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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 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

  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

    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

  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 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.

  13. 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

  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. 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

  2. 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

  3. 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

  4. 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.

  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. 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.

  13. 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

  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. 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

  17. 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

  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. 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

  10. 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

  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. 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

  13. 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

  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. 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

  3. 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

  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. 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

  7. 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

  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 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

  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

    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. [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

  1. 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

  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. 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

  13. 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

  14. 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.

  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. 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

  17. 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

  18. 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

  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. 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

  8. 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

  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. 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

  16. 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

  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. 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

  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 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

  4. 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

  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. 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

  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. 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

  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. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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. ...

  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. 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

  17. 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

  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. 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

  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. 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

  4. 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

  5. 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

  6. 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

  7. [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

  8. 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

  9. [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

  10. 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

  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. 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

  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. 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

  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. 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

  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. 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

  7. 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

  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. 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

  10. 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

  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. 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…

  13. 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

  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. [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

  16. 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

  17. 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

  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

    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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  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