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Sample records for factor cbf acute

  1. Genetics Home Reference: core binding factor acute myeloid leukemia

    MedlinePlus

    ... acute myeloid leukemia core binding factor acute myeloid leukemia Enable Javascript to view the expand/collapse boxes. ... Close All Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  2. Acute effects of electroconvulsive therapy on regional cerebral blood flow (rCBF) in psychiatric disorders

    SciTech Connect

    Prohovnik, I.; Alderson, P.O.; Sackheim, H.A.; Decina, P.; Kahn, D.

    1984-01-01

    Electroconvulsive therapy (ECT) is frequently used in the treatment of major depression and other psychiatric disorders; its mechanism of action is not established, but previous evidence suggests that it is associated with postictal metabolic suppression. The authors have used measurements of rCBF as an index of cortical metabolic activity to study the acute effects of ECT. Measurements of rCBF were made in 32 cortical regions in 10 patients (pts) following one minute breathing of Xe-133 (5mCi/L); the measurements were performed 30min before and 50min after ECT. Bilateral ECT was administered to six pts (five diagnosed as major depressives and one schizophrenic) and unilateral ECT to four (all diagnosed as unipolar or bipolar affective disorder). The total rCBF material consists of 52 measurements in these pts, made before and after 16 bilateral and 10 unilateral treatments. ECT was found to cause significant reduction of rCBF. Mean hemispheric flows (using the Initial Slope Index to measure grey-matter flow) were reduced by about 5% in both hemispheres following bilateral treatment. Unilateral treatment caused a 9% reduction of flow in the treated hemisphere, but only 2% contralaterally. Regional patterns of flow decreases also differed between the two treatment modes: bilateral frontal reductions were found after bilateral treatment, whereas unilateral ECT caused a widespread flow reduction in the treated hemisphere, and almost no effect contralaterally. These results suggest that rCBF studies are useful for assessing ECT, and indicate that the acute cerebral effects of ECT vary with the mode of treatment.

  3. Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

    PubMed Central

    2011-01-01

    Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

  4. Vaccine Potential and Diversity of the Putative Cell Binding Factor (CBF, NMB0345/NEIS1825) Protein of Neisseria meningitidis.

    PubMed

    Humbert, María Victoria; Hung, Miao-Chiu; Phillips, Renee; Akoto, Charlene; Hill, Alison; Tan, Wei-Ming; Heckels, John Edward; Christodoulides, Myron

    2016-01-01

    The cbf gene from Neisseria meningitidis strain MC58 encoding the putative Cell Binding Factor (CBF, NMB0345/NEIS1825) protein was cloned into the pRSETA system and a ~36-kDa recombinant (r)CBF protein expressed in Escherichia coli and purified by metal affinity chromatography. High titres of rCBF antibodies were induced in mice following immunization with rCBF-saline, rCBF-Al(OH)3, rCBF-Liposomes or rCBF-Zwittergent (Zw) 3-14 micelles, both with and without incorporated monophosphoryl lipid A (MPLA) adjuvant. Anti-rCBF sera reacted in western blots of meningococcal lysates with a single protein band of molecular mass ~29.5 kDa, indicative of mature CBF protein, but did not react with a lysate of a Δnmb0345 mutant (CBF-), demonstrating specificity of the murine immune responses. CBF protein was produced by all strains of meningococci studied thus far and the protein was present on the surface of MC58 (CBF+) bacteria, but absent on Δnmb0345 mutant (CBF-) bacteria, as judged by FACS reactivity of anti-rCBF sera. Analysis of the NEIS1825 amino acid sequences from 6644 N. meningitidis isolates with defined Alleles in the pubmlst.org/Neisseria database showed that there were 141 ST types represented and there were 136 different allelic loci encoding 49 non-redundant protein sequences. Only 6/6644 (<0.1%) of N. meningitidis isolates lacked the nmb0345 gene. Amongst serogroup B isolates worldwide, ~68% and ~20% expressed CBF encoded by Allele 1 and 18 respectively, with the proteins sharing >99% amino acid identity. Murine antisera to rCBF in Zw 3-14 micelles + MPLA induced significant serum bactericidal activity (SBA) against homologous Allele 1 and heterologous Allele 18 strains, using both baby rabbit serum complement and human serum complement (h)SBA assays, but did not kill strains expressing heterologous protein encoded by Alelle 2 or 3. Furthermore, variable bactericidal activity was induced by murine antisera against different meningococcal strains in the h

  5. Vaccine Potential and Diversity of the Putative Cell Binding Factor (CBF, NMB0345/NEIS1825) Protein of Neisseria meningitidis

    PubMed Central

    Akoto, Charlene; Hill, Alison; Tan, Wei-Ming; Heckels, John Edward; Christodoulides, Myron

    2016-01-01

    The cbf gene from Neisseria meningitidis strain MC58 encoding the putative Cell Binding Factor (CBF, NMB0345/NEIS1825) protein was cloned into the pRSETA system and a ~36-kDa recombinant (r)CBF protein expressed in Escherichia coli and purified by metal affinity chromatography. High titres of rCBF antibodies were induced in mice following immunization with rCBF-saline, rCBF-Al(OH)3, rCBF-Liposomes or rCBF-Zwittergent (Zw) 3–14 micelles, both with and without incorporated monophosphoryl lipid A (MPLA) adjuvant. Anti-rCBF sera reacted in western blots of meningococcal lysates with a single protein band of molecular mass ~29.5 kDa, indicative of mature CBF protein, but did not react with a lysate of a Δnmb0345 mutant (CBF-), demonstrating specificity of the murine immune responses. CBF protein was produced by all strains of meningococci studied thus far and the protein was present on the surface of MC58 (CBF+) bacteria, but absent on Δnmb0345 mutant (CBF-) bacteria, as judged by FACS reactivity of anti-rCBF sera. Analysis of the NEIS1825 amino acid sequences from 6644 N. meningitidis isolates with defined Alleles in the pubmlst.org/Neisseria database showed that there were 141 ST types represented and there were 136 different allelic loci encoding 49 non-redundant protein sequences. Only 6/6644 (<0.1%) of N. meningitidis isolates lacked the nmb0345 gene. Amongst serogroup B isolates worldwide, ~68% and ~20% expressed CBF encoded by Allele 1 and 18 respectively, with the proteins sharing >99% amino acid identity. Murine antisera to rCBF in Zw 3–14 micelles + MPLA induced significant serum bactericidal activity (SBA) against homologous Allele 1 and heterologous Allele 18 strains, using both baby rabbit serum complement and human serum complement (h)SBA assays, but did not kill strains expressing heterologous protein encoded by Alelle 2 or 3. Furthermore, variable bactericidal activity was induced by murine antisera against different meningococcal strains in the h

  6. Mutational Evidence for the Critical Role of CBF Transcription Factors in Cold Acclimation in Arabidopsis.

    PubMed

    Zhao, Chunzhao; Zhang, Zhengjing; Xie, Shaojun; Si, Tong; Li, Yuanya; Zhu, Jian-Kang

    2016-08-01

    The three tandemly arranged CBF genes, CBF1, CBF2, and CBF3, are involved in cold acclimation. Due to the lack of stable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants deficient in all three CBF genes, it is still unclear whether the CBF genes are essential for freezing tolerance and whether they may have other functions besides cold acclimation. In this study, we used the CRISPR/Cas9 system to generate cbf single, double, and triple mutants. Compared to the wild type, the cbf triple mutants are extremely sensitive to freezing after cold acclimation, demonstrating that the three CBF genes are essential for cold acclimation. Our results show that the three CBF genes also contribute to basal freezing tolerance. Unexpectedly, we found that the cbf triple mutants are defective in seedling development and salt stress tolerance. Transcript profiling revealed that the CBF genes regulate 414 cold-responsive (COR) genes, of which 346 are CBF-activated genes and 68 are CBF-repressed genes. The analysis suggested that CBF proteins are extensively involved in the regulation of carbohydrate and lipid metabolism, cell wall modification, and gene transcription. Interestingly, like the triple mutants, cbf2 cbf3 double mutants are more sensitive to freezing after cold acclimation compared to the wild type, but cbf1 cbf3 double mutants are more resistant, suggesting that CBF2 is more important than CBF1 and CBF3 in cold acclimation-dependent freezing tolerance. Our results not only demonstrate that the three CBF genes together are required for cold acclimation and freezing tolerance, but also reveal that they are important for salt tolerance and seedling development. PMID:27252305

  7. CsICE1 and CsCBF1: two transcription factors involved in cold responses in Camellia sinensis.

    PubMed

    Wang, Yu; Jiang, Chang-Jun; Li, Ye-Yun; Wei, Chao-Ling; Deng, Wei-Wei

    2012-01-01

    C-repeat/dehydration-responsive element binding factors (CBFs) can induce the expression of a suite of cold-responsive genes to increase plant cold tolerance, and inducer of CBF expression 1 (ICE1) is a major activator for CBF. In the present study, we isolated the full-length cDNAs of ICE1 and CBF from Camellia sinensis, designated as CsICE1 and CsCBF1, respectively. The deduced protein CsICE1 contains a highly conserved basic helix-loop-helix (bHLH) domain and C-terminal region of ICE1-like proteins. CsCBF1 contains all conserved domains of CBFs in other plant species and can specifically bind to the C-repeat/dehydration-responsive element (CRT/DRE) as confirmed by electrophoretic mobility shift assay. The transcription of CsICE1 had no apparent alteration after chilling treatment (4°C). CsCBF1 expression was not detected in normal temperature (20°C) but was induced immediately and significantly by low temperature (4°C). Our results suggest that ICE1-CBF cold-response pathway is conserved in tea plants. CsICE1 and CsCBF1, two components of this pathway, play roles in cold responses in tea plants. PMID:21850593

  8. Ectopic Overexpression of SsCBF1, a CRT/DRE-Binding Factor from the Nightshade Plant Solanum lycopersicoides, Confers Freezing and Salt Tolerance in Transgenic Arabidopsis

    PubMed Central

    Zhang, Lili; Li, Zhenjun; Li, Jingfu; Wang, Aoxue

    2013-01-01

    The C-repeat (CRT)/dehydration-responsive element (DRE) binding factor (CBF/DREB1) transcription factors play a key role in cold response. However, the detailed roles of many plant CBFs are far from fully understood. A CBF gene (SsCBF1) was isolated from the cold-hardy plant Solanum lycopersicoides. A subcellular localization study using GFP fusion protein indicated that SsCBF1 is localized in the nucleus. We delimited the SsCBF1 transcriptional activation domain to the C-terminal segment comprising amino acid residues 193–228 (SsCBF1193–228). The expression of SsCBF1 could be dramatically induced by cold, drought and high salinity. Transactivation assays in tobacco leaves revealed that SsCBF1 could specifically bind to the CRT cis-elements in vivo to activate the expression of downstream reporter genes. The ectopic overexpression of SsCBF1 conferred increased freezing and high-salinity tolerance and late flowering phenotype to transgenic Arabidopsis. RNA-sequencing data exhibited that a set of cold and salt stress responsive genes were up-regulated in transgenic Arabidopsis. Our results suggest that SsCBF1 behaves as a typical CBF to contribute to plant freezing tolerance. Increased resistance to high-salinity and late flowering phenotype derived from SsCBF1 OE lines lend more credence to the hypothesis that plant CBFs participate in diverse physiological and biochemical processes related to adverse conditions. PMID:23755095

  9. CT-CBF Maps Optimally Correlate with Admission DWI in Acute Stroke, but Thresholds Vary by Post-Processing Platform

    PubMed Central

    Kamalian, Shahmir; Kamalian, Shervin; Maas, Matthew B.; Goldmacher, Greg V; Payabvash, Seyedmehdi; Akbar, Adnan; Schaefer, Pamela W; Furie, Karen L; Gilberto Gonzalez, R.; Lev, Michael H

    2011-01-01

    Purpose Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hrs) stroke. Our purpose was to: (1) determine the optimal CT perfusion (CTP) parameter to define infarct core using various post-processing platforms, and (2) establish the degree of variability in threshold values between these different platforms. Methods We evaluated 48 consecutive cases with vessel occlusion and admission CTP and DWI within 3 hours of each other. CTP was acquired with a “second-generation” 66-second biphasic cine protocol, and post-processed using “standard” (from two vendors, “A-std” and “B-std”) and “delay-corrected” (from one vendor, “A-dc”) commercial software. ROC curve analysis was performed comparing each CTP parameter - both absolute and normalized to the contralateral uninvolved hemisphere - between infarcted and non-infarcted regions, as defined by co-registered DWI. Results Cerebral blood flow (CBF) had the highest accuracy (ROC “area under curve”, AUC), for all three platforms (p<0.01). The maximal AUC's for each parameter were: absolute CBF 0.88, CBV 0.81, and MTT 0.82, and relative CBF 0.88, CBV 0.83, and MTT 0.82. Optimal ROC operating point thresholds varied significantly between different platforms (Friedman test, p<0.01). Conclusion Admission absolute and normalized “second-generation” cine acquired CT-CBF lesion volumes correlate more closely with DWI defined infarct core than do those of CT-CBV or MTT. Although limited availability of DWI for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification amongst different post-processing software limits generalizability of parameter map thresholds between platforms. PMID:21546490

  10. Functional Analysis of the Maize C-Repeat/DRE Motif-Binding Transcription Factor CBF3 Promoter in Response to Abiotic Stress

    PubMed Central

    Liu, Jinliang; Wang, Fengting; Yu, Gang; Zhang, Xianghui; Jia, Chengguo; Qin, Jianchun; Pan, Hongyu

    2015-01-01

    The ZmCBF3 gene is a member of AP2/ERF transcription factor family, which is a large family of plant-specific transcription factors that share a well-conserved DNA-binding domain. To understand the regulatory mechanism of ZmCBF3 gene expression, we isolated and characterized the ZmCBF3 promoter (PZmCBF3). Three deletion fragments of PZmCBF3 were generated, C1–C3, from the translation start codon at position −1079, −638, and −234, and fused to the GUS reporter gene. Each deletion construct was analyzed by Agrobacterium-mediated stable transformation and expression in Arabidopsis thaliana. GUS expression assays indicated that the PZmCBF3 exhibited root-specific expression activity. A 234-bp fragment upstream of the ZmCBF3 gene conferred a high level of GUS activity in Arabidopsis. Some cis-acting elements involved in the down-regulation of gene expression were detected in the promoter, encompassing positions −1079 to −234. PZmCBF3 was activated by cold stress. The MYCCONSENSUSAT elements (CANNTG) were responsible for the ability of PZmCBF3 to respond to cold stress. The results of the present study suggest that PZmCBF3 might play a role in cold tolerance in maize. PMID:26030672

  11. Functional Analysis of the Maize C-Repeat/DRE Motif-Binding Transcription Factor CBF3 Promoter in Response to Abiotic Stress.

    PubMed

    Liu, Jinliang; Wang, Fengting; Yu, Gang; Zhang, Xianghui; Jia, Chengguo; Qin, Jianchun; Pan, Hongyu

    2015-01-01

    The ZmCBF3 gene is a member of AP2/ERF transcription factor family, which is a large family of plant-specific transcription factors that share a well-conserved DNA-binding domain. To understand the regulatory mechanism of ZmCBF3 gene expression, we isolated and characterized the ZmCBF3 promoter (PZmCBF3). Three deletion fragments of PZmCBF3 were generated, C1-C3, from the translation start codon at position -1079, -638, and -234, and fused to the GUS reporter gene. Each deletion construct was analyzed by Agrobacterium-mediated stable transformation and expression in Arabidopsis thaliana. GUS expression assays indicated that the PZmCBF3 exhibited root-specific expression activity. A 234-bp fragment upstream of the ZmCBF3 gene conferred a high level of GUS activity in Arabidopsis. Some cis-acting elements involved in the down-regulation of gene expression were detected in the promoter, encompassing positions -1079 to -234. PZmCBF3 was activated by cold stress. The MYCCONSENSUSAT elements (CANNTG) were responsible for the ability of PZmCBF3 to respond to cold stress. The results of the present study suggest that PZmCBF3 might play a role in cold tolerance in maize. PMID:26030672

  12. Nitric oxide modulates Lycopersicon esculentum C-repeat binding factor 1 (LeCBF1) transcriptionally as well as post-translationally by nitrosylation.

    PubMed

    Kashyap, Prakriti; Sehrawat, Ankita; Deswal, Renu

    2015-11-01

    Nitric oxide (NO) production increases in the cold stress. This cold enhanced NO manifests its effect either by regulating the gene expression or by modulating proteins by NO based post-translational modifications (PTMs) including S-nitrosylation. CBF (C-repeat binding factor) dependent cold stress signaling is most studied cold stress-signaling pathway in plants. SNP (sodium nitroprusside, a NO donor) treatment to tomato seedlings showed four fold induction of LeCBF1 (a cold inducible CBF) transcript in cold stress. S-nitrosylation as PTM of CBF has not been analyzed till date. In silico analysis using GPS-SNO 1.0 software predicted Cys 68 as the probable site for nitrosylation in LeCBF1. The 3D structure and motif prediction showed it to be present in the beta hairpin loop and hence available for S-nitrosylation. LeCBF1 was cloned and expressed in Escherichia coli. LeCBF1 accumulated in the inclusion bodies, which were solubilized under denaturing conditions and purified after on column refolding by Ni-NTA His tag affinity chromatography. Purified LeCBF1 resolved as a 34 kDa spot with a slightly basic pI (8.3) on a 2-D gel. MALDI-TOF mass spectrometry identified it as LeCBF1 and western blotting using anti-LeCBF1 antibodies confirmed its purification. Biotin switch assay and neutravidin affinity chromatography showed LeCBF1 to be S-nitrosylated in presence of GSNO (NO donor) as well as endogenously (without donor) in cold stress treated tomato seedlings. Dual regulation of LeCBF1 by NO at both transcriptional as well as post-translational level (by S-nitrosylation) is shown for the first time. PMID:26255539

  13. A R2R3 type MYB transcription factor is involved in the cold regulation of CBF genes and in acquired freezing tolerance.

    PubMed

    Agarwal, Manu; Hao, Yujin; Kapoor, Avnish; Dong, Chun-Hai; Fujii, Hiroaki; Zheng, Xianwu; Zhu, Jian-Kang

    2006-12-01

    Cold temperatures trigger the expression of the CBF family of transcription factors, which in turn activate many downstream genes that confer freezing tolerance to plants. It has been shown previously that the cold regulation of CBF3 involves an upstream bHLH-type transcription factor, ICE1. ICE1 binds to the Myc recognition sequences in the CBF3 promoter. Apart from Myc recognition sequences, CBF promoters also have Myb recognition sequences. We report here that the Arabidopsis MYB15 is involved in cold-regulation of CBF genes and in the development of freezing tolerance. The MYB15 gene transcript is up-regulated by cold stress. The MYB15 protein interacts with ICE1 and binds to Myb recognition sequences in the promoters of CBF genes. Overexpression of MYB15 results in reduced expression of CBF genes whereas its loss-of-function leads to increased expression of CBF genes in the cold. The myb15 mutant plants show increased tolerance to freezing stress whereas its overexpression reduces freezing tolerance. Our results suggest that MYB15 is part of a complex network of transcription factors controlling the expression of CBFs and other genes in response to cold stress. PMID:17015446

  14. Functional Characterization of Hevea brasiliensis CRT/DRE Binding Factor 1 Gene Revealed Regulation Potential in the CBF Pathway of Tropical Perennial Tree.

    PubMed

    Cheng, Han; Cai, Haibin; Fu, Haitian; An, Zewei; Fang, Jialin; Hu, Yanshi; Guo, Dianjing; Huang, Huasun

    2015-01-01

    Rubber trees (Hevea brasiliensis) are susceptible to low temperature and therefore are only planted in the tropical regions. In the past few decades, although rubber trees have been successfully planted in the northern margin of tropical area in China, they suffered from cold injury during the winter. To understand the physiological response under cold stress, we isolated a C-repeat binding factor 1 (CBF1) gene from the rubber tree. This gene (HbCBF1) was found to respond to cold stress but not drought or ABA stress. The corresponding HbCBF1 protein showed CRT/DRE binding activity in gel shift experiment. To further characterize its molecular function, the HbCBF1 gene was overexpressed in Arabidopsis. The HbCBF1 over expression (OE) line showed enhanced cold resistance and relatively slow dehydration, and the expression of Arabidopsis CBF pathway downstream target genes, e.g. AtCOR15a and AtRD29a, were significantly activated under non-acclimation condition. These data suggest HbCBF1 gene is a functional member of the CBF gene family, and may play important regulation function in rubber tree. PMID:26361044

  15. Functional Characterization of Hevea brasiliensis CRT/DRE Binding Factor 1 Gene Revealed Regulation Potential in the CBF Pathway of Tropical Perennial Tree

    PubMed Central

    Cheng, Han; Cai, Haibin; Fu, Haitian; An, Zewei; Fang, Jialin; Hu, Yanshi; Guo, Dianjing; Huang, Huasun

    2015-01-01

    Rubber trees (Hevea brasiliensis) are susceptible to low temperature and therefore are only planted in the tropical regions. In the past few decades, although rubber trees have been successfully planted in the northern margin of tropical area in China, they suffered from cold injury during the winter. To understand the physiological response under cold stress, we isolated a C-repeat binding factor 1 (CBF1) gene from the rubber tree. This gene (HbCBF1) was found to respond to cold stress but not drought or ABA stress. The corresponding HbCBF1 protein showed CRT/DRE binding activity in gel shift experiment. To further characterize its molecular function, the HbCBF1 gene was overexpressed in Arabidopsis. The HbCBF1 over expression (OE) line showed enhanced cold resistance and relatively slow dehydration, and the expression of Arabidopsis CBF pathway downstream target genes, e.g. AtCOR15a and AtRD29a, were significantly activated under non-acclimation condition. These data suggest HbCBF1 gene is a functional member of the CBF gene family, and may play important regulation function in rubber tree. PMID:26361044

  16. Jasmonate regulates the inducer of cbf expression-C-repeat binding factor/DRE binding factor1 cascade and freezing tolerance in Arabidopsis.

    PubMed

    Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

    2013-08-01

    The inducer of cbf expression (ICE)-C-repeat binding factor/DRE binding factor1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several jasmonate ZIM-domain (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance. PMID:23933884

  17. Jasmonate Regulates the INDUCER OF CBF EXPRESSION–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 Cascade and Freezing Tolerance in Arabidopsis[W

    PubMed Central

    Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

    2013-01-01

    The INDUCER OF CBF EXPRESSION (ICE)–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance. PMID:23933884

  18. [Nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana and its molecular evolution analyses].

    PubMed

    Hao, Gang-Ping; Wu, Zhong-Yi; Cao, Ming-Qing; Pelletier, Georges; Brunel, Dominique; Huang, Cong-Lin; Yang, Qing

    2004-12-01

    Intraspecific nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana was analyzed with 17 core accessions growing in different ecoclimate. High density of single nucleotide polymorphism (SNP) and insertion/deletion (Indel) were found, on average 1 SNP per 35.8 bp and 1 Indel per 143 bp. Nucleotide polymorphism in non-coding region was three times higher than that in coding region. In coding region of CBF4, SNP frequency is one SNP per 96.4 bp, one nonsynonymous mutation was detected from 25 av, 203 av and 244 av accessions, which is the 205th site amino acid variation: gly <--> val caused by the 1034th site (corresponding to 19,696 site nucleotide of GenBank No. AB015478 as 1) nucleotide variation: G <--> T. Statistical result of nucleotide diversity showed that linkage disequilibrium (LD) existed in large-scale region of CBF4 and recombination event was also detected in 5' non-coding region. Identical to the results of other genes of Arabidopsis, different regions of the gene were seemingly under different selective pressures. Balancing selection resulted in high nucleotide diversity in 3' non-coding region, and the neutral mutation hypothesis can explain the DNA polymorphism in coding region, whereas, nature positive selection in the population affected nucleotide variation in 5' non-coding region of gene. PMID:15633649

  19. The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape

    PubMed Central

    Tillett, Richard L.; Wheatley, Matthew D.; Tattersall, Elizabeth A.R.; Schlauch, Karen A.; Cramer, Grant R.; Cushman, John C.

    2014-01-01

    Summary Chilling and freezing can reduce significantly vine survival and fruit set in Vitis vinifera wine grape. To overcome such production losses, a recently identified grapevine C-repeat binding factor (CBF) gene, VvCBF4, was overexpressed in grape vine cv. “Freedom” and found to improve freezing survival and reduced freezing-induced electrolyte leakage by up to 2°C in non-cold-acclimated vines. In addition, overexpression of this transgene caused a reduced growth phenotype similar to that observed for CBF overexpression in Arabidopsis and other species. Both freezing tolerance and reduced growth phenotypes were manifested in a transgene dose-dependent manner. To understand the mechanistic basis of VvCBF4 transgene action, one transgenic line (9–12) was genotyped using microarray-based mRNA expression profiling. Forty-seven and 12 genes were identified in unstressed transgenic shoots with either a greater than 1.5-fold increase or decrease in mRNA abundance, respectively. Comparison of mRNA changes with characterized CBF regulons in woody and herbaceous species revealed partial overlaps suggesting that CBF-mediated cold acclimation responses are widely conserved. Putative VvCBF4-regulon targets included genes with functions in cell wall structure, lipid metabolism, epicuticular wax formation, and stress-responses suggesting that the observed cold tolerance and dwarf phenotypes are the result of a complex network of diverse functional determinants. PMID:21914113

  20. Comprehensive mutational profiling of core binding factor acute myeloid leukemia.

    PubMed

    Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

    2016-05-19

    Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. PMID:26980726

  1. Comparison of CBF1, CBF2, CBF3 and CBF4 expression in some grapevine cultivars and species under cold stress

    PubMed Central

    Karimi, Maryam; Ebadi, Ali; Mousavi, Seyed Amir; Salami, Seyed Alireza; Zarei, Abdolkarim

    2015-01-01

    Grapevine, an important horticultural crop in the world, is moderately tolerant to cold conditions and is subjected to the cold injuries at different regions. So studies on different aspects of tolerance mechanism to unexpected cold of late spring as well as winter freezing seems necessary about this vine. For this reason, study on genes responsible for acquiring cold tolerance is very important. Transcription factors are among regulatory proteins that are responsible for cold acclimation. In this research work, expression levels of CBF1, CBF2, CBF3, and CBF4 transcription factors were studied on two cvs of Vitis vinifera (“Khalili-Danedar” and “Shahroodi”) as well as one Vitis riparia at different times after treating at 4 °C. Results showed that two vinifera cultivars, “Khalili-Danedar” and “Shahroodi”, had similar trend for each transcription factor. Gene expression increased at the beginning of cold stress and then decreased. Expression of these TF started some minutes (CBF1) after cold treatment and continued for several hours (CBF2), even till the tenth day (CBF4). All together V. riparia which is endemic to the cold regions behaved stronger and showed higher expression for all studied transcription factors. Among two V. vinifera cultivars, “Khalili-Danedar” showed significantly higher expression compared with “Shahroodi”. The comparison of expression levels of these four transcription factors revealed that the least and the greatest expressions were recorded for CBF1 and CBF3 respectively, and two CBF2 and CBF4 had approximately the same expression levels. PMID:26973374

  2. Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia

    PubMed Central

    Mosna, Federico

    2016-01-01

    Even though clonally originated from a single cell, acute leukemia loses its homogeneity soon and presents at clinical diagnosis as a hierarchy of cells endowed with different functions, of which only a minority possesses the ability to recapitulate the disease. Due to their analogy to hematopoietic stem cells, these cells have been named “leukemia stem cells,” and are thought to be chiefly responsible for disease relapse and ultimate survival after chemotherapy. Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) is cytogenetically characterized by either the t(8;21) or the inv(16)/t(16;16) chromosomal abnormalities, which, although being pathognomonic, are not sufficient per se to induce overt leukemia but rather determine a preclinical phase of disease when preleukemic subclones compete until the acquisition of clonal dominance by one of them. In this review we summarize the concepts regarding the application of the “leukemia stem cell” theory to the development of CBF AML; we will analyze the studies investigating the leukemogenetic role of t(8;21) and inv(16)/t(16;16), the proposed theories of its clonal evolution, and the role played by the hematopoietic niches in preserving the disease. Finally, we will discuss the clinical implications of stem cell modeling of CBF AML for the therapy of the disease. PMID:26880987

  3. Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4/K10) Is a Novel Interaction Partner of CSL/CBF1, the Major Downstream Effector of Notch Signaling▿

    PubMed Central

    Heinzelmann, Katharina; Scholz, Barbara A.; Nowak, Agnes; Fossum, Even; Kremmer, Elisabeth; Haas, Juergen; Frank, Ronald; Kempkes, Bettina

    2010-01-01

    In cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes the survival of KSHV-infected cells. CSL/CBF1 is a DNA adaptor molecule which recruits coactivator and corepressor complexes to regulate viral and cellular gene transcription and which is a major downstream effector molecule of activated Notch. The interaction of KSHV RTA and LANA with CSL/CBF1 has been shown to balance the lytic and latent viral life cycle. Here we report that a third KSHV protein, viral interferon regulatory factor 4 (vIRF4/K10), but none of the three other KSHV-encoded vIRFs, interacts with CSL/CBF1. Two regions of vIRF4 with dissimilar affinities contribute to CSL/CBF1 binding. Similar to Notch, vIRF4 targets the hydrophobic pocket in the beta trefoil domain of CSL/CBF1 through a short peptide motif which closely resembles a motif found in Notch but does not strictly follow the ΦWΦP consensus conserved in human and mouse Notch proteins. Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling. PMID:20861242

  4. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling.

    PubMed

    Heinzelmann, Katharina; Scholz, Barbara A; Nowak, Agnes; Fossum, Even; Kremmer, Elisabeth; Haas, Juergen; Frank, Ronald; Kempkes, Bettina

    2010-12-01

    In cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes the survival of KSHV-infected cells. CSL/CBF1 is a DNA adaptor molecule which recruits coactivator and corepressor complexes to regulate viral and cellular gene transcription and which is a major downstream effector molecule of activated Notch. The interaction of KSHV RTA and LANA with CSL/CBF1 has been shown to balance the lytic and latent viral life cycle. Here we report that a third KSHV protein, viral interferon regulatory factor 4 (vIRF4/K10), but none of the three other KSHV-encoded vIRFs, interacts with CSL/CBF1. Two regions of vIRF4 with dissimilar affinities contribute to CSL/CBF1 binding. Similar to Notch, vIRF4 targets the hydrophobic pocket in the beta trefoil domain of CSL/CBF1 through a short peptide motif which closely resembles a motif found in Notch but does not strictly follow the ΦWΦP consensus conserved in human and mouse Notch proteins. Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling. PMID:20861242

  5. Vitis CBF1 and Vitis CBF4 differ in their effect on Arabidopsis abiotic stress tolerance, development and gene expression.

    PubMed

    Siddiqua, Mahbuba; Nassuth, Annette

    2011-08-01

    Plants growing in temperate regions encode several C-repeat binding factor/dehydration responsive element binding factors (CBF/DREB1) and the question is whether these transcription factors have different functions. In this study, Arabidopsis transformed with grape CBF1 (VrCBF1) or grape CBF4 (VrCBF4) were characterized. Electrolyte leakage assays showed that the freezing tolerance of transgenic lines was correlated with the level of VrCBF expression irrespective of the type of CBF, while drought tolerance was most increased by VrCBF1. VrCBF overexpression coincided with an increase in the expression of the cold-regulated genes AtCOR15a, AtRD29A, AtCOR6.6 and AtCOR47. In addition, the development of grape CBF overexpressing plants was seen to be altered and resulted in dwarf plants which flowered later and had thicker rosette leaves with a higher stomatal density. Analysis of gene expression showed that these morphological changes may be because of an increase in the expression of AtRGL3 in VrCBF4 lines or AtGA2ox7 in VrCBF1 lines, and AtFLC in both. In addition, the results show for the first time that CBFs can positively affect the expression of AtICE1/SCREAM1, the gene that is known to induce AtCBF3 expression. The difference in gene induction by VrCBF1 compared with VrCBF4 suggests that these CBFs have different regulons. PMID:21486303

  6. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial.

    PubMed

    Willekens, Christophe; Blanchet, Odile; Renneville, Aline; Cornillet-Lefebvre, Pascale; Pautas, Cécile; Guieze, Romain; Ifrah, Norbert; Dombret, Hervé; Jourdan, Eric; Preudhomme, Claude; Boissel, Nicolas

    2016-03-01

    In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558). PMID:26635039

  7. Induction of Dormancy in Arabidopsis Summer Annuals Requires Parallel Regulation of DOG1 and Hormone Metabolism by Low Temperature and CBF Transcription Factors[W][OA

    PubMed Central

    Kendall, Sarah L.; Hellwege, Anja; Marriot, Poppy; Whalley, Celina; Graham, Ian A.; Penfield, Steven

    2011-01-01

    Summer annuals overwinter as seeds in the soil seed bank. This is facilitated by a cold-induced increase in dormancy during seed maturation followed by a switch to a state during seed imbibition in which cold instead promotes germination. Here, we show that the seed maturation transcriptome in Arabidopsis thaliana is highly temperature sensitive and reveal that low temperature during seed maturation induces several genes associated with dormancy, including DELAY OF GERMINATION1 (DOG1), and influences gibberellin and abscisic acid levels in mature seeds. Mutants lacking DOG1, or with altered gibberellin or abscisic acid synthesis or signaling, in turn show reduced ability to enter the deeply dormant states in response to low seed maturation temperatures. In addition, we find that DOG1 promotes gibberellin catabolism during maturation. We show that C-REPEAT BINDING FACTORS (CBFs) are necessary for regulation of dormancy and of GA2OX6 and DOG1 expression caused by low temperatures. However, the temperature sensitivity of CBF transcription is markedly reduced in seeds and is absent in imbibed seeds. Our data demonstrate that inhibition of CBF expression is likely a critical feature allowing cold to promote rather than inhibit germination and support a model in which CBFs act in parallel to a low-temperature signaling pathway in the regulation of dormancy. PMID:21803937

  8. Regulation of the Arabidopsis CBF regulon by a complex low-temperature regulatory network.

    PubMed

    Park, Sunchung; Lee, Chin-Mei; Doherty, Colleen J; Gilmour, Sarah J; Kim, YongSig; Thomashow, Michael F

    2015-04-01

    Exposure of Arabidopsis thaliana plants to low non-freezing temperatures results in an increase in freezing tolerance that involves action of the C-repeat binding factor (CBF) regulatory pathway. CBF1, CBF2 and CBF3, which are rapidly induced in response to low temperature, encode closely related AP2/ERF DNA-binding proteins that recognize the C-repeat (CRT)/dehydration-responsive element (DRE) DNA regulatory element present in the promoters of CBF-regulated genes. The CBF transcription factors alter the expression of more than 100 genes, known as the CBF regulon, which contribute to an increase in freezing tolerance. In this study, we investigated the extent to which cold induction of the CBF regulon is regulated by transcription factors other than CBF1, CBF2 and CBF3, and whether freezing tolerance is dependent on a functional CBF-CRT/DRE regulatory module. To address these issues we generated transgenic lines that constitutively overexpressed a truncated version of CBF2 that had dominant negative effects on the function of the CBF-CRT/DRE regulatory module, and 11 transcription factors encoded by genes that were rapidly cold-induced in parallel with the 'first-wave' CBF genes, and determined the effects that overexpressing these proteins had on global gene expression and freezing tolerance. Our results indicate that cold regulation of the CBF regulon involves extensive co-regulation by other first-wave transcription factors; that the low-temperature regulatory network beyond the CBF pathway is complex and highly interconnected; and that the increase in freezing tolerance that occurs with cold acclimation is only partially dependent on the CBF-CRT/DRE regulatory module. PMID:25736223

  9. Overexpression of a blueberry-derived CBF enhances cold tolerance in a southern highbush blueberry cultivar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberry cultivars are subject to freezing damage in the winter and early spring. C-repeat binding factor (CBF) genes are transcription factors known to induce the expression of genes associated with cold acclimation and freezing tolerance. A CBF-encoding gene (BB-CBF) was isolated from the northe...

  10. Molecular cloning and characterization of a novel freezing-inducible DREB1/CBF transcription factor gene in boreal plant Iceland poppy (Papaver nudicaule).

    PubMed

    Huang, Zhuo; He, Jiao; Zhong, Xiao-Juan; Guo, Han-Du; Jin, Si-Han; Li, Xi; Sun, Ling-Xia

    2016-07-25

    DREB1 of the AP2/ERF superfamily plays a key role in the regulation of plant response to low temperatures. In this study, a novel DREB1/CBF transcription factor, PnDREB1, was isolated from Iceland poppy (Papaver nudicaule), a plant adaptive to low temperature environments. It is homologous to the known DREB1s of Arabidopsis and other plant species. It also shares similar 3D structure, and conserved and functionally important motifs with DREB1s of Arabidopsis. The phylogenetic analysis indicated that the AP2 domain of PnDREB1 is similar to those of Glycine max, Medicago truncatula, and M. sativa. PnDREB1 is constitutively expressed in diverse tissues and is increased in roots. qPCR analyses indicated that PnDREB1 is significantly induced by freezing treatment as well as by abscissic acid. The expression levels induced by freezing treatment were higher in the variety with higher degree of freezing tolerance. These results suggested that PnDREB1 is a novel and functional DREB1 transcription factor involved in freezing response and possibly in other abiotic stresses. Furthermore, the freezing-induction could be suppressed by exogenous gibberellins acid, indicating that PnDREB1 might play some role in the GA signaling transduction pathway. This study provides a basis for better understanding the roles of DREB1 in adaption of Iceland poppy to low temperatures. PMID:27459263

  11. The effect of overexpression of two Brassica CBF/DREB1-like transcription factors on photosynthetic capacity and freezing tolerance in Brassica napus.

    PubMed

    Savitch, Leonid V; Allard, Ghislaine; Seki, Motoaki; Robert, Laurian S; Tinker, Nicholas A; Huner, Norman P A; Shinozaki, Kazuo; Singh, Jas

    2005-09-01

    The effects of overexpression of two Brassica CBF/DREB1-like transcription factors (BNCBF5 and 17) in Brassica napus cv. Westar were studied. In addition to developing constitutive freezing tolerance and constitutively accumulating COR gene mRNAs, BNCBF5- and 17-overexpressing plants also accumulate moderate transcript levels of genes involved in photosynthesis and chloroplast development as identified by microarray and Northern analyses. These include GLK1- and GLK2-like transcription factors involved in chloroplast photosynthetic development, chloroplast stroma cyclophilin ROC4 (AtCYP20-3), beta-amylase and triose-P/Pi translocator. In parallel with these changes, increases in photosynthetic efficiency and capacity, pigment pool sizes, increased capacities of the Calvin cycle enzymes, and enzymes of starch and sucrose biosynthesis, as well as glycolysis and oxaloacetate/malate exchange are seen, suggesting that BNCBF overexpression has partially mimicked cold-induced photosynthetic acclimation constitutively. Taken together, these results suggest that BNCBF/DREB1 overexpression in Brassica not only resulted in increased constitutive freezing tolerance but also partially regulated chloroplast development to increase photochemical efficiency and photosynthetic capacity. PMID:16024910

  12. Core binding factor acute myeloid leukaemia and c-KIT mutations.

    PubMed

    Riera, Ludovica; Marmont, Filippo; Toppino, Daniela; Frairia, Chiara; Sismondi, Francesca; Audisio, Ernesta; Di Bello, Cristiana; D'Ardia, Stefano; Di Celle, Paola Francia; Messa, Emanuela; Inghirami, Giorgio; Vitolo, Umberto; Pich, Achille

    2013-05-01

    Core binding factor (CBF) acute myeloid leukaemia (AML) represents 5-8% of all AMLs and has a relatively favourable prognosis. However, activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. To verify the incidence and prognostic value of c-KIT mutations in CBF AML, we retrospectively analysed bone marrow samples of 23 consecutive adult patients with de novo CBF AML [14 inv(16) and 9 t(8;21)] treated at a single institution from 2000 to 2011. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide; 13 underwent allogeneic stem cell transplantation. c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. c-KIT mutations (3 in exon 10 and 4 in exon 17) were detected in 7/23 (30.4%) patients, 3 with t(8;21) and 4 with inv(16). No difference in c-KIT mutation status was observed between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association between gender, age, white blood cell and platelet count, peripheral blood and bone marrow blast cells at diagnosis, achievement of complete remission, cytogenetic risk groups and Wilms tumour gene 1 (WT1) levels was found. On the contrary, lactate dehydrogenase (LDH) values were higher in mutated than in non-mutated patients (p=0.01). Overall survival (OS) rates were longer in CBF compared to the other types of AML and disease-free survival (DFS) was longer in inv(16) than in t(8;21) AML. OS and DFS were similar in mutated and non-mutated CBF AML patients. Our results confirm a better prognosis for CBF AML than all other AML categories, and for inv(16) than t(8;21) AML. However, no prognostic value for c-KIT mutational status was found in our series. The association between LDH levels and c-KIT mutation would indicate a more active proliferation for mutated CBF AML. PMID:23467883

  13. CBF gene expression in peach leaf and bark tissues is gated by a circadian clock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CBF transcription factors are part of the AP2/ERF domain family of DNA-binding proteins that recognize a C-repeat response cis-acting element that regulates a number of cold-responsive genes (CBF-regulon). In peach (Prunus persica), five CBF genes are situated in tandem on scaffold (Linkage Group) ...

  14. An essential yeast protein, CBF5p, binds in vitro to centromeres and microtubules.

    PubMed Central

    Jiang, W; Middleton, K; Yoon, H J; Fouquet, C; Carbon, J

    1993-01-01

    Yeast centromere DNA (CEN) affinity column chromatography has been used to purify several putative centromere and kinetochore proteins from yeast chromatin extracts. The single yeast gene (CBF5) specifying one of the major low-affinity centromere-binding proteins (p64'/CBF5p) has been cloned and shown to be essential for viability of Saccharomyces cerevisiae. CBF5 specifies a 55-kDa highly charged protein that contains a repeating KKD/E sequence domain near the C terminus, similar to known microtubule-binding domains in microtubule-associated proteins 1A and 1B, CBF5p, obtained by overexpression in bacterial cells, binds microtubules in vitro, whereas C-terminal deleted proteins lacking the (KKD/E)n domain do not. Dividing yeast cells containing a C-terminal truncated CBF5 gene, producing CBF5p containing only three copies of the KKD/E repeat, delay with replicated genomes at the G2/M phase of the cell cycle, while depletion of CBF5p arrests most cells in G1/S. Overproduction of CBF5p in S. cerevisiae complements a temperature sensitivity mutation in the gene (CBF2) specifying the 110-kDa subunit of the high-affinity CEN DNA-binding factor CBF3, suggesting in vivo interaction of CBF5p and CBF3. A second low-affinity centromere-binding factor has been identified as topoisomerase II. Images PMID:8336724

  15. CBF-dependent signaling pathway: a key responder to low temperature stress in plants.

    PubMed

    Zhou, M Q; Shen, C; Wu, L H; Tang, K X; Lin, J

    2011-06-01

    Plants under low temperature (LT) stress exhibit a C-repeat binding factor (CBF)-dependent responsive pathway. The transcription factors in the CBF family, existing in multiple plant species, are the key regulators of the cold-responsive (COR) genes. CBF1 and CBF3 are regulated in a different way from CBF2, and CBF4 is the only known CBF gene definitely involved in abscisic acid (ABA)-dependent signaling pathways. RAP2.1 and RAP2.6 are the downstream regulators under CBFs. The upstream regulators of the CBF named inducer of CBF expression (ICE) acts as a positive regulator of CBFs. Meanwhile, these CBF signaling pathway components could associate with many other transcription activators and repressors in regulating gene expression when plants are under LT stress. HOS1 negatively regulates ICE1, which down regulates MYB15, an upstream repressor of CBFs. ZAT12 participates in the repression of CBFs, while ZAT10 and FRY2 negatively regulate the CBF-target genes. ADF5 was recently also found to repress CBFs. LOS2 works against ZAT10, and LOS4 positively regulates CBFs. SFR6 is involved in the modification of CBFs to activate the COR genes, and SIZ1-dependent sumoylation plays a positive role in the regulation of ICE1. The utilization of CBF-dependent signaling components has a broad perspective in the field of plant breeding for enhancing crop LT tolerance. PMID:20919819

  16. An apple rootstock overexpressing a peach CBF gene alters growth and flowering in the scion but does not impact cold hardiness or dormancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The C-repeat Binding Factor (CBF) transcription factor is involved in responses to low temperature and water deficit in many plant species. Overexpression of CBF genes leads to enhanced freezing tolerance and growth inhibition in many species. The overexpression of a peach CBF (PpCBF1) gene in a t...

  17. Copy number variation at the HvCBF4-HvCBF2 genomic segment is a major component of frost resistance in barley.

    PubMed

    Francia, Enrico; Morcia, Caterina; Pasquariello, Marianna; Mazzamurro, Valentina; Milc, Justyna Anna; Rizza, Fulvia; Terzi, Valeria; Pecchioni, Nicola

    2016-09-01

    A family of CBF transcription factors plays a major role in reconfiguring the plant transcriptome in response to low-freezing temperature in temperate cereals. In barley, more than 13 HvCBF genes map coincident with the major QTL FR-H2 suggesting them as candidates to explain the function of the locus. Variation in copy number (CNV) of specific HvCBFs was assayed in a panel of 41 barley genotypes using RT-qPCR. Taking advantage of an accurate phenotyping that combined Fv/Fm and field survival, resistance-associated variants within FR-H2 were identified. Genotypes with an increased copy number of HvCBF4 and HvCBF2 (at least ten and eight copies, respectively) showed greater frost resistance. A CAPS marker able to distinguish the CBF2A, CBF2B and CBF2A/B forms was developed and showed that all the higher-ranking genotypes in term of resistance harbour only CBF2A, while other resistant winter genotypes harbour also CBF2B, although at a lower CNV. In addition to the major involvement of the HvCBF4-HvCBF2 genomic segment in the proximal cluster of CBF elements, a negative role of HvCBF3 in the distal cluster was identified. Multiple linear regression models taking into account allelic variation at FR-H1/VRN-H1 explained 0.434 and 0.550 (both at p < 0.001) of the phenotypic variation for Fv/Fm and field survival respectively, while no interaction effect between CNV at the HvCBFs and FR-H1/VRN-H1 was found. Altogether our data suggest a major involvement of the CBF genes located in the proximal cluster, with no apparent involvement of the central cluster contrary to what was reported for wheat. PMID:27338258

  18. [Etiological factors of acute pancreatitis].

    PubMed

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  19. Prognostic Significance of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Hongxiang; Chen, Li; Sun, Yi; Chen, Zhichao; Li, Qiubai

    2016-01-01

    The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20–1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31–2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97–1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52–1.74), relapse risk (RR, 1.12; 95% CI, 0.90–1.41) or OS (RR, 1.03; 95% CI, 0.90–1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02–4.05), relapse risk (RR, 1.89; 95%CI: 1.51–2.37) and OS (RR, 2.26; 95%CI: 1.35–3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19–1.95) or OS (RR, 1.12; 95%CI: 0.90–1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings. PMID:26771376

  20. Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

    PubMed

    Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

    2015-07-01

    Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. PMID:26025521

  1. Complementary regulation of four Eucalyptus CBF genes under various cold conditions

    PubMed Central

    Navarro, M.; Marque, G.; Ayax, C.; Keller, G.; Borges, J. P.; Marque, C.; Teulières, C.

    2009-01-01

    CBF transcription factors play central roles in the control of freezing tolerance in plants. The isolation of two additional CBF genes, EguCBF1c and EguCBF1d, from E. gunnii, one of the cold-hardiest Eucalyptus species, is described. While the EguCBF1D protein sequence is very similar to the previously characterized EguCBF1A and EguCBF1B sequences, EguCBF1C is more distinctive, in particular in the AP2-DBD (AP2-DNA binding domain). The expression analysis of the four genes by RT-qPCR reveals that none of them is specific to one stress but they are all preferentially induced by cold, except for the EguCBF1c gene which is more responsive to salt. The calculation of the transcript copy number enables the quantification of constitutive CBF gene expression. This basal level, significant for the four genes, greatly influences the final EguCBF1 transcript level in the cold. A cold shock at 4 °C, as well as a progressive freezing which mimics a natural frost episode, trigger a fast and strong response of the EguCBF1 genes, while growth at acclimating temperatures results in a lower but more durable induction. The differential expression of the four EguCBF1 genes under these cold regimes suggests that there is a complementary regulation. The high accumulation of the CBF transcript, observed in response to the different types of cold conditions, might be a key for the winter survival of this evergreen broad-leaved tree. PMID:19457981

  2. Banana fruit NAC transcription factor MaNAC1 is a direct target of MaICE1 and involved in cold stress through interacting with MaCBF1.

    PubMed

    Shan, Wei; Kuang, Jian-Fei; Lu, Wang-Jin; Chen, Jian-Ye

    2014-09-01

    Our previous studies have indicated that the banana ripening-induced MaNAC1, a NAC (NAM, ATAF1/2 and CUC2) transcription factor (TF) gene, is regulated by ethylene during fruit ripening, and propylene, a functional ethylene analogue, induces cold tolerance of banana fruits. However, the involvement of MaNAC1 in propylene-induced cold tolerance of banana fruits is not understood. In the present work, the possible involvement of MaNAC1 in cold tolerance of banana fruits was investigated. MaNAC1 was noticeably induced by cold stress or following propylene treatment during cold storage. Transient protoplast assays showed that MaNAC1 promoter was activated by cold stress and ethylene treatment. Yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA) and transient expression assays demonstrated MaNAC1 as a novel direct target of MaICE1, and that the ability of MaICE1 binding to MaNAC1 promoter might be enhanced by MaICE1 phosphorylation and cold stress. Moreover, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses revealed physical interaction between MaNAC1 and MaCBF1, a downstream component of inducer of C-repeat binding factor (CBF) expression 1 (ICE1) in cold signalling. Taken together, these results suggest that the cold-responsive MaNAC1 may be involved in cold tolerance of banana fruits through its interaction with ICE1-CBF cold signalling pathway, providing new insights into the regulatory activity of NAC TF. PMID:24548087

  3. Cbf11 and Cbf12, the fission yeast CSL proteins, play opposing roles in cell adhesion and coordination of cell and nuclear division

    SciTech Connect

    Prevorovsky, Martin; Grousl, Tomas; Stanurova, Jana; Rynes, Jan; Nellen, Wolfgang; Puta, Frantisek; Folk, Petr

    2009-05-01

    The CSL (CBF1/RBP-J{kappa}/Suppressor of Hairless/LAG-1) family is comprised of transcription factors essential for metazoan development, mostly due to their involvement in the Notch receptor signaling pathway. Recently, we identified two novel classes of CSL genes in the genomes of several fungal species, organisms lacking the Notch pathway. In this study, we characterized experimentally cbf11{sup +} and cbf12{sup +}, the two CSL genes of Schizosaccharomyces pombe, in order to elucidate the CSL function in fungi. We provide evidence supporting their identity as genuine CSL genes. Both cbf11{sup +} and cbf12{sup +} are non-essential; they have distinct expression profiles and code for nuclear proteins with transcription activation potential. Significantly, we demonstrated that Cbf11 recognizes specifically the canonical CSL response element GTG{sup A}/{sub G}GAA in vitro. The deletion of cbf11{sup +} is associated with growth phenotypes and altered colony morphology. Furthermore, we found that Cbf11 and Cbf12 play opposite roles in cell adhesion, nuclear and cell division and their coordination. Disturbed balance of the two CSL proteins leads to cell separation defects (sep phenotype), cut phenotype, and high-frequency diploidization in heterothallic strains. Our data show that CSL proteins operate in an organism predating the Notch pathway, which should be of relevance to the understanding of (Notch-independent) CSL functions in metazoans.

  4. Assessment of cerebral blood flow autoregulation (CBF AR) with rheoencephalography (REG): studies in animals

    NASA Astrophysics Data System (ADS)

    Popovic, Djordje; Bodo, Michael; Pearce, Frederick; van Albert, Stephen; Garcia, Alison; Settle, Tim; Armonda, Rocco

    2013-04-01

    The ability of cerebral vasculature to regulate cerebral blood flow (CBF) in the face of changes in arterial blood pressure (SAP) or intracranial pressure (ICP) is an important guard against secondary ischemia in acute brain injuries, and official guidelines recommend that therapeutic decisions be guided by continuous monitoring of CBF autoregulation (AR). The common method for CBF AR monitoring, which rests on real-time derivation of the correlation coefficient (PRx) between slow oscillations in SAP and ICP is, however, rarely used in clinical practice because it requires invasive ICP measurements. This study investigated whether the correlation coefficient between SAP and the pulsatile component of the non-invasive transcranial bioimpedance signal (rheoencephalography, REG) could be used to assess the state and lower limit of CBF AR. The results from pigs and rhesus macaques affirm the utility of REG; however, additional animal and clinical studies are warranted to assess selectivity of automatic REG-based evaluation of CBF AR.

  5. The unified ICE-CBF pathway provides a transcriptional feedback control of freezing tolerance during cold acclimation in Arabidopsis.

    PubMed

    Kim, Ye Seul; Lee, Minyoung; Lee, Jae-Hyung; Lee, Hyo-Jun; Park, Chung-Mo

    2015-09-01

    During cold acclimation, C-repeat binding factors (CBFs) activate downstream targets, such as cold-regulated genes, leading to the acquisition of freezing tolerance in plants. Inducer of CBF expression 1 (ICE1) plays a key role by activating CBF3 expression in shaping the cold-induced transcriptome. While the ICE1-CBF3 regulon constitutes a major cold acclimation pathway, gene regulatory networks governing the CBF signaling are poorly understood. Here, we demonstrated that ICE1 and its paralog ICE2 induce CBF1, CBF2, and CBF3 by binding to the gene promoters. ICE2, like ICE1, was ubiquitinated by the high expression of osmotically responsive gene 1 (HOS1) E3 ubiquitin ligase. Whereas ICE2-defective ice2-2 mutant did not exhibit any discernible freezing-sensitive phenotypes, ice1-2 ice2-2/+ plant, which is defective in ICE1 and has a heterozygotic ice2 mutation, exhibited significantly reduced freezing tolerance. Accordingly, all three CBF genes were markedly down-regulated in the ice1-2 ice2-2/+ plant, indicating that ICE1 and ICE2 are functionally redundant with different implementations in inducing CBF genes. Together with the negative regulation of CBF3 by CBF2, we propose that the unified ICE-CBF pathway provides a transcriptional feedback of freezing tolerance to sustain plant development and survival during cold acclimation. PMID:26311645

  6. [Acute heart failure: precipitating factors and prevention].

    PubMed

    Aramburu Bodas, Oscar; Conde Martel, Alicia; Salamanca Bautista, Prado

    2014-03-01

    Acute heart failure episodes, whether onset or decompensation of a chronic form, are most often precipitated by a concurrent process or disease, described as precipitating factors of heart failure. In this article, we review these precipitating factors, their proportions and clinical relevance in general and in subgroups of patients, their relationship with prognosis, and their possible prevention. PMID:24930077

  7. Sequence analysis of three CBF-like genes from apple (Malus x domestica)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The CBF/DREB family of transcription factors has been demonstrated to have an integral role in the response of plants to low temperatures and water deficit, binding to a cis-acting regulatory element called the C-repeat/dehydration response element (CRT/ DRE) in genes induced by those stresses. CBF...

  8. Adaptation to warmer climates by parallel functional evolution of CBF genes in Arabidopsis thaliana.

    PubMed

    Monroe, J Grey; McGovern, Cullen; Lasky, Jesse R; Grogan, Kelsi; Beck, James; McKay, John K

    2016-08-01

    The evolutionary processes and genetics underlying local adaptation at a specieswide level are largely unknown. Recent work has indicated that a frameshift mutation in a member of a family of transcription factors, C-repeat binding factors or CBFs, underlies local adaptation and freezing tolerance divergence between two European populations of Arabidopsis thaliana. To ask whether the specieswide evolution of CBF genes in Arabidopsis is consistent with local adaptation, we surveyed CBF variation from 477 wild accessions collected across the species' range. We found that CBF sequence variation is strongly associated with winter temperature variables. Looking specifically at the minimum temperature experienced during the coldest month, we found that Arabidopsis from warmer climates exhibit a significant excess of nonsynonymous polymorphisms in CBF genes and revealed a CBF haplotype network whose structure points to multiple independent transitions to warmer climates. We also identified a number of newly described mutations of significant functional effect in CBF genes, similar to the frameshift mutation previously indicated to be locally adaptive in Italy, and find that they are significantly associated with warm winters. Lastly, we uncover relationships between climate and the position of significant functional effect mutations between and within CBF paralogs, suggesting variation in adaptive function of different mutations. Cumulatively, these findings support the hypothesis that disruption of CBF gene function is adaptive in warmer climates, and illustrate how parallel evolution in a transcription factor can underlie adaptation to climate. PMID:27247130

  9. RNA-seq analysis of oil palm under cold stress reveals a different C-repeat binding factor (CBF) mediated gene expression pattern in Elaeis guineensis compared to other species.

    PubMed

    Lei, Xintao; Xiao, Yong; Xia, Wei; Mason, Annaliese S; Yang, Yaodong; Ma, Zilong; Peng, Ming

    2014-01-01

    Elaeis guineensis as a tropical oil-crop is particularly sensitive to low temperature. Improvement of cold-tolerance may significantly increase the total cultivation area of this tropical oil-crop worldwide. We sequenced cold-treated and control (untreated) samples of Elaeis guineensis. De novo assembly generated 51,452 unigenes with an average length of 703 bp. Subsequently, these expressed sequences were functionally annotated. In the K category (transcription factors) of COG (Cluster of Orthologous Group) annotation, the largest proportion of genes induced and repressed at least two-fold under cold stress were from the AP2/ERE family, indicating that C-repeat binding factor, (CBFs, members of the AP2/ERE family) may play a central role in cold tolerance in Elaeis guineensis. Subsequently, the CBF-mediated signal transduction pathway was reconstructed based on transcriptome data and the gene expression profile involving the pathway was examined using real-time quantitative RT-PCR (qRT-PCR). CBFs reached maximum transcript level both at medium (4 h) and long period time points (7 days), contrary to the expression pattern of CBFs in Arabidopsis and rice. Moreover, the promoters of downstream Cold Responsive gene (CORs) regulated by CBFs were analyzed. Conservation, mutation and absence of the DRE core motif were detected in the promoters of six CORs. These mutations in DRE motifs suggest that CORs may not be induced via cold stress in Elaeis guineensis. PMID:25479236

  10. RNA-Seq Analysis of Oil Palm under Cold Stress Reveals a Different C-Repeat Binding Factor (CBF) Mediated Gene Expression Pattern in Elaeis guineensis Compared to Other Species

    PubMed Central

    Xia, Wei; Mason, Annaliese S.; Yang, Yaodong; Ma, Zilong; Peng, Ming

    2014-01-01

    Elaeis guineensis as a tropical oil-crop is particularly sensitive to low temperature. Improvement of cold-tolerance may significantly increase the total cultivation area of this tropical oil-crop worldwide. We sequenced cold-treated and control (untreated) samples of Elaeis guineensis. De novo assembly generated 51,452 unigenes with an average length of 703 bp. Subsequently, these expressed sequences were functionally annotated. In the K category (transcription factors) of COG (Cluster of Orthologous Group) annotation, the largest proportion of genes induced and repressed at least two-fold under cold stress were from the AP2/ERE family, indicating that C-repeat binding factor, (CBFs, members of the AP2/ERE family) may play a central role in cold tolerance in Elaeis guineensis. Subsequently, the CBF-mediated signal transduction pathway was reconstructed based on transcriptome data and the gene expression profile involving the pathway was examined using real-time quantitative RT-PCR (qRT-PCR). CBFs reached maximum transcript level both at medium (4 h) and long period time points (7 days), contrary to the expression pattern of CBFs in Arabidopsis and rice. Moreover, the promoters of downstream Cold Responsive gene (CORs) regulated by CBFs were analyzed. Conservation, mutation and absence of the DRE core motif were detected in the promoters of six CORs. These mutations in DRE motifs suggest that CORs may not be induced via cold stress in Elaeis guineensis. PMID:25479236

  11. Factoring in Factor VIII With Acute Ischemic Stroke

    PubMed Central

    Siegler, James E.; Samai, Alyana; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl

    2016-01-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. PMID:25669199

  12. The Box H/ACA snoRNP assembly factor Shq1p is a chaperone protein homologous to Hsp90 co-chaperones that binds to the Cbf5p enzyme

    PubMed Central

    Godin, Katherine S.; Walbott, Hélène; Leulliot, Nicolas; van Tilbeurgh, Herman; Varani, Gabriele

    2009-01-01

    Box H/ACA small nucleolar ribonucleoproteins (snoRNPs) are responsible for the formation of pseudouridine in a variety of RNAs, and are essential for ribosome biogenesis, modification of spliceosomal RNAs and telomerase stability. The mature snoRNP has been reconstituted in vitro and is composed of a single RNA and four proteins. However, snoRNP biogenesis in vivo requires multiple factors to coordinate a complex and poorly understood assembly and maturation process. Among the factors required for snoRNP biogenesis in yeast is Shq1p, an essential protein necessary for the snoRNA stable expression. We have found that Shq1p consists of two independent domains that contain Casein Kinase 1 phosphorylation sites. We also demonstrate that Shq1p binds the pseudourydilating enzyme Cbf5p through the C-terminal domain in synergy with the N-terminal domain. The NMR solution structure of the N-terminal domain has striking homology to the ‘Chord and Sgt1’ (CS) domain of known Hsp90 co-chaperones, yet Shq1p does not interact with the yeast Hsp90 homologue in vitro. Surprisingly, Shq1p has stand-alone chaperone activity in vitro. This activity is harbored by the C-terminal domain but it is increased by the presence of the N-terminal domain. These results provide the first evidence of a specific biochemical activity for Shq1p and a direct link to the H/ACA snoRNP. PMID:19426738

  13. The Box H/ACA snoRNP Assembly Factor Shq1p is a Chaperone Protein Homologous to Hsp90 Cochaperones that Binds to the Cbf5p Enzyme

    SciTech Connect

    Godin, Katherine S.; Walbott, Helene; Leulliot, Nicolas; van Tilbeurgh, Herman; Varani, Gabriele

    2009-05-06

    Box H/ACA small nucleolar (sno) ribonucleoproteins (RNPs) are responsible for the formation of pseudouridine in a variety of RNAs and are essential for ribosome biogenesis, modification of spliceosomal RNAs, and telomerase stability. A mature snoRNP has been reconstituted in vitro and is composed of a single RNA and four proteins. However, snoRNP biogenesis in vivo requires multiple factors to coordinate a complex and poorly understood assembly and maturation process. Among the factors required for snoRNP biogenesis in yeast is Shq1p, an essential protein necessary for stable expression of box H/ACA snoRNAs. We have found that Shq1p consists of two independent domains that contain casein kinase 1 phosphorylation sites. We also demonstrate that Shq1p binds the pseudourydilating enzyme Cbf5p through the C-terminal domain, in synergy with the N-terminal domain. The NMR solution structure of the N-terminal domain has striking homology to the ‘Chord and Sgt1’ domain of known Hsp90 cochaperones, yet Shq1p does not interact with the yeast Hsp90 homologue in vitro. Surprisingly, Shq1p has stand-alone chaperone activity in vitro. This activity is harbored by the C-terminal domain, but it is increased by the presence of the N-terminal domain. These results provide the first evidence of a specific biochemical activity for Shq1p and a direct link to the H/ACA snoRNP.

  14. The CBF1-dependent low temperature signalling pathway, regulon and increase in freeze tolerance are conserved in Populus spp.

    PubMed

    Benedict, Catherine; Skinner, Jeffrey S; Meng, Rengong; Chang, Yongjian; Bhalerao, Rishikesh; Huner, Norman P A; Finn, Chad E; Chen, Tony H H; Hurry, Vaughan

    2006-07-01

    The meristematic tissues of temperate woody perennials must acclimate to freezing temperatures to survive the winter and resume growth the following year. To determine whether the C-repeat binding factor (CBF) family of transcription factors contributing to this process in annual herbaceous species also functions in woody perennials, we investigated the changes in phenotype and transcript profile of transgenic Populus constitutively expressing CBF1 from Arabidopsis (AtCBF1). Ectopic expression of AtCBF1 was sufficient to significantly increase the freezing tolerance of non-acclimated leaves and stems relative to wild-type plants. cDNA microarray experiments identified genes up-regulated by ectopic AtCBF1 expression in Populus, demonstrated a strong conservation of the CBF regulon between Populus and Arabidopsis and identified differences between leaf and stem regulons. We studied the induction kinetics and tissue specificity of four CBF paralogues identified from the Populus balsamifera subsp. trichocarpa genome sequence (PtCBFs). All four PtCBFs are cold-inducible in leaves, but only PtCBF1 and PtCBF3 show significant induction in stems. Our results suggest that the central role played by the CBF family of transcriptional activators in cold acclimation of Arabidopsis has been maintained in Populus. However, the differential expression of the PtCBFs and differing clusters of CBF-responsive genes in annual (leaf) and perennial (stem) tissues suggest that the perennial-driven evolution of winter dormancy may have given rise to specific roles for these 'master-switches' in the different annual and perennial tissues of woody species. PMID:17080948

  15. Perinatal risk factors for acute myeloid leukemia.

    PubMed

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2015-12-01

    Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June-August), incidence rate ratios for AML were 1.72 (95 % CI 1.25-2.38; P = 0.001) for winter (December-February), 1.37 (95 % CI 0.99-1.90; P = 0.06) for spring (March-May), and 1.27 (95 % CI 0.90-1.80; P = 0.17) for fall (September-November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML. PMID:26113060

  16. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial

    PubMed Central

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline; Guièze, Romain; Himberlin, Chantal; Randriamalala, Edouard; Preudhomme, Claude; Jourdan, Eric; Dombret, Hervé; Ifrah, Norbert

    2015-01-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18–60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12). PMID:25715404

  17. RDM4 modulates cold stress resistance in Arabidopsis partially through the CBF-mediated pathway.

    PubMed

    Chan, Zhulong; Wang, Yanping; Cao, Minjie; Gong, Yuehua; Mu, Zixin; Wang, Haiqing; Hu, Yuanlei; Deng, Xin; He, Xin-Jian; Zhu, Jian-Kang

    2016-03-01

    The C-REPEAT-BINDING FACTOR (CBF) pathway has important roles in plant responses to cold stress. How the CBF genes themselves are activated after cold acclimation remains poorly understood. In this study, we characterized cold tolerance of null mutant of RNA-DIRECTED DNA METHYLATION 4 (RDM4), which encodes a protein that associates with RNA polymerases Pol V and Pol II, and is required for RNA-directed DNA methylation (RdDM) in Arabidopsis. The results showed that dysfunction of RDM4 reduced cold tolerance, as evidenced by decreased survival and increased electrolyte leakage. Mutation of RDM4 resulted in extensive transcriptomic reprogramming. CBFs and CBF regulon genes were down-regulated in rdm4 but not nrpe1 (the largest subunit of PolV) mutants, suggesting that the role of RDM4 in cold stress responses is independent of the RdDM pathway. Overexpression of RDM4 constitutively increased the expression of CBFs and regulon genes and decreased cold-induced membrane injury. A great proportion of genes affected by rdm4 overlapped with those affected by CBFs. Chromatin immunoprecipitation results suggested that RDM4 is important for Pol II occupancy at the promoters of CBF2 and CBF3. We present evidence of a considerable role for RDM4 in regulating gene expression at low temperature, including the CBF pathway in Arabidopsis. PMID:26522658

  18. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePlus

    ... lymphocytic leukemia? What are the risk factors for acute lymphocytic leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  19. Oil palm EgCBF3 conferred stress tolerance in transgenic tomato plants through modulation of the ethylene signaling pathway.

    PubMed

    Ebrahimi, Mortaza; Abdullah, Siti Nor Akmar; Abdul Aziz, Maheran; Namasivayam, Parameswari

    2016-09-01

    CBF/DREB1 is a group of transcription factors that are mainly involved in abiotic stress tolerance in plants. They belong to the AP2/ERF superfamily of plant-specific transcription factors. A gene encoding a new member of this group was isolated from ripening oil palm fruit and designated as EgCBF3. The oil palm fruit demonstrates the characteristics of a climacteric fruit like tomato, in which ethylene has a major impact on the ripening process. A transgenic approach was used for functional characterization of the EgCBF3, using tomato as the model plant. The effects of ectopic expression of EgCBF3 were analyzed based on expression profiling of the ethylene biosynthesis-related genes, anti-freeze proteins (AFPs), abiotic stress tolerance and plant growth and development. The EgCBF3 tomatoes demonstrated altered phenotypes compared to the wild type tomatoes. Delayed leaf senescence and flowering, increased chlorophyll content and abnormal flowering were the consequences of overexpression of EgCBF3 in the transgenic tomatoes. The EgCBF3 tomatoes demonstrated enhanced abiotic stress tolerance under in vitro conditions. Further, transcript levels of ethylene biosynthesis-related genes, including three SlACSs and two SlACOs, were altered in the transgenic plants' leaves and roots compared to that in the wild type tomato plant. Among the eight AFPs studied in the wounded leaves of the EgCBF3 tomato plants, transcript levels of SlOSM-L, SlNP24, SlPR5L and SlTSRF1 decreased, while expression of the other four, SlCHI3, SlPR1, SlPR-P2 and SlLAP2, were up-regulated. These findings indicate the possible functions of EgCBF3 in plant growth and development as a regulator of ethylene biosynthesis-related and AFP genes, and as a stimulator of abiotic stress tolerance. PMID:27513726

  20. The Indeterminate Domain Protein ROC1 Regulates Chilling Tolerance via Activation of DREB1B/CBF1 in Rice

    PubMed Central

    Dou, Mingzhu; Cheng, Shuai; Zhao, Baotian; Xuan, Yuanhu; Shao, Minglong

    2016-01-01

    Abiotic stress, including salinity, drought and cold, severely affect diverse aspects of plant development and production. Rice is an important crop that does not acclimate to cold; therefore, it is relatively sensitive to low temperature stress. Dehydration-responsive element-binding protein 1s (DREB1s)/C-repeat binding factors (CBFs) are well known for their function in cold tolerance, but the transcriptional regulation of CBFs remains elusive, especially in rice. Here, we performed a yeast one-hybrid assay using the promoter of CBF1, a cold-induced gene, to isolate transcriptional regulators of CBF1. Among the seven candidates identified, an indeterminate domain (IDD) protein named ROC1 (a regulator of CBF1) was further analyzed. The ROC1 transcript was induced by exogenously-treated auxin, while it was not altered by cold or ABA stimuli. ROC1-GFP was localized at the nucleus, and ROC1 showed trans-activation activity in yeast. The electrophoretic mobility shift assay (EMSA) and ChIP analyses revealed that ROC1 directly bound to the promoter of CBF1. Furthermore, ROC1 mutants exhibited chilling-sensitive symptoms and inhibited cold-mediated induction of CBF1 and CBF3, indicating that ROC1 is a positive regulator of cold stress responses. Taken together, this study identified the CBF1 regulator, and the results are important for rice plant adaptation to chilling stress. PMID:26927068

  1. The Indeterminate Domain Protein ROC1 Regulates Chilling Tolerance via Activation of DREB1B/CBF1 in Rice.

    PubMed

    Dou, Mingzhu; Cheng, Shuai; Zhao, Baotian; Xuan, Yuanhu; Shao, Minglong

    2016-01-01

    Abiotic stress, including salinity, drought and cold, severely affect diverse aspects of plant development and production. Rice is an important crop that does not acclimate to cold; therefore, it is relatively sensitive to low temperature stress. Dehydration-responsive element-binding protein 1s (DREB1s)/C-repeat binding factors (CBFs) are well known for their function in cold tolerance, but the transcriptional regulation of CBFs remains elusive, especially in rice. Here, we performed a yeast one-hybrid assay using the promoter of CBF1, a cold-induced gene, to isolate transcriptional regulators of CBF1. Among the seven candidates identified, an indeterminate domain (IDD) protein named ROC1 (a regulator of CBF1) was further analyzed. The ROC1 transcript was induced by exogenously-treated auxin, while it was not altered by cold or ABA stimuli. ROC1-GFP was localized at the nucleus, and ROC1 showed trans-activation activity in yeast. The electrophoretic mobility shift assay (EMSA) and ChIP analyses revealed that ROC1 directly bound to the promoter of CBF1. Furthermore, ROC1 mutants exhibited chilling-sensitive symptoms and inhibited cold-mediated induction of CBF1 and CBF3, indicating that ROC1 is a positive regulator of cold stress responses. Taken together, this study identified the CBF1 regulator, and the results are important for rice plant adaptation to chilling stress. PMID:26927068

  2. Trans-species polymorphism and allele-specific expression in the CBF gene family of wild tomatoes.

    PubMed

    Mboup, Mamadou; Fischer, Iris; Lainer, Hilde; Stephan, Wolfgang

    2012-12-01

    Abiotic stresses such as drought, extreme temperatures, and salinity have a strong impact on plant adaptation. They act as selective forces on plant physiology and morphology. These selective pressures leave characteristic footprints that can be detected at the DNA sequence level using population genetic tools. On the basis of a candidate gene approach, we investigated signatures of adaptation in two wild tomato species, Solanum peruvianum and S. chilense. These species are native to western South America and constitute a model system for studying adaptation, due to their ability to colonize diverse habitats and the available genetic resources. We have determined the selective forces acting on the C-repeat binding factor (CBF) gene family, which consists of three genes, and is known to be involved in tolerance to abiotic stresses, in particular in cold tolerance. We also analyzed the expression pattern of these genes after drought and cold stresses. We found that CBF3 evolves under very strong purifying selection, CBF2 is under balancing selection in some populations of both species (S. peruvianum/Quicacha and S. chilense/Nazca) maintaining a trans-species polymorphism, and CBF1 is a pseudogene. In contrast to previous studies of cultivated tomatoes showing that only CBF1 was cold induced, we found that all three CBF genes are cold induced in wild tomatoes. All three genes are also drought induced. CBF2 exhibits an allele-specific expression pattern associated with the trans-species polymorphism. PMID:22787283

  3. Prognostic factors in neonatal acute renal failure

    SciTech Connect

    Chevalier, R.L.; Campbell, F.; Brenbridge, A.N.

    1984-08-01

    Sixteen infants, 2 to 35 days of age, had acute renal failure, a diagnosis based on serum creatinine concentrations greater than 1.5 mg/dL for at least 24 hours. Eight infants were oliguric (urine flow less than 1.0 mL/kg/h) whereas the remainder were nonoliguric. To determine clinical parameters useful in prognosis, urine flow rate, duration of anuria, peak serum creatinine, urea (BUN) concentration, and nuclide uptake by scintigraphy were correlated with recovery. Nine infants had acute renal failure secondary to perinatal asphyxia, three had acute renal failure as a result of congenital cardiovascular disease, and four had major renal anomalies. Four oliguric patients died: three of renal failure and one of heart failure. All nonoliguric infants survived with mean follow-up serum creatinine concentration of 0.8 +/- 0.5 (SD) mg/dL whereas that of oliguric survivors was 0.6 +/- 0.3 mg/dL. Peak serum creatinine concentration did not differ between those patients who were dying and those recovering. All infants who were dying remained anuric at least four days and revealed no renal uptake of nuclide. Eleven survivors were anuric three days or less, and renal perfusion was detectable by scintigraphy in each case. However, the remaining survivor (with bilateral renal vein thrombosis) recovered after 15 days of anuria despite nonvisualization of kidneys by scintigraphy. In neonates with ischemic acute renal failure, lack of oliguria and the presence of identifiable renal uptake of nuclide suggest a favorable prognosis.

  4. Prognostic factors in neonatal acute renal failure.

    PubMed

    Chevalier, R L; Campbell, F; Brenbridge, A N

    1984-08-01

    Sixteen infants, 2 to 35 days of age, had acute renal failure, a diagnosis based on serum creatinine concentrations greater than 1.5 mg/dL for at least 24 hours. Eight infants were oliguric (urine flow less than 1.0 mL/kg/h) whereas the remainder were nonoliguric. To determine clinical parameters useful in prognosis, urine flow rate, duration of anuria, peak serum creatinine, urea (BUN) concentration, and nuclide uptake by scintigraphy were correlated with recovery. Nine infants had acute renal failure secondary to perinatal asphyxia, three had acute renal failure as a result of congenital cardiovascular disease, and four had major renal anomalies. Four oliguric patients died: three of renal failure and one of heart failure. All nonoliguric infants survived with mean follow-up serum creatinine concentration of 0.8 +/- 0.5 (SD) mg/dL whereas that of oliguric survivors was 0.6 +/- 0.3 mg/dL. Peak serum creatinine concentration did not differ between those patients who were dying and those recovering. All infants who were dying remained anuric at least four days and revealed no renal uptake of nuclide. Eleven survivors were anuric three days or less, and renal perfusion was detectable by scintigraphy in each case. However, the remaining survivor (with bilateral renal vein thrombosis) recovered after 15 days of anuria despite nonvisualization of kidneys by scintigraphy. In neonates with ischemic acute renal failure, lack of oliguria and the presence of identifiable renal uptake of nuclide suggest a favorable prognosis. PMID:6462825

  5. Sequence and expression analysis of three CBF-like genes from apple (Malus x domestica)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The CBF/DREB family of transcription factors has been demonstrated to play an integral role in the response of plants to low temperatures and water deficit, binding to a cis-acting regulatory element called the C-repeat/dehydration response element (CRT/DRE) in genes induced by those stresses. In t...

  6. JcCBF2 gene from Jatropha curcas improves freezing tolerance of Arabidopsis thaliana during the early stage of stress.

    PubMed

    Wang, Linghui; Gao, Jihai; Qin, Xiaobo; Shi, Xiaodong; Luo, Lin; Zhang, Guozhen; Yu, Hongwu; Li, Chenyang; Hu, Minchao; Liu, Qifan; Xu, Ying; Chen, Fang

    2015-05-01

    High chilling-susceptibility is becoming the bottleneck for cultivation and commercialization of Jatropha curcas L. For insights to chilling resistance ability of this plant species, a cold response transcription factor, JcCBF2, was cloned and studied. It codes a 26 kDa protein, which contains all conserved motifs unique to the C-repeat binding factor (CBF) family and has high similarity to CBFs of Ricinus communis and Populus. Its transcripts express specifically in leaves of Jatropha at cold temperature. After transmitting the report vector, 35S::JcCBF2-GFP, into Arabidopsis thaliana, JcCBF2 protein is main detected in cell nucleus, being consistent to the nuclear orientation signal in its N-terminal. Compared to the control Arabidopsis, the frozen leaves of JcCBF2-overexpressed seedlings grow stronger with less malondialdehyde, smaller leaf conductivity and activer superoxide dismutase, showing their higher freezing tolerance. RT-PCR tests revealed that JcCBF2 functioned mainly at the early stage (0-6 h) of resistance events in Arabidopsis, and its transcripts reduced after 6 h. In addition, JcCBF2 could quickly regulate transcripts of some cold-responsive (COR) genes such as RD29A, COR105A and COR6.6, also during the early stage of frozen treatment. This study not only proves the chilling resistance roles of JcCBF2, but also presents a candidate gene engineering for improvement of chilling tolerance in J. curcas. PMID:25433432

  7. Vif determines the requirement for CBF-β in APOBEC3 degradation

    PubMed Central

    Yoshikawa, Rokusuke; Takeuchi, Junko S.; Yamada, Eri; Nakano, Yusuke; Ren, Fengrong; Tanaka, Hiroshi; Münk, Carsten; Harris, Reuben S.; Miyazawa, Takayuki; Koyanagi, Yoshio

    2015-01-01

    APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3) proteins are cellular DNA deaminases that restrict a broad spectrum of lentiviruses. This process is counteracted by Vif (viral infectivity factor) of lentiviruses, which binds APOBEC3s and promotes their degradation. CBF-β (core binding factor subunit β) is an essential co-factor for the function of human immunodeficiency virus type 1 Vif to degrade human APOBEC3s. However, the requirement for CBF-β in Vif-mediated degradation of other mammalian APOBEC3 proteins is less clear. Here, we determined the sequence of feline CBFB and performed phylogenetic analyses. These analyses revealed that mammalian CBFB is under purifying selection. Moreover, we demonstrated that CBF-β is dispensable for feline immunodeficiency virus Vif-mediated degradation of APOBEC3s of its host. These findings suggested that primate lentiviruses have adapted to use CBF-β, an evolutionary stable protein, to counteract APOBEC3 proteins of their hosts after diverging from other lentiviruses. PMID:25516542

  8. 103. (Credit CBF) Adding sections to the standpipe at the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    103. (Credit CBF) Adding sections to the standpipe at the corner of Texas and Hope streets. Date of photo unknown. The standpipe, 20 feet in diameter by 110 feet high, was originally erected in 1887. (Credit CBF and Grabill, photographer, Shreveport, Louisiana) - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  9. Acute heart failure: Epidemiology, risk factors, and prevention.

    PubMed

    Farmakis, Dimitrios; Parissis, John; Lekakis, John; Filippatos, Gerasimos

    2015-03-01

    Acute heart failure represents the first cause of hospitalization in elderly persons and is the main determinant of the huge healthcare expenditure related to heart failure. Despite therapeutic advances, the prognosis of acute heart failure is poor, with in-hospital mortality ranging from 4% to 7%, 60- to 90-day mortality ranging from 7% to 11%, and 60- to 90-day rehospitalization from 25% to 30%. Several factors including cardiovascular and noncardiovascular conditions as well as patient-related and iatrogenic factors may precipitate the rapid development or deterioration of signs and symptoms of heart failure, thus leading to an acute heart failure episode that usually requires patient hospitalization. The primary prevention of acute heart failure mainly concerns the prevention, early diagnosis, and treatment of cardiovascular risk factors and heart disease, including coronary artery disease, while the secondary prevention of a new episode of decompensation requires the optimization of heart failure therapy, patient education, and the development of an effective transition and follow-up plan. PMID:25659507

  10. PpCBF3 from Cold-Tolerant Kentucky Bluegrass Involved in Freezing Tolerance Associated with Up-Regulation of Cold-Related Genes in Transgenic Arabidopsis thaliana

    PubMed Central

    Chen, Yu; Xu, Bin; Yang, Zhimin; Huang, Bingru

    2015-01-01

    Dehydration-Responsive Element Binding proteins (DREB)/C-repeat (CRT) Binding Factors (CBF) have been identified as transcriptional activators during plant responses to cold stress. The objective of this study was to determine the physiological roles of a CBF gene isolated from a cold-tolerant perennial grass species, Kentucky bluegrass (Poa pratensis L.), which designated as PpCBF3, in regulating plant tolerance to freezing stress. Transient transformation of Arabidopsis thaliana mesophyll protoplast with PpCBF3-eGFP fused protein showed that PpCBF3 was localized to the nucleus. RT-PCR analysis showed that PpCBF3 was specifically induced by cold stress (4°C) but not by drought stress [induced by 20% polyethylene glycol 6000 solution (PEG-6000)] or salt stress (150 mM NaCl). Transgenic Arabidopsis overexpressing PpCBF3 showed significant improvement in freezing (-20°C) tolerance demonstrated by a lower percentage of chlorotic leaves, lower cellular electrolyte leakage (EL) and H2O2 and O2.- content, and higher chlorophyll content and photochemical efficiency compared to the wild type. Relative mRNA expression level analysis by qRT-PCR indicated that the improved freezing tolerance of transgenic Arabidopsis plants overexpressing PpCBF3 was conferred by sustained activation of downstream cold responsive (COR) genes. Other interesting phenotypic changes in the PpCBF3-transgenic Arabidopsis plants included late flowering and slow growth or ‘dwarfism’, both of which are desirable phenotypic traits for perennial turfgrasses. Therefore, PpCBF3 has potential to be used in genetic engineering for improvement of turfgrass freezing tolerance and other desirable traits. PMID:26177510

  11. PpCBF3 from Cold-Tolerant Kentucky Bluegrass Involved in Freezing Tolerance Associated with Up-Regulation of Cold-Related Genes in Transgenic Arabidopsis thaliana.

    PubMed

    Zhuang, Lili; Yuan, Xiuyun; Chen, Yu; Xu, Bin; Yang, Zhimin; Huang, Bingru

    2015-01-01

    Dehydration-Responsive Element Binding proteins (DREB)/C-repeat (CRT) Binding Factors (CBF) have been identified as transcriptional activators during plant responses to cold stress. The objective of this study was to determine the physiological roles of a CBF gene isolated from a cold-tolerant perennial grass species, Kentucky bluegrass (Poa pratensis L.), which designated as PpCBF3, in regulating plant tolerance to freezing stress. Transient transformation of Arabidopsis thaliana mesophyll protoplast with PpCBF3-eGFP fused protein showed that PpCBF3 was localized to the nucleus. RT-PCR analysis showed that PpCBF3 was specifically induced by cold stress (4°C) but not by drought stress [induced by 20% polyethylene glycol 6000 solution (PEG-6000)] or salt stress (150 mM NaCl). Transgenic Arabidopsis overexpressing PpCBF3 showed significant improvement in freezing (-20°C) tolerance demonstrated by a lower percentage of chlorotic leaves, lower cellular electrolyte leakage (EL) and H2O2 and O2.- content, and higher chlorophyll content and photochemical efficiency compared to the wild type. Relative mRNA expression level analysis by qRT-PCR indicated that the improved freezing tolerance of transgenic Arabidopsis plants overexpressing PpCBF3 was conferred by sustained activation of downstream cold responsive (COR) genes. Other interesting phenotypic changes in the PpCBF3-transgenic Arabidopsis plants included late flowering and slow growth or 'dwarfism', both of which are desirable phenotypic traits for perennial turfgrasses. Therefore, PpCBF3 has potential to be used in genetic engineering for improvement of turfgrass freezing tolerance and other desirable traits. PMID:26177510

  12. Mouse models for core binding factor leukemia.

    PubMed

    Chin, D W L; Watanabe-Okochi, N; Wang, C Q; Tergaonkar, V; Osato, M

    2015-10-01

    RUNX1 and CBFB are among the most frequently mutated genes in human leukemias. Genetic alterations such as chromosomal translocations, copy number variations and point mutations have been widely reported to result in the malfunction of RUNX transcription factors. Leukemias arising from such alterations in RUNX family genes are collectively termed core binding factor (CBF) leukemias. Although adult CBF leukemias generally are considered a favorable risk group as compared with other forms of acute myeloid leukemia, the 5-year survival rate remains low. An improved understanding of the molecular mechanism for CBF leukemia is imperative to uncover novel treatment options. Over the years, retroviral transduction-transplantation assays and transgenic, knockin and knockout mouse models alone or in combination with mutagenesis have been used to study the roles of RUNX alterations in leukemogenesis. Although successful in inducing leukemia, the existing assays and models possess many inherent limitations. A CBF leukemia model which induces leukemia with complete penetrance and short latency would be ideal as a platform for drug discovery. Here, we summarize the currently available mouse models which have been utilized to study CBF leukemias, discuss the advantages and limitations of individual experimental systems, and propose suggestions for improvements of mouse models. PMID:26165235

  13. Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

    SciTech Connect

    Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion; E-mail: bkatz@tasmc.healt.gov.il

    2005-10-07

    Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RAR{alpha} and PLZF-RAR{alpha} fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RAR{alpha} from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

  14. Structure and functional analysis of wheat ICE (inducer of CBF expression) genes.

    PubMed

    Badawi, Mohamed; Reddy, Yedulla Venkat; Agharbaoui, Zahra; Tominaga, Yoko; Danyluk, Jean; Sarhan, Fathey; Houde, Mario

    2008-08-01

    Two different inducers of CBF expression (ICE1-like genes), TaICE41 and TaICE87, were isolated from a cDNA library prepared from cold-treated wheat aerial tissues. TaICE41 encodes a protein of 381 aa with a predicted MW of 39.5 kDa while TaICE87 encodes a protein of 443 aa with a predicted MW of 46.5 kDa. TaICE41 and TaICE87 share 46% identity while they share 50 and 47% identity with Arabidopsis AtICE1 respectively. Expression analysis revealed that mRNA accumulation was not altered by cold treatment suggesting that both genes are expressed constitutively. Gel mobility shift analysis showed that TaICE41 and TaICE87 bind to different MYC elements in the wheat TaCBFIVd-B9 promoter. Transient expression assays in Nicotiana benthamiana, showed that both TaICE proteins can activate TaCBFIVd-B9 transcription. The different affinities of TaICE41 and TaICE87 for MYC variants suggest that ICE binding specificity may be involved in the differential expression of wheat CBF genes. Furthermore, analysis of MYC elements demonstrates that a specific variant is present in the wheat CBF group IV that is associated with freezing tolerance. Overexpression of either TaICE41 or TaICE87 genes in Arabidopsis enhanced freezing tolerance only upon cold acclimation suggesting that other factors induced by low temperature are required for their activity. The increased freezing tolerance in transgenic Arabidopsis is associated with a higher expression of the cold responsive activators AtCBF2, AtCBF3, and of several cold-regulated genes. PMID:18635580

  15. The MYB96-HHP module integrates cold and abscisic acid signaling to activate the CBF-COR pathway in Arabidopsis.

    PubMed

    Lee, Hong Gil; Seo, Pil Joon

    2015-06-01

    Various environmental stresses limit plant growth, development, and reproductive success. Plants have therefore evolved sophisticated adaptive responses to deal with environmental challenges. The responses of plants to environmental stresses are mainly mediated by abscisic acid (ABA)-dependent and ABA-independent signaling pathways. While these two pathways have been implicated to play discrete roles in abiotic stress responses, accumulating evidence suggests that they are also intertwined. Here, we report that an R2R3-type MYB transcription factor, MYB96, integrates the ABA and cold signaling pathways. In addition to its role in ABA-mediated drought responses, MYB96 is also induced by cold stress in an ABA-independent manner and subsequently activates freezing tolerance. Notably, MYB96 regulates HEPTAHELICAL PROTEIN (HHP) genes by binding to their promoters. The HHP proteins, in turn, interact with C-REPEAT BINDING FACTOR (CBF) upstream regulators, such as INDUCER OF CBF EXPRESSION 1 (ICE1), ICE2, and CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR 3 (CAMTA3). The specific interactive networks of HHPs with the CBF upstream regulators are necessary to facilitate transcriptional activation of the CBF regulon under stressful conditions. Together, the MYB96-HHP module integrates ABA-dependent and ABA-independent signals and activates the CBF pathway, ensuring plant adaptation to a wide range of adverse environmental fluctuations. PMID:25912720

  16. 88. (Credit CBF) Twelve Mile Bayou Pumping Station and force ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    88. (Credit CBF) Twelve Mile Bayou Pumping Station and force main for pumping water over levee and into the canal (Blind Bayou), March 1913. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  17. 75. (Credit CBF) Settling basins and south elevation of pumping ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    75. (Credit CBF) Settling basins and south elevation of pumping station, March 1913. Two aerators are visible to the left. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  18. Growth factors in the management of adult acute leukemia.

    PubMed

    Bernstein, S H

    1993-02-01

    This review has explored the various ways that growth factors may be used in the management of adult acute leukemia. Growth factors have the potential to reduce the morbidity and mortality of both induction and postremission therapy by enhancing hematopoietic recovery or, when used as an adjunct to standard antimicrobial therapy, reducing the infectious complications of chemotherapy. In addition, they may have favorable effects on the biology of leukemia either by recruitment of leukemic progenitors into cycle, rendering them more sensitive to the cytotoxic effects of chemotherapy, or by inducing the terminal differentiation of the leukemic clone. Finally, disruption of aberrant growth factor networks, thought to play a role in the pathogenesis of leukemia, may be a therapeutic strategy now that soluble receptors and receptor antagonists to such growth factors as IL-1 are available. Whether growth factors used in such ways will have beneficial, or in fact adverse, effects on the treatment outcome for acute leukemia is not yet known. As such, the use of growth factors in the management of adults with acute leukemia is still experimental and needs to be studied in the context of clinical trials. Perhaps the ultimate benefit to be derived from the study of these growth factors will be a deeper understanding of the genetic perturbations that define the leukemic state. The development of molecular therapeutic techniques, such as gene transfer technology and the use of antisense oligonucleotides, has paralleled our increasing knowledge of cytokines. The hope is that as we come to understand leukemia at the molecular level, we will be able to develop the new therapeutic tools necessary to increase the numbers of patients cured. PMID:8449861

  19. Identification of SFR6, a key component in cold acclimation acting post-translationally on CBF function.

    PubMed

    Knight, Heather; Mugford, Sarah G; Ulker, Bekir; Gao, Dahai; Thorlby, Glenn; Knight, Marc R

    2009-04-01

    The sfr6-1 mutant of Arabidopsis thaliana was identified previously on the basis of its failure to undergo acclimation to freezing temperatures following exposure to low positive temperatures. This failure is attributed to a defect in the pathway leading to cold on-regulated (COR) gene expression via CBF (C-box binding factor) transcription factors. We identified a region of chromosome 4 containing SFR6 by positional mapping. Fine mapping of the sfr6-1 mutation proved impossible as the locus resides very close to the centromere. Therefore, we screened 380 T-DNA lines with insertions in genes within the large region to which sfr6-1 mapped. This resulted in the identification of two further mutant alleles of SFR6 (sfr6-2 and sfr6-3); like the original sfr6-1 mutation, these disrupt freezing tolerance and COR gene expression. To determine the protein sequence, we cloned an SFR6 cDNA based on the predicted coding sequence, but this offered no indication as to the mechanism by which SFR6 acts. The SFR6 gene itself is not strongly regulated by cold, thus discounting regulation of SFR6 activity at the transcriptional level. We show that over-expression of CBF1 or CBF2 transcription factors, which constitutively activate COR genes in the wild-type, cannot do so in sfr6-1. We demonstrate that CBF protein accumulates to wild-type levels in response to cold in sfr6-1. These results indicate a role for the SFR6 protein in the CBF pathway -downstream of CBF translation. The fact that the SFR6 protein is targeted to the nucleus may suggest a direct role in modulating gene expression. PMID:19067974

  20. Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor.

    PubMed

    Maeda, T; Katayama, Y; Kawamata, T; Aoyama, N; Mori, T

    1997-01-01

    Cerebrovascular damages leading to subsequent reductions in regional cerebral blood flow (rCBF) may play an important role in secondary cell damages following traumatic brain injury (TBI). Recent studies have demonstrated that rCBF markedly decrease in experimental model of TBI (e.g. fluid percussion injury, acute subdural hematoma, contusion). However, precise mechanisms underlying post-traumatic CBF reduction remain unclear. In the present study, the rCBF changes and microthrombosis formation were investigated in a cortical contusional model in rats, and the effects of etizolam (platelet activating factor antagonist) on microthrombosis were tested. The rCBF in the peripheral areas increased transiently, and decreased to ischemic level 3 hours post- injury. The histological examinations revealed microthrombosis formation in the contused area, extending from the center to the peripheral areas within 6 hours post-injury. The rCBF decrease and the contusion necrosis volume were significantly attenuated by etizolam administration. These results indicate that platelet activating factor is involved in microthrombosis formation and hemodynamic depression, and resultant ischemic damages within areas surrounding the contusion. PMID:9416292

  1. Cloning and transformation of INDUCER of CBF EXPRESSION1 (ICE1) in tomato.

    PubMed

    Yu, X H; Juan, J X; Gao, Z L; Zhang, Y; Li, W Y; Jiang, X M

    2015-01-01

    The tomato plant (Solanum lycopersicum Mill.) is sensitive to cold, and low field temperatures can result in shortened growth periods and decreased crop yield. Transcription of CRT/DRE-binding factor (CBF) is regulated by INDUCER of CBF EXPRESSION1 (ICE1). CBF activates many downstream genes that confer cold tolerance on plants. ICE1 has been used in genetic engineering to improve cold-resistance in several plant species. Here, ICE1 in a plant expression vector was used to transform a tissue-cultured rhubarb tomato variety using Agrobacterium tumefaciens. The transgenic and control plants were compared at 4°C for 0, 24, and 72 h. We measured leaf physiological indicators related to cold resistance, including malondialdehyde (MDA) and proline (Pro) contents, and peroxidase (POD) and catalase (CAT) activities. At 72 h, the MDA content in transgenic plants was significantly lower than in control plants, indicating a lower membrane lipid injury. The Pro contents and the CAT and POD activities in the transgenic plants increased significantly compared with those of the control plants. For Pro, the increase continued over the prolonged stress exposure, while CAT and POD activities reached peak levels at 24 h. These results are consistent with the roles of Pro, CAT, and POD in defending the integrity of plant cells. Our study not only improves the cold resistance of tomato, but also provides the foundation for further research on the role of ICE1 as a transcription factor in plant cold resistance. PMID:26535626

  2. SIZ1-mediated sumoylation of ICE1 controls CBF3/DREB1A expression and freezing tolerance in Arabidopsis.

    PubMed

    Miura, Kenji; Jin, Jing Bo; Lee, Jiyoung; Yoo, Chan Yul; Stirm, Vicki; Miura, Tomoko; Ashworth, Edward N; Bressan, Ray A; Yun, Dae-Jin; Hasegawa, Paul M

    2007-04-01

    SIZ1 is a SUMO E3 ligase that facilitates conjugation of SUMO to protein substrates. siz1-2 and siz1-3 T-DNA insertion alleles that caused freezing and chilling sensitivities were complemented genetically by expressing SIZ1, indicating that the SIZ1 is a controller of low temperature adaptation in plants. Cold-induced expression of CBF/DREB1, particularly of CBF3/DREB1A, and of the regulon genes was repressed by siz1. siz1 did not affect expression of ICE1, which encodes a MYC transcription factor that is a controller of CBF3/DREB1A. A K393R substitution in ICE1 [ICE1(K393R)] blocked SIZ1-mediated sumoylation in vitro and in protoplasts identifying the K393 residue as the principal site of SUMO conjugation. SIZ1-dependent sumoylation of ICE1 in protoplasts was moderately induced by cold. Sumoylation of recombinant ICE1 reduced polyubiquitination of the protein in vitro. ICE1(K393R) expression in wild-type plants repressed cold-induced CBF3/DREB1A expression and increased freezing sensitivity. Furthermore, expression of ICE1(K393R) induced transcript accumulation of MYB15, which encodes a MYB transcription factor that is a negative regulator of CBF/DREB1. SIZ1-dependent sumoylation of ICE1 may activate and/or stabilize the protein, facilitating expression of CBF3/DREB1A and repression of MYB15, leading to low temperature tolerance. PMID:17416732

  3. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

    PubMed

    Kim, Bong-Sung; Rongisch, Robert; Hager, Stephan; Grieb, Gerrit; Nourbakhsh, Mahtab; Rennekampff, Hans-Oliver; Bucala, Richard; Bernhagen, Juergen; Pallua, Norbert

    2015-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell

  4. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation

    PubMed Central

    Kim, Bong-Sung; Rongisch, Robert; Hager, Stephan; Grieb, Gerrit; Nourbakhsh, Mahtab; Rennekampff, Hans-Oliver; Bucala, Richard; Bernhagen, Juergen; Pallua, Norbert

    2015-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif–/–and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif–/–mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell

  5. Functional identification of a blueberry CBF/DREB-like element associated with cold acclimation and freezing tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highbush blueberry (Vaccinium corymbosum L.) is susceptible to winter freezing injury and frost damage in the spring. As part of an ongoing project to understand the process of cold acclimation, we isolated a CBF/DREB-like (C-repeat binding factor/dehydration-responsive element binding protein) gene...

  6. Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

    PubMed Central

    Tujios, Shannan R.; Hynan, Linda S.; Vazquez, Miguel A.; Larson, Anne M.; Seremba, Emmanuel; Sanders, Corron M.; Lee, William M.

    2016-01-01

    BACKGROUND & AIMS Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. METHODS We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). RESULTS Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. CONCLUSIONS Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have

  7. Genome-wide characterization of the CBF/DREB1 gene family in Brassica rapa.

    PubMed

    Lee, Sang-Choon; Lim, Myung-Ho; Yu, Jae-Gyeong; Park, Beom-Seok; Yang, Tae-Jin

    2012-12-01

    The C-repeat/dehydration-responsive element binding transcription factors (CBF/DREBs) are important proteins in involved in responses to abiotic stress in plants. We identified ten BrDREB1 genes belonging to the CBF/DREB1 gene family in the Brassica rapa whole genome sequence, whereas six genes are found in the Arabidopsis thaliana genome. The deduced amino acid sequences of the B. rapa genes showed conserved motifs shared with other known plant CBF/DREB1s. Comparative analysis revealed that nine of the BrDREB1 genes were derived from the recent genome triplication in the tribe Brassiceae and the other one was translocated. The nine genes were located in seven of the 12 macrosyntenic blocks that are triplicated counterparts of four Arabidopsis macrosyntenic blocks harboring six CBF/DREB1 genes: one gene on each of three blocks and three tandemly arrayed genes on another block. We inspected the expression patterns of eight BrDREB1 genes by RT-PCR and microarray database searches. All eight genes were highly up-regulated during cold (4 °C) treatment, and some of them were also responsive to salt (250 mM NaCl), drought (air drying), and ABA (100 μM) treatment. Microarray data for plant developmental stages revealed that BrDREB1C2 was highly expressed during a period of cold treatment for vernalization, similar to abiotic stress-inducible genes homologous to Bn28a, Bn47, Bn115, and BoRS1, but almost opposite of BrFLC genes. Taken together, the number of BrDREB1 genes increased to 10 by genome triplication and reorganization, providing additional functions in B. rapa abiotic stress responses and development, as distinct from their Arabidopsis homologs. PMID:23148914

  8. Novel risk factors for acute coronary syndromes and emerging therapies.

    PubMed

    Tong, David C; Wilson, Andrew M; Layland, Jamie

    2016-10-01

    Acute coronary syndromes represent not merely disrupted atherosclerotic plaques or luminal stenoses but rather a complex clinical syndrome. The traditional conception of pathogenesis and management of ACS has been challenged by numerous recent landmark ACS trials. Current prognostication models lack clinical precision and can be challenging to the clinicians in tailoring management strategies for individual patients. In this review we summarise the emerging evidence of novel risk factors (plaque phenotype, coronary blood flow, endothelial dysfunction, microvascular dysfunction, and inflammation) in predicting future events and outcomes in ACS population. As the search for miracle cure for ischaemic heart disease continues, one is hopeful that emerging therapeutic approaches targeting these novel risk factors will improve long-term outcomes of ACS. PMID:27394979

  9. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  10. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

    Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality. PMID:18205255

  11. 47. (Credit CBF) High service pumping room, November 1911. The ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. (Credit CBF) High service pumping room, November 1911. The two high service Worthington horizontal triple expansion pumps (installed c1900 and c1905) are in the foreground. The Blake high service horizontal compound unit (installed c1904) is in the background. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  12. 86. (Credit CBF) Canal between Twelve Mile Bayou and Cross ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    86. (Credit CBF) Canal between Twelve Mile Bayou and Cross Bayou in the bed of Blind Bayou (constructed 1901-1903). Photo taken in November of 1911. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  13. 74. (Credit CBF) Partition between east and west settling basins ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    74. (Credit CBF) Partition between east and west settling basins c1912 with Adolphous Custodis stack (installed 1901) in background. The aerator in the west and the baffles in the east settling basin are visible. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  14. Cerebral hemodynamics in patients with chronic obstructive carotid disease by rCBF, rCBV, and rCBV/rCBF ratio using SPECT

    SciTech Connect

    Toyama, H.; Takeshita, G.; Takeuchi, A.; Anno, H.; Ejiri, K.; Maeda, H.; Katada, K.; Koga, S.; Ishiyama, N.; Kanno, T. )

    1990-01-01

    To evaluate cerebral hemodynamics, 21 patients with chronic occlusion or severe stenosis of the internal carotid or middle cerebral artery with normal or only lacunar infarction on x-ray CT were studied using single photon emission computed tomography (SPECT). We measured rCBV with 99mTc erythrocytes after rCBF with 133Xe, and calculated rCBV/rCBF. rCBF and rCBV of the 25 affected hemispheres were classified as (a) patients with normal rCBF (type I (n = 7) and type II (n = 3)); (b) patients with decreased rCBF (type III (n = 6) and type IV (n = 9)). These two groups then could be subdivided according to findings of rCBV, normal, and increased blood volumes. rCBV/rCBF increased as the cerebral perfusion pressure dropped from type I to type III. In type IV, other situations but cerebral autoregulation could be assumed. rCBV/rCBF signifies vascular mean transit time. Type III (high rCBV/rCBF) assumed as the increased OEF, misery perfusion as reported in PET. We propose rCBF, rCBV and rCBV/rCBF using SPECT can be an index for cerebral circulatory reserve.

  15. ZmCBF3 overexpression improves tolerance to abiotic stress in transgenic rice (Oryza sativa) without yield penalty.

    PubMed

    Xu, Miaoyun; Li, Luhui; Fan, Yunliu; Wan, Jianmin; Wang, Lei

    2011-10-01

    Plant productivity is greatly affected by environmental stresses such as drought, salt, and freezing. We previously described a C-repeat binding transcription factor from maize (ZmCBF3) that was upregulated by both abscisic acid and low-temperature and actively expressed during embryogenesis. To understand the stress response in rice, transgenic ZmCBF3 rice with ubiquitin promoter was developed. T3 generation was planted and analyzed. The results showed that overexpression of ZmCBF3 in rice did not cause growth retardation under normal growth conditions with improved tolerance to drought, high-salt, and low-temperature stresses. Moreover, the transgenic rice grain yield was similar to wild type plants under normal conditions. The transgenic plants showed enhanced survival rate and reduced malondialdehyde content and relative conductivity under drought, salt, and low-temperature stresses. ZmCBF3 overexpression in transgenic rice increased the transcript levels of stress-induced genes and enhanced the tolerance to drought, salt, and low-temperature stresses. PMID:21811828

  16. Transcriptomic and field evaluation of apple trees overexpressing a peach CBF gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of CBF genes in cold response and acclimation has been well documented in both herbaceous and woody plants. Our initial research demonstrated that overexpression of a peach CBF gene (PpCBF1) in ‘M.26’ apple increases freezing tolerance of non-acclimated plants and unexpectedly also results...

  17. Acute Liver Failure in Pregnancy: Causative and Prognostic Factors

    PubMed Central

    Sahai, Shweta; Kiran, Ravi

    2015-01-01

    Background/Aims: Acute liver failure (ALF) in pregnancy is often associated with a poor prognosis. In this single-center observational study we aim to study the incidence, causes, and factors affecting mortality in pregnant women with ALF. Patients and Methods: Sixty-eight pregnant women reporting with clinical features of liver dysfunction were enrolled as cases. Their clinical course was followed and laboratory studies were performed. The presence of ALF was defined as the appearance of encephalopathy. The results were compared with a control group of 16 nonpregnant women presenting with similar complaints. The cases were further subdivided into two groups of survivors and nonsurvivors and were compared to find out the factors that contribute to mortality. Results: ALF was seen in significantly more number of pregnant women than the controls (P = 0.0019). The mortality rate was also significantly higher (P = 0.0287). Hepatitis E virus (HEV) caused jaundice in a higher number of pregnant women (P < 0.001). It also caused ALF in majority (70.3%) of pregnant women, but HEV infection was comparable between the survivors and nonsurvivors (P = 0.0668), hence could not be correlated with mortality. Conclusions: Pregnant women appear to be more susceptible for HEV infection and development of ALF. The mortality of jaundiced pregnant women increased significantly with appearance of ALF, higher bilirubin, lower platelet count, higher international normalized ratio, and spontaneous delivery. PMID:25672236

  18. Factor Structure of the Acute Stress Disorder Scale in a Sample of Hurricane Katrina Evacuees

    ERIC Educational Resources Information Center

    Edmondson, Donald; Mills, Mary Alice; Park, Crystal L.

    2010-01-01

    Acute stress disorder (ASD) is a poorly understood and controversial diagnosis (A. G. Harvey & R. A. Bryant, 2002). The present study used confirmatory factor analysis (CFA) to test the factor structure of the most widely used self-report measure of ASD, the Acute Stress Disorder Scale (R. A. Bryant, M. L. Moulds, & R. M. Guthrie, 2000), in a…

  19. Effects of finite spatial resolution on quantitative CBF images from dynamic PET

    SciTech Connect

    Phelps, M.E.; Huang, S.C.; Mahoney, D.K.

    1985-05-01

    The finite spatial resolution of PET causes the time-activity responses on pixels around the boundaries between gray and white matter regions to contain kinetic components from tissues of different CBF's. CBF values estimated from kinetics of such mixtures are underestimated because of the nonlinear relationship between the time-activity response and the estimated CBF. Computer simulation is used to investigate these effects on phantoms of circular structures and realistic brain slice in terms of object size and quantitative CBF values. The CBF image calculated is compared to the case of having resolution loss alone. Results show that the size of a high flow region in the CBF image is decreased while that of a low flow region is increased. For brain phantoms, the qualitative appearance of CBF images is not seriously affected, but the estimated CBF's are underestimated by 11 to 16 percent in local gray matter regions (of size 1 cm/sup 2/) with about 14 percent reduction in global CBF over the whole slice. It is concluded that the combined effect of finite spatial resolution and the nonlinearity in estimating CBF from dynamic PET is quite significant and must be considered in processing and interpreting quantitative CBF images.

  20. A comparison of the low temperature transcriptomes and CBF regulons of three plant species that differ in freezing tolerance: Solanum commersonii, Solanum tuberosum, and Arabidopsis thaliana

    PubMed Central

    Pino, María-Teresa; Jeknić, Zoran; Zou, Cheng; Shiu, Shin-Han; Chen, Tony H. H.; Thomashow, Michael F.

    2011-01-01

    Solanum commersonii and Solanum tuberosum are closely related plant species that differ in their abilities to cold acclimate; whereas S. commersonii increases in freezing tolerance in response to low temperature, S. tuberosum does not. In Arabidopsis thaliana, cold-regulated genes have been shown to contribute to freezing tolerance, including those that comprise the CBF regulon, genes that are controlled by the CBF transcription factors. The low temperature transcriptomes and CBF regulons of S. commersonii and S. tuberosum were therefore compared to determine whether there might be differences that contribute to their differences in ability to cold acclimate. The results indicated that both plants alter gene expression in response to low temperature to similar degrees with similar kinetics and that both plants have CBF regulons composed of hundreds of genes. However, there were considerable differences in the sets of genes that comprised the low temperature transcriptomes and CBF regulons of the two species. Thus differences in cold regulatory programmes may contribute to the differences in freezing tolerance of these two species. However, 53 groups of putative orthologous genes that are cold-regulated in S. commersonii, S. tuberosum, and A. thaliana were identified. Given that the evolutionary distance between the two Solanum species and A. thaliana is 112–156 million years, it seems likely that these conserved cold-regulated genes—many of which encode transcription factors and proteins of unknown function—have fundamental roles in plant growth and development at low temperature. PMID:21511909

  1. Effect of an acute increase in central blood volume on cerebral hemodynamics.

    PubMed

    Ogoh, Shigehiko; Hirasawa, Ai; Raven, Peter B; Rebuffat, Thomas; Denise, Pierre; Lericollais, Romain; Sugawara, Jun; Normand, Hervé

    2015-10-15

    Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV. PMID:26310936

  2. Identification of CBF14 and NAC2 Genes in Aegilops tauschii Associated with Resistance to Freezing Stress.

    PubMed

    Masoomi-Aladizgeh, Farhad; Aalami, Ali; Esfahani, Masoud; Aghaei, Mohamad Jaafar; Mozaffari, Khadijeh

    2015-06-01

    Low temperature as one of the most important environmental factors limits the productivity of plants across the world. Aegilops, as a wild species of Poaceae, contains low temperature-responsive genes. In this study, we analyzed morphological (wilting, chlorosis, and recovery) and physiological (ion leakage) characteristics to identification of a cold-tolerant genotype. In this experiment, we introduced two transcription factors (TFs) in Aegilops species for the first time. Bioinformatics analysis demonstrated that our nucleotide sequences have high similarity with CBF14 (C-repeat-binding factor) and NAC2 (NAM, ATAF, and CUC) in Triticum aestivum. Based on the physiological and morphological data, one genotype (Aladizgeh) was identified as the most resistant genotype which was selected for further gene expression analysis. The real-time PCR results indicated that the CBF14 gene was not expressed 3 h following cold treatment, but the highest expression was observed after 6, 12, and 24 h of cold treatment; however, a sudden decrease was observed in its expression after 30 h. The NAC2 gene also was not expressed 3 h after cold stress, but the highest expression was at 24 h and similar to the CBF14 gene; its expression suddenly decreased after 30 h. Our results indicated that this genotype can tolerate -4 °C for 3 h, but the CBF14 and NAC2 genes were activated when treated for longer durations. Expression of TFs studied in this experiment had decreased after 30 h, in which cell death seems to be the important reason. PMID:25900437

  3. Incidence and Risk Factors for Acute Kidney Injury Following Mannitol Infusion in Patients With Acute Stroke: A Retrospective Cohort Study.

    PubMed

    Lin, Shin-Yi; Tang, Sung-Chun; Tsai, Li-Kai; Yeh, Shin-Joe; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Jeng, Jiann-Shing

    2015-11-01

    Mannitol, an osmotic diuretic, is commonly used to treat patients with acute brain edema, but its use also increases the risk of developing acute kidney injury (AKI). In this study, we investigated the incidence and risk factors of mannitol-related AKI in acute stroke patients.A total of 432 patients (ischemic stroke 62.3%) >20 years of age who were admitted to the neurocritical care center in a tertiary hospital and received mannitol treatment were enrolled in this study. Clinical parameters including the scores of National Institutes of Health Stroke Scale (NIHSS) at admission, vascular risk factors, laboratory data, and concurrent nephrotoxic medications were registered. Acute kidney injury was defined as an absolute elevation in the serum creatinine (Scr) level of ≥0.3 mg/dL from the baseline or a ≥50% increase in Scr.The incidence of mannitol-related AKI was 6.5% (95% confidence interval, 4.5%-9.3%) in acute stroke patients, 6.3% in patients with ischemic stroke, and 6.7% in patients with intracerebral hemorrhage. Multivariate analysis revealed that diabetes, lower estimated glomerular filtration rate at baseline, higher initial NIHSS score, and concurrent use of diuretics increased the risk of mannitol-related AKI. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.839 (95% confidence interval, 0.770-0.909). In conclusion, mannitol-related AKI is not uncommon in the treatment of acute stroke patients, especially in those with vulnerable risk factors. PMID:26632702

  4. Chlamydia trachomatis Antigens Recognized by Women With Tubal Factor Infertility, Normal Fertility, and Acute Infection

    PubMed Central

    Budrys, Nicole M.; Gong, Siqi; Rodgers, Allison K.; Wang, Jie; Louden, Christopher; Shain, Rochelle; Schenken, Robert S.; Zhong, Guangming

    2015-01-01

    Objective To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. Methods A C. trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C. trachomatis infection. Results Thirteen immunodominant antigens reacted with 50% or more sera from all women (N=73). Six C. trachomatis antigens were uniquely recognized by women diagnosed with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.91–1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C. trachomatis-exposed women with a detection sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.95–1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. Conclusion A sequential screening of antibodies against panels of C. trachomatis antigens can be used to identify women with tubal factor infertility and acute C. trachomatis infection. PMID:22525912

  5. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke

    PubMed Central

    Arboix, Adrià

    2015-01-01

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  6. A Role for SKIP in EBNA2 Activation of CBF1-Repressed Promoters

    PubMed Central

    Zhou, Sifang; Fujimuro, Masahiro; Hsieh, James J.-D.; Chen, Lin; Hayward, S. Diane

    2000-01-01

    EBNA2 is essential for Epstein-Barr virus (EBV) immortalization of B lymphocytes. EBNA2 functions as a transcriptional activator and targets responsive promoters through interaction with the cellular DNA binding protein CBF1. We have examined the mechanism whereby EBNA2 overcomes CBF1-mediated transcriptional repression. A yeast two-hybrid screen performed using CBF1 as the bait identified a protein, SKIP, which had not previously been recognized as a CBF1-associated protein. Protein-protein interaction assays demonstrated contacts between SKIP and the SMRT, CIR, Sin3A, and HDAC2 proteins of the CBF1 corepressor complex. Interestingly, EBNA2 also interacted with SKIP in glutathione S-transferase affinity and mammalian two-hybrid assays and colocalized with SKIP in immunofluorescence assays. Interaction with SKIP was not affected by mutation of EBNA2 conserved region 6, the CBF1 interaction region, but was abolished by mutation of conserved region 5. Mutation of conserved region 5 also severely impaired EBNA2 activation of a reporter containing CBF1 binding sites. Thus, interaction with both CBF1 and SKIP is necessary for efficient promoter activation by EBNA2. A model is presented in which EBNA2 competes with the SMRT-corepressor complex for contacts on SKIP and CBF1. PMID:10644367

  7. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

    PubMed Central

    Wegenka, U M; Buschmann, J; Lütticken, C; Heinrich, P C; Horn, F

    1993-01-01

    Interleukin-6 (IL-6) is known to be a major mediator of the acute-phase response in liver. We show here that IL-6 triggers the rapid activation of a nuclear factor, termed acute-phase response factor (APRF), both in rat liver in vivo and in human hepatoma (HepG2) cells in vitro. APRF bound to IL-6 response elements in the 5'-flanking regions of various acute-phase protein genes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha 1-acid glycoprotein genes). These elements contain a characteristic hexanucleotide motif, CTGGGA, known to be required for the IL-6 responsiveness of these genes. Analysis of the binding specificity of APRF revealed that it is different from NF-IL6 and NF-kappa B, transcription factors known to be regulated by cytokines and involved in the transcriptional regulation of acute-phase protein genes. In HepG2 cells, activation of APRF was observed within minutes after stimulation with IL-6 or leukemia-inhibitory factor and did not require ongoing protein synthesis. Therefore, a preexisting inactive form of APRF is activated by a posttranslational mechanism. We present evidence that this activation occurs in the cytoplasm and that a phosphorylation is involved. These results lead to the conclusions that APRF is an immediate target of the IL-6 signalling cascade and is likely to play a central role in the transcriptional regulation of many IL-6-induced genes. Images PMID:7678052

  8. Melatonin induces the transcripts of CBF/DREB1s and their involvement in both abiotic and biotic stresses in Arabidopsis.

    PubMed

    Shi, Haitao; Qian, Yongqiang; Tan, Dun-Xian; Reiter, Russel J; He, Chaozu

    2015-10-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring small molecule that acts as an important secondary messenger in plant stress responses. However, the mechanism underlying the melatonin-mediated signaling pathway in plant stress responses has not been established. C-repeat-binding factors (CBFs)/Drought response element Binding 1 factors (DREB1s) encode transcription factors that play important roles in plant stress responses. This study has determined that endogenous melatonin and transcripts level of CBFs (AtCBF1, AtCBF2, and AtCBF3) in Arabidopsis leaves were significantly induced by salt, drought, and cold stresses and by pathogen Pseudomonas syringe pv. tomato (Pst) DC3000 infection. Moreover, both exogenous melatonin treatment and overexpression of CBFs conferred enhanced resistance to both abiotic and biotic stresses in Arabidopsis. Notably, AtCBFs and exogenous melatonin treatment positively regulated the mRNA expression of several stress-responsive genes (COR15A, RD22, and KIN1) and accumulation of soluble sugars content such as sucrose in Arabidopsis under control and stress conditions. Additionally, exogenous sucrose also conferred improved resistance to both abiotic and biotic stresses in Arabidopsis. Taken together, this study indicates that AtCBFs confer enhanced resistance to both abiotic and biotic stresses, and AtCBF-mediated signaling pathway and sugar accumulation may be involved in melatonin-mediated stress response in Arabidopsis, at least partially. PMID:26182834

  9. Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

    PubMed

    Lewis, J; Salem, M M; Chertow, G M; Weisberg, L S; McGrew, F; Marbury, T C; Allgren, R L

    2000-10-01

    Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality. PMID:11007679

  10. Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation.

    PubMed

    Tanimura, Yuko; Aoi, Wataru; Takanami, Yoshikazu; Kawai, Yukari; Mizushima, Katsura; Naito, Yuji; Yoshikawa, Toshikazu

    2016-06-01

    Fibroblast growth factor 21, a metabolic regulator, plays roles in lipolysis and glucose uptake in adipose tissues and skeletal muscles. Its expression in skeletal muscle is upregulated upon activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, which is induced by exercise and muscle contraction. We examined the increase of fibroblast growth factor 21 after acute exercise in metabolic organs, especially skeletal muscles and circulation. Participants exercised on bicycle ergometers for 60 min at 75% of their V˙O2max. Venous blood samples were taken before exercise and immediately after exercise. In an animal study, male ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed treadmill exercises at 30 m min(-1) for 60 min. Shortly thereafter, blood, liver, and skeletal muscle samples were taken from mice. Acute exercise induced the increase of serum fibroblast growth factor 21 in both humans and mice, and increased fibroblast growth factor 21 expression in the skeletal muscles and the liver of mice. Acute exercise activated Akt in mice skeletal muscle. Acute exercise increases fibroblast growth factor 21 concentrations in both serum and metabolic organs. Moreover, results show that acute exercise increased the expression of fibroblast growth factor 21 in skeletal muscle, accompanied by the phosphorylation of Akt in mice. PMID:27335433

  11. Factors influencing acute thrombus formation on carotid artery vascular grafts

    SciTech Connect

    Torem, S.; Schneider, P.A.; Paxton, L.D.; Yasuda, H.; Hanson, S.R.

    1988-10-01

    Scintillation camera imaging of 111Indium-labeled platelets has been used to measure acute thrombus formation on modified expanded Teflon (ePTFE) vascular grafts placed in the carotid arteries of normal baboons. Platelet deposition plateaued over 2 hr postoperatively and occurred primarily at the graft-vessel anastomoses. A positive correlation was found between the circulating platelet count in individual animals and the extent of early platelet thrombus deposition. Unmodified ePTFE grafts accumulated 4.6 +/- 1.2 x 10(9) platelets per graft, or 2.3 +/- 0.71 x 10(9) platelets per anastomosis. Acutely, platelet accumulation was reduced versus control graft results by coating the graft lumenal surfaces with a smooth layer of silicone rubber polymer (0.60 +/- 0.19 x 10(9) platelets per anastomosis; P less than 0.02) but not by coating the grafts using a plasma polymer based on methane, which did not modify graft texture (8.2 +/- 1.7 x 10(9) platelets per graft; P greater than 0.10). The benefit of the silicone rubber coating persisted for at least 48 hr. However, longer term patency was not preserved because 10 of 12 grafts placed had failed within 1 to 2 months.

  12. CBF gene expression in peach leaf and bark tissues is gated by a circadian clock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CBFs regulate a host of genes (CBF-regulon) that respond to low temperature and play a role in cold acclimation. In peach, (Prunus persica) there are at least 4 CBF genes situated in tandem on scaffold 5 of the peach genome. This is in contrast to apple (Malus x domestica) where there are 5 comple...

  13. Structural and functional evidence of high specificity of Cbf5 for ACA trinucleotide

    SciTech Connect

    Zhou, Jing; Liang, Bo; Li, Hong

    2012-07-24

    Cbf5 is the catalytic subunit of the H/ACA small nucleolar/Cajal body ribonucleoprotein particles (RNPs) responsible for site specific isomerization of uridine in ribosomal and small nuclear RNA. Recent evidence from studies on archaeal Cbf5 suggests its second functional role in modifying tRNA U55 independent of guide RNA. In order to act both as a stand-alone and a RNP pseudouridine synthase, Cbf5 must differentiate features in H/ACA RNA from those in tRNA or rRNA. Most H/ACA RNAs contain a hallmark ACA trinucleotide downstream of the H/ACA motif. Here we challenged an archaeal Cbf5 (in the form of a ternary complex with its accessory proteins Nop10 and Gar1) with T-stem-loop RNAs with or without ACA trinucleotide in the stem. Although these substrates were previously shown to be substrates for the bacterial stand-alone pseudouridine synthase TruB, the Cbf5-Nop10-Gar1 complex was only able to modify those without ACA trinucleotide. A crystal structure of Cbf5-Nop10-Gar1 trimer bound with an ACA-containing T-stem-loop revealed that the ACA trinucleotide detracted Cbf5 from the stand-alone binding mode, thereby suggesting that the H/ACA RNP-associated function of Cbf5 likely supersedes its stand-alone function.

  14. [Xenon CT CBF mapping derived from two minutes inhalation].

    PubMed

    Toshima, R; Toyohara, K; Ebisawa, T; Ishikawa, K; Karashima, H; Shimojo, S; Miyahara, T

    1988-04-01

    Although xenon enhanced CT method for local cerebral blood flow measurement has been brought into a clinical practice, the technique has inherent limitations including anesthetic effects and expensive cost of xenon by a large consumption. To overcome these problems a modified method with a short-duration inhalation was developed and its validity was attested. Siemens Somatom SF with a resolution of 256 X 256 pixels and a scan time of 10 seconds was used. The subjects inhaled 50% Xe/O2 gas mixture from an apparatus consisted of Douglas bag and an open circuit. Xenon concentration in the expired gas was continuously monitored and estimated for arterial blood concentration by using a hematocrit correction. PaCO2 was monitored throughout the study. At the starting point and the endpoint of the inhalation two scans were performed respectively. Thus obtained four images were processed for CT noise cancellation, summation and subtraction to produce an in vivo autoradiography image. Local CBF was calculated from equations derived from the autoradiographic technique with a fixed partition coefficient of lambda = 1. Computer simulation studies were performed to find the optimal scan point to obtain an autoradiographic image and to estimate the calculation errors of this method. One minute and forty-five seconds was found to be the optimal scan point to gain an autoradiographic image in view of a balance between linearity of CBF/enhancement curve and total amount of tissue enhancement. The theoretical errors due to the assumption for a fixed partition coefficient were calculated to be 8% underestimation for gray matter and 5% overestimation for white matter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3401410

  15. Factor structure of the Acute Stress Disorder Scale in a Sample of Hurricane Katrina evacuees

    PubMed Central

    Edmondson, Donald; Mills, Mary Alice; Park, Crystal L.

    2010-01-01

    Acute stress disorder (ASD) is a poorly understood and controversial diagnosis (Harvey & Bryant, 2002). The present study used confirmatory factor analysis (CFA) to test the factor structure of the most widely used self-report measure of ASD, the Acute Stress Disorder Scale, in a sample of Hurricane Katrina evacuees relocated to a Red Cross emergency shelter in Austin, Texas. Results indicated that the proposed four-factor structure did not fit the data well. However, an alternate 2-factor model did fit the data well. This model included a second-order Distress factor (onto which the Reexperiencing, Arousal, and Avoidance factors loaded strongly) that was positively correlated with the Dissociation factor. Implications for the ASD construct and its measurement are discussed. PMID:20528054

  16. Depolarization of cell membrane is associated with an increase in ciliary beat frequency (CBF).

    PubMed

    Mao, H; Wong, L B

    1995-10-24

    We hypothesize that activation of muscarinic cholinergic receptors depolarizes the cell membrane of the mammalian ciliated cells which in turn causes an increase of CBF. To test this hypothesis, a di-8-ANEPPS fluorescence photon counting and nonstationary heterodyne laser light scattering system was developed to measure cell membrane potential (psi) and CBF in cultured ovine tracheal ciliated cells simultaneously. Carbachol dose dependently depolarized the cell membrane with a corresponding stimulation of CBF. The carbachol induced depolarization of cell membrane and increases of CBF were inhibited by prior application of either atropine or verapamil or amiloride. These novel data suggest that depolarization of the cell membrane and the corresponding stimulation of CBF caused by the activation of muscarinic receptors of the mammalian ciliated cells are dependent on the influx of either extracellular Ca2+ or Na+. PMID:7488025

  17. Role of endogenous atrial natriuretic factor in acute congestive heart failure.

    PubMed Central

    Lee, M E; Miller, W L; Edwards, B S; Burnett, J C

    1989-01-01

    The current studies were designed to investigate the functional significance of elevated endogenous atrial natriuretic factor (ANF) in acute congestive heart failure (CHF). Integrated cardiorenal and endocrine function were measured in three models of acute low-output congestive heart failure with comparably reduced cardiac output (CO) and mean arterial pressure (MAP). Acute CHF was produced by rapid right ventricular pacing (group I, n = 5) which decreases CO and increases atrial pressures and plasma ANF. In group II, n = 5, thoracic inferior vena caval constriction (TIVCC) was produced to decrease venous return and CO but without increases in atrial pressure or plasma ANF. In group III, n = 5, TIVCC was performed and exogenous ANF infused to achieve plasma concentrations observed in acute CHF. In acute CHF with increases in endogenous ANF, sodium excretion (UNaV), renal blood flow (RBF), plasma renin activity (PRA), and plasma aldosterone (PA) were maintained despite decreases in CO and MAP. In contrast, TIVCC with similar reductions in CO and MAP but without increases in ANF resulted in decreases in UNaV and RBF and increases in PRA and PA. Exogenous administration of ANF in TIVCC to mimic levels in acute CHF prevented sodium retention, renal vasoconstriction, and activation of renin and aldosterone. These studies demonstrate that endogenous ANF serves as an important physiologic volume regulator in acute CHF to maintain sodium excretion and possibly participate in the suppression of activation of the renin-angiotensin-aldosterone system despite the stimulus of arterial hypotension. Images PMID:2531762

  18. An apple rootstock overexpressing a peach CBF gene alters growth and flowering in the scion but does not impact cold hardiness or dormancy.

    PubMed

    Artlip, Timothy S; Wisniewski, Michael E; Arora, Rajeev; Norelli, John L

    2016-01-01

    The C-repeat binding factor (CBF) transcription factor is involved in responses to low temperature and water deficit in many plant species. Overexpression of CBF genes leads to enhanced freezing tolerance and growth inhibition in many species. The overexpression of a peach CBF (PpCBF1) gene in a transgenic line of own-rooted apple (Malus×domestica) M.26 rootstock (T166) trees was previously reported to have additional effects on the onset of dormancy and time of spring budbreak. In the current study, the commercial apple cultivar 'Royal Gala' (RG) was grafted onto either non-transgenic M.26 rootstocks (RG/M.26) or transgenic M.26 (T166) rootstocks (RG/T166) and field grown for 3 years. No PpCBF1 transcript was detected in the phloem or cambium of RG scions grafted on T166 rootstocks indicating that no graft transmission of transgene mRNA had occurred. In contrast to own-rooted T166 trees, no impact of PpCBF1 overexpression in T166 rootstocks was observed on the onset of dormancy, budbreak or non-acclimated leaf-cold hardiness in RG/T166 trees. Growth, however, as measured by stem caliper, current-year shoot extension and overall height, was reduced in RG/T166 trees compared with RG/M.26 trees. Although flowering was evident in both RG/T166 and RG/M.26 trees in the second season, the number of trees in flower, the number of shoots bearing flowers, and the number of flower clusters per shoot was significantly higher in RG/M.26 trees than RG/T166 trees in both the second and third year after planting. Elevated levels of RGL (DELLA) gene expression were observed in RG/T166 trees and T166 trees, which may play a role in the reduced growth observed in these tree types. A model is presented indicating how CBF overexpression in a rootstock might influence juvenility and flower abundance in a grafted scion. PMID:26981253

  19. An apple rootstock overexpressing a peach CBF gene alters growth and flowering in the scion but does not impact cold hardiness or dormancy

    PubMed Central

    Artlip, Timothy S; Wisniewski, Michael E; Arora, Rajeev; Norelli, John L

    2016-01-01

    The C-repeat binding factor (CBF) transcription factor is involved in responses to low temperature and water deficit in many plant species. Overexpression of CBF genes leads to enhanced freezing tolerance and growth inhibition in many species. The overexpression of a peach CBF (PpCBF1) gene in a transgenic line of own-rooted apple (Malus×domestica) M.26 rootstock (T166) trees was previously reported to have additional effects on the onset of dormancy and time of spring budbreak. In the current study, the commercial apple cultivar ‘Royal Gala’ (RG) was grafted onto either non-transgenic M.26 rootstocks (RG/M.26) or transgenic M.26 (T166) rootstocks (RG/T166) and field grown for 3 years. No PpCBF1 transcript was detected in the phloem or cambium of RG scions grafted on T166 rootstocks indicating that no graft transmission of transgene mRNA had occurred. In contrast to own-rooted T166 trees, no impact of PpCBF1 overexpression in T166 rootstocks was observed on the onset of dormancy, budbreak or non-acclimated leaf-cold hardiness in RG/T166 trees. Growth, however, as measured by stem caliper, current-year shoot extension and overall height, was reduced in RG/T166 trees compared with RG/M.26 trees. Although flowering was evident in both RG/T166 and RG/M.26 trees in the second season, the number of trees in flower, the number of shoots bearing flowers, and the number of flower clusters per shoot was significantly higher in RG/M.26 trees than RG/T166 trees in both the second and third year after planting. Elevated levels of RGL (DELLA) gene expression were observed in RG/T166 trees and T166 trees, which may play a role in the reduced growth observed in these tree types. A model is presented indicating how CBF overexpression in a rootstock might influence juvenility and flower abundance in a grafted scion. PMID:26981253

  20. Genome-Wide Analysis of the AP2/ERF Family in Eucalyptus grandis: An Intriguing Over-Representation of Stress-Responsive DREB1/CBF Genes

    PubMed Central

    SanClemente, H.; Mounet, F.; Dunand, C.; Marque, G.; Marque, C.; Teulières, C.

    2015-01-01

    Background The AP2/ERF family includes a large number of developmentally and physiologically important transcription factors sharing an AP2 DNA-binding domain. Among them DREB1/CBF and DREB2 factors are known as master regulators respectively of cold and heat/osmotic stress responses. Experimental Approaches The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus and Vitis genomes allowed a complete phylogenetic study for comparing the structure of this family in woody species and the model Arabidopsis thaliana. Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were investigated through RNAseq database survey and RT-qPCR analyses. Results The structure and the size of the AP2/ERF family show a global conservation for the plant species under comparison. In addition to an expansion of the ERF subfamily, the tree genomes mainly differ with respect to the group representation within the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature is the presence of 17 DREB1/CBF genes, the maximum reported to date for dicotyledons. In contrast, only six DREB2 have been identified, which is similar to the other plants species under study, except for Malus. All the DREB1/CBF and DREB2 genes from E. grandis are expressed in at least one condition and all are heat-responsive. Regulation by cold and drought depends on the genes but is not specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is mainly drought responsive. Conclusion These features suggest that the dramatic expansion of the DREB1/CBF group might be related to the adaptation of this evergreen tree to climate changes when it expanded in Australia. PMID:25849589

  1. [Aphasia in acute apoplexy. Incidence, background factors and course].

    PubMed

    Pedersen, P M; Jørgensen, H S; Nakayama, H; Raaschou, H O; Olsen, T S

    1997-02-17

    Knowledge of the frequency and remission of aphasia is essential for the rehabilitation of stroke patients. Information on its determinants provides insight on brain organization of language. Therefore, a community based sample of 881 unselected, acute stroke patients was studied prospectively and consecutively. Assessment of aphasia was done on admission, weekly during hospital stay, and again at a six-month follow-up using the aphasia score of the Scandinavian Stroke Scale. Thirty-eight percent had aphasia at the time of admission, while at discharge it was 18%. Sex was not a significant determinant of aphasia in stroke, and no sex difference was found in the anterior-posterior distribution of lesions causing aphasia. There was, however, a higher rate of women with aphasia with right-sided lesions. The remission curve was steep: stationary language function in 95% was reached within two weeks in those with initial mild aphasia, within six weeks with moderate, and within ten weeks with severe aphasia. Initial severity of aphasia was the only clinically relevant predictor of aphasia outcome in multiple linear regression analysis. Sex, handedness, and side of stroke lesion were not independent outcome predictors, and the influence of age was minimal. PMID:9072858

  2. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461

    PubMed Central

    Farag, Sherif S.; Archer, Kellie J.; Mrózek, Krzysztof; Ruppert, Amy S.; Carroll, Andrew J.; Vardiman, James W.; Pettenati, Mark J.; Baer, Maria R.; Qumsiyeh, Mazin B.; Koduru, Prasad R.; Ning, Yi; Mayer, Robert J.; Stone, Richard M.; Larson, Richard A.; Bloomfield, Clara D.

    2006-01-01

    We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including “rare aberrations” predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P < .001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care. (Blood. 2006;108:63-73) PMID:16522815

  3. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  4. Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis.

    PubMed

    Shinozuka, Yasunori; Kaneko, Sohei; Kurose, Tomoyasu; Watanabe, Aiko; Kuruhara, Kana; Kawai, Kazuhiro

    2016-06-01

    Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss. PMID:26860356

  5. Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis

    PubMed Central

    SHINOZUKA, Yasunori; KANEKO, Sohei; KUROSE, Tomoyasu; WATANABE, Aiko; KURUHARA, Kana; KAWAI, Kazuhiro

    2016-01-01

    Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss. PMID:26860356

  6. CBF measured by Xe-CT: Approach to analysis and normal values

    SciTech Connect

    Yonas, H.; Darby, J.M.; Marks, E.C.; Durham, S.R.; Maxwell, C. )

    1991-09-01

    Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. The authors measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 {plus minus} 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flow values in each hemisphere, averaged 84 {plus minus} 14 and 20 {plus minus} 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.

  7. Factors Contributing to Readmission of Seniors into Acute Care Hospitals

    ERIC Educational Resources Information Center

    DeCoster, Vaughn; Ehlman, Katie; Conners, Carolyn

    2013-01-01

    Medicare spending is expected to increase by 79% between the years 2010 and 2020, caused, in-part, by hospital readmissions within 30 days of discharge. This study identified factors contributing to hospital readmissions in a midwest heath service area (HSA), using Coleman's Transition Care Model as the theoretical framework. The researchers…

  8. Factors associated with self-reported symptoms of acute pesticide poisoning among farmers in northwestern Jamaica

    PubMed Central

    Ncube, Ngqabutho M.; Fogo, Christopher; Bessler, Patricia; Jolly, Curtis M.; Jolly, Pauline E.

    2011-01-01

    Pesticide poisoning is a major public health concern in developing countries. We conducted a population survey among farmers in three parishes of northwestern Jamaica to determine the occurrence of acute pesticide poisoning and to identify factors associated with pesticide poisoning. Approximately 16% of 359 farmers who participated in the study reported one or more incidents of acute pesticide poisoning within the last two years. Only 25% of the farmers reported ever receiving training in pesticide handling or safety. The majority (68%) of farmers who reported pesticide poisoning never sought medical attention for poisoning. The factors found to be associated with pesticide poisoning in this study indicate that implementation of specific intervention strategies and education of farmers is needed in order to improve safe handling, use and disposal of pesticides and reduce incidents of acute pesticide poisoning. PMID:24484363

  9. The absolute CBF response to activation is preserved during elevated perfusion: Implications for neurovascular coupling measures

    PubMed Central

    Whittaker, Joseph R.; Driver, Ian D.; Bright, Molly G.; Murphy, Kevin

    2016-01-01

    Functional magnetic resonance imaging (fMRI) techniques in which the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) response to a neural stimulus are measured, can be used to estimate the fractional increase in the cerebral metabolic rate of oxygen consumption (CMRO2) that accompanies evoked neural activity. A measure of neurovascular coupling is obtained from the ratio of fractional CBF and CMRO2 responses, defined as n, with the implicit assumption that relative rather than absolute changes in CBF and CMRO2 adequately characterise the flow-metabolism response to neural activity. The coupling parameter n is important in terms of its effect on the BOLD response, and as potential insight into the flow-metabolism relationship in both normal and pathological brain function. In 10 healthy human subjects, BOLD and CBF responses were measured to test the effect of baseline perfusion (modulated by a hypercapnia challenge) on the coupling parameter n during graded visual stimulation. A dual-echo pulsed arterial spin labelling (PASL) sequence provided absolute quantification of CBF in baseline and active states as well as relative BOLD signal changes, which were used to estimate CMRO2 responses to the graded visual stimulus. The absolute CBF response to the visual stimuli were constant across different baseline CBF levels, meaning the fractional CBF responses were reduced at the hyperperfused baseline state. For the graded visual stimuli, values of n were significantly reduced during hypercapnia induced hyperperfusion. Assuming the evoked neural responses to the visual stimuli are the same for both baseline CBF states, this result has implications for fMRI studies that aim to measure neurovascular coupling using relative changes in CBF. The coupling parameter n is sensitive to baseline CBF, which would confound its interpretation in fMRI studies where there may be significant differences in baseline perfusion between groups. The absolute change in

  10. Overexpression of a peach CBF gene in apple: a model for understanding the integration of growth, dormancy, and cold hardiness in woody plants

    PubMed Central

    Wisniewski, Michael; Norelli, John; Artlip, Timothy

    2015-01-01

    The timing of cold acclimation and deacclimation, dormancy, and budbreak play an integral role in the life cycle of woody plants. The molecular events that regulate these parameters have been the subject of much study, however, in most studies these events have been investigated independently of each other. Ectopic expression of a peach CBF (PpCBF1) in apple increases the level of both non-acclimated and acclimated freezing tolerance relative to the non-transformed control, and also inhibits growth, induces early bud set and leaf senescence, and delays bud break in the spring. The current study examined differences in the seasonal expression of genes (CBF, DAM, RGL, and EBB) that have been reported to be associated with freezing tolerance, dormancy, growth, and bud break, respectively, in the PpCBF1 T166 transgenic apple line and the non-transformed M.26 control. Results indicated that expression of several of these key genes, including MdDAM, MdRGL, and MdEBB was altered in transgenic T166 trees relative to non-transformed M.26 trees. In particular, several putative MdDAM genes, associated with the dormancy-cycle in other species of woody plants in the Rosaceae, exhibited different patterns of expression in the T166 vs. M.26 trees. Additionally, for the first time a putative APETALA2/Ethylene-responsive transcription factor, originally described in poplar and shown to regulate the timing of bud break, was shown to be associated with the timing of bud break in apple. Since the overexpression of PpCBF1 in apple results in a dramatic alteration in cold acclimation, dormancy, and growth, this transgenic line (T166) may represent a useful model for studying the integration of these seasonal life-cycle parameters. PMID:25774159

  11. Purification of a novel MHC class I element binding activity from thymus nuclear extracts reveals that thymic RBP-Jkappa/CBF1 binds to NF-kappaB-like elements.

    PubMed

    Shirakata, Y; Shuman, J D; Coligan, J E

    1996-06-15

    We purified a DNA binding protein that recognizes a portion of the MHC class I regulatory element region 1/NF-kappaB binding site whose expression correlates with the expression of a MHC class I transgene in the thymus. The N-terminal amino acid sequence and the molecular size matched the RBP-Jkappa protein, also known as the EBV C-promoter binding factor, CBF1. Anti-peptide sera reactive with RBP-Jkappa/CBF1 also reacted with this protein in gel mobility shift assays. Although RBP-Jkappa/CBF1 is ubiquitously expressed, binding to the MHC class Ia NF-kappaB site was limited to the thymus. Comparison of the DNA binding specificities of RBP-Jkappa/CBF1 in thymic and splenic nuclear extracts revealed strong binding from both extracts to an IFN-beta kappaB site containing the RBP-Jkappa/CBF1 consensus sequence (CGTGGGAA). In contrast, only the thymic nuclear extract showed strong DNA binding activity with probes containing the NF-kappaB recognition sequences present in the MHC class Ia, IL-2Ralpha, and granulocyte-macrophage CSF promoters. Thus, RBP-Jkappa/CBF1 in thymic extracts demonstrates a clearly distinguishable DNA binding specificity that correlates with tissue-specific expression of a class I transgene. This, coupled with the fact that our previous study showed enhanced expression of the transgene in CD4+CD8+ thymocytes, suggests that RBP-Jkappa/CBF1 may play a role in the development of the immune system. PMID:8648111

  12. 76. (Credit CBF) Inside of laboratory at McNeil Street Station, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    76. (Credit CBF) Inside of laboratory at McNeil Street Station, c1912. Laboratory located over clear water well at this time. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  13. Effect of ethanol on cerebral blood flow (CBF) and metabolism (CMRO2) in conscious sheep

    SciTech Connect

    Krasney, J.A.; Zubkov, B.; Iwamoto, J. )

    1991-03-11

    A moderate dose of ethanol severely depresses CBF and CMRO2 in the awake sheep fetus. However, the effects of ethanol on CBF and CMRO2 in the adult are unclear. The same dose of ethanol was infused for 2 hr in 5 ewes instrumented with aortic, left ventricular and sagittal sinus catheters. Ethanol caused ataxia accompanied by early modest and variable increases of total and regional CBF and CMRO2, followed by later modest and variable decreases of total and regional CBF (cerebellum) and CMRO2. Ethanol caused a cerebral transcapillary fluid shift as indicated by significant increases of the arterial-cerebral venous differences for hematocrit and hemoglobin. Brain wet-dry ratios increased by 10% above control levels. However, cerebral venous pressures were unchanged. The authors conclude that the adult cerebral response to ethanol differs quantitatively from that of the fetus. The functional significance of the cerebral fluid shift is unclear.

  14. Early seizures in patients with acute stroke: Frequency, predictive factors, and effect on clinical outcome

    PubMed Central

    Alberti, Andrea; Paciaroni, Maurizio; Caso, Valeria; Venti, Michele; Palmerini, Francesco; Agnelli, Giancarlo

    2008-01-01

    Background Early seizure (ES) may complicate the clinical course of patients with acute stroke. The aim of this study was to assess the rate of and the predictive factors for ES as well the effects of ES on the clinical outcome at hospital discharge in patients with first-ever stroke. Patients and methods A total of 638 consecutive patients with first-ever stroke (543 ischemic, 95 hemorrhagic), admitted to our Stroke Unit, were included in this prospective study. ES were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy were excluded. Results Thirty-one patients (4.8%) had ES. Seizures were significantly more common in patients with cortical involvement, severe and large stroke, and in patient with cortical hemorrhagic transformation of ischemic stroke. ES was not associated with an increase in adverse outcome (mortality and disability). After multivariate analysis, hemorrhagic transformation resulted as an independent predictive factor for ES (OR = 6.5; 95% CI: 1.95–22.61; p = 0.003). Conclusion ES occur in about 5% of patients with acute stroke. In these patients hemorrhagic transformation is a predictive factor for ES. ES does not seem to be associated with an adverse outcome at hospital discharge after acute stroke. PMID:18827922

  15. Causal factors of acute gastroenteritis in infants and young children.

    PubMed

    Zvizdić, Sukrija; Kapić, Elvedina; Hamzić, Sadeta

    2005-02-01

    Respiratory, gastrointestinal and skin diseases represent the most common diseases in infants and young children. Causal factors of these diseases are important infectious agents and causes of pathological conditions in children, but they are also very important for their parents, as well as for people in their close environment. Greater incidence of infections in infants and young children can be explained in different ways. A cause can be insufficient maturity of their immune system, but also their exposure to infections within collective accommodations (cribs, nurseries, pre-school institutions), where they are, at the same time, exposed to a number of unknown agents. Today, a great emphasis is devoted to the ways and kinds of children's nutrition. The problem of relation between infected young organism and infectious agent itself, is also reflected in a long resistance and excretion of microorganisms in their exterior environment. It is well-known that microorganisms resist and excrete much longer in younger organisms, compared to adults, where their resistance and excretion is much shorter or very rare. Actually, adults have already formed protective immunity against particular infectious agents. It doesn't prevent infections in adults, colonization of pathogens, nor eventual development of disease. Established immunity can shorten the time necessary for excretion of microorganisms in their exterior environment and, if disease gets developed, it is of shorter duration and slower progress. PMID:15771601

  16. Association of cardiovascular risk factors with the different presentations of acute coronary syndrome1

    PubMed Central

    Brunori, Evelise Helena Fadini Reis; Lopes, Camila Takáo; Cavalcante, Agueda Maria Ruiz Zimmer; Santos, Vinicius Batista; Lopes, Juliana de Lima; de Barros, Alba Lucia Bottura Leite

    2014-01-01

    OBJECTIVE: to identify the relationship between different presentations of acute coronary syndrome and cardiovascular risk factors among hospitalized individuals. METHOD: cross-sectional study performed in a teaching hospital in São Paulo, in the State of São Paulo (SP). Socio-demographic, clinical and anthropometric data of 150 individuals hospitalized due to acute coronary syndrome were collected through interviews and review of clinical charts. Association between these data and the presentation of the syndrome were investigated. RESULTS: there was a predominance of ST segment elevation acute myocardial infarction. There was significant association of systemic hypertension with unstable angina and high values of low density lipoprotein with infarction, without influence from socio-demographic characteristics. CONCLUSION: arterial hypertension and high levels of low-density lipoprotein were associated with different presentations of coronary syndrome. The results can provide support for health professionals for secondary prevention programs aimed at behavioural changing. PMID:25296136

  17. Risk factors for relapse after allogeneic transplantation in acute myeloid leukemia

    PubMed Central

    Ossenkoppele, Gert J.; Janssen, Jeroen J.W.M.; van de Loosdrecht, Arjan A.

    2016-01-01

    Acute myeloid leukemia is a clonal neoplasm derived from myeloid progenitor cells with a varying outcome. The initial goal of treatment is the achievement of complete remission, defined for over 40 years by morphology. However, without additional post-remission treatment the majority of patients relapse. In many cases of acute myeloid leukemia, allogeneic stem cell transplantation offers the best prospects of cure. In 2013, 5608 stem cell transplantations in acute myeloid leukemia were performed in Europe (5228 allogeneic and 380 autologous stem cell transplantations). Most stem cell transplantations are performed in first complete remission. However, despite a considerable reduction in the chance of relapse, in most studies, overall survival benefit of allogeneic stem cell transplantation is modest due to substantial non-relapse mortality. Here we discuss the many factors related to the risk of relapse after allogeneic stem cell transplantation. PMID:26721801

  18. Towards a scheme of toxic equivalency factors (TEFs) for the acute toxicity of PAHs in sediment.

    PubMed

    Fisher, Tom T; Law, Robin J; Rumney, Heather S; Kirby, Mark F; Kelly, Carole

    2011-11-01

    Toxic equivalency factors/quotients (TEF/TEQs) express the toxicity of complex mixtures. For PAHs, TEF values are available for assessing their carcinogenic potential and are expressed as benzo[a]pyrene equivalents. This study develops a similar approach for their acute toxicity in sediments. Acute toxicity (10 day EC₅₀) values were generated using the marine amphipod Corophium volutator bioassay for twelve low molecular weight PAHs. The results ranged from 24 to > 1000 mg/Kg sediment dry weight for 4-methyldibenzothiophene and anthracene, respectively. Phenanthrene was used as the reference compound (TEF=1) and so the TEQ values derived are expressed as phenanthrene equivalents. In order to illustrate the applicability of this approach to the development of marine indicators we plotted TEQ values for acute toxicity to UK environmental monitoring data. Further work is required to validate the TEF values produced and to extend the TEQ approach to include a wider range of low molecular weight PAHs. PMID:21885125

  19. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

  20. Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro.

    PubMed

    Witkowski, Sarah; Guhanarayan, Gayatri; Burgess, Rachel

    2016-02-01

    Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony-forming unit CAC (CFU-CAC) were cultured from young active men (n = 9, 24 ± 2 years) at rest and after exercise under normal (5 mmol/L) and elevated (15 mmol/L) glucose. Preliminary relative multiplex cytokine analysis revealed that CAC conditioned culture media contained three of six measured cytokines: transforming growth factor-beta-1 (TGFβ1), tumor necrosis factor alpha (TNFα), and monocyte chemotactic protein-1 (MCP-1). Single quantitative cytokine analysis was used to determine the concentration of each cytokine from the four conditions. NO was measured via Griess assay. There was a significant effect of CAC exposure to in vivo exercise on in vitro TGFβ1 secretion (P = 0.024) that was independent of glucose concentration. There was no effect of glucose or acute exercise on TNFα or MCP-1 concentration (both P > 0.05). The concentration of NO from CFU-CAC cultured in elevated glucose was lower following acute exercise (P = 0.002) suggesting that exercise did not maintain NO secretion under hyperglycemic conditions. Our results identify paracrine signaling factors that may be responsible for the proangiogenic function of CFU-CAC and an influence of acute exercise and elevated glucose on CFU-CAC soluble factor secretion. PMID:26847726

  1. Pulmonary and urinary clearance of atrial natriuretic factor in acute congestive heart failure in dogs.

    PubMed Central

    Perrella, M A; Margulies, K B; Wei, C M; Aarhus, L L; Heublein, D M; Burnett, J C

    1991-01-01

    Atrial natriuretic factor (ANF) is a peptide hormone of cardiac origin elevated in acute congestive heart failure (CHF), which is degraded by the enzyme neutral endopeptidase 24.11 (NEP). This study was designed to investigate the pulmonary and urinary clearance of ANF before and after the initiation of acute experimental CHF in dogs, and to assess the contribution of enzymatic degradation to these clearances in CHF. This study demonstrated a significant clearance of plasma ANF across the pulmonary circulation at baseline, and a tendency for pulmonary clearance to decrease in CHF (1115 +/- 268 to 498 +/- 173 ml/min, NS). The pulmonary extraction of ANF present at baseline was not altered with acute CHF (36.0 +/- 7.8 to 34.9 +/- 12.1%, NS). NEP inhibition (NEPI) abolished both the clearance and extraction of plasma ANF across the lung in CHF. Similarly, significant urinary clearance of ANF was present at baseline, and in acute CHF the urinary clearance of ANF decreased (0.14 +/- 0.02 to 0.02 +/- 0.01 ml/min, P less than 0.05). NEPI prevented the decrease in the urinary clearance of ANF, and enhanced the renal response to endogenous ANF, independent of further increases in plasma ANF during CHF. This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF. Images PMID:1850758

  2. Heart Block in Acute Myocardial Infarction: Prognostic Factors and Role of Transvenous Catheter Pacemaker

    PubMed Central

    Narvas, R. M.; Kilgour, J. M.; Basu, S. K.

    1970-01-01

    A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%. PMID:5410415

  3. Prognosis of patients with core binding factor acute myeloid leukemia after first relapse

    PubMed Central

    Kurosawa, Saiko; Miyawaki, Shuichi; Yamaguchi, Takuhiro; Kanamori, Heiwa; Sakura, Toru; Moriuchi, Yukiyoshi; Sano, Fumiaki; Kobayashi, Takeshi; Yasumoto, Atsushi; Hatanaka, Kazuo; Yanada, Masamitsu; Nawa, Yuichiro; Takeuchi, Jin; Nakamura, Yukinori; Fujisawa, Shin; Shibayama, Hirohiko; Miura, Ikuo; Fukuda, Takahiro

    2013-01-01

    Core binding factor acute myeloid leukemia is known to have a favorable prognosis, however, there have been no detailed analyses on prognostic factors after first relapse. Using a nationwide database, we retrospectively analyzed core binding factor acute myeloid leukemia patients who relapsed after being treated with chemotherapy alone during their first complete remission. Of a total of 397 patients who were diagnosed with core binding factor acute myeloid leukemia, 208 experienced a first relapse, and analyses were performed in 139 patients for whom additional data were available. In the entire cohort, the overall survival rate after relapse was 48% at 3 years. By multivariate analysis, younger age at diagnosis, a longer interval before relapse, and inv(16) were shown to be independently associated with better survival after relapse. Although there was no significant difference in survival after relapse between patients who underwent allogeneic hematopoietic cell transplantation and those who did not in the overall series of relapsed patients, we found that transplantation significantly improved survival among patients who had t(8;21) (54% versus 26% at 3 years, P=0.002). In addition, among patients with t(8;21), those who had different cytogenetics at relapse had a significantly improved survival after transplantation, while those who had same cytogenetics did not. We showed that the prognosis differs significantly and optimal treatment strategies may vary between groups of patients with core binding factor acute myeloid leukemia with different cytogenetic profiles at relapse. These findings may help to guide therapeutic decisions after first relapse. PMID:23716553

  4. Interstitial Outburst of Angiogenic Factors During Skeletal Muscle Regeneration After Acute Mechanical Trauma.

    PubMed

    Ceafalan, Laura Cristina; Manole, Emilia; Tanase, Cristiana Pistol; Codrici, Elena; Mihai, Simona; Gonzalez, Aldebarani; Popescu, Bogdan Ovidiu

    2015-11-01

    Angiogenesis is a key event during tissue regeneration, but the intimate mechanisms controlling this process are still largely unclear. Therefore, the cellular and molecular interplay along normal tissue regeneration should be carefully unveiled. To this matter, we investigated by xMAP assay the dynamics of some angiogenic factors known to be involved in tissue repair, such as follistatin (FST), Placental Growth Factor-2 (PLGF-2), epidermal growth factor (EGF), betacellulin (BTC), and amphiregulin (AREG) using an animal model that mimics acute muscle contusion injuries. In situ immunofluorescence was used for the evaluation and tissue distribution of their cellular sources. Tissue levels of explored factors increased significantly during degeneration and inflammatory stage of regeneration, peaking first week postinjury. However, except for PLGF-2 and EGF, their levels remained significantly elevated after the inflammatory process started to fade. Serum levels were significantly increased only after 24 h for AREG and EGF. Though, for all factors except FST, the levels in injured samples did not correlate with serum or contralateral tissue levels, excluding the systemic influence. We found significant correlations between the levels of EGF and AREG, BTC, FST and FST and AREG in injured samples. Interstitial cells expressing these factors were highlighted by in situ immunolabeling and their number correlated with measured levels dynamics. Our study provides evidence of a dynamic level variation along the regeneration process and a potential interplay between selected angiogenic factors. They are synthesized, at least partially, by cell populations residing in skeletal muscle interstitium during regeneration after acute muscle trauma. PMID:26260512

  5. What factors determine the severity of hepatitis A-related acute liver failure?

    PubMed Central

    Ajmera, V.; Xia, G.; Vaughan, G.; Forbi, J. C.; Ganova-Raeva, L. M.; Khudyakov, Y.; Opio, C. K.; Taylor, R.; Restrepo, R.; Munoz, S.; Fontana, R. J.; Lee, W. M.

    2016-01-01

    SUMMARY The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were subgenotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare subgenotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345

  6. Salivary cortisol and psychological factors in women with chronic and acute oro-facial pain.

    PubMed

    Jasim, H; Louca, S; Christidis, N; Ernberg, M

    2014-02-01

    The aim of this study was to compare the salivary cortisol level, pain intensity and psychological factors between patients with chronic and acute oro-facial pain (OP) and pain-free subjects. Twenty-seven females with chronic OP (a diagnosis of myofascial pain according to the Research Diagnostic Criteria for Temporomandibular Disorders with at least 6 months duration), 24 females with acute OP (<10 days duration) and 27 pain-free females participated. Morning saliva was collected from all participants for analyses of the cortisol level. The pain intensity was assessed on a 0-10 numeric rating scale. The participants were evaluated by the Symptom Checklist 90-revised for levels of depression and somatisation, and the Perceived Stress Scale. The cortisol levels among the three patient groups were similar with no significant group differences. The median (interquartile range) current pain level did not differ between chronic and acute OP and was, respectively, 5 (4) and 5 (3). Patients with chronic OP showed significantly higher scores for depression, somatisation and perceived stress compared with patients with acute OP (Ps < 0.001), but there were no significant differences between acute OP and controls. To conclude, there were no differences in cortisol level between groups, despite significant higher levels of depression, somatisation and perceived stress in patients with chronic OP. This shows that psychological distress has a more important role in chronic than in acute OP. However, the relation between pain, adreno-cortical activity and psychological distress is complex and warrants further investigation. PMID:24313837

  7. The role of prostanoids in the production of acute acalculous cholecystitis by platelet-activating factor.

    PubMed Central

    Kaminski, D L; Andrus, C H; German, D; Deshpande, Y G

    1990-01-01

    Gallbladder tissue from patients with acute acalculous cholecystitis contains increased amounts of prostanoids when compared to normal gallbladder tissue. Platelet-activating factor (PAF) is a potent stimulus of eicosanoid formation. It has been implicated as a mediator of acute inflammatory processes and systemic responses to shock. In this study the role of PAF in acute acalculous cholecystitis was evaluated. Anesthetized cats underwent gallbladder perfusion with a physiologic buffer solution containing [14C]polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Platelet-activating factor was infused into the hepatic artery for 2 hours. Control experiments were performed when vehicle alone was infused. Experiments also were performed when indomethacin was administered intravenously and when indomethacin and PAF were administered. Gallbladder mucosal absorption/secretion and perfusate and tissue prostaglandin E (PGE) and 6 keto prostaglandin F1 alpha (6-keto PGF1 alpha) levels were evaluated. Gallbladder inflammation was evaluated by beta-glucuronidase and myeloperoxidase tissue concentrations and by a histologic scoring system. Platelet-activating factor eliminated gallbladder absorption and produced net fluid secretion associated with dose-related increases in perfusate PGE concentrations and gallbladder tissue PGE and 6 keto PGF1 alpha levels when compared to control values. Platelet-activating factor produced significant inflammation in the gallbladder with increases in the histologic score of inflammation and tissue lysosomal enzyme activities. Indomethacin significantly decreased the fluid secretion, prostanoid levels, and inflammation produced by PAF. The results suggest that PAF may induce acute gallbladder inflammation associated with systemic stress through a prostanoid-mediated mechanism. Images Fig. 2. PMID:2171443

  8. Bilateral self-enucleation in acute transient psychotic disorder: the influence of sociocultural factors on psychopathology.

    PubMed

    Harish, Thippeswamy; Chawan, Namdev; Rajkumar, Ravi Philip; Chaturvedi, Santosh Kumar

    2012-07-01

    Self-inflicted eye injuries are rare but a devastating consequence of a serious mental disorder. Bilateral self-enucleation also known as oedipism has been documented in ancient texts and myths. Various biologic, psychologic, and social theories have been put forward to explain this rare phenomenon. In this report, we describe a case of oedipism, which highlights the influence of sociocultural factors on the psychopathology in acute transient psychotic disorder. PMID:21864835

  9. Hepatocyte Growth Factor Prevents Acute Renal Failure of Accelerates Renal Regeneration in mice

    NASA Astrophysics Data System (ADS)

    Kawaida, Kouichi; Matsumoto, Kunio; Shimazu, Hisaaki; Nakamura, Toshikazu

    1994-05-01

    Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl_2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis of renal tubular cells after renal injuries caused by HgCl_2 administration and unilateral nephrectomy and induced reconstruction of the normal renal tissue structure in vivo. Taken together with our previous finding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought renotropic factor for renal regeneration and may prove to be effective treatment for patients with renal dysfunction, especially that caused by cisplatin.

  10. Coagulation factors and recurrence of ischemic and bleeding adverse events in patients with acute coronary syndromes.

    PubMed

    Campo, Gianluca; Pavasini, Rita; Pollina, Alberto; Tebaldi, Matteo; Ferrari, Roberto

    2013-08-01

    In the last years, management and prognosis of patients with acute coronary syndromes (ACS) are significantly improved. Nowadays antithrombotic (antiplatelet plus anticoagulant drugs) therapy represents the main treatment of ACS patients. Anticoagulant drugs are particularly helpful in the acute phase of ACS, whereas in the chronic phase are maintained only in selected cases. Many studies demonstrate that exists a significant variability in the coagulation factor levels between patients affected by ACS. This variation on coagulation factors levels is due to environmental (smoking, inflammation, sex, oral contraceptive, triglycerides, diabetes mellitus) and genetic determinants. Particularly several gene polymorphisms have been selected and clearly associated with significant variations in the coagulation factors values. The heightened levels of tissue factor, factor VII and fibrinogen are related with a "hypercoagulable status" and with a higher occurrence of ischemic complications after ACS and/or PCI. On the contrary, less data are available regarding the relationship between coagulation factors levels (or their gene polymorphisms) and bleeding complications. Recently, new anticoagulant drugs have been developed. They show less side effects and a better tolerability and, probably, their selected use in patients with a "hypercoagulable status" may improve the clinical outcome after ACS. In this review we analyze the current available data and we discuss how this finding may be useful for planning future studies to optimize the treatment of ACS patients. PMID:23827698

  11. Risk factors for early readmission to acute care for persons with schizophrenia taking antipsychotic medications.

    PubMed

    Boaz, Timothy L; Becker, Marion Ann; Andel, Ross; Van Dorn, Richard A; Choi, Jiyoon; Sikirica, Mirko

    2013-12-01

    OBJECTIVE The study examined risk factors for readmission to acute care among Florida Medicaid enrollees with schizophrenia treated with antipsychotics. METHODS Medicaid and service use data for 2004 to 2008 were used to identify adults with schizophrenia discharged from hospitals and crisis units who were taking antipsychotics. Data were extracted on demographic characteristics, service use before admission, psychopharmacologic treatment after discharge, and readmission to acute behavioral health care. Cox proportional hazards regression estimated readmission risk in the 30 days after discharge and in the period after 30 days for participants not readmitted in the first 30 days. RESULTS The mean±SD age of the 3,563 participants was 43.4±11.1; 61% were male, and 38% were white. Participants had 6,633 inpatient episodes; duration of hospitalization was 10.6±7.0 days. Readmission occurred for 84% of episodes, 23% within 30 days. Variables associated with an increased readmission risk in the first 30 days were shorter hospitalization (hazard ratio [HR]=1.18, 95% confidence interval [CI]=1.10-1.27, p<.001), shorter time on medication before discharge (HR=1.19, CI=1.06-1.35, p=.003), greater prehospitalization use of acute care (HR=2.64, CI=2.29-3.05, p<.001), serious general medical comorbidity (HR=1.21, CI=1.06-1.38, p=.005), and prior substance abuse treatment (HR=1.58, CI=1.37-1.83, p<.001). After 30 days, hospitalization duration and time on medication were not significant risk factors. CONCLUSIONS Short hospital stays for persons with schizophrenia may be associated with risk of early readmission, possibly because the person is insufficiently stabilized. More chronic risk factors include prior acute care, general medical comorbidity, and substance abuse. PMID:23945797

  12. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    PubMed Central

    Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

    2015-01-01

    Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

  13. Analysis of the risk factors for the short-term prognosis of acute ischemic stroke

    PubMed Central

    Liang, Jin; Liu, Wenbo; Sun, Jianping; Gu, Xinyi; Ma, Qiang; Tong, Weijun

    2015-01-01

    This study investigated the risk factors for the short-term prognosis of acute ischemic stroke to provide a scientific evidence for improving prevention and treatment. A total of 2557 cases of acute ischemic stroke were included in the study. We collected the data on demographic characteristics, life style-related risk factors, clinical feature, and other clinical characteristics for all the participants. The outcomes were assessed using the modified Rankin scale (mRs) on day 14 or at discharge. According to the mRs score, the subjects were divided into three groups, namely, the control group (0≤ mRs ≤2), the disability group (3≤ mRs ≤5), and the death group (mRs = 6). The general conditions of these three groups were compared. An mRs score of 3≤ mRs ≤6 belonged to the composite outcome group. Logistic regression was also applied to analyze the risk factors of short-term prognosis. Monovariant logistic regression showed that age, on-set admission, hospital stays, temperature, heart rate, stroke subtype, hypertension, hyperglycemia, history of heart disease, history of atrial fibrillation, history of cerebral stroke, drinking, count of WBC, count of mononuclear leucocyte, and rate of neutrophile granulocyte were statically significant. To further control the confounding factors, multivariant logistic regression analysis was carried out. The result showed that age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were related to the short-term prognosis. Age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were the risk factors of the short-term prognosis of acute ischemic stroke. PMID:26885162

  14. A systematic review of early prognostic factors for persistent pain following acute orthopedic trauma

    PubMed Central

    Clay, Fiona J; Watson, Wendy L; Newstead, Stuart V; McClure, Roderick J

    2012-01-01

    BACKGROUND: Acute orthopedic trauma contributes substantially to the global burden of disease. OBJECTIVES: The present systematic review aimed to summarize the current knowledge concerning prognostic factors for the presence of persistent pain, pain severity and pain-related disability following acute orthopedic trauma involving a spectrum of pathologies to working-age adults. METHODS: The Ovid MEDLINE and EMBASE databases were searched for level II prognostic studies published between January 1996 and October 2010. Studies that were longitudinal and reported results with multivariate analyses appropriate for prognostic studies were included. Studies that addressed two specific injury types that have been the subject of previous reviews, namely, injuries to the spinal column and amputations, were excluded. RESULTS: The searches yielded 992 studies; 10 studies met the inclusion criteria and were rated for methodological quality. Seventeen factors were considered in more than one cohort. There was strong evidence supporting the association of female sex, older age, high pain intensity, preinjury anxiety or depression, and fewer years of education with persistent pain outcomes. There was moderate evidence supporting the association between postinjury depression or anxiety with persistent pain, and that injury severity was not a risk factor for ongoing pain. CONCLUSION: Many individuals experience persistent pain following acute trauma. Due to the lack of studies, the use of different constructs to measure the same factor and the methodological limitations associated with many of the studies, the present review was only able to reliably identify a limited set of factors that predicted persistent pain. Recommendations for the conduct of future methodologically rigorous studies of persistent pain are provided. PMID:22518366

  15. Factors Influencing Rate of Testicular Salvage in Acute Testicular Torsion at a Tertiary Pediatric Center

    PubMed Central

    Ramachandra, Puneeta; Palazzi, Kerrin L.; Holmes, Nicholas M.; Marietti, Sarah

    2015-01-01

    Introduction Studies have demonstrated that variables other than duration of symptoms can affect outcomes in children with acute testicular torsion. We examined demographic and logistical factors, including inter-hospital transfer, which may affect outcomes at a tertiary pediatric referral center. Methods We reviewed charts of all pediatric patients with acute testicular torsion during a five-year period. Data were collected regarding age, insurance type, socioeconomic status, duration of symptoms prior to presentation, transfer status, time of day, time to surgical exploration, and testicular salvage. Results Our study included 114 patients. Testicular salvage was possible in 55.3% of patients. Thirty-one percent of patients included in the study were transferred from another facility. Inter-hospital transfer did not affect testicular salvage rate. Time to surgery and duration of pain were higher among patients who underwent orchiectomy versus orchidopexy. Patients older than eight years of age were more likely to undergo orchidopexy than those younger than eight (61.5% vs. 30.4%, p=0.01). Ethnicity, insurance type, or time of day did not affect the testicular salvage rates. On multivariate analysis, only duration of symptoms less than six hours predicted testicular salvage (OR 22.5, p<0.001). Conclusion Even though inter-hospital transfer delays definitive surgical management, it may not affect testicular salvage rates. Time to presentation is the most important factor in predicting outcomes in children with acute testicular torsion. PMID:25671040

  16. Genotyping Test with Clinical Factors: Better Management of Acute Postoperative Pain?

    PubMed Central

    Hajj, Aline; Peoc’h, Katell; Laplanche, Jean-Louis; Jabbour, Hicham; Naccache, Nicole; Abou Zeid, Hicham; Yazbeck, Patricia; Rabbaa Khabbaz, Lydia

    2015-01-01

    Individualization of acute postoperative pain treatment on an evidence-based decision process is a major health concern. The aim of this study is to investigate the influence of genetic and non-genetic factors on the variability of response to morphine in acute postoperative pain. A group of nighty-five patients undergoing major surgery were included prospectively. At 24 h, a logistic regression model was carried out to determine the factors associated with morphine doses given by a Patient Controlled Analgesia device. The dose of morphine was associated with age (p = 0.011), patient weight (p = 0.025) and the duration of operation (p = 0.030). This dose decreased with patient’s age and duration of operation and increased with patient’s weight. OPRM1 and ABCB1 polymorphisms were significantly associated with administered dose of morphine (p = 0.038 and 0.012 respectively). Patients with at least one G allele for c.118A>G OPRM1 polymorphism (AG/GG) needed 4 times the dose of morphine of AA patients. Additionally, patients with ABCB1 CT and CC genotypes for c.3435C>T polymorphism were 5.6 to 7.1 times more prone to receive higher dose of morphine than TT patients. Our preliminary results support the evidence that OPRM1/ABCB1 genotypes along with age, weight and duration of operation have an impact on morphine consumption for acute postoperative pain treatment. PMID:25809606

  17. Transcriptome Profiling of Pediatric Core Binding Factor AML

    PubMed Central

    Hsu, Chih-Hao; Nguyen, Cu; Yan, Chunhua; Ries, Rhonda E.; Chen, Qing-Rong; Hu, Ying; Ostronoff, Fabiana; Stirewalt, Derek L.; Komatsoulis, George; Levy, Shawn

    2015-01-01

    The t(8;21) and Inv(16) translocations disrupt the normal function of core binding factors alpha (CBFA) and beta (CBFB), respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML) patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq) to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21) (N = 17), Inv(16) (N = 14), and normal karyotype (NK, N = 33) were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21) and 474 genes in Inv(16) were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10−30) are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs) differentially expressed across subtypes, with 337 t(8;21)-specific and 407 Inv(16)-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5x10-51 and p = 1.8x10-54 for the two subsets). In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six patients

  18. A practical assessment of magnetic resonance diffusion-perfusion mismatch in acute stroke: observer variation and outcome.

    PubMed

    Kane, I; Hand, P J; Rivers, C; Armitage, P; Bastin, M E; Lindley, R; Dennis, M; Wardlaw, J M

    2009-11-01

    MR diffusion/perfusion mismatch may help identify patients for acute stroke treatment, but mixed results from clinical trials suggest that further evaluation of the mismatch concept is required. To work effectively, mismatch should predict prognosis on arrival at hospital. We assessed mismatch duration and associations with functional outcome in acute stroke. We recruited consecutive patients with acute stroke, recorded baseline clinical variables, performed MR diffusion and perfusion imaging and assessed 3-month functional outcome. We assessed practicalities, agreement between mismatch on mean transit time (MTT) or cerebral blood flow (CBF) maps, visually and with lesion volume, and the relationship of each to functional outcome. Of 82 patients starting imaging, 14 (17%) failed perfusion imaging. Overall, 42% had mismatch (56% at <6 h; 41% at 12-24 h; 23% at 24-48 h). Agreement for mismatch by visual versus volume assessment was fair using MTT (kappa 0.59, 95% CI 0.34-0.84) but poor using CBF (kappa 0.24, 95% CI 0.01-0.48). Mismatch by either definition was not associated with functional outcome, even when the analysis was restricted to just those with mismatch. Visual estimation is a reasonable proxy for mismatch volume on MTT but not CBF. Perfusion is more difficult for acute stroke patients than diffusion imaging. Mismatch is present in many patients beyond 12 h after stroke. Mismatch alone does not distinguish patients with good and poor prognosis; both can do well or poorly. Other factors, e.g. reperfusion, may influence outcome more strongly, even in patients without mismatch. PMID:19536582

  19. Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy

    PubMed Central

    McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.

    2011-01-01

    Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847

  20. The use of safety or uncertainty factors in the setting of acute reference doses.

    PubMed

    Renwick, A G

    2000-07-01

    A 100-fold safety or uncertainty factor has been used for about 40 years to derive safe daily intakes for humans based on animal studies; the 100-fold factor comprises separate 10-fold factors to allow for species differences and inter-individual variability. Each factor has to allow for toxicokinetic and toxicodynamic differences. Sub-dividing the 10-fold factors into kinetic and dynamic defaults, which when multiplied give a product of 10, offers a number of advantages. The main rationale for this sub-division is so that chemical-specific data can be introduced to replace one or more of the default sub-factors, hence contributing to a chemical-related overall factor. However, sub-division of the 10-fold factors has allowed analysis of the appropriateness of the overall 10-fold defaults, and analysis of special situations, such as infants and children. The establishment of an acute reference dose based on animal studies has to allow for both species differences and inter-individual variability; comparison with the factors used for chronic effects suggests that modification of the usual defaults may be appropriate under certain specific circumstances, but that the usual default of 100 remains appropriate for most cases. PMID:10983588

  1. Molecular and physiological changes in response to salt stress in Citrus macrophylla W plants overexpressing Arabidopsis CBF3/DREB1A.

    PubMed

    Alvarez-Gerding, Ximena; Espinoza, Carmen; Inostroza-Blancheteau, Claudio; Arce-Johnson, Patricio

    2015-07-01

    Plant stress induced by high salinity has leading to an important reduction in crop yields. Due to their tropical origin, citrus fruits are highly sensitive to salts. Rootstocks are the root system of fruit trees, regulating ion uptake and transport to the canopy. Therefore, increasing their salt tolerance could improve the salt tolerance of the fruit tree. For this, we genetically-transformed an important rootstock for lemon, Citrus macrophylla W, to constitutively express the CBF3/DREB1A gene from Arabidopsis, a well-studied salinity tolerance transcription factor. Transgenic lines showed normal size, with no dwarfism. Under salt stress, some transgenic lines showed greater growth, similar accumulation of chloride and sodium in the leaves and better stomatal conductance, in comparison to wild-type plants. Quantitative real-time analyses showed a similar expression of several CBF3/DREB1A target genes, such as COR15A, LEA 4/5, INV, SIP1, P5CS, GOLS, ADC2 and LKR/SDH, in transgenic lines and wild type plants, with the exception of INV that shows increased expression in line 4C15. Under salt stress, all measured transcript increased in both wild type and transgenics lines, with the exception of INV. Altogether, these results suggest a higher salt tolerance of transgenic C. macrophylla plants induced by the overexpression of AtCBF3/DREB1A. PMID:25914135

  2. A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes.

    PubMed

    Casey-Sawicki, Kate; Zhang, Mei; Kim, Sunghee; Zhang, Amy; Zhang, Steven B; Zhang, Zhenhuan; Singh, Ravi; Yang, Shanmin; Swarts, Steven; Vidyasagar, Sadasivan; Zhang, Lurong; Zhang, Aiguo; Okunieff, Paul

    2014-06-01

    The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration. PMID:24776903

  3. Acute Suicidal Affective Disturbance (ASAD): A confirmatory factor analysis with 1442 psychiatric inpatients.

    PubMed

    Stanley, Ian H; Rufino, Katrina A; Rogers, Megan L; Ellis, Thomas E; Joiner, Thomas E

    2016-09-01

    Acute Suicidal Affective Disturbance (ASAD) is a newly proposed diagnostic entity that characterizes rapid onset suicidal intent. This study aims to confirm the factor structure of ASAD among psychiatric inpatients, and to determine the clinical utility of ASAD in predicting suicide attempt status. Overall, 1442 psychiatric inpatients completed a battery of self-report questionnaires assessing symptoms theorized to comprise the ASAD construct. Utilizing these data, a confirmatory factor analysis with a one-factor solution was performed. Regression analyses were employed to determine if the ASAD construct predicted past suicide attempts, and analyses of variance (ANOVAs) were employed to determine if ASAD symptoms differed by the presence and number of past suicide attempts. The one-factor solution indicated good fit: χ(2)(77) = 309.1, p < 0.001, Tucker-Lewis Index (TLI) = 0.96, comparative fit index (CFI) = 0.97, root-mean-square error of approximation (RMSEA) = 0.05. Controlling for depressive disorders and current symptoms, the ASAD construct significantly predicted the presence of a past suicide attempt. Moreover, ASAD differentiated in the expected directions between individuals with a history of multiple suicide attempts, individuals with a single suicide attempt, and individuals with no history of a suicide attempt. Acute Suicidal Affective Disturbance (ASAD) appears to be a unified construct that predicts suicidal behavior and is distinct from an already-defined mood disorder. PMID:27344228

  4. ACUTE PANCREATITIS GRAVITY PREDICTIVE FACTORS: WHICH AND WHEN TO USE THEM?

    PubMed Central

    FERREIRA, Alexandre de Figueiredo; BARTELEGA, Janaina Alves; URBANO, Hugo Corrêa de Andrade; de SOUZA, Iure Kalinine Ferraz

    2015-01-01

    Introduction: Acute pancreatitis has as its main causes lithiasic biliary disease and alcohol abuse. Most of the time, the disease shows a self-limiting course, with a rapid recovery, only with supportive treatment. However, in a significant percentage of cases, it runs with important local and systemic complications associated with high mortality rates. Aim: To present the current state of the use of these prognostic factors (predictive scores) of gravity, as the time of application, complexity and specificity. Method: A non-systematic literature review through 28 papers, with emphasis on 13 articles published in indexed journals between 2008 and 2013 using Lilacs, Medline, Pubmed. Results: Several clinical, laboratory analysis, molecular and image variables can predict the development of severe acute pancreatitis. Some of them by themselves can be determinant to the progression of the disease to a more severe form, such as obesity, hematocrit, age and smoking. Hematocrit with a value lower than 44% and serum urea lower than 20 mg/dl, both at admission, appear as risk factors for pancreatic necrosis. But the PCR differentiates mild cases of serious ones in the first 24 h. Multifactorial scores measured on admission and during the first 48 h of hospitalization have been used in intensive care units, being the most ones used: Ranson, Apache II, Glasgow, Iget and Saps II. Conclusion: Acute pancreatitis is a disease in which several prognostic factors are employed being useful in predicting mortality and on the development of the severe form. It is suggested that the association of a multifactorial score, especially the Saps II associated with Iget, may increase the prognosis accuracy. However, the professional's preferences, the experience on the service as well as the available tools, are factors that have determined the choice of the most suitable predictive score. PMID:26537149

  5. Acute hepatitis A in Italy: incidence, risk factors and preventive measures.

    PubMed

    Tosti, M E; Spada, E; Romanò, L; Zanetti, A; Mele, A

    2008-10-01

    The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures. PMID:18837830

  6. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic

  7. Bone marrow transplantation for acute myelogenous leukemia: factors associated with early mortality

    SciTech Connect

    Bortin, M.M.; Gale, R.P.; Kay, H.E.; Rimm, A.A.

    1983-03-04

    Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells.It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team.

  8. Factors Associated with Acute Malnutrition among Children Admitted to a Diarrhoea Treatment Facility in Bangladesh

    PubMed Central

    Fuchs, Connor; Sultana, Tania; Ahmed, Tahmeed; Iqbal Hossain, M.

    2014-01-01

    To assess the risk factors for acute malnutrition (weight-for-height z-score (WHZ) < −2), a case-control study was conducted during June–September 2012 in 449 children aged 6–59 months (178 with WHZ < −2 and 271 comparing children with WHZ ≥ −2 and no edema) admitted to the Dhaka Hospital of icddr,b in Bangladesh. The overall mean ± SD age was 12.0 ± 7.6 months, 38.5% (no difference between case and controls). The mean ± SD WHZ of cases and controls was −3.24 ± 1.01 versus −0.74 ± 0.95 (P < 0.001), respectively. Logistic regression analysis revealed that children with acute malnutrition were more likely than controls to be older (age > 1 year) (adjusted OR (AOR): 3.1, P = 0.004); have an undernourished mother (body mass index < 18.5), (AOR: 2.8, P = 0.017); have a father with no or a low-paying job (AOR: 5.8, P < 0.001); come from a family having a monthly income of <10,000 taka, (1 US$ = 80 taka) (AOR: 2.9, P = 0.008); and often have stopped predominant breastfeeding before 4 months of age (AOR: 2.7, P = 0.013). Improved understanding of these characteristics enables the design and targeting of preventive-intervention programs of childhood acute malnutrition. PMID:24734048

  9. Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

    PubMed Central

    Yang, Suqiao; Yang, Yuanhua; Zhai, Zhenguo; Kuang, Tuguang; Gong, Juanni; Zhang, Shuai; Zhu, Jianguo; Liang, Lirong; Shen, Ying H.

    2015-01-01

    Background Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE). Methods In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA). Results Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH. Conclusions CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH. PMID:26716031

  10. Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia

    PubMed Central

    Somasundaram, Rajesh; Prasad, Mahadesh A. J.; Ungerbäck, Jonas

    2015-01-01

    B-lymphocyte development in the bone marrow is controlled by the coordinated action of transcription factors creating regulatory networks ensuring activation of the B-lymphoid program and silencing of alternative cell fates. This process is tightly connected to malignant transformation because B-lineage acute lymphoblastic leukemia cells display a pronounced block in differentiation resulting in the expansion of immature progenitor cells. Over the last few years, high-resolution analysis of genetic changes in leukemia has revealed that several key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and PAX5, are genetically altered in a large portion of the human B-lineage acute leukemias. This opens the possibility of directly linking the disrupted development as well as aberrant gene expression patterns in leukemic cells to molecular functions of defined transcription factors in normal cell differentiation. This review article focuses on the roles of transcription factors in early B-cell development and their involvement in the formation of human leukemia. PMID:25990863

  11. Intrinsic factors influencing help-seeking behaviour in an acute stroke situation.

    PubMed

    Zock, Elles; Kerkhoff, Henk; Kleyweg, Ruud Peter; van de Beek, Diederik

    2016-09-01

    The proportion of stroke patients eligible for intravenous or intra-arterial treatment is still limited because many patients do not seek medical help immediately after stroke onset. The aim of our study was to explore which intrinsic factors and considerations influence help-seeking behaviour of relatively healthy participants, confronted with stroke situations. Semi-structured interviews were conducted with 25 non-stroke participants aged 50 years or older. We presented 5 clinical stroke situations as if experienced by the participants themselves. Recognition and interpretation of symptoms were evaluated and various factors influencing help-seeking behaviour were explored in-depth. We used the thematic synthesis method for data analysis. Five themes influencing help-seeking behaviour in a stroke situation were identified: influence of knowledge, views about seriousness, ideas about illness and health, attitudes towards others and beliefs about the emergency medical system. A correct recognition of stroke symptoms or a correct interpretation of the stroke situations did not automatically result in seeking medical help. Interestingly, similar factors could lead to different types of actions between participants. Many intrinsic, as well as social and environmental factors are of influence on help-seeking behaviour in an acute stroke situation. All these factors seem to play a complex role in help-seeking behaviour with considerable inter-individual variations. Accomplishing more patients eligible for acute stroke treatment, future research should focus on better understanding of all factors at various levels grounded in a theory of help-seeking behaviour. PMID:26732617

  12. Institutional adherence to cardiovascular risk factor screening guidelines for young survivors of acute lymphoblastic leukemia.

    PubMed

    Lin, Maria H; Wood, Jamie R; Mittelman, Steven D; Freyer, David R

    2015-05-01

    Survivors of acute lymphoblastic leukemia have increased risk for long-term cardiovascular complications. Early identification of cardiovascular risk factors (CVRF) may allow for effective interventions. In this retrospective cohort study of 194 patients at Children's Hospital Los Angeles, we investigated CVRF screening practices in an established childhood cancer survivorship program relative to both the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines and American Academy of Pediatrics (AAP) recommendations. CVRF screening practices met COG but not the more stringent AAP recommendations, particularly in areas of dyslipidemia and diabetes screening. Implications of our findings are discussed. PMID:25757021

  13. PEBP2-beta/CBF-beta-dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis.

    PubMed

    Wee, Hee-Jun; Voon, Dominic Chih-Cheng; Bae, Suk-Chul; Ito, Yoshiaki

    2008-11-01

    The heterodimeric transcription factor RUNX1/PEBP2-beta (also known as AML1/CBF-beta) is essential for definitive hematopoiesis. Here, we show that interaction with PEBP2-beta leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser(249), Ser(273), and Thr(276) in RUNX1, in a manner that is also dependent on the RUNX1 PY motif. Importantly, we observed the in vitro disruption of this phosphorylation cascade by multiple leukemogenic genetic defects targeting RUNX1/CBFB. In particular, the oncogenic protein PEBP2-beta-SMMHC prevents RUNX1/p300 phosphorylation by sequestering HIPK2 to mislocalized RUNX1/beta-SMMHC complexes. Therefore, phosphorylation of RUNX1 appears a critical step in its association with and phosphorylation of p300, and its disruption may be a common theme in RUNX1-associated leukemogenesis. PMID:18695000

  14. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.

    PubMed

    Oliveira, Marina C; Tavares, Luciana P; Vago, Juliana P; Batista, Nathália V; Queiroz-Junior, Celso M; Vieira, Angelica T; Menezes, Gustavo B; Sousa, Lirlândia P; van de Loo, Fons A J; Teixeira, Mauro M; Amaral, Flávio A; Ferreira, Adaliene V M

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  15. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis

    PubMed Central

    Oliveira, Marina C.; Tavares, Luciana P.; Vago, Juliana P.; Batista, Nathália V.; Queiroz-Junior, Celso M.; Vieira, Angelica T.; Menezes, Gustavo B.; Sousa, Lirlândia P.; van de Loo, Fons A. J.; Teixeira, Mauro M.; Amaral, Flávio A.; Ferreira, Adaliene V. M.

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  16. Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.

    PubMed

    Kaur, Rupinder; Das, Reena; Ahluwalia, Jasmina; Kumar, Rohit Manoj; Talwar, K K

    2016-03-01

    This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients. PMID:25155498

  17. Recipient Clinical Risk Factors Predominate in Possible Transfusion-Related Acute Lung Injury

    PubMed Central

    Toy, Pearl; Bacchetti, Peter; Grimes, Barbara; Gajic, Ognjen; Murphy, Edward L.; Winters, Jeffrey L.; Gropper, Michael A.; Hubmayr, Rolf D.; Matthay, Michael A.; Wilson, Gregory; Koenigsberg, Monique; Lee, Deanna C.; Hirschler, Nora V.; Lowell, Clifford A.; Schuller, Randy M.; Gandhi, Manish J.; Norris, Philip J.; Mair, David C.; Rosen, Rosa Sanchez; Looney, Mark R.

    2014-01-01

    Background Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI. Study Design and Methods In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year period at the University of California, San Francisco and the Mayo Clinic, Rochester. Results For pTRALI, we found evidence against transfusion being important: receipt of plasma from female donors (OR 0.82, 95% CI 0.29 – 2.3, p=0.70), total number of units transfused (OR 0.99, 95% CI 0.89 – 1.10, p=0.86), and number of red blood cell and whole blood units transfused (OR 0.78, 95% CI 0.59 –1.03, p=0.079). In contrast, we found that risk for pTRALI was associated with additional recipient factors: chronic alcohol abuse (OR 12.5, 95% CI 2.8 – 55, p<0.001), current smoker (OR 4.2, 95% CI 1.67 – 10.8, p=0.0024), shock before transfusion (OR 4.6, 95% CI 2.0 – 10.7, p<0.001), and positive fluid balance before transfusion (OR 1.32 per liter, 95% CI 1.20 – 1.44, p<0.001). Conclusion Recipient risk factors for ARDS rather than transfusion risk factors predominate in pTRALI. PMID:25488517

  18. CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing

    SciTech Connect

    Maita, Hiroshi; Kitaura, Hirotake; Ariga, Hiroyoshi . E-mail: hiro@pharm.hokudai.ac.jp; Iguchi-Ariga, Sanae M.M.

    2005-02-15

    We have reported that PAP-1, a product of a causative gene for autosomal retinitis pigmentosa, plays a role in splicing. In this study, CIR, a protein originally identified as a CBF1-interacting protein and reported to act as a transcriptional corepressor, was identified as a PAP-1 binding protein and its function as a splicing factor was investigated. In addition to a basic lysine and acidic serine-rich (BA) domain and a zinc knuckle-like motif, CIR has an arginine/serine dipeptide repeat (RS) domain in its C terminal region. The RS domain has been reported to be present in the superfamily of SR proteins, which are involved in splicing reactions. We generated CIR mutants with deletions of each BA and RS domain and studied their subcellular localizations and interactions with PAP-1 and other SR proteins, including SC35, SF2/ASF, and U2AF{sup 35}. CIR was found to interact with U2AF{sup 35} through the BA domain, with SC35 and SF2/ASF through the RS domain, and with PAP-1 outside the BA domain in vivo and in vitro. CIR was found to be colocalized with SC35 and PAP-1 in nuclear speckles. Then the effect of CIR on splicing was investigated using the E1a minigene as a reporter in HeLa cells. Ectopic expression of CIR with the E1a minigene changed the ratio of spliced isoforms of E1a that were produced by alternative selection of 5'-splice sites. These results indicate that CIR is a member of the family of SR-related proteins and that CIR plays a role in splicing regulation.

  19. Pharmacokinetics and acute tolerance of a double virus inactivated plasma derived factor VIII concentrate.

    PubMed

    Saez, A; Bosh, N; Boadas, N; Arguello, A; Horvat, D; Dinapoli, G; Lisciani, R

    1999-07-01

    To further reduce the risk of possible viral disease transmission, an additional virucidal step was performed in the manufacturing process of a solvent/detergent treated factor VIII concentrate, which consisted of heating the lyophilized preparation at 100 degrees C for 30 min (Emoclot DI; ISI, Italy). Because thermal treatment may modify factor VIII bioavailability, the pharmacokinetic parameters and the acute tolerance of the single viral inactivated concentrate (preparation A) were compared with that of the double viral inactivated one (preparation B). Fifteen patients with severe haemophilia A and positive for HAV Ab were enrolled in a double-blind cross-over study and injected with 32.5 IU kg-1 of preparation A and 27 IU kg-1 of the preparation B. No significant differences between terminal half-life, area under the curve/dose, clearance/kg, volume of distribution at the steady state, in vivo recovery and acute tolerance of the two preparations was observed. The only statistical difference was restricted to Cmax. PMID:10469180

  20. 62. (Credit CBF) Operating floor of filter room, c1912. The ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    62. (Credit CBF) Operating floor of filter room, c1912. The remodeled New York horizontal pressure filters (now gravity filters) are in the foreground; the remodelled Hyatt tub filters are in the background. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  1. Field performance of transgenic 'M.26' apples overexpressing a peach CBF gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to cold acclimate and undergo a period of dormancy is essential to temperate woody plants in order to survive freezing winter temperatures. CBF genes have been shown to regulate a large number of cold-regulated (COR) genes whose products are thought to contribute to freezing tolerance. ...

  2. 7. (Credit CBF) View of the McNeil Street Station from ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. (Credit CBF) View of the McNeil Street Station from across Cross Bayou in March 1913, after completion of the auxiliary pump pit. The tool shed and tool supply house of the Shreveport Water Works Company is on the right edge of the photo. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  3. 32. (Credit CBF) Boilers in the McNeil Street Station, November ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. (Credit CBF) Boilers in the McNeil Street Station, November 1911: two 100 hp Atlas boilers and one Chattanooga boiler. The Atlas boilers were installed c1892, the Chattanooga boiler c1897. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  4. Short-term prognostic factors in the patients after acute heart failure.

    PubMed

    Wang, Xinliang; Liu, Yingfeng; Yuan, Yong; Feng, Li; Ning, Ye

    2015-01-01

    To explore risk factors of short-term prognosis of acute heart failure (AHF) patients and compare the difference between acute heart failure with reduced ejection fraction (AHFREF) and acute heart failure with preserved ejection fraction (AHFPEF). A retrospective analysis of medical records of AHF patients was performed. Eligible patients were at the age of more than 18 years old, excluding malignancy, acute pulmonary embolism, heart valve diseases (such as mild valvular regurgitation), severe renal insufficiency, and N-terminal pro-brain natriuretic peptide (NT-proBNP) < 300 pg/ml. AHFREF group (LVEF < 0.5) and AHFPEF group (LVEF ≥ 0.5) were classified depending on the left ventricular ejection fraction (LVEF). The involved patients were followed up via telephone contact and consult of medical recording. Unfavorable prognosis was defined upon the cardiac death and re-hospitalization within 6 months; otherwise they had a favorable prognosis. We analyzed the impact factors of short-term prognosis, including patient's age, gender, systolic blood pressure, diastolic blood pressure, heart rate, NT-proBNP, blood glucose, heart ultrasound LVEF, cardiothoracic ration in chest radiograph, history of hypertension, coronary heart disease and diabetes mellitus, for multivariate logistic regression analysis. A total of 130 AHF patients were included in the analysis, including 79 male (60.8%) and 51 female (39.2%). The average age of all involved patients was 74.0 years [M (P 25, P 75) = 64.0, 80.0]. Fifteen cases (11.5%) had unfavorable prognosis and 35 cases (27.0%) had favorable prognosis in the AHFREF group, while the cases in the AHFPEF group were respectively 31 (23.8%) and 49 (37.7%). There was no significant difference in the short-term prognosis between the two groups (χ (2) = 1.030, P = 0.310). The short-term prognosis in AHF patients was mainly influenced by NT-proBNP (r = -0.263, P = 0.035), blood glucose (r = -0.090, P = 0.049) and systolic blood pressure (r = 0

  5. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study

    PubMed Central

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-01-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011–2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  6. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    PubMed

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  7. Risk factors and prognostic factors of acute kidney injury in children: A retrospective study between 2003 and 2013.

    PubMed

    Zhou, Yan-mei; Yin, Xiao-ling; Huang, Zhi-bin; He, Yong-hua; Qiu, Li-ru; Zhou, Jian-hua

    2015-12-01

    Recent report on epidemiology of acute kidney injury (AKI) is lacking for Chinese children. We aimed to investigate the risk factors for stage and prognostic factors for renal recovery in hospitalized children. Pediatric patients (≤18 years old) admitted during 2003 to 2013 were enrolled in this study. AKI was defined and staged using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression analysis was performed to determine the risk factors and prognostic factors. The morbidity of pediatric AKI was 0.31% (205/65 237). There were 45 (22.0%) cases in stage III, 30 (14.6%) cases in stage II and 130 (63.4%) cases in stage III. The majority of etiologies were intrinsic renal defects (85.4%). Age, weight, vomit, etiology, blood urea nitrogen (BUN) at admission and several blood gas measurements were associated with AKI stage III. Age (OR=0.894; 95% CI, 0.832-0.962; P=0.003), vomit (OR=2.375; 95% CI, 1.058-5.333; P=0.036) and BUN at admission (OR=1.135; 95% CI, 1.085-1.187; P<0.001) were identified as independent risk factors for AKI stage III. After treatment, 172 (83.9%) patients achieved complete or partial recovery. The mortality was 3.9%. Variables were found as prognostic factors for renal recovery, such as age, stage, hospital stay, BUN at discharge, white blood cells, red blood cells, platelets (PLTs), blood pH and urine blood. Among them, AKI stage (stage III vs. stage I; OR, 6.506; 95% CI, 1.640-25.816; P=0.008), BUN at discharge (OR, 0.918; 95% CI, 0.856-0.984; P=0.016) and PLTs (OR, 1.007; 95% CI, 1.001-1.013; P=0.027) were identified as independent prognostic factors. AKI is still common in Chinese hospitalized children. Identified risk factors and prognostic factors provide guiding information for clinical management of AKI. PMID:26670426

  8. Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

    PubMed

    Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

    2015-01-01

    OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI. PMID:25627761

  9. Taxanes as a Risk Factor for Acute Adverse Reactions to Iodinated Contrast Media in Cancer Patients

    PubMed Central

    Farolfi, Alberto; Della Luna, Corradina; Ragazzini, Angela; Carretta, Elisa; Gentili, Nicola; Casadei, Carla; Aquilina, Michele; Barone, Domenico; Minguzzi, Martina; Amadori, Dino; Nanni, Oriana

    2014-01-01

    Background. The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. Methods. We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. Results. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74–1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14–2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02–4.16). Conclusion. Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs. PMID:25063226

  10. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity. PMID:24164734

  11. Clinical and radiological factors affecting progressive collapse of acute osteoporotic compression spinal fractures.

    PubMed

    Goldstein, Sergei; Smorgick, Yossi; Mirovsky, Yigal; Anekstein, Yoram; Blecher, Ronen; Tal, Sigal

    2016-09-01

    Osteoporotic compression spine fractures have a different clinical course and outcomes when compared to spinal fractures occurring in the younger population. Only a few studies have investigated the risk factors for progressive osteoporotic compression spine fractures. The purpose of this study was to investigate clinical and radiological factors related to progressive collapse following acute osteoporotic compression spine fractures. We retrospectively identified all patients treated for thoracolumbar fractures in our institution between January 2008 and July 2013. Included cases were examined by plain radiographs and CT scans. For each patient we classified the fracture according to the AOSpine Thoracolumbar Spine Injury Classification System. The difference between initial and final height loss and initial and final local kyphosis was documented as height loss difference and kyphotic angle difference. The presence of old fractures and intravertebral cleft were also documented. The study included 153 patients, comprising 102 women and 51 men. The mean patient age was 68.9years. The mean length of follow up was 15months. A statistically significant correlation was found between patient age, final height loss, height loss difference and kyphotic angle difference. Height loss difference and kyphotic angle difference were significantly correlated to type of fracture according to the AO classification system. The height loss difference was 18.1% in A1 type fractures, 27.1% in A2 type fractures, 24.2% in A3 type fractures and 25.7% in A4 type fractures. During a minimum 3-month follow up of conservative treatment for acute osteoporotic vertebral compression fractures, age and the AOSpine Thoracolumbar Spine Injury Classification System were predictive factors for progressive collapse. PMID:27387197

  12. Acute Lung Injury Complicating Blood Transfusion in Post-Partum Hemorrhage: Incidence and Risk Factors

    PubMed Central

    Teofili, Luciana; Bianchi, Maria; Zanfini, Bruno A.; Catarci, Stefano; Sicuranza, Rossella; Spartano, Serena; Zini, Gina; Draisci, Gaetano

    2014-01-01

    Background We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH). Methods We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed. Results Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27–604.3, p=0.034). Conclusions Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended. PMID:25408855

  13. Selective Activation of Transcription by a Novel CCAAT Binding Factor

    NASA Astrophysics Data System (ADS)

    Maity, Sankar N.; Golumbek, Paul T.; Karsenty, Gerard; de Crombrugghe, Benoit

    1988-07-01

    A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α 2(I) collagen, the α 1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.

  14. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization.

    PubMed Central

    Sasse, J; Hemmann, U; Schwartz, C; Schniertshauer, U; Heesel, B; Landgraf, C; Schneider-Mergener, J; Heinrich, P C; Horn, F

    1997-01-01

    Signal transducer and transcription (STAT) factors are activated by tyrosine phosphorylation in response to a variety of cytokines, growth factors, and hormones. Tyrosine phosphorylation triggers dimerization and nuclear translocation of these transcription factors. In this study, the functional role of carboxy-terminal portions of the STAT family member acute-phase response factor/Stat3 in activation, dimerization, and transactivating potential was analyzed. We demonstrate that truncation of 55 carboxy-terminal amino acids causes constitutive activation of Stat3 in COS-7 cells, as is known for the Stat3 isoform Stat3beta. By the use of deletion and point mutants, it is shown that both carboxy- and amino-terminal portions of Stat3 are involved in this phenomenon. Dimerization of Stat3 was blocked by point mutations affecting residues both in the vicinity of the tyrosine phosphorylation site (Y705) and more distant from this site, suggesting that multiple interactions are involved in dimer formation. Furthermore, by reporter gene assays we demonstrate that carboxy-terminally truncated Stat3 proteins are incapable of transactivating an interleukin-6-responsive promoter in COS-7 cells. In HepG2 hepatoma cells, however, these truncated Stat3 forms transmit signals from the interleukin-6 signal transducer gp130 equally well as does full-length Stat3. We conclude that, dependent on the cell type, different mechanisms allow Stat3 to regulate target gene transcription either with or without involvement of its putative carboxy-terminal transactivation domain. PMID:9234724

  15. Risk Factors for Acute Kidney Injury in Visceral Leishmaniasis (Kala-Azar)

    PubMed Central

    Oliveira, Michelle J. C.; Silva Júnior, Geraldo B.; Abreu, Krasnalhia Lívia S.; Rocha, Natália A.; Garcia, Ana Valeska V.; Franco, Luiz F. L. G.; Mota, Rosa M. S.; Libório, Alexandre B.; Daher, Elizabeth F.

    2010-01-01

    The aim of this study was to investigate the factors associated with acute kidney injury (AKI) in patients with visceral leishmaniasis (VL). The study patients had a diagnosis of VL and were admitted to a tertiary hospital. A multivariate analysis was performed to analyze the risk factors for AKI. A total of 224 patients were included. The mean age was 36 ± 15 years. AKI was observed in 33.9% of cases. Risk factors associated with AKI were male gender (odds ratio [OR] = 2.2; P = 0.03), advanced age (OR = 1.05; P < 0.001), and jaundice (OR = 2.9; P = 0.002). There was an association between amphotericin B use and AKI (OR = 18.4; P < 0.0001), whereas glucantime use was associated with lower incidence of AKI compared with amphotericin B use (OR = 0.05; P < 0.0001). Mortality was 13.3%, and it was higher in AKI patients (30.2%). Therefore, factors associated with AKI were male gender, advanced age, and jaundice. Amphotericin B was an important cause of AKI in VL. PMID:20207871

  16. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.

    PubMed

    Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A; Novak, Vera

    2015-08-01

    Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood-brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423

  17. Mutations of Complement Factor I and Potential Mechanisms of Neuroinflammation in Acute Hemorrhagic Leukoencephalitis

    PubMed Central

    Broderick, Lori; Gandhi, Chhavi; Mueller, James L.; Putnam, Christopher D.; Shayan, Katayoon; Giclas, Patricia C.; Peterson, Karin S.; Aceves, Seema S.; Sheets, Robert M.; Peterson, Bradley M.; Newbury, Robert O.; Hoffman, Hal M.; Bastian, John F.

    2012-01-01

    Purpose Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder. Methods Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms. Results Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1. Conclusions We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease. PMID:22926405

  18. Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management

    PubMed Central

    Blasco-Algora, Sara; Masegosa-Ataz, José; Gutiérrez-García, María Luisa; Alonso-López, Sonia; Fernández-Rodríguez, Conrado M

    2015-01-01

    Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies. PMID:26576097

  19. Incidence of acute volleyball injuries: a prospective cohort study of injury mechanisms and risk factors.

    PubMed

    Bahr, R; Bahr, I A

    1997-06-01

    The purpose of the study was to examine the incidence and mechanisms of acute volleyball injuries, with particular reference to possible risk factors for ankle injuries. Coaches and players in the top two divisions of the Norwegian Volleyball Federation were asked to keep records of exposure time and all acute volleyball injuries causing a player to miss at least one playing day during one season. We found 89 injuries among 272 players during 51588 player hours, 45837 h of training and 5751 h of match play. The total injury incidence was 1.7 +/- 0.2 per 1000 h of play, 1.5 +/- 0.2 during training and 3.5 +/- 0.8 during match play. The ankle (54%) was the most commonly injured region, followed by the lower back (11%), knee (8%), shoulder (8%) and fingers (7%). Of the ankle injuries, 79% were recurrences, and the relative risk of injury was 3.8 (P < 0.0001) for previously injured ankles (38 of 232) vs. non-injured ankles (10 of the 234). Moreover, a reinjury was observed in 21 of the 50 ankles that had suffered an ankle sprain within the last 6 months (42.0 +/- 7.0%; risk ratio: 9.8 vs. uninjured ankles; P < 0.000001). The data indicate that external supports should be worn for 6-12 months after an ankle sprain and that specific injury prevention programs may be developed for ankle sprains in volleyball. PMID:9200321

  20. The CBF gene family in apple (malus x domestica Borkh.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many vascular plants have evolved mechanisms for protecting themselves from freeze damage. One of the key pathways controlling higher plant responses to low temperature involves a family of genes which belong to the AP2 domain class of transcription factors. The promoters of many genes involved in...

  1. Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.

    PubMed

    Satriotomo, I; Nichols, N L; Dale, E A; Emery, A T; Dahlberg, J M; Mitchell, G S

    2016-05-13

    Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies. PMID:26944605

  2. BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia.

    PubMed

    Roe, Jae-Seok; Mercan, Fatih; Rivera, Keith; Pappin, Darryl J; Vakoc, Christopher R

    2015-06-18

    The bromodomain and extraterminal (BET) protein BRD4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that BRD4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) PU.1, FLI1, ERG, C/EBPα, C/EBPβ, and MYB at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate BRD4 recruitment to their occupied sites to promote transcriptional activation. Chemical inhibition of BET bromodomains was found to suppress the functional output of each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and BRD4 that supports leukemia maintenance and is suppressed by BET bromodomain inhibition. PMID:25982114

  3. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke

    PubMed Central

    Samai, Alyana A.; Boehme, Amelia K.; Shaban, Amir; George, Alexander J.; Dowell, Lauren; Monlezun, Dominique J.; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl

    2016-01-01

    Background and Purpose Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. Methods AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Results Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0–5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63–66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82–57.5, P = .0083) increased 10 times. Conclusion Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. PMID:26777556

  4. Acute Coronary Syndrome in the Young: Clinical Characteristics, Risk Factors and Prognosis

    PubMed Central

    Esteban, Marcos R; Montero, Sara M; Sánchez, José J. A; Hernández, Horacio P; Pérez, José J. G; Afonso, Julio H; Pérez, del C. R; Díaz, Buenaventura B; de León, Antonio C

    2014-01-01

    Background: To describe the characteristics of patients ≤40 years of age hospitalized for acute coronary syndrome, analyze the risk factors and identify the variables associated with prognosis. Methods: Case series of patients admitted between 2003 and 2012 inclusive in a tertiary hospital (123 consecutive cases admitted between 2003 and 2012), and case-control study (369 controls selected from the general population matched for sex and age with cases, at a ratio of 3:1). Outcome variables: Mortality, likelihood of survival without readmission for heart-related problems, extent of coronary disease as determined by coronary angiography and cardiovascular risk factors. Results: Mean age was 35.4±4.8 years and 83.7% of the participants were men. Myocardial infarction with abnormal Q wave (48%) and single-vessel involvement (44.7%) predominated. Intrahospital mortality was 1.6%. For the 108 patients eventually included in the follow-up, likelihood of readmission-free survival after 60 months was 69.3±4.8%. In the case group 36% of the patients admitted to using cocaine. Compared to controls, the prevalence in patients was higher for smoking (74.8 vs 33.1%, p<0001), diabetes (14.6% vs 5.1%, p=0.001), low HDL-cholesterol (82.9 vs 34.1%, p<0.001) and obesity (30.0 vs 20.3%, p=0.029). Decreased left ventricular ejection fraction (odds ratio=2.2, p=0.033) and smoking (odds ratio=7.8, p=0.045) were associated with readmission for coronary syndrome. Conclusion: Acute coronary syndrome in people younger than 40 years is associated with diabetes and unhealthy lifestyle: smoking, sedentary behavior (low HDL-cholesterol), cocaine use and obesity. The readmission rate is high, and readmission is associated with smoking and decreased ejection fraction. PMID:25152777

  5. [Risk factors for severe acute lower respiratory tract infection in Bogota, 2001].

    PubMed

    Jaimes, María Belén; Cáceres, Diana C; de la Hoz, Fernando; Gutiérrez, Camilo; Herrera, Diana; Pinilla, Jairo; Porras, Alexandra; Rodríguez, Fabio; Velandia, Martha

    2003-09-01

    Severity of acute respiratory infection is higher in developing countries, especially among the socioeconomically underprivileged. Viral pneumonias are more common, especially among children. A prospective hospital-based case control study was undertaken in Bogota between November 2000 and August 2001, aimed to identify factors related to severe low acute respiratory infection (SLARI). Cases were limited to children aged between 2 months and 5 years who filled WHO criteria for SLARI. Controls were children at the same hospital with ARI in a similar age range, but without symptoms of chest drawing. A total of 638 children (277 cases and 361 controls) were included. The most important risk factors included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95% Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7), living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was the most frequently identified virus (41.8%), followed by influenza A virus (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B were sent to the United States Center for Disease Control (CDC) in Atlanta, where they were classified as influenza A/PANAMA/2007/99-like and influenza B/SICHUAN/379/99-like, respectively. PMID:14582331

  6. Factors Associated with Follow-Up Attendance among Rape Victims Seen in Acute Medical Care

    PubMed Central

    Darnell, Doyanne; Peterson, Roselyn; Berliner, Lucy; Stewart, Terri; Russo, Joan; Whiteside, Lauren; Zatzick, Douglas

    2016-01-01

    Objective Rape is associated with Posttraumatic Stress Disorder and related comorbidities. Most victims do not obtain treatment for these conditions. Acute care medical settings are well-positioned to link patients to services; however, difficulty engaging victims and low attendance at provided follow-up appointments is well documented. Identifying factors associated with follow-up can inform engagement and linkage strategies. Method Administrative, patient self-report, and provider observational data from Harborview Medical Center were combined for the analysis. Using logistic regression, we examined factors associated with follow-up health service utilization after seeking services for rape in the emergency department. Results Of the 521 diverse female (n=476) and male (n=45) rape victims, 28% attended the recommended medical/counseling follow-up appointment. In the final (adjusted) logistic regression model, having a developmental or other disability (OR=0.40, 95% CI=0.21-0.77), having a current mental illness (OR=0.25, 95% CI=0.13-0.49), and being assaulted in public (OR=0.50, 95% CI=0.28-0.87) were uniquely associated with reduced odds of attending the follow-up. Having a prior mental health condition (OR= 3.02 95% CI=1.86-4.91), a completed SANE examination (OR=2.97, 95% CI=1.84-4.81), and social support available to help cope with the assault (OR=3.54, 95% CI=1.76-7.11) were associated with an increased odds of attending the follow-up. Conclusions Findings point to relevant characteristics ascertained at the acute care medical visit for rape that may be used to identify victims less likely to obtain posttraumatic medical and mental health services. Efforts to improve service linkage among these patients is warranted and may require alternative models to engage these patients to support posttraumatic recovery. PMID:26168030

  7. Risk factors for school absence after acute orthopaedic injury in new york city.

    PubMed

    Hyman, Joshua E; Jewetz, Shari T; Matsumoto, Hiroko; Choe, Julie C; Vitale, Michael G

    2007-06-01

    The purpose of our study is to identify specific factors that affect a child's ability to attend school after an acute orthopaedic injury. One hundred and sixty-four school-aged patients receiving treatment for an acute orthopaedic injury at the Division of Pediatric Orthopaedics were interviewed along with their parents. Most participants were Hispanic, which reflects the population of the Washington Heights section of Manhattan served by our hospital. Follow-up telephone interviews were conducted with those parents whose children were unable to return to school. The parents were asked of both the total number of school absences and whether the child received home instruction. A survey regarding official school attendance policy was mailed to the principals of all the schools attended by the children in our study. Forty-seven percent of the children were unable to return to school immediately after their injuries. Nearly 70% (n = 51) of the children who did not immediately return to school attributed their nonattendance to their school's attendance policy. Only half of the absentees received home instruction. A multivariate analysis showed that both the type of school (public vs private) and the use of crutches were statistically significant risk factors for school absence. The median household income also trended toward significance in predicting school attendance. The responses to our survey regarding official school attendance policy demonstrated considerable variability among the schools. This study indicates that pediatric orthopaedic injuries and their treatment impact the ability of school-aged patients to attend school. Our study shows that children's socioeconomic background influences their ability to attend school while injured. PMID:17513963

  8. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

    PubMed

    Lang, C H; Pollard, V; Fan, J; Traber, L D; Traber, D L; Frost, R A; Gelato, M C; Prough, D S

    1997-07-01

    The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection. PMID:9249574

  9. Risk factors for recurrent cystitis following acute cystitis in female patients.

    PubMed

    Yoon, Byung Il; Kim, Sun Wook; Ha, U-Syn; Sohn, Dong Wan; Cho, Yong-Hyun

    2013-08-01

    We conducted a retrospective analysis of acute cystitis (AC) patients to evaluate the risk factors of recurrent cystitis (RC) patients following AC. The clinical records of 254 subjects with a confirmed diagnosis of AC and 90 healthy subjects who visited the Health Promotion Center between 2008 and 2012 were reviewed. A patient was diagnosed with RC if she was treated for three or more symptomatic episodes of cystitis over a 12-month period. Results were analyzed according to three groups: normal control (group A, n = 90), AC (group B, n = 121), and RC (group C, n = 133). Women in the cystitis groups (groups B and C) were more likely to have diabetes, be menopausal, have a history of catheterization or sexually transmitted infections (STI), have a low daily water intake, have frequent sexual intercourse, and to use contraception more frequently than the normal control group (P < 0.05). In groups B and C, Escherichia coli was the most common uropathogen, followed by Staphylococcus saprophyticus, Enterococcus species, and Klebsiella species. There were no differences between groups in the detection rates of these uropathogens. Factors that affected progression to RC were diabetes, catheterization history, STI history, sexual intercourse more than four times per month, sexual intercourse in the last month, and the use of contraceptives (P < 0.05). The identification of these factors may help develop preventive, diagnostic, and therapeutic strategies for treating RC that has progressed from AC. PMID:23380970

  10. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation.

    PubMed

    Arai, Y; Kanda, J; Nakasone, H; Kondo, T; Uchida, N; Fukuda, T; Ohashi, K; Kaida, K; Iwato, K; Eto, T; Kanda, Y; Nakamae, H; Nagamura-Inoue, T; Morishima, Y; Hirokawa, M; Atsuta, Y; Murata, M

    2016-01-01

    Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients. PMID:26367230

  11. Risk Factors for Extended Duration of Acute Diarrhea in Young Children

    PubMed Central

    Strand, Tor A.; Sharma, Pushpa R.; Gjessing, Håkon K.; Ulak, Manjeswori; Chandyo, Ram K.; Adhikari, Ramesh K.; Sommerfelt, Halvor

    2012-01-01

    Objective and Background We sought to identify predictors of extended duration of diarrhea in young children, which contributes substantially to the nearly 1 1/2 million annual diarrheal deaths globally. Methods We followed 6-35 month old Nepalese children enrolled in the placebo-arm of a randomized controlled trial with 391 episodes of acute diarrhea from the day they were diagnosed until cessation of the episode. Using multiple logistic regression analysis, we identified independent risk factors for having diarrhea for more than 7 days after diagnosis. Results Infants had a 17 (95% CI 3.5, 83)-fold and toddlers (12 to 23 month olds) a 9.9 (95% CI 2.1, 47)-fold higher odds of having such illness duration compared to the older children. Not being breastfed was associated with a 9.3 (95% CI 2.4, 35.7)-fold increase in the odds for this outcome. The odds also increased with increasing stool frequency. Furthermore, having diarrhea in the monsoon season also increased the risk of prolonged illness. Conclusion We found that high stool frequency, not being breastfed, young age and acquiring diarrhea in the rainy season were risk factors for prolonged diarrhea. In populations such as ours, breastfeeding may be the most important modifiable risk factor for extended duration of diarrhea. PMID:22590543

  12. [Influence of cortical neurotrophic factors on the neurocytokine production system in acute hemorrhagic stroke].

    PubMed

    Kul'chikov, A E; Kositsyn, N S; Svinov, M M; Vasil'eva, I G; Makarenko, A N

    2009-01-01

    The mechanism of therapeutic action of cortical neurotropic factors (CNTF) was studied in hemorrhagic stroke. In intracerebral hemorrhage, CNTFs were shown to elevate the level of nerve growth factor mRNA and at the same time, produce no effect on its level in intact animals. The neuroactivating action of CNTF in the acute phase of hemorrhagic stroke was achieved by intranasal administration due to the retrograde axon transport of CNTF molecules along the olfactory nerve fibers to the brain, by passing the blood-brain barrier. It was ascertained that the molecules of tritium-labeled CHTF accumulated in the central nervous system following 20 minutes and the level of label accumulation is proportionally increased after 120 minutes. The pattern of accumulation of the intranasally administered label in the olfactory tract and olfactory bulb proves CNTF transportation along these structures of the nervous system. Therefore, when intranasally administered, CNTFs are able to transport to the central nervous system along the olfactory tract and to enhance the expression of nerve growth factor mRNA in hemorrhagic stroke. PMID:19919011

  13. The Relation Between GABA and L-Arginine Levels With Some Stroke Risk Factors in Acute Ischemic Stroke Patients

    PubMed Central

    Hosinian, Mohsen; Qujeq, Durdi; Ahmadi Ahangar, Alijan

    2016-01-01

    Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. PMID:27478806

  14. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

    PubMed

    Lagier, D; Platon, L; Chow-Chine, L; Sannini, A; Bisbal, M; Brun, J-P; Blache, J-L; Faucher, M; Mokart, D

    2016-09-01

    Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome. PMID:27418297

  15. The Relation Between GABA and L-Arginine Levels With Some Stroke Risk Factors in Acute Ischemic Stroke Patients.

    PubMed

    Hosinian, Mohsen; Qujeq, Durdi; Ahmadi Ahangar, Alijan

    2016-01-01

    Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. PMID:27478806

  16. Perinatal and Familial Risk Factors for Acute Lymphoblastic Leukemia in a Swedish National Cohort

    PubMed Central

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Kristina

    2015-01-01

    Background Perinatal factors including high birth weight have been associated with acute lymphoblastic leukemia (ALL) in case-control studies. However, these findings have seldom been examined in large population-based cohort studies, and the specific contributions of gestational age and fetal growth remain unknown. Methods We conducted a national cohort study of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008, followed up for ALL incidence through 2010 (maximum age 38 years) to examine perinatal and familial risk factors. Results There were 1,960 ALL cases in 69.7 million person-years of follow-up. After adjusting for potential confounders, risk factors for ALL included high fetal growth (incidence rate ratio [IRR] per additional 1 standard deviation, 1.07; 95% CI, 1.02-1.11, P=0.002; IRR for large vs. appropriate for gestational age, 1.22; 95% CI, 1.06-1.40; P=0.005), first-degree family history of ALL (IRR, 7.41; 95% CI, 4.60-11.95, P<0.001), male sex (IRR, 1.20; 95% CI, 1.10-1.31; P<0.001), and parental country of birth (IRR for both parents born in Sweden vs. other countries, 1.13; 95% CI, 1.00-1.27, P=0.045). These risk factors did not appear to vary by age at ALL diagnosis. Gestational age at birth, season of birth, birth order, multiple birth, parental age, and parental education level were not associated with ALL. Conclusions In this large cohort study, high fetal growth was associated with an increased risk of ALL in childhood through young adulthood, independently of gestational age at birth, suggesting that growth factor pathways may play an important long-term role in the etiology of ALL. PMID:25417823

  17. The Related Risk Factors Analysis of Snake-Bite Induced Acute Kidney Injury.

    PubMed

    Li, Wei; Chen, Fang; Wu, Shukun

    2016-01-01

    BACKGROUND The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. MATERIAL AND METHODS This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People's Hospital from January 2011 to September 2013. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Gender, age, and clinical examination data of the patients were recorded. The Mann-Whitney U test and Fisher exact test were performed to analyze the collected data; preliminary analysis of independent risk factors was performed with multivariate logistic regression. RESULTS Among the snake-bite patients, 98.3% were farmers. The mean age of patients was 46±12 years. Of the 119 patients (13.4%), 16 suffered from AKI. There were statistically significant differences between the AKI and non-AKI groups with respect to age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin. Preliminary analysis with multivariate logistic regression showed that advanced age and increased time interval from snake bite to antivenin therapy might be independent risk factors for snake-bite induced AKI. CONCLUSIONS Age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin were risk factors for snake-bite induced AKI. Advanced age and delayed antivenin therapy might be independent risk factors for snake-bite induced AKI. PMID:27377078

  18. The Related Risk Factors Analysis of Snake-Bite Induced Acute Kidney Injury

    PubMed Central

    Li, Wei; Chen, Fang; Wu, Shukun

    2016-01-01

    Background The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. Material/Methods This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People’s Hospital from January 2011 to September 2013. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Gender, age, and clinical examination data of the patients were recorded. The Mann-Whitney U test and Fisher exact test were performed to analyze the collected data; preliminary analysis of independent risk factors was performed with multivariate logistic regression. Results Among the snake-bite patients, 98.3% were farmers. The mean age of patients was 46±12 years. Of the 119 patients (13.4%), 16 suffered from AKI. There were statistically significant differences between the AKI and non-AKI groups with respect to age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin. Preliminary analysis with multivariate logistic regression showed that advanced age and increased time interval from snake bite to antivenin therapy might be independent risk factors for snake-bite induced AKI. Conclusions Age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin were risk factors for snake-bite induced AKI. Advanced age and delayed antivenin therapy might be independent risk factors for snake-bite induced AKI. PMID:27377078

  19. Combination of dynamic and integral methods for generating reproducible functional CBF images

    SciTech Connect

    Lammertsma, A.A.; Cunningham, V.J.; Deiber, M.P.; Heather, J.D.; Bloomfield, P.M.; Nutt, J.; Frackowiak, R.S.; Jones, T. )

    1990-09-01

    A new method to measure regional CBF is presented, applying both dynamic and integral analyses to a dynamic sequence of positron emission tomographic scans collected during and following the administration of H2(15)O (inhalation of C15O2). The dynamic analysis is used to correct continuously monitored arterial whole-blood activity for delay and dispersion relative to tissue scans. An integral analysis including corrections for this delay and dispersion is then used to calculate CBF on a pixel-by-pixel basis. Normal values and reproducibility over a 2-h period are presented, together with the results of validation and simulation studies. The results indicate that the single-tissue compartment model adequately describes the distribution of H2(15)O in the brain, without recourse to postulating a nonexchanging water pool.

  20. 61. (Credit CBF) Operating floor of filter room, c1912. A ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    61. (Credit CBF) Operating floor of filter room, c1912. A remodeled Hyatt pressure filter, now operating as a tub, gravity, rapid sand filter, is in the foreground (the remodeling took place c1908-1909). The remodeled New York horizontal pressure filters (installed 01900, remodeled c1908-1909) are in the background. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  1. 12. (Credit CBF) West end of McNeil Street Station in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. (Credit CBF) West end of McNeil Street Station in November 1911. The settling basins are visible on the far right. In the foreground is a pile of filter sand and several barrels of chemicals (probably lime or alum). The box car is delivering chemicals to storage in the west wing of the station. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  2. Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.

    PubMed

    Fu, Jingqi; Zheng, Hongzhi; Wang, Huihui; Yang, Bei; Zhao, Rui; Lu, Chunwei; Liu, Zhiyuan; Hou, Yongyong; Xu, Yuanyuan; Zhang, Qiang; Qu, Weidong; Pi, Jingbo

    2015-01-01

    Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes. PMID:25949772

  3. Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow: Toward finding the determinants in maintaining the CBF homeostasis.

    PubMed

    Kanno, I; Masamoto, K

    2016-01-01

    Methods exist to evaluate the cerebral blood flow (CBF) at both the macroscopic and microscopic spatial scales. These methods provide complementary information for understanding the mechanism in maintaining an adequate blood supply in response to neural demand. The macroscopic CBF assesses perfusion flow, which is usually measured using radioactive tracers, such as diffusible, nondiffusible, or microsphere. Each of them determines CBF based on indicator dilution principle or particle fraction principle under the assumption that CBF is steady state during the measurement. Macroscopic CBF therefore represents averaged CBF over a certain space and time domains. On the other hand, the microscopic CBF assesses bulk flow, usually measures using real-time microscopy. The method assesses hemodynamics of microvessels, ie, vascular dimensions and flow velocities of fluorescently labeled or nonlabeled RBC and plasma markers. The microscopic CBF continuously fluctuates in time and space. Smoothing out this heterogeneity may lead to underestimation in the macroscopic CBF. To link the two measurements, it is needed to introduce a common parameter which is measurable for the both methods, such as mean transit time. Additionally, applying the defined physiological and/or pharmacological perturbation may provide a good exercise to determine how the specific perturbations interfere the quantitative relationships between the macroscopic and microscopic CBF. Finally, bridging these two-scale methods potentially gives a further indication how the absolute CBF is regulated with respect to a specific type of the cerebrovascular tones or capillary flow velocities in the brain. PMID:27130412

  4. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine

    SciTech Connect

    Olesen, J.; Larsen, B.; Lauritzen, M.

    1981-04-01

    Regional cerebral blood flow (rCBF) was measured in 254 areas of a hemisphere with the xenon 133 intraarterial injection method. Six cases of classic migraine were followed from the normal state into the prodromal phase, and in 3 cases further into the headache phase. One patient with common migraine was similarly followed during his only classic attack. The attacks were initiated by focal hyperemia in 3 patients. During prodromes all patients displayed occipitoparietal rCBF reduction (oligemia), but in only 1 case did the reduction approach critical values. Oligemia gradually spread anteriorly in the course of 15 to 45 minutes. In 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech, and similar activities) was impaired in 6 patients. The results indicate that the vasospastic model of the migraine attack is too simplistic.

  5. Pulmonary function abnormalities in adult patients with acute exacerbation of bronchiectasis: A retrospective risk factor analysis.

    PubMed

    Ma, Yanliang; Niu, Yuqian; Tian, Guizhen; Wei, Jingan; Gao, Zhancheng

    2015-08-01

    Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People's Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709-6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696-37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403-6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495-7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient's age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia. PMID:25882894

  6. Factors associated with variations in hospital expenditures for acute heart failure in the United States

    PubMed Central

    Ziaeian, Boback; Sharma, Puza P.; Yu, Tzy-Chyi; Johnson, Katherine Waltman; Fonarow, Gregg C.

    2015-01-01

    Background Relatively little contemporary data are available that describe differences in acute heart failure (AHF) hospitalization expenditures as a function of patient and hospital characteristics, especially from a population-based investigation. This study aimed to evaluate factors associated with variations in hospital expenditures for AHF in the United States. Methods A cross-sectional analysis using discharge data from the 2011 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, was conducted. Discharges with primary International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes for AHF in adults were included. Costs were estimated by converting Nationwide Inpatient Sample charge data using the Healthcare Cost and Utilization Project Cost-to-Charge Ratio File. Discharges with highest (≥80th percentile) versus lowest (≤20th percentile) costs were compared for patient characteristics, hospital characteristics, utilization of procedures, and outcomes. Results Of the estimated 1 million AHF hospital discharges, the mean cost estimates were $10,775 per episode. Younger age, higher percentage of obesity, atrial fibrillation, pulmonary disease, fluid/electrolyte disturbances, renal insufficiency, and greater number of cardiac/noncardiac procedures were observed in stays with highest versus lowest costs. Highest-cost discharges were more likely to be observed in urban and teaching hospitals. Highest-cost AHF discharges also had 5 times longer length of stay, were 9 times more costly, and had higher in-hospital mortality (5.6% vs 3.5%) compared with discharges with lowest costs (all P < .001). Conclusions Acute heart failure hospitalizations are costly. Expenditures vary markedly among AHF hospitalizations in the United States, with substantial differences in patient and hospital characteristics, procedures, and in-hospital outcomes among discharges with highest compared with lowest costs. PMID:25641538

  7. Clinical Characteristics and Factors Influencing the Occurrence of Acute Eosinophilic Pneumonia in Korean Military Personnel

    PubMed Central

    Lee, Ji Eun

    2016-01-01

    Acute eosinophilic pneumonia (AEP) is an uncommon inflammatory lung disease, and limited data exist concerning the clinical characteristics and factors that influence its occurrence. We retrospectively reviewed the records of AEP patients treated at Korean military hospitals between January 2007 and December 2013. In total, 333 patients were identified; their median age was 22 years, and all were men. All patients presented with acute respiratory symptoms (cough, sputum, dyspnea, or fever) and had elevated levels of inflammatory markers including median values of 13,185/µL for white blood cell count and 9.51 mg/dL for C-reactive protein. All patients showed diffuse ground glass opacity/consolidation, and most had pleural effusion (n = 265; 80%) or interlobular septal thickening (n = 265; 85%) on chest computed tomography. Most patients had normal body mass index (n = 255; 77%), and only 30 (9%) patients had underlying diseases including rhinitis, asthma, or atopic dermatitis. Most patients had recently changed smoking habits (n = 288; 87%) and were Army personnel (n = 297; 89%).The AEP incidence was higher in the Army group compared to the Navy or Air Force group for every year (P = 0.002). Both the number of patients and patients with high illness severity (oxygen requirement, intensive care unit admission, and pneumonia severity score class ≥ III) tended to increase as seasonal temperatures rose. We describe the clinical characteristics of AEP and demonstrate that AEP patients have recently changed smoking habits and work for the Army. There is an increasing tendency in the numbers of patients and those with higher AEP severity with rising seasonal temperatures. PMID:26839479

  8. Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

    PubMed

    Leeper-Woodford, S K; Carey, D; Byrne, K; Walsh, C; Fisher, B; Sugerman, H J; Fowler, A A

    1998-02-01

    Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury. PMID:9488252

  9. The factors affecting early death after the initial therapy of acute myeloid leukemia

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Etgul, Sezgin; Aslan, Tuncay; Yayar, Okan; Aydin, Seda; Demiroglu, Haluk; Ozcebe, Osman Ilhami; Sayinalp, Nilgun; Goker, Hakan; Aksu, Salih; Buyukasik, Yahya

    2015-01-01

    There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML. PMID:26885243

  10. A functional receptor for B-cell activating factor is expressed on human acute lymphoblastic leukemias

    PubMed Central

    Parameswaran, Reshmi; Muschen, Markus; Kim, Yong-mi; Groffen, John; Heisterkamp, Nora

    2010-01-01

    B-lineage acute lymphoblastic leukemia (ALL) arises by transformation of a progenitor (pre-B) cell. Cure rates in adults remain low and treatment is complicated by support provided by the microenvironment to the leukemic cells, indicating an urgent need to better understand the factors that promote their survival. B cell activating factor (BAFF) and its receptor BAFF-R are important for survival and growth of mature normal and malignant B-cells but are not expressed on pre-B cells. Unexpectedly, all cells in the primary Philadelphia-chromosome positive and negative ALL samples tested were positive for high BAFF-R cell surface expression. The BAFF-R was fully competent to bind BAFF and stimulation of the receptor activated both the classical and the non-canonical NFκB pathways. Recombinant BAFF supported survival of the ALL cells in the absence of stroma, and it significantly attenuated the rate of apoptosis caused by exposure to nilotinib, a drug used therapeutically to treat Philadelphia-chromosome positive ALLs. Surprisingly, BAFF mRNA and protein were also expressed in the same cells but BAFF was not shed into the medium. Our report is the first showing universal expression of the BAFF-R by pre-B ALL cells and opens the possibility of blocking its function as an adjuvant therapeutic strategy. PMID:20460528

  11. Acute handling disturbance modulates plasma insulin-like growth factor binding proteins in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of acute stressor exposure on proximal (growth hormone; GH) and distal (insulin-like growth factor-I; IGF-I and IGF-binding proteins) components of the somatotropic axis are poorly understood in finfish. We exposed rainbow trout (Oncorhynchus mykiss) to a 5-minute handling disturbance to...

  12. Corrigendum: The Associations Between Maternal Factors During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis.

    PubMed

    Yan, Kangkang; Xu, Xuejing; Liu, Xiaodong; Wang, Xikui; Hua, Shucheng; Wang, Chunpeng; Liu, Xin

    2016-05-01

    Because of the erroneous application of multiple publications, the conclusions of our recent paper (Pediatr Blood Cancer 2015;62:1162-70) were not reliable. The corrected results show that coffee drinking during pregnancy was risk factor for childhood acute lymphoblastic leukemia (OR = 1.44, 95% confidence interval = 1.07-1.92). PMID:26999072

  13. Factors Affecting Nurse Staffing in Acute Care Hospitals: A Review and Critique of the Literature. Nurse Planning Information Series 17.

    ERIC Educational Resources Information Center

    Young, John P.; And Others

    A critical review of literature on factors affecting nurse staffing in acute care hospitals, with particular regard for the consequences of a movement from team nursing to primary nursing care, was conducted. The literature search revealed a need for more research on the philosophy of nursing and nursing goals and policy as they relate to nurse…

  14. Risk Factors for Acute Toxoplasma gondii Diseases in Taiwan: A Population-Based Case-Control Study

    PubMed Central

    Chiang, Ting-Yi; Kuo, Ming-Chu; Chen, Chang-Hsun; Yang, Jyh-Yuan; Kao, Cheng-Feng; Ji, Dar-Der; Fang, Chi-Tai

    2014-01-01

    Although human toxoplasmosis is a notifiable disease in Taiwan since 2007, little is known about its risk factors. This study aimed to investigate the risk factors for acute Toxoplasma gondii diseases in Taiwan. We conducted a nationwide population-based case-control study. Cases of acute human toxoplasmosis notified to the Taiwan Centers for Diseases Control (Taipei, Taiwan) during 2008–2013 were compared with controls that were randomly selected from healthy T. gondii-seronegative blood donors who participated in a nationwide T. gondii seroepidemiologic study during 2009–2010. Cases and controls were matched according to age, gender and residency at an 1∶8 ratio. Structured questionnaires were used to gather information regarding risk factors. A total of 30 laboratory-confirmed acute T. gondii disease cases and 224 controls were enrolled. The most common clinical manifestation of the cases was flu-like symptoms (n = 20), followed by central nervous system disease (n = 4), ocular diseases (n = 3), abortion (n = 2), and congenital infection (n = 1). Multivariate conditional logistic regression showed that raw clam consumption (adjusted odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.4–9.9) and having a cat in the household (adjusted OR = 2.9; 95% CI = 1.1–7.9) were two independent risk factors for acute T. gondii disease. We conclude that raw shellfish consumption and domestic cat exposure were risk factors for acquiring acute T. gondii diseases in Taiwan. This finding may guide future research and control policies. PMID:24609112

  15. The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

    PubMed

    Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

    2014-01-01

    The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced. PMID:24415770

  16. [Acute ICU syndrome. Contributing factors and attitude of the nursing staff].

    PubMed

    Rodríguez Mondéjar, J J; Martín Lozano, R; Jorge Guillem, R M; Iniesta Sánchez, J; Palazón Sánchez, C; Carrión Tortosa, F; Parra Dormal, F; López Amorós, A; Martínez Huéscar, M

    2001-01-01

    It is not uncommon for patients in intensive care units (ICUs) to suddenly and unexpectedly present what is known as acute ICU syndrome. This syndrome appears independently of the patient's situation and diagnosis. The aim of the present study was to determine the incidence of this nursing diagnosis in our department, to identify the possible environmental factors that could contribute to its appearance and to evaluate nursing interventions to resolve this syndrome in the ICU.Data were collected from a register of 62 items containing information on the health status of the patient on presenting the syndrome (vital signs, laboratory investigations, etc.), data on the environment, drugs used and other factors that could, a priori, play a role. The statistical analysis was performed using the SPSS program. This prospective study was carried out in a general ICU with ten beds: six beds in an open ward and four individual rooms. Two hundred forty-three patients were admitted during the 6-month study period. The incidence of ICU syndrome was 8.1 % (20 cases). Factors influencing its appearance were the timing of the shifts, the temperature, and whether patients were in individual rooms or open wards. The frequency of the syndrome was much higher in open wards and in the afternoon (from 15:00 to 22:00). In conclusion, the attitude of the nursing staff should be alert to identify the syndrome early and initiate appropriate measures, such as orienting the patient in time and space, achieving an appropriate temperature, using relaxation techniques, facilitating access to the family, etc., since in 35 % of cases these measures are sufficient to stabilize and/or resolve the problem, without the need of drugs. PMID:11459534

  17. Hematogones: a sensitive prognostic factor for Chinese adult patients with acute myeloid leukemia

    PubMed Central

    Li, L.; Fu, R.; Zhang, T.; Xie, X.; Liu, J.; Tao, J.; Song, J.; Liu, H.; Zhang, W.; Lu, W.; Shao, Z.

    2016-01-01

    Background Hematogones (hgs) are normal B-lymphocyte precursors that increase in some hematologic diseases. Many studies indicate that hgs might be a favourable prognostic factor. We thus considered it important to determine whether hgs are also a prognostic factor for Chinese adult patients with acute myeloid leukemia (aml) and whether the hg-positive and hg-negative groups show any serologic or phenotypic differences. Methods Chinese adult aml patients (n = 177) who were all initially hg-negative underwent standard chemotherapy and were thereafter divided into hg-positive and hg-negative groups according to hg levels in bone marrow during their first remission. Results The follow-up study confirmed that survival duration (both leukemia-free and overall) was significantly greater in the hg-positive group than in the hg-negative group and was accompanied by a lower relapse rate. A retrospective study of patient characteristics at the time of first diagnosis revealed some differences between the hg-positive and the hg-negative groups, including elevations in white blood cells, lactate dehydrogenase, and β2-microglobulin in the hg-negative group. Retrospective phenotypic analysis revealed a significantly lower proportion of abnormal chromosome karyotype and CD34 expression in hg-positive patients. Finally, we evaluated whether additional intensive chemotherapy after standard chemotherapy could further increase hgs. Conclusions The present work verified the validity of hgs as a prognostic factor for Chinese adult patients with aml. Compared with hg-negative patients, hg-positive patients not only experienced longer survival and a lower relapse rate, but they also had some serologic and phenotypic characteristics that are all considered indicators of better outcome. Additional intensive chemotherapy could further increase the level of hgs, which might imply better clinical results. PMID:27122980

  18. Macrophage migration inhibitory factor drives neutrophil accumulation by facilitating IL-1β production in a murine model of acute gout.

    PubMed

    Galvão, Izabela; Dias, Ana Carolina Fialho; Tavares, Livia Duarte; Rodrigues, Irla Paula Stopa; Queiroz-Junior, Celso Martins; Costa, Vivian Vasconcelos; Reis, Alesandra Corte; Ribeiro Oliveira, Rene Donizeti; Louzada-Junior, Paulo; Souza, Daniele Glória; Leng, Lin; Bucala, Richard; Sousa, Lirlândia Pires; Bozza, Marcelo Torres; Teixeira, Mauro Martins; Amaral, Flávio Almeida

    2016-06-01

    This study evaluated the role of macrophage migration inhibitory factor in inflammation caused by monosodium urate crystals. The concentration of macrophage migration inhibitory factor was increased in synovial fluid of patients with acute gout, and there was a positive correlation between intra-articular macrophage migration inhibitory factor and IL-1β concentrations. In mice, the injection of monosodium urate crystals into the knee joint increased the levels of macrophage migration inhibitory factor in macrophages and in inflamed tissue. The injection of recombinant macrophage migration inhibitory factor into the joint of mice reproduced the inflammatory response observed in acute gout, including histologic changes, the recruitment of neutrophils, and increased levels of IL-1β and CXCL1. Importantly, the accumulation of neutrophils and the amount IL-1β in the joints were reduced in macrophage migration inhibitory factor-deficient mice when injected with monosodium urate crystals. We observed a similar effect when we blocked macrophage migration inhibitory factor with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid or anti-macrophage migration inhibitory factor. In addition, the blockade of IL-1R and CXCR2 reduced recombinant macrophage migration inhibitory factor-induced neutrophil recruitment. Mechanistically, recombinant macrophage migration inhibitory factor is important for the synthesis of il1β mRNA in vivo and in isolated macrophages. Altogether, macrophage migration inhibitory factor promotes neutrophil accumulation and is important for IL-1β production, which are 2 crucial events contributing to the pathogenesis of acute gout. PMID:26868525

  19. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Abstract Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process. We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients. We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04. Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  20. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy.

    PubMed

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-11-01

    Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  1. Factors determining the clinical outcome of acute variceal bleed in cirrhotic patients.

    PubMed

    Majid, Shahid; Azam, Zahid; Shah, Hasnain Ali; Salih, Mohammad; Hamid, Saeed; Abid, Shahab; Jafri, Wasim

    2009-01-01

    Variceal bleed is a severe complication of portal hypertension. We studied the predictors of failure to control variceal bleed and re-bleed in patients with cirrhosis. We reviewed the case records of 382 consecutive patients admitted with variceal bleed from January 2001 to December 2005. Diagnosis of cirrhosis was made on clinical, laboratory, and radiological parameters. Acute variceal bleeding, failure to control bleed, and re-bleeding were defined according to Baveno III consensus report. Failure to control bleed was observed in 39 (10.2%) patients while in hospital re-bleed occurred in 49 (12.8%) patients. Thirty-four patients died. Diabetes was present in 148 (39%) patients. On multivariate logistic regression analysis, predictors of failure to control bleed were presence of diabetes mellitus and active bleeding at the time of endoscopy; predictors of in-hospital re-bleed were diabetes mellitus and serum bilirubin >3 mg/dL. Diabetes mellitus, active bleeding at endoscopy and bilirubin >3 mg/dL are bad prognostic factors for initial control of variceal bleed, and recurrent bleed in patients with cirrhosis. PMID:19907958

  2. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury.

    PubMed

    Shaver, Ciara M; Grove, Brandon S; Clune, Jennifer K; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF(∆mye), LysM.Cre(+/-)TF(flox/flox)) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  3. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

    PubMed Central

    Shaver, Ciara M.; Grove, Brandon S.; Clune, Jennifer K.; Mackman, Nigel; Ware, Lorraine B.; Bastarache, Julie A.

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF∆mye, LysM.Cre+/−TFflox/flox) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  4. Frequency and Factors Associated with Unexpected Death in an Acute Palliative Care Unit: Expect the Unexpected

    PubMed Central

    Bruera, Sebastian; Chisholm, Gary; Santos, Renata Dos; Bruera, Eduardo; Hui, David

    2015-01-01

    Context Few studies have examined the frequency of unexpected death and its associated factors in a palliative care setting. Objectives To determine the frequency of unexpected death in two acute palliative care units (APCUs); to compare the frequency of signs of impending death between expected and unexpected deaths; and to determine the predictors associated with unexpected death. Methods In this prospective, longitudinal, observational study, consecutive patients admitted to two APCUs were enrolled and physical signs of impending death were documented twice daily until discharge or death. Physicians were asked to complete a survey within 24 hours of APCU death. The death was considered unexpected if the physician answered “yes” to the question “Were you surprised by the timing of the death?” Results In total, 193 of 203 after-death assessments (95%) were collected for analysis. Nineteen of 193 patients died unexpectedly (10%). Signs of impending death, including nonreactive pupils, inability to close eyelids, decreased response to verbal stimuli, drooping of nasolabial folds, peripheral cyanosis, pulselessness of the radial artery, and respiration with mandibular movement, were documented more frequently in expected deaths than unexpected deaths (P < 0.05). Longer disease duration was associated with unexpected death (33 months vs. 12 months, P=0.009). Conclusion Unexpected death occurred in an unexpectedly high proportion of patients in the APCU setting, and was associated with fewer signs of impending death. Our findings highlight the need for palliative care teams to be prepared for the unexpected. PMID:25499421

  5. Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia

    PubMed Central

    Lee, Ho Jin; Kim, Dong Hyun; Lee, Seul; Koh, Myeong Seok; Kim, So Yeon; Lee, Ji Hyun; Lee, Suee; Oh, Sung Yong; Han, Jin Yeong; Kim, Hyo-Jin; Kim, Sung-Hyun

    2015-01-01

    Background/Aims: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis. Methods: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012. Results: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS). Conclusions: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS. PMID:26552464

  6. GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells.

    PubMed

    Katsumura, Koichi R; Ong, Irene M; DeVilbiss, Andrew W; Sanalkumar, Rajendran; Bresnick, Emery H

    2016-08-30

    The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts. PMID:27545880

  7. von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes

    PubMed Central

    Koprivica, Zoran; Djordjevic, Dusica; Vuletic, Milena; Zivkovic, Vladimir; Barudzic, Nevena; Andjelkovic, Nebojsa; Djuric, Dragan; Iric-Cupic, Violeta; Krkeljic, Jelena; Jakovljevic, Vladimir

    2011-01-01

    Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites–NO2 −), superoxide anion radical (O2 −), hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence. PMID:21904649

  8. BIOPSYCHOSOCIAL FACTORS ASSOCIATED WITH THE SUBCATEGORIES OF ACUTE TEMPOROMANDIBULAR JOINT DISORDERS*

    PubMed Central

    Dougall, Angela Liegey; Jimenez, Carmen A.; Haggard, Robbie A.; Stowell, Anna W.; Riggs, Richard R.; Gatchel, Robert J.

    2012-01-01

    Aims The purpose of this study was to assess the biopsychosocial factors associated with acute temporomandibular joint disorders (TMD) based upon the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Methods Participants were assessed in community-based dental clinics, and evaluated by trained clinicians on physical and psychosocial measures. A total of 207 subjects were evaluated. Patients’ high-risk versus low-risk status for potentially developing chronic TMD was also determined. Analyses of variance and chi square analyses were applied to these data. Results Participants’ characteristic pain intensity differed among RDC/TMD Axis I diagnoses. They also significantly varied in their: self-reported graded chronic pain; depression; somatization, pain inclusive; somatization, pain excluded, and physical well-being. In addition, participants with differing RDC/TMD Axis I diagnoses varied in self-reported pain during their chewing performance. Finally, there were also significant differences in chewing performance between high-risk vs. low-risk (for developing chronic TMD) patients. Conclusions Participants with multiple diagnoses reported higher pain, as well as other symptoms, relative to participants without a TMD diagnosis. For chewing performance, participants with mutual diagnoses reported more pain compared to other participants. Finally, the risk-status of patients significantly affected chewing performance. PMID:22292135

  9. Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia.

    PubMed

    Kim, Jin-A; Shim, Jae-Seung; Lee, Ga-Young; Yim, Hyeon Woo; Kim, Tae-Min; Kim, Myungshin; Leem, Sun-Hee; Lee, Jong-Wook; Min, Chang-Ki; Oh, Il-Hoan

    2015-06-01

    Acute myelogenous leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow (BM); however, their unique cellular interaction within the BM microenvironment and its functional significance remain unclear. Here, we assessed the BM microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells (MSC). The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL12 and JAG1) in MSCs to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in BM. The distinct pattern of stromal changes in leukemic BM at initial diagnosis was associated with a heterogeneous posttreatment clinical course with respect to the maintenance of complete remission for 5 to 8 years and early or late relapse. Thus, remodeling of mesenchymal niche by leukemia cells is an intrinsic self-reinforcing process of leukemogenesis that can be a parameter for the heterogeneity in the clinical course of leukemia and hence serve as a potential prognostic factor. PMID:25791383

  10. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    PubMed

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise. PMID:27450438

  11. Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study

    PubMed Central

    Wozniak, Amy W.; Hough, Catherine L.; Morris, Peter E.; Dinglas, Victor D.; Jackson, James C.; Mendez-Tellez, Pedro A.; Shanholtz, Carl; Ely, E. Wesley; Colantuoni, Elizabeth

    2014-01-01

    Rationale: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. Objectives: To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization. Methods: A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness–related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. Measurements and Main Results: At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes. Conclusions: Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors’ physical outcomes. PMID:24716641

  12. Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

    PubMed Central

    Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam

    2006-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544

  13. Risk factors for early rebleeding and mortality in acute variceal hemorrhage

    PubMed Central

    Zhao, Jing-Run; Wang, Guang-Chuan; Hu, Jin-Hua; Zhang, Chun-Qing

    2014-01-01

    AIM: To investigate the risk factors for 6-wk rebleeding and mortality in acute variceal hemorrhage (AVH) patients treated by percutaneous transhepatic variceal embolization (PTVE). METHODS: A retrospective cohort study of AVH patients who had undergone PTVE treatment was conducted between January 2010 and December 2012. Demographic information, medical histories, physical examination findings, and laboratory test results were collected. The PTVE procedure was performed as a rescue therapy for patients who failed endoscopic and pharmacologic treatment. Survival analysis was estimated using the Kaplan-Meier method and compared using the log-rank test. The multivariate analysis was performed using the Cox regression test to identify independent risk factors for rebleeding and mortality. RESULTS: One hundred and one patients were included; 71 were males and the average age was 51 years. Twenty-one patients rebled within 6 wk. Patients with high-risk stigmata, PTVE with trunk obliteration, and a hepatic vein pressure gradient (HVPG) ≥ 20 mmHg were at increased risk for rebleeding (OR = 5.279, 95%CI: 2.782-38.454, P = 0.003; OR = 4.309, 95%CI: = 2.144-11.793, P < 0.001; and OR = 1.534, 95%CI: 1.062-2.216, P = 0.022, respectively). Thirteen patients died within 6 wk. A model for end-stage liver disease (MELD) score ≥ 18 and an HVPG ≥ 20 mmHg were associated with 6-wk mortality (OR = 2.162, 95%CI: 1.145-4.084, P = 0.017 and OR = 1.423, 95%CI: 1.222-1.657, P < 0.001, respectively). CONCLUSION: MELD score and HVPG in combination allow for early identification of patients with AVH who are at substantially increased risk of death over the short term. PMID:25548492

  14. Emergency department management of acute exacerbations of chronic obstructive pulmonary disease and factors associated with hospitalization

    PubMed Central

    Khialani, Bharat; Sivakumaran, Pathmanathan; Keijzers, Gerben; Sriram, Krishna Bajee

    2014-01-01

    Background: Currently there is a paucity of information about biomarkers that can predict hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients presenting to the emergency department (ED). There is limited data on the consistency of ED management of AECOPD with local COPD guidelines. The aim of this study was to identify biomarkers associated with hospitalization in AECOPD patients and to determine if the ED management was concordant with local COPD guidelines. Materials and Methods: We performed a retrospective audit of consecutive AECOPD patients presenting to the Gold Coast Hospital ED over a 6-month period. Results: During the study period, 122 AECOPD patients (51% male, mean age (SE) 71 (±11) years) presented to the ED. Ninety-eight (80%) patients were hospitalized. Univariate analysis identified certain factors associated with hospitalization: Older age, former smokers, home oxygen therapy, weekday presentation, SpO2 < 92%, and raised inflammatory markers (white cell count (WCC) and C-reactive protein (CRP)). After adjustment for multiple variable, increased age was significantly associated with hospitalization (odds ratio (OR) 1.09; 95% confidence interval (CI): 1.00-1.18; P = 0.05). Radiology assessment and pharmacological management was in accordance with COPD guidelines. However, spirometry was performed in 17% of patients and 28% of patients with hypercapneic respiratory failure received noninvasive ventilation (NIV). Conclusion: We identified several factors on univariate analysis that were associated with hospitalization. Further research is required to determine the utility of these biomarkers in clinical practice. Also, while overall adherence to local COPD guidelines was good, there is scope for improvement in performing spirometry and provision of NIV to eligible patients. PMID:25097600

  15. Serum Level of Fibroblast Growth Factor 21 Is Independently Associated with Acute Myocardial Infarction

    PubMed Central

    Ding, Wenhui; Wang, Fang

    2015-01-01

    Background Fibroblast growth factor 21 (FGF21) has been described as a metabolic hormone critical for glucose and lipid metabolism. Previously, high levels of FGF21 were observed in patients with coronary heart disease and non-acute myocardial infarction (non-AMI). In this study, we investigated the changes in FGF21 levels in Chinese patients with AMI. Methodology/Principal Findings We used ELISA to measure circulating FGF21 levels in 55 AMI patients and 45 non-AMI control patients on the 1st day after syndrome onset. All patients were followed-up within 30 days. FGF21 levels in AMI patients were significantly higher than those in non-AMI controls (0.25 (0.16–0.34) vs. 0.14 (0.11–0.20) ng/mL, P < 0.001). FGF21 levels reached the maximum within approximately 24 h after the onset of AMI and remained at high for 7 days, and the FGF21 level (OR: 16.93; 95% confidence interval (CI): 2.65–108.05; P = 0.003) was identified as an independent factor associated with the presence of AMI. On the 7th day, FGF21 levels were significantly higher in the patients who subsequently developed re-infarction within 30 days than in the patients who did not develop re-infarction (with vs. without re-infarction: 0.45 (0.22–0.64) vs. 0.21 (0.15–0.29) ng/mL, P = 0.014). Conclusions/Significance The level of serum FGF21 is independently associated with the presence of AMI in Chinese patients. High FGF21 levels might be related to the incidence of re-infarction within 30 days after onset. PMID:26091256

  16. Concomitant renal insufficiency and diabetes mellitus as prognostic factors for acute myocardial infarction

    PubMed Central

    2011-01-01

    Background Diabetes mellitus and renal dysfunction are prognostic factors after acute myocardial infarction (AMI). However, few studies have assessed the effects of renal insufficiency in association with diabetes in the context of AMI. Here, we investigated the clinical outcomes according to the concomitance of renal dysfunction and diabetes mellitus in patients with AMI. Methods From November 2005 to August 2008, 9905 patients (63 ± 13 years; 70% men) with AMI were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) and were categorized into 4 groups: Group I (n = 5700) had neither diabetes nor renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m2), Group II (n = 1730) had diabetes but no renal insufficiency, Group III (n = 1431) had no diabetes but renal insufficiency, and Group IV (n = 1044) had both diabetes and renal insufficiency. The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft after 1-year clinical follow-up. Results Primary endpoints occurred in 1804 (18.2%) patients. There were significant differences in composite MACE among the 4 groups (Group I, 12.5%; Group II, 15.7%; Group III, 30.5%; Group IV, 36.5%; p < 0.001). In a Cox proportional hazards model, after adjusting for multiple covariates, the 1-year mortality increased stepwise from Group III to IV as compared with Group I (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.34-2.86; p = 0.001; and HR, 2.42; 95% CI, 1.62-3.62; p < 0.001, respectively). However, Kaplan-Meier analysis showed no significant difference in probability of death at 1 year between Group III and IV (p = 0.288). Conclusions Renal insufficiency, especially in association with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in patients with AMI. Categorization of patients with

  17. Calcitriol inhibits tumor necrosis factor alpha and macrophage inflammatory protein-2 during lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Tan, Zhu-Xia; Chen, Yuan-Hua; Xu, Shen; Qin, Hou-Ying; Wang, Hua; Zhang, Cheng; Xu, De-Xiang; Zhao, Hui

    2016-08-01

    Acute lung injury is a common complication of sepsis in intensive care unit patients with an extremely high mortality. The present study investigated the effects of calcitriol, the active form of vitamin D, on tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in sepsis-induced acute lung injury. Mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS, 1.0mg/kg) to establish the animal model of sepsis-induced acute lung injury. Some mice were i.p. injected with calcitriol (1.0μg/kg) before LPS injection. An obvious infiltration of inflammatory cells in the lungs was observed beginning at 1h after LPS injection. Correspondingly, TNF-α and MIP-2 in sera and lung homogenates were markedly elevated in LPS-treated mice. Interestingly, calcitriol obviously alleviated LPS-induced infiltration of inflammatory cells in the lungs. Moreover, calcitriol markedly attenuated LPS-induced elevation of TNF-α and MIP-2 in sera and lung homogenates. Further analysis showed that calcitriol repressed LPS-induced p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation. In addition, calcitriol blocked LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunit in the lungs. Taken together, these results suggest that calcitriol inhibits inflammatory cytokines production in LPS-induced acute lung injury. PMID:27216047

  18. Effective antimicrobial activity of Cbf-14, derived from a cathelin-like domain, against penicillin-resistant bacteria.

    PubMed

    Ma, Lingman; Wang, Yanrong; Wang, Mengxiao; Tian, Yuwei; Kang, Wei; Liu, Hanhan; Wang, Hui; Dou, Jie; Zhou, Changlin

    2016-05-01

    Cbf-14, a cationic peptide derived from a cathelin-like domain, was designed by inserting the highly α-helical sequence RLLR into an antibacterial sequence and deleting the inactive amino acids in Cbf-K16. Clinical penicillin-resistant isolates as well as NDM-1-carrying Escherichia coli and a correspondingly infected mice model were employed to evaluate Cbf-14 antibacterial activity. The results showed that Cbf-14 possessed potent antimicrobial effects with an MIC of 8-64 μg/ml, and killed almost all bacteria within 240 min. Cbf-14-treated mice achieved an 80% survival rate and approximate 2.5 log unit reduction in CFU in tissues; additionally, this peptide significantly suppressed the production of pro-inflammatory cytokines by the disaggregation of lipopolysaccharide (LPS), suggesting its anti-inflammatory effects. Furthermore, Cbf-14, concentration higher than 2 × MIC value, increased membrane uptake to NPN and PI dye by 96.2% and 63.7%, respectively, neutralised the negative zeta potential of LPS and bacteria surface, and induced 100% leakage of liposome-entrapped calcein and cytoplasmic membrane disruption of E. coli, indicating obvious membrane permeation. Finally, it bound to DNA and respectively evoked 85.0% and 63.3% inhibition of gene replication and protein expression of NDM-1 at sub-MIC concentration in E. coli BL21 (DE3)-NDM-1. These data indicated that Cbf-14 possessed effective antimicrobial activity against penicillin-resistant bacteria in vitro/vivo through membrane disruption, DNA binding, down-regulating NDM-1 expression by plasmid replication inhibition, and anti-inflammatory activity by LPS disaggregation, suggesting a potential anti-infective clinical agent. PMID:26897538

  19. Factors associated with lipid goal attainment among acute coronary syndrome patients

    PubMed Central

    Mohd-Zulkefli, Siti-Zainora; Omar, Marhanis-Salihah; Md-Redzuan, Adyani

    2016-01-01

    Background The incidence of acute coronary syndrome (ACS), one of the most common cardiovascular diseases, is high. Lipid goal attainment is one of the important factors to reduce the risk of recurrent heart attack. Identification of factors influencing lipid goal attainment such as age, female, race, underlying comorbidities, intensity of lipid-lowering therapy, patients’ knowledge, and patients’ belief about medicine would be beneficial in achieving the lipid goal. This study is aimed to determine lipid profile attainment and prescribing pattern of lipid-lowering therapy as well as to identify factors influencing lipid profile attainment among ACS patients. Patients and methods This researcher-assisted cross-sectional survey was carried out at a cardiology clinic in a tertiary hospital from March to May 2015. Results A total of 101 ACS patients were involved in this study. The mean values for low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol levels were 2.75 (0.82) mmol/L and 1.14 (0.27) mmol/L, respectively, while the median value for triglyceride level was 2.75 (0.82) mmol/L. Only 15.8% of our participants achieved the targeted LDL-C. Simvastatin 20 mg was the most common regimen prescribed. Predictors for better LDL-C attainment were younger age (β=−0.228; P=0.032) and higher knowledge score (β=−0.255; P=0.049), while predictors for high-density lipoprotein cholesterol attainment were male (β=0.268; P=0.006), smoking (β=−0.192; P=0.045), and higher knowledge score (β=−0.195; P=0.039). Smoking (β=−0.361; P<0.0001) was the only predictor for higher triglyceride level. Conclusion Younger age, female, lower knowledge score, and smoking status are good predictors for lipid attainment among ACS patients. PMID:27601888

  20. Blocking macrophage migration inhibitory factor activity alleviates mouse acute otitis media in vivo.

    PubMed

    Zhang, Jin; Xu, Min; Zheng, Qingyin; Zhang, Yan; Ma, Weijun; Zhang, Zhaoqiang

    2014-11-01

    This study was to investigate the role of macrophage migration inhibitory factor (MIF) in mouse acute otitis media (AOM), we hypothesize that blocking MIF activity will relieve mouse AOM. A mouse AOM model was constructed by injecting lipopolysaccharide (LPS) into the middle ear of C57BL/6 mice through the tympanic membrane (TM). MIF levels were measured by real-time PCR (RT-PCR) and ELISA after LPS application. Normal or AOM mice were given PBS or ISO-1 (MIF antagonist) every day for 10 days and the hearing levels were determined by measuring auditory brainstem response (ABR) threshold. After the ABR test finished, H&E staining was conducted and the inflammation was also measured by detecting interleukin (IL)-1β, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) levels with RT-PCR and ELISA. TLR-4 expression was determined by western blotting and NF-κB activation was determined by electrophoretic mobility shift assays. Compared with the normal control, MIF levels in the middle ear of LPS-induced AOM mice were significant increased. The ABR results showed that mean ABR thresholds in ISO-1 treated AOM mice were significantly reduced compared with PBS treated AOM mice since day 7, indicating that ISO-1 treatment potentially improved the hearing levels of AOM mice. H&E staining showed that ISO-1 treatment could reduce the mucosal thickness of AOM mice. In ISO-1 treated mice, TLR-4 expression and levels of IL-1β, TNF-α and VEGF were significantly lower compared with PBS treated AOM mice. ISO-1 treatment also significantly inhibited NF-κB activation in AOM mice compared with PBS treated AOM mice. These results suggested that blocking the activity of MIF by ISO-1 could reduce the inflammation in AOM mice in which process TLR-4 and NF-κB were involved. The reduction in MIF activity is conducive to alleviate mouse AOM, which may serve as a potential therapeutic target for the treatment of AOM. PMID:25108100

  1. [The role of radiation and non-radiation factors in the development and progression of acute leukemia in children].

    PubMed

    Bebeshko, V H; Bruslova, K M; Kuznietsova, O É; Tsvietkova, N M; Honchar, L O; Iatsemyrs'kyĭ, S M; Samson, Iu M; Pushkar'ova, T I

    2012-12-01

    At 278 ALL and AML patients the kind of hereditary pathology in the family; clinikal-laboratory features and a course of acute leukemia and terms of longevity of children were studied. Degree of integrated pollution of territory (air, water, soil) by heavy metals and radionuclides and also the irradiation doses have been considered. Results which have been received testify about the certain contribution of genetic components and adverse factors of environment in of development of acute leukemia and their course at children. The definition of different leukemogenic factors action on the condition of hemopoietic system gives the chance to generate the abnormally high risk groups of oncological hematological pathologies among the children's population and to improve the diagnostic and treatment-and-prophylactic actions. PMID:23786007

  2. Tumor Necrosis Factor Alpha Promoter Polymorphism and Severity of Acute Kidney Injury

    PubMed Central

    Susantitaphong, Paweena; Perianayagam, Mary C.; Tighiouart, Hocine; Liangos, Orfeas; Bonventre, Joseph V.; Jaber, Bertrand L.

    2016-01-01

    Background Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI). Methods We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults. Results In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis. Conclusions The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships. PMID:23796916

  3. Brain-derived neurotrophic factor acutely inhibits AMPA-mediated currents in developing sensory relay neurons.

    PubMed

    Balkowiec, A; Kunze, D L; Katz, D M

    2000-03-01

    Brain-derived neurotrophic factor (BDNF) is expressed by many primary sensory neurons that no longer require neurotrophins for survival, indicating that BDNF may be used as a signaling molecule by the afferents themselves. Because many primary afferents also express glutamate, we investigated the possibility that BDNF modulates glutamatergic AMPA responses of newborn second-order sensory relay neurons. Perforated-patch, voltage-clamp recordings were made from dissociated neurons of the brainstem nucleus tractus solitarius (nTS), a region that receives massive primary afferent input from BDNF-containing neurons in the nodose and petrosal cranial sensory ganglia. Electrophysiological analysis was combined in some experiments with anterograde labeling of primary afferent terminals to specifically analyze responses of identified second-order neurons. Our data demonstrate that BDNF strongly inhibits AMPA-mediated currents in a large subset of nTS cells. Specifically, AMPA responses were either completely abolished or markedly inhibited by BDNF in 73% of postnatal day (P0) cells and in 82% of identified P5 second-order sensory relay neurons. This effect of BDNF is mimicked by NT-4, but not NGF, and blocked by the Trk tyrosine kinase inhibitor K252a, consistent with a requirement for TrkB receptor activation. Moreover, analysis of TrkB expression in culture revealed a close correlation between the percentage of nTS neurons in which BDNF inhibits AMPA currents and the percentage of neurons that exhibit TrkB immunoreactivity. These data document a previously undefined mechanism of acute modulation of AMPA responses by BDNF and indicate that BDNF may regulate glutamatergic transmission at primary afferent synapses. PMID:10684891

  4. Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions.

    PubMed

    Zakharov, Sergey; Kotikova, Katerina; Vaneckova, Manuela; Seidl, Zdenek; Nurieva, Olga; Navratil, Tomas; Caganova, Blazena; Pelclova, Daniela

    2016-08-01

    The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. PMID:26806851

  5. Human immunodeficiency virus infection, cardiovascular risk factor profile and risk for acute myocardial infarction

    PubMed Central

    Anne-Lise, Paisible; Chang, Chung-Chou H.; So-Armah, Kaku A.; Butt, Adeel A.; Leaf, David A.; Budoff, Matthew; Rimland, David; Bedimo, Roger; Goetz, Matthew B.; Rodriguez-Barradas, Maria C.; Crane, Heidi M.; Gibert, Cynthia L.; Brown, Sheldon T.; Tindle, Hilary A.; Warner, Alberta L.; Alcorn, Charles; Skanderson, Melissa; Justice, Amy C.; Freiberg, Matthew

    2015-01-01

    Background Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV infected (HIV+) patients. We assessed the association between HIV and incident AMI within CVDRF strata. Methods Cohort 81322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study-Virtual Cohort (prospective study of HIV+ and matched HIV− veterans). Veterans were followed from first clinical encounter on/after 4/1/2003 until AMI/death/last follow-up date (12/31/2009). Predictors HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood-pressure (BP), BP medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ non-optimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome Incident AMI (defined using enzyme, EKG clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates). Statistics: Cox models adjusted for demographics, comorbidity, and substance use. Results 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared to HIV− veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared to HIV− veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0 95%CI: 1.0–3.9, p=0.044). Conclusion The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared to HIV− veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people. PMID:25588033

  6. Perspectives of patients on factors relating to adherence to post-acute coronary syndrome medical regimens

    PubMed Central

    Lambert-Kerzner, Anne; Havranek, Edward P; Plomondon, Mary E; Fagan, Katherine M; McCreight, Marina S; Fehling, Kelty B; Williams, David J; Hamilton, Alison B; Albright, Karen; Blatchford, Patrick J; Mihalko-Corbitt, Renee; Bryson, Chris L; Bosworth, Hayden B; Kirshner, Miriam A; Giacco, Eric J Del; Ho, P Michael

    2015-01-01

    Purpose Poor adherence to cardioprotective medications after acute coronary syndrome (ACS) hospitalization is associated with increased risk of rehospitalization and mortality. Clinical trials of multifaceted interventions have improved medication adherence with varying results. Patients’ perspectives on interventions could help researchers interpret inconsistent outcomes. Identifying factors that patients believe would improve adherence might inform the design of future interventions and make them more parsimonious and sustainable. The objective of this study was to obtain patients’ perspectives on adherence to medical regimens after experiencing an ACS event and their participation in a medication adherence randomized control trial following their hospitalization. Patients and methods Sixty-four in-depth interviews were conducted with ACS patients who participated in an efficacious, multifaceted, medication adherence randomized control trial. Interview transcripts were analyzed using the constant comparative approach. Results Participants described their post-ACS event experiences and how they affected their adherence behaviors. Patients reported that adherence decisions were facilitated by mutually respectful and collaborative provider–patient treatment planning. Frequent interactions with providers and medication refill reminder calls supported improved adherence. Additional facilitators included having social support, adherence routines, and positive attitudes toward an ACS event. The majority of patients expressed that being active participants in health care decision-making contributed to their health. Conclusion Our findings demonstrate that respectful collaborative communication can contribute to medication adherence after ACS hospitalization. These results suggest a potential role for training health-care providers, including pharmacists, social workers, registered nurses, etc, to elicit and acknowledge the patients’ views regarding medication

  7. Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients

    PubMed Central

    Shao, Min; Li, Guangxi; Sarvottam, Kumar; Wang, Shengyu; Thongprayoon, Charat; Dong, Yue; Gajic, Ognjen

    2016-01-01

    Introduction Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. Material and Methods This is a single-center, retrospective cohort study at Mayo Clinic Hospital—Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. Results A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96–104) vs. 102 mmol/L (98–105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ≤94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1–2.6; P = .01). Discussion Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury. PMID:27490461

  8. Insulinlike Growth Factor I Plus Insulinlike Growth Factor Binding Protein 3 Attenuates the Proinflammatory Acute Phase Response in Severely Burned Children

    PubMed Central

    Jeschke, Marc G.; Barrow, Robert E.; Herndon, David N.

    2000-01-01

    Objective To determine the effect of insulinlike growth factor I (IGF-I) in combination with its principal binding protein (IGFBP-3) on the hepatic acute phase response in severely burned children. Summary Background Data The hepatic acute phase response is a cascade of events initiated to restore homeostasis after trauma. A prolonged response, however, may contribute to multiple organ failure, hypermetabolism, complications, and death. Methods Twenty-two children with a mean total body surface area (TBSA) burn of 57 ± 3% were given a continuous infusion of 1 to 4 mg/kg/day IGF-I/BP-3 for 5 days after wound excision and grafting. Eight children with a TBSA burn of 54 ± 4% were given saline as controls. Before and 5 days after excision and grafting, blood samples were taken for serum hepatic constitutive protein, acute phase protein, and proinflammatory cytokine analysis. Results Serum IGF-I levels in burned children given the IGF-I/BP-3 complex increased from 113 ± 15 to 458 ± 40 ng/mL and IGFBP-3 levels increased from 1.8 ± 0.2 to 3.1 ± 0.3 ng/mL. Levels of serum constitutive hepatic proteins (prealbumin, retinol-binding protein, and transferrin) increased with IGF-I/BP-3, whereas levels of type I acute phase proteins (C-reactive protein, α1-acid glycoprotein, and complement C-3) decreased when compared with controls. The complex had no effect on type II acute phase proteins. Tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type I acute phase proteins that was associated with a concomitant increase in constitutive hepatic proteins. Attenuating the proinflammatory acute phase with IGF-1/BP-3 response may prevent multiple organ failure and improve clinical outcomes after thermal injury without any detectable adverse side effects. PMID

  9. Risk Factors for Development of Acute Kidney Injury in Patients with Urinary Tract Infection

    PubMed Central

    Hsiao, Meng-Chang; Hung, Peir-Haur; Wang, Ming-Cheng

    2015-01-01

    Acute kidney injury (AKI) is associated with high morbidity and mortality. Urinary tract infection (UTI) may be associated with sepsis or septic shock, and cause sudden deterioration of renal function. This study investigated the clinical characteristics and change of renal function to identify the risk factors for development of AKI in UTI patients. This retrospective study was conducted in a tertiary referral center. From January 2006 to January 2013, a total of 790 UTI patients necessitating hospital admission were included for final analysis. Their demographic and clinical characteristics and comorbidities were collected and compared. Multivariate logistic regression analysis was performed to evaluate the risk factors for AKI in UTI patients. There were 97 (12.3%) patients developing AKI during hospitalization. Multivariate logistic regression analysis showed that patients with older age (OR 1.02, 95% CI 1.00–1.04, P = 0.04), diabetes mellitus (DM) (OR 2.23, 95% CI 1.35–3.68, P = 0002), upper UTI (OR 2.63, 95% CI 1.53–4.56, P = 0001), afebrile during hospitalization (OR 1.71, 95% CI 1.04–2.83, P = 0036) and lower baseline eGFR [baseline eGFR 45–59 mL/min/1.73 m2 (OR 2.12, 95% CI 1.12–4.04, P = 0.022), baseline eGFR 30-44 mL/min/1.73 m2 (OR 4.44, 95% CI 2.30–8.60 P < 0.001) baseline eGFR < 30 mL/min/1.73 m2 (OR 4.72, 95% CI 2.13–10.45, P <0.001), respectively] were associated with increased risk for development of AKI. were associated with increased risk for development of AKI. Physicians should pay attention to UTI patients at risk of AKI (advancing age, DM, upper UTI, afebrile, and impaired baseline renal function). PMID:26213991

  10. Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury

    PubMed Central

    Hsu, Chien-Ning; Lee, Chien-Te; Su, Chien-Hao; Wang, Yu-Ching Lily; Chen, Hsiao-Ling; Chuang, Jiin-Haur; Tain, You-Lin

    2016-01-01

    Abstract The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort. This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission. AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI. Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals. PMID:27175701

  11. Prevalence and Risk Factors of Acute Lower Gastrointestinal Bleeding in Crohn Disease

    PubMed Central

    Li, Guanwei; Ren, Jianan; Wang, Gefei; Wu, Qin; Gu, Guosheng; Ren, Huajian; Liu, Song; Hong, Zhiwu; Li, Ranran; Li, Yuan; Guo, Kun; Wu, Xiuwen; Li, Jieshou

    2015-01-01

    Abstract Acute lower gastrointestinal bleeding (ALGIB) is a rare but potentially life-threatening complication of Crohn disease (CD). Thus far, few studies of ALGIB in the context of CD have been published, most of which were case reports with limited value. We aimed to explore the prevalence of ALGIB in CD patients, evaluate risk factors for hemorrhagic CD and its recurrence, and analyze clinical data of the death cases. A total of 1374 CD patients registered from January 2007 to June 2013 were examined. Medical records of 73 patients with ALGIB and 146 matched as controls were reviewed and analyzed retrospectively. Logistic regression and Cox proportional hazards analyses were performed to identify risk factors for ALGIB and the cumulative probability of rebleeding. Kaplan–Meier curves with log-rank tests were used to demonstrate the cumulative survival rates of rebleeding. The prevalence of ALGIB was 5.31% (73/1374) in this study. In the univariate analysis, possible risk factors for ALGIB were duration of CD (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.33–1.09, P = 0.095), perianal disease (OR 1.96, 95% CI 0.92–4.20, P = 0.082), left colon involvement (OR 2.16, 95% CI 1.10–4.24, P = 0.025), azathioprine use ≥1 year (OR 0.46, 95% CI 0.23–0.90, P = 0.023), and previous hemorrhage history (OR 11.86, 95% CI 5.38–26.12, P < 0.0001). In the multivariate analysis, left colon involvement (OR 2.26, 95% CI 1.04–4.91, P = 0.039), azathioprine use ≥1 year (OR 0.44, 95% CI 0.20–0.99, P = 0.044), and previous hemorrhage history (OR 13.04, 95% CI 5.66–30.04, P < 0.0001) remained independent influencing factors. Older age (HR 0.23, 95% CI 0.07–0.77, P = 0.018), surgical treatment (HR 0.17, 95% CI 0.06–0.50, P < 0.001), and having bleeding episodes >3 months ago (HR 0.24, 95% CI 0.07–0.82, P = 0.022) resulted to be predictors associated with rebleeding after discharge. Patients who died often

  12. Molecular and functional characterization of cold-responsive C-repeat binding factors from Brachypodium distachyon

    PubMed Central

    2014-01-01

    Background Adverse environmental conditions severely influence various aspects of plant growth and developmental processes, causing worldwide reduction of crop yields. The C-repeat binding factors (CBFs) are critical transcription factors constituting the gene regulatory network that mediates the acclimation process to low temperatures. They regulate a large number of cold-responsive genes, including COLD-REGULATED (COR) genes, via the CBF-COR regulon. Recent studies have shown that the CBF transcription factors also play a role in plant responses to drought and salt stresses. Putative CBF gene homologues and their downstream genes are also present in the genome of Brachypodium distachyon, which is perceived as a monocot model in recent years. However, they have not been functionally characterized at the molecular level. Results Three CBF genes that are responsive to cold were identified from Brachypodium, designated BdCBF1, BdCBF2, and BdCBF3, and they were functionally characterized by molecular biological and transgenic approaches in Brachypodium and Arabidopsis thaliana. Our results demonstrate that the BdCBF genes contribute to the tolerance response of Brachypodium to cold, drought, and salt stresses by regulating downstream targets, such as DEHYDRIN5.1 (Dhn5.1) and COR genes. The BdCBF genes are induced under the environmental stress conditions. The BdCBF proteins possess transcriptional activation activity and bind directly to the promoters of the target genes. Transgenic Brachypodium plants overexpressing the BdCBF genes exhibited enhanced resistance to drought and salt stresses as well as low temperatures, and accordingly endogenous contents of proline and soluble sugars were significantly elevated in the transgenic plants. The BdCBF transcription factors are also functional in the heterologous system Arabidopsis. Transgenic Arabidopsis plants overexpressing the BdCBF genes were also tolerant to freezing, drought, and salt stresses, and a set of stress

  13. The Impact of Climatic Risk Factors on the Prevalence, Distribution, and Severity of Acute and Chronic Trachoma

    PubMed Central

    Ramesh, Anita; Kovats, Sari; Haslam, Dominic; Schmidt, Elena; Gilbert, Clare E.

    2013-01-01

    Background and Objectives Trachoma is the most common cause of infectious blindness. Hot, dry climates, dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear. The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic factors explain the current prevalence, distribution, and severity of acute and chronic trachoma. Understanding the present relationship between climate and trachoma could help inform current and future disease elimination. Methods A systematic review of peer-reviewed literature was conducted to identify observational studies which quantified an association between climate factors and acute or chronic trachoma and which met the inclusion and exclusion criteria. Studies that assessed the association between climate types and trachoma prevalence were also reviewed. Results Only eight of the 1751 papers retrieved met the inclusion criteria, all undertaken in Africa. Several papers reported an association between trachoma prevalence and altitude in highly endemic areas, providing some evidence of a role for temperature in the transmission of acute disease. A robust mapping study found strong evidence of an association between low rainfall and active trachoma. There is also consistent but weak evidence that the prevalence of trachoma is higher in savannah-type ecological zones. There were no studies on the effect of climate in low endemic areas, nor on the effect of dust on trachoma. Conclusion Current evidence on the potential role of climate on trachoma distribution is limited, despite a wealth of anecdotal evidence. Temperature and rainfall appear to play a role in the transmission of acute trachoma, possibly mediated through reduced activity of flies at lower temperatures. Further research is needed on climate and other environmental and behavioural factors, particularly in arid and savannah areas. Many studies did not adequately control for

  14. Predictive Factors for Acute and Late Urinary Toxicity After Permanent Prostate Brachytherapy: Long-Term Outcome in 712 Consecutive Patients

    SciTech Connect

    Keyes, Mira Miller, Stacy; Moravan, Veronika; Pickles, Tom; McKenzie, Michael; Pai, Howard; Liu, Mitchell; Kwan, Winkle; Agranovich, Alexander; Spadinger, Ingrid; Lapointe, Vincent; Halperin, Ross; Morris, W. James

    2009-03-15

    Purpose: To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. Methods and Materials: Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. Results: The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). Conclusion: Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low

  15. Incidence, prognosis, and factors associated with cardiac arrest in patients hospitalized with acute coronary syndromes (the Global Registry of Acute Coronary Events Registry)

    PubMed Central

    McManus, David D.; Aslam, Farhan; Goyal, Parag; Goldberg, Robert J.; Huang, Wei; Gore, Joel M.

    2013-01-01

    Objectives Contemporary data are lacking with respect to the incidence rates of, factors associated with, and impact of cardiac arrest from ventricular fibrillation or tachycardia (VF-CA) on hospital survival in patients admitted with an acute coronary syndrome (ACS). The objectives of this multinational study were to characterize trends in the magnitude of in-hospital VF-CA complicating an ACS and to describe its impact over time on hospital prognosis. Methods In 59 161 patients enrolled in the Global Registry of Acute Coronary Events Study between 2000 and 2007, we determined the incidence, prognosis, and factors associated with VF-CA. Results Overall, 3618 patients (6.2%) developed VF-CA during their hospitalization for an ACS. Incidence rates of VF-CA declined over time. Patients who experienced VF-CA were on average older and had a greater burden of cardiovascular disease, yet were less likely to receive evidence-based cardiac therapies than patients in whom VF-CA did not occur. Hospital death rates were 55.3% and 1.5% in patients with and without VF-CA, respectively. There was a greater than 50% decline in the hospital death rates associated with VF-CA during the years under study. Patients with a VF-CA occurring after 48 h were at especially high risk for dying during hospitalization (82.8%). Conclusion Despite reductions in the magnitude of, and short-term mortality from, VF-CA, VF-CA continues to exert an adverse effect on survival among patients hospitalized with an ACS. Opportunities exist to improve the identification and treatment of ACS patients at risk for VF-CA to reduce the incidence of, and mortality from, this serious arrhythmic disturbance. PMID:22157357

  16. Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in rat cardiac allografts.

    PubMed

    Keränen, M A I; Nykänen, A I; Krebs, R; Tuuminen, R; Sandelin, H; Koskinen, P K; Lemström, K B

    2006-12-01

    Hypoxia plays an integral part in cardiac transplantation as prolonged graft preservation is an individual risk factor for the development of cardiac allograft vasculopathy (CAV). In this study we characterized the role of hypoxia-inducible factor-1 (HIF-1) during prolonged graft preservation, ischemia-reperfusion (I/R), acute rejection, and chronic rejection. Heart transplantations were performed from Dark Agouti (DA) to Wister-Furth (allo) or DA to DA (syn) rats, without immunosuppression (acute rejection model, harvested at day 5) or with cyclosporine (chronic rejection model, harvested at day 60). To study the effect of preservation on HIF-1 regulation, normal DA hearts were subjected to different cold ischemia times with or without 45 minutes of additional warm ischemia. The role of I/R was studied by harvesting syngrafts at different time points after reperfusion. Real-time reverse-transcriptase polymerase chain reaction quantified total HIF-1 mRNA, while enzyme-linked immunosorbent assay and immunohistochemistry quantified and localized HIF-1 protein. Our results show that HIF-1 nuclear immunoreactivity is increased during graft preservation and I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute rejection induced HIF-1 in mRNA level. Our findings thus indicated that HIF-1 is activated during transplantation and suggested that manipulation of the HIF-1 pathway might reveal new therapeutic options to manage CAV. PMID:17175275

  17. Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

    PubMed Central

    Riesle, E; Friess, H; Zhao, L; Wagner, M; Uhl, W; Baczako, K; Gold, L I; Korc, M; Büchler, M W

    1997-01-01

    BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the

  18. Risk factors for winter outbreak of acute diarrhoea in France: case-control study.

    PubMed Central

    Letrilliart, L.; Desenclos, J. C.; Flahault, A.

    1997-01-01

    OBJECTIVES: To assess the potential role of consumption of shellfish (particularly raw oysters) and tap water in the winter epidemic of acute diarrhoea in France. DESIGN: Population based, case-control study during the 1995-6 winter epidemic of acute diarrhoea in France. SETTING: A national network comprising 1% of general practitioners in France. SUBJECTS: 568 pairs of cases and controls consulting in general practice and interviewed by 209 doctors from 26 December 1995 to 31 January 1996. Cases and controls were matched for age, doctor, and time of consultation. MAIN OUTCOME MEASURES: Adjusted relative risk of diarrhoea estimated from conditional logistic regression. RESULTS: The risk of acute diarrhoea was not increased in people who had recently eaten raw oysters (odds ratio 1.1; 95% confidence interval 0.9% to 1.4%) or other shellfish such as clams, cockles, and mussels, or in those people who usually consumed tap water rather than bottled water (0.8; 0.6% to 1.1%). The risk was, however, increased in people who had had recent contact wit ha person with diarrhoea either within the household (adjusted odds ratio 5.0) or in the workplace (3.1), and in people who lived with a child < or = 2 years of age (1.6). Recent treatment with either oral penicillin or cephalosporin was also independently associated with acute diarrhoea in winter. CONCLUSIONS: The winter epidemic of acute diarrhoea in France is probably not caused by consumption of either shellfish or tap water. A viral aetiology, however, is suggested by the speed with which the acute diarrhoea is transmitted. PMID:9448526

  19. Risk Factors for Acute Kidney Injury in Older Adults With Critical Illness: A Retrospective Cohort Study

    PubMed Central

    Kane-Gill, Sandra L.; Sileanu, Florentina E.; Murugan, Raghavan; Trietley, Gregory S.; Handler, Steven M.; Kellum, John A.

    2014-01-01

    Background Risk for acute kidney injury (AKI) in older adults has not been systematically evaluated. We sought to delineate the determinants of risk for AKI in older compared to younger adults. Study Design Retrospective analysis of patients hospitalized in July 2000–September 2008. Setting & Participants We identified all adult patients admitted to an intensive care unit (ICU) (n=45,655) in a large tertiary care university hospital system. We excluded patients receiving dialysis or kidney transplant prior to hospital admission, and patients with baseline creatinine ≥ 4 mg/dl, liver transplantation, indeterminate AKI status, or unknown age, leaving 39,938 patients. Predictor We collected data on multiple susceptibilities and exposures including age, sex, race, body mass, comorbid conditions, severity of illness, baseline kidney function, sepsis, and shock. Outcomes We defined AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. We examined susceptibilities and exposures across age strata for impact on development of AKI. Measurements We calculated area under the receiver operating characteristic curve (AUC) for prediction of AKI across age groups. Results 25,230 patients (63.2%) were aged 55 years or older. Overall 25,120 patients (62.9%) developed AKI (69.2% aged 55 years or older). Examples of risk factors for AKI in the oldest age category (75 years or older) were drugs (vancomycin, aminoglycosides, nonsteroidal anti-inflammatories), history of hypertension (OR, 1.13; 95% CI, 1.02–1.25) and sepsis (OR, 2.12; 95% CI, 1.68–2.67). Fewer variables remained predictive of AKI as age increased and the model for older patients was less predictive (p<0.001). For the age categories 18–54, 55–64, 65–74, and 75 years or older, the AUCs were 0.744 (95% CI, 0.735–0.752), 0.714 (95% CI, 0.702–0.726), 0.706 (95% CI, 0.693–0.718), and 0.673 (95% CI, 0.661–0.685), respectively. Limitations Analysis may not apply to non-ICU patients

  20. Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

    PubMed Central

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients. Methodology A total 667 dengue patients (2008–2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods. Results There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001], rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction [OR (95% CI): 34.6 (14.14–84.73), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR (95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3 days) was also observed among AKI patients (OR = 1.3, P = 0.044). Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI. Conclusions The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians’ alertness to this highly morbid and potentially fatal complication for optimal prevention and management. PMID:26421839

  1. Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement

    PubMed Central

    Lau, Anthony G.; Sun, Junjiang; Hannah, William B.; Livingston, Eric W.; Heymann, Dominique; Bateman, Ted A.; Monahan, Paul E.

    2015-01-01

    Introduction While chronic degenerative arthropathy is the main morbidity of hemophilia, a very high prevalance of low bone density is also seen in men and boys with hemophilia. The current study investigates bone degradation in the knee joint of hemophilic mice resulting from hemarthrosis and the efficacy of aggressive treatment with factor VIII in the period surrounding injury to prevent bone pathology. Methods Skeletally mature factor VIII knock-out mice were subjected to knee joint hemorrhage induced by puncture of the left knee joint capsule. Mice received either intravenous Factor VIII treatment or placebo immediately prior to injury and at hours 4, 24, 48, 72 and 96 after hemorrhage. Mice were euthanized two-weeks after injury and the joint morphology and loss of bone in the proximal tibia was assessed using microCT imaging. Results Quantitative microCT imaging of the knee joint found acute bone loss at the proximal tibia following injury including loss of trabecular bone volumetric density and bone mineral density, as well as trabecular connectivity density, number, and thickness. Unexpectedly, joint injury also resulted in calcification of the joint soft tissues including the tendons, ligaments, menisci, and cartilage. Treatment with factor VIII prevented this bone and soft tissue degeneration. Conclusion Knee joint hemorrhage resulted in acute changes of adjacent bone including loss of bone density and mineralization of joint soft tissues. The rapid calcification and loss of bone has implications for the initiation and progression of osteoarthritic degradation following joint bleeding. PMID:24712867

  2. Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement.

    PubMed

    Lau, A G; Sun, J; Hannah, W B; Livingston, E W; Heymann, D; Bateman, T A; Monahan, P E

    2014-09-01

    While chronic degenerative arthropathy is the main morbidity of haemophilia, a very high prevalence of low bone density is also seen in men and boys with haemophilia. This study investigates bone degradation in the knee joint of haemophilic mice resulting from haemarthrosis and the efficacy of aggressive treatment with factor VIII in the period surrounding injury to prevent bone pathology. Skeletally mature factor VIII knock-out mice were subjected to knee joint haemorrhage induced by puncture of the left knee joint capsule. Mice received either intravenous factor VIII treatment or placebo immediately prior to injury and at hours 4, 24, 48, 72 and 96 after haemorrhage. Mice were killed 2-weeks after injury and the joint morphology and loss of bone in the proximal tibia was assessed using microCT imaging. Quantitative microCT imaging of the knee joint found acute bone loss at the proximal tibia following injury including loss of trabecular bone volumetric density and bone mineral density, as well as trabecular connectivity density, number and thickness. Unexpectedly, joint injury also resulted in calcification of the joint soft tissues including the tendons, ligaments, menisci and cartilage. Treatment with factor VIII prevented this bone and soft tissue degeneration. Knee joint haemorrhage resulted in acute changes in adjacent bone including loss of bone density and mineralization of joint soft tissues. The rapid calcification and loss of bone has implications for the initiation and progression of osteoarthritic degradation following joint bleeding. PMID:24712867

  3. Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li; Caywood, Emi H

    2015-10-01

    Growing insight into prognosis of pediatric acute myeloid leukemia (AML) survival has led to improved outcome over time and could be further enhanced through investigation using a large number of patients. To characterize the extent of the association of pediatric AML survival with its identified prognostic factors, we analyzed the United States population-based Surveillance Epidemiology and End Results (SEER) large dataset of 3442 pediatric AML patients diagnosed and followed between 1973 and 2011 using a Cox proportional hazards model stratified by year of diagnosis. Patients diagnosed between 10 and 19 years of age were at a higher risk of death compared to those diagnosed before age 10 (adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.17-1.44). African Americans (1.27, 1.09-1.48) and Hispanics (1.15, 1.00-1.32) had an elevated risk of mortality than Caucasians. Compared to the subtype acute promyelocytic leukemia, AML with minimal differentiation (2.44, 1.78-3.35); acute erythroid leukemia (2.34, 1.60-3.40); AML without maturation (1.87, 1.35-2.59); and most other AML subtypes had a higher risk of mortality, whereas AML with inv(16) had a substantially lower risk. Age at diagnosis, race-ethnicity, AML subtype, county level poverty and geographic region appeared as significant prognostic factors of pediatric AML survival in the US. Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome. PMID:26159683

  4. Prognostics factors for mortality and renal recovery in critically ill patients with acute kidney injury and renal replacement therapy

    PubMed Central

    Gaião, Sérgio Mina; Gomes, André Amaral; Paiva, José Artur Osório de Carvalho

    2016-01-01

    Objective Identify prognostic factors related to mortality and non-recovery of renal function. Methods A prospective single-center study was conducted at the intensive care medicine department of a university hospital between 2012 and 2015. Patients with acute kidney injury receiving continuous renal replacement therapy were included in the study. Clinical and analytical parameters were collected, and the reasons for initiation and discontinuation of renal replacement therapy were examined. Results A total of 41 patients were included in the study, of whom 43.9% had sepsis. The median Simplified Acute Physiology Score II (SAPSII) was 56 and the mortality was 53.7%, with a predicted mortality of 59.8%. The etiology of acute kidney injury was often multifactorial (56.1%). Survivors had lower cumulative fluid balance (median = 3,600mL, interquartile range [IQR] = 1,175 - 8,025) than non-survivors (median = 12,000mL, IQR = 6,625 - 17,875; p = 0.004). Patients who recovered renal function (median = 51.0, IQR = 45.8 - 56.2) had lower SAPS II than those who do not recover renal function (median = 73, IQR = 54 - 85; p = 0.005) as well as lower fluid balance (median = 3,850, IQR = 1,425 - 8,025 versus median = 11,500, IQR = 6,625 - 16,275; p = 0.004). Conclusions SAPS II at admission and cumulative fluid balance during renal support therapy were risk factors for mortality and non-recovery of renal function among critically ill patients with acute kidney injury needing renal replacement therapy. PMID:27096679

  5. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation

    PubMed Central

    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-01-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. PMID:20030669

  6. Factors predisposing to acute and recurrent bacterial non-necrotizing cellulitis in hospitalized patients: a prospective case-control study.

    PubMed

    Karppelin, M; Siljander, T; Vuopio-Varkila, J; Kere, J; Huhtala, H; Vuento, R; Jussila, T; Syrjänen, J

    2010-06-01

    Acute non-necrotizing cellulitis is a skin infection with a tendency to recur. Both general and local risk factors for erysipelas or cellulitis have been recognized in previous studies using hospitalized controls. The aim of this study was to identify risk factors for cellulitis using controls recruited from the general population. We also compared patients with a history of previous cellulitis with those suffering a single episode, with regard to the risk factors: length of stay in hospital, duration of fever, and inflammatory response as measured by C-reactive protein (CRP) level and leukocyte count. Ninety hospitalized cellulitis patients and 90 population controls matched for age and sex were interviewed and clinically examined during the period April 2004 to March 2005. In multivariate analysis, chronic oedema of the extremity, disruption of the cutaneous barrier and obesity were independently associated with acute cellulitis. Forty-four (49%) patients had a positive history (PH) of at least one cellulitis episode before entering the study. Obesity and previous ipsilateral surgical procedure were statistically significantly more common in PH patients, whereas a recent (<1 month) traumatic wound was more common in patients with a negative history (NH) of cellulitis. PH patients had longer duration of fever and hospital stay, and their CRP and leukocyte values more often peaked at a high level than those of NH patients. Oedema, broken skin and obesity are risk factors for acute cellulitis. The inflammatory response as indicated by CRP level and leukocyte count is statistically significantly more severe in PH than NH patients. PMID:19694769

  7. Burden of acute infections (except respiratory and diarrheal) and its risk factors among under-five children in India: A systematic review and meta-analysis

    PubMed Central

    Ganguly, Enakshi; Sharma, Pawan K; Bunker, Clareann H

    2016-01-01

    Context Acute infections of eyes, ears, skin, and others are a common cause of morbidity in under-five children. The overall burden of other infections and their risk factors is not known. Evidence Acquisition Available literature was searched comprehensively using PubMed for acute infections (except acute respiratory and diarrheal diseases) using the relevant medical subject heading terms. Extracted articles were independently reviewed against inclusion/exclusion criteria and rated for quality. 10 articles were abstracted and reviewed to identify the reported prevalence and risk factors for acute infections among children. Results The pooled prevalence of infections (not including acute respiratory and diarrhea) between 2002 and 2013 was 18.42 (95% confidence interval: 9.30–30.62), with reported range of 3.7–50.8%. The significantly positively associated factors reported in single studies were young age of the child, malnutrition, poor breastfeeding, low socio-economic status, animal rearing near household and mothers’ illiteracy for independent morbidities. Conclusion The evidence on risk factors including breastfeeding, vaccination, age, and sex that predispose under-five Indian children to different infections is inconclusive. There is a need to conduct more studies on acute infections other than acute respiratory and diarrhea, to establish their determinants in Indian children. PMID:27170943

  8. Systolic Blood Pressure Variability is a Novel Risk Factor for Rebleeding in Acute Subarachnoid Hemorrhage

    PubMed Central

    Lin, Qing-Song; Ping-Chen; Lin, Yuan-Xiang; Lin, Zhang-Ya; Yu, Liang-Hong; Dai, Lin-Sun; Kang, De-Zhi

    2016-01-01

    Abstract Rebleeding of an aneurysm is a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Whereas numerous studies have demonstrated predictors of rebleeding and effect of systolic blood pressure variability (SBPV) on stroke, few data on the association between SBPV and rebleeding. Here, we sought to identify the effect of SBPV on rebleeding in acute aneurysmal SAH. Case–control study. From January 2010 to June 2015, 612 patients with aneurysmal SAH were enrolled in our tertiary care medical center. Main outcome measures: Consecutive patients with acute (<3 days from ictus) aneurismal rebleeding or repair or death were retrospectively included. Antihypertensive therapy based on a predefined standardized protocol was prescribed to lower and maintain SBP between 120 and 160 mm Hg. SBP was measured hourly until a censoring event occurred. SBPV was determined as standard deviation (SD) and successive variation (SV). Binary logistic regression was used to assess the association between SBPV and rebleeding. Rebleeding occurred in 61 (10.0%) of the 612 patients. We identified 47 acute rebleeding as cases and 382 early repair or early death as controls. On binary logistic regression analysis, rebleeding was associated with the SD of SBP (odds ratio [OR], 1.254; 95% confidence interval [CI], 1.131–1.391; P < 0.001) and the SV of SBP (OR, 1.131; 95% CI, 1.039–1.231; P = 0.004). No significant difference was seen between rebleeding and mean systolic blood pressure (MSBP). SBPV is associated with increased rates of acute aneurysmal rebleeding. Further prospective research is warranted to confirm that SBP stability prevents acute aneurysm rebleeding. PMID:26986118

  9. Mutations in the Ca2+/H+ transporter CAX1 increase CBF/DREB1 expression and the cold-acclimation response in Arabidopsis.

    PubMed

    Catala, Rafael; Santos, Elisa; Alonso, Jose M; Ecker, Joseph R; Martinez-Zapater, Jose M; Salinas, Julio

    2003-12-01

    Transient increases in cytosolic free calcium concentration ([Ca2+]cyt) are essential for plant responses to a variety of environmental stimuli, including low temperature. Subsequent reestablishment of [Ca2+]cyt to resting levels by Ca2+ pumps and antiporters is required for the correct transduction of the signal [corrected]. C-repeat binding factor/dehydration responsive element binding factor 1 (Ca2+/H+) antiporters is required for the correct transduction of the signal. We have isolated a cDNA from Arabidopsis that corresponds to a new cold-inducible gene, rare cold inducible4 (RCI4), which was identical to calcium exchanger 1 (CAX1), a gene that encodes a vacuolar Ca2+/H+ antiporter involved in the regulation of intracellular Ca2+ levels. The expression of CAX1 was induced in response to low temperature through an abscisic acid-independent pathway. To determine the function of CAX1 in Arabidopsis stress tolerance, we identified two T-DNA insertion mutants, cax1-3 and cax1-4, that display reduced tonoplast Ca2+/H+ antiport activity. The mutants showed no significant differences with respect to the wild type when analyzed for dehydration, high-salt, chilling, or constitutive freezing tolerance. However, they exhibited increased freezing tolerance after cold acclimation, demonstrating that CAX1 plays an important role in this adaptive response. This phenotype correlates with the enhanced expression of CBF/DREB1 genes and their corresponding targets in response to low temperature. Our results indicate that CAX1 ensures the accurate development of the cold-acclimation response in Arabidopsis by controlling the induction of CBF/DREB1 and downstream genes. PMID:14630965

  10. Draft Genome Sequence of Pseudomonas putida CBF10-2, a Soil Isolate with Bioremediation Potential in Agricultural and Industrial Environmental Settings

    PubMed Central

    Damania, Ashish

    2016-01-01

    Pseudomonas putida CBF10-2 is a microorganism isolated from farmland soil in Fairchild, TX, found to degrade high-impact xenobiotics, including organophosphate insecticides, petroleum hydrocarbons, and both monocyclic and polycyclic aromatics. The versatility of CBF10-2 makes it useful for multipurpose bioremediation of contaminated sites in agricultural and industrial environments. PMID:27417844

  11. Draft Genome Sequence of Pseudomonas putida CBF10-2, a Soil Isolate with Bioremediation Potential in Agricultural and Industrial Environmental Settings.

    PubMed

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Pseudomonas putida CBF10-2 is a microorganism isolated from farmland soil in Fairchild, TX, found to degrade high-impact xenobiotics, including organophosphate insecticides, petroleum hydrocarbons, and both monocyclic and polycyclic aromatics. The versatility of CBF10-2 makes it useful for multipurpose bioremediation of contaminated sites in agricultural and industrial environments. PMID:27417844

  12. Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks

    PubMed Central

    Jann, Kay; Gee, Dylan G.; Kilroy, Emily; Schwab, Simon; Smith, Robert X.; Cannon, Tyrone D.; Wang, Danny J.J.

    2014-01-01

    Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain’s intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2 × 2 × 2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test–retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905 ± 0.033 between-sessions; 0.885 ± 0.052 between-scanners) than ASL (0.545 ± 0.048; 0.575 ± 0.059). Nevertheless, ASL provided highly reproducible (0.955 ± 0.021; 0.970 ± 0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners. PMID:25463468

  13. Intravitreal Anti-vascular Endothelial Growth Factor versus Observation in Acute Central Serous Chorioretinopathy: One-year Results

    PubMed Central

    Park, Sang-Uk; Lee, Seung-Jun

    2014-01-01

    Purpose To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) compared with observation for treating acute central serous chorioretinopathy (CSC). Methods A retrospective study of 36 patients with acute CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15 patients with observation (observation group). Patients in the anti-VEGF group received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of the foveal inner segment/outer segment (IS/OS) line at 12 months was also analyzed. Results Resolution of SRF was achieved in 20 of 21 eyes in the anti-VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA and CFT were not different between the two groups at 12 months (p > 0.05). The amount of change in BCVA, however, differed significantly between the groups (p = 0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF group than in the observation group (p = 0.012). Conclusions In terms of BCVA, anti-VEGF and observation only had similar therapeutic effects in acute CSC patients. In some patients, however, the rapid resolution of SRF by anti-VEGF might reduce the risk of photoreceptor degeneration and improve long-term visual acuity. PMID:25120339

  14. Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

    PubMed Central

    Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

    2014-01-01

    Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

  15. Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation.

    PubMed

    Fan, Yu-Ting; Yin, Guo-Jian; Xiao, Wen-Qin; Qiu, Lei; Yu, Ge; Hu, Yan-Ling; Xing, Miao; Wu, De-Qing; Cang, Xiao-Feng; Wan, Rong; Wang, Xing-Peng; Hu, Guo-Yong

    2015-01-01

    Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 μ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits. PMID:26364660

  16. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  17. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

    PubMed

    Ricken, Roland; Adli, Mazda; Lange, Claudia; Krusche, Esther; Stamm, Thomas J; Gaus, Sebastian; Koehler, Stephan; Nase, Sarah; Bschor, Tom; Richter, Christoph; Steinacher, Bruno; Heinz, Andreas; Rapp, Michael A; Borgwardt, Stefan; Hellweg, Rainer; Lang, Undine E

    2013-12-01

    In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms. PMID:24018547

  18. Analysis of factors related to short-term prognosis in patients undergoing percutaneous coronary intervention for acute myocardial infarction

    PubMed Central

    MA, YI; LI, LI; SHANG, XIAO-MING; TAN, ZHENG; GENG, XUE-BIN; ZHAO, BI-QIONG; TIAN, MEI-RONG

    2013-01-01

    The present study aimed to investigate the factors related to short-term prognosis in patients undergoing direct percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). A total of 805 patients were included and divided into a control group and an adverse cardiovascular events group based on the prognosis, to compare risk factors and coronary angiographic characteristics in the two groups. In the adverse events group, the ages, admission blood glucose, uric acid (UA), homocysteine (HCY), creatine kinase (CK) and peak creatine kinase-MB (CKMB) isozyme levels were clearly higher compared with those in the control group, while the levels of total cholesterol (TC), triglycerides (TGs) and low-density lipoprotein (LDL) were lower compared with those in the control group. The incidence of hypertension in females in the adverse events group was markedly higher compared with that in the control group, while the diabetes rate was lower compared with that in the control group. Logistic regression analysis revealed that age, gender, hypertension, diabetes and admission blood glucose, HCY, TC and UA levels were independent risk factors of short-term prognosis in patients undergoing emergency PCI. The majority of the patients in the adverse events group were elderly females with hypertension, a large area of myocardial infarction and increased admission blood glucose, UA and HCY levels, as well as a low diabetes rate and decreased levels of acute-phase TC and LDL. PMID:23596491

  19. [Research Progress on the Role of Chromatin Remodeling Factor BRG1 in Acute Myeloid Leukemia].

    PubMed

    Gao, Shuo; Xu, Xue-Jing; Zhang, Kui

    2016-06-01

    BRG1 (Brahma-related gene 1, BRG1) is the ATPase subunit of SWI/SNF chromatin remodeling complexes, which plays an important role in cell cycle regulation, DNA repair and tumor development. Unlike the evidence as tumor suppressor genes in the past reports, latest researches show that BRG1 plays an important role in sustaining the growth of leukemia cells in acute myeloid leukemia, and these effects on normal hematopoietic stem cells are dispensable. Further studies of the role and mechanism of BRG1 in acute myeloid leukemia will contribute to the development of a new and promising targeted therapy strategy. This article reviews the role of BRG1 on leukemia cells and leukemia stem cells in AML and discusses the related mechanism, which providing some reference for the targeted treatment strategy of AML. PMID:27342536

  20. A proinflammatory factor in lymphocytes. Its role in the development of acute, non-immunological inflammatory reactions.

    PubMed Central

    Leme, J. C.; Bechara, G. H.; Dos Santos, R. R.

    1976-01-01

    Drug-induced leucopenia renders rats hyporeactive to various inflammatory stimuli. Administration to leucopenic rats of suspensions of lymphocytes, sufficient to apparently correct the induced lymphocytopenia, led to a partial but marked reversal of the inhibited responses. Similar results were observed when lysates of lymphocytes or filtrates of the disintegrated cells were injected. Suspensions of polymorphonuclear granulocytes, on the contrary, were ineffective in producing a reversal of inhibited inflammatory reactions in leucopenic rats. The presence of a proinflammatory factor (LpIF) in lymphocytes, which might be involved in the modulation of acute inflammatory responses is suggested. PMID:971405

  1. The fibroblast growth factor receptor mediates the increased FGF23 expression in acute and chronic uremia.

    PubMed

    Hassan, Alia; Durlacher, Karina; Silver, Justin; Naveh-Many, Tally; Levi, Ronen

    2016-02-01

    Serum FGF23 is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. FGF23 expression is increased by activation of the FGF receptor 1 (FGFR1) in rats with normal renal function and in vitro in bone-derived osteoblast-like cells. We studied the regulation of FGF23 by FGFR1 in vivo in acute and chronic uremia in mice and rats. Folic acid-induced acute kidney injury increased calvaria FGF23 mRNA and serum FGF23 and parathyroid hormone (PTH) levels at 6 h. The FGFR1 receptor inhibitor PD173074 prevented the folic acid-induced increase in both FGF23 mRNA and serum levels but had no effect on serum PTH levels. A more prolonged uremia due to an adenine high-phosphorus diet for 14 days resulted in high levels of FGF23 mRNA and serum FGF23 and PTH. PD173074 decreased serum FGF23 and mRNA levels with no effect on PTH in the adenine high phosphorus-induced uremic rats. Therefore, a derangement in FGF23 regulation starts early in the course of acute kidney injury, is in part independent of the increase in serum PTH, and involves activation of FGFR1. It is possible that FGFR1 in the osteocyte is activated by locally produced canonical FGFs, which are increased in uremia. This is the first demonstration that activation of FGFR1 is essential for the high levels of FGF23 in acute and chronic experimental uremia. PMID:26311115

  2. The Cbf5-Nop10 Complex is a Molecular Bracket that Organizes Box H/ACA RNPs

    SciTech Connect

    Hamma, Tomoko; Reichow, Steve L.; Varani, Gabriele; Ferre-D'Amare, Adrian R.

    2005-12-01

    Box H/ACA ribonucleoprotein particles (RNPs) catalyze RNA pseudouridylation and direct processing of ribosomal RNA, and are essential architectural components of vertebrate telomerases. H/ACA RNPs comprise four proteins and a multihelical RNA. Two proteins, Cbf5 and Nop10, suffice for basal enzymatic activity in an archaeal in vitro system. We now report their cocrystal structure at 1.95-A resolution. We find that archaeal Cbf5 can assemble with yeast Nop10 and with human telomerase RNA, consistent with the high sequence identity of the RNP componenets between archaea and eukarya. Thus, the Cbf5-Nop10 architecture is phylogenetically conserved. The structure shows how Nop10 buttresses the active site of Cbf5, and it reveals two basic troughs that bidirectionally extend the active site cleft. Mutagenesis results implicate an adjacent basic patch in RNA binding. This tripartite RNA-binding surface may function as a molecular bracket that organizes the multihelical H/ACA and telomerase RNAs.

  3. Cold acclimation and BnCBF17-over-expression enhance photosynthetic performance and energy conversion efficiency during long-term growth of Brassica napus under elevated CO2 conditions.

    PubMed

    Dahal, Keshav; Gadapati, Winona; Savitch, Leonid V; Singh, Jas; Hüner, Norman P A

    2012-11-01

    The effects of cold acclimation and long-term elevated CO(2) on photosynthetic performance of wild-type (WT) and BnCBF17-over-expressing line of Brassica napus cv. Westar (BnCBF17-OE) grown at either 20/16 °C (non-acclimated) or 5/5 °C (cold acclimated) and at either ambient (380 μmol C mol(-1)) or elevated (700 μmol C mol(-1)) CO(2) were studied. Compared with non-acclimated WT, the BnCBF17-OE grown at 20 °C mimicked the effects of cold acclimation on WT B. napus with respect to compact dwarf phenotype and increased rates of light-saturated CO(2) assimilation and photosynthetic electron transport. This was associated with enhanced energy conversion efficiency into biomass as assessed by decreased excitation pressure coupled to decreased dependence on non-photochemical energy dissipation for a given irradiance. Growth at elevated CO(2) decreased the light and CO(2)-saturated rates of photosynthesis by 30 % for non-acclimated WT relative to growth at ambient CO(2). This was associated with inhibition in electron transport rates (20 %), decrease in amount of rbcL (35 %) and cytosolic FBPase (70 %) and increased excitation pressure and non-photochemical quenching in elevated versus ambient CO(2)-grown non-acclimated WT. In contrast, light and CO(2)-saturated rates of photosynthesis, electron transport, excitation pressure, non-photochemical quenching and levels of rbcL, cytosolic FBPase and Lhcb1 were insensitive to growth under elevated CO(2) in BnCBF17-OE and cold-acclimated WT. Thus, BnCBF17-over-expression and cold acclimation maintain enhanced energy conversion efficiency and reduced sensitivity to feedback-limited photosynthesis during long-term growth of B. napus under elevated CO(2). Our results indicated that CBFs transcription factors regulate not only freezing tolerance but also has major whole plant effects. PMID:22847022

  4. Limited Reliability of CT perfusion acute infarct volume measurements compared to DWI in anterior circulation stroke

    PubMed Central

    Schaefer, Pamela W.; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A.; Yoo, Albert J.; Kamalian, Shahmir; Gonzalez, R. Gilberto; Lev, Michael H.

    2015-01-01

    Background and Purpose DWI can reliably identify critically ischemic tissue (CIT) shortly after stroke onset. We tested if thresholded CT-CBF and CT-CBV maps are sufficiently accurate to substitute for DWI for estimating CIT volume. Methods Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation, and CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast-to-noise ratios (CNR) of ischemic regions on the DWI and CTP images were measured. Correlation and Bland-Altman analyses were used to assess reliability of CTP. Results Mean CNRs for DWI, CT-CBF and CT-CBV were 4.3, 0.9 and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R2=0.87 for CT-CBF; R2=0.83 for CT-CBV; p<0.001). Bland-Altman analyses revealed little systemic bias (−2.6 ml) but high measurement variability (95% CI ±56.7 ml) between mean CT-CBF and DWI lesion volumes, and systemic bias (−26 ml) and high measurement variability (95% CI ±64.0 ml) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. Conclusions The poor CNRs of CT-CBV and CT-CBF compared to DWI result in large measurement error making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than if DWI is used. PMID:25550366

  5. Heterogeneity of Clonal Expansion and Maturation-Linked Mutation Acquisition in Hematopoietic Progenitors in Human Acute Myeloid Leukemia

    PubMed Central

    Walter, Roland B.; Laszlo, George S.; Lionberger, Jack M.; Pollard, Jessica A.; Harrington, Kimberly H.; Gudgeon, Chelsea J.; Othus, Megan; Rafii, Shahin; Meshinchi, Soheil; Appelbaum, Frederick R.; Bernstein, Irwin D.

    2014-01-01

    Recent technological advances led to an appreciation of the genetic complexity of human acute myeloid leukemia (AML) but underlying progenitor cells remain poorly understood because their rarity precludes direct study. We developed a co-culture method integrating hypoxia, aryl hydrocarbon receptor inhibition, and micro-environmental support via human endothelial cells to isolate these cells. X-chromosome inactivation studies of the least mature precursors derived following prolonged culture of CD34+/CD33− cells revealed polyclonal growth in highly curable AMLs, suggesting mutations necessary for clonal expansion were acquired in more mature progenitors. Consistently, in core-binding factor (CBF) leukemias with known complementing mutations, immature precursors derived following prolonged culture of CD34+/CD33− cells harbored neither mutation or the CBF mutation alone, whereas more mature precursors often carried both mutations. These results were in contrast to those with leukemias with poor prognosis that showed clonal dominance in the least mature precursors. These data indicate heterogeneity among progenitors in human AML that may have prognostic and therapeutic implications. PMID:24721792

  6. Suppression of proliferation of a human B-cell leukaemic cell line derived from acute lymphoblastic leukaemia by soluble factor(s) from Campylobacter rectus.

    PubMed

    Saito, S; Hayakawa, M; Takiguchi, H; Abiko, Y

    1993-06-01

    Soluble sonic extracts of several strains were examined for their ability to alter proliferation of a cell line derived from acute lymphoblastic leukaemia (BALL-1). Extracts of all strains tested caused dose-dependent suppression of proliferation when assessed by DNA (tritiated thymidine incorporation), RNA (tritiated uridine incorporation) and protein (tritiated leucine incorporation) synthesis. There was no effect on the viability of BALL-1 as measured by either trypan-blue exclusion or extracellular release of the cytoplasmic enzyme lactate dehydrogenase. The suppressive factor(s) was separated in a well-defined peak by high-pressure liquid DEAE ion-exchange chromatography, which revealed a single active peak with a molecular mass of 48 kDa. Characterization of the peak indicated that the suppressive factor(s) was heat labile (activity destroyed at 80 degrees C) and sensitive to the proteolytic enzyme pronase P. The soluble suppressive factor(s) from Campylobacter rectus thus has protein-like properties and no cytotoxicity to a human B-cell leukaemic cell line. PMID:8343067

  7. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  8. Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.

    PubMed

    Mullinger, K J; Mayhew, S D; Bagshaw, A P; Bowtell, R; Francis, S T

    2014-07-01

    Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR. PMID:24632092

  9. Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

    PubMed Central

    Goekint, Maaike; Bos, Inge; Heyman, Elsa; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF. PMID:22134693

  10. Types, Risk Factors, Clinical symptoms and Diagnostic Tests of Acute Adult Meningitis in Northern Iran During 2006-2012

    PubMed Central

    Bagheri-Nesami, Masoumeh; Babamahmoodi, Farhang

    2015-01-01

    Background Acute bacterial meningitis is a medical emergency condition that requires prompt diagnosis and treatment and otherwise associated with serious morbidity and mortality. Aim The aim of this study was to assess types, risk factors, clinical symptoms and diagnostic tests of meningitis in hospitalized patients of Mazandaran University of medical sciences hospitals during 2006-2012. Matherials and Methods This is a retrospective descriptive study. Following approval of the ethics committee of Mazandaran University of Medical Sciences, records of adult patients diagnosed with acute meningitis from 2006 to 2012 were extracted from Mazandaran Provincial Health Center and patients attending hospitals affiliated to Mazandaran University of Medical Sciences. Statistical Analysis Data were analyzed with SPSS-16 using descriptive statistics (frequency, mean, standard deviation, and median). Results In this study, of the 137 patients with meningitis, 73 (53.9%) were viral, 61 (46%) bacterial, 1 (0.7%) fungal, and 2 (1.4%) unknown. The majority of risk factors in patients were head trauma, upper respiratory infection, and drug addiction. The most common clinical signs were headache, fever, nausea and vomiting, and stiff neck. Conclusion In this study, the incidence of meningitis was much lower than any other country. It could be due to geographic variation or incomplete recording of patient's data. It is recommended to perform a longitudinal study during the coming years on patients with meningitis. PMID:26155497

  11. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer

    PubMed Central

    Zhao, Yaqin; Chen, Lu; Zhang, Shu; Wu, Qiang; Jiang, Xiaoqin; Zhu, Hong; Wang, Jin; Li, Zhiping; Xu, Yong; Zhang, Ying Jie; Bai, Sen; Xu, Feng

    2015-01-01

    Background Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. Methods We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Results Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Conclusion Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning. PMID:26273335

  12. Risk Factors for Acute Graft-Versus-Host Disease After Human Leukocyte Antigen–Identical Sibling Transplants for Adults With Leukemia

    PubMed Central

    Hahn, Theresa; McCarthy, Philip L.; Zhang, Mei-Jie; Wang, Dan; Arora, Mukta; Frangoul, Haydar; Gale, Robert Peter; Hale, Gregory A.; Horan, John; Isola, Luis; Maziarz, Richard T.; van Rood, Jon J.; Gupta, Vikas; Halter, Joerg; Reddy, Vijay; Tiberghien, Pierre; Litzow, Mark; Anasetti, Claudio; Pavletic, Stephen; Ringdén, Olle

    2008-01-01

    Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may

  13. Cerebral hemodynamics in human acute ischemic stroke: a study with diffusion- and perfusion-weighted magnetic resonance imaging and SPECT.

    PubMed

    Liu, Y; Karonen, J O; Vanninen, R L; Ostergaard, L; Roivainen, R; Nuutinen, J; Perkiö, J; Könönen, M; Hämäläinen, A; Vanninen, E J; Soimakallio, S; Kuikka, J T; Aronen, H J

    2000-06-01

    Nineteen patients with acute ischemic stroke (<24 hours) underwent diffusion-weighted and perfusion-weighted (PWI) magnetic resonance imaging at the acute stage and 1 week later. Eleven patients also underwent technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (SPECT) at the acute stage. Relative (ischemic vs. contralateral control) cerebral blood flow (relCBF), relative cerebral blood volume, and relative mean transit time were measured in the ischemic core, in the area of infarct growth, and in the eventually viable ischemic tissue on PWI maps. The relCBF was also measured from SPECT. There was a curvilinear relationship between the relCBF measured from PWI and SPECT (r = 0.854; P < 0.001). The tissue proceeding to infarction during the follow-up had significantly lower initial CBF and cerebral blood volume values on PWI maps (P < 0.001) than the eventually viable ischemic tissue had. The best value for discriminating the area of infarct growth from the eventually viable ischemic tissue was 48% for PWI relCBF and 87% for PWI relative cerebral blood volume. Combined diffusion and perfusion-weighted imaging enables one to detect hemodynamically different subregions inside the initial perfusion abnormality. Tissue survival may be different in these subregions and may be predicted. PMID:10894174

  14. Acute kidney injury: risk factors and management challenges in developing countries.

    PubMed

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  15. Acute kidney injury: risk factors and management challenges in developing countries

    PubMed Central

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  16. The central metabolism regulator EIIAGlc switches Salmonella from growth arrest to acute virulence through activation of virulence factor secretion.

    PubMed

    Mazé, Alain; Glatter, Timo; Bumann, Dirk

    2014-06-12

    The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2) involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism. PMID:24835993

  17. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  18. Changes in apoptotic factors in hypothalamus and hippocampus after acute and subchronic stress induction during conditioned place preference paradigm

    PubMed Central

    Haghparast, Abbas; Fatahi, Zahra; Alamdary, Shabnam Zeighamy; Khodagholi, Fariba

    2013-01-01

    The hypothalamus (HYP) and hippocampus (HIP) are important regions involved in stress responses. These areas are also associated with reward processing. In this study, the effects of acute and subchronic stress on the changes in apoptotic factors (Bax/Bcl-2 ratio, caspase-3 activation and PARP degradation) in the HYP and HIP during conditioned place preference (CPP) paradigm were evaluated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup contained control, acute stress (AS) and subchronic stress (SS) groups. In all groups, CPP paradigm was done and thereinafter alterations of apoptotic factors were measured by western blot. The results revealed that in the HYP, all mentioned factors increased significantly in saline- or morphine-treated animals during AS and SS. On the other hand, in the HIP, Bax/Bcl-2 ratio in saline-treated animals increased significantly during AS and SS, while in morphine-treated animals this ratio did not have any significant alteration during AS and was decreased during SS compared with morphine-control group. Caspase-3 and PARP increased during AS and SS in saline- or morphine-treated animals. For example, caspase-3 increased during AS and SS in morphine-treated animals by 2.4 folds and PARP (89 KDa) increased by 3.1 and 3.5 folds, respectively. Interestingly, the increase of apoptotic factors in morphine-treated animals was more considerable than that of saline-treated animals. These results strongly implied that AS and SS trigger apoptotic events in the HYP and HIP of saline- and/or morphine-treated animals as well as morphine reinforces the effect of stress on the induction of apoptosis. PMID:27385959

  19. Association of lifestyle-related factors with circadian onset patterns of acute myocardial infarction: a prospective observational study in Japan

    PubMed Central

    Edahiro, Ryuya; Sakata, Yasuhiko; Nakatani, Daisaku; Suna, Shinichiro; Usami, Masaya; Matsumoto, Sen; Hara, Masahiko; Kitamura, Tetsuhisa; Sato, Hiroshi; Yamashita, Shizuya; Nanto, Shinsuke; Hikoso, Shungo; Sakata, Yasushi; Hori, Masatsugu; Hamasaki, Toshimitsu; Komuro, Issei

    2014-01-01

    Objective The onset of acute myocardial infarction (AMI) shows characteristic circadian variations involving a definite morning peak and a less-defined night-time peak. However, the factors influencing the circadian patterns of AMI onset and their influence on morning and night-time peaks have not been fully elucidated. Design, setting and participants An analysis of patients registered between 1998 and 2008 in the Osaka Acute Coronary Insufficiency Study, which is a prospective, multicentre observational study of patients with AMI in the Osaka region of Japan. The present study included 7755 consecutive patients with a known time of AMI onset. Main outcomes and measures A mixture of two von Mises distributions was used to examine whether a circadian pattern of AMI had uniform, unimodal or bimodal distribution, and the likelihood ratio test was then used to select the best circadian pattern among them. The hierarchical likelihood ratio test was used to identify factors affecting the circadian patterns of AMI onset. The Kaplan-Meier method was used to estimate survival curves of 1-year mortality according to AMI onset time. Results The overall population had a bimodal circadian pattern of AMI onset characterised by a high and sharp morning peak and a lower and less-defined night-time peak (bimodal p<0.001). Although several lifestyle-related factors had a statistically significant association with the circadian patterns of AMI onset, serum triglyceride levels had the most prominent association with the circadian patterns of AMI onset. Patients with triglyceride ≥150 mg/dL on admission had only one morning peak in the circadian pattern of AMI onset during weekdays, with no peaks detected on weekends, whereas all other subgroups had two peaks throughout the week. Conclusions The circadian pattern of AMI onset was characterised by bimodality. Notably, several lifestyle-related factors, particularly serum triglyceride levels, had a strong relation with the circadian

  20. Effect of granulocyte colony-stimulating factor administration on renal regeneration after experimentally induced acute kidney injury in dogs.

    PubMed

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the effects of granulocyte colony-stimulating factor (GCSF) administration in dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), the dogs were randomly assigned into 2 groups (n = 3 dogs/group). Then dogs immediately received GCSF (10 μg/kg) or 1 mL of saline (0.9% NaCl) solution (control group) SC; this treatment was repeated once daily for 4 additional days (days 1 through 4). A once-daily CBC (day 0 to 4), serum biochemical analysis (day 0 to 3), and urinalysis (day 0 to 3) were performed for each dog; samples were collected before administration of cisplatin (day 0) and before treatment with GCSF or saline solution (days 1 through 4). After sample collection and treatment on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analyses, and cytokine profiling via reverse transcriptase PCR assay. RESULTS In the GCSF-treated group, the histologic evaluation and immunohistochemical analyses of kidney tissue revealed less fibrotic change and greater proliferation of renal tubular epithelial cells, compared with findings in the control group. The mRNA profiles of kidney tissue from the GCSF-treated group indicated lower expression of tumor necrosis factor-α and tumor growth factor-β, compared with findings in the control group; however, concentrations of factors related to renal regeneration were not greater in the GCSF-treated group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that GCSF treatment can impede renal fibrosis and increase proliferation of renal tubules after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:199-207). PMID:27027715

  1. Diapers in War Zones: Ethnomedical Factors in Acute Childhood Gastroenteritis in Peshawar, Pakistan

    PubMed Central

    Zaidi, Saira H.; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services’ admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient’s parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  2. Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress.

    PubMed

    Li, Kun-Cheng; Ho, Yu-Ling; Chen, Cing-Yu; Hsieh, Wen-Tsong; Chang, Yuan-Shiun; Huang, Guan-Jhong

    2016-05-01

    Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression. Lobeline was tested by inhibiting phosphorylation of mitogen-activated protein kinases (MAPKs), NF-κB and IκBα in LPS-stimulated RAW 264.7 cells. When RAW 264.7 macrophages were given lobeline with LPS, a significant concentration-dependent inhibition of NO production was detected. In vivo tests, mice were either treated with normal saline, 10mg/kg dexmethasone or 5, 10, 20mg/kg lobeline intraperitoneally, and after an hour, the administration of 5mg/kg of LPS was given intratracheally. External performance, cytokines, MAPK pathways and antioxidative enzymes (AOEs) were also carried out to evaluate the effects of these drugs. This is the first investigation in which lobeline was found to effectively inhibit acute lung edema, which may provide a potential target for treating ALI. Lobeline may utilize MAPKs pathways as well as AOEs activity to attenuate LPS-induced nonspecific pulmonary inflammation. PMID:26702732

  3. Parkinson syndrome. A significant risk factor in the patient with acute surgical disorder.

    PubMed

    Simon, D; Shapira, O M; Mor, E; Pfefferman, R

    1992-01-01

    Ten Parkinsonic patients presenting with acute surgical disease were studied to determine the effects of both conditions on each other and the patient's outcome. Severe motion and communication disturbances led, invariably, to a delay in seeking medical assistance, with most of the patients' presenting symptoms and signs being non-specific and misleading. As a result half the patients presented already in a state of septic shock, and a correct preoperative diagnosis could be achieved in three patients only. The functional status significantly deteriorated in six patients, in four of whom a prolonged rehabilitation course was necessary. Although there was no immediate perioperative mortality, morbidity was significant as 50% and 100% major "surgery-related" and "Parkinson-related" complications accordingly. It is concluded that the coexistence of acute surgical disease with Parkinson syndrome has a profound adverse effect on the patient's outcome. High index of suspicion, early mobilisation, intense physiotherapy and early resumption of the anti-Parkinson drugs are the key points in the management of these patients. PMID:1478816

  4. Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in Peshawar, Pakistan.

    PubMed

    Zaidi, Saira H; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services' admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient's parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  5. Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals.

    PubMed Central

    Brandes, M E; Allen, J B; Ogawa, Y; Wahl, S M

    1991-01-01

    Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent. Images PMID:1999490

  6. Factors affecting the estimated probabilistic acute dietary exposure to captan from apple consumption.

    PubMed

    Zentai, A; Sali, J; Szabó, I J; Szeitzné-Szabó, M; Ambrus, A; Vásárhelyi, A

    2013-01-01

    The effect of the number of pesticide residue values below the LOQ/LOD of analytical methods, the variability of residues in individual fruits, mass of fruit units and the number of bootstrap iterations was studied on the probabilistically estimated acute exposure of consumers. The 4720 daily apple consumption data and the results of 1239 apple sample analyses for captan residues, performed within the Hungarian monitoring programme between 2005 and 2011, were used in this study as model matrix. Up to about 95th percentile exposure (µg/(kg bw·day)), simply multiplying each residue in composite samples with each consumption value gave similar estimates to those obtained with the complex procedure taking also into account the mass of and residues in individual fruits. However, the exposure above the 95th percentile calculated with the complex procedure gradually increased with increasing percentile level compared to the simple procedure. Including the high number of non-detects reduced the estimated exposure, which was the highest when only the residues measured in treated fruits were taken into account. The number of bootstrap iterations between 100 and 10,000 did not significantly affect the calculated exposure. The 99.99th percentile exposure amounted to 17.9% of the acute reference dose of 300 µg/(kg bw·day) for women of childbearing age. PMID:23742211

  7. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol

    PubMed Central

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S.; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    Aims: With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. Background: DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. Methods/Design: A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting

  8. Fission Yeast CSL Transcription Factors: Mapping Their Target Genes and Biological Roles

    PubMed Central

    Převorovský, Martin; Oravcová, Martina; Tvarůžková, Jarmila; Zach, Róbert; Folk, Petr; Půta, František; Bähler, Jürg

    2015-01-01

    Background Cbf11 and Cbf12, the fission yeast CSL transcription factors, have been implicated in the regulation of cell-cycle progression, but no specific roles have been described and their target genes have been only partially mapped. Methodology/Principal Findings Using a combination of transcriptome profiling under various conditions and genome-wide analysis of CSL-DNA interactions, we identify genes regulated directly and indirectly by CSL proteins in fission yeast. We show that the expression of stress-response genes and genes that are expressed periodically during the cell cycle is deregulated upon genetic manipulation of cbf11 and/or cbf12. Accordingly, the coordination of mitosis and cytokinesis is perturbed in cells with genetically manipulated CSL protein levels, together with other specific defects in cell-cycle progression. Cbf11 activity is nutrient-dependent and Δcbf11-associated defects are mitigated by inactivation of the protein kinase A (Pka1) and stress-activated MAP kinase (Sty1p38) pathways. Furthermore, Cbf11 directly regulates a set of lipid metabolism genes and Δcbf11 cells feature a stark decrease in the number of storage lipid droplets. Conclusions/Significance Our results provide a framework for a more detailed understanding of the role of CSL proteins in the regulation of cell-cycle progression in fission yeast. PMID:26366556

  9. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    PubMed

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain. PMID:22775297

  10. Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus.

    PubMed

    Scaini, Giselli; Mello-Santos, Lis Mairá; Furlanetto, Camila B; Jeremias, Isabela C; Mina, Francielle; Schuck, Patrícia F; Ferreira, Gustavo C; Kist, Luiza W; Pereira, Talita C B; Bogo, Maurício R; Streck, Emilio L

    2013-12-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase leading to accumulation of the branched-chain amino acids (BCAA) and their corresponding branched-chain α-keto acids. In this study, we examined the effects of acute and chronic administration of BCAA on protein levels and mRNA expression of nerve growth factor (NGF) considering that patients with MSUD present neurological dysfunction and cognitive impairment. Considering previous observations, it is suggested that oxidative stress may be involved in the pathophysiology of the neurological dysfunction of MSUD. We also investigated the influence of antioxidant treatment (N-acetylcysteine and deferoxamine) in order to verify the influence of oxidative stress in the modulation of NGF levels. Our results demonstrated decreased protein levels of NGF in the hippocampus after acute and chronic administration of BCAA. In addition, we showed a significant decrease in the expression of ngf in the hippocampus only following acute administration in 10-day-old rats. Interestingly, antioxidant treatment was able to prevent the decrease in NGF levels by increasing ngf expression. In conclusion, the results suggest that BCAA is involved in the regulation of NGF in the developing rat. Thus, it is possible that alteration of neurotrophin levels during brain maturation could be of pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the decrease in NGF levels was prevented by antioxidant treatment, reinforcing that the hypothesis of oxidative stress can be an important pathophysiological mechanism underlying the brain damage observed in MSUD. PMID:23559405

  11. Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

    PubMed Central

    Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

    2012-01-01

    Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

  12. Multi-factor analysis of failure of renal replacement therapy in acute renal failure developed after cardiac surgery

    PubMed Central

    Szwedo, Ireneusz; Tyc, Joanna; Hawrysz, Anna; Janiak, Kamila; Cichoń, Romuald

    2015-01-01

    Introduction Acute renal failure (ARF) is a rare (2-15%), but severe complication of cardiac surgery with overall mortality reaching 40-80%. In order to save patients’ lives they are treated with renal replacement therapy (RRT). The aim of our study was to assess the impact of different perioperative factors on mortality among patients treated with RRT because of acute renal failure, which occurred as a complication of a heart surgery. Material and methods Retrospective analysis included 45 patients, operated in the years 2009-2013, who underwent renal replacement therapy in order to treat postoperative ARF. The perioperative factors were analysed in two groups: group 1 – patients who died before discharge; and group 2 – those who survived until hospital discharge. Results Forty-five of 3509 cardiac surgical patients (1.25%) required RRT after the surgery. A total of 23 (51.11%) died before discharge (group 1). Patients in group 1 were characterised by older age (70.21 vs. 67 years), higher mean EuroSCORE value (9.28 vs. 7.15) (p < 0.05), higher percentage of concomitant surgery (63.63% vs. 28.57%) (p < 0.05) and of admission of catecholamines in the postoperative period (100% vs. 68.42%) (p < 0.005), and higher mean urea blood level prior to RRT initiation (156.65 vs. 102.54 mg/dl) (p < 0.05). Conclusions The statistically relevant death predictors proved to be: high EuroSCORE, concomitant surgery, and high urea level at RRT initiation and admission of catecholamines in the postoperative period. After conformation in further studies, those factors may prove useful in stratification of death risk among surgical patients requiring RRT. PMID:26702273

  13. Factors Related to Successful Transition to Practice for Acute Care Nurse Practitioners.

    PubMed

    Dillon, Deborah L; Dolansky, Mary A; Casey, Kathy; Kelley, Carol

    2016-01-01

    The transition from student to acute care nurse practitioner (ACNP) has been recognized as a time of stress. The purpose of this descriptive, correlational-comparative design pilot study was to examine: (1) the relationships among personal resources, community resources, successful transition, and job retention; (2) the difference between ACNPs with 0 to 4 years and ACNPs with more than 4 years of prior experience as a registered nurse in an intensive care unit or emergency department; and (3) the skills/procedures that ACNPs found difficult to perform independently. Thirty-four participants were recruited from a social media site for nurse practitioners. Organizational support, communication, and leadership were the most important elements of successful transition into the ACNP role. This information can help ACNP faculty and hospital orientation/fellowship program educators to help ACNPs transition into their first position after graduation. PMID:27153306

  14. Knowledge, attitude and practice factors in childhood acute respiratory infections in a peninsular Malaysia health district.

    PubMed

    Vasanthamala, A; Arokiasamy, J T

    1989-01-01

    This study compares the knowledge, attitudes and practice of mothers in two ethnic groups with regard to acute respiratory infections (ARI) in their child. Most had traditional beliefs as to the cause of ARI with only a minority knowing the causes. Most mothers were aware of the effect of frequent attacks of ARI on the health status of their child and of the importance of early treatment. Reasons for their becoming worried during an episode of ARI in their child indicated that problems of distance, transportation and arrangements for care of their other children predominate. A large proportion of the respondents felt that their present knowledge of ARI was inadequate and were thus interested in obtaining more information. PMID:2620023

  15. Effects of acute aerobic exercise on a task-switching protocol and brain-derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness.

    PubMed

    Tsai, Chia-Liang; Pan, Chien-Yu; Chen, Fu-Chen; Wang, Chun-Hao; Chou, Feng-Ying

    2016-07-01

    What is the central question of this study? Neurocognitive functions can be enhanced by acute aerobic exercise, which could be associated with changes in serum brain-derived neurotrophic factor (BDNF) concentrations. We aimed to explore acute exercise-induced changes in BDNF concentrations, neuropsychological and neurophysiological performances when individuals with different levels of cardiorespiratory fitness performed a cognitive task. What is the main finding and its importance? Only young adults with higher cardiorespiratory fitness could attain switching cost and neurophysiological benefits via acute aerobic exercise. The mechanisms might be fitness dependent. Although acute aerobic exercise could enhance serum BDNF concentrations, changes in peripheral BDNF concentrations could not be the potential factor involved in the beneficial effects on neurocognitive performance. This study investigated the effects of acute aerobic exercise on neuropsychological and neurophysiological performances in young adults with different cardiorespiratory fitness levels when performing a task-switching protocol and explored the potential associations between acute aerobic exercise-induced changes in serum brain-derived neurotrophic factor (BDNF) concentrations and various neurocognitive outcomes. Sixty young adults were categorized into one control group (i.e. non-exercise-intervention; n = 20) and two exercise-intervention (EI) groups [i.e. higher (EIH , n = 20) and lower (EIL , n = 20) cardiorespiratory fitness] according to their maximal oxygen consumption. At baseline and after either an acute bout of 30 min of moderate-intensity aerobic exercise or a control period, the neuropsychological and neurophysiological performances and serum BDNF concentrations were measured when the participants performed a task-switching protocol involving executive control and greater demands on working memory. The results revealed that although acute aerobic exercise decreased reaction

  16. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  17. Effect of acute and chronic administration of L-tyrosine on nerve growth factor levels in rat brain.

    PubMed

    Ferreira, Gabriela K; Jeremias, Isabela C; Scaini, Giselli; Carvalho-Silva, Milena; Gomes, Lara M; Furlanetto, Camila B; Morais, Meline O; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2013-08-01

    Most inborn errors of tyrosine catabolism produce hypertyrosinemia. Neurological manifestations are variable and some patients are developmentally normal, while others show different degrees of developmental retardation. Considering that current data do not eliminate the possibility that elevated levels of tyrosine and/or its derivatives may have noxious effects on central nervous system development in some patients, the present study evaluated nerve growth factor (NGF) levels in hippocampus, striatum and posterior cortex of young rats. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal administration of L-tyrosine (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); the rats were killed 12 h after the last injection. NGF levels were then evaluated. Our findings showed that acute administration of L-tyrosine decreased NGF levels in striatum of 10-day-old rats. In the 30-day-old rats, NGF levels were decreased in hippocampus and posterior cortex. On the other hand, chronic administration of L-tyrosine increased NGF levels in posterior cortex. Decreased NGF may impair growth, differentiation, survival and maintenance of neurons. PMID:23690230

  18. Inhibition of acute lung injury by rubriflordilactone in LPS-induced rat model through suppression of inflammatory factor expression

    PubMed Central

    Wang, Yan-Ying; Qiu, Xin-Guang; Ren, Hong-Liang

    2015-01-01

    The present study demonstrates the effect of rubriflordilactone on lipopolysaccharide (LPS)-induced acute kidney injury in rats and MLE-15 cells. LPS administration in rats resulted in formation of edema which was inhibited by pretreatment with rubriflordilactone. The pulmonary tissues of LPS administered rats and MLE-15 cells showed a significant increase in the expression of matrix metalloproteinase-9, interleukin-6 and inducible nitric oxide synthase. However, rubriflordilactone treatment prior to LPS administration caused a significant reduction in the expression of these factors at a concentration of 10 nm/kg. Analysis of the Sirtuin 1 (Sirt1) expression revealed significant (P=0.002) reduction on exposure to LPS in MLE-15 cells. However, rubriflordilactone treatment at 10 nm/ml concentration before LPS exposure caused inhibition of LPS induced reduction in Sirt1 expression. Silencing of Sirt1 by siRNA in MLE-15 cells led to inhibition of increased Sirt1 expression by rubriflordilactone in LPS administered rats. These findings suggest that rubriflordilactone inhibits LPS induced acute lung injury in rats and MLE-15 cells through promotion of Sirt1 expression. PMID:26884869

  19. Inhibition of acute lung injury by rubriflordilactone in LPS-induced rat model through suppression of inflammatory factor expression.

    PubMed

    Wang, Yan-Ying; Qiu, Xin-Guang; Ren, Hong-Liang

    2015-01-01

    The present study demonstrates the effect of rubriflordilactone on lipopolysaccharide (LPS)-induced acute kidney injury in rats and MLE-15 cells. LPS administration in rats resulted in formation of edema which was inhibited by pretreatment with rubriflordilactone. The pulmonary tissues of LPS administered rats and MLE-15 cells showed a significant increase in the expression of matrix metalloproteinase-9, interleukin-6 and inducible nitric oxide synthase. However, rubriflordilactone treatment prior to LPS administration caused a significant reduction in the expression of these factors at a concentration of 10 nm/kg. Analysis of the Sirtuin 1 (Sirt1) expression revealed significant (P=0.002) reduction on exposure to LPS in MLE-15 cells. However, rubriflordilactone treatment at 10 nm/ml concentration before LPS exposure caused inhibition of LPS induced reduction in Sirt1 expression. Silencing of Sirt1 by siRNA in MLE-15 cells led to inhibition of increased Sirt1 expression by rubriflordilactone in LPS administered rats. These findings suggest that rubriflordilactone inhibits LPS induced acute lung injury in rats and MLE-15 cells through promotion of Sirt1 expression. PMID:26884869

  20. The role of placenta growth factor in the hyperoxia-induced acute lung injury in an animal model.

    PubMed

    Zhang, Liang; Yuan, Li-Jie; Zhao, Shuang; Shan, Yu; Wu, Hong-Min; Xue, Xin-Dong

    2015-01-01

    Prolonged exposure to hyperoxia leads to acute lung injury. Alveolar type II cells are main target of hyperoxia-induced lung injury. However, the cellular and molecular mechanisms remain unknown. Here, we aimed to investigate the role of placental growth factor (PLGF) in hyperoxia-induced lung injury. Using experimental hyperoxia-induced lung injury model of neonatal rat and mouse lung epithelial type II cells (MLE-12), we examined the levels of PLGF in bronchoalveolar lavage fluid and in the supernatants of MLE-12 cells. Our results revealed that exogenous PLGF induced hyperoxia-induced lung injury. Furthermore, PLGF triggered a shift of vinculin from insoluble to soluble cell fraction, similar to the observation under hyperoxia stimulation. Moreover, we observed significantly reduced phosphorylation of focal adhesion kinase and increased permeability in MLE-12 cells treated with PLGF. These results suggest that PLGF triggers focal adhesion disassembly in alveolar type II cells via inhibiting the activation of focal adhesion kinase. Our findings reveal a novel role of PLGF in hyperoxia-induced lung injury and provide a potential target for the management of hyperoxia-induced acute lung injury. PMID:25515701

  1. Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease▿

    PubMed Central

    Waghabi, Mariana C.; de Souza, Elen M.; de Oliveira, Gabriel M.; Keramidas, Michelle; Feige, Jean-Jacques; Araújo-Jorge, Tania C.; Bailly, Sabine

    2009-01-01

    Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration. PMID:19738024

  2. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    PubMed

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations. PMID:15613917

  3. Use of Therapeutic Neuroscience Education to address psychosocial factors associated with acute low back pain: a case report.

    PubMed

    Zimney, Kory; Louw, Adriaan; Puentedura, Emilio J

    2014-04-01

    Acute low back pain (LBP) from injuries is prevalent in the work place. It has been shown that patients with psychosocial factors often progress with persistent pain and lead to significant workers compensation costs. Therapeutic Neuroscience Education (TNE) has been shown to be beneficial in changing a patient's cognition regarding their pain state, which may result in decrease fear, anxiety and catastrophization. A 19-year-old female who developed LBP from a work injury was the patient for this case report. A physical examination, Numeric Pain Rating Scale (NRPS), Oswestry Disability Index (ODI), Fear-Avoidance Beliefs Questionnaire (FABQ), Keele STarT Back Screening Tool (Keele SBST) and Acute Low Back Pain Screening (ALBPS) Questionnaires were assessed during initial physical therapy visit and discharge. Treatment consisted of use of TNE, manual therapy and exercises. She attended five total visits over a 2-week period prior to full discharge. During the initial visit the patient reported NRPS = 3/10, ODI = 36%, FABQ-PA = 23, FABQ-W = 30, Keele SBST = 4/9, ALBPS = 101. At discharge the patient reported a 0 on all outcome questionnaires with ability to return to full work and no pain complaints. PMID:24252071

  4. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    PubMed Central

    Hacioglu, Gulay; Senturk, Ayse; Ince, Imran; Alver, Ahmet

    2016-01-01

    Objective(s): Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain. PMID:27279982

  5. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

    PubMed Central

    Qian, X; Samadani, U; Porcella, A; Costa, R H

    1995-01-01

    Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF-3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1-HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due

  6. Acute cholesterol depletion impairs functional expression of tissue factor in fibroblasts: modulation of tissue factor activity by membrane cholesterol

    PubMed Central

    Mandal, Samir K.; Iakhiaev, Alexei; Pendurthi, Usha R.; Mohan Rao, L. Vijaya

    2010-01-01

    Cholesterol, in addition to providing rigidity to the fluid membrane, plays a critical role in receptor function, endocytosis, recycling, and signal transduction. In the present study, we examined the effect of membrane cholesterol on functional expression of tissue factor (TF), a cellular receptor for clotting factor VIIa. Depletion of cholesterol in human fibroblasts (WI-38) with methyl-β-cyclodextrin–reduced TF activity at the cell surface. Binding studies with radiolabeled VIIa and TF monoclonal antibody (mAB) revealed that reduced TF activity in cholesterol-depleted cells stems from the impairment of VIIa interaction with TF rather than the loss of TF receptors at the cell surface. Repletion of cholesterol-depleted cells with cholesterol restored TF function. Loss of caveolar structure on cholesterol removal is not responsible for reduced TF activity. Solubilization of cellular TF in different detergents indicated that a substantial portion of TF in fibroblasts is associated with noncaveolar lipid rafts. Cholesterol depletion studies showed that the TF association with these rafts is cholesterol dependent. Overall, the data presented herein suggest that membrane cholesterol functions as a positive regulator of TF function by maintaining TF receptors, probably in noncaveolar lipid rafts, in a high-affinity state for VIIa binding. PMID:15328160

  7. Am80 inhibits stromal cell-derived factor-1-induced chemotaxis in T-cell acute lymphoblastic leukemia cells.

    PubMed

    Matsumoto, Taichi; Jimi, Shiro; Hara, Shuuji; Takamatsu, Yasushi; Suzumiya, Junji; Tamura, Kazuo

    2010-03-01

    C-X-C motif chemokine receptor 4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) play a potent role in metastasis and infiltration of many types of tumors, including T-cell acute lymphoblastic leukemia (T-ALL), into the central nervous system or lymph nodes. Although higher levels of CXCR4 expression have been shown to correlate with shorter survival of patients, effective drugs affecting cell surface CXCR4 expression are still unknown. In the present study, we examined the effects of a synthetic retinoid Am80 on CXCR4 expression of cultured T-ALL cells, such as Jurkat. Am80 inhibited surface CXCR4 expression and SDF-1-induced chemotaxis by the acceleration of CXCR4 internalization via activation of conventional PKC. Am80 may be an effective drug to inhibit the extramedullary infiltration of T-ALL cells. PMID:20141446

  8. Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia

    PubMed Central

    Nelson, Dwella M.; Joseph, Biju; Hillion, Joelle; Segal, Jodi; Karp, Judith E.; Resar, Linda M. S.

    2011-01-01

    Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol and suggest that blocking anti-apoptotic pathways could enhance cytotoxicity and improve outcomes in patients treated with flavopiridol. PMID:21728742

  9. Serum homocysteine as a risk factor for carotid intimal thickening in acute stroke: A cross sectional observational study

    PubMed Central

    Devasia, Anup J.; Joy, Binu; Tarey, Subhash D.

    2016-01-01

    Introduction: The present study aimed to analyse if there is a correlation between carotid intima medial thickening (CIMT) and Hcy in stroke patients. Methodology: We studied 100 consecutive cases of acute anterior circulation strokes at St. John's Medical College, Bangalore, India. Fasting serum samples for homocysteine were sent within 24 hours of admission and all patients underwent a carotid Doppler scan and carotid intima-medial thickness (CIMT) was estimated on both sides. Results: There was significant correlation between serum homocysteine levels and carotid intima-medial thickness (r = 0.409, p = 0.000). Also after controlling for other possible risk factors it was found that elevations in serum homocysteine levels would cause a variation of 60% in the carotid intima-medial thickening. Conclusion: Serum Hcy levels correlate well with CIMT and hence may predict atherothrombotic events. PMID:27011628

  10. Association of transcription factor YY1 with the high molecular weight Notch complex suppresses the transactivation activity of Notch.

    PubMed

    Yeh, Tien-Shun; Lin, Yu-Min; Hsieh, Rong-Hong; Tseng, Min-Jen

    2003-10-24

    Notch receptors are evolutionarily conserved from Drosophila to human and play important roles in cell fate decisions. After ligand binding, Notch receptors are cleaved to release their intracellular domains. The intracellular domains, the activated form of Notch receptors, are then translocated into the nucleus where they interact with other transcriptional machinery to regulate the expression of cellular genes. To dissect the molecular mechanisms of Notch signaling, the cellular targets that interact with Notch1 receptor intracellular domain (N1IC) were screened. In this study, we found that endogenous transcription factor Ying Yang 1 (YY1) was associated with exogenous N1IC in human K562 erythroleukemic cells. The ankyrin (ANK) domain of N1IC and zinc finger domains of YY1 were essential for the association of N1IC and YY1 according to the pull-down assay of glutathione S-transferase fusion proteins. Furthermore, both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling. The transcription factor YY1 indirectly regulated the transcriptional activity of the wild-type CBF1-response elements via the direct interaction of N1IC and CBF1. We also demonstrated the association between endogenous N1IC and intrinsic YY1 in human acute T-cell lymphoblastic leukemia cell lines. Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex. PMID:12913000

  11. Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level

    PubMed Central

    Joung, Kyoung-Woon; Choi, Seong-Soo; Kong, Yu-Gyeong; Yu, Jihion; Lim, Jinwook; Hwang, Jai-Hyun; Kim, Young-Kug

    2015-01-01

    Background: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy. Methods: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses. Results: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy. Conclusions: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy. PMID:26283877

  12. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia

    PubMed Central

    Klein, Hans-Ulrich; Hascher, Antje; Isken, Fabienne; Tickenbrock, Lara; Thoennissen, Nils; Agrawal-Singh, Shuchi; Tschanter, Petra; Disselhoff, Christine; Wang, Yipeng; Becker, Anke; Thiede, Christian; Ehninger, Gerhard; zur Stadt, Udo; Koschmieder, Steffen; Seidl, Matthias; Müller, Frank U.; Schmitz, Wilhelm; Schlenke, Peter; McClelland, Michael; Berdel, Wolfgang E.; Dugas, Martin; Serve, Hubert

    2010-01-01

    Acute myeloid leukemia (AML) is commonly associated with alterations in transcription factors because of altered expression or gene mutations. These changes might induce leukemia-specific patterns of histone modifications. We used chromatin-immunoprecipitation on microarray to analyze histone 3 lysine 9 trimethylation (H3K9me3) patterns in primary AML (n = 108), acute lymphoid leukemia (n = 28), CD34+ cells (n = 21) and white blood cells (n = 15) specimens. Hundreds of promoter regions in AML showed significant alterations in H3K9me3 levels. H3K9me3 deregulation in AML occurred preferentially as a decrease in H3K9me3 levels at core promoter regions. The altered genomic regions showed an overrepresentation of cis-binding sites for ETS and cyclic adenosine monophosphate response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML-specific H3K9me3 patterns were not associated with known cytogenetic abnormalities. But a signature derived from H3K9me3 patterns predicted event-free survival in AML patients. When the H3K9me3 signature was combined with established clinical prognostic markers, it outperformed prognosis prediction based on clinical parameters alone. These findings demonstrate widespread changes of H3K9me3 levels at gene promoters in AML. Signatures of histone modification patterns are associated with patient prognosis in AML. PMID:20498303

  13. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection

    PubMed Central

    Benfield, Camilla T. O.; Ren, Hongwei; Lucas, Stuart J.; Bahsoun, Basma

    2013-01-01

    Vaccinia virus (VACV) encodes many proteins that antagonize the innate immune system including a family of intracellular proteins with a B-cell lymphoma (Bcl)-2-like structure. One of these Bcl-2 proteins called K7 binds Toll-like receptor-adaptor proteins and the DEAD-box RNA helicase DDX3 and thereby inhibits the activation of NF-κB and interferon regulatory factor 3. However, the contribution of K7 to virus virulence is not known. Here a VACV lacking the K7R gene (vΔK7) was constructed and compared with control viruses that included a plaque purified wt (vK7), a revertant with the K7R gene reinserted (vK7-rev) and a frame-shifted virus in which the translational initiation codon was mutated to prevent K7 protein expression (vK7-fs). Data presented show that loss of K7 does not affect virus replication in cell culture or in vivo; however, viruses lacking the K7 protein were less virulent than controls in murine intradermal (i.d.) and intranasal (i.n.) infection models and there was an altered acute immune response to infection. In the i.d. model, vΔK7 induced smaller lesions than controls, and after i.n. infection vΔK7 induced a reduced weight loss and signs of illness, and more rapid clearance of virus from infected tissue. Concomitantly, the intrapulmonary innate immune response to infection with vΔK7 showed increased infiltration of NK cells and CD8+ T-cells, enhanced MHC class II expression by macrophages, and enhanced cytolysis of target cells by NK cells and VACV-specific CD8+ T-cells. Thus protein K7 is a virulence factor that affects the acute immune response to infection. PMID:23580427

  14. Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors

    PubMed Central

    Damiani, Daniela; Tiribelli, Mario; Raspadori, Donatella; Sirianni, Santina; Meneghel, Alessia; Cavalllin, Margherita; Michelutti, Angela; Toffoletti, Eleonora; Geromin, Antonella; Simeone, Erica; Bocchia, Monica; Fanin, Renato

    2015-01-01

    CD200, a protein belonging to the immunoglobulin superfamily, has been associated with a poor prognosis in lymphoproliferative disorders and in acute leukemia. We studied the expression of CD200 in a series of 244 patients with diagnosis of acute myeloid leukemia (AML), to evaluate its impact on outcome and its possible association with other known prognostic factors. CD200 was found in 136/244 (56%) patients, in 41 of whom (30%) with high intensity of expression (MFI ≥ 11). CD200 was more frequent in secondary compared to de novo leukemia (p = 0.0006), in CD34 positive cases (p = 0.00001), in Bcl2 overexpressing cases (p = 0.01), in those wild-type Flt3 (p = 0.004) and with favorable or unfavorable compared to intermediate karyotype (p = 0.0003). CD200+ patients have a two-fold lower probability to attain complete remission, both in univariate (p = 0.006) and multivariate (p = 0.04) analysis. The negative impact of CD200 was found also in overall survival (p = 0.02) and was correlated with the intensity of expression of the molecule (p = 0.024). CD200 has an additive negative impact on survival in patients with unfavorable cytogenetic (p = 0.046) and in secondary leukemia (p = 0.05), and is associate with a worsening of outcome in patients with favorable biological markers, such as mutated NPM (p = 0.02), wild-type Flt3 (p = 0.034), negativity of CD34 (p = 0.03) and of CD56 (p = 0.03). In conclusion, CD200 is emerging as both a prognostic factor and a potential target of novel therapeutic approaches for AML, aiming to reverse the “do not eat me” signal of CD200 or to manipulate the suppressive immune microenvironment induced by CD200 binding to its receptor. PMID:26338961

  15. Methylation of CTNNA1 promoter: frequent but not an adverse prognostic factor in acute myeloid leukemia.

    PubMed

    Chen, Xing-xing; Lin, Jiang; Qian, Jun; Qian, Wei; Yang, Jing; Ma, Ji-chun; Deng, Zhao-qun; An, Cui; Tang, Chun-yan; Qian, Zhen; Liu, Qing

    2014-05-01

    The reduced expression of CTNNA1 gene, a putative tumor suppressor gene, has been found in several cancers including acute myeloid leukemia (AML). CTNNA1 expression is regulated by methylation and histone deacetylation. However, the clinical significance of CTNNA1 methylation in AML is rarely known. The present study was aimed to investigate the methylation status of CTNNA1 promoter region using methylation-specific PCR (MSP) and its clinical relevance in Chinese AML patients. Patients with CTNNA1 hypermethylation had significantly lower level of CTNNA1 transcript than those without CTNNA1 hypermethylation (P=0.031). The relationship of CTNNA1 methylation with clinical parameters was evaluated. Aberrant hypermethylation of CTNNA1 gene was found in 23.9% (37/155) AML cases. The status of CTNNA1 methylation was not correlated with the mutations of seven genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). There was no significant difference in the rates of complete remission (CR) between patients with and without CTNNA1 methylation. Although the overall survival (OS) time of the CTNNA1-methylated AML was shorter than that of CTNNA1-unmethylated group (6 months vs 9 months), the difference was not statistically significant (P=0.681). Our data suggest that CTNNA1 methylation is a recurrent event but has no influence on prognosis in AML. PMID:24685333

  16. Factors Associated with Early Hospital Arrival in Patients with Acute Ischemic Stroke

    PubMed Central

    Song, Dongbeom; Tanaka, Eijirou; Lee, Kijeong; Sato, Shoichiro; Koga, Masatoshi; Kim, Young Dae; Nagatsuka, Kazuyuki; Toyoda, Kazunori

    2015-01-01

    Background and Purpose Factors associated with early arrival may vary according to the characteristics of the hospital. We investigated the factors associated with early hospital arrival in two different stroke centers located in Korea and Japan. Methods Consecutive patients with ischemic stroke arrived hospital within 48 hours of onset between January 2011 and December 2012 were identified and the clinical and time variables were retrieved from the prospective stroke registries of Severance Hospital of Yonsei University Health System (YUHS; Seoul, Korea) and National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan). Subjects were dichotomized into early (time from onset to arrival ≤4.5 hours) and late (>4.5 hours) arrival groups. Univariate and multivariate analyses were performed to evaluate factors associated with early hospital arrival. Results A total of 1,966 subjects (992 from YUHS; 974 from NCVC) were included in this study. The median time from onset to arrival was 6.1 hours [interquartile range, 1.7-17.8 hours]. In multivariate analysis, the factors associated with early arrival were atrial fibrillation (Odds ratio [OR], 1.505; 95% confidence interval [CI], [1.168-1.939]), higher initial National Institute of Health Stroke Scale scores (OR, 1.037; 95% CI [1.023-1.051]), onset during daytime (OR, 2.799; 95% CI [2.173-3.605]), and transport by an emergency medical service (OR, 2.127; 95% CI [1.700-2.661]). These factors were consistently associated with early arrival in both hospitals. Conclusions Despite differences between the hospitals, there were common factors related to early arrival. Efforts to identify and modify these factors may promote early hospital arrival and improve stroke outcome. PMID:26060803

  17. Increased drought tolerance through the suppression of ESKMO1 gene and overexpression of CBF-related genes in Arabidopsis.

    PubMed

    Xu, Fuhui; Liu, Zhixue; Xie, Hongyan; Zhu, Jian; Zhang, Juren; Kraus, Josef; Blaschnig, Tasja; Nehls, Reinhard; Wang, Hong

    2014-01-01

    Improved drought tolerance is always a highly desired trait for agricultural plants. Significantly increased drought tolerance in Arabidopsis thaliana (Columbia-0) has been achieved in our work through the suppression of ESKMO1 (ESK1) gene expression with small-interfering RNA (siRNA) and overexpression of CBF genes with constitutive gene expression. ESK1 has been identified as a gene linked to normal development of the plant vascular system, which is assumed directly related to plant drought response. By using siRNA that specifically targets ESK1, the gene expression has been reduced and drought tolerance of the plant has been enhanced dramatically in the work. However, the plant response to external abscisic acid application has not been changed. ICE1, CBF1, and CBF3 are genes involved in a well-characterized plant stress response pathway, overexpression of them in the plant has demonstrated capable to increase drought tolerance. By overexpression of these genes combining together with suppression of ESK1 gene, the significant increase of plant drought tolerance has been achieved in comparison to single gene manipulation, although the effect is not in an additive way. Accompanying the increase of drought tolerance via suppression of ESK1 gene expression, the negative effect has been observed in seeds yield of transgenic plants in normal watering conditions comparing with wide type plant. PMID:25184213

  18. The Revolving Door Phenomenon in an Italian Acute Psychiatric Ward: A 5-Year Retrospective Analysis of the Potential Risk Factors.

    PubMed

    Di Lorenzo, Rosaria; Sagona, Marco; Landi, Giulia; Martire, Lisa; Piemonte, Chiara; Del Giovane, Cinzia

    2016-09-01

    To highlight the revolving door (RD) phenomenon in an acute psychiatric ward, we retrospectively identified the patients hospitalized three or more times in a calendar year from 1/1/2009 to 31/12/2013 as RD patients (RDP). We collected sociodemographic and clinical variables of RDP and statistically analyzed the potential RD risk factors. We divided RDP into "high" and "extremely high" utilizers and evaluated the variables related to more frequent readmissions. RDP represented 5.68% of all patients and their hospitalizations (RDH) 25% of all admissions. The statistically significant risk factors for all RDH were "disability pension," "substance abuse/dependence," "mild/severe aggressiveness," and "psychiatric and social rehabilitative programs". The comparison between "high" and "extremely high" utilizers showed that "manic episodes" and "personality disorders," among the diagnoses, "familial relational conflicts" and "violence/suicidality", among the hospitalization reasons, were statistically significant risk factors for more frequent readmissions. RD phenomenon was greatly affected by severe clinical conditions with social disability. PMID:27227558

  19. The epidemiology and prognostic factors of mortality in critically ill children with acute kidney injury in Taiwan.

    PubMed

    Chang, Jei-Wen; Jeng, Mei-Jy; Yang, Ling-Yu; Chen, Tzeng-Ji; Chiang, Shu-Chiung; Soong, Wen-Jue; Wu, Keh-Gong; Lee, Yu-Sheng; Wang, Hsin-Hui; Yang, Chia-Feng; Tsai, Hsin-Lin

    2015-03-01

    The incidence of acute kidney injury (AKI) in critically ill children varies among countries. Here we used claims data from the Taiwanese National Health Insurance program from 2006 to 2010 to investigate the epidemiological features and identify factors that predispose individuals to developing AKI and mortality in critically ill children with AKI. Of 60,338 children in this nationwide cohort, AKI was identified in 850, yielding an average incidence rate of 1.4%. Significant independent risk factors for AKI were the use of extracorporeal membrane oxygenation, mechanical ventilation or vasopressors, intrinsic renal diseases, sepsis, and age more than 1 year. Overall, of the AKI cases, 46.5% were due to sepsis, 36.1% underwent renal replacement therapy, and the mortality rate was 44.2%. Multivariate analysis showed that the use of vasopressors, mechanical ventilation, and hemato-oncological disorders were independent predictors of mortality in AKI patients. Thirty-two of the 474 patients who survived had progression to chronic kidney disease or end-stage renal disease. Thus, although not common, AKI in critically ill children still has a high mortality rate associated with a variety of factors. Long-term close follow-up to prevent progressive chronic kidney disease in survivors of critical illnesses with AKI is mandatory. PMID:25252027

  20. Potential factors associated with fruit and vegetable intake after premature acute coronary syndrome: a prospective cohort study.

    PubMed

    Leung Yinko, Sylvie S L; Pelletier, Roxanne; Behlouli, Hassan; Bacon, Simon L; Karp, Igor; Thanassoulis, George; Daskalopoulou, Stella S; Eisenberg, Mark J; Khan, Nadia A; Lavoie, Kim L; Pilote, Louise

    2015-01-01

    Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations. PMID:26529090

  1. Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke

    PubMed Central

    Wicking, Manon; Bellebaum, Christian; Hermann, Dirk M.

    2016-01-01

    Background Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described. Methods We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years), whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group. Results In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030), but not the acquisition phase (F[2,30] = 1.01; p = 0.376) and the acquired equivalence (F[2,30] = 1.04; p = 0.367) tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012), but not acquisition learning (r = -0.20, p = 0.121) or acquired equivalence (r = -0.22, p = 0.096). Conclusions The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies. PMID:27163585

  2. The predictability of renin-angiotensin-aldosterone system factors for clinical outcome in patients with acute decompensated heart failure.

    PubMed

    Nakada, Yasuki; Takahama, Hiroyuki; Kanzaki, Hideaki; Sugano, Yasuo; Hasegawa, Takuya; Ohara, Takahiro; Amaki, Makoto; Funada, Akira; Yoshida, Akemi; Yasuda, Satoshi; Ogawa, Hisao; Anzai, Toshihisa

    2016-06-01

    Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02-1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01-1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events. PMID:25964073

  3. Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation

    PubMed Central

    Lee, Sung Woo; Yu, Mi-yeon; Lee, Hajeong; Ahn, Shin Young; Kim, Sejoong; Chin, Ho Jun; Na, Ki Young

    2015-01-01

    Background and Objectives Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality. Methods Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality. Results Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI. Conclusion The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI. PMID:26469793

  4. Effect of Acute Hypercapnia on Outcomes and Predictive Risk Factors for Complications among Patients Receiving Bronchoscopic Interventions under General Anesthesia

    PubMed Central

    Wang, Hongwu; Zhang, Rujin; Yue, Yun; Li, Lei

    2015-01-01

    Background The aim of this study is to investigate the effect of acute hypercapnia on surgery outcomes among patients receiving bronchoscopic interventions under general anesthesia. Furthermore, independent predictive factors for surgery complications were analyzed. Method A total of 323 patients with airway stenosis were enrolled in this retrospective study. Each patient underwent interventional rigid bronchoscopy under general anesthesia. Arterial blood gas (ABG) was measured intraoperatively. In light of PaCO2 levels in ABG, patients were divided into three groups: Group C (control) (PaCO2:≤ 60 mmHg), Group M (moderate) (PaCO2:61–100 mmHg), and Group S (severe) (PaCO2: >100 mmHg). Parameters, including PaO2 levels and recovery delays, were compared across three groups. Complications among patients receiving bronchoscopic interventions were evaluated as well. Independent predictive factors for surgery related complications were analyzed by multivariable regression method. Results Significant differences in weight (p=0.04), ASA IV (p=0.008), dyspnea index (p=0.003),COPD (p=0.02), dynamic airway collapse (p=0.002), severe stenosis severity (p=0.02), and stenosis locations among three groups were observed. Mild (PaCO2:~60 mmHg) to moderate (PaCO2:60–100 mmHg) hypercapnia was not associated with delayed recovery, whereas severe hypercapnia (PaCO2:>100 mmHg) was associated with delayed recovery, as well as declined PaO2 (p=0.00) and elevated blood glucose levels (p=0.00). The complications of bronchoscopic interventions included postoperative congestive heart failure (14 cases, 4.3%), tracheorrhagia (8 cases, 2.5%), delayed recovery (19 cases, 5.9%), and transfers to ICU after surgery (10 cases, 3.1%). The multivariable regression analysis showed that procedure duration (p=0.003), lobectomy (p=0.007), dynamic airway collapse (p=0.01), severe bronchial stenosis (p=0.01) and hypercapnia (p=0.02) were independent predictive factors for surgery related complications

  5. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients.

    PubMed

    Testa, Ugo; Lo-Coco, Francesco

    2016-04-01

    All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease. PMID:26920716

  6. Quantitative Functional Arterial Spin Labeling (fASL) MRI – Sensitivity and Reproducibility of Regional CBF Changes Using Pseudo-Continuous ASL Product Sequences

    PubMed Central

    Steketee, Rebecca M. E.; Mutsaerts, Henri J. M. M.; Bron, Esther E.; van Osch, Matthias J. P.; Majoie, Charles B. L. M.; van der Lugt, Aad; Nederveen, Aart J.; Smits, Marion

    2015-01-01

    Arterial spin labeling (ASL) magnetic resonance imaging is increasingly used to quantify task-related brain activation. This study assessed functional ASL (fASL) using pseudo-continuous ASL (pCASL) product sequences from two vendors. By scanning healthy participants twice with each sequence while they performed a motor task, this study assessed functional ASL for 1) its sensitivity to detect task-related cerebral blood flow (CBF) changes, and 2) its reproducibility of resting CBF and absolute CBF changes (delta CBF) in the motor cortex. Whole-brain voxel-wise analyses showed that sensitivity for motor activation was sufficient with each sequence, and comparable between sequences. Reproducibility was assessed with within-subject coefficients of variation (wsCV) and intraclass correlation coefficients (ICC). Reproducibility of resting CBF was reasonably good within (wsCV: 14.1–15.7%; ICC: 0.69–0.77) and between sequences (wsCV: 15.1%; ICC: 0.69). Reproducibility of delta CBF was relatively low, both within (wsCV: 182–297%; ICC: 0.04–0.32) and between sequences (wsCV: 185%; ICC: 0.45), while inter-session variation was low. This may be due to delta CBF’s small mean effect (0.77–1.32 mL/100g gray matter/min). In conclusion, fASL seems sufficiently sensitive to detect task-related changes on a group level, with acceptable inter-sequence differences. Resting CBF may provide a consistent baseline to compare task-related activation to, but absolute regional CBF changes are more variable, and should be interpreted cautiously when acquired with two pCASL product sequences. PMID:26172381

  7. Optimization of methods for quantification of rCBF using high-resolution [15O]H2O PET images

    NASA Astrophysics Data System (ADS)

    Walker, M. D.; Feldmann, M.; Matthews, J. C.; Anton-Rodriguez, J. M.; Wang, S.; Koepp, M. J.; Asselin, M.-C.

    2012-04-01

    This study aimed to derive accurate estimates of regional cerebral blood flow (rCBF) from noisy dynamic [15O]H2O PET images acquired on the high-resolution research tomograph, while retaining as much as possible the high spatial resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET autoradiographic method and generalized linear least-squares (GLLS), with fixed or extended to include spatially variable estimates of the dispersion of the measured input function, were compared to nonlinear least-squares (NLLS) for rCBF estimation. Six healthy volunteers underwent two [15O]H2O PET scans with continuous arterial blood sampling. rCBF estimates were obtained from three image reconstruction methods (one analytic and two iterative, of which one includes a resolution model) to which a range of post-reconstruction filters (3D Gaussian: 2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to be around 11 MBq kg-1 (800 MBq) by extrapolation of patient-specific noise equivalent count rates. Whole-brain rCBF values were found to be relatively insensitive to the method of reconstruction and rCBF quantification. The grey and white matter rCBF for analytic reconstruction and NLLS were 0.44 ± 0.03 and 0.15 ± 0.03 mL min-1 cm-3, respectively, in agreement with literature values. Similar values were obtained from the other methods. For generation of parametric images using GLLS or the autoradiographic method, a filter of ⩾4 mm was required in order to suppress noise in the PET images which otherwise produced large biases in the rCBF estimates.

  8. Metabolism of choline in brain of the aged CBF-1 mouse

    SciTech Connect

    Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

    1986-01-01

    In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM (/sup 3/H) choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain.

  9. Factors Affecting Trial Without Catheter for First Spontaneous Acute Urinary Retention

    PubMed Central

    Vaddi, Surya Prakash; Godala, Chandra-Mohan; Reddy, V. Vijaya Kumar; Sambar, Venkat Krishna

    2013-01-01

    Purpose To find the association of trial without catheter (TWOC) outcome for first spontaneous acute urinary retention (AUR) in benign prostatic obstruction with age, prior lower urinary tract symptoms (LUTS), retention volume at catheterization (RV), and size of prostate. Methods Our prospective observational analytical (interventional) study enrolled 77 cases of spontaneous AUR over 24 months. After clinical evaluation, digital rectal examination, and transabdominal ultrasonography, all patients were catheterized per urethra and their RV was recorded. TWOC was administered after 2 or 3 doses of 0.4 mg tamsulosin-oral absorption control system and after 48-72 hours had passed. A successful endpoint was defined as a maximum flow-rate, >5 mL/sec; voided volume, >100 mL; postvoid residue, <200 mL; and voiding within 6 hours of catheter removal. Data obtained from 58 patients were analyzed after excluding the cases lost to follow-up and secondary exclusion. Age, RV, duration of LUTS, and prostate volume on examination and ultrasonography (PUSG) were recorded and statistically analyzed. Prostate-specific antigen levels were obtained on follow-up and cases of cancer, as seen on transrectal ultrasound-guided biopsy, were secondarily excluded. Results The patients had a mean age of 65.89±8.67 years. Prior LUTS was seen in 35 patients (2.07±2.91 months). The mean PUSG and RV were 46.81±20.58 mL and 854.8±36.26 mL, respectively. Thirty patients underwent a successful TWOC; a mean age of 63.13±8.58 years (mean±standard deviation; unpaired t-test; P=0.0053) and a PUSG of ≤45 mL (Pearson chi-square test; P=0.0427) were significantly associated with a successful outcome. Conclusions There is a significant association between TWOC outcome, age (P=0.0053), and PUSG (P=0.0427). PMID:24143290

  10. Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

    PubMed

    Daniel, Maria; Ekenbäck, Christina; Agewall, Stefan; Brolin, Elin B; Caidahl, Kenneth; Cederlund, Kerstin; Collste, Olov; Eurenius, Lars; Frick, Mats; Younis-Hassan, Shams; Henareh, Loghman; Jernberg, Tomas; Malmqvist, Karin; Spaak, Jonas; Sörensson, Peder; Hofman-Bang, Claes; Tornvall, Per

    2015-09-15

    Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA. PMID:26251000

  11. TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uveitis and pediatric uveitis

    PubMed Central

    2013-01-01

    Introduction TNF Receptor-Associated Factor 5 (TRAF5) has been shown to be associated with autoimmune disease. The current study sought to investigate the potential association of TRAF5 with acute anterior uveitis (AAU) and pediatric uveitis in Han Chinese. Methods Three TRAF5 SNPs were analyzed in 450 AAU patients with or without ankylosing spondylitis (AS), 458 pediatric uveitis patients, and 1,601 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP Genotyping Assay. Numerous variables were evaluated, including age, sex distribution, and clinical and laboratory observations. Results Two SNPs (rs6540679, rs12569232) of TRAF5 were associated with pediatric uveitis, and rs12569232 also showed a relation with the presence of microvascular leakage. No significant associations were found when patients were subdivided according to their rheumatoid factor (RF) or anti-nuclear antibody (ANA) status or whether they had juvenile idiopathic arthritis (JIA). Rs12569232 predisposed to AAU and its subgroups (with ankylosing spondylitis (AS) or HLA-B27 positive). No association was found between rs10863888 and either pediatric uveitis or AAU. Conclusion This study revealed that TRAF5 is involved in the development of AAU and pediatric uveitis. Further stratified analysis according to the clinical and laboratory observations suggested that rs12569232/TRAF5 may play a role in the development of retinal vasculitis. PMID:24020968

  12. Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

    PubMed Central

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-01-01

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  13. Aberrant nuclear factor-kappa B activity in acute myeloid leukemia: from molecular pathogenesis to therapeutic target.

    PubMed

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-03-20

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  14. Low levels of tissue factor lead to alveolar hemorrhage, potentiating murine acute lung injury and oxidative stress

    PubMed Central

    Bastarache, J.A.; Sebag, S. C.; Clune, J.K.; Grove, B.S.; Lawson, W.E.; Janz, D. R.; Roberts, L. J.; Dworski, R; Mackman, N.; Ware, L. B.

    2013-01-01

    Background Systemic blockade of Tissue Factor (TF) attenuates acute lung injury (ALI) in animal models of sepsis but the effects of global TF deficiency are unknown. Hypothesis We used mice with complete knockout of mouse TF and low levels (~1%) of human TF (LTF mice) to test the hypothesis that global TF deficiency attenuates lung inflammation in direct lung injury. Methods LTF mice were treated with 10 μg of lipopolysaccharide (LPS) or vehicle administered by direct intratracheal (IT) injection and studied at 24 hours. Results Contrary to our hypothesis, LTF mice had increased lung inflammation and injury as measured by bronchoalveolar lavage cell count (3.4 × 105 WT LPS versus 3.3 × 105 LTF LPS, p=0.947) and protein (493 μg/ml WT LPS versus 1014 μg/ml LTF LPS, p=0.006), proinflammatory cytokines (TNF-α, IL-10, IL-12, p<0.035 WT LPS versus LTF LPS) and histology compared to wild type mice. LTF mice also had increased hemorrhage and free hemoglobin in the airspace accompanied by increased oxidant stress as measured by lipid peroxidation products (F2-Isoprostanes and Isofurans). Conclusions These findings indicate that global TF deficiency does not confer protection in a direct lung injury model. Rather, TF deficiency causes increased intra-alveolar hemorrhage following LPS leading to increased lipid peroxidation. Strategies to globally inhibit tissue factor may be deleterious in patients with ALI. PMID:23033361

  15. Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection.

    PubMed

    Weber, Erica; Morgan, Erin E; Iudicello, Jennifer E; Blackstone, Kaitlin; Grant, Igor; Ellis, Ronald J; Letendre, Scott L; Little, Susan; Morris, Sheldon; Smith, Davey M; Moore, David J; Woods, Steven Paul

    2013-02-01

    The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naive adults with median duration of infection of 75 days relative to a sample of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States, a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly fivefold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, the results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use. PMID:23250704

  16. Inhibition of cytochrome P450 2E1 and activation of transcription factor Nrf2 are renoprotective in myoglobinuric acute kidney injury.

    PubMed

    Wang, Zhe; Shah, Sudhir V; Liu, Hua; Baliga, Radhakrishna

    2014-08-01

    Rhabdomyolysis accounts for ∼10% of acute kidney injuries. In glycerol-induced myoglobinuric acute kidney injury, we found an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear protein, a key redox-sensitive transcription factor, and Nrf2-regulated genes and proteins including upregulation of heme oxygenase-1. In in vitro studies, pretreatment of LLC-PK1 cells with an activator of Nrf2 before myoglobin exposure significantly decreased oxidant generation and cytotoxicity, whereas Nrf2 inhibition and gene silencing exacerbated the injury. Chlormethiazole, a specific CYP2E1 transcription inhibitor, prevented an increase in catalytic iron in the kidneys, decreased oxidative stress, blocked nuclear translocation of the Nrf2 protein, decreased heme oxygenase-1 upregulation, and provided functional and histological protection against acute kidney injury. CYP2E1 inhibitors and gene silencing in renal tubular epithelial cells significantly decreased reactive oxygen species generation and provided marked protection against myoglobin-induced cytotoxicity. Thus, during CYP2E1-induced oxidative stress, the transcription factor Nrf2 has a pivotal role in the early adaptive response. Inhibition of CYP2E1 coupled with the prior induction of Nrf2 may be a valuable tool to reduce CYP2E1-mediated rhabdomyolysis-induced acute kidney injury. PMID:24717297

  17. Melatonin-induced CBF/DREB1s are essential for diurnal change of disease resistance and CCA1 expression in Arabidopsis.

    PubMed

    Shi, Haitao; Wei, Yunxie; He, Chaozu

    2016-03-01

    Melatonin (N-acetyl-5-methoxytryptamine) is an important regulator of circadian rhythms and immunity in animals. However, the diurnal changes of endogenous melatonin and melatonin-mediated diurnal change of downstream responses remain unclear in Arabidopsis. Using the publicly available microarray data, we found that the transcript levels of two melatonin synthesis genes (serotonin N-acetyltransferase (SNAT) and caffeate O-methyltransferase (COMT)) and endogenous melatonin level were regulated by diurnal cycles, with different magnitudes of change. Moreover, the transcripts of C-repeat-binding factors (CBFs)/Drought response element Binding 1 factors (DREB1s) were co-regulated by exogenous melatonin and diurnal changes, indicating the possible correlation among clock, endogenous melatonin level and AtCBFs expressions. Interestingly, diurnal change of plant immunity against Pst DC3000 and CIRCADIANCLOCK ASSOCIATED 1 (CCA1) expression were largely lost in AtCBFs knockdown line-amiR-1. Taken together, this study identifies the molecular pathway underlying the diurnal changes of immunity in Arabidopsis. Notably, the diurnal changes of endogenous melatonin may regulate corresponding changes of AtCBF/DREB1s expression and their underlying diurnal cycle of plant immunity and AtCCA1. PMID:26828406

  18. A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia.

    PubMed

    Crysandt, Martina; Kramer, Michael; Ehninger, Gerhard; Bornhäuser, Martin; Berdel, Wolfgang E; Serve, Hubert; Röllig, Christoph; Kaifie, Andrea; Jost, Edgar; Brummendorf, Tim H; Wilop, Stefan

    2016-07-01

    Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 patients with AML treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analyses, we identified BMI as an independent risk factor for both DFS (HR 1.014, P = 0.0217) and OS (HR 1.015, P < 0.0036). Interestingly, overweight and obesity seemed to be a risk factor predominantly in patients with de novo AML younger than 65 yr with intermediate risk and adverse cytogenetics. Overweight with a BMI ≥25 kg/m² best discriminated the worse outcome and led to an absolute reduction in long-term survival of 5-7% in the group of all younger patients (3-yr OS 39.9% vs. 47.3%; 10-yr OS 28.7% vs. 33.8%, P = 0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, P < 0.0001). Thus, in younger patients with de novo AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose-capping at a body surface area of 2 m². PMID:26277604

  19. Risk factors for adverse in-hospital outcomes in acute colonic diverticular hemorrhage

    PubMed Central

    Nagata, Naoyoshi; Niikura, Ryota; Aoki, Tomonori; Moriyasu, Shiori; Sakurai, Toshiyuki; Shimbo, Takuro; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Yokoi, Chizu; Akiyama, Junichi; Yanase, Mikio; Mizokami, Masashi; Fujimoto, Kazuma; Uemura, Naomi

    2015-01-01

    AIM: To investigate the factors associated with transfusion, further bleeding, and prolonged length of stay. METHODS: In total, 153 patients emergently hospitalized for diverticular bleeding who were examined by colonoscopy were prospectively enrolled. Patients in whom the bleeding source was identified received endoscopic treatment such as clipping or endoscopic ligation. After spontaneous cessation of bleeding with conservative treatment or hemostasis with endoscopic treatment, all patients were started on a liquid food diet and gradually progressed to a solid diet over 3 d, and were discharged. At enrollment, we assessed smoking, alcohol, medications [non-steroidal anti-inflammatory drugs (NSAIDs)], low-dose aspirin, and other antiplatelets, warfarin, acetaminophen, and oral corticosteroids), and co-morbidities [hypertension, diabetes mellitus, dyslipidemia, cerebro-cardiovascular disease, chronic liver disease, and chronic kidney disease (CKD)]. The in-hospital outcomes were need for transfusion, further bleeding after spontaneous cessation of hemorrhage, and length of hospital stay. The odds ratio (OR) for transfusion need, further bleeding, and prolonged length of stay were estimated by logistic regression analysis. RESULTS: No patients required angiographic embolization or surgery. Stigmata of bleeding occurred in 18% of patients (27/153) and was treated by endoscopic procedures. During hospitalization, 40 patients (26%) received a median of 6 units of packed red blood cells. Multivariate analysis revealed that female sex (OR = 2.5, P = 0.02), warfarin use (OR = 9.3, P < 0.01), and CKD (OR = 5.9, P < 0.01) were independent risk factors for transfusion need. During hospitalization, 6 patients (3.9%) experienced further bleeding, and NSAID use (OR = 5.9, P = 0.04) and stigmata of bleeding (OR = 11, P < 0.01) were significant risk factors. Median length of hospital stay was 8 d. Multivariate analysis revealed that age > 70 years (OR = 2.1, P = 0.04) and NSAID

  20. Clinical factors associated with early readmission among acutely decompensated heart failure patients

    PubMed Central

    Pierre-Louis, Bredy; Rodriques, Shareen; Gorospe, Vanessa; Guddati, Achuta K.; Ahn, Chul; Wright, Maurice

    2016-01-01

    Introduction Congestive heart failure (CHF) is a common cause of hospital readmission. Material and methods A retrospective study was conducted at Harlem Hospital in New York City. Data were collected for 685 consecutive adult patients admitted for decompensated CHF from March, 2009 to December, 2012. Variables including patient demographics, comorbidities, laboratory studies, and medical therapy were compared between CHF patient admissions resulting in early CHF readmission and not resulting in early CHF readmission. Results Clinical factors found to be independently significant for early CHF readmission included chronic obstructive pulmonary disease (odds ratio (OR) = 6.4), HIV infection (OR = 3.4), African-American ethnicity (OR = 2.2), systolic heart failure (OR = 1.9), atrial fibrillation (OR = 2.3), renal disease with glomerular filtration rate < 30 ml/min (OR = 2.7), evidence of substance abuse (OR = 1.7), and absence of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy after discharge (OR = 1.8). The ORs were used to develop a scoring system regarding the risk for early readmission. Conclusions Identifying patients with clinical factors associated with early CHF readmission after an index hospitalization for CHF using the proposed scoring system would allow for an early CHF readmission risk stratification protocol to target particularly high-risk patients. PMID:27279845

  1. Competitive binding of viral E2 protein and mammalian core-binding factor to transcriptional control sequences of human papillomavirus type 8 and bovine papillomavirus type 1.

    PubMed Central

    Schmidt, H M; Steger, G; Pfister, H

    1997-01-01

    The promoter P7535 of human papillomavirus type 8 and the promoter P7185 of bovine papillomavirus type 1 are negatively regulated by viral E2 proteins via the promoter proximal binding sites P2 and BS1, respectively. Mutations of these E2 binding sites can reduce basal promoter activity. This suggests binding of a transcription-stimulating factor and may indicate that repression by E2 is due to competitive binding of viral and cellular proteins. A computer search revealed putative binding sites for core-binding factor (CBF; also referred to as PEA2, PEBP2, or AML), overlapping with P2 and BS1. Binding of recombinant CBF proteins to these sites was confirmed by band shift analysis. Competition of CBF and E2 protein for DNA binding was shown for both human papillomavirus type 8 and bovine papillomavirus type 1. The importance of CBF-E2 competition in E2-mediated repression could be demonstrated by comparing the E2 effect on P7185 activity in two cell lines containing different amounts of endogenous CBF. In cells with large amounts of CBF, E2 repressed P7185 wild-type constructs to the basal promoter activity of a mutant (50%) that could not bind this protein any more. In contrast, in a cell line containing small amounts of CBF, the promoter activities of constructs with wild-type and mutated CBF binding sites hardly differed and specific repression by E2 was not detectable. PMID:9311900

  2. [Expression and Clinical Significance of Lymphoid Enhancer-Binding Factor 1 in Acute Leukemias].

    PubMed

    Huo, Wan-Ying; Gao, Ju

    2015-06-01

    Lymphoid enhancer-binding factor 1 (LEF1), a key downstream effector of Wnt/β-catenin signal transduction pathway, plays a crucial role in the maintenance, proliferation and differentiation of normal hematopoietic stem/progenitor cells through regulating the transcription of its target genes. Aberrant LEF1 expression has been documented in a variety of leukemias, and implicated in the prediction of prognosis. Nevertheless, discrepancies exist regarding the expression level and clinical implication of LEF1 in different types of leukemias, suggesting LEF1 might exert distinct roles in different types of leukemia. In the present article, recent research advances of the relationship of LEF1 and regulation of hematopoiesis and leukemogenesis are reviewed. PMID:26117056

  3. Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts

    PubMed Central

    Ono, Takaaki; Takeshita, Akihiro; Kishimoto, Yuji; Kiyoi, Hitoshi; Okada, Masaya; Yamauchi, Takahiro; Emi, Nobuhiko; Horikawa, Kentaro; Matsuda, Mitsuhiro; Shinagawa, Katsuji; Monma, Fumihiko; Ohtake, Shigeki; Nakaseko, Chiaki; Takahashi, Masatomo; Kimura, Yukihiko; Iwanaga, Masako; Asou, Norio; Naoe, Tomoki

    2014-01-01

    Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56+ APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 109/L or more, EFS and cumulative incidence of relapse in CD56+ APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor. PMID:24206578

  4. The Effects of Insulin-Like Growth Factor-1 Gene Therapy and Cell Transplantation on Rat Acute Wound Model

    PubMed Central

    Talebpour Amiri, Fereshteh; Fadaei Fathabadi, Fatemeh; Mahmoudi Rad, Mahnaz; Piryae, Abbas; Ghasemi, Azar; Khalilian, Alireza; Yeganeh, Farshid; Mosaffa, Nariman

    2014-01-01

    Background: Wound healing is a complex process. Different types of skin cells, extracellular matrix and variety of growth factors are involved in wound healing. The use of recombinant growth factors in researches and production of skin substitutes are still a challenge. Objectives: Much research has been done on the effects of gene therapy and cell therapy on wound healing. In this experimental study, the effect of insulin-like growth factor (IGF-1) gene transfer in fibroblast cells was assessed on acute dermal wound healing. Materials and Methods: Fibroblasts were cultured and transfected with IGF-1. Lipofectamine 2000 was used as a reagent of transfection. Transgene expression levels were measured by the enzyme linked immunosorbent assay (ELISA). To study in vivo, rats (weighing 170-200 g) were randomly divided into three groups (five/group) and full-thickness wounds were created on the dorsum region. Suspensions of transfected fibroblast cells were injected into the wound and were compared with wounds treated with native fibroblast cells and normal saline. For the microscopic examination, biopsy was performed on day seven. Results: In vitro, the maximum expression of IGF1 (96.95 pg/mL) in transfected fibroblast cells was 24 hours after gene transfer. In vivo, it was clear that IGF-1 gene therapy caused an increase in the number of keratinocyte cells during the wound healing process (mean of group A vs. group B with P value = 0.01, mean of group A vs. group C with P value = 0.000). Granulation of tissue formation in the transfected fibroblast group was more organized when compared with the normal saline group and native fibroblast cells. Conclusions: This study indicated that the optimization of gene transfer increases the expression of IGF-1. High concentrations of IGF-1, in combination with cell therapy, have a significant effect on wound healing. PMID:25558384

  5. Correlation between vascular endothelial growth factor and long-term prognosis in patients with acute myocardial infarction

    PubMed Central

    NIU, JIAMIN; HAN, XIA; QI, HUAXIN; YIN, JIE; ZHANG, ZHIQIANG; ZHANG, ZENGTANG

    2016-01-01

    The aim of the present study was to investigate the correlation between plasma the levels of vascular endothelial growth factor (VEGF) and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). A total of 124 patients with AMI undergoing emergency percutaneous coronary intervention (PCI) were selected, and plasma VEGF levels were measured 7 days after the onset of AMI using an enzyme-linked immunosorbent assay. The patients were divided into the L (≤190 pg/ml VEGF) and H (>190 pg/ml VEGF) groups, and were followed up every 2 months for an average of 12 months. MACE were recorded during follow-up. On the basis of these results, the patients were further divided into the MACE and non-MACE (N-MACE) groups, and the serum VEGF concentration was compared between the two groups. At the 6-month follow-up, the incidence of MACE in the H group was found to be significantly reduced compared with the L group. The serum VEGF concentration in the N-MACE group was significantly higher compared with the MACE group. Multinomial logistic regression revealed that reduced VEGF levels (β=1.243; 95% CI, 1.018–1.326; P=0.026) were independent risk factors for MACE. In conclusion, high plasma VEGF levels at 7 days after AMI onset facilitate the long-term prognosis in the same infarct zone in patients with AMI, while low plasma VEGF levels are independent risk factors for MACE. PMID:27347081

  6. CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY

    PubMed Central

    LUNA, Leonardo Duarte Sobreira; SOARES, Douglas de Sousa; JUNIOR, Geraldo Bezerra da SILVA; CAVALCANTE, Malena Gadelha; MALVEIRA, Lara Raissa Cavalcante; MENESES, Gdayllon Cavalcante; PEREIRA, Eanes Delgado Barros; DAHER, Elizabeth De Francesco

    2016-01-01

    SUMMARY Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001). Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death. PMID:27410912

  7. Diarrhoea and acute respiratory infections prevalence and risk factors among under-five children in Iraq in 2000

    PubMed Central

    Siziya, Seter; Muula, Adamson S; Rudatsikira, Emmanuel

    2009-01-01

    Background Diarrhoea and acute respiratory conditions are common medical conditions among under-five children in resource-limited and conflict situations. The present study was conducted to estimate the prevalence and associated factors for acute respiratory conditions and diarrhoea among children under the age of five years in Iraq in 2000. Methods Data for the Iraqi Multiple Indicator Cluster Survey were obtained from UNICEF. We estimated the prevalence of acute respiratory conditions and diarrhoea. Assessment of the associations between these two medical conditions on one hand and socio-demographic and environmental variables on the other was done using logistic regression analysis. Weighted analysis was conducted to account for complex survey design. Results A total of 14,676 children under the age of 5 years were reported by their mothers in the study. Of these 50.4% were males. About half (53.9%) of the children had complete vaccination status. Overall, 21.3% of the children had diarrhoea, and 6.9% had acute respiratory infection (ARI) in the last two weeks. In multivariate analysis, diarrhoea was associated with age of child, area of residence, maternal education, source of water, toilet facility, disposal of children' stool and disposal of dirty water. Compared to children aged 48–59 months, children in the age groups 6–11 months and 12–23 months were 2.22 (95%CI [2.02, 2.44]) and 1.84 (95%CI [1.71, 2.00]) times more likely, respectively, to have diarrhoea. Children whose mothers had no formal education were 11% (AOR = 1.11, 95%CI [1.04, 1.18]) more likely to have diarrhoea compared to children with mothers who had attained secondary level of education. Compared to children who belonged to households with unprotected well or river as the main source of water, children who belonged to households with piped water were 32% (AOR = 1.32, 95%CI [1.17, 1.48]) more likely to have diarrhoea while those who belonged to households with protected well were 26

  8. Etiology and Risk Factors of Acute Gastroenteritis in a Taipei Emergency Department: Clinical Features for Bacterial Gastroenteritis

    PubMed Central

    Lai, Chao-Chih; Ji, Dar-Der; Wu, Fang-Tzy; Mu, Jung-Jung; Yang, Ji-Rong; Jiang, Donald Dah-Shyong; Lin, Wen-Yun; Chen, Wei-Ting; Yen, Muh-Yong; Wu, Ho-Sheng; Chen, Tony Hsiu-Hsi

    2016-01-01

    Background The causative pathogen is rarely identified in the emergency department (ED), since the results of cultures are usually unavailable. As a result, antimicrobial treatment may be overused. The aim of our study was to investigate the pathogens, risk factors of acute gastroenteritis, and predictors of acute bacterial gastroenteritis in the ED. Methods We conducted a matched case-control study of 627 stool samples and 612 matched pairs. Results Viruses (41.3%) were the leading cause of gastroenteritis, with noroviruses (32.2%) being the most prevalent, followed by bacteria (26.8%) and Giardia lamblia (12.4%). Taking antacids (adjusted odds ratio [aOR] 4.10; 95% confidence interval [CI], 2.57–6.53), household members/classmates with gastroenteritis (aOR 4.69; 95% CI, 2.76–7.96), attending a banquet (aOR 2.29; 95% CI, 1.64–3.20), dining out (aOR 1.70; 95% CI, 1.13–2.54), and eating raw oysters (aOR 3.10; 95% CI, 1.61–5.94) were highly associated with gastroenteritis. Elders (aOR 1.04; 05% CI, 1.02–1.05), those with CRP >10 mg/L (aOR 2.04; 95% CI, 1.15–3.62), or those who were positive for fecal leukocytes (aOR 2.04; 95% CI, 1.15–3.62) or fecal occult blood (aOR 1.97; 95% CI, 1.03–3.77) were more likely to be hospitalized in ED. In addition, presence of fecal leukocytes (time ratio [TR] 1.22; 95% CI, 1.06–1.41), abdominal pain (TR 1.20; 95% CI, 1.07–1.41), and frequency of vomiting (TR 0.79; 95% CI, 0.64–0.98) were significantly associated with the duration of acute gastroenteritis. Presence of fecal leukocytes (aOR 2.08; 95% CI, 1.42–3.05), winter season (aOR 0.45; 95% CI, 0.28–0.74), frequency of diarrhea (aOR 1.69; 95% CI, 1.01–2.83), and eating shrimp or crab (aOR 1.53; 95% CI, 1.05–2.23) were highly associated with bacterial gastroenteritis. The area under the receiver operating characteristic curve of the final model was 0.68 (95% CI, 0.55–0.63). Conclusions Acute bacterial gastroenteritis was highly associated with season

  9. Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.

    PubMed

    van Miert, A S; van Duin, C T; Wensing, T

    1992-12-01

    Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r

  10. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  11. Arterial Spin Labeling for Acute Stroke: Practical Considerations

    PubMed Central

    Zaharchuk, Greg

    2014-01-01

    Arterial spin labeling is a non-contrast method of measuring cerebral perfusion with MRI. It has several advantages over traditional contrast-based perfusion-weighted imaging, including non-invasiveness, more straightforward cerebral blood flow (CBF) quantification, and repeatability. However, because of its lower signal-to-noise ratio (SNR) per unit time and its high sensitivity to arterial transit delays, it has not been used frequently in acute stroke, where arterial delays and time-efficiency are of the essence. This is beginning to change, driven by higher SNR implementations of ASL and the increasing use of 3T scanners. Furthermore, velocity selective ASL sequences that are largely insensitive to arrival times are beginning to be applied to patients with cerebrovascular disease, and promise the ability to quantify CBF even in regions supplied by late-arriving collateral flow. Despite these advances, many practical issues must be addressed to optimize ASL for use in acute stroke studies. These include optimizing the trade-off between time, SNR, imaging resolution, and sensitivity to slow flow. Rapid and robust post-processing of image data must be made routine, such that CBF maps are available in real-time so that they can be considered when making treatment decisions. Lastly, automated software needs to be developed to delineate hypoperfused tissue volumes, with attention to the inherent differences between gray and white matter CBF. Attention to these details is critical to translate this promising research tool into mainstream clinical trials and practice in acute stroke. PMID:24323778

  12. Acute lower respiratory illness in under-five children in Rio Grande, Rio Grande do Sul State, Brazil: prevalence and risk factors.

    PubMed

    Prietsch, Silvio O M; Fischer, Gilberto B; César, Juraci A; Lempek, Berenice S; Barbosa, Luciano V; Zogbi, Luciano; Cardoso, Olga C; Santos, Adriana M

    2008-06-01

    This study aimed to determine the prevalence of acute lower respiratory illness and to identify associated factors among children less than five years of age in the city of Rio Grande, southern Brazil. Using a cross-sectional survey, a standardized household questionnaire was applied to mothers or guardians. Information was collected on household conditions, socioeconomic status, and parental smoking. Prenatal care attendance, nutritional status, breastfeeding pattern, and use of health services for the children were also investigated. Data analysis was based on prevalence ratios and logistic regression, using a conceptual framework. Among 771 children studied, 23.9% presented acute lower respiratory illness. The main risk factors were previous episodes of acute lower respiratory infection or wheezing, crowding, maternal schooling less than five years, monthly family income less than US$ 200, four or more people per room, asthma in family members, and maternal smoking. Mothers 30 years or older were identified as a protective factor. These results can help define specific measures to reduce morbidity and mortality due to acute lower respiratory illness in this setting. PMID:18545768

  13. The ‘Perfect Storm’ and Acute Coronary Syndrome Onset: Do Psychosocial Factors Play a Role?

    PubMed Central

    Burg, Matthew M.; Edmondson, Donald; Shimbo, Daichi; Shaffer, Jonathan; Kronish, Ian M.; Whang, William; Alcántara, Carmela; Schwartz, Joseph E.; Muntner, Paul; Davidson, Karina W.

    2013-01-01

    The revolution in cardiac care over the past two decades, characterized by emergent revascularization, drug eluting stents, anti-platelet medications, and advanced imaging has had little impact on overall ACS recurrence, or ACS prevention. The “Perfect Storm” refers to a confluence of events and processes, including atherosclerotic plaque, coronary flow dynamics, hemostatic and fibrinolytic function, metabolic and inflammatory conditions, neurohormonal dysregulation, and environmental events that give rise to, and result in an ACS event. In this article we illustrate the limits of the traditional main effect research model, giving a brief description of the current state of knowledge regarding the development of atherosclerotic plaque and the rupturing of these plaques that defines an ACS event. We then apply the Perfect Storm conceptualization to describe a program of research concerning a psychosocial vulnerability factor that contributes to increased risk of recurrent ACS and early mortality, and that has defied our efforts to identify underlying pathophysiology and successfully mount efforts to fully mitigate this risk. PMID:23621970

  14. Multiple Immune Factors Are Involved in Controlling Acute and Chronic Chikungunya Virus Infection

    PubMed Central

    Poo, Yee Suan; Rudd, Penny A.; Gardner, Joy; Wilson, Jane A. C.; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T.; Nakaya, Helder I.; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A.; Khromykh, Alexander A.; Lopez, José A.; Suhrbier, Andreas

    2014-01-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. PMID:25474568

  15. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    PubMed

    Poo, Yee Suan; Rudd, Penny A; Gardner, Joy; Wilson, Jane A C; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T; Nakaya, Helder I; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A; Khromykh, Alexander A; Lopez, José A; Suhrbier, Andreas

    2014-12-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. PMID:25474568

  16. Analyzing the Expression Profile of AREB/ABF and DREB/CBF Genes under Drought and Salinity Stresses in Grape (Vitis vinifera L.)

    PubMed Central

    Zandkarimi, Hana; Ebadi, Ali; Salami, Seyed Alireza; Alizade, Houshang; Baisakh, Niranjan

    2015-01-01

    Expression patterns of four candidate AREB/ABF genes and four DREB/CBF genes were evaluated in leaf and root tissues of five grape varieties (‘Qalati’, ‘Kaj Angoor’, ‘Sabz Angoor’, ‘Siahe Zarghan’, ‘Bidane Safid’) with differential response to drought stress. Among the AREB/ABF genes, AREB1 and ABF2 showed up-regulation in response to drought stress in leaf and root tissues of all varieties while AREB2 and ABF1 showed down-regulation in both leaf and root tissues of the sensitive variety ‘Bidane Sefid’ in response to drought and salt stress. Among the DREB/CBF genes, CBF4 was the most responsive to drought stress in both leaf and root tissues. CBF2 and CBF3 showed up-regulation in all varieties in response to drought stress in leaf except in ‘Bidane Sefid’. Under salinity stress, AREB2 and ABF2 showed up-regulation in response to the increasing level of salinity in the leaf tissues but in the root tissues ABF2 was up-regulated in response to increasing NaCl concentration while AREB2 was down-regulated. Therefore, it seems AREB2 has tissue-specific response to salinity stress. All CBF genes were up-regulated in response to salinity stress in the leaf and root tissues. Expression data suggested that CBF2 is more responsive to NaCl stress. Among all four promising and stress tolerant varieties ‘Siah Zarghan’ and ‘Kaj Angoor’ were more tolerant than ‘Qalati’ and ‘Sabz Angoor’ to drought and salinity. PMID:26230273

  17. Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis.

    PubMed

    Müller, M J; Wetzel, H; Benkert, O

    2002-09-01

    While many acutely ill schizophrenic patients suffer from depressive symptoms, most studies on the efficacy of antipsychotic drugs focus on positive and negative symptoms. Dimensional models of schizophrenic symptoms, based on confirmatory factor analysis (CFA) using structural equation modelling, offer a methodological alternative to compare antipsychotics on empirically justified latent factors. The present report is a refined analysis of a published double-blind study on the D2/D3-selective antagonist amisulpride (ASP) versus the mixed D1-5/5-HT2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Rafaelsen Melancholia Scale and Simpson-Angus Scale subscores to examine differential effects of high doses of ASP and FPX on negative and depressive symptom dimensions in 126 acutely ill schizophrenic patients. A four-factor model comprising the full spectrum of acute symptomatology and a three-factor model ('negative', 'anhedonia-apathy', 'depressive') restricted to negative and depressive symptoms were yielded with an identical 'depressive' dimension in both models. Analyses of CFA-derived factor scores showed that ASP was significantly superior to FPX regarding the latent 'depressive' dimension, independent of baseline scores, dosage and changes in akinesia. Neither the negative' dimension nor 'anhedonia-apathy' showed significantly different treatment effects. CFA-based analyses appear to be suitable for psychotropic drug evaluation when more refined and data-related information on drug efficacy profiles are required. PMID:12177587

  18. Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

    PubMed

    Seo, Joo Youn; Choi, Bo Youl; Ki, Moran; Jang, Hye Lim; Park, Hee Suk; Son, Hyun Jin; Bae, Si Hyun; Kang, Jin Han; Jun, Dae Won; Lee, Jin-Woo; Hong, Young Jin; Kim, Young Seok; Kim, Chang-Hwi; Chang, U Im; Kim, Jong-Hyun; Yang, Hyeon Woong; Kim, Hong Soo; Park, Kyeong Bae; Hwang, Jae Seok; Heo, Jeong; Kim, In Hee; Kim, Jung Soo; Cheon, Gab Jin

    2013-06-01

    This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas. PMID:23772157

  19. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

    PubMed Central

    Xie, Jieshi; Yang, Le; Tian, Lei; Li, Weiyang; Yang, Lin; Li, Liying

    2016-01-01

    Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID:27273604

  20. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  1. Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice.

    PubMed

    Wu, Dongdong; Pan, Pinhua; Su, Xiaoli; Zhang, Lemeng; Qin, Qingwu; Tan, Hongyi; Huang, Li; Li, Yuanyuan

    2016-09-01

    Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation. PMID:26939040

  2. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury.

    PubMed

    Xie, Jieshi; Yang, Le; Tian, Lei; Li, Weiyang; Yang, Lin; Li, Liying

    2016-01-01

    Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID:27273604

  3. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group

    PubMed Central

    Hilden, Joanne M.; Dinndorf, Patricia A.; Meerbaum, Sharon O.; Sather, Harland; Villaluna, Doojduen; Heerema, Nyla A.; McGlennen, Ron; Smith, Franklin O.; Woods, William G.; Salzer, Wanda L.; Johnstone, Helen S.; Dreyer, Zoann; Reaman, Gregory H.

    2006-01-01

    Infant acute lymphoblastic leukemia (ALL) has a poor therapeutic outcome despite attempts to treat it based on prognostic factor–guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/11q23 rearrangement. All infants enrolled on Children's Cancer Group (CCG) 1953 were tested for MLL rearrangement by Southern blot and the 11q23 translocation partner was identified (4;11, 9;11, 11;19, or “other”) by reverse-transcriptase polymerase chain reaction (PCR). One hundred fifteen infants were enrolled; overall event-free survival (EFS) was 41.7% (SD = 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL-rearranged cases was 33.6% and for MLL-nonrearranged cases was 60.3%. The difference in EFS between the 3 major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age younger than 6 months, and MLL rearrangement, in that order. Toxicity was the most frequent cause of death. Relapse as a first event in CCG 1953 was later (median, 295 days) compared with CCG 1883 historic control (median, 207 days). MLL/11q23 rearrangement, CD10 expression, and age are important prognostic factors in infant ALL, but molecular 11q23 translocation partners do not predict outcome. PMID:16556894

  4. Regulation of alveolar procoagulant activity and permeability in direct acute lung injury by lung epithelial tissue factor.

    PubMed

    Shaver, Ciara M; Grove, Brandon S; Putz, Nathan D; Clune, Jennifer K; Lawson, William E; Carnahan, Robert H; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2015-11-01

    Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI. PMID:25884207

  5. A case-control study to identify risk factors for acute salmonellosis in New Zealand dairy herds, 2011-2012.

    PubMed

    Stevenson, M A; Morgan, P L; Sanhueza, J; Oakley, G E; Bateman, R S; McFADDEN, A; MacPHERSON, N; Owen, K L; Burton, L; Walsh, S; Weston, J; Marchant, R

    2016-07-01

    In late 2011 the New Zealand Ministry for Primary Industries reported an increase in confirmed laboratory diagnoses of salmonellosis in dairy herds. To identify risk factors for herd-level outbreaks of salmonellosis we conducted a case-control study of New Zealand dairy herds in 2011-2012. In a multivariable analysis, use of continuous feed troughs [adjusted odds ratio (aOR) 6·2, 95% confidence interval (CI) 2·0-20], use of pelletized magnesium supplements (aOR 10, 95% CI 3·3-33) and use of palm kernel meal as a supplementary feed (aOR 8·7, 95% CI 2·5-30) were positively associated with a herd-level outbreak of salmonellosis between 1 July 2011 and 31 January 2012. We conclude that supplementary feeds used on dairy farms (regardless of type) need to be stored and handled appropriately to reduce the likelihood of bacterial contamination, particularly from birds and rodents. Magnesium supplementation in the pelletized form played a role in triggering outbreaks of acute salmonellosis in New Zealand dairy herds in 2011-2012. PMID:26956947

  6. Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice

    PubMed Central

    Wu, Dongdong; Pan, Pinhua; Su, Xiaoli; Zhang, Lemeng; Qin, Qingwu; Tan, Hongyi; Huang, Li; Li, Yuanyuan

    2016-01-01

    ABSTRACT Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation. PMID:26939040

  7. An Epstein-Barr Virus Encoded Inhibitor of Colony Stimulating Factor-1 Signaling Is an Important Determinant for Acute and Persistent EBV Infection

    PubMed Central

    Ohashi, Makoto; Fogg, Mark H.; Orlova, Nina; Quink, Carol; Wang, Fred

    2012-01-01

    Acute Epstein-Barr virus (EBV) infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1) signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV), naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1). Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection. PMID:23300447

  8. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program

    PubMed Central

    Mengesha, Melkamu Merid; Deyessa, Negussie; Tegegne, Balewgizie Sileshi; Dessie, Yadeta

    2016-01-01

    Background The outpatient therapeutic care program (OTP) of children with severe acute malnutrition (SAM) has been decentralized to health post level in Ethiopia since 2008–2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. Objective This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. Design Health facility–based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. Result 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97)]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56)]. However, children who gained Mid-Upper Arm Circumference (MUAC) ≥ 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06)]. Conclusions Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome. PMID:27396484

  9. Risk Factors for Acute Kidney Injury after Coronary Artery Bypass Surgery and Its Detection Using Neutrophil Gelatinase-Associated Lipocalin

    PubMed Central

    Onk, Oruç Alper; Onk, Didem; Ozcelik, Fatih; Gunay, Murat; Turkmen, Kultigin

    2016-01-01

    Introduction Acute kidney injury (AKI) is an important complication of cardiac surgery due to its high mortality. The aim of the present study was to detect the factors leading to AKI in patients who underwent coronary artery bypass surgery (CABS) and also to determine the optimal timing for detecting AKI using the biomarker neutrophil gelatinase-associated lipocalin (NGAL). Materials and Methods The records of 375 patients who underwent CABS were reviewed in this case-control study. Ejection fraction (EF), common carotid artery intima-media thickness (CCA-IMT) and cross-clamp (C-C) time of the patients were recorded. Blood samples were taken from all patients on preoperative day 1 as well as 6, 12, 24, 36, 48 h and 7 days after operation. Biochemical parameters were studied in patients with and without AKI. Results According to the Risk Injury Failure Loss End Stage criteria, 24 patients had renal risk, 17 had injury and 4 had failure. Postoperative 24-hour serum creatinine levels indicated the risk of renal dysfunction for only 4 patients in the AKI group. CCA-IMT, C-C time, haematocrit (HCT) and preoperative interleukin-6 levels were significantly higher in the AKI group than in the non-AKI group. Postoperative 6- and 12-hour NGAL levels in the AKI group correlated with postoperative 36-hour serum creatinine levels. The optimal cut-off values for postoperative 6- and 12-hour NGAL test were 310 and 283 ng/ml, respectively. The area under the curve was higher in the 12-hour NGAL test (p < 0.0086). Conclusion The number of stenotic coronary arteries, EF, CCA-IMT and HCT are all important risk factors. Early postoperative NGAL results were highly specific for the early recognition of AKI. PMID:27275158

  10. Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

    PubMed Central

    Gao, Dan-Dan; Fu, Jia; Qin, Bo; Huang, Wen-Xiang; Yang, Chun; Jia, Bei

    2016-01-01

    AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF). METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes. RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter group. CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects. PMID:27122664

  11. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis

    PubMed Central

    Thaler, Roman; Sturmlechner, Ines; Spitzer, Silvia; Riester, Scott M.; Rumpler, Monika; Zwerina, Jochen; Klaushofer, Klaus; van Wijnen, Andre J.; Varga, Franz

    2015-01-01

    Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis.—Thaler, R., Sturmlechner, I., Spitzer, S., Riester, S. M., Rumpler, M., Zwerina, J., Klaushofer, K., van Wijnen, A. J., Varga, F. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis. PMID:25491310

  12. Association of Streptococcus pneumoniae nasopharyngeal colonization and other risk factors with acute otitis media in an unvaccinated Indian birth cohort.

    PubMed

    Rupa, V; Isaac, R; Rebekah, G; Manoharan, A

    2016-07-01

    In order to study the epidemiology of acute otitis media (AOM) and Streptococcus pneumoniae nasopharyngeal colonization in the first 2 years of life, we followed up an unvaccinated birth cohort monthly and at visits when sick, with otoscopy to detect AOM and performed nasopharyngeal swabbing to detect S. pneumoniae. Serotyping of positive cultures was also performed. Of 210 babies who were enrolled at birth, 61 (29·05%) experienced 128 episodes of AOM [relative risk 2·63, 95% confidence interval (CI) 1·21-5·75] with maximum incidence in the second half of the first year of life. Episodes ranged from 1 to 7 (mean 2·1 episodes). Most (86·9%) babies with AOM had a positive culture swab giving an odds ratio (OR) of 1·93 (95% CI 1·03-3·62, P = 0·041) for this association. Other risk factors identified for AOM were winter season (OR 3·46, 95% CI 1·56-7·30, P = 0·001), upper respiratory infection (OR 2·43, 95% CI 1·43-4·51, P = 0·005); residents of small households were less likely to develop AOM (OR 0·32, 95% CI 0·17-0·57, P < 0·01). Common S. pneumoniae serotypes isolated during episodes were 19, 6, 15, 35, 7, 23, 9 and 10 which indicated a theoretical coverage for pneumococcal vaccines PCV10 and PCV13 constituent serotypes of 62·8%. We conclude that AOM in Indian infants is often associated with S. pneumoniae colonization of the nasopharynx as well as other risk factors. PMID:26931207

  13. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

    PubMed

    Karol, Seth E; Mattano, Leonard A; Yang, Wenjian; Maloney, Kelly W; Smith, Colton; Liu, ChengCheng; Ramsey, Laura B; Fernandez, Christian A; Chang, Tamara Y; Neale, Geoffrey; Cheng, Cheng; Mardis, Elaine; Fulton, Robert; Scheet, Paul; San Lucas, F Anthony; Larsen, Eric C; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Devidas, Meenakshi; Relling, Mary V

    2016-02-01

    Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children <10 years incompletely understood. Here, we perform the first evaluation of genetic risk factors for osteonecrosis in children <10 years. The discovery cohort comprised 82 cases of osteonecrosis and 287 controls treated on Children's Oncology Group (COG) standard-risk ALL protocol AALL0331 (NCT00103285, https://clinicaltrials.gov/ct2/show/NCT00103285), with results tested for replication in 817 children <10 years treated on COG protocol AALL0232 (NCT00075725, https://clinicaltrials.gov/ct2/show/NCT00075725). The top replicated single nucleotide polymorphisms (SNPs) were near bone morphogenic protein 7 [BMP7: rs75161997, P = 5.34 × 10(-8) (odds ratio [OR] 15.0) and P = .0498 (OR 8.44) in the discovery and replication cohorts, respectively] and PROX1-antisense RNA1 (PROX1-AS1: rs1891059, P = 2.28 × 10(-7) [OR 6.48] and P = .0077 [OR 3.78] for the discovery and replication cohorts, respectively). The top replicated nonsynonymous SNP, rs34144324, was in a glutamate receptor gene (GRID2, P = 8.65 × 10(-6) [OR 3.46] and P = .0136 [OR 10.8] in the discovery and replication cohorts, respectively). In a meta-analysis, the BMP7 and PROX1-AS1 variants (rs75161997 and rs1891059, respectively) met the significance threshold of <5 × 10(-8). Top replicated SNPs were enriched in enhancers active in mesenchymal stem cells, and analysis of annotated genes demonstrated enrichment in glutamate receptor and adipogenesis pathways. These data may provide new insights into the pathophysiology of osteonecrosis. PMID:26590194

  14. Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

    PubMed

    Bryce, Courtney A; Floresco, Stan B

    2016-07-01

    Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. PMID:26830960

  15. Substance Use is a Risk Factor for Neurocognitive Deficits and Neuropsychiatric Distress in Acute and Early HIV Infection

    PubMed Central

    Weber, Erica; Morgan, Erin E.; Iudicello, Jennifer E.; Blackstone, Kaitlin; Grant, Igor; Ellis, Ronald J.; Letendre, Scott L.; Little, Susan; Morris, Sheldon; Smith, Davey M.; Moore, David J.; Woods, Steven Paul

    2012-01-01

    The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naïve adults with median duration of infection of 75 days, relative to sample a of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States (POMS), a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly five-fold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use. PMID:23250704

  16. Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

    PubMed Central

    2014-01-01

    Background To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy. Methods Seventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE. Results Seventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, OR = 1.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; OR = 9.686) and V50 (p<0.001; OR = 1.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (p = 0.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC. Conclusions Concomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to

  17. Hospital Performance Indicators and Their Associated Factors in Acute Child Poisoning at a Single Poison Center, Central Saudi Arabia.

    PubMed

    Alanazi, Menyfah Q; Al-Jeriasy, Majed I; Al-Assiri, Mohammed H; Afesh, Lara Y; Alhammad, Fahad; Salam, Mahmoud

    2015-12-01

    Admission rate and length of stay (LOS) are two hospital performance indicators that affect the quality of care, patients' satisfaction, bed turnover, and health cost expenditures. The aim of the study was to identify factors associated with higher admission rates and extended average LOS among acutely poisoned children at a single poison center, central Saudi Arabia.This is a cross-sectional, poison and medical chart review between 2009 and 2011. Exposures were child characteristics, that is, gender, age, body mass index (BMI), health history, and Canadian 5-level triage scale. Poison incident characteristics were, that is, type, exposure route, amount, form, home remedy, and arrival time to center. Admission status and LOS were obtained from records. Chronic poisoning, plant allergies, and venomous bites were excluded. Bivariate and regression analyses were applied. Significance at P < 0.05.Of the 315 eligible cases, (72%) were toddlers with equal gender distribution, (58%) had normal BMI, and (77%) were previously healthy. Poison substances were pharmaceutical drugs (63%) versus chemical products (37%). Main exposure route was oral (98%). Home remedy was observed in (21.9%), which were fluids, solutes, and/or gag-induced vomiting. Almost (52%) arrived to center >1 h. Triage levels: non-urgent cases (58%), less urgent (11%), urgent (18%), emergency (12%), resuscitative (1%). Admission rate was (20.6%) whereas av. LOS was 13 ± 22 h. After adjusting and controlling for confounders, older children (adj.OR = 1.19) and more critical triage levels (adj.OR = 1.35) were significantly associated with higher admission rates compared to younger children and less critical triage levels (adj.P = 0.006) and (adj.P = 0.042) respectively. Home remedy prior arrival was significantly associated with higher av. LOS (Beta = 9.48, t = 2.99), compared to those who directly visited the center, adj.P = 0.003.Hospital administrators are cautioned

  18. Acute Pneumonia.

    PubMed

    Arshad, Hammad; Fasanya, Adebayo; Cheema, Tariq; Singh, Anil C

    2016-01-01

    Acute pneumonia is an active infection of the lungs that results when an individual at risk gets exposed to a particular microbiological pathogen. Acute pneumonia is the leading cause of death in the United States that is attributable to an infection. The risk factors, pathogenesis, and microbiological organisms involved differ if the pneumonia develops in the community versus health care-associated environment. The development of concise and comprehensive guidelines has led to an improvement in the management of the problem. However, the emergence of multidrug-resistant organisms and the increase in the percentage of elderly population keep mortality risk very substantial. PMID:26919676

  19. The Time between Paraquat Ingestion and a Negative Dithionite Urine Test in an Independent Risk Factor for Death and Organ Failure in Acute Paraquat Intoxication

    PubMed Central

    Seok, Sujin; Kim, Young-hee; Gil, Hyo-wook; Song, Ho-yeon

    2012-01-01

    To identify a prognostic marker that is less sensitive to variations in the elapsed time since paraquat ingestion, we assessed the time between paraquat ingestion and a negative dithionite urine test as a prognostic parameter in patients with acute paraquat intoxication. Forty-one patients with acute paraquat intoxication were enrolled in this study and analyzed to verify significant determinants of mortality and organ dysfunction. The amount of paraquat ingested, paraquat plasma levels, and the time to a negative urine dithionite test were significant independent risk factors predicting mortality. The amount of paraquat ingestion, and the time to a negative urine dithionite test were independent risk factors predicting organ dysfunction. With a cut-off value of 34.5 hr for the time to negative conversion of the urine dithionite test, the sensitivity and specificity for mortality were 71.4% and 75.0%, respectively. The incidence of acute kidney injury and respiratory failure above 34.5 hr were 100% and 85.0%, respectively. In conclusion, the time to a negative urine dithionite test is the reliable marker for predicting mortality and/or essential organ failure in patients with acute paraquat intoxication, who survive 72 hr. PMID:22969243

  20. Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study.

    PubMed

    Bhat, Zeenat Yousuf; Cadnapaphornchai, Pravit; Ginsburg, Kevin; Sivagnanam, Milani; Chopra, Shamit; Treadway, Corey K; Lin, Ho-Sheng; Yoo, George; Sukari, Ammar; Doshi, Mona D

    2015-01-01

    Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long

  1. Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study

    PubMed Central

    Bhat, Zeenat Yousuf; Cadnapaphornchai, Pravit; Ginsburg, Kevin; Sivagnanam, Milani; Chopra, Shamit; Treadway, Corey K.; Lin, Ho-Sheng; Yoo, George; Sukari, Ammar; Doshi, Mona D.

    2015-01-01

    Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long

  2. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  3. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  4. Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow

    PubMed Central

    Colace, T. V.; Diamond, S. L.

    2013-01-01

    Objective In severe stenosis, von Willebrand Factor (vWF) experiences millisecond exposures to pathological wall shear rates (γw). We sought to evaluate the deposition of vWF onto collagen surfaces under flow in these environments. Methods and Results Distinct from shear experiments that last many seconds, we deployed microfluidic devices for single-pass perfusion of whole blood or platelet free plasma (PFP) over fibrillar type 1 collagen (< 50 msec transit time) at pathological γw or spatial wall shear rate gradient (grad γw). Using fluorescent anti-vWF, long thick vWF fibers (>20 μm) bound to collagen were visualized at constant γw > 30,000 s−1 during perfusion of PFP, a process enhanced by EDTA. Rapid acceleration or deceleration of EDTA-PFP at grad γw = ± 5.5 × 105 to 4.3 × 107 s−1/cm did not promote vWF deposition. At 19,400 s−1, EDTA-blood perfusion resulted in rolling vWF-platelet nets, while blood perfusion (normal Ca2+) generated large vWF/platelet deposits that repeatedly embolized and were blocked by anti-GPIb or the α IIbβ3 inhibitor GR144053 and did not require grad γw. Blood perfusion at venous shear rate (200 s−1) produced a stable platelet deposit that was a substrate for massive but unstable vWF-platelet aggregates when flow was increased to 7800 s−1. Conclusion Triggered by collagen and enhanced by platelet GPIb and α IIbβ3, vWF fiber formation occurred during acute exposures to pathological γw and did not require gradients in wall shear rate. PMID:23104847

  5. Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor.

    PubMed

    Lin, Xiao-Cong; Xu, Yong; Sun, Guo-Ping; Wen, Jin-Li; Li, Ning; Zhang, Yu-Ming; Yang, Zhi-Gang; Zhang, Hai-Tao; Dai, Yong

    2016-06-01

    Acute myeloid leukemia (AML) is a heterogenic hematological malignancy with pathogenesis that has yet to be elucidated. MicroRNAs (miRNAs) and transcription factors (TFs) are two major regulators of gene expression, which may play important roles in the etiology of AML. However, the global regulation of gene expression in AML, involving miRNAs and TFs, still remains elusive. To characterize the global role of miRNAs and TFs in AML pathogenesis, large scale expression profiling of miRNA and TF was performed using miRNA sequencing and TF array technology, respectively, and validated by qPCR. In the present study, 308 miRNAs and 84 TFs were identified to be differentially expressed (fold-change ≥2.0) in AML samples relative to their controls. After integrating the expression profiling data into bioinformatic analysis, we identified 1,462 miRNA-gene pairs, 982 TF-gene pairs and 296 TF-miRNA pairs. By merging these regulatory relations together, we constructed a comprehensive AML-specific miRNA-TF regulatory network. In this network, we identified 22 hub miRNAs and 11 hub TFs. KEGG pathway analysis showed that the network nodes were significantly enriched in 33 different pathways, of which the AML pathway was the most significant. After analyzing the topology of the subnetwork, we propose that TCF3 was a potential key regulator in this regulatory network. In conclusion, this is the first study perform on global expression profiling of miRNAs and TFs relating to AML. These results may enhance our understanding of the molecular mechanisms underlying AML and provide potential targets for future therapeutics. PMID:27082628

  6. Circulating Influenza Virus, Climatic Factors, and Acute Myocardial Infarction: A Time Series Study in England and Wales and Hong Kong

    PubMed Central

    Bhaskaran, Krishnan; Hayward, Andrew; Leung, Gabriel M.; Wong, Chit-Ming; Ellis, Joanna; Pebody, Richard; Smeeth, Liam; Cowling, Benjamin J.

    2011-01-01

    (See the editorial commentary by Finelli and Chaves, on pages 1701-4.) Background. Previous studies identifying associations between influenza and acute cardiac events may have been confounded by climatic factors. Differing seasonal patterns of influenza activity in Hong Kong and England and Wales provide a natural experiment to examine associations with myocardial infarction (MI) independent of cold weather effects. Methods. Weekly clinical and laboratory influenza surveillance data, environmental temperature and humidity data, and counts of MI-associated hospitalizations and deaths were obtained for England and Wales and for Hong Kong for the period 1998–2008. We used Poisson regression models that included environmental and seasonal variables to investigate the relationship between influenza and MI. Results. There were ≥1.2 million MI-associated hospitalizations and 410,204 MI-associated deaths in England and Wales, with a marked peak in the winter season. In Hong Kong, the incidence of MI, on the basis of 65,108 hospitalizations and 18,780 deaths, had a large winter and smaller summer peak, mirroring patterns of influenza activity. There was strong evidence for a link between influenza and MI both in England and Wales, where 3.1%–3.4% of MI-associated deaths (P < .001) and 0.7%–1.2% of MI-associated hospitalizations (P < .001) were attributable to influenza, and in Hong Kong, where the corresponding figures were 3.9%–5.6% (P = .018) and 3.0%–3.3% (P = .002). Conclusions. Influenza was associated with an increase in MI-associated deaths and hospitalizations in 2 contrasting settings. PMID:21606529

  7. Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

    PubMed Central

    Conger, J D; Robinette, J B; Schrier, R W

    1988-01-01

    Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels. PMID:3261301

  8. Medication use as a risk factor for inpatient falls in an acute care hospital: a case-crossover study

    PubMed Central

    Shuto, Hideki; Imakyure, Osamu; Matsumoto, Junichi; Egawa, Takashi; Jiang, Ying; Hirakawa, Masaaki; Kataoka, Yasufumi; Yanagawa, Takashi

    2010-01-01

    AIMS The present study aimed to evaluate the associations between medication use and falls and to identify high risk medications that acted as a trigger for the onset of falls in an acute care hospital setting. METHODS We applied a case-crossover design wherein cases served as their own controls and comparisons were made within each participant. The 3-day period (days 0 to −2) and the 3-day periods (days −6 to −8, days −9 to −11 and days −12 to −14) before the fall event were defined as the case period and the control periods, respectively. Exposures to medications were compared between the case and control periods. Odds ratios (OR) and 95% confidence intervals (CI) for the onset of falls with respect to medication use were computed using conditional logistic regression analyses. RESULTS A total of 349 inpatients who fell during their hospitalization were recorded on incident report forms between March 2003 and August 2005. The initial use of antihypertensive, antiparkinsonian, anti-anxiety and hypnotic agents as medication classes was significantly associated with an increased risk of falls, and these ORs (95% CI) were 8.42 (3.12, 22.72), 4.18 (1.75, 10.02), 3.25 (1.62, 6.50) and 2.44 (1.32, 4.51), respectively. The initial use of candesartan, etizolam, biperiden and zopiclone was also identified as a potential risk factor for falls. CONCLUSIONS Medical professionals should be aware of the possibility that starting a new medication such as an antihypertensive agent, including candesartan, and antiparkinsonian, anti-anxiety and hypnotic agents, may act as a trigger for the onset of a fall. PMID:20573090

  9. Long-Term Effects of Autologous Bone Marrow Stem Cell Treatment in Acute Myocardial Infarction: Factors That May Influence Outcomes

    PubMed Central

    Clifford, David M.; Fisher, Sheila A.; Brunskill, Susan J.; Doree, Carolyn; Mathur, Anthony; Clarke, Mike J.; Watt, Suzanne M.; Martin-Rendon, Enca

    2012-01-01

    Aims To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. Methods and Results MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005–2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 108 cells and to patients with more severe heart dysfunction. Conclusions Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials. PMID:22655042

  10. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    PubMed

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  11. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis.

    PubMed

    Zhong, Weibin; Geng, Na; Wang, Pengfei; Li, Zhenguang; Cao, Lili

    2016-08-01

    Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge. PMID:27129874

  12. Effect of acute and chronic insulin administrations on major factors involved in the control of muscle protein turnover in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Seiliez, Iban; Panserat, Stéphane; Skiba-Cassy, Sandrine; Polakof, Sergio

    2011-07-01

    In this study, the effect of acute and chronic insulin treatments on major factors involved in the control of muscle protein turnover were investigated in rainbow trout (Oncorhynchus mykiss). We found that acute but not chronic insulin administration leads to the induction of the phosphorylation of several key factors (IRS1, TOR and 4E-BP1) involved in the control of the protein synthesis and to the concomitant down-regulation of the expression of ubiquitin-proteasome-related genes (atrogin1, C2, C9) and the calpains inhibitor calpastatin. In contrast, no modification of autophagy-related gene (LC3B, gabarpl1, atg4b) expressions was observed suggesting that the mechanisms controlling this proteolytic route have diverged throughout the evolution. Overall, these results provide a possible explanation of the growth-promoting properties of insulin previously described in fish and indicate that this hormone acutely administrated is able to exert a regulatory influence on various factors associated with growth in skeletal muscle. PMID:21463630

  13. Study of differences in presentation, risk factors and management in diabetic and nondiabetic patients with acute coronary syndrome

    PubMed Central

    Sharma, Krishna Kumar; Mathur, Mukul; Lodha, Sailesh; Sharma, Surendra Kumar; Sharma, Niharika; Gupta, Rajeev

    2016-01-01

    Objectives: To compare clinical characteristics, treatment, and utilization of evidence-based medicines at discharge from hospital in acute coronary syndrome (ACS) patients with or without diabetes at a tertiary care cardiac center in India. Methods: We performed an observational study in consecutive patients discharged following management of ACS. We obtained demographic details, comorbid conditions, and cardiovascular risk factors, physical and biochemical parameters, and management. Descriptive statistics are reported. Results: We enrolled 100 patients (diabetics = 28) with mean age of 59.0 ± 10.8 years (diabetics 59.3 ± 11.6, nondiabetics 58.9 ± 8.5). Forty-nine patients had ST-elevation myocardial infarction (STEMI) (diabetics = 14, 28.7%) while 51 had nonSTEMI/unstable angina (diabetics = 14, 27.4%) (P = nonsignificant). Among diabetics versus nondiabetics there was greater prevalence (%) of hypertension (78.6% vs. 44.4%), obesity (25.0% vs. 8.3%), abdominal obesity (85.7% vs. 69.4%) and sedentary activity (89.2% vs. 77.8%), and lower prevalence of smoking/tobacco use (10.7% vs. 25.0%) (P < 0.05). In STEMI patients 28 (57.1%) were thrombolysed (diabetes 17.8% vs. 31.9%), percutaneous coronary interventions (PCI) was in 67.8% diabetics versus 84.7% nondiabetics and coronary bypass surgery in 21.4% versus 8.3%. At discharge, in diabetics versus nondiabetics, there was similar use of angiotensin converting enzyme inhibitors (67.9% vs. 69.4%) and statins (100.0% vs. 98.6%) while use of dual antiplatelet therapy (85.7% vs. 95.8%) and beta-blockers (64.3% vs. 73.6%) was lower (P < 0.05). Conclusions: Diabetic patients with ACS have greater prevalence of cardiometabolic risk factors (obesity, abdominal obesity, and hypertension) as compared to nondiabetic patients. Less diabetic patients undergo PCIs and receive lesser dual anti-platelet therapy and beta-blockers. PMID:27186553

  14. Factors Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke: Lessons from China

    PubMed Central

    Feng, Juan; Cheng, Wei-yang; Jia, Jian-ping; Song, Hai-qing; Chang, Hong; Wu, Jian

    2015-01-01

    In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay

  15. Factors Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke: Lessons from China.

    PubMed

    Huang, Qiang; Ma, Qing-feng; Feng, Juan; Cheng, Wei-yang; Jia, Jian-ping; Song, Hai-qing; Chang, Hong; Wu, Jian

    2015-01-01

    In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60 min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135 min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay

  16. Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury: A Retrospective Cohort Study.

    PubMed

    Hsu, Chien-Ning; Lee, Chien-Te; Su, Chien-Hao; Wang, Yu-Ching Lily; Chen, Hsiao-Ling; Chuang, Jiin-Haur; Tain, You-Lin

    2016-05-01

    The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort.This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission.AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI.Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals. PMID:27175701

  17. Factors Affecting Well-being and Socio-occupational Functioning in Schizophrenia Patients Following an Acute Exacerbation: A Hospital Based Observational Study

    PubMed Central

    Gopalakrishnan, Roopa; Behere, Rishikesh V.; Sharma, P.S.V.N.

    2015-01-01

    Background: Improving functioning levels are an important goal of treatment in schizophrenia. Most studies have described long-term course and outcome in schizophrenia. However, understanding factors influencing functioning in the immediate recovery period following an acute exacerbation may be of important clinical relevance. Aim: The aim of this study is to assess the factors that influence well-being and socio-occupational functioning following an acute exacerbation in schizophrenia patients. Materials and Methods: The study included 40 patients during the period from June 2013 to June 2014. The possible effect of gender, duration of illness, duration of untreated psychosis, premorbid adjustment, cognitive impairment, facial affect perception and treatment compliance on well-being, and socio-occupational functioning was examined. Results: About 45% of the individuals experienced below average well-being. On logistic regression analysis poor compliance with medication and poorer cognitive functioning significantly differentiated the patient group with below average well-being from those with an above average well-being. Male gender, poor premorbid adjustment, poor compliance to treatment, poor cognitive functioning, and greater duration of untreated psychosis were found to be associated with a poorer socio-occupational functioning. Conclusion: Clinical interventions focusing on improving cognitive impairment and compliance to treatment could play a role in improving well-being, and socio-occupational functioning in schizophrenia patients following an acute exacerbation. PMID:26702175

  18. Diarrhoea Complicating Severe Acute Malnutrition in Kenyan Children: A Prospective Descriptive Study of Risk Factors and Outcome

    PubMed Central

    Talbert, Alison; Thuo, Nahashon; Karisa, Japhet; Chesaro, Charles; Ohuma, Eric; Ignas, James; Berkley, James A.; Toromo, Christopher; Atkinson, Sarah; Maitland, Kathryn

    2012-01-01

    Background Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. Methods A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (≥3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. Results At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Χ2 = 17.6 p<0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Χ2 = 16.6 p<0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference <10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p<0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Χ2 = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. Conclusion Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting. PMID:22675542

  19. Myeloid Differentiation Factor 88–Dependent Signaling Is Critical for Acute Organic Dust–Induced Airway Inflammation in Mice

    PubMed Central

    Bauer, Christopher; Kielian, Tammy; Wyatt, Todd A.; Romberger, Debra J.; West, William W.; Gleason, Angela M.

    2013-01-01

    Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust–induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-α, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule–1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust–induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by

  20. Conventional Risk Factors and Acute Coronary Syndrome during a Period of Socioeconomic Transition: Population-based Case-control Study in Tirana, Albania

    PubMed Central

    Burazeri, Genc; Goda, Artan; Sulo, Gerhard; Stefa, Jonida; Roshi, Enver; Kark, Jeremy D.

    2007-01-01

    Aim To assess the association between conventional risk factors and acute coronary syndrome in Albania, a transitional country in Southeast Europe. Methods A population-based case-control study was conducted in Tirana in 2003-2006. A total of 467 consecutive patients with nonfatal acute coronary syndrome were recruited. There were 370 men with mean ± standard deviation (SD) age of 59.1 ± 8.7 years and 97 women with mean±SD age of 63.3 ± 7.1 years. The control group comprised a population-representative sample of Tirana residents. In the control group, there were 469 men with mean±SD age of 53.1 ± 10.4 years and 268 women aged 54.0 ± 10.9 years. A structured questionnaire on demographic, socioeconomic, psychosocial factors, and health behaviors was administered. Physical measurements included anthropometrics and blood pressure. Venous blood and adipose tissue aspirations from the gluteal region were frozen-stored for future analysis. Multivariable-adjusted logistic regression was used to assess the independent associations of conventional risk factors with acute coronary syndrome. Results Upon adjustment for covariates, family history of coronary heart disease was found to be a strong predictor of acute coronary syndrome in both men (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.58-5.30) and women (OR, 4.53; 2.40-8.57). Waist-to-hip ratio in men (OR, 4.03; 2.83-5.73) and obesity in women (OR, 3.31; 1.54-7.14) were strongly associated with acute coronary syndrome. In men, but not in women, there was a significant association with hypertension and current smoking (P = 0.011 and P<0.001, respectively). Diabetes was not significantly independently associated in either sex. Conclusion Classical risk factors predicted coronary heart disease in Albania, similarly as in the rest of the world, although associations with family history and anthropometric indices were stronger. These findings are resulting largely from the heterogeneous

  1. Modulation of gastrin and epidermal growth factor by pyrrolizidine alkaloids obtained from Senecio brasiliensis in acute and chronic induced gastric ulcers.

    PubMed

    Toma, Walber; Trigo, José Roberto; Bensuaski de Paula, Ana Cláudia; Monteiro Souza Brito, Alba Regina

    2004-05-01

    We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis. The PA extract demonstrated significantly activity in both, acute and chronic gastric ulcers on rats. The effects of PA extract were dose dependent. The mechanisms implicated on this activity were evaluated by determination of gastrin plasma levels in rats subjected to the acute treatment with PA extract and by expression of mRNA of Epidermal Growth Factor (EGF) after chronic treatment with this extract. The results showed that the PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF. PMID:15213731

  2. Overexpression of a peach cbf-transcription factor gene in apple regulates both dormancy and freezing tolerance in apple

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Economic production of fruit trees in a temperate climate is dependent upon seasonal changes in cold acclimation and dormancy. Evidence indicates that these processes will be greatly affected by climate change (higher atmospheric carbon dioxide and temperatures). This problem may also be exacerbat...

  3. Enhanced cortisol increase upon awakening is associated with greater pain ratings but not salivary cortisol or soluble tumor necrosis factor-α receptor II responses to acute pain

    PubMed Central

    Goodin, Burel R.; Quinn, Noel B.; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

    2011-01-01

    Objectives The cortisol awakening response (CAR) is related with psychosocial factors and health in potentially significant ways, suggesting that it may be a distinctive marker of hypothalamic-pituitary-adrenal (HPA) axis function and dysfunction. This sought to expand upon previous work that examined the association between CAR and ratings of laboratory-evoked acute pain stimulation. In addition to evoked pain ratings, this study also tested whether CAR was prospectively related with salivary cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses to acute pain stimulation. Methods This study included 36 healthy, pain-free volunteers of both sexes recruited via posted study flyers. Prior to completion of laboratory pain testing, salivary cortisol samples were obtained at home over the course of a single morning according to the following time frame: upon awakening, and 15, 30, and 60 min after awakening. Following collection of saliva, study participants brought their home saliva samples to the laboratory for assay and subsequently completed acute experimental pain testing procedures. Results Cluster analysis of CAR revealed two distinct groups with similar patterns of cortisol response to awakening; increased and flattened. Relative to flattened CAR, increased CAR was associated with greater ratings of pain intensity and unpleasantness. Salivary cortisol was significantly increased and sTNFαRII significantly decreased following pain testing, but neither of these responses differed as a function of increased versus flattened CAR. Discussion CAR may be a marker for stress sensitivity and/or the anticipation of impending stress, which could explain why the increased CAR cohort reported greater acute pain ratings. PMID:21904196

  4. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  5. Evaluation of the survival of bone marrow-derived mononuclear cells and the growth factors<