them to be similar to that which they experience at times of paroxysm. After administration of a nerve block, symptoms disappeared completely in 65 percent of the patients and decreased in 25 percent. These data suggest that the pathogenesis of proctalgia fugax is neuralgia of the pudendal nerves.

  2. Fatal Primary Meningoencephalitis Caused By Naegleria Fowleri

    International Nuclear Information System (INIS)

    Shariq, A.; Afridi, F. I.; Farooqi, B. J.; Husaain, A.; Ahmed, S.

    2014-01-01

    Naegleria fowleri is a free living parasite which habitats in fresh water reservoirs. It causes a fatal nervous system infection known as primary amoebic meningoencephalitis by invading through cribriform plate of nose and gaining entry into brain. We report a case of primary amoebic meningoencephalitis caused by Naegleria fowleri in Karachi, Pakistan, in a 42 years old male poultry farm worker having no history of swimming. Clinical course was fulminant and death occurred within one week of hospital admission. Naegleria fowleri was detected by wet mount technique in the sample of cerebrospinal fluid collected by lumbar puncture of patient. This is a serious problem and requires immediate steps to prevent general population to get affected by this lethal neurological infection. (author)

  3. Gasoline ingestion: a rare cause of pancytopenia.

    Science.gov (United States)

    Rahman, Ifad; Narasimhan, Kanakasabai; Aziz, Shahid; Owens, William

    2009-11-01

    The majority of reported cases of gasoline intoxication involves inhalation or percutaneous absorption. Data are scarce on complications and outcomes after gasoline poisoning by oral ingestion. The major cause of mortality and morbidity associated with the ingestion of gasoline is related to pulmonary aspiration. Despite the high frequency of the ingestions, there is little documentation of nonpulmonary toxic effects of gasoline. After ingestion, the principal toxicity is aspiration pneumonia, but any documented extra pulmonary manifestations of this condition may be important in the overall management of these patients. We are reporting a rare case of pancytopenia along with aspiration pneumonia and multisystem organ failure in a 58-year-old male after prolonged intentional ingestion of gasoline. To our knowledge, this is the only reported case of gasoline toxicity causing pancytopenia.

  4. Hypokalemic periodic paralysis: Three rare secondary causes

    Directory of Open Access Journals (Sweden)

    Prasanna Eswaradass Venkatesan

    2015-01-01

    Full Text Available Periodic paralysis is a rare neuromuscular disorder, related to a defect in muscle ion channels, characterized by episodes of painless muscle weakness, which may be precipitated by heavy exercise, fasting, or high-carbohydrate meals. Hypokalemic periodic paralysis may be familial (primary or secondary. Here, we report three cases of secondary causes of hypokalemic periodic paralysis. On evaluation, case 1 had distal renal tubular acidosis (RTA due to Sjogren′s syndrome, case 2 had drug induced proximal RTA (Fanconi′s syndrome and case 3 had thyrotoxicosis. Clinician must be aware of causes of secondary PP as recognition and diagnosis can completely prevent further attacks of periodic paralysis. Each of the above case is rare, but completely treatable if diagnosed. Low dose steroids with bicarbonate replacement in case 1, stopping tenofovir in case 2 and carbimazole therapy in case 3 prevented further attacks of periodic paralysis and cardiopulmonary complications.

  5. The Monju accident. Causes and effects

    International Nuclear Information System (INIS)

    Marth, W.

    1996-01-01

    On December 8, 1995, the Japanese prototype fast breeder reactor, Monju, suffered an accident which aroused considerable national and international attention. A thermocouple in a pipe carrying sodium in the secondary plant system had broken, causing some 700 kg of non-radioactive sodium to be spilled. The safety of the reactor, of the plant crew, and of the environment was not jeopardized. However, as a consequence of some badly handled public relations, rather negative reactions of the public authorities and of the public at large were encountered. One member of the investigating committee, facing a conflict of loyalities not uncommon in Japan, even committed suicide. According to current estimates, Monju will be down for at least two years, thus causing major financial problems to the operator, PNC. On the political level, more difficulties are expected to arise in the introduction of plutonium recycling. (orig.) [de

  6. Male infertility and its causes in human.

    Science.gov (United States)

    Miyamoto, Toshinobu; Tsujimura, Akira; Miyagawa, Yasushi; Koh, Eitetsu; Namiki, Mikio; Sengoku, Kazuo

    2012-01-01

    Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings.

  7. Allergic contact dermatitis caused by cosmetic products.

    Science.gov (United States)

    González-Muñoz, P; Conde-Salazar, L; Vañó-Galván, S

    2014-11-01

    Contact dermatitis due to cosmetic products is a common dermatologic complaint that considerably affects the patient's quality of life. Diagnosis, treatment, and preventive strategies represent a substantial cost. This condition accounts for 2% to 4% of all visits to the dermatologist, and approximately 60% of cases are allergic in origin. Most cases are caused by skin hygiene and moisturizing products, followed by cosmetic hair and nail products. Fragrances are the most common cause of allergy to cosmetics, followed by preservatives and hair dyes; however, all components, including natural ingredients, should be considered potential sensitizers. We provide relevant information on the most frequent allergens in cosmetic products, namely, fragrances, preservatives, antioxidants, excipients, surfactants, humectants, emulsifiers, natural ingredients, hair dyes, sunscreens, and nail cosmetics. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  8. Measuring the Noise Caused by Tehran Metro

    Directory of Open Access Journals (Sweden)

    Majid Abbas Pour

    1999-03-01

    Full Text Available One of the most common and important sources of noise in the residential environments are vehicles such as airplanes and subways. Trafficking of vehicles in streets and highways, psychologically, have damaging impacts on people living close to such areas. The development and expansion of the trading and industrial units is another factor that causes more and more exposure to noise.We have aimed at measuring the noises caused by vibration of subways of the Line of Karaj-Tehran-Mehrshahr and its effect on its surrounding area.To study this effect we designed a mathematical model and put the information of this subway line in the mentioned model. Then we analyzed the findings.This model demonstrated that we can control the harsh noise of the subway by reducing the speed of the train to 60Km/h in some points and increase in other parts to 130Km/h.

  9. Essential thrombocythemia: Rare cause of chorea

    Directory of Open Access Journals (Sweden)

    Eswaradass Prasanna Venkatesan

    2014-01-01

    Full Text Available Essential thrombocythemia (ET is a clonal myeloproliferative disorder (MPD, characterized predominantly by a markedly elevated platelet count without known cause. It is rare hematological disorder. In ET clinical picture is dominated by a predisposition to vascular occlusive events and hemorrhages. Headache, transient ischemic attack, stroke, visual disturbances and light headedness are some of the neurological manifestations of ET. Here, we describe a 55 year-old female who presented to us with generalized chorea. On evaluation, she was found to have thrombocytosis. After ruling out the secondary causes of thrombocytosis and other MPD we confirmed diagnosis of ET in her by bone marrow studies. Polycythemia vera (PV another MPD closely related to ET may be present with generalized chorea. There are few case reports of PV presenting as chorea in the literature, but none with ET. We report the first case of ET presenting as generalized chorea.

  10. Factitious disorder: a rare cause of haematemesis.

    Science.gov (United States)

    McFarlane, Michael; Eaden, Jayne; Burch, Nicola; Disney, Ben

    2017-10-01

    Acute upper gastrointestinal (GI) bleeding is a common condition in the UK with 50-70,000 admissions per year. In 20% of cases no cause can be found on endoscopy. Here, we present the case of a young female patient who was admitted on three occasions with large volume haematemesis and bleeding from other sites. She was extensively investigated and underwent multiple endoscopic procedures. She was eventually diagnosed with factitious disorder after concerns were raised about the inconsistent nature of her presentations. She was found to be venesecting herself from her intravenous cannula, and ingesting the blood to simulate upper GI bleeding. This is a rare cause of 'haematemesis' but perhaps not as rare as is thought.

  11. Foreign Debt: Causes and Measures Taken

    Directory of Open Access Journals (Sweden)

    Ion Botescu

    2016-01-01

    Full Text Available In an increasingly globalized world, any crisis, including the ones caused by the foreign debtdefault of a country, may have a negative impact which can be contagious both at regional and atglobal level. Taking into account all the risks to which international creditors were subjectedover time, thestock of foreign debt worldwide has experienced a significant increase in the current millennium,actually demonstrating that international lending is profitable. The causes of default, the measures taken by the concerned countries to get out of this situationand the specific examples were the elements which I have tried to capture in this paper. Last butnot least, I have performed an analysis of the evolution of the foreign debt stock and the repaymentcapacity of small and medium-income countries, respectively the most vulnerable countries interms of debt repayment.

  12. Male Infertility and Its Causes in Human

    Directory of Open Access Journals (Sweden)

    Toshinobu Miyamoto

    2012-01-01

    Full Text Available Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings.

  13. Allergic Bronchopulmonary Mycosis Caused by Cladosporidium

    Science.gov (United States)

    2017-05-23

    Mycosis Caused by Cladosporidium presented at/published to 2017 American Thoracic Society International Conference, Washington D.C., 23 May 2017 (Poster...Clinical Research Division may pay for your basic journal publishing charges (to include costs for tables and black and white photos). We cannot pay for...GHSE) (SGS O&M); SGS R&D; Tri-Service Nursing Research Program (TSNRP): Defense Medical Research & Development Program (OMRDP): NIH: Congressionally

  14. Sports causing most injuries in Hong Kong.

    OpenAIRE

    Chan, K M; Yuan, Y; Li, C K; Chien, P; Tsang, G

    1993-01-01

    A prospective survey was carried out on 2293 patients attending the Sports Injury Clinic in the Prince of Wales Hospital between May 1984 and December 1990. A Sports Injury Report Form was completed for each patient. Subjects in this study represent a group of nonprofessional and non-élite athletes in a metropolitan area. Soccer, basketball, volleyball, long-distance running and cycling in descending order were the five most common sports causing injury. Different sports produced different in...

  15. Information system conflicts: causes and types

    OpenAIRE

    Boonstra, Albert; de Vries, Jan

    2015-01-01

    Conflicts are an inherent part of organizational life and managers deal with confrontations and conflicts on an almost daily basis. Information Systems (IS) implementations are a type of change that often leads to open or hidden conflicts. Managers and others involved can only deal with such conflicts effectively if they understand the nature and causes of information system conflicts (IS conflicts). To contribute to such an understanding, this study focuses on the analysis of IS conflicts. I...

  16. First human systemic infection caused by Spiroplasma.

    Science.gov (United States)

    Aquilino, Ana; Masiá, Mar; López, Pilar; Galiana, Antonio J; Tovar, Juan; Andrés, María; Gutiérrez, Félix

    2015-02-01

    Spiroplasma species are organisms that normally colonize plants and insects. We describe the first case of human systemic infection caused by Spiroplasma bacteria in a patient with hypogammaglobulinemia undergoing treatment with biological disease-modifying antirheumatic agents. Spiroplasma turonicum was identified through molecular methods in several blood cultures. The infection was successfully treated with doxycycline plus levofloxacin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Conditional Deletion of Pten Causes Bronchiolar Hyperplasia

    OpenAIRE

    Davé, Vrushank; Wert, Susan E.; Tanner, Tiffany; Thitoff, Angela R.; Loudy, Dave E.; Whitsett, Jeffrey A.

    2007-01-01

    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (PtenΔ/Δ) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as in...

  18. Factors causing stress among Pakistani working women

    OpenAIRE

    Arif, Ahmed; Naveed, Shaheryar; Aslam, Ramsha

    2017-01-01

    Women are traditionally considered to be confined within the four walls of their houses in the developing countries. They are still unable to play an active role in the development of society. They are striving to make their identity as an integral part of the society. Being a member of conservative developing society, women are still facing many hindrances, causing stressful situation for them, which prohibits them to participate actively in the economic development. This paper attempts to e...

  19. The Prime Cause and Treatment of Cancer

    OpenAIRE

    Somayeh Zaminpira; Somayeh Zaminpira

    2017-01-01

    This meta-analysis research has gone through more than 200 studies from 1934 to 2016 to find the differences and similarities in cancer cells, mostly the cause. The most important difference between normal cells and cancer cells is how they respire. Normal cells use the sophisticated process of respiration to efficiently turn any kind of nutrient that is fat, carbohydrate or protein into high amounts of energy in the form of ATP. This process requires oxygen and breaks food down completely in...

  20. Acid rain may cause senile dementia

    Energy Technology Data Exchange (ETDEWEB)

    Pearce, F

    1985-04-25

    Aluminium, released from the soil by acid rain, may be a cause of several forms of senile dementia including Parkinson's disease and Alzheimer's disease. Many upland reservoirs, fed by acid rain, supply homes with water laced with significant amounts of aluminium. Studies in the Pacific have shown that communities living on soils that are extremely rich in bauxite, the rock containing aluminium, have a very high incidence of Alzheimer's disease.

  1. [Enterobius vermicularis causing symptoms of acute appendicitis].

    Science.gov (United States)

    Antal, András; Kocsis, Béla

    2008-08-01

    The authors present a case of enterobiasis of the appendix. Enterobius infection is an uncommon cause of acute appendicitis. Preoperative diagnosis of pinworm infestation is almost impossible unless there is a strong clinical suspicion. Parasites may produce symptoms which resemble acute appendicitis. Careful observation of the appendix stump may lead to intraoperative diagnosis of enterobiasis. A quick diagnosis and appropriate treatment may prevent future complications.

  2. Flavonoid intake and all-cause mortality.

    Science.gov (United States)

    Ivey, Kerry L; Hodgson, Jonathan M; Croft, Kevin D; Lewis, Joshua R; Prince, Richard L

    2015-05-01

    Flavonoids are bioactive compounds found in foods such as tea, chocolate, red wine, fruit, and vegetables. Higher intakes of specific flavonoids and flavonoid-rich foods have been linked to reduced mortality from specific vascular diseases and cancers. However, the importance of flavonoids in preventing all-cause mortality remains uncertain. The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition databases to assess flavonoid intake. The study population included 1063 randomly selected women aged >75 y. All-cause, cancer, and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System. Two estimates of flavonoid intake (total flavonoidUSDA and total flavonoidPE) were determined by using food composition data from the USDA and the Phenol-Explorer (PE) databases, respectively. During the 5-y follow-up period, 129 (12%) deaths were documented. Participants with high total flavonoid intake were at lower risk [multivariate-adjusted HR (95% CI)] of 5-y all-cause mortality than those with low total flavonoid consumption [total flavonoidUSDA: 0.37 (0.22, 0.58); total flavonoidPE: 0.36 (0.22, 0.60)]. Similar beneficial relations were observed for both cardiovascular disease mortality [total flavonoidUSDA: 0.34 (0.17, 0.69); flavonoidPE: 0.32 (0.16, 0.61)] and cancer mortality [total flavonoidUSDA: 0.25 (0.10, 0.62); flavonoidPE: 0.26 (0.11, 0.62)]. Using the most comprehensive flavonoid databases, we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women. The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease. © 2015 American Society for Nutrition.

  3. Causes And Effects Of Fast Food

    Directory of Open Access Journals (Sweden)

    Eman Al-Saad

    2015-08-01

    Full Text Available Fast food affects our life in many aspects. In fact There are many reasons that have been shown why people continuing eating fast food while they knew about its negative effects on their health and family because of eating fast food. The commercial advertisements play a major role in consuming fast food. In this research I will focus on causes and effects of eating fast food.

  4. Chernobylsk accident (Causes and Consequences)- Part 2

    International Nuclear Information System (INIS)

    Esteves, D.

    1986-09-01

    The causes and consequences of the nuclear accident at Chernobylsk-4 reactor are shortly described. The informations were provided by Russian during the specialist meeting, carried out at seat of IAEA. The Russian nuclear panorama; the site, nuclear power plant characteristics and sequence of events; the immediate measurements after accident; monitoring/radioactive releases; environmental contamination and ecological consequences; measurements of emergency; recommendations to increase the nuclear safety; and recommendations of work groups, are presented. (M.C.K.) [pt

  5. Spine fractures caused by horse riding

    OpenAIRE

    Siebenga, Jan; Segers, Michiel J. M.; Elzinga, Matthijs J.; Bakker, Fred C.; Haarman, Henk J. T. M.; Patka, Peter

    2006-01-01

    Study Design: Retrospective study and review of literature. Objectives: Study of demographic data concerning spinal fractures caused by horse riding, classification of fractures according to the AO and Load Sharing classifications, evaluation of mid-term radiological results and long-term functional results. Methods: A review of medical reports and radiological examinations of patients presented to our hospital with horse riding-related spine fractures over a 13-year period; long-term functio...

  6. The Causes of Boat Hull Blisters

    Science.gov (United States)

    1987-05-01

    blistering. The report is divided into the following sections: Introduction; How Blisters Form; the Hull Material; Manufacturing Processes; Water Diffusion...Term Effects of Water Up-Takeo " The much more detailed and highly technical report of thia-Vsrk is entitled "The Causes of Blistering in Boat Building...Chemical Engineering, ably assisted by several graduate students, and was completed in the fall of 1986. The report itself, d List-ribution/_ Availabilit

  7. An Unexpected Cause of Severe Hypokalemia

    Directory of Open Access Journals (Sweden)

    Fernando Caravaca-Fontan

    2015-01-01

    Full Text Available We describe an unusual case of severe hypokalemia with electrocardiographic changes, due to licorice consumption, in a 15-year-old female student with no previous medical history. Prompt replacement of potassium and cessation of licorice ingestion resulted in a favourable outcome. We also discuss the pathophysiology and diagnosis, emphasizing the importance of a detailed anamnesis to rule out an often forgotten cause of hypokalemia as the licorice poisoning.

  8. Hyperthyroidism as a cause of persistent vomiting.

    Science.gov (United States)

    Hoogendoorn, E H; Cools, B M

    2004-09-01

    A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her free thyroxine level was still high. Hyperthyroidism is an uncommon, but previously reported cause of persistent vomiting.

  9. Hyperthyroidism as a cause of persistent vomiting.

    OpenAIRE

    Hoogendoorn, E.H.; Cools, B.M.

    2004-01-01

    A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her free thyroxine level was still high. Hyperthyroidism is an uncommon, but previously reported cause of persistent vomiting.

  10. Phytodermatitis caused by Ceratocephalus falcatus (Ranunculacea).

    Science.gov (United States)

    Karaca, Semsettin; Kulac, Mustafa; Kucuker, Hudaverdi

    2005-01-01

    Ceratocephalus falcatus is a member of Ranunculacea family that forms part of the flora of the Sinanpasa and Dinar regions of Afyon city in Turkey. Ceratocephalus falcatus has laxative properties and has been used for treating hemorrhoids, rheumatismal diseases and wounds. Here, a case of phytodermatitis caused by this remedy used for relieving knee pain is presented. This plant should be kept in mind when a case of phytodermatitis with vesicles or bullae presents at clinics.

  11. Corruption in India: Causes and Remedial Measures

    OpenAIRE

    Ghulam Nabi Naz

    2017-01-01

    After independence, the popular belief that Gandhian will not indulge in corruption got a setback, post-independence setup paved the way for heavy corruption. The menace which would have dealt with strong legal provisions has become a way of life of Indian society. Corruption is recognized as the single biggest problem facing the country today. It undermines democracy and rule of law, violates human rights, distorts market and corrodes the moral fibre of people. The paper discusses the causes...

  12. Common cause failures - a dilemma in perspective

    International Nuclear Information System (INIS)

    Smith, A.M.; Watson, I.A.

    1980-01-01

    This paper identifies the broad spectrum of common cause failure (CCF) definitions used by various authors. These definitions, as applied to real aircraft and nuclear reactor failure events, lead to a divergence of interpretation and a resultant confusion that obscures meaningful progress in CCF analysis. A new definition is proposed, explained, and tested against the examples. Technical as well as administrative practices are cited as ways to control or eliminate the product defects that lead to CCF. (author)

  13. Causes And Effects Of Fast Food

    OpenAIRE

    Eman Al-Saad

    2015-01-01

    Fast food affects our life in many aspects. In fact There are many reasons that have been shown why people continuing eating fast food while they knew about its negative effects on their health and family because of eating fast food. The commercial advertisements play a major role in consuming fast food. In this research I will focus on causes and effects of eating fast food.

  14. Causes of death among cancer patients.

    Science.gov (United States)

    Zaorsky, N G; Churilla, T M; Egleston, B L; Fisher, S G; Ridge, J A; Horwitz, E M; Meyer, J E

    2017-02-01

    The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. The greatest relative decrease in index-cancer death (generally from > 60% to deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among 1,000 for lymphomas, P death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Politrauma as a cause of raquimedular injury

    International Nuclear Information System (INIS)

    Esparza, Erick; Pinos, Angel; Mayorga Patricio; Torres, Neira

    2005-01-01

    The raquimedular injury constitutes an important chapter inside the Neurotraumatology, due to its frequent association in the politrauma it forms part of and to the serious consequences that it causes. The collection of data for this is taken from the patient's medical histories: age, causes, associated wounds, the surgical procedure carried out, and the results obtained are taken into consideration. The backbone is divided in various segments with the purpose of classifying the wound as well as to appreciate the treatment performed in each case. The Frankel scale that's reports the neurological commitment in this type of wound is utilized in the initial appraisal and in the monitoring of the patient. Of the total of cases (n=55), the most frequent age of presentation was in the rank from 30 to 60 years old, with 35 cases (63%) free falls and traffic accidents are registered as the most frequent causes with 36 cases (65%), and 11 cases (20%) respectively, the raquideo level most affected is found in the lower cervical column with 20 cases (36.3%) and the hinge toracolumbar with 22 cases (40%). We found 17 cases (30.9) in the degree A of the Frankel scale, and of these, 12 cases (21%) corresponds to cervical injury. Imaging studies, computer tomography CT and magnetic nuclear resonance MRI were used. (The author)

  16. Periportal halo on CT: spectrum of causes

    International Nuclear Information System (INIS)

    Volpacchio, Mariano; Baltazar, Alberto D.; Santamarina, Mario G.; Casetta, Liliana; Cione, Rodrigo; Sanchez, Gimena; Vallejos, Nancy

    2003-01-01

    Purpose: A periportal hypodense halo is a relatively frequent CT finding. This halo is attributed to the presence of edema or ecstatic lymphatic channels. In our series we illustrate the CT appearance of periportal edema and analyze its causes. Material and Methods: In a retrospective study we analyze a 78 patients series who showed periportal edema on e.v. contrast-enhanced abdominal CTs. The different causes of hepatic periportal edema (demonstrated on CT exams), were established by clinical, laboratory, surgical and anatomo-pathologic correlation. Results: In this study, 49 cases were diagnosed as having congestive heart failure (62,8%), 14 patients had viral hepatitis (18%), 5 patients had recently undergone orthotopic liver transplantation (6.4%), 3 patients had a diagnosis of infectious cholangitis (3.8%), 3 patients had abdominal trauma (3.8%), 2 patients had neoplastic disease (2.6%) and 2 patients had toxic hepatitis (2.6%). Conclusion: Periportal edema is a frequent and nonspecific finding associated with systemic diseases as well as liver specific entities. The integration of CT findings and clinical picture of periportal edema leads to a confident diagnosis of the main cause in most patients. (author)

  17. Primary lung abscess caused by Staphylococcus lugdunensis.

    Science.gov (United States)

    Chou, Deng-Wei; Lee, Chao-Tai

    2017-11-01

    Staphylococcus lugdunensis, a strain of coagulase-negative staphylococci, is part of the normal flora of human skin but can cause multiple infections at various sites. This microorganism has emerged as a major human pathogen. However, no study has reported primary lung abscess caused by S. lugdunensis. A 54-year-old alcoholic man without relevant past medical history was admitted because of primary lung abscesses. Empirical amoxicillin/clavulanate therapy was initially administered; however, the patient had persistent pleuritic chest pain and fever. He subsequently underwent resection of the lung abscess and removal of exudative pleural effusion on the fourth hospital day. Histopathologic examination confirmed the diagnosis of lung abscess, and colonies of gram-positive bacteria were identified. The culture specimen from the abscess was positive for S. lugdunensis, which was susceptible to amoxicillin/clavulanate, cefazolin, ciprofloxacin, clindamycin, erythromycin, oxacillin, teicoplanin, tetracycline, and vancomycin. Following resection and 3 weeks of amoxicillin/clavulanate therapy, the patient eventually recovered well without relapse. This case report is the first to describe S. lugdunensis as a cause of primary lung abscess; this microorganism should be considered a potential monomicrobial pathogen in primary lung abscess. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Genetic Causes of Recurrent Pregnancy Loss.

    Science.gov (United States)

    Page, Jessica M; Silver, Robert M

    2016-09-01

    Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted.

  19. Physical Analysis of the Biomolecules Causing Periodontitis

    Science.gov (United States)

    Shin, Jehun; Lee, Seong Hyeon; Kim, Chai Rin

    Periodontitis caused by microorganisms that adhere to and grow on the tooth's surfaces, is an inflammatory diseases causing gum infection. The disease damages the soft tissues that surround and support the teeth and destroys the bone that supports teeth and finally causes tooth loss. An increased risk of stroke and heart attack problems are related to the periodontitis as well. Most bacteria or pathogens attach to gum surface where they form a biofilm. Bacterial cells in biofilms are well protected against antibiotics. The mechanisms of action are still unknown, and it is difficult to control pathogens with antibiotics in biofilm infections and thus the study on the antibiotics is needed. In this research, a number of natural water soluble, small-sized antibiotics molecules and their derivatives are studied. Molecular editing programs such as Gamess, Chemcraft and Avogadro, with an auto-optimization feature that determines the theoretical values of the structure's atomic properties are used to build virtually any molecule with the optimized geometry according to various force field options. The UFF (Universal Force Field) is used for optimizing most molecules.

  20. Coronary Arteriovenous Fistula Causing Hydrops Fetalis

    Directory of Open Access Journals (Sweden)

    Nilüfer Çetiner

    2014-01-01

    Full Text Available Fetal heart failure and hydrops fetalis may occur due to systemic arteriovenous fistula because of increased cardiac output. Arteriovenous fistula of the central nervous system, liver, bone or vascular tumors such as sacrococcygeal teratoma were previously reported to be causes of intrauterine heart failure. However, coronary arteriovenous fistula was not reported as a cause of fetal heart failure previously. It is a rare pathology comprising 0.2–0.4% of all congenital heart diseases even during postnatal life. Some may remain asymptomatic for many years and diagnosed by auscultation of a continuous murmur during a routine examination, while a larger fistulous coronary artery opening to a low pressure cardiac chamber may cause ischemia of the affected myocardial region due to steal phenomenon and may present with cardiomyopathy or congestive heart failure during childhood. We herein report a neonate with coronary arteriovenous fistula between the left main coronary artery and the right ventricular apex, who presented with hydrops fetalis during the third trimester of pregnancy.

  1. Stuck pipe: Causes, detection and prevention

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, L; Jomnes, T [Schlumberger Cambridge Research (UK); Belaskie, J; Orban, J; Sheppard, M [Anadrill, Sugarland, TX (USA); Houwen, O; Jardine, S; McCann, D [Sedco Forex, Montrouge (France)

    1991-10-01

    Stuck pipe remains a major headache that demands and is getting industry-wide attention. It costs the oil industry between $200 and $500 million each year, occurs in 15% of wells, and in many cases is preventable. Several operators are making determined efforts to codify the warning signs and to improve communication for all on-site drilling and service company personnel, for which the data gathering ability of a computerized information system is a necessity. Meanwhile, better rig sensors and information systems are providing rig-floor smart'' alarms to help the driller recognize trouble before it gets out of hand. The causes of stuck pipe can be divided broadly among differential sticking, formation-related sticking and mechanical sticking. One of the results of the industry's current attention is a better understanding of the events leading up to stuck pipe and their interpretationn in terms of the causes of sticking. Knowing the causes is essential for taking remedial action. 15 figs., 19 refs.

  2. Cancer Cachexia: Cause, Diagnosis, and Treatment.

    Science.gov (United States)

    Mattox, Todd W

    2017-10-01

    Patients with cancer frequently experience unintended weight loss due to gastrointestinal (GI) dysfunction caused by the malignancy or treatment of the malignancy. However, others may present with weight loss related to other symptoms not clearly associated with identifiable GI dysfunction such as anorexia and early satiety. Cancer cachexia (CC) is a multifactorial syndrome that is generally characterized by ongoing loss of skeletal muscle mass with or without fat loss, often accompanied by anorexia, weakness, and fatigue. CC is associated with poor tolerance of antitumor treatments, reduced quality of life (QOL), and negative impact on survival. Symptoms associated with CC are thought to be caused in part by tumor-induced changes in host metabolism that result in systemic inflammation and abnormal neurohormonal responses. Unfortunately, there is no single standard treatment for CC. Nutrition consequences of oncologic treatments should be identified early with nutrition screening and assessment. Pharmacologic agents directed at improving appetite and countering metabolic abnormalities that cause inefficient nutrient utilization are currently the foundation for treating CC. Multiple agents have been investigated for their effects on weight, muscle wasting, and QOL. However, few are commercially available for use. Considerations for choosing the most appropriate treatment include effect on appetite, weight, QOL, risk of adverse effects, and cost and availability of the agent.

  3. [Amblyopia. Epidemiology, causes and risk factors].

    Science.gov (United States)

    Elflein, H M

    2016-04-01

    Amblyopia is the main cause for mostly monocular, impaired vision in childhood. Treatment and prevention of amblyopia is only effective during childhood. Ophthalmological screening of children does not yet exist in Germany. The prevalence of amblyopia in Germany is 5.6%, which is higher than in reports from studies in Australia; however, the prevalence of amblyopia is not comparable in these studies due to different definitions of amblyopia and the inclusion/exclusion criteria of the study cohorts. At present it is unknown at what age ophthalmological screening should be carried out to prevent amblyopia and the appropriate frequency of screening examinations. Amblyopia is a disorder of the visual cortex that is due to suppression and deprivation of one eye leading to unilateral visual impairment. Approximately 50% of cases of amblyopia are caused by anisometropia, 25% by strabismus and in every sixth person by a combination of both. Other causes, such as unilateral congenital cataracts are relatively rare. A variety of factors, such as ocular pathologies, premature birth, familial disposition and general diseases are associated with an increased risk for amblyopia.

  4. Evaluation of common organisms causing vaginal discharge.

    Science.gov (United States)

    Khan, Shazia A; Amir, Fauzia; Altaf, Shagufta; Tanveer, Raazia

    2009-01-01

    Vaginal discharge is very common problem among females. Alteration in balance of normal vaginal organisms can cause the overgrowth of the bacteria that creates vaginal discharge. It is common among sexually active women yet there still remain gaps in our knowledge of this infectious disorder. To evaluate the frequency of bacterial vaginosis (BV), vaginal candidiasis (VC), vaginal trichomoniasis and Group B streptococcus in women complaining of vaginal discharge in our setup. A total of 100 women of reproductive age group with the complaint of vaginal discharge were included in the study. After filling proforma patients were examined by speculum examination and two high vaginal swabs (HVS) were collected aseptically from each patient. One swab was used for making wet mount for clue cells, pus cells and for motility of Trichomonas vaginalis. The other swab was used to check pH and Amine test. The growth was confirmed by Gram staining in each case. Gardnerrella vaginalis were isolated in 28%, Group B streptococcus in 5% and T. vaginolis in 4% of women. Gardnerella vaginalis causing BV is the most common cause of vaginal discharge in otherwise healthy women of reproductive age group in our setup.

  5. Amyotrophic lateral sclerosis: one or multiple causes?

    Science.gov (United States)

    Bastos, Aline Furtado; Orsini, Marco; Machado, Dionis; Mello, Mariana Pimentel; Nader, Sergio; Silva, Júlio Guilherme; da Silva Catharino, Antonio M.; de Freitas, Marcos R.G.; Pereira, Alessandra; Pessoa, Luciane Lacerda; Sztajnbok, Flavio R.; Leite, Marco Araújo; Nascimento, Osvaldo J.M.; Bastos, Victor Hugo

    2011-01-01

    The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients. PMID:21785676

  6. Atopy and cause-specific mortality

    DEFF Research Database (Denmark)

    Skaaby, T; Husemoen, L L N; Thuesen, Betina Heinsbæk

    2014-01-01

    BACKGROUND: Atopy is the familial or personal propensity to develop immunoglobulin E (IgE) antibodies against common environmental allergens and is associated with high risk of allergic disease. It has been proposed that atopy may have effects on risk of cardiovascular disease and cancer...... followed by linkage to the Danish Registry of Causes of Death to obtain information on mortality status and cause of death (median follow-up time 11.3 years). The relative mortality risk was estimated by Cox regression and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: A total...... of 1776 person died during follow-up. The mortality risk for atopics vs. non-atopics was: for all-cause mortality (HR = 1.03, 95% CI: 0.90, 1.17); neoplasms (HR = 0.86, 95% CI: 0.69, 1.06); endocrine, nutritional and metabolic disorders (HR = 1.48, 95% CI: 0.71, 3.08); mental and behavioural disorders (HR...

  7. Stuck pipe: Causes, detection and prevention

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, L.; Jomnes, T. (Schlumberger Cambridge Research (UK)); Belaskie, J.; Orban, J.; Sheppard, M (Anadrill, Sugarland, TX (USA)); Houwen, O.; Jardine, S.; McCann, D. (Sedco Forex, Montrouge (France))

    1991-10-01

    Stuck pipe remains a major headache that demands and is getting industry-wide attention. It costs the oil industry between $200 and $500 million each year, occurs in 15% of wells, and in many cases is preventable. Several operators are making determined efforts to codify the warning signs and to improve communication for all on-site drilling and service company personnel, for which the data gathering ability of a computerized information system is a necessity. Meanwhile, better rig sensors and information systems are providing rig-floor smart'' alarms to help the driller recognize trouble before it gets out of hand. The causes of stuck pipe can be divided broadly among differential sticking, formation-related sticking and mechanical sticking. One of the results of the industry's current attention is a better understanding of the events leading up to stuck pipe and their interpretationn in terms of the causes of sticking. Knowing the causes is essential for taking remedial action. 15 figs., 19 refs.

  8. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  9. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  10. The Root Cause of the Overheating Problem

    Science.gov (United States)

    Liou, Meng-Sing

    2017-01-01

    Previously we identified the receding flow, where two fluid streams recede from each other, as an open numerical problem, because all well-known numerical fluxes give an anomalous temperature rise, thus called the overheating problem. This phenomenon, although presented in several textbooks, and many previous publications, has scarcely been satisfactorily addressed and the root cause of the overheating problem not well understood. We found that this temperature rise was solely connected to entropy rise and proposed to use the method of characteristics to eradicate the problem. However, the root cause of the entropy production was still unclear. In the present study, we identify the cause of this problem: the entropy rise is rooted in the pressure flux in a finite volume formulation and is implanted at the first time step. It is found theoretically inevitable for all existing numerical flux schemes used in the finite volume setting, as confirmed by numerical tests. This difficulty cannot be eliminated by manipulating time step, grid size, spatial accuracy, etc, although the rate of overheating depends on the flux scheme used. Finally, we incorporate the entropy transport equation, in place of the energy equation, to ensure preservation of entropy, thus correcting this temperature anomaly. Its applicability is demonstrated for some relevant 1D and 2D problems. Thus, the present study validates that the entropy generated ab initio is the genesis of the overheating problem.

  11. Alcohol skin preparation causes surgical fires.

    Science.gov (United States)

    Rocos, B; Donaldson, L J

    2012-03-01

    Surgical fires are a rare but serious preventable safety risk in modern hospitals. Data from the US show that up to 650 surgical fires occur each year, with up to 5% causing death or serious harm. This study used the National Reporting and Learning Service (NRLS) database at the National Patient Safety Agency to explore whether spirit-based surgical skin preparation fluid contributes to the cause of surgical fires. The NRLS database was interrogated for all incidents of surgical fires reported between 1 March 2004 and 1 March 2011. Each report was scrutinised manually to discover the cause of the fire. Thirteen surgical fires were reported during the study period. Of these, 11 were found to be directly related to spirit-based surgical skin preparation or preparation soaked swabs and drapes. Despite manufacturer's instructions and warnings, surgical fires continue to occur. Guidance published in the UK and US states that spirit-based skin preparation solutions should continue to be used but sets out some precautions. It may be that fire risk should be included in pre-surgical World Health Organization checklists or in the surgical training curriculum. Surgical staff should be aware of the risk that spirit-based skin preparation fluids pose and should take action to minimise the chance of fire occurring.

  12. Causes of death among females-investigating beyond maternal causes: a community-based longitudinal study.

    Science.gov (United States)

    Melaku, Yohannes Adama; Weldearegawi, Berhe; Aregay, Alemseged; Tesfay, Fisaha Haile; Abreha, Loko; Abera, Semaw Ferede; Bezabih, Afework Mulugeta

    2014-09-10

    In developing countries, investigating mortality levels and causes of death among all age female population despite the childhood and maternal related deaths is important to design appropriate and tailored interventions and to improve survival of female residents. Under Kilite-Awlealo Health and Demographic Surveillance System, we investigated mortality rates and causes of death in a cohort of female population from 1st of January 2010 to 31st of December 2012. At the baseline, 33,688 females were involved for the prospective follow-up study. Households under the study were updated every six months by fulltime surveillance data collectors to identify vital events, including deaths. Verbal Autopsy (VA) data were collected by separate trained data collectors for all identified deaths in the surveillance site. Trained physicians assigned underlining causes of death using the 10th edition of International Classification of Diseases (ICD). We assessed overall, age- and cause-specific mortality rates per 1000 person-years. Causes of death among all deceased females and by age groups were ranked based on cause specific mortality rates. Analysis was performed using Stata Version 11.1. During the follow-up period, 105,793.9 person-years of observation were generated, and 398 female deaths were recorded. This gave an overall mortality rate of 3.76 (95% confidence interval (CI): 3.41, 4.15) per 1,000 person-years. The top three broad causes of death were infectious and parasitic diseases (1.40 deaths per 1000 person-years), non-communicable diseases (0.98 deaths per 1000 person-years) and external causes (0.36 per 1000 person-years). Most deaths among reproductive age female were caused by Human Deficiency Virus/Acquired Immune Deficiency Virus (HIV/AIDS) and tuberculosis (0.14 per 1000 person-years for each cause). Pregnancy and childbirth related causes were responsible for few deaths among women of reproductive age--3 out of 73 deaths (4.1%) or 5.34 deaths per 1,000 person

  13. Man-caused seismicity of Kuzbass

    Science.gov (United States)

    Emanov, Alexandr; Emanov, Alexey; Leskova, Ekaterina; Fateyev, Alexandr

    2010-05-01

    A natural seismicity of Kuznetsk Basin is confined in the main to mountain frame of Kuznetsk hollow. In this paper materials of experimental work with local station networks within sediment basin are presented. Two types of seismicity display within Kuznetsk hollow have been understood: first, man-caused seismic processes, confined to mine working and concentrated on depths up to one and a half of km; secondly, seismic activations on depths of 2-56 km, not coordinated in plan with coal mines. Every of studied seismic activations consists of large quantity of earthquakes of small powers (Ms=1-3). From one to first tens of earthquakes were recorded in a day. The earthquakes near mine working shift in space along with mine working, and seismic process become stronger at the instant a coal-plough machine is operated, and slacken at the instant the preventive works are executed. The seismic processes near three lavas in Kuznetsk Basin have been studied in detail. Uplift is the most typical focal mechanism. Activated zone near mine working reach in diameter 1-1,5 km. Seismic activations not linked with mine working testify that the subsoil of Kuznetsk hollow remain in stress state in whole. The most probable causes of man-caused action on hollow are processes, coupled with change of physical state of rocks at loss of methane from large volume or change by mine working of rock watering in large volume. In this case condensed rocks, lost gas and water, can press out upwards, realizing the reverse fault mechanism of earthquakes. A combination of stress state of hollow with man-caused action at deep mining may account for incipient activations in Kuznetsk Basin. Today earthquakes happen mainly under mine workings, though damages of workings themselves do not happen, but intensive shaking on surface calls for intent study of so dangerous phenomena. In 2009 replicates of the experiment on research of seismic activations in area of before investigated lavas have been conducted

  14. Causes of visual loss in uveitis

    Directory of Open Access Journals (Sweden)

    Stanković Zora

    2009-01-01

    Full Text Available Background/Aim. Epidemiological studies of blindness in a working age population require a precise definition of the true connection of uveitis and visual damage. Since most patients with more severe types of uveitis are hospitalized in tertiary referral uveitis service, our aim was to determine whether age, sex and age of onset of uveitis, as well as duration of visual loss and its causes influence the degree of visual damage in patients with different types of uveitis. Methods. The data were collected from medical records of 237 patients at the Department for Uveitis of the Institute for Eye Diseases in Belgrade over a three-year period (March 2005 to March 2008. Results. Visual acuity reduction (≤ 0.3 was found in 161/237 (67.9% patients, 85 of whom had visual acuity of ≤ 0.1 later. Working age patients (up to 60 years of age most often suffered from uveitis (173/237; 73%. The highest number of patients with visual loss was in the group suffering from panuveitis (77/94; 81.91%. The age of onset of uveitis and sex have no statistically significant influence on visual loss. The most common causes of visual loss (34/161; 21.1% were cystoid macular oedema (CMO (43/161; 26.7%, cataract (28/161; 17.39% and combination of CMO and cataract. Conclusion. The risk factors for severe visual loss (≤ 0.1 are panuveitis, bilateral inflammation, prolonged visual reduction and a significant number of relapses. The main causes of visual loss in 65.2% of our patients were CMO and cataract.

  15. [Managing and identifying the causes of IUGR].

    Science.gov (United States)

    Salomon, L J; Malan, V

    2013-12-01

    The management and identification of the causes for a small for gestational age (SGA) and/or an intrauterine growth restriction (IUGR) fetus is a common but complex problem in Obstetrics. The Medline, Embase and the Cochrane Library databases were examined over the last 15 years, with no language restrictions, using a combination of the words PAG (SGA), IUGR (IUGR), fetal weight (Fetal weight), sonography (ultrasound), management, cause (etiology), examinations (examinations). Some references not selected by this strategy, but associated with these publications or suggested by members of the working group were also added. The relevant articles were used to establish the text of recommendation following discussion between experts of the working group. Once the diagnosis of SGA is raised (whether on clinical, echocardiographic or Doppler), a management strategy to look for potential causes must be proposed and discussed with parents (Expert reviews). The extent of additional explorations varies depending on the exact presentation of the case (term at diagnosis, severity of anomalies). Additional explorations only make sense if they are likely to change the management of the current pregnancy and particularly to reduce perinatal morbidity and mortality. Explorations have two main objectives: (i) assess fetal vitality and possibilities for continuing the pregnancy in terms of safety for the mother and the foetus; (ii) establish the origin of SGA. The latter is detailed in this chapter recommendation. The earlier and the more severe the biometric anomalies, the more comprehensive the investigations. Maternal symptoms or fetal Doppler anomalies also require urgent management. Explorations to establish the origin of SGA and/or IUGR must follow a rigorous and systematic approach. In all cases, the practitioner will provide clear information to parents and collect information including detailed clinical and ultrasound examinations. Additional tests and in particular fetal

  16. The nuclear accidents: Causes and consequences

    International Nuclear Information System (INIS)

    Rochd, M.

    1988-01-01

    The author discussed and compared the real causes of T.M.I. and Chernobyl accidents and cited their consequences. To better understand how these accidents occurred, a brief description of PWR type (reactor type of T.M.I.) and of RBMK type (reactor type of Chernobyl) has been presented. The author has also set out briefly the safety analysis objectives and the three barriers established to protect the public against the radiological consequences. To distinguish failures that cause severe accidents and to analyze them in details, it is necessary to classify the accidents. There are many ways to do it according to their initiator event, or to their frequency, or to their degree of gravity. The safety criteria adopted by nuclear industry have been explained. These criteria specify the limits of certain physical parameters that should not be exceeded in case of incidents or accidents. To compare the real causes of T.M.I. and Chernobyl accidents, the events that led to both have been presented. As observed the main common contributing factors in both cases are that the operators did not pay attention to warnings and signals that were available to them and that they were not trained to handle these accident sequences. The essential conclusions derived from these severe accidents are: -The improvement of operators competence contribute to reduce the accident risks; -The rapid and correct diagnosis of real conditions at each point of the accidents permits an appropriate behavior that would bring the plant to a stable state; -Competent technical teams have to intervene and to assist the operators in case of emergency; -Emergency plans and an international collaboration are necessary to limit the accident risks. 11 figs. (author)

  17. A morbillivirus causing mass mortality in seals.

    Science.gov (United States)

    Osterhaus, A

    1989-12-01

    During an outbreak of a serious apparently infectious disease among harbour seals (Phoca vitulina), which started in the Kattegat area in April 1988 and rapidly spread to the North sea, the Wadden sea and the Baltic sea, greater than 17,000 animals died within a period of eight months. In August 1988 it was realized that the clinical symptoms and pathological lesions were similar to those found in canine distemper: apart from general depression and fever, the animals suffered from severe respiratory, gastrointestinal and central nervous disease and a variety of viral, bacterial and parasitic infections were frequently encountered, suggesting a severe malfunctioning of the immune system. At different expert meetings, held in several of the countries involved, possible explanations for the deaths were not only attributed to an infectious agent, but also to effects of overpopulation and environmental pollution. Seroepizootiological studies and the failure of vaccination experiments suggested that a herpesvirus and a picornavirus, which had been isolated from dead seals at the beginning of the outbreak, were opportunistic infections occurring in animals suffering from another infection rather than being the primary cause of the outbreaks. Serological studies were then extended to other viruses of carnivores, known to cause similar symptoms. Screening of a large panel of seal sera from the Netherlands, Denmark, FRG, Sweden and the UK, collected before and during the outbreak, in a virus neutralization test for the presence of canine distemper virus (CDV) neutralizing antibodies, indicated that CDV or a closely related morbillivirus was the primary cause of the disease outbreak.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. PPIB mutations cause severe osteogenesis imperfecta.

    Science.gov (United States)

    van Dijk, Fleur S; Nesbitt, Isabel M; Zwikstra, Eline H; Nikkels, Peter G J; Piersma, Sander R; Fratantoni, Silvina A; Jimenez, Connie R; Huizer, Margriet; Morsman, Alice C; Cobben, Jan M; van Roij, Mirjam H H; Elting, Mariet W; Verbeke, Jonathan I M L; Wijnaendts, Liliane C D; Shaw, Nick J; Högler, Wolfgang; McKeown, Carole; Sistermans, Erik A; Dalton, Ann; Meijers-Heijboer, Hanne; Pals, Gerard

    2009-10-01

    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I.

  19. BUSINESS PROCESS REENGINEERING: CONCEPTS CAUSES AND EFFECT

    Directory of Open Access Journals (Sweden)

    Bernardo Nugroho Yahya

    2002-01-01

    Full Text Available Some people made a wrong concept about Business Process Reengineering (BPR. Some were misunderstanding about the BPR term. In other way, so many researches were introduced to describe a better definition about BPR. The thinking about concepts, causes, and effect of BPR will make a new perception about the term of BPR itself as a better methodology instead of the other Quality Management Methodology such as Total Quality Management (TQM, Just In Time (JIT, etc. This paper will mention the context of BPR in some of case study's journal.

  20. [Hemiparesis and facial palsy caused by methotrexate].

    Science.gov (United States)

    Rueda Arenas, E; García Corzo, J; Franco Ospina, L

    2013-12-01

    Methotrexate used in the treatment of acute lymphocytic leukemia, can cause neurotoxicity, including a rare presentation with hemiparesis. We describe two teenagers, who during the implementation of the M phase of the protocol, suffered hemiparesis, facial paresis and dysarthria which quickly reversed. Leukemia involvement of the central nervous system and stroke, were ruled out. We briefly review the pathophysiology of methotrexate neurotoxicity, the characteristics of the focal paresis presentation and magnetic resonance image findings. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  1. Granulocytic sarcoma: a rare cause of sciatica.

    Science.gov (United States)

    Valsamis, Epaminondas Markos; Glover, Thomas Edward

    2017-02-15

    We describe a case report of a man aged 56 years with a 4-month history of right-sided sciatica-type pain with subclinical disc prolapse evident on MRI. Worsening pain together with the appearance of a tender mass in his right buttock prompted further imaging, which demonstrated an infiltrative mass engulfing the lumbosacral plexus. This was later shown to be a granulocytic sarcoma on biopsy. Intervertebral disc herniation can be an incidental finding and is not always the cause of sciatica. 2017 BMJ Publishing Group Ltd.

  2. Nuclear education and training: cause for concern?

    International Nuclear Information System (INIS)

    2000-01-01

    Mankind now enjoys many benefits from nuclear-related technologies. There is, however, growing concern in many OECD countries that nuclear education and training is decreasing, perhaps to problematic levels. This booklet, a summary of the full report, conveys the results of a pioneering survey on nuclear education and training in almost 200 organisations in 16 countries. The current situation is presented and causes for concern are examined. Recommendations are made as to the actions governments, academia and industry must take in order to assure that crucial present requirements are met and future options are not precluded. (authors)

  3. Respiratory Depression Caused by Heroin Use

    Directory of Open Access Journals (Sweden)

    Kadir Hakan Cansiz

    2012-04-01

    Full Text Available Summary Heroin is a semisynthetic narcotic analgesic and heroin abuse is common due to its pleasure-inducing effect. For the last 30 years heroin abuse has become an important worldwide public health problem. Heroin can be administered in many different ways as preferred. Heroin affects many systems including respiratory system, cardiovascular system and particulary the central nervous system. Overdose use of heroin intravenously can be fatal due to respiratory depression. In this letter, we wanted to engage attention to respiratory depression caused by heroin abuse and potential benefits of using naloxone. [TAF Prev Med Bull 2012; 11(2.000: 248-250

  4. Radiation injury caused by internal contamination

    International Nuclear Information System (INIS)

    Petyrek, P.

    1988-01-01

    Basic data are given of radiation injury of the respiratory organs, digestive tract, hematogenous tissues and the thyroid due to internal contamination. Attention is drawn to the complexity of the problem and to the effect of the various factors affecting the picture and course of the radiation damage. The treatment is based on the assumption that fundamental is the damage of the stem cells of the critical organs. Discussed are also the basic clinical pictures that can occur due to internal contamination with activities causing radiation injury. (B.S.). 27 refs

  5. An Infant with Splenohepatomegaly: A Rare Cause

    Directory of Open Access Journals (Sweden)

    Kathiravan Kalyanasundaram

    2014-01-01

    Full Text Available Osteopetrosis is a rare congenital disorder of bone resorption, caused by failure of osteoclasts to reabsorb immature bone. Malignant infantile osteopetrosis presents in early life with generalized osteosclerosis and decreased bone marrow spaces, resulting in anemia, splenohepatomegaly due to extramedullary hematopoiesis, cranial nerve compression, and growth failure. It is a fatal condition with death occurring within the first year of life. Bone marrow transplant remains the only curative treatment. We present a report of an infant with splenohepatomegaly, who was diagnosed with malignant infantile osteopetrosis.

  6. CAUSE AND EFFECT IN PROMOTING A PROJECT

    Directory of Open Access Journals (Sweden)

    SEVERIAN-VLĂDUȚ IACOB

    2013-12-01

    Full Text Available For a project to be considered successful it is necessary, besides a proper coordination, to be also done a good and wide promotion. In view of communication, promotion and maintenance ensures the organization's image. Disturbances occurring in any type of project, as a result of poor promotion, affect the image of the team and highlight the weaknesses in its management. Therefore, the promotion should be permanently monitored and evaluated. Cause-effect analysis is one of the ways we can identify some of nonconformities of the promotion process within a project.

  7. Thermophysical lesions caused by HZE particles

    International Nuclear Information System (INIS)

    Tobias, C.A.; Malachowski, M.; Nelson, A.; Philpott, D.E.

    1980-01-01

    This paper deals with a type of damage caused by heavy particles that may occur in subcellular structures. These lesions are called thermophysical radiation injury and are similar to damage produced in solids by HZE particles. This chapter summarizes some of the experimental evidence for the presence of these lesions in certain mammalian tissues including the retina, brain, cornea, lens of mice and seeds of corn. Of all tissues examined, only the cornea exhibited a type of lesion which would fulfill the criteria of thermophysical lesions

  8. The Legal Cause of Unfair Terms

    Directory of Open Access Journals (Sweden)

    Maximiliano Arango Grajales

    2016-01-01

    Full Text Available Unfair terms are outside the field of abuse. There’s not a potential risk of damage, there’s not an injury caused. Unfair terms belong to the field of the principle of equivalency of the contract. And through it, that the criterion of regulatory imbalance of the contract takes on meaning. The correction of such unfair clauses does not depend on weak parts or abuse but rather the existence of a breach of equivalence: an absence of consideration in the contract.

  9. The Euro crisis. Causes and Symptoms

    Directory of Open Access Journals (Sweden)

    Christoph S. Weber

    2015-06-01

    Full Text Available The Euro crisis is mainly a consequence of the international financial crisis of 2008. Thereby, the term Euro crisis is misleading as there is no currency crisis. First, the article shows some of the birth defects of the Euro. Second, it shows that the increase in public debt was caused by rescue measures for banks and anti-cyclical fiscal policy. Third, we argue that the Euro crisis is not just one crisis (a sovereign debt crisis but it is a combination of several macroeconomic crises including a growth crisis, a labour market crisis, a public debt crisis, and a current account crisis.

  10. [Megadolichobasilar anomaly causing acute deafness with vertigo].

    Science.gov (United States)

    Unkelbach, M H; Radeloff, A; Bink, A; Gstöttner, W; Ziemann, U

    2008-01-01

    Megadolichobasilar anomaly, a dilatant arteriopathy of the basilar artery attributable to chronic arterial hypertension, can cause cranial nerve compression syndromes of the cerebellopontine angle or infarcts of the vertebrobasilar circulation. In this paper, we report on a patient with known megadolichobasilar anomaly and a partially thrombosed fusiform aneurysm of the basilar artery, who presented with acute-onset vertigo and subsequent deafness due to thromboembolic occlusion of the labyrinthine artery. Because of the vascular origin of the patient's symptoms, his vertigo disappeared over time while the deafness persisted.

  11. The Chernobyl accidents: Causes and Consequences

    International Nuclear Information System (INIS)

    Chihab-Eddine, A.

    1988-01-01

    The objective of this communication is to discuss the causes and the consequences of the Chernobyl accident. To facilitate the understanding of the events that led to the accident, the author gave a simplified introduction to the important physics that goes on in a nuclear reactor and he presented a brief description and features of chernobyl reactor. The accident scenario and consequences have been presented. The common contribution factors that led to both Three Mile Island and Chernobyl accidents have been pointed out.(author)

  12. CAUSES AND CONSEQUENCES OF CLIMATE CHANGE

    OpenAIRE

    Adrian Stanisoara

    2014-01-01

    Climate change, arising from the greenhouse effect of heattrapping gases, is a global problem. All nations are involved in both its causes and consequences. Currently developed nations are the largest emitters of greenhouse gases, but emissions by developing nations will grow considerably in coming decades. The most recent scientific evidence indicates that effects during the twenty-first century may range from a global temperature increase of 1.1ºC (2ºF) up to 6.4ºC. In addition to simply wa...

  13. Necrotizing fasciitis caused by group A streptococcus

    Directory of Open Access Journals (Sweden)

    Mikić Dragan

    2002-01-01

    Full Text Available The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region. Parenteral antibiotic, substitution and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue. The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment. He was released from the hospital as completely cured two months after the admission.

  14. Indoor air pollution caused by geothermal gases

    International Nuclear Information System (INIS)

    Durand, Michael

    2006-01-01

    This paper discusses the little-known but potentially serious indoor air quality problems that may occur where buildings are constructed on geothermal ground. The main problems are related to seepage of carbon dioxide, hydrogen sulphide, radon and other gases from soil cavities directly into indoor air through perforations in the structure. These gases present a health hazard, and hydrogen sulphide, which is particularly corrosive, may cause problems electrical and electronic systems. Counter-measures are not always effective, so developments in such areas should only be undertaken with a clear understanding of site-specific issues and their possible solutions. (author)

  15. Matrimonial Causes Rules, 1986, 30 January 1987.

    Science.gov (United States)

    1987-01-01

    These Rules are made under Section 4 of the Matrimonial Causes Law, 1976 and contain provisions on applications for leave to present a petition for divorce, documents to accompany the petition, information to be contained in the petition, service of the petition, pleadings subsequent to the petition, directions for trial, security for costs, decrees, and enforcement of orders, among other things. The Rules also stipulate that when "it appears that there is a child of the marriage under the age of sixteen, the record shall show specifically that the question of provision for such child has been considered and dealt with by the Court." full text

  16. Allergic contact dermatitis caused by dorzolamide eyedrops

    Directory of Open Access Journals (Sweden)

    Lee SJ

    2015-04-01

    Full Text Available Seung-Jun Lee, Moosang KimDepartment of Ophthalmology, School of Medicine, Kangwon National University, Chuncheon, KoreaAbstract: The side effects of topical dorzolamide hydrochloride, such as conjunctivitis, eyelid edema, and eye lid irritation, are well known. However, allergic contact dermatitis due to dorzolamide is rare, although the product has been commonly used worldwide in patients with glaucoma. To the best of our knowledge, this is the first report of allergic contact dermatitis caused by topical dorzolamide hydrochloride in Korea. Herein we report a case of allergic contact dermatitis due to topical dorzolamide eyedrops.Keywords: allergic contact dermatitis, dorzolamide, side effects

  17. Complications after osteosynthesis and their causes

    International Nuclear Information System (INIS)

    Lechner, S.

    1982-01-01

    From 1976 to 1981, 1,426 osteosyntheses were carried through according to the methods of the study group on questions of osteosynthesis. Complications occurred in 73 patients and consisted in the fracture or bending of the implant, or non-union. This led to an epicritical scrutiny of the case histories and X-ray images of these 73 patients in order to ascertain the causes underlying these complications, and to find out to what extent these problems can be recognized at an early date after the operation. (orig./MG) [de

  18. Cause of Damage. Hot cracking; Schadensursache Heissrissigkeit

    Energy Technology Data Exchange (ETDEWEB)

    Wader, Therese [BENTELER Steel/Tube GmbH, Paderborn (Germany). Vorentwicklung Werkstoffe

    2016-10-15

    Under certain conditions, Nb-containing stainless steels are susceptible to hot cracking. Such conditions include low melting phases on the grain boundaries, a coarse-grained microstructure such as cast structures, microstructure orientations towards the main tensile direction and high processing temperatures. The case of damage was characterized using metallographic and microanalytical methods. In the laboratory, the critical temperature range for the formation of hot cracks could furthermore specifically be localized under mechanical stresses by means of a dilatometer aiming at clearly verifying the cause of the damage, namely ''hot cracks''.

  19. Significant events caused by extraneous acts

    International Nuclear Information System (INIS)

    Verlaeken, J.

    1987-01-01

    The operating experience feedback system of VINCOTTE, called ARIANE, consists, among others, of preparing synthesis reports on specific safety concerns. A recent report deals with significant events caused by extranous acts. Events attributable to human error are numerous. Confusion errors have already been analysed in several publications (NES IRS 664 etc.). However, are described here some ten incidents where extranous acts occurred: ZION 2 (September 76), OYSTER CREEK (May 79), PALISADES (January 81), CATAWBA (August 85), etc. The contributing factors for these unfortunate initiatives are explained; several resort to psychological influences. Corrective actions are discussed, and some general lessons are drawn. (author)

  20. Injuries caused by firewood splitting machines.

    Science.gov (United States)

    Hellstrand, P H

    1989-01-01

    The aim of this paper is to present the types of injury caused by firewood splitting machines and also to elucidate the accident mechanism. The study is based on 15 cases. The machine has a rotating spiral cone, and usually the victims' gloved fingertips were caught by the point of the cone. This led to either amputations, usually of radial fingers and/or penetrating wounds through the middle of the hand. In most cases the accidents could not be blamed on bad working techniques. The study of the mechanisms of injury points to insufficient protective devices in a machine construction which has a potentially dangerous working principle.

  1. Delayed dermal burns caused by dimethyl acetylenedicarboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Slovak, A J; Payne, A R

    1984-07-01

    A chemical operator handling dimethyl acetylenedicarboxylate (DMAD) developed delayed and pain-free burns on one of his feet 2 days after a supposed spillage of DMAD. The injuries were confirmed to be associated with DMAD by chemical analysis of the operator's safety boot and patch tests. DMAD easily penetrates some protective clothing and dilute solutions can still be hazardous: the toxic effect is compounded by being delayed and painless. The lachrymatory irritant properties of undiluted DMAD are not adequate warning of its presence or spillage in quantities sufficient to cause significant skin damage.

  2. Snapping Knee Caused by Medial Meniscal Cyst

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Ohishi

    2014-01-01

    Full Text Available Snapping phenomenon around the medial aspect of the knee is rare. We present this case of snapping knee caused by the sartorius muscle over a large medial meniscal cyst in a 66-year-old female. Magnetic resonance images demonstrated a large medial meniscal cyst with a horizontal tear of the medial meniscus. Arthroscopic cyst decompression with limited meniscectomy resulted in the disappearance of snapping, and no recurrence of the cyst was observed during a 2-year follow-up period.

  3. Craniocervical mycetoma caused bu Streptomyces somaliensis

    International Nuclear Information System (INIS)

    Ramboer, J.H.; De Graaf, A.S.; Hewlett, R.H.; Kirby, P.A.; Robson, R.A.

    1989-01-01

    Magnetic resonance (MR) imaging, computerized tomography (CT) and clinical-pathological findings are described in a case of craniocervical mycetoma caused by the actinomycete Streptomyces somaliensis. Clinical features includes epilepsy, visual and hearing disturbance, quadriplegia and incontinence. CT revealed a hyperdense, diffusely enhancing intra-extracranial mass, further defined by MR to involve the oropharyngeal region, skull base, cranial-cervical peridural spaces and brain. On treatment with Dapsone, the lesion decreased in size, with recovery of spinal cord function. The combined plain film, CT and MR images are considered to be diagnostic of this form of mycetoma. (author). 10 refs.; 4 figs

  4. Craniocervical mycetoma caused bu Streptomyces somaliensis

    Energy Technology Data Exchange (ETDEWEB)

    Ramboer, J.H.; De Graaf, A.S. (Tygerberg Hospital, Bellville (South Africa). Dept. of Internal Medicine); Hewlett, R.H. (Tygerberg Hospital, Bellville (South Africa). Dept. of Radiology); Kirby, P.A. (Tygerberg Hospital, Cape Town (South Africa). Department of Anatomical Pathology); Robson, R.A. (Tygerberg Hospital, Capetown (South Africa). Department of Microbiology)

    Magnetic resonance (MR) imaging, computerized tomography (CT) and clinical-pathological findings are described in a case of craniocervical mycetoma caused by the actinomycete Streptomyces somaliensis. Clinical features includes epilepsy, visual and hearing disturbance, quadriplegia and incontinence. CT revealed a hyperdense, diffusely enhancing intra-extracranial mass, further defined by MR to involve the oropharyngeal region, skull base, cranial-cervical peridural spaces and brain. On treatment with Dapsone, the lesion decreased in size, with recovery of spinal cord function. The combined plain film, CT and MR images are considered to be diagnostic of this form of mycetoma. (author). 10 refs.; 4 figs.

  5. Pituitary gigantism: Causes and clinical characteristics.

    Science.gov (United States)

    Rostomyan, Liliya; Daly, Adrian F; Beckers, Albert

    2015-12-01

    Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Does occupational noise cause asymmetric hearing loss?

    Science.gov (United States)

    Dobie, Robert A

    2014-01-01

    Determine whether occupational noise exposure increases audiometric asymmetry. Audiograms were performed on 2044 men from the Occupational Noise and Hearing Survey, representing four groups based on preliminary screening (for previous noise exposure, otologic history, and otoscopy) and current occupational noise exposure. The effects of current noise exposure on audiometric asymmetry were tested using ANCOVA, with binaural average thresholds as covariates. There were no significant differences in asymmetry attributable to current occupational noise exposure. Occupational noise exposure does not usually cause or exacerbate audiometric asymmetry.

  7. Infectious endocarditis caused by Escherichia coli

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Arpi, Magnus; Fritz-Hansen, Thomas

    2011-01-01

    Although Escherichia coli is among the most common causes of Gram-negative bacteraemia, infectious endocarditis (IE) due to this pathogen is rare. A 67-y-old male without a previous medical history presented with a new mitral regurgitation murmur and persisting E. coli bacteraemia in spite of broad......-spectrum intravenous antibiotics. Transthoracic and transoesophageal echocardiography revealed a severe mitral endocarditis. E. coli DNA was identified from the mitral valve and the vegetation, and no other pathogen was found. The case was further complicated by spondylodiscitis and bilateral endophthalmitis. Extra...

  8. [Obstructive renal insufficiency caused by amoxicillin crystalluria].

    Science.gov (United States)

    Boursas, M; Benhassine, L; Kempf, J; Petit, B; Vuillemin, F

    1997-01-01

    A 76-year-old woman was admitted to the ICU for a meningitis with rhombencephalitis due to Listeria monocytogenes. The treatment included amoxicillin (250 mg.kg-1.day-1) and gentamicin (3 mg.kg-1.day-1 over 6 days). Neurological outcome was favourable. However at the 14th day, an acute renal failure occurred, following macroscopic haematuria and milkiness urine. CT scan and sonography confirmed the diagnosis of obstructive renal failure with bilateral ureteral obstruction. Crystalluria caused by amoxicillin was suspected. Endoscopic ureteral insertion of double-J catheters permitted the recovery of a normal renal function.

  9. Space storms and radiation causes and effects

    CERN Document Server

    Schrijver, Carolus J

    2010-01-01

    Heliophysics is a fast-developing scientific discipline that integrates studies of the Sun's variability, the surrounding heliosphere, and the environment and climate of planets. The Sun is a magnetically variable star and for planets with intrinsic magnetic fields, planets with atmospheres, or planets like Earth with both, there are profound consequences. This 2010 volume, the second in this series of three heliophysics texts, integrates the many aspects of space storms and the energetic radiation associated with them - from causes on the Sun to effects in planetary environments. It reviews t

  10. Mass Estinctions Caused by Large Bolide Impacts

    Energy Technology Data Exchange (ETDEWEB)

    Lavarez, Luis W.

    1987-01-01

    In this talk, I will describe the wealth of evidence that has forced my colleagues and me to conclude that the great mass extinctions, 65 million years ago, were caused by a large bolide impact on the earth. Bolide is a new word to most people, and it means any piece of solar system debris, such as a meteorite, asteroid, or comet nucleus. As I will show, the bolide responsible for the extinction of most of the then existing species, including the dinosaurs, was about 10 kilometers in diameter.

  11. The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

    Science.gov (United States)

    Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

  12. Gastric antral vascular ectasia causing severe anemia.

    Science.gov (United States)

    Toyota, M; Hinoda, Y; Nakagawa, N; Arimura, Y; Tokuchi, S; Takaoka, A; Kitagawa, S; Usuki, T; Yabana, T; Yachi, A; Imai, K

    1996-10-01

    Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal bleeding is reported in a 76-year-old woman who had been treated with repeated blood transfusions because of severe anemia. Endoscopic examination was performed and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory data showed SGOT > SGPT, decreased chE level and the increased levels of serum gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination revealed splenomegaly. There was no family history of telangiectasia, and no telangiectasia was found in other organs. The diagnosis was established as GAVE with liver cirrhosis. Surgical resection of the distal stomach resulted in termination of the bleeding, and the cirrhotic changes of the surface of the liver were revealed at that time, providing further evidence of liver cirrhosis. Although the pathogenesis of GAVE is unknown, liver cirrhosis and hypergastrinemia are thought to be associated with the condition. Importantly, this condition is a cause of severe gastrointestinal bleeding in elderly patients.

  13. Prevalence and causes of corneal blindness.

    Science.gov (United States)

    Wang, Haijing; Zhang, Yaoguang; Li, Zhijian; Wang, Tiebin; Liu, Ping

    2014-04-01

    The study aimed to assess the prevalence and causes of corneal blindness in a rural northern Chinese population. Cross-sectional study. The cluster random sampling method was used to select the sample. This population-based study included 11 787 participants of all ages in rural Heilongjiang Province, China. These participants underwent a detailed interview and eye examination that included the measurement of visual acuity, slit-lamp biomicroscopy and direct ophthalmoscopy. An eye was considered to have corneal blindness if the visual acuity was blindness and low vision. Among the 10 384 people enrolled in the study, the prevalence of corneal blindness is 0.3% (95% confidence interval 0.2-0.4%). The leading cause was keratitis in childhood (40.0%), followed by ocular trauma (33.3%) and keratitis in adulthood (20.0%). Age and illiteracy were found to be associated with an increased prevalence of corneal blindness. Blindness because of corneal diseases in rural areas of Northern China is a significant public health problem that needs to be given more attention. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  14. Leech in urinary bladder causing hematuria.

    Science.gov (United States)

    Alam, Shadrul; Das Choudhary, Mrigen Kumar; Islam, Kabirul

    2008-02-01

    To estimate efficacy of normal saline in the management of hematuria caused by accidental entry of a leech per urethra into the urinary bladder. An intervention study was carried out in the Department of Pediatric Surgery of Sylhet MAG Osmani Medical College between January 1998 and December 2003. A total of 43 boys (mean age 8 years, SD+/-2.6) were enrolled. In all cases, a leech had entered the urinary bladder through the urethra causing hematuria. All patients were equipped with a self-retaining Foley catheter. They were managed by infusing 50ml of normal saline into the urinary bladder through the catheter that was then clamped for 3h. After removing the catheter, in all cases the whole leech was spontaneously expelled intact, dead or alive, within 2-24h during the subsequent act of micturition. Hematuria gradually diminished to a clear flow within the next 6h in 27 cases, 12h in 14 cases and 24h in two cases. All patients were followed up for 2 weeks, and none developed recurrent hematuria. Catheterization and irrigation of the urinary bladder with normal saline is a relatively simple, safe and inexpensive method of removing the leech and controlling hematuria.

  15. Re-visiting the Causes of Cancer

    Science.gov (United States)

    Sir Richard Peto, FRS, is Professor of Medical Statistics and Epidemiology at the University of Oxford, UK, and Co-Director of the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU). He collaborated for decades with Richard Doll on cancer epidemiology, and in 1981, they co-authored an influential report, “The Causes of Cancer – Quantitative estimates of avoidable risks of cancer in the US today” (JNCI 66:1191). Since then, his close attention to the details of how epidemiological evidence and trial evidence is interpreted has shown that the importance of factors such as tobacco, blood pressure and cholesterol have been much underestimated: we actually know more than we thought we did about major avoidable causes of cancer and of vascular disease. In 1989, Peto was made a Fellow of the Royal Society of London for introducing meta-analyses of randomised trials, was knighted by Queen Elizabeth in 1999 for services to epidemiology, and received in 2010 and 2011 the Cancer Research UK and the BMJ Lifetime Achievement Award.

  16. Lingual thyroid causing dysphonia: case report

    Directory of Open Access Journals (Sweden)

    Alfio José Tincani

    Full Text Available CONTEXT: Lingual thyroid gland is a rare clinical entity that is caused by the failure of the thyroid gland to descend to a normal cervical location during embryogenesis. The occurrence of an ectopic thyroid gland located at the base of the tongue may cause problems for the patient, with symptoms of dysphagia, dysphonia, upper airway obstruction or even hemorrhage at any time from infancy through adulthood. CASE REPORT: We report on a case of lingual thyroid gland in a 41-year-old female patient. The embryology and diagnosis of ectopic thyroid are discussed and its management is outlined. Features of the diagnostic and therapeutic evaluation are described with attention to the clinical findings, laboratory tests, thyroid scan and computed tomography imaging studies employed in the confirmation of diagnosis and planning of appropriate treatment. The history of the condition is reviewed and a treatment strategy is outlined. Surgical excision of the gland is reserved for cases of gland enlargement that result in compromised airways (dysphagia or dysphonia or recurrent hemorrhage.

  17. Dysfunctional health service conflict: causes and accelerants.

    Science.gov (United States)

    Nelson, H Wayne

    2012-01-01

    This article examines the causes and accelerants of dysfunctional health service conflict and how it emerges from the health system's core hierarchical structures, specialized roles, participant psychodynamics, culture, and values. This article sets out to answer whether health care conflict is more widespread and intense than in other settings and if it is, why? To this end, health care power, gender, and educational status gaps are examined with an eye to how they undermine open communication, teamwork, and collaborative forms of conflict and spark a range of dysfunctions, including a pervasive culture of fear; the deny-and-defend lawsuit response; widespread patterns of hierarchical, generational, and lateral bullying; overly avoidant conflict styles among non-elite groups; and a range of other behaviors that lead to numerous human resource problems, including burnout, higher staff turnover, increased errors, poor employee citizenship behavior, patient dissatisfaction, increased patient complaints, and lawsuits. Bad patient outcomes include decreased compliance and increased morbidity and mortality. Health care managers must understand the root causes of these problems to treat them at the source and implement solutions that avoid negative conflict spirals that undermine organizational morale and efficiency.

  18. Causes for contemporary regional sea level changes.

    Science.gov (United States)

    Stammer, Detlef; Cazenave, Anny; Ponte, Rui M; Tamisiea, Mark E

    2013-01-01

    Regional sea level changes can deviate substantially from those of the global mean, can vary on a broad range of timescales, and in some regions can even lead to a reversal of long-term global mean sea level trends. The underlying causes are associated with dynamic variations in the ocean circulation as part of climate modes of variability and with an isostatic adjustment of Earth's crust to past and ongoing changes in polar ice masses and continental water storage. Relative to the coastline, sea level is also affected by processes such as earthquakes and anthropogenically induced subsidence. Present-day regional sea level changes appear to be caused primarily by natural climate variability. However, the imprint of anthropogenic effects on regional sea level-whether due to changes in the atmospheric forcing or to mass variations in the system-will grow with time as climate change progresses, and toward the end of the twenty-first century, regional sea level patterns will be a superposition of climate variability modes and natural and anthropogenically induced static sea level patterns. Attribution and predictions of ongoing and future sea level changes require an expanded and sustained climate observing system.

  19. Conditional deletion of Pten causes bronchiolar hyperplasia.

    Science.gov (United States)

    Davé, Vrushank; Wert, Susan E; Tanner, Tiffany; Thitoff, Angela R; Loudy, Dave E; Whitsett, Jeffrey A

    2008-03-01

    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (Pten(Delta/Delta)) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by beta-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, beta-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles.

  20. Root cause of waterborne diseases in Pakistan

    International Nuclear Information System (INIS)

    Hashml, H.N.; Ghumman, A.R.; Malik, N.E.

    2005-01-01

    The waterborne diseases are increasing rapidly at an alarming rate in Pakistan due to poor sanitation and unsafe drinking water supplies. This study shows that about 25 percent of all the illnesses in Lahore are due to severe cases of waterborne diseases. Unhygienic sanitation system is the root cause for this scenario. Drinking water, samples were collected from different zones of the city to find out the root cause of waterborne diseases. The samples from the distribution system serving 'Kachi Abbadies' (Underdeveloped areas) were much more contaminated, may be due to non-chlorination as compared to the water which is regularly chlorinated in posh areas of the city. Contribution of soakage pits in groundwater contamination is more significant at shallow depths. From the laboratory results it is clear that water distribution in underdeveloped areas of the city is highly contaminated and ground water available at shallow depth is also infected by microbial activities. Data collected from the different hospitals to investigate the problem shows that waterborne diseases vary their trend seasonally. Here in Pakistan, rainy season (July-August) reveals maximum number of cases of waterborne diseases. Proper sanitation and water supply systems are more essential to control the influence of waterborne diseases within the country. It is strongly recommended that reputable ways of communications are urgently required to highlight the diseases related to unsafe drinking water. (author)