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Sample records for factor cbf acute

  1. Core binding factor acute myeloid leukemia (CBF-AML) in México: a single institution experience.

    PubMed

    Ruiz-Delgado, Guillermo J; Macías-Gallardo, Julio; Lutz-Presno, Julia; Garcés-Eisele, Javier; Hernández-Arizpe, Ana; Montes-Montiel, Maryel; Ruiz-Argüelles, Guillermo J

    2011-01-01

    Twenty one patients with CBF-AML presented prospectively in the Centro de Hematología y Medicina Interna de Puebla (Puebla, México) between February 1995 and March 2010, 14 with the t(8;21)(q22;q22) and 7 with the inv(16)(p13;q22)/t(16;16)(p13;q22); they represent 13% of all cases of AML. The median age of the patients was 24 years (range 1 to 61). Seven of 14 patients with t(8;21)(q22;q22) had an M2 morphology whereas 3/7 with the inv(16) had an M4 morphology; in addition to the myeloid markers identified by flow-cytometry (surface CD13, surface CD33, and cytoplasmic myeloperoxidase) lymphoid markers were identified in the blast cells of 8/14 cases of the t(8;21) patients, but in no patient with the inv(16). Nineteen patients were treated with combined chemotherapy and 16 (84%) achieved a complete molecular remission. Seven patients were auto or allografted. Relapses presented in 10/16 patients. The median probability of overall survival (OS) has not been reached being above 165 months, whereas the 165-month probability of OS and leukemia-free survival was 52%; despite a tendency for a better outcome of patients with the t(8;21), there were no significant differences in survival of patients with either the t(8;21) or the inv(16). In this single institution experience in México, we found that the CBF variants of AML have a similar prevalence as compared with Caucasian populations, that the co-expression of lymphoid markers in the blast cells was frequent in the t(8;21) and that these two AML subtypes were associated with a relatively good long-term prognosis. Further studies are needed to describe with more detail the precise biological features of these molecular subtypes of acute leukemia.

  2. High prognostic value of minimal residual disease detected by flow-cytometry-enhanced fluorescence in situ hybridization in core-binding factor acute myeloid leukemia (CBF-AML).

    PubMed

    Wang, Libing; Gao, Lei; Xu, Sheng; Gong, Shenglan; Liu, Min; Qiu, Huiying; Xu, Xiaoqian; Ni, Xiong; Chen, Li; Lu, Shuqing; Chen, Jie; Song, Xianmin; Zhang, Weiping; Yang, Jianmin; Hu, Xiaoxia; Wang, Jianmin

    2014-10-01

    Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.

  3. Acute marijuana effects on rCBF and cognition: a PET study.

    PubMed

    O'Leary, D S; Block, R I; Flaum, M; Schultz, S K; Boles Ponto, L L; Watkins, G L; Hurtig, R R; Andreasen, N C; Hichwa, R D

    2000-11-27

    The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

  4. 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 ...

  5. 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.

  6. 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

  7. Involvement of CBF Transcription Factors in Winter Hardiness in Birch1[W][OA

    PubMed Central

    Welling, Annikki; Palva, E. Tapio

    2008-01-01

    Cold acclimation of plants involves extensive reprogramming of gene expression. In Arabidopsis (Arabidopsis thaliana), three cold-inducible transcriptional activators designated CBF1 to -3/DREB1a to -c have been shown to play an important regulatory role in this acclimation process. Similarly to Arabidopsis, boreal zone trees can increase their freezing tolerance (FT) in response to low temperature during the growing season. However, maximal FT of these trees requires short daylength-induced dormancy development followed by exposure to both low and freezing temperatures. To elucidate the molecular basis of FT in overwintering trees, we characterized the role of birch (Betula pendula) CBF transcription factors in the cold acclimation process. We identified four putative CBF orthologs in a birch expressed sequence tag collection designated BpCBF1 to -4. Ectopic expression of birch CBFs in Arabidopsis resulted in constitutive expression of endogenous CBF target genes and increased FT of nonacclimated transgenic plants. In addition, these plants showed stunted growth and delayed flowering, typical features for CBF-overexpressing plants. Expression analysis in birch showed that BpCBF1 to -4 are low temperature responsive but differentially regulated in dormant and growing plants, the expression being delayed in dormant tissues. Freeze-thaw treatment, simulating wintertime conditions in nature, resulted in strong induction of BpCBF genes during thawing, followed by induction of a CBF target gene, BpLTI36. These results suggest that in addition to their role in cold acclimation during the growing season, birch CBFs appear to contribute to control of winter hardiness in birch. PMID:18467468

  8. 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

  9. 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

  10. Characterization and expression analysis of three CBF/DREB1 transcriptional factor genes from mangrove Avicennia marina.

    PubMed

    Peng, Ya-Lan; Wang, You-Shao; Cheng, Hao; Sun, Cui-Ci; Wu, Peng; Wang, Li-Ying; Fei, Jiao

    2013-09-15

    Three CBF/DREB1 (C-repeat binding factor/dehydration responsive element-binding factor 1) homologues were isolated from mangrove Avicennia marina and designated AmCBF1, 2 and 3. Multiple sequence analysis showed that the three deduced proteins all contain an AP2 DNA-binding domain and two CBF signature sequences. According to the phylogenetic analysis, these proteins belong to the A-1 subgroup of the DREB subfamily. Expression analyses based on quantitative real-time PCR revealed that the AmCBF2 displayed relatively high expression under normal conditions, with the highest level in stems, while both AmCBF1 and 3 were weakly expressed without stress. The three genes also showed different responses to various environmental stimuli. The AmCBF2 was inducible by cold, drought, high salinity, heavy metals, as well as abscisic acid (ABA), and exhibited much stronger induction by cold, drought, Pb(2+) or Zn(2+) than by NaCl, ABA or Cd(2+). In contrast, both AmCBF1 and AmCBF3 displayed insignificant changes under these stimuli. These results indicate that the three AmCBF genes play different roles in A. marina and the AmCBF2 might be involved in the signaling pathway of cold, drought and heavy metal stress response.

  11. Characterization and expression analysis of a gene encoding CBF/DREB1 transcription factor from mangrove Aegiceras corniculatum.

    PubMed

    Peng, Ya-Lan; Wang, You-Shao; Cheng, Hao; Wang, Li-Ying

    2015-10-01

    Several transcription factors play important roles in survival of plants under cold, drought and salt stresses by serving as master regulator of sets of downstream stress-responsive genes. A gene encoding CBF/DREB1 transcription factor (C-repeat binding factor/dehydration responsive element-binding factor 1) was isolated from mangrove Aegiceras corniculatum and designated AcCBF1. The full-length cDNA of AcCBF1 was 896 bp containing 618 bp ORF encoding a protein of 205 amino acids. Multiple sequence analysis showed that the corresponding protein had 100 % identity to AmCBF1 (KC776908) from mangrove Avicennia marina, and contains an AP2/ERE DNA-binding domain and two CBF signature sequences. Expression analyses based on quantitative real-time PCR revealed that the AcCBF1 gene was expressed in all tissues of A. corniculatum under normal condition with the highest expression level detected in leaves. When exposed to abiotic stresses, AcCBF1 gene showed different expression patterns in different tissues. Generally, AcCBF1 gene could be rapidly and strongly induced by cold and drought, while slightly induced by abscisic acid and salinity. Furthermore, light could positively regulate the cold-induction level of AcCBF1. These results suggest that the AcCBF1 may be playing important role in the signaling pathway of cold stress and also involved in the cross-talk among abiotic stresses. Further studies focusing on the promotors and downstream stress-responsive genes of AcCBF1 will help to better understand the regulatory mechanisms of mangrove A. corniculatum under abiotic stresses. PMID:25976917

  12. Characterization and expression analysis of a gene encoding CBF/DREB1 transcription factor from mangrove Aegiceras corniculatum.

    PubMed

    Peng, Ya-Lan; Wang, You-Shao; Cheng, Hao; Wang, Li-Ying

    2015-10-01

    Several transcription factors play important roles in survival of plants under cold, drought and salt stresses by serving as master regulator of sets of downstream stress-responsive genes. A gene encoding CBF/DREB1 transcription factor (C-repeat binding factor/dehydration responsive element-binding factor 1) was isolated from mangrove Aegiceras corniculatum and designated AcCBF1. The full-length cDNA of AcCBF1 was 896 bp containing 618 bp ORF encoding a protein of 205 amino acids. Multiple sequence analysis showed that the corresponding protein had 100 % identity to AmCBF1 (KC776908) from mangrove Avicennia marina, and contains an AP2/ERE DNA-binding domain and two CBF signature sequences. Expression analyses based on quantitative real-time PCR revealed that the AcCBF1 gene was expressed in all tissues of A. corniculatum under normal condition with the highest expression level detected in leaves. When exposed to abiotic stresses, AcCBF1 gene showed different expression patterns in different tissues. Generally, AcCBF1 gene could be rapidly and strongly induced by cold and drought, while slightly induced by abscisic acid and salinity. Furthermore, light could positively regulate the cold-induction level of AcCBF1. These results suggest that the AcCBF1 may be playing important role in the signaling pathway of cold stress and also involved in the cross-talk among abiotic stresses. Further studies focusing on the promotors and downstream stress-responsive genes of AcCBF1 will help to better understand the regulatory mechanisms of mangrove A. corniculatum under abiotic stresses.

  13. 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

  14. Arabidopsis CBF1 and CBF3 have a different function than CBF2 in cold acclimation and define different gene classes in the CBF regulon

    PubMed Central

    Novillo, Fernando; Medina, Joaquín; Salinas, Julio

    2007-01-01

    The C-repeat-binding factor (CBF)/dehydration-responsive element-binding factor (DREB1) proteins constitute a small family of Arabidopsis transcriptional activators (CBF1/DREB1B, CBF2/DREB1C, and CBF3/DREB1A) that play a prominent role in cold acclimation. A fundamental question about these factors that remains to be answered is whether they are functionally equivalent. Recently, we reported that CBF2 negatively regulates CBF1 and CBF3 expression, and that CBFs are subjected to different temporal regulation during cold acclimation, which suggested this might not be the case. In this study, we have analyzed the expression of CBF genes in different tissues of Arabidopsis, during development and in response to low temperature, and characterized RNA interference (RNAi) and antisense lines that fail to accumulate CBF1 or/and CBF3 mRNAs under cold conditions. We found that CBF1 and CBF3 are regulated in a different way than CBF2. Moreover, in contrast to CBF2, CBF1 and CBF3 are not involved in regulating other CBF genes and positively regulate cold acclimation by activating the same subset of CBF-target genes. All these results demonstrate that CBF1 and CBF3 have different functions than CBF2. We also found that the CBF regulon is composed of at least two different kind of genes, one of them requiring the simultaneous expression of both CBF1 and CBF3 to be properly induced. This indicates that CBF1 and CBF3 have a concerted additive effect to induce the whole CBF regulon and the complete development of cold acclimation. PMID:18093929

  15. Ectopic overexpression of SsCBF1, a CRT/DRE-binding factor from the nightshade plant Solanum lycopersicoides, confers freezing and salt tolerance in transgenic Arabidopsis.

    PubMed

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

    2014-01-01

    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 (SsCBF1(193-228)). 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.

  16. 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

  17. The yeast nucleolar protein Cbf5p is involved in rRNA biosynthesis and interacts genetically with the RNA polymerase I transcription factor RRN3.

    PubMed Central

    Cadwell, C; Yoon, H J; Zebarjadian, Y; Carbon, J

    1997-01-01

    Yeast Cbf5p was originally isolated as a low-affinity centromeric DNA binding protein (W. Jiang, K. Middleton, H.-J. Yoon, C. Fouquet, and J. Carbon, Mol. Cell. Biol. 13:4884-4893, 1993). Cbf5p also binds microtubules in vitro and interacts genetically with two known centromere-related protein genes (NDC10/CBF2 and MCK1). However, Cbf5p was found to be nucleolar and is highly homologous to the rat nucleolar protein NAP57, which coimmunoprecipitates with Nopp140 and which is postulated to be involved in nucleolar-cytoplasmic shuttling (U. T. Meier, and G. Blobel, J. Cell Biol. 127:1505-1514, 1994). The temperature-sensitive cbf5-1 mutant demonstrates a pronounced defect in rRNA biosynthesis at restrictive temperatures, while tRNA transcription and pre-rRNA and pre-tRNA cleavage processing appear normal. The cbf5-1 mutant cells are deficient in cytoplasmic ribosomal subunits at both permissive and restrictive temperatures. A high-copy-number yeast genomic library was screened for genes that suppress the cbf5-1 temperature-sensitive growth phenotype. SYC1 (suppressor of yeast cbf5-1) was identified as a multicopy suppressor of cbf5-1 and subsequently was found to be identical to RRN3, an RNA polymerase I transcription factor. A cbf5delta null mutant is not rescued by plasmid pNOY103 containing a yeast 35S rRNA gene under the control of a Pol II promoter, indicating that Cbf5p has one or more essential functions in addition to its role in rRNA transcription. PMID:9315678

  18. 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

  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. A C-Repeat Binding Factor Transcriptional Activator (CBF/DREB1) from European Bilberry (Vaccinium myrtillus) Induces Freezing Tolerance When Expressed in Arabidopsis thaliana

    PubMed Central

    Oakenfull, Rachael J.; Baxter, Robert; Knight, Marc R.

    2013-01-01

    Freezing stress affects all plants from temperate zones to the poles. Global climate change means such freezing events are becoming less predictable. This in turn reduces the ability of plants to predict the approaching low temperatures and cold acclimate. This has consequences for crop yields and distribution of wild plant species. C-repeat binding factors (CBFs) are transcription factors previously shown to play a vital role in the acclimation process of Arabidopsis thaliana, controlling the expression of hundreds of genes whose products are necessary for freezing tolerance. Work in other plant species cements CBFs as key determinants in the trait of freezing tolerance in higher plants. To test the function of CBFs from highly freezing tolerant plants species we cloned and sequenced CBF transcription factors from three Vaccinium species (Vaccinium myrtillus, Vaccinium uliginosum and Vaccinium vitis-idaea) which we collected in the Arctic. We tested the activity of CBF transcription factors from the three Vaccinium species by producing transgenic Arabidopsis lines overexpressing them. Only the Vaccinium myrtillus CBF was able to substantially activate COR (CBF-target) gene expression in the absence of cold. Correspondingly, only the lines expressing the Vaccinium myrtillus CBF were constitutively freezing tolerant. The basis for the differences in potency of the three Vaccinium CBFs was tested by observing cellular localisation and protein levels. All three CBFs were correctly targeted to the nucleus, but Vaccinium uliginosum CBF appeared to be relatively unstable. The reasons for lack of potency for Vaccinium vitis-idaea CBF were not due to stability or targeting, and we speculate that this was due to altered transcription factor function. PMID:23349799

  1. Ectopic expression of a novel peach (Prunus persica) CBF transcription factor in apple (Malus × domestica) results in short-day induced dormancy and increased cold hardiness.

    PubMed

    Wisniewski, Michael; Norelli, John; Bassett, Carole; Artlip, Timothy; Macarisin, Dumitru

    2011-05-01

    Low, non-freezing temperatures and/or short daylength (SD) regulates cold acclimation and dormancy in fruit trees. Regarding cold acclimation, C-repeat binding factor (CBF/DREB) transcriptional activator genes have the well-documented ability to induce the expression of a suite of genes associated with increased cold tolerance. We isolated a full-length cDNA of a peach CBF gene, designated PpCBF1 (GenBank Accession HM992943), and constitutively expressed it using an enhanced 35S promoter in apple. Unexpectedly, constitutive overexpression of the PpCBF1 in apple resulted in strong sensitivity to short daylength. Growth cessation and leaf senescence were induced in transgenic lines exposed to SD and optimal growth temperatures of 25°C over a 4-week period. Following 1-4 weeks of SD and 25°C trees were returned to LD and 25°C in the greenhouse. Control (untransformed) plants continued to grow while transgenic lines receiving two or more weeks of SD remained dormant and began to drop leaves. Constitutive overexpression of the PpCBF1 in apple resulted in a 4-6°C increase in freezing tolerance in both the non-acclimated and acclimated states, respectively, compared with untransformed M.26 trees. This is the first instance that constitutive overexpression of a CBF gene has resulted in SD-induction of dormancy and to our knowledge the first time apple has been shown to strongly respond to short daylength as a result of the insertion of a transgene.

  2. Ectopic expression of a novel peach (Prunus persica) CBF transcription factor in apple (Malus × domestica) results in short-day induced dormancy and increased cold hardiness.

    PubMed

    Wisniewski, Michael; Norelli, John; Bassett, Carole; Artlip, Timothy; Macarisin, Dumitru

    2011-05-01

    Low, non-freezing temperatures and/or short daylength (SD) regulates cold acclimation and dormancy in fruit trees. Regarding cold acclimation, C-repeat binding factor (CBF/DREB) transcriptional activator genes have the well-documented ability to induce the expression of a suite of genes associated with increased cold tolerance. We isolated a full-length cDNA of a peach CBF gene, designated PpCBF1 (GenBank Accession HM992943), and constitutively expressed it using an enhanced 35S promoter in apple. Unexpectedly, constitutive overexpression of the PpCBF1 in apple resulted in strong sensitivity to short daylength. Growth cessation and leaf senescence were induced in transgenic lines exposed to SD and optimal growth temperatures of 25°C over a 4-week period. Following 1-4 weeks of SD and 25°C trees were returned to LD and 25°C in the greenhouse. Control (untransformed) plants continued to grow while transgenic lines receiving two or more weeks of SD remained dormant and began to drop leaves. Constitutive overexpression of the PpCBF1 in apple resulted in a 4-6°C increase in freezing tolerance in both the non-acclimated and acclimated states, respectively, compared with untransformed M.26 trees. This is the first instance that constitutive overexpression of a CBF gene has resulted in SD-induction of dormancy and to our knowledge the first time apple has been shown to strongly respond to short daylength as a result of the insertion of a transgene. PMID:21274560

  3. 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

  4. Core binding factor beta (Cbfβ) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation.

    PubMed

    Tian, Fei; Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Ma, Junqing; Gao, Bo; Wang, Lin; Li, Yi-Ping; Chen, Wei

    2014-07-01

    Core binding factor beta (Cbfβ) is essential for embryonic bone morphogenesis. Yet the mechanisms by which Cbfβ regulates chondrocyte proliferation and differentiation as well as postnatal cartilage and bone formation remain unclear. Hence, using paired-related homeobox transcription factor 1-Cre (Prx1-Cre) mice, mesenchymal stem cell-specific Cbfβ-deficient (Cbfβ(f/f) Prx1-Cre) mice were generated to study the role of Cbfβ in postnatal cartilage and bone development. These mutant mice survived to adulthood but exhibited severe sternum and limb malformations. Sternum ossification was largely delayed in the Cbfβ(f/f) Prx1-Cre mice and the xiphoid process was noncalcified and enlarged. In newborn and 7-day-old Cbfβ(f/f) Prx1-Cre mice, the resting zone was dramatically elongated, the proliferation zone and hypertrophic zone of the growth plates were drastically shortened and disorganized, and trabecular bone formation was reduced. Moreover, in 1-month-old Cbfβ(f/f) Prx1-Cre mice, the growth plates were severely deformed and trabecular bone was almost absent. In addition, Cbfβ deficiency impaired intramembranous bone formation both in vivo and in vitro. Interestingly, although the expression of Indian hedgehog (Ihh) was largely reduced, the expression of parathyroid hormone-related protein (PTHrP) receptor (PPR) was dramatically increased in the Cbfβ(f/f) Prx1-Cre growth plate, indicating that that Cbfβ deficiency disrupted the Ihh-PTHrP negative regulatory loop. Chromatin immunoprecipitation (ChIP) analysis and promoter luciferase assay demonstrated that the Runx/Cbfβ complex binds putative Runx-binding sites of the Ihh promoter regions, and also the Runx/Cbfβ complex directly upregulates Ihh expression at the transcriptional level. Consistently, the expressions of Ihh target genes, including CyclinD1, Ptc, and Pthlh, were downregulated in Cbfβ-deficient chondrocytes. Taken together, our study reveals not only that Cbfβ is essential for chondrocyte

  5. Regulatory interrelations among topographic molecules CBF1, CBF2 and EphA3 in the developing chick retina.

    PubMed

    Yamagata, M; Mai, A; Pollerberg, G E; Noda, M

    1999-10-01

    It has been shown that topographic expression of two winged-helix transcription factors, CBF1/c-qin and CBF2, and a receptor tyrosine kinase EphA3 (Mek4/Cek4) play important roles in establishing the topographic retinotectal projection map along the rostrocaudal axis. The interrelationship among these topographic molecules in the chick retina was studied during development. The topographic expression of CBF1 and CBF2 preluded the graded expression of EphA3, but their precise expression profiles did not exactly fit together. However, interestingly, CBF1 and CBF2 were properly expressed, together with EphA3, in immortalized cell lines derived from the quail retina, which maintained position-specific characteristics. The expression of another topographic molecule SOHo-1, the sensory organ homeobox-1 transcription factor, was separate from EphA3 expression. Ectopic expression of CBF1 using in ovo electroporation repressed the expression of CBF2, and misexpression of CBF2 influenced the graded localization of EphA3 in the retina, albeit imperfectly. Taken together, it is suggested that retinal cells first begin to express CBF1 or CBF2 according to their topographic positions, generate cellular descendants in which the expression of CBF1 and CBF2 is maintained cell-autonomously, and then establish the nasotemporal gradient of EphA3 under the control of CBF2, although indirect.

  6. 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

  7. 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

  8. Involvement of a common progenitor cell in core binding factor acute myeloid leukaemia associated with mastocytosis.

    PubMed

    Cornet, Edouard; Dumézy, Florent; Roumier, Christophe; Lepelley, Pascale; Jouy, Nathalie; Philippe, Nathalie; Renneville, Aline; Berthon, Céline; Nelken, Brigitte; Quesnel, Bruno; Preudhomme, Claude

    2012-11-01

    In core binding factor (CBF) acute myeloid leukaemia (AML), realtime quantitative PCR is useful to quantify the fusion transcript ratio (CBFβ-MYH11 and AML1-ETO, in case of inv(16) and t(8;21) respectively) in peripheral blood and bone marrow during the courses of chemotherapy, in order to monitor minimal residual disease (MRD). In two cases of CBF AML associated with systemic mastocytosis (SM), the persistence of mast cells and the detection of a high ratio of fusion transcript, in bone marrow, during the courses of chemotherapy, led us to determine whether the mast cell component of the disease carried the same molecular alterations as leukaemic blasts. We demonstrate that sorted mast cells carried CBF abnormality. These observations point out the lack of specificity of MRD monitoring by RQ-PCR in these exceptional AML cases with SM. Moreover, this suggests that leukaemic blasts and mast cells derive from a common malignant progenitor.

  9. 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).

  10. CBF2/DREB1C is a negative regulator of CBF1/DREB1B and CBF3/DREB1A expression and plays a central role in stress tolerance in Arabidopsis

    PubMed Central

    Novillo, Fernando; Alonso, José M.; Ecker, Joseph R.; Salinas, Julio

    2004-01-01

    CBF/DREB1 (C-repeat-binding factor/dehydration responsive element-binding factor 1) genes encode a small family of transcriptional activators that have been described as playing an important role in freezing tolerance and cold acclimation in Arabidopsis. To specify this role, we used a reverse genetic approach and identified a mutant, cbf2, in which the CBF2/DREB1C gene was disrupted. Here, we show that cbf2 plants have higher capacity to tolerate freezing than WT ones before and after cold acclimation and are more tolerant to dehydration and salt stress. All these phenotypes correlate with a stronger and more sustained expression of CBF/DREB1-regulated genes, which results from an increased expression of CBF1/DREB1B and CBF3/DREB1A in the mutant. In addition, we show that the expression of CBF1/DREB1B and CBF3/DREB1A in response to low temperature precedes that of CBF2/DREB1C. These results indicate that CBF2/DREB1C negatively regulates CBF1/DREB1B and CBF3/DREB1A, ensuring that their expression is transient and tightly controlled, which, in turn, guarantees the proper induction of downstream genes and the accurate development of Arabidopsis tolerance to freezing and related stresses. PMID:15004278

  11. Using an apple microarray to characterize the CBF-regulon in transgenic 'M.26' apple trees overexpressing a peach CBF gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CBF proteins belong to the CBF/DRE binding sub-family of the Apetala2-ethylene responsive factor (AP2/ERF) super family of transcription factors that bind to a cis-element containing a conserved CCGA core sequence. CBF genes have been shown to regulate a large number of cold-regulated genes that ar...

  12. 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) ...

  13. 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

  14. 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...

  15. 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.

  16. Cbfβ deletion in mice recapitulates cleidocranial dysplasia and reveals multiple functions of Cbfβ required for skeletal development

    PubMed Central

    Chen, Wei; Ma, Junqing; Zhu, Guochun; Jules, Joel; Wu, Mengrui; McConnell, Matthew; Tian, Fei; Paulson, Christie; Zhou, Xuedong; Wang, Lin; Li, Yi-Ping

    2014-01-01

    The pathogenesis of cleidocranial dysplasia (CCD) as well as the specific role of core binding factor β (Cbfβ) and the Runt-related transcription factor (RUNX)/Cbfβ complex in postnatal skeletogenesis remain unclear. We demonstrate that Cbfβ ablation in osteoblast precursors, differentiating chondrocytes, osteoblasts, and odontoblasts via Osterix-Cre, results in severe craniofacial dysplasia, skeletal dysplasia, abnormal teeth, and a phenotype recapitulating the clinical features of CCD. Cbfβf/fOsterix-Cre mice have fewer proliferative and hypertrophic chondrocytes, fewer osteoblasts, and almost absent trabecular bone, indicating that Cbfβ may maintain trabecular bone formation through its function in hypertrophic chondrocytes and osteoblasts. Cbfβf/fCollagen, type 1, alpha 1 (Col1α1)–Cre mice show decreased bone mineralization and skeletal deformities, but no radical deformities in teeth, mandibles, or cartilage, indicating that osteoblast lineage-specific ablation of Cbfβ results in milder bone defects and less resemblance to CCD. Activating transcription factor 4 (Atf4) and Osterix protein levels in both mutant mice are dramatically reduced. ChIP assays show that Cbfβ directly associates with the promoter regions of Atf4 and Osterix. Our data further demonstrate that Cbfβ highly up-regulates the expression of Atf4 at the transcriptional regulation level. Overall, our genetic dissection approach revealed that Cbfβ plays an indispensable role in postnatal skeletal development and homeostasis in various skeletal cell types, at least partially by up-regulating the expression of Atf4 and Osterix. It also revealed that CCD may result from functional defects of the Runx2/Cbfβ heterodimeric complex in various skeletal cells. These insights into the role of Cbfβ in postnatal skeletogenesis and CCD pathogenesis may assist in the development of new therapies for CCD and osteoporosis. PMID:24850862

  17. [Analysis of codon use features of CBF gene in Camellia sinensis].

    PubMed

    Guo, Xiu-Li; Wang, Yu; Yang, Lu-Cheng; Ding, Zhao-Tang

    2012-12-01

    CBF (C-repeat-binding factor) transcription factor exists widely in all kinds of plants. It is an important regulative factor in the process of plant resistance adversity. In this paper, Camellia sinensis CBF1 gene sequence was analyzed by Codon W, CHIPS, and CUSP programs online, and then compared with C. sinensis genes, genomes in other species, and CBF genes from 39 plant species. It is important to identify the codon usage of CsCBF1 gene and select appropriate expression systems. The results showed that CsCBF1 gene and selected 70 C. sinensis genes had distinct usage differences. CsCBF1 gene was bias toward the synonymous codons with G and C at the third codon position, but 70 C. sinensis genes were bias toward the synonymous codons with A and T. The differences in codon usage frequency between CsCBF1 gene and dicotyledons such as Arabidopsis thaliana and Nicotiana tobacum were less than monocotyledons such as wheat (Triticum aestivum) and corn (Zea mays). Therefore, A. thaliana and N. tobacum expression systems may be more suitable for the expression of CsCBF1 gene. The analysis results of CBF genes from 40 plant species also showed that most of the CBF genes were bias toward the synonymous codons with G and C at the third codon position. The reason of this phenomenon is possible due to special functions of these genes.

  18. 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.

  19. 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

  20. The cold response of CBF genes in barley is regulated by distinct signaling mechanisms.

    PubMed

    Marozsán-Tóth, Zsuzsa; Vashegyi, Ildikó; Galiba, Gábor; Tóth, Balázs

    2015-06-01

    Cold acclimation ability is crucial in the winter survival of cereals. In this process CBF transcription factors play key role, therefore understanding the regulation of these genes might provide useful knowledge for molecular breeding. In the present study the signal transduction pathways leading to the cold induction of different CBF genes were investigated in barley cv. Nure using pharmacological approach. Our results showed that the cold induced expression of CBF9 and CBF14 transcription factors is regulated by phospholipase C, phospholipase D pathways and calcium. On the contrary, these pathways have negative effect on the cold induction of CBF12 that is regulated by a different, as yet unidentified pathway. The diversity in the regulation of these transcription factors corresponds to their sequence based phylogenetic relationships suggesting that their evolutionary separation happened on structural, functional and regulational levels as well. On the CBF effector gene level, the signaling regulation is more complex, resultant effect of multiple pathways.

  1. [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

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

    PubMed

    Chen, Wenlan; Xie, Hui; 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

  5. 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

  6. The cbfs triple mutants reveal the essential functions of CBFs in cold acclimation and allow the definition of CBF regulons in Arabidopsis.

    PubMed

    Jia, Yuxin; Ding, Yanglin; Shi, Yiting; Zhang, Xiaoyan; Gong, Zhizhong; Yang, Shuhua

    2016-10-01

    In Arabidopsis, the C-repeat binding factors (CBFs) have been extensively studied as key transcription factors in the cold stress response. However, their exact functions in the cold response remains unclear due to the lack of a null cbf triple mutant. In this study, we used CRISPR/Cas9 technology to mutate CBF1 or CBF1/CBF2 in a cbf3 T-DNA insertion mutant to generate cbf1,3 double and cbf1 cbf2 cbf3 (cbfs) triple mutants. The response of the cbfs triple mutants to chilling stress is impaired. Furthermore, no significant difference in freezing tolerance was observed between the wild-type and the cbf1,3 and cbfs mutants without cold acclimation. However, the cbfs mutants were extremely sensitive to freezing stress after cold acclimation, and freezing sensitivity ranking was cbfs > cbf1,3 > cbf3. RNA-Seq analysis showed that 134 genes were CBF regulated, of which 112 were regulated positively and 22 negatively by CBFs. Our study reveals the essential functions of CBFs in chilling stress response and cold acclimation, as well as defines a set of genes as CBF regulon. It also provides materials for the genetic dissection of components in CBF-dependent cold signaling. PMID:27353960

  7. 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.

  8. 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.

  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. 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.

  12. Transcriptional regulation of APOBEC3 antiviral immunity through the CBF-β/RUNX axis

    PubMed Central

    Anderson, Brett D.; Harris, Reuben S.

    2015-01-01

    A diverse set of innate immune mechanisms protects cells from viral infections. The APOBEC3 family of DNA cytosine deaminases is an integral part of these defenses. For instance, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H would have the potential to destroy HIV-1 complementary DNA replication intermediates if not for neutralization by a proteasomal degradation mechanism directed by the viral protein Vif. At the core of this complex, Vif heterodimerizes with the transcription cofactor CBF-β, which results in fewer transcription complexes between CBF-β and its normal RUNX partners. Recent studies have shown that the Vif/CBF-β interaction is specific to the primate lentiviruses HIV-1 and SIV (simian immunodeficiency virus), although related nonprimate lentiviruses still require a Vif-dependent mechanism for protection from host species’ APOBEC3 enzymes. We provide a molecular explanation for this evolutionary conundrum by showing that CBF-β is required for expression of the aforementioned HIV-1–restrictive APOBEC3 gene repertoire. Knockdown and knockout studies demonstrate that CBF-β is required for APOBEC3 mRNA expression in the nonpermissive T cell line H9 and in primary CD4+ T lymphocytes. Complementation experiments using CBF-β separation-of-function alleles show that the interaction with RUNX transcription factors is required for APOBEC3 transcriptional regulation. Accordingly, the infectivity of Vif-deficient HIV-1 increases in cells lacking CBF-β, demonstrating the importance of CBF-β/RUNX–mediated transcription in establishing the APOBEC3 antiviral state. These findings demonstrate a major layer of APOBEC3 gene regulation in lymphocytes and suggest that primate lentiviruses evolved to hijack CBF-β in order to simultaneously suppress this potent antiviral defense system at both transcriptional and posttranslational levels. PMID:26601257

  13. A novel role for the CBF3 kinetochore–scaffold complex in regulating septin dynamics and cytokinesis

    PubMed Central

    Gillis, Amethyst N.; Thomas, Scott; Hansen, Scott D.; Kaplan, Kenneth B.

    2005-01-01

    In budding yeast, the kinetochore scaffold complex centromere binding factor 3 (CBF3) is required to form kinetochores on centromere DNA and to allow proper chromosome segregation. We have previously shown that SKP1 and SGT1 balance the assembly and turnover of CBF3 complexes, a cycle that we suggest is independent of its role in chromosome segregation (Rodrigo-Brenni, M.C., S. Thomas, D.C. Bouck, and K.B. Kaplan. 2004. Mol. Biol. Cell. 15:3366–3378). We provide evidence that this cycle contributes to a second, kinetochore-independent function of CBF3. In this study, we show that inhibiting the assembly of CBF3 causes disorganized septins and defects in cell polarity that give rise to cytokinesis failures. Specifically, we show that septin ring separation and disassembly is delayed in anaphase, suggesting that CBF3 regulates septin dynamics. Only mutations that affect the CBF3 cycle, and not mutants in outer kinetochore subunits, cause defects in septins. These results demonstrate a novel role for CBF3 in regulating cytokinesis, a role that is reminiscent of passenger proteins. Consistent with this possibility, we find that CBF3 interacts with Bir1p, the homologue of the passenger protein Survivin. Mutants in Bir1p similarly affect septin organization, leading us to propose that CBF3 and Bir1p act as passenger proteins to coordinate chromosome segregation with cytokinesis. PMID:16330709

  14. 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.

  15. 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.

  16. CbCBF from Capsella bursa-pastoris enhances cold tolerance and restrains growth in Nicotiana tabacum by antagonizing with gibberellin and affecting cell cycle signaling.

    PubMed

    Zhou, Mingqi; Xu, Ming; Wu, Lihua; Shen, Chen; Ma, Hong; Lin, Juan

    2014-06-01

    Plant cells respond to cold stress via a regulatory mechanism leading to enhanced cold acclimation accompanied by growth retardation. The C-repeat binding factor (CBF) signaling pathway is essential for cold response of flowering plants. Our previously study documented a novel CBF-like gene from the cold-tolerant Capsella bursa-pastoris named CbCBF, which was responsive to chilling temperatures. Here, we show that CbCBF expression is obviously responsive to chilling, freezing, abscisic acid, gibberellic acid (GA), indoleacetic acid or methyl jasmonate treatments and that the CbCBF:GFP fusion protein was localized to the nucleus. In addition, CbCBF overexpression conferred to the cold-sensitive tobacco plants enhanced tolerance to chilling and freezing, as well as dwarfism and delayed flowering. The leaf cells of CbCBF overexpression tobacco lines attained smaller sizes and underwent delayed cell division with reduced expression of cyclin D genes. The dwarfism of CbCBF transformants can be partially restored by GA application. Consistently, CbCBF overexpression reduced the bioactive gibberellin contents and disturbed the expression of gibberellin metabolic genes in tobacco. Meanwhile, cold induced CbCBF expression and cold tolerance in C. bursa-pastoris are reduced by GA. We conclude that CbCBF confers cold resistance and growth inhibition to tobacco cells by interacting with gibberellin and cell cycle pathways, likely through activation of downstream target genes.

  17. Transgenic barley lines prove the involvement of TaCBF14 and TaCBF15 in the cold acclimation process and in frost tolerance.

    PubMed

    Soltész, Alexandra; Smedley, Mark; Vashegyi, Ildikó; Galiba, Gábor; Harwood, Wendy; Vágújfalvi, Attila

    2013-04-01

    The enhancement of winter hardiness is one of the most important tasks facing breeders of winter cereals. For this reason, the examination of those regulatory genes involved in the cold acclimation processes is of central importance. The aim of the present work was the functional analysis of two wheat CBF transcription factors, namely TaCBF14 and TaCBF15, shown by previous experiments to play a role in the development of frost tolerance. These genes were isolated from winter wheat and then transformed into spring barley, after which the effect of the transgenes on low temperature stress tolerance was examined. Two different types of frost tests were applied; plants were hardened at low temperature before freezing, or plants were subjected to frost without a hardening period. The analysis showed that TaCBF14 and TaCBF15 transgenes improve the frost tolerance to such an extent that the transgenic lines were able to survive freezing temperatures several degrees lower than that which proved lethal for the wild-type spring barley. After freezing, lower ion leakage was measured in transgenic leaves, showing that these plants were less damaged by the frost. Additionally, a higher Fv/Fm parameter was determined, indicating that photosystem II worked more efficiently in the transgenics. Gene expression studies showed that HvCOR14b, HvDHN5, and HvDHN8 genes were up-regulated by TaCBF14 and TaCBF15. Beyond that, transgenic lines exhibited moderate retarded development, slower growth, and minor late flowering compared with the wild type, with enhanced transcript level of the gibberellin catabolic HvGA2ox5 gene.

  18. Heterology expression of the sweet pepper CBF3 gene confers elevated tolerance to chilling stress in transgenic tobacco.

    PubMed

    Yang, Sha; Tang, Xian-Feng; Ma, Na-Na; Wang, Li-Yan; Meng, Qing-Wei

    2011-10-15

    Various studies have confirmed that the CBF (C-repeat binding factor) family of transcription factors has a key role in regulating many plants' responses to cold stress. Here we isolated CBF3 from sweet pepper (Capsicum frutescens). Green fluorescent protein (GFP) fusion protein of CfCBF3 was targeted to the nucleus of the onion epidermis cell. RNA gel blot analysis indicated that CfCBF3 was expressed in leaves of sweet pepper and the expression was induced by low temperature, drought and salinity stresses but not by ABA. Overexpression of CfCBF3 under the control of the CaMV35S promoter in tobacco induced expression of orthologs of CBF3-targeted genes and increased chilling tolerance without a dwarf phenotype. Indeed it also led to multiple biochemical and physiological changes associated with chilling stress. Higher levels of proline (Pro) and soluble sugars and lower content of reactive oxygen species (ROS) were observed in transgenic plants. Our results demonstrated that the increase in total unsaturated fatty acids, especially in phosphatidylglycerol (PG) was detected by overexpression of CfCBF3. During exposure to chilling stress, the transgenic lines were less susceptible to chilling-induced photoinhibition than wild-type (WT) plants. These results suggest that overexpression of CfCBF3 led to modification of the fatty acid unsaturation and alleviated the injuries under chilling stress.

  19. Image presentation and normal SPECT rCBF

    SciTech Connect

    Devous, M.D. Sr.

    1991-12-31

    The appearance of images of normal regional cerebral blood flow (rCBF) obtained from single photon emission computed tomography (SPECT) is influenced by several factors, including (1) the environmental conditions at the time of administration of the radiotracer, (2) the characteristics of the subject (eg. age, gender, and handedness), (3) the format used for image presentation, (4) the quality of the tomographic device, (5) the choices of image-processing techniques, and (6) the radiopharmaceutical used. The first three of these topics are briefly reviewed here; topics 4, 5 and 6 are reviewed by others in this workshop summary. 27 refs.

  20. Tissue factor in predicted severe acute pancreatitis

    PubMed Central

    Andersson, Ellen; Axelsson, Jakob; Eckerwall, Gunilla; Ansari, Daniel; Andersson, Roland

    2010-01-01

    AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation II score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6. PMID:21182229

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

    PubMed

    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

    2015-06-01

    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).

  2. 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.

  3. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells

    PubMed Central

    Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A.; Mizukawa, Benjamin; Grimes, H. Leighton; Kurokawa, Mineo; Liu, P. Paul; Huang, Gang; Mulloy, James C.

    2013-01-01

    RUNX1 is generally considered a tumor suppressor in myeloid neoplasms. Inactivating RUNX1 mutations have frequently been found in patients with myelodysplastic syndrome (MDS) and cytogenetically normal acute myeloid leukemia (AML). However, no somatic RUNX1 alteration was found in AMLs with leukemogenic fusion proteins, such as core-binding factor (CBF) leukemia and MLL fusion leukemia, raising the possibility that RUNX1 could actually promote the growth of these leukemia cells. Using normal human cord blood cells and those expressing leukemogenic fusion proteins, we discovered a dual role of RUNX1 in myeloid leukemogenesis. RUNX1 overexpression inhibited the growth of normal cord blood cells by inducing myeloid differentiation, whereas a certain level of RUNX1 activity was required for the growth of AML1-ETO and MLL-AF9 cells. Using a mouse genetic model, we also showed that the combined loss of Runx1/Cbfb inhibited leukemia development induced by MLL-AF9. RUNX2 could compensate for the loss of RUNX1. The survival effect of RUNX1 was mediated by BCL2 in MLL fusion leukemia. Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a promising therapeutic strategy for AMLs with leukemogenic fusion proteins. PMID:23979164

  4. 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

  5. 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.

  6. 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

  7. 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 ...

  8. Genetic and Molecular Analyses of Natural Variation Indicate CBF2 as a Candidate Gene for Underlying a Freezing Tolerance Quantitative Trait Locus in Arabidopsis1[w

    PubMed Central

    Alonso-Blanco, Carlos; Gomez-Mena, Concepción; Llorente, Francisco; Koornneef, Maarten; Salinas, Julio; Martínez-Zapater, José M.

    2005-01-01

    Natural variation for freezing tolerance is a major component of adaptation and geographic distribution of plant species. However, little is known about the genes and molecular mechanisms that determine its naturally occurring diversity. We have analyzed the intraspecific freezing tolerance variation existent between two geographically distant accessions of Arabidopsis (Arabidopsis thaliana), Cape Verde Islands (Cvi) and Landsberg erecta (Ler). They differed in their freezing tolerance before and after cold acclimation, as well as in the cold acclimation response in relation to photoperiod conditions. Using a quantitative genetic approach, we found that freezing tolerance differences after cold acclimation were determined by seven quantitative trait loci (QTL), named FREEZING TOLERANCE QTL 1 (FTQ1) to FTQ7. FTQ4 was the QTL with the largest effect detected in two photoperiod conditions, while five other FTQ loci behaved as photoperiod dependent. FTQ4 colocated with the tandem repeated genes C-REPEAT BINDING FACTOR 1 (CBF1), CBF2, and CBF3, which encode transcriptional activators involved in the cold acclimation response. The low freezing tolerance of FTQ4-Cvi alleles was associated with a deletion of the promoter region of Cvi CBF2, and with low RNA expression of CBF2 and of several CBF target genes. Genetic complementation of FTQ4-Cvi plants with a CBF2-Ler transgene suggests that such CBF2 allelic variation is the cause of CBF2 misexpression and the molecular basis of FTQ4. PMID:16244146

  9. Association genetics and expression patterns of a CBF4 homolog in Populus under abiotic stress.

    PubMed

    Li, Ying; Xu, Baohua; Du, Qingzhang; Zhang, Deqiang

    2015-06-01

    New strategies for prevention and treatment of abiotic stress require an improved understanding of stress responses. Here, we examined response differences of a C-repeat binding factor gene (PsCBF4) between five species in the genus Populus. We also used a candidate gene-based approach to identify single nucleotide polymorphisms (SNPs) within PsCBF4 that were associated with physiological and biochemical traits in a natural population (528 unrelated individuals) of Populus simonii. We first isolated a 1,044-bp PsCBF4 cDNA encoding a polypeptide of 256 amino acids. Expression profiling revealed that CBF4 is differentially expressed under cold, heat, drought, and salt conditions among five Populus species. Cold stress is the most significant interspecific difference, and PsCBF4 transcript levels ranged from 6.5 to 379.5 times higher than in unstressed controls. A natural population of P. simonii showed high nucleotide diversity (π T = 0.00880, θ w = 0.01192) and low linkage disequilibrium (r (2) ≥ 0.1, within 700 bp) across PsCBF4. Association analysis showed that nine SNPs (false discovery rate Q < 0.10) and two haplotypes (Q < 0.10) were significantly associated with six physiological and biochemical traits, with each marker explaining 3.36-6.12 % of the phenotypic variance in the corresponding trait. Transcript analysis further detected significant differences among genotypic classes for all significant SNPs. Identification of these significant associations will help reveal the molecular bases of physiological and biochemical differences and provide a starting point for marker-assisted selection for traits involved in stress tolerance in P. simonii.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Overexpression of the CBF2 transcriptional activator in Arabidopsis suppresses the responsiveness of leaf tissue to the stress hormone ethylene.

    PubMed

    Sharabi-Schwager, M; Samach, A; Porat, R

    2010-07-01

    The plant hormone ethylene affects myriad developmental processes ranging from seed germination to organ senescence, and plays a crucial role in plant resistance to environmental stresses. The C-repeat/dehydration-responsive element binding factor genes (CBF1-3) are transcriptional activators involved in plant low-temperatures responses; their overexpression enhances frost tolerance, but also has various pleiotropic effects on growth and development, mainly growth retardation and delay of flowering and senescence. We found that overexpression of CBF2 in Arabidopsis suppressed leaf tissue responsiveness to ethylene as compared with wild-type plants, as manifested in significantly delayed senescence and chlorophyll degradation. In wild-type plants, exposure to ethylene at 0.1 microl.l(-1) for 48 h caused 50% reduction in chlorophyll levels as compared to leaves held in air alone, whereas CBF2-overexpressing plants required an ethylene concentration of 10.0 microl.l(-1) to cause the same effect. Furthermore, continuous exposure to ethylene at 1.0 microl.l(-1) reduced chlorophyll content in wild-type leaves by 50% after 42 h but took 72 h in CBF2-overexpressing plants. Transcript profiling of ethylene receptors and signal transduction genes in leaves of wild-type and CBF2-overexpressing plants, by means of the Affymetrix ATH1 genome array, revealed only minor differences in gene expression patterns - insufficient to explain the observed responsiveness differences. Nevertheless, we found that overexpression of CBF2 significantly increased transcript levels of 17 ABA biosynthetic and responsive genes and, thus, may have affected leaf responsiveness to ethylene via contrasting interactions with other hormones, mainly ABA. Overall, the current findings suggest that overexpression of the CBF2 transcriptional activator in Arabidopsis may, at least in part, contribute to the observed delay of leaf senescence and enhanced plant fitness by suppressing leaf responsiveness to

  17. 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.

  18. Incidence and Risk Factors for Acute Kidney Injury Following Mannitol Infusion in Patients With Acute Stroke

    PubMed Central

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

    2015-01-01

    Abstract 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

  19. 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.

  20. Simultaneous Imaging of CBF Change and BOLD with Saturation-Recovery-T1 Method.

    PubMed

    Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

    2015-01-01

    A neuroimaging technique based on the saturation-recovery (SR)-T1 MRI method was applied for simultaneously imaging blood oxygenation level dependence (BOLD) contrast and cerebral blood flow change (ΔCBF), which is determined by CBF-sensitive T1 relaxation rate change (ΔR1CBF). This technique was validated by quantitatively examining the relationships among ΔR1CBF, ΔCBF, BOLD and relative CBF change (rCBF), which was simultaneously measured by laser Doppler flowmetry under global ischemia and hypercapnia conditions, respectively, in the rat brain. It was found that during ischemia, BOLD decreased 23.1±2.8% in the cortical area; ΔR1CBF decreased 0.020±0.004s-1 corresponding to a ΔCBF decrease of 1.07±0.24 ml/g/min and 89.5±1.8% CBF reduction (n=5), resulting in a baseline CBF value (=1.18 ml/g/min) consistent with the literature reports. The CBF change quantification based on temperature corrected ΔR1CBF had a better accuracy than apparent R1 change (ΔR1app); nevertheless, ΔR1app without temperature correction still provides a good approximation for quantifying CBF change since perfusion dominates the evolution of the longitudinal relaxation rate (R1app). In contrast to the excellent consistency between ΔCBF and rCBF measured during and after ischemia, the BOLD change during the post-ischemia period was temporally disassociated with ΔCBF, indicating distinct CBF and BOLD responses. Similar results were also observed for the hypercapnia study. The overall results demonstrate that the SR-T1 MRI method is effective for noninvasive and quantitative imaging of both ΔCBF and BOLD associated with physiological and/or pathological changes.

  1. 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.

  2. 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

  3. CBF mediates adenovirus Ela trans-activation by interaction at the C-terminal promoter targeting domain of conserved region 3.

    PubMed

    Agoff, S N; Wu, B

    1994-12-01

    Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts with promoter-specific transcription factors, thereby bringing the activation region of Ela CR3 in proximity of the promoter. Here we report that CBF, a CCAAT-box-binding factor that regulates hsp70 gene expression and mediates Ela trans-activation in vivo, interacts with the promoter targeting region of Ela CR3 in vitro. Point mutations in Ela CR3 that are defective in stimulating transcription from the hsp70 promoter are also defective in stimulating transcription directed by a synthetic activator, GAL-CBF, composed of the DNA-binding domain of yeast GAL4 fused to CBF. These mutations fall into two classes with respect to their abilities to interact with CBF in vitro. Mutations in the transcriptional activation region of Ela CR3 do not affect binding to CBF, but mutation of the promoter targeting region of Ela CR3 prevents association with CBF in vitro.

  4. Large deletions in the CBF gene cluster at the Fr-B2 locus are associated with reduced frost tolerance in wheat

    PubMed Central

    Pearce, Stephen; Zhu, Jie; Boldizsár, Ákos; Vágújfalvi, Attila; Burke, Adrienne; Garland-Campbell, Kimberley; Galiba, Gábor; Dubcovsky, Jorge

    2016-01-01

    Wheat plants which are exposed to periods of low temperatures (cold acclimation) exhibit increased survival rates when they are subsequently exposed to freezing temperatures. This process is associated with large-scale changes in the transcriptome which are modulated by a set of tandemly duplicated CBF (C-repeat Binding Factor) transcription factors located at the Fr-2 (Frost Resistance-2) locus. While Arabidopsis has three tandemly duplicated CBF genes, the CBF family in wheat has undergone an expansion and at least 15 CBF genes have been identified, eleven of which are present at the Fr-2 loci on homoeologous group 5 chromosomes. We report here the discovery of three large deletions which eliminate six, nine, and all eleven CBF genes from the Fr-B2 locus in tetraploid and hexaploid wheat. In wild emmer wheat, the Fr-B2 deletions were found only among the accessions from the southern sub-populations. Among cultivated wheats, the Fr-B2 deletions were more common among varieties with a spring growth habit than among those with a winter growth habit. Replicated freezing tolerance experiments showed that both the deletion of nine CBF genes in tetraploid wheat and the complete Fr-B2 deletion in hexaploid wheat are associated with significant reductions in survival after exposure to freezing temperatures. Our results suggest that selection for the wild type Fr-B2 allele may be beneficial for breeders selecting for varieties with improved frost tolerance. PMID:23884601

  5. 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

  6. 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

  7. Cold induction of Arabidopsis CBF genes involves multiple ICE (inducer of CBF expression) promoter elements and a cold-regulatory circuit that is desensitized by low temperature.

    PubMed

    Zarka, Daniel G; Vogel, Jonathan T; Cook, Daniel; Thomashow, Michael F

    2003-10-01

    The Arabidopsis CBF1, 2, and 3 genes (also known as DREB1b, c, and a, respectively) encode transcriptional activators that have a central role in cold tolerance. CBF1-3 are rapidly induced upon exposing plants to low temperature, followed by expression of CBF-targeted genes, the CBF regulon, resulting in an increase in plant freezing tolerance. At present, little is known about the cold-sensing mechanism that controls CBF expression. Results presented here indicate that this mechanism does not require a cold shock to bring about the accumulation of CBF transcripts, but instead, absolute temperature is monitored with a greater degree of input, i.e. lower temperature, resulting in a greater output, i.e. higher levels of CBF transcripts. Temperature-shift experiments also indicate that the cold-sensing mechanism becomes desensitized to a given low temperature, such as 4 degrees C, and that resensitization to that temperature requires between 8 and 24 h at warm temperature. Gene fusion experiments identified a 125-bp section of the CBF2 promoter that is sufficient to impart cold-responsive gene expression. Mutational analysis of this cold-responsive region identified two promoter segments that work in concert to impart robust cold-regulated gene expression. These sequences, designated ICEr1 and ICEr2 (induction of CBF expression region 1 or 2), were also shown to stimulate transcription in response to mechanical agitation and the protein synthesis inhibitor, cycloheximide.

  8. Risk Factors for Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis

    PubMed Central

    Ohtaka, Kazuto; Shoji, Yasuhito; Ichimura, Tatsunosuke; Fujita, Miri; Senmaru, Naoto; Hirano, Satoshi

    2016-01-01

    Background and Objectives: Factors that contribute to difficult laparoscopic cholecystectomy (LC) in acute cholecystitis (AC) that would affect the performance of early surgery remain unclear. The purpose of this study was to identify such risk factors. Methods: One hundred fifty-four patients who underwent LC for AC were retrospectively analyzed. The patients were categorized into early surgery and delayed surgery. Factors predicting difficult LC were analyzed for each group. The operation time, bleeding, and cases of difficult laparoscopic surgery (CDLS)/conversion rate were analyzed as an index of difficulty. Analyses of patients in the early group were especially focused on 3 consecutive histopathological phases: edematous cholecystitis (E), necrotizing cholecystitis (N), suppurative/subacute cholecystitis (S). Results: In the early group, the CDLS/conversion rate was highest in necrotizing cholecystitis. Its rate was significantly higher than that of the other 2 histopathological types (N 27.9% vs E and S 7.4%; P = .037). In the delayed-surgery group, a higher white blood cell (WBC) count and older age showed significant correlations with the CDLS/conversion rate (P = .034 and P = .004). Conclusion: In early surgery, histopathologic necrotizing cholecystitis is a risk factor for difficult LC in AC. A higher WBC count and older age are risk factors for delayed surgery.

  9. Factors associated with acute respiratory illness in day care children.

    PubMed

    Hatakka, Katja; Piirainen, Laura; Pohjavuori, Sara; Poussa, Tuija; Savilahti, Erkki; Korpela, Riitta

    2010-09-01

    The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.

  10. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

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

  11. Investigating intrinsic connectivity networks using simultaneous BOLD and CBF measurements.

    PubMed

    Mayhew, S D; Mullinger, K J; Bagshaw, A P; Bowtell, R; Francis, S T

    2014-10-01

    When the sensory cortex is stimulated and directly receiving afferent input, modulations can also be observed in the activity of other brain regions comprising spatially distributed, yet intrinsically connected networks, suggesting that these networks support brain function during task performance. Such networks can exhibit subtle or unpredictable task responses which can pass undetected by conventional general linear modelling (GLM). Additionally, the metabolic demand of these networks in response to stimulation remains incompletely understood. Here, we recorded concurrent BOLD and CBF measurements during median nerve stimulation (MNS) and compared GLM analysis with independent component analysis (ICA) for identifying the spatial, temporal and metabolic properties of responses in the primary sensorimotor cortex (S1/M1), and in the default mode (DMN) and fronto-parietal (FPN) networks. Excellent spatial and temporal agreement was observed between the positive BOLD and CBF responses to MNS detected by GLM and ICA in contralateral S1/M1. Values of the change in cerebral metabolic rate of oxygen consumption (Δ%CMRO2) and the Δ%CMRO2/Δ%CBF coupling ratio were highly comparable when using either GLM analysis or ICA to extract the contralateral S1/M1 responses, validating the use of ICA for estimating changes in CMRO2. ICA identified DMN and FPN network activity that was not detected by GLM analysis. Using ICA, spatially coincident increases/decreases in both BOLD and CBF signals to MNS were found in the FPN/DMN respectively. Calculation of CMRO2 changes in these networks during MNS showed that the Δ%CMRO2/Δ%CBF ratio is comparable between the FPN and S1/M1 but is larger in the DMN than in the FPN, assuming an equal value of the parameter M in the DMN, FPN and S1/M1. This work suggests that metabolism-flow coupling may differ between these two fundamental brain networks, which could originate from differences between task-positive and task-negative fMRI responses

  12. Risk factors of delayed diagnosis of acute appendicitis in children: for early detection of acute appendicitis

    PubMed Central

    Choi, Jea Yeon; Jo, Jeong Hyun; Hann, Tchah; Kim, Seong Min

    2016-01-01

    Purpose This study examined the risk factors of a delayed diagnosis of acute appendicitis in children undergoing an appendectomy. Methods This retrospective study involved children aged below 18 years, who underwent an appendectomy. After dividing them into a delayed diagnosis group and nondelayed diagnosis group according to the time interval between the initial hospital visit and final diagnosis, the risk factors of delayed diagnosis were identified using logistic regression analysis. Results Among 712 patients, 105 patients (14.7%) were classified in the delayed diagnosis group; 92 patients (12.9%) were diagnosed using ultrasonography (US), and both US and computed tomography were performed in 38 patients (5.3%). More patients in the delayed diagnosis group underwent US (P=0.03). Spring season and prior local clinic visit were significantly associated with a delayed diagnosis. Fever and diarrhea were more common in the delayed diagnosis group (fever: odds ratio [OR], 1.37; 95% confidence interval [CI], 1.05–1.81; diarrhea: OR, 1.94; 95% CI, 1.08–3.46; P<0.05). These patients showed symptoms for a longer duration (OR, 2.59; 95% CI, 1.78–3.78; P<0.05), and the admission course (OR, 1.26; 95% CI, 1.11–1.44; P<0.05) and C-reactive protein (CRP) levels (OR, 1.47; 95% CI, 1.19–1.82; P<0.05) were associated with the delayed diagnosis. Conclusion To decrease the rate of delayed diagnoses of acute appendicitis, symptoms such as fever and diarrhea, seasonal variations, admission course, and CRP levels should be considered and children with a longer duration of symptoms should be closely monitored. PMID:27721841

  13. Effects of background suppression on the sensitivity of dual-echo arterial spin labeling MRI for BOLD and CBF signal changes.

    PubMed

    Ghariq, Eidrees; Chappell, Michael A; Schmid, Sophie; Teeuwisse, Wouter M; van Osch, Matthias J P

    2014-12-01

    Dual-echo arterial spin labeling (DE-ASL) enables the simultaneous acquisition of BOLD and CBF fMRI data and is often used for calibrated BOLD and cerebrovascular CO2 reactivity measurements. DE-ASL, like all ASL techniques, suffers from a low intrinsic CBF SNR, which can be improved by suppressing the background signal via the inclusion of additional inversion pulses. However, until now this approach has been considered to be undesirable for DE-ASL, because the BOLD signal is extracted from the background signal and attenuating the background signal could decrease the sensitivity of DE-ASL scans for BOLD changes. In this study, the effect of background suppression on the sensitivity of DE-ASL MRI for BOLD and CBF signal changes with a visual stimulation paradigm was studied. Results showed that with an average background suppression level of 70% the BOLD sensitivity of DE-ASL MRI decreases slightly (15%), while the CBF sensitivity of the scans increased by almost a factor-of-two (81%). These findings support the conclusion that the gains in CBF sensitivity of DE-ASL MRI due to background suppression outweigh the slight decrease in sensitivity of these scans for BOLD changes, and thus that background suppression is highly recommended for DE-ASL.

  14. 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.

  15. Factors influencing prognosis in adults with acute myelogenous leukaemia.

    PubMed Central

    Crowther, D.; Beard, M. E.; Bateman, C. J.; Sewell, R. L.

    1975-01-01

    A study of the thymidine labelling index (TLI) of bone marrow blast cells in 58 untreated patients with acute myelogenous leukemia showed no correlation with remission rate but there was a strong correlation between labelling index and remission length in the 21 patients who achieved remission. The median remission length of the patients was 33 weeks. Of the 12 patients with initial labelling indices greater than 10%, only 2 had remissions longer than 33 weeks whereas 8 of the 9 patients with labelling indices less than 10% had remissions longer than 33 weeks. No correlation could be found between the degree of cytological differentiation and remission induction, remission length or survival. No correlation was found between the TLI and the degree of cytological differentiation. Age and initial platelet count were confirmed to be important factors influencing complete remission rate, but these factors did not correlate with remission length. Sixteen patients had their pretreatment sera assayed for mouse marrow colony stimulating activity and inhibitor levels but there was no correlation with subsequent response to treatment, although the number of patients examined was clearly too small for any definite conclusions to be drawn. PMID:1082343

  16. Acute kidney injury in dengue fever using Acute Kidney Injury Network criteria: incidence and risk factors.

    PubMed

    Mehra, Nikita; Patel, Amish; Abraham, Georgi; Reddy, Yogesh N V; Reddy, Yuvaram N V

    2012-07-01

    The aim of this study was to assess incidence and risk factors for acute kidney injury (AKI) in patients with dengue fever (DF). A total of 223 patients (males, 130; females, 93; mean age, 26.2 ± 18.2 years) from a tertiary care centre in southern India were retrospectively analysed. Acute renal failure (ARF) developed in 24 (10.8%) patients. Based on the Acute Kidney Injury Network (AKIN) criteria, the results revealed that: 12 (5.4%) had mild AKI; seven (3.1%) had moderate AKI; and five (2.2%) had severe AKI. A further 54 (24%) were diagnosed with dengue haemorrhagic fever (DHF); 11 (5%) were co-infected with leptospirosis; thrombocytopenia was present in 157 (70%); and 64 (29%) were hypotensive. Patients were divided into either group A (with AKI) or group B (without AKI), and group A was divided into mild (A1), moderate (A2) and severe (A3) subgroups. We recorded: a higher total white count (A = 9824; B = 6706; P = 0.01); serum glutamic pyruvic transaminase (SGPT; A = 450; B = 144; P = 0.001); alkaline phosphatase (ALP) levels (A = 207; B = 42; P = 0.001); lower albumin (A = 2.65; B = 3.09; P < 0.001); and serum bicarbonate (A = 20.57; B = 23.21; P = 0.009). Hypotension (P = 0.01), coexisting viral hepatitis (P < 0.001), sepsis (P < 0.001), multiple organ dysfunction syndrome (MODS; P < 0.001) and the need for inotropes (P < 0.001) were associated with DF. Total white count (P = 0.038), glomerular filtration rate (GFR) on discharge (P = 0.034), specific gravity of urine (P = 0.006), ALP (P = 0.013), SGPT (P = 0.042), MODS (P = 0.05) and use of platelet fresh frozen plasma (FFP; P = 0.007) were significantly different between mild, moderate and severe AKI subgroups. Twenty-two (9%) died. AKI is associated with an increased mortality in DF (P = 0.005).

  17. 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…

  18. 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

  19. Cerebral blood flow in volunteers measured by PET and Xe CT/CBF. A comparison.

    PubMed

    Bergholt, B; Ostergaard, L; von Oettingen, G; Johannsen, P; Poulsen, P H; Bundgaard, H; Asboe, H; Cold, G E; Gjedde, A; Gyldensted, C; Astrup, J

    2000-02-01

    Aim of this study was to compare two quantitative CBF methods. Seven young, healthy volunteers were studied with PET (15-0 labelled water) and afterwards with Xe CT/CBF (30% xenon in oxygen, 3 minutes wash-in, 5 minutes washout protocol). Xe CT/CBF showed greater differences between high and low flow areas than PET CBF. Correlation was found within subjects between ROI's, but no agreement or correlation between the methods could be demonstrated. The disagreement in this study could be due to changes in PCO2.

  20. Potato plants ectopically expressing Arabidopsis thaliana CBF3 exhibit enhanced tolerance to high-temperature stress.

    PubMed

    Dou, Haiou; Xv, Kunpeng; Meng, Qingwei; Li, Gang; Yang, Xinghong

    2015-01-01

    CBF3, a known cold-inducible gene that encodes a transcription factor, was isolated from Arabidopsis thaliana and introduced into the potato (Solanum tuberosum cv. 'luyin NO.1') under the control of the CaMV35S promoter or the rd29A promoter. Our results revealed that temperature of 40 °C or higher can significantly induce AtCBF3 expression. After heat stress, the net photosynthetic rate (Pn ), the maximal photochemical efficiency of photosystem II (PSII) (Fv /Fm ) and the accumulation of the D1 protein were higher in the transgenic lines than in the wild-type (WT) line. Moreover, compared with the WT line, O2 (●-) and H2 O2 accumulation in the transgenic lines were reduced. A Q-PCR assay of a subset of the genes involved in photosynthesis and antioxidant defence further verified the above results. Interestingly, under heat stress conditions, the accumulation of heat-shock protein 70 (HSP70) increased in the WT line but decreased in the transgenic lines. These results suggest that potato plants ectopically expressing AtCBF3 exhibited enhanced tolerance to high temperature, which is associated with improved photosynthesis and antioxidant defence via induction of the expression of many stress-inducible genes. However, this mechanism may not depend upon the regulatory pathways in which HSP70 is involved. PMID:24811248

  1. Exogenous application of molybdenum affects the expression of CBF14 and the development of frost tolerance in wheat.

    PubMed

    Al-Issawi, Mohammed; Rihan, Hail Z; Woldie, Wondwossen Abate; Burchett, Stephen; Fuller, Michael P

    2013-02-01

    Wheat is able to cold acclimate in response to low temperatures and thereby increase its frost tolerance and the extent of this acclimation is greater in winter genotypes compared to spring genotypes. Such up-regulation of frost tolerance is controlled by Cbf transcription factors. Molybdenum (Mo) application has been shown to enhance frost tolerance of wheat and this study aimed to investigate the effect of Mo on the development of frost tolerance in winter and spring wheat. Results showed that Mo treatment increased the expression of Cbf14 in wheat under non-acclimating condition but did not alter frost tolerance. However, when Mo was applied in conjunction with exposure of plants to low temperature, Mo increased the expression of Cbf14 and enhanced frost tolerance in both spring and winter genotypes but the effect was more pronounced in the winter genotype. It was concluded that the application of Mo could be useful in situations where enhanced frost resistance is required. Further studies are proposed to elucidate the effect of exogenous of applications of Mo on frost resistance in spring and winter wheat at different growth stages.

  2. Acute Pre-operative Infarcts and Poor Cerebrovascular Reserve are Independent Risk Factors for Severe Ischemic Complications Following Direct Extracranial-Intracranial Bypass for Moyamoya Disease

    PubMed Central

    Pulling, T. Michael; Rosenberg, Jarrett; Marks, Michael P.; Steinberg, Gary K.; Zaharchuk, Greg

    2015-01-01

    Background and Purpose Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to middle cerebral artery (STA MCA) bypass in Moyamoya patients. This study was undertaken to determine whether pre-operative MR imaging and/or cerebrovascular reserve (CVR) assessment using reference standard stable xenon enhanced computed tomography (xeCT) could predict such complications. Materials and Methods Among all adult patients receiving direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xeCT examination, we identified index cases (patients with >15 ml post-operative infarcts) and control cases (patients without post-operative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated using the Mann Whitney test. Univariate and multivariate generalized linear model regression were employed to test predictors of post-operative infarct. Results Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95±55 ml. Four of six index cases (67%), but no control patients, had pre-operative acute infarcts. Baseline CBF was similar, but CVR was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median CVR was 0.4% (range: −38.0% to 16.6%) in index vs. 26.3% (range: −8.2% to 60.5%) in control patients (p=0.003). Multivariate analysis demonstrated that the presence of a small pre-operative infarct (regardless of location) and impaired CVR were independent, significant predictors of severe post-operative ischemic injury. Conclusion Acute infarcts and impaired CVR on pre operative imaging are independent risk factors for severe ischemic complications following STA MCA bypass in Moyamoya disease. PMID:26564435

  3. 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.

  4. Structure-function relationships of archaeal Cbf5 during in vivo RNA-guided pseudouridylation.

    PubMed

    Majumder, Mrinmoyee; Bosmeny, Michael S; Gupta, Ramesh

    2016-10-01

    In Eukarya and Archaea, in addition to protein-only pseudouridine (Ψ) synthases, complexes containing one guide RNA and four proteins can also produce Ψ. Cbf5 protein is the Ψ synthase in the complex. Previously, we showed that Ψ's at positions 1940, 1942, and 2605 of Haloferax volcanii 23S rRNA are absent in a cbf5-deleted strain, and a plasmid-borne copy of cbf5 can rescue the synthesis of these Ψ's. Based on published reports of the structure of archaeal Cbf5 complexed with other proteins and RNAs, we identified several potential residues and structures in H. volcanii Cbf5, which were expected to play important roles in pseudouridylation. We mutated these structures and determined their effects on Ψ production at the three rRNA positions under in vivo conditions. Mutations of several residues in the catalytic domain and certain residues in the thumb loop either abolished Ψ's or produced partial modification; the latter indicates a slower rate of Ψ formation. The universal catalytic aspartate of Ψ synthases could be replaced by glutamate in Cbf5. A conserved histidine, which is common to Cbf5 and TruB is not needed, but another conserved histidine of Cbf5 is required for the in vivo RNA-guided Ψ formation. We also identified a previously unreported novelty in the pseudouridylation activity of Cbf5 where a single stem-loop of a guide H/ACA RNA is used to produce two closely placed Ψ's and mutations of certain residues of Cbf5 abolished one of these two Ψ's. In summary, this first in vivo study identifies several structures of an archaeal Cbf5 protein that are important for its RNA-guided pseudouridylation activity.

  5. Structure-function relationships of archaeal Cbf5 during in vivo RNA-guided pseudouridylation.

    PubMed

    Majumder, Mrinmoyee; Bosmeny, Michael S; Gupta, Ramesh

    2016-10-01

    In Eukarya and Archaea, in addition to protein-only pseudouridine (Ψ) synthases, complexes containing one guide RNA and four proteins can also produce Ψ. Cbf5 protein is the Ψ synthase in the complex. Previously, we showed that Ψ's at positions 1940, 1942, and 2605 of Haloferax volcanii 23S rRNA are absent in a cbf5-deleted strain, and a plasmid-borne copy of cbf5 can rescue the synthesis of these Ψ's. Based on published reports of the structure of archaeal Cbf5 complexed with other proteins and RNAs, we identified several potential residues and structures in H. volcanii Cbf5, which were expected to play important roles in pseudouridylation. We mutated these structures and determined their effects on Ψ production at the three rRNA positions under in vivo conditions. Mutations of several residues in the catalytic domain and certain residues in the thumb loop either abolished Ψ's or produced partial modification; the latter indicates a slower rate of Ψ formation. The universal catalytic aspartate of Ψ synthases could be replaced by glutamate in Cbf5. A conserved histidine, which is common to Cbf5 and TruB is not needed, but another conserved histidine of Cbf5 is required for the in vivo RNA-guided Ψ formation. We also identified a previously unreported novelty in the pseudouridylation activity of Cbf5 where a single stem-loop of a guide H/ACA RNA is used to produce two closely placed Ψ's and mutations of certain residues of Cbf5 abolished one of these two Ψ's. In summary, this first in vivo study identifies several structures of an archaeal Cbf5 protein that are important for its RNA-guided pseudouridylation activity. PMID:27539785

  6. 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.

  7. 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...

  8. 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

  9. Acute Otitis Media Severity: Association with Cytokine Gene polymorphisms and other Risk Factors

    PubMed Central

    McCormick, David P.; Grady, James J.; Diego, Alejandro; Matalon, Reuben; Revai, Krystal; Patel, Janak A.; Han, Yimei; Chonmaitree, Tasnee

    2011-01-01

    Background We have previously shown an association between polymorphisms of proinflammatory cytokine genes and susceptibility to upper respiratory tract infection and acute otitis media. It has not been known whether polymorphisms or risk factors are associated with the severity of acute otitis media. Objective To evaluate the influences of proinflammatory cytokine gene polymorphisms and other risk factors on severity of acute otitis media following upper respiratory infection. Methods In a prospective, longitudinal study, children aged 6-35 months were followed for one year for occurrences of upper respiratory tract infection and acute otitis media. Children were studied for TNFα-308, interleukin (IL)- 6-174 and IL-1 ß+3953 polymorphisms, taking into account age, gender, race, family history of otitis, tobacco smoke exposure, breast feeding, day of upper respiratory tract infection at the time of diagnosis and pneumococcal vaccine status. Symptoms and signs of acute otitis media were graded according to a validated scale. The association between acute otitis media clinical severity, polymorphic genotypes, and risk factors was analyzed using statistical models that account for multiple episodes of acute otitis media per child. Results A total of 295 episodes of acute otitis media in 128 subjects were included. More severe acute otitis media symptoms were associated with young age (P=0.01), family history of acute otitis media (P=0.002), tobacco smoke exposure (P=0.008), and early diagnosis of otitis after onset of upper respiratory tract infection (P=0.02). Among children with a bulging or perforated tympanic membrane (206 episodes, 104 subjects), those who had the IL- 1 ß+3953 polymorphism, experienced higher symptom scores (P<0.02). Conclusion This is the first report of the association between risk factors and acute otitis media severity. Risk factors such as tobacco smoke exposure and a positive family history appear to be more significantly associated with

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

    PubMed

    Arboix, Adrià

    2015-05-16

    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.

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

    PubMed

    Arboix, Adrià

    2015-05-16

    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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Factor V Leiden mutation is not a predisposing factor for acute coronary syndromes

    PubMed Central

    Himabindu, G.; Rajasekhar, D.; Latheef, K.; Sarma, P.V.G.K.; Vanajakshamma, V.; Chaudhury, Abhijit; Bitla, Aparna R.

    2012-01-01

    Background The prevalence of Coronary artery disease (CAD) in India has increased considerably over the past few years and could become the number one killer disease if interventions are not done. Factor V Leiden (FVL) mutation and FII G20210A polymorphism are two recently described genetic factors with a propensity towards venous thrombosis. This warrants the investigations for thrombophilia in myocardial infarction patients in India. Methods The study cohort consisted of 51 patients aged below 50 years presenting with acute coronary syndromes. In both patient group and normal individuals the major risk factors Protein C deficiency, Protein S deficiency, anticardiolipin antibodies, Fibrinogen and Lipoprotein [a] were studied. Factor V Leiden (FVL) G1691A mutation in both control and patient group was looked by using Polymerase chain reaction (PCR) followed by sequencing of the PCR products. Results Our results indicated significantly higher levels of anticardiolipin antibodies and fibrinogen in the patients and absence of FVL (G1691A) mutation in our study cohort. One of the patients (H5) showed insertion of an extra A nucleotide in exon 10 of the Factor V gene resulting in frame shift mutation in this patient. Conclusion The results of present study showed absence of FVL mutation in our population. However, there is a need to confirm the above findings on patients from different populations from different parts of the country. The insertion of an extra A in exon 10 in the patient needs to be ascertained to confirm that it is one of its kinds or is prevalent in the population. PMID:23253409

  18. 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.

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

    PubMed

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

    2016-01-15

    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

  20. 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

  1. 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.

  2. 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.

  3. Activation of clotting factors XI and IX in patients with acute myocardial infarction.

    PubMed

    Minnema, M C; Peters, R J; de Winter, R; Lubbers, Y P; Barzegar, S; Bauer, K A; Rosenberg, R D; Hack, C E; ten Cate, H

    2000-11-01

    In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.

  4. Factor structure of the acute stress disorder scale in a sample of Hurricane Katrina evacuees.

    PubMed

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

    2010-06-01

    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 sample of Hurricane Katrina evacuees relocated to a Red Cross emergency shelter in Austin, Texas. Results indicated that the proposed 4-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.

  5. 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

  6. The incidence of acute pancreatitis: impact of social deprivation, alcohol consumption, seasonal and demographic factors1

    PubMed Central

    Roberts, SE; Akbari, A; Thorne, K; Atkinson, M; Evans, PA

    2013-01-01

    Background The incidence of acute pancreatitis has increased sharply in many European countries and the USA in recent years. Aim To establish trends in incidence and mortality for acute pancreatitis in Wales, UK, and to assess how incidence may be linked to factors including social deprivation, seasonal effects and alcohol consumption. Methods Use of record linked inpatient, mortality and primary care data for 10 589 hospitalised cases of acute pancreatitis between 1999 and 2010. Results The incidence of acute pancreatitis was 30.0 per 100 000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100 000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year), there was little trend in mortality (0.2% average annual reduction). The largest increases in incidence were among women aged <35 years (7.9% per year) and men aged 35–44 (5.7%) and 45–54 (5.3%). Incidence was 1.9 times higher among the most deprived quintile of patients compared with the most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for gallstone acute pancreatitis). Acute pancreatitis was increased significantly during the Christmas and New Year weeks by 48% (95% CI = 24–77%) for alcoholic aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were increased with higher consumption of spirits and beer, but not wine. Conclusions The study shows an elevated rate of alcoholic acute pancreatitis during the Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly for young women, while alcoholic acute pancreatitis is linked strongly with social deprivation. PMID:23859492

  7. 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

  8. 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

  9. 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…

  10. Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

    PubMed

    Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    2015-08-28

    A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

  11. Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study.

    PubMed

    Frei, Ulrich; Daloze, Pierre; Vítko, Stefan; Klempnauer, Jürgen; Reyes-Acevedo, Rafael; Titiz, Izzet; Fricke, Lutz; Bernasconi, Corrado; Ekberg, Henrik

    2010-01-01

    The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.

  12. Risk Factors for Acute Endophthalmitis following Cataract Surgery: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Liping; Lo, SingKai

    2013-01-01

    Background Acute endophthalmitis is one of the most serious complications of cataract surgery and often results in severe visual impairment. Several risk factors for acute postoperative endophthalmitis (POE) following cataract surgery have been reported but the level of evidence and strength of association is varied. The purpose of this study was to critically appraise published reports on and to summarize clinical risk factors associated with acute POE which could be easily assessed by ophthalmologists for the introduction and implementation of preventive measure. Methods A systematic review and meta-analysis of observational studies was performed. Six databases were searched with no limits on the year or language of publication. Study-specific odds ratios (Ors) or relative risk (RR) of each risk factor were pooled using a random effect model. Results A total of 6 686 169 participants with 8 963 endophthalmitis in 42 studies were analyzed. Of the nine risk factors identified in our systematic review and meta-analysis, extra- or intracapsular cataract extraction, a clear corneal incision, without intracameral cefazolin (1 mg in 0.1 ml solution), without intracameral cefuroxime (1 mg in 0.1 ml solution), post capsular rupture, silicone intraocular lenses and intraoperative complications were found strongly associated with acute endophthalmitis. Other significant factors with a lower strength of association (risk estimates generally 1.5 or less) were male gender and old age (85 years and older). Conclusions Our study provides summary data on the risk factors for acute POE. Identifying patients at high risk of this sight-threatening eye disease is important from both the public health and clinical perspectives as this would facilitate detection of disease before the onset of irreversible visual loss enabling earlier intervention. PMID:23990980

  13. Conserved Gene Regulatory Function of the Carboxy-Terminal Domain of Dictyostelid C-Module-Binding Factor

    PubMed Central

    Schmith, Anika; Groth, Marco; Ratka, Josephine; Gatz, Sara; Spaller, Thomas; Siol, Oliver; Glöckner, Gernot

    2013-01-01

    C-module-binding factor A (CbfA) is a jumonji-type transcription regulator that is important for maintaining the expression and mobility of the retrotransposable element TRE5-A in the social amoeba Dictyostelium discoideum. CbfA-deficient cells have lost TRE5-A retrotransposition, are impaired in the ability to feed on bacteria, and do not enter multicellular development because of a block in cell aggregation. In this study, we performed Illumina RNA-seq of growing CbfA mutant cells to obtain a list of CbfA-regulated genes. We demonstrate that the carboxy-terminal domain of CbfA alone is sufficient to mediate most CbfA-dependent gene expression. The carboxy-terminal domain of CbfA from the distantly related social amoeba Polysphondylium pallidum restored the expression of CbfA-dependent genes in the D. discoideum CbfA mutant, indicating a deep conservation in the gene regulatory function of this domain in the dictyostelid clade. The CbfA-like protein CbfB displays ∼25% sequence identity with CbfA in the amino-terminal region, which contains a JmjC domain and two zinc finger regions and is thought to mediate chromatin-remodeling activity. In contrast to CbfA proteins, where the carboxy-terminal domains are strictly conserved in all dictyostelids, CbfB proteins have completely unrelated carboxy-terminal domains. Outside the dictyostelid clade, CbfA-like proteins with the CbfA-archetypical JmjC/zinc finger arrangement and individual carboxy-terminal domains are prominent in filamentous fungi but are not found in yeasts, plants, and metazoans. Our data suggest that two functional regions of the CbfA-like proteins evolved at different rates to allow the occurrence of species-specific adaptation processes during genome evolution. PMID:23355006

  14. Evaluation of affecting factors for conversion to open cholecystectomy in acute cholecystitis

    PubMed Central

    Ucar, Ahmet Deniz; Aydogan, Serdar; Sari, Erdem; Erkan, Nazif; Yildirim, Mehmet

    2014-01-01

    Introduction Laparoscopic cholecystectomy has become the gold standard for the surgical treatment of gallbladder disease. Severe inflammation makes laparoscopic dissection technically more demanding in acute cholecystitis. Conversion to open cholecystectomy due to adverse conditions is still required in some patients. Aim To evaluate predictive risk factors associated with conversion to open cholecystectomy in acute cholecystitis. Material and methods A retrospective analysis was performed on 165 patients who underwent a laparoscopic cholecystectomy for acute cholecystitis in our clinic. Patients who completed laparoscopic cholecystectomy and required conversion to open cholecystectomy were compared in terms of age, sex, fever, laboratory and USG findings, operation timing, complications, and duration of hospital stay. Results There were 53 (32%) male and 112 (68%) female patients; the mean age was 52.4 ±12.5 years. Forty-six (27.9%) of the 165 patients were converted to open cholecystectomy. Male sex of the patients who underwent conversion (47.1%) was found to be statistically significant (p < 0.001). Preoperative white blood count, blood glucose and amylase values, morbidity rate, and hospital stay were raised in patients who underwent conversion, and all were found to be statistically significant (p < 0.05). Conclusions Male sex, blood leucocyte, glucose, and raised amylase emerged as the effective factors for conversion cholecystectomy in our study. These factors should help the clinical decision-making process when planning laparoscopic cholecystectomy in acute cholecystitis. By predicting these risk factors for conversion, preoperative patient counselling can be improved. PMID:25653728

  15. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury

    PubMed Central

    Togbe, Dieudonnée; Schnyder-Candrian, Silvia; Schnyder, Bruno; Doz, Emilie; Noulin, Nicolas; Janot, Laure; Secher, Thomas; Gasse, Pamela; Lima, Carla; Coelho, Fernando Rodrigues; Vasseur, Virginie; Erard, François; Ryffel, Bernhard; Couillin, Isabelle; Moser, Rene

    2007-01-01

    Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory response in the lung are reviewed. The acute airway inflammatory response to inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 and keratinocyte-derived chemokine (KC) production, protein leak and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor protein (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced TNF is required for bronchoconstriction, but dispensable for inflammatory cell recruitment. Lipopolysaccharide induces activation of the p38 mitogen-activated protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS-induced TNF production, bronchoconstriction, neutrophil recruitment into the lungs and broncho-alveolar space. In conclusion, TLR4-mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and MyD88, while TRIF, IL-1R1 or IL-18R signalling pathways are dispensable. Further downstream in this axis of signalling, TNF blockade reduces only acute bronchoconstriction, while MAPK inhibition abrogates completely endotoxin-induced inflammation. PMID:18039275

  16. Pseudouridine-guide RNAs and other Cbf5p-associated RNAs in Euglena gracilis.

    PubMed

    Russell, Anthony G; Schnare, Murray N; Gray, Michael W

    2004-07-01

    In eukaryotes, box H/ACA small nucleolar RNAs (snoRNAs) guide sites of pseudouridine (Psi) formation in rRNA. These snoRNAs reside in RNP complexes containing the putative Psi synthase, Cbf5p. In this study we have identified Cbf5p-associated RNAs in Euglena gracilis, an early diverging eukaryote, by immunoprecipitating Cbf5p-containing complexes from cellular extracts. We characterized one box H/ACA-like RNA which, however, does not appear to guide Psi formation in rRNA. We also identified four single Psi-guide box AGA RNAs. We determined target sites for these putative Psi-guide RNAs and confirmed that the predicted Psi modifications do, in fact, occur at these positions in Euglena rRNA. The Cbf5p-associated snoRNAs appear to be encoded by multicopy genes, some of which are clustered in the genome together with methylation-guide snoRNA genes. These modification-guide snoRNAs and snoRNA genes are the first ones to be reported in euglenid protists, the evolutionary sister group to the kinetoplastid protozoa. Unexpectedly, we also found and have partially characterized a selenocysteine tRNA homolog in the anti-Cbf5p-immunoprecipitated sample.

  17. Regional cerebral blood flow (rCBF) in man during perception of radiant warmth and heat pain.

    PubMed

    Ryding, E; Eriksson, M B; Rosén, I; Ingvar, D H

    1985-08-01

    The present study concerns the effects of experimental pain (radiant warmth and heat pain) on regional cerebral blood flow (rCBF) in pretrained subjects. The radiant warmth caused a general rCBF increase. However, if anxiety was avoided, heat pain caused the general rCBF level to return towards the level at rest. Thus, pain sensation per se may not cause a larger rCBF (and metabolic) response than that of the localized tactile stimulation, provided that the element of psychic apprehension and anxiety is eliminated or controlled.

  18. Reassessing the clinical efficacy of two MR quantitative DSC PWI CBF algorithms following cross-calibration with PET images

    NASA Astrophysics Data System (ADS)

    Chen, Jean J.; Frayne, Richard; Smith, Michael R.

    2005-03-01

    Clinical cerebral blood flow (CBF) maps generated through dynamic- susceptibility contrast (DSC) magnetic resonance (MR) perfusion imaging are currently cross-calibrated with PET studies. The cross-calibration is achieved by rescaling the MR CBF values so that normal white matter CBF corresponds to 22 ml/100 g/min. Examples are provided in this paper to show how this rescaling procedure changes both the clinical interpretation of CBF maps and the manner by which the performance of a given deconvolution algorithm should be assessed. (i) Singular-value decomposition-based (SVD) algorithms produce absolute CBF estimates that are inherently under-estimated for all tissue mean transit times (MTT) but, after rescaling, will generate CBF maps that are over-estimated for MTT >4.8 s. (ii) In principle, frequency-domain modelling techniques are expected to be inherently less sensitive to contrast recirculation biases than the time-domain SVD algorithms. However, it is shown that both CBF algorithms become greatly less sensitive to distortions from recirculation after clinical cross-calibration through rescaling has been performed. It is concluded that, when rescaling procedures are employed, it is relatively more important to develop deconvolution algorithms that produce CBF estimates with accuracies that vary little with MTT than to produce algorithms that provide inherently more accurate CBF estimates, but whose relative accuracy varies significantly with MTT. A portion of this work was presented at the 2004 Annual Scientific Meeting of the ISMRM, 15-21 May, Kyoto, Japan.

  19. A case-crossover study of transient risk factors for occupational acute hand injury

    PubMed Central

    Sorock, G; Lombardi, D; Hauser, R; Eisen, E; Herrick, R; Mittleman, M

    2004-01-01

    Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work. PMID:15031387

  20. Effect of precipitating factors of acute heart failure on readmission and long‐term mortality

    PubMed Central

    Arrigo, Mattia; Tolppanen, Heli; Sadoune, Malha; Feliot, Elodie; Teixeira, Antonio; Laribi, Said; Plaisance, Patrick; Nouira, Semir; Yilmaz, Mehmet Birhan; Gayat, Etienne

    2016-01-01

    Abstract Aims Acute heart failure (AHF) is one of the leading causes of unscheduled hospitalization and is associated with frequent readmissions and substantial mortality. Precipitating factors of AHF influence short‐term mortality, but their effect on outcome after hospital discharge is unknown. The present study assessed the effect of precipitating factors on readmission and long‐term survival in the overall population and in patients aged 75 years or younger. Methods and results Patients admitted with AHF (n = 755) included in the multicentre cohort ‘Biomarcoeurs’ were included in the study. Precipitating factors of AHF were classified in four main groups: acute coronary syndrome, atrial fibrillation, acute pulmonary disease and other causes. Hospital readmission during 90 days after discharge and survival at 1 year were analysed. Precipitating factors influenced readmissions and survival. Acute pulmonary disease was associated with fewer readmissions (HR 0.61, 95% confidence interval (CI) 0.37–0.99, P = 0.049), especially in patients aged 75 years or younger (HR 0.20, 95% CI 0.06–0.63, P = 0.006), whereas atrial fibrillation (HR 2.23, 95% CI 1.29–3.85, P = 0.004) and acute coronary syndrome (HR 2.23, 95% CI 1.02–4.86, P = 0.044) were associated with more readmissions. Patients with acute pulmonary disease at admission showed higher mortality (HR 1.59, 95% CI 1.04–2.43, P = 0.034), especially in subjects aged 75 years or younger (HR 2.52, 95% CI 1.17–5.41, P = 0.018). Conclusions Precipitating factors of AHF substantially influenced outcome after hospitalization. In particular, patients with AHF precipitated by acute pulmonary disease showed fewer readmissions and higher 1 year mortality, especially in patients aged 75 years or younger.

  1. 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

  2. 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

  3. 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

  4. Acute severe asthma. A prospective study of the precipitating factors in 40 children.

    PubMed

    Potter, P C; Weinberg, E; Shore, S C

    1984-09-15

    A prospective study was undertaken to determine the factors precipitating acute severe asthma in children attending the Red Cross War Memorial Children's Hospital, Cape Town. A comparison in terms of recent exposure to possible precipitating factors was made between 40 known asthmatics presenting with acute severe asthma and 40 known asthmatics who were clinically well. Exposure to known allergens had occurred in 7 cases. The time of onset of symptoms bore no relationship to meteorological changes in temperature, humidity or average pressure. Drug compliance in both groups was of the order of 50%. The majority of severe asthma attacks were associated with infection of the respiratory tract. The importance of infection as a precipitating factor in a severe asthma attack is discussed with reference to the cholinergic, adrenergic and immunological mechanisms.

  5. [Background factors in the detection of drug-resistant bacteria in adult patients with acute rhinosinusitis].

    PubMed

    Tomiyama, Michio

    2014-02-01

    In the treatment of adult patients with acute rhinosinusitis, it has been assumed that subjects over 65 years of age or living with children attending a day nursery, are at higher risk for infection with drug-resistant bacteria. However there are few reports which have discussed the relationship between those risk factors and adult patients with acute rhinosinusitis. I investigated the association between adult patients with acute rhinosinusitis living with children attending a day nursery and gender, ages, and frequency of detection of drug-resistant bacteria. From 2010 to 2012, a total of 598 adult patients with acute rhinosinusitis were enrolled. The majority of the study subjects were women, and the largest 10-year age group was 30-39 years. By sex, a greater proportion of the female subjects than the male subjects lived with children attending a day nursery. By age, the proportion of subjects who lived with children attending a day nursery was significantly higher in the 30-39-year age group than other age groups. Drug-resistant Streptococcus pneumoniae and ampicillin (ABPC)-resistant Haemophilus influenzae were detected at significantly higher rates in subjects with children attending a day nursery than in those without. There were no significant difference in drug-resistant bacteria detection between subjects over 65 years of age, and under 65 years. These findings suggested that living with children attending a day nursery is a risk factor and source of infection by drug-resistant organisms that may cause intra-familial infections of adult patients with acute rhinosinusitis. These results suggested we must ask adult patients with acute rhinosinusitis whether they are living with children attending a day nursery or not, when we plan their treatment strategy.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    PubMed Central

    Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

    2016-01-01

    Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

  11. Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events

    PubMed Central

    Hamzic-Mehmedbasic, Aida

    2016-01-01

    Introduction: Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events. Aim: This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS. Methods: In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality. Results: Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018). Conclusion: Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS. PMID:27703283

  12. Transcriptome Profiling of Pediatric Core Binding Factor AML.

    PubMed

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

    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 = 1.5 x 10(-51) and p = 1.8 x 10(-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

  13. 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

  14. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  15. 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.

  16. Archaeal proteins Nop10 and Gar1 increase the catalytic activity of Cbf5 in pseudouridylating tRNA.

    PubMed

    Kamalampeta, Rajashekhar; Kothe, Ute

    2012-01-01

    Cbf5 is a pseudouridine synthase that usually acts in a guide RNA-dependent manner as part of H/ACA small ribonucleoproteins; however archaeal Cbf5 can also act independently of guide RNA in modifying uridine 55 in tRNA. This guide-independent activity of Cbf5 is enhanced by proteins Nop10 and Gar1 which are also found in H/ACA small ribonucleoproteins. Here, we analyzed the specific contribution of Nop10 and Gar1 for Cbf5-catalyzed pseudouridylation of tRNA. Interestingly, both Nop10 and Gar1 not only increase Cbf5's affinity for tRNA, but they also directly enhance Cbf5's catalytic activity by increasing the k(cat) of the reaction. In contrast to the guide RNA-dependent reaction, Gar1 is not involved in product release after tRNA modification. These results in conjunction with structural information suggest that Nop10 and Gar1 stabilize Cbf5 in its active conformation; we hypothesize that this might also be true for guide-RNA dependent pseudouridine formation by Cbf5.

  17. 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.

  18. 9. (Credit CBF) The McNeil Street Station from the northwest, ...

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

    9. (Credit CBF) The McNeil Street Station from the northwest, March 1913. The low service pump room is on the right, the clear water well (installed c1900) and filter house are on the left. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  19. 10. (Credit CBF) The McNeil Street Station from the west, ...

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

    10. (Credit CBF) The McNeil Street Station from the west, March 1913. The low service pump room is on the left. The 'coal shed' which housed the laboratory (after 1908), the alum and lime rooms, and chemical storage is on the right. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

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

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

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

  1. 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

  2. Evaluation of MRI Models in the Measurement of CMRO2 and Its Relationship With CBF

    PubMed Central

    Lin, Ai-Ling; Fox, Peter T.; Yang, Yihong; Lu, Hanzhang; Tan, Li-Hai; Gao, Jia-Hong

    2008-01-01

    The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO2) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single-compartment model (SCM) and the multi-compartment model (MCM), were used to determine the relative changes in CMRO2 using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; α = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and α from measured δCBV and δCBF); and [3] MCM. The magnitude of relative changes in CMRO2 and the nonlinear relationship between CBF and CMRO2 obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO2 and determining the flow-metabolism relationship. PMID:18666102

  3. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances.

    PubMed

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  4. 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

  5. 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

  6. Simulation of LV pacemaker lead in marginal vein: potential risk factors for acute dislodgement.

    PubMed

    Zhao, Xuefeng; Burger, Mike; Liu, Yi; Das, Mithilesh K; Combs, William; Wenk, Jonathan F; Guccione, Julius M; Kassab, Ghassan S

    2011-03-01

    Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design. PMID:21303182

  7. Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner

    PubMed Central

    Al-Matary, Yahya S.; Botezatu, Lacramioara; Opalka, Bertram; Hönes, Judith M.; Lams, Robert F.; Thivakaran, Aniththa; Schütte, Judith; Köster, Renata; Lennartz, Klaus; Schroeder, Thomas; Haas, Rainer; Dührsen, Ulrich; Khandanpour, Cyrus

    2016-01-01

    The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo. These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia. PMID:27390361

  8. Risk factors for acute myocardial infarction in a southern Chinese population.

    PubMed

    Donnan, S P; Ho, S C; Woo, J; Wong, S L; Woo, K S; Tse, C Y; Chan, K K; Kay, C S; Cheung, K O; Mak, K H

    1994-01-01

    Although the mortality rate from coronary artery disease in Hong Kong is only one-fourth of that of northern Europe and the United States, the disease has been and remains the second major cause of death (after all cancers combined). Beginning in 1987, we have conducted a case-control study of acute myocardial infarction in four Hong Kong hospitals. This study, one of the biggest case-control studies conducted in the Chinese population of both men and women, confirms the importance of several risk factors--cigarette smoking, history of hypertension, history of diabetes, body fatness, and lack of physical activity--previously described in data collected in western populations. In addition, more adverse childhood experience was also found to be an important risk factor of acute myocardial infarction. Further research in appropriate intervention measures in education in the prevention and cessation of smoking, the control of blood pressure, diabetes, and overweight, and adequate exercise could significantly help reduce the risk of acute myocardial infarction in the Hong Kong Chinese population.

  9. Acute Targeting of General Transcription Factor IIB Restricts Cardiac Hypertrophy via Selective Inhibition of Gene Transcription

    PubMed Central

    Sayed, Danish; Yang, Zhi; He, Minzhen; Pfleger, Jessica M.; Abdellatif, Maha

    2014-01-01

    Background We previously reported that specialized and housekeeping genes are differentially regulated via de novo recruitment and pause-release of RNA polymerase II (pol II), respectively, during cardiac hypertrophy. However, the significance of this finding remains to be examined. Therefore, the purpose of this study was to determine the mechanisms that differentially regulate these gene groups and exploit them for therapeutic targeting. Methods and Results Here we show that general transcription factor IIB (TFIIB) and cyclin-dependent kinase 9 are upregulated during hypertrophy, both targeted by miR-1, and play preferential roles in regulating those two groups of genes. Chromatin immunoprecipitation-sequencing reveals that TFIIB is constitutively bound to all paused, housekeeping, promoters, whereas, de novo recruitment of TFIIB and pol II is required for specialized genes that are induced during hypertrophy. We exploited this dichotomy to acutely inhibit induction of the latter set, which encompasses cardiomyopathy, immune reaction, and extracellular matrix genes, using locked nucleic acid (LNA)-modified antisense TFIIB oligonucleotide treatment. This resulted in suppression of all specialized genes, while sparing the housekeeping ones, and, thus, attenuated pathological hypertrophy. Conclusions The data for the first time reveal distinct general transcription factor IIB dynamics that regulate specialized vs. housekeeping genes during cardiac hypertrophy. Thus, by acutely targeting TFIIB we were able to selectively inhibit the former set of genes and ameliorate pressure overload hypertrophy. We also demonstrate the feasibility of acutely and reversibly targeting cardiac mRNA for therapeutic purposes using LNA-modified antisense oligonucleotides. PMID:25398966

  10. Factors impacting on doctors' management of acute low back pain: a systematic review.

    PubMed

    Fullen, Brona M; Baxter, G David; O'Donovan, Barry G G; Doody, Catherine; Daly, Leslie E; Hurley, Deirdre A

    2009-10-01

    The aim of this review was to determine the factors that impact on doctors' management of patients with acute low back pain. A methodological assessment of databases (Medline, EMBASE, Psychinfo, BIOSIS, CINAHL, and the Cochrane Central Register of Controlled Trials) identified papers which were screened for inclusion criteria by two independent reviewers. Data were extracted from accepted papers, and the internal validity and strength of the evidence were determined using valid and reliable scales. The search generated a total of 28 papers [quantitative (n=27), qualitative (n=1) methodologies]. Themes were identified from the accepted papers: education (n=18), knowledge of clinical guidelines and impact on management (n=7), and doctors' demographics (n=4). There was consistent evidence that doctors did not adhere to clinical guidelines when performing a spinal assessment. There was inconsistent evidence that education increased adherence with acute LBP guideline recommendations in terms of referral rates to physiotherapy, for investigations, to secondary care and for maintaining patients at work. Strategies to address the factors impacting on doctors' management of acute LBP are required; these would lead to improvement in patient outcomes and reduce healthcare costs. PMID:19110456

  11. Brain-derived neurotrophic factor and substrate utilization following acute aerobic exercise in obese individuals.

    PubMed

    Slusher, A L; Whitehurst, M; Zoeller, R F; Mock, J T; Maharaj, A; Huang, C-J

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity-related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal-weight subjects. Furthermore, we aimed to investigate whether acute exercise-induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty-two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m(2)) and 11 normal-weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m(2))] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal-weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal-weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P < 0.001). These findings suggest that acute exercise-elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.

  12. Selection of Reversions and Suppressors of a Mutation in the CBF Binding Site of a Lymphomagenic Retrovirus

    PubMed Central

    Martiney, Marita J.; Rulli, Karen; Beaty, Robert; Levy, Laura S.; Lenz, Jack

    1999-01-01

    The retrovirus SL3 induces T-cell lymphomas in mice. The transcriptional enhancer in the long terminal repeat (LTR) of SL3 contains two 72-bp repeats. Each repeat contains a binding site for the transcription factor CBF (also called AML1). The CBF binding sites are called core elements. SAA is a mutant that is identical to SL3 except for the presence of a single-base-pair substitution in each of the two core elements. This mutation significantly attenuates viral lymphomagenicity. Most lymphomas that occur in SAA-infected mice contain proviruses with reversions or second-site suppressor mutations within the core element. We examined the selective pressures that might account for the predominance of the reversions and suppressor mutations in tumor proviruses by analyzing when proviruses with altered core sequences became abundant during the course of lymphomagenesis. Altered core sequences were easily detected in thymus DNAs by 4 to 6 weeks after SAA infection of mice, well before lymphomas were grossly evident. This result is consistent with the hypothesis that viruses with the core sequence alterations emerged because they replicated more effectively in mice than SAA. The number of 72-bp tandem, repeats in the viral LTR was found to vary, presumably as a consequence of reverse transcriptase slippage during polymerization. Proviruses with two repeats predominated in the thymuses of SAA- and SL3-infected mice before lymphomas developed, although LTRs with one or three repeats were also present. This suggested that two was the optimal number of 72-bp repeats for viral replication. However, in lymphomas, proviruses with three or four repeats usually predominated. This suggested that a late step in the process of lymphomagenesis led to the abundance of proviruses with additional repeats. We hypothesize that proviruses with additional 72-bp repeats endowed the cells containing them with a selective growth advantage. PMID:10438850

  13. 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

  14. Incidence and risk factors for acute low back pain in active duty infantry.

    PubMed

    Ernat, Justin; Knox, Jeffrey; Orchowski, Joseph; Owens, Brett

    2012-11-01

    Although much research has been performed on occupational risk factors for low back pain, little has been published on low back pain among infantrymen. This purpose of this study is to evaluate the incidence of acute low back pain amongst active duty infantrymen as compared to a matched control population. The Defense Medical Epidemiology Database was searched and incidence rates were calculated and compared between infantry and noninfantry soldiers. Data was stratified and controlled for age, race, marital status, rank, and branch of service using the Poisson multivariate regression analysis. Significantly lower rates of acute low back pain were discovered in active duty infantrymen when compared to matched controls (32.9 versus 49.5 cases per 1,000 person-years). Additionally, significantly lower rates were identified in the Marines versus the Army, and among junior enlisted compared to senior enlisted service members. PMID:23198512

  15. Independent risk factors for hypoxemia after surgery for acute aortic dissection

    PubMed Central

    Sheng, Wei; Yang, Hai-Qin; Chi, Yi-Fan; Niu, Zhao-Zhuo; Lin, Ming-Shan; Long, Sun

    2015-01-01

    Objectives: To determine risk factors associated with postoperative hypoxemia after surgery for acute type A aortic dissection. Methods: We retrospectively analyzed the clinical data of 192 patients with acute type A aortic dissection who underwent surgery in Qingdao Municipal Hospital, Medical College of Qingdao University, Qingdao, China between January 2007 and December 2013. Patients were divided into hypoxemia group (n=55) [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤200 mm Hg] and non-hypoxemia group (n=137) [PaO2/FiO2 >200 mm Hg]. Perioperative clinical data were analyzed and compared between the 2 groups. Results: The incidence of postoperative hypoxemia after surgery for acute aortic dissection was 28.6% (55/192). Perioperative death occurred in 13 patients (6.8%). Multivariate regression identified body mass index (BMI) >25 kg/m2 (OR=21.929, p=0.000), deep hypothermic circulatory arrest (DHCA) (OR=11.551, p=0.000), preoperative PaO2/FiO2 ≤300 mm Hg (OR=7.830, p=0.000) and blood transfusion >6U in 24 hours postoperatively (OR=12.037, p=0.000) as independent predictors of postoperative hypoxemia for patients undergoing Stanford A aortic dissection surgery. Conclusion: Our study demonstrated that BMI >25 kg/m2, DHCA, preoperative PaO2/FiO2 ≤300 mm Hg, and blood transfusion in 24 hours postoperatively >6U were independent risk factors of the hypoxemia after acute type A aortic dissection aneurysm surgery. PMID:26219444

  16. 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

  17. 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

  18. 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

  19. 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

  20. Opposing Control by Transcription Factors MYB61 and MYB3 Increases Freezing Tolerance by Relieving C-Repeat Binding Factor Suppression1[OPEN

    PubMed Central

    Zhang, Yunqin; Miao, Zhenyan; Xie, Can; Meng, Xiangzhao; Deng, Jie; Mysore, Kirankumar S.; Frugier, Florian; Wang, Tao

    2016-01-01

    Cold acclimation is an important process by which plants respond to low temperature and enhance their winter hardiness. C-REPEAT BINDING FACTOR1 (CBF1), CBF2, and CBF3 genes were shown previously to participate in cold acclimation in Medicago truncatula. In addition, MtCBF4 is transcriptionally induced by salt, drought, and cold stresses. We show here that MtCBF4, shown previously to enhance drought and salt tolerance, also positively regulates cold acclimation and freezing tolerance. To identify molecular factors acting upstream and downstream of the MtCBF4 transcription factor (TF) in cold responses, we first identified genes that are differentially regulated upon MtCBF4 overexpression using RNAseq Digital Gene Expression Profiling. Among these, we showed that MtCBF4 directly activates the transcription of the COLD ACCLIMATION SPECIFIC15 (MtCAS15) gene. To gain insights into how MtCBF4 is transcriptionally regulated in response to cold, an R2R3-MYB TF, MtMYB3, was identified based on a yeast one-hybrid screen as binding directly to MYB cis-elements in the MtCBF4 promoter, leading to the inhibition of MtCBF4 expression. In addition, another MYB TF, MtMYB61, identified as an interactor of MtMYB3, can relieve the inhibitory effect of MtMYB3 on MtCBF4 transcription. This study, therefore, supports a model describing how MtCBF4 is regulated by antagonistic MtMYB3/MtMYB61 TFs, leading to the up-regulation of downstream targets such as MtCAS15 acting in cold acclimation in M. truncatula. PMID:27578551

  1. Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias.

    PubMed

    Poirel, H; Radford-Weiss, I; Rack, K; Troussard, X; Veil, A; Valensi, F; Picard, F; Guesnu, M; Leboeuf, D; Melle, J

    1995-03-01

    Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.

  2. Keratinocyte growth factor-2 is protective in lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Tong, Lin; Bi, Jing; Zhu, Xiaodan; Wang, Guifang; Liu, Jie; Rong, Linyi; Wang, Qin; Xu, Nuo; Zhong, Ming; Zhu, Duming; Song, Yuanlin; Bai, Chunxue

    2014-09-15

    Keratinocyte growth factor-2 (KGF-2) plays a key role in lung development, but its role in acute lung injury has not been well characterized. Lipopolysaccharide instillation caused acute lung injury, which significantly elevated lung wet-to-dry weight ratio, protein and neutrophils in bronchoalveolar lavage fluid (BALF), inhibited surfactant protein A and C expression in lung tissue, and increased pathological injury. Pretreatment with KGF-2 improved the above lung injury parameters, partially restored surfactant protein A and C expression, and KGF-2 given 2-3 days before LPS challenge showed maximum lung injury improvement. Pretreatment with KGF-2 also markedly reduced the levels of TNF-α, MIP-2, IL-1β and IL-6 in BALF and the levels of IL-1β and IL-6 in lung tissue. Histological analysis showed there was increased proliferation of alveolar type II epithelial cells in lung parenchyma, which reached maximal 2 days after KGF-2 instillation. Intratracheal administration of KGF-2 attenuates lung injury induced by LPS, suggesting KGF-2 may be potent in the intervention of acute lung injury.

  3. Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

    PubMed

    Newsholme, S J; Thudium, D T; Gossett, K A; Watson, E S; Schwartz, L W

    2000-01-01

    Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.

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

    PubMed

    Somasundaram, Rajesh; Prasad, Mahadesh A J; Ungerbäck, Jonas; Sigvardsson, Mikael

    2015-07-01

    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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Precipitating Factors for Acute Heart Failure Hospitalization and Long-Term Survival.

    PubMed

    Berkovitch, Anat; Maor, Elad; Sabbag, Avi; Chernomordik, Fernando; Elis, Avishay; Arbel, Yaron; Goldenberg, Ilan; Grossman, Ehud; Klempfner, Robert

    2015-12-01

    Heart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations.Different precipitating factors have various effects on long-term survival.We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality.Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43-0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01-1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value <0.001). Subgroup analysis showed that among the nonischemic precipitant, the presence of renal dysfunction and infection were both associated with poor short-term outcomes (OR 1.56, [P < 0.001] and OR 1.35 [P < 0.001], respectively), as well as long-term (HR 1.59 [P < 0.001] and HR 1.24 [P < 0.001], respectively).Identification of precipitating factors for acute HF hospitalization has important short- and long-term implications that can be used for improved risk stratification and management. PMID:26717369

  12. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

    PubMed

    Connolly, Stuart J; Milling, Truman J; Eikelboom, John W; Gibson, C Michael; Curnutte, John T; Gold, Alex; Bronson, Michele D; Lu, Genmin; Conley, Pamela B; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L; Siegal, Deborah M; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W Ting; Crowther, Mark

    2016-09-22

    Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. Results The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. Conclusions On the basis of a

  13. 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.

  14. 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

  15. 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

  16. Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis.

    PubMed

    de Souza, L J; Sampietre, S N; Assis, R S; Knowles, C H; Leite, K R; Jancar, S; Monteiro Cunha, J E; Machado, M C

    2001-01-01

    Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.

  17. [Factors associated with acute malnutrition in migrating pre-school children from the sugar cane region of Jalisco].

    PubMed

    Salcedo-Rocha, A L; Prado-Aguilar, C A

    1991-03-01

    The purpose of this study is to identify the association between socioeconomic, environmental, feeding and individual factors involved in the acute malnutrition of the migrating pre-schooler. A comparative, transversal, observational study was conducted in 511 children between the ages of 1 and 5 from child care centers in the Jalisco sugar cane area. Using anthropometric indicators, classified according to Waterlow, their nutritional state was evaluated. The prevalence of the malnutrition was 79.0 per 100 preschoolers (68.1% adapted, 21.5% acutely chronic and 10.4% acute). Those factors associated with acute malnutrition included: a family income of less than the established minimum wage (O.R. = 6.32, P = 0.00), a lesser amount with an acute pathology (O.R. = 3.34, P = 0.00) and being a year old (O.R. = 2.22, P = 0.01). Significant differences were found among children of parents who: did not have an education (P = 0.04) and who were sugar cane cutters (P = 0.05). The findings identify risk factors for acute malnutrition, probably modifiable using nutritional epidemiological surveillance strategies.

  18. Autocrine motility factor receptor promotes the proliferation of human acute monocytic leukemia THP-1 cells

    PubMed Central

    WANG, YINGCHAO; MA, LINA; WANG, CHUNMEI; SHENG, GUANGYAO; FENG, LEI; YIN, CHUYUN

    2015-01-01

    The aberrant activation of autocrine motility factor receptor (AMFR) has been implicated in several types of human cancer. The present study aimed to elucidate the effect of AMFR on the regulation of proliferation in an acute monocytic leukemia cell line, THP-1. THP-1 cells were transfected with AMFR-targeted small interfering (si)RNA and a plasmid encoding a truncated AMFR, AMFR-C, (pcDNA3.1-AMFR-C). The mRNA and protein levels of AMFR and the downstream targets, rho-associated, coiled-coil containing protein kinase 2 (ROCK2), cyclin D1, and B-cell lymphoma (Bcl)-2, were measured using reverse transcription-quantitatibe polymerase chain reaction and immunoblot analyses. The effects on cell cycle and apoptosis were investigated using flow cytometry. The present study successfully established the knockdown of AMFR and expression of AMFR-C in the THP-1 cells. Downregulation of AMFR induced cell cycle arrest at the G0/G1 phase, and increased apoptosis of the THP-1 cells (all P<0.05). The AMFR siRNA increased the percentage of early apoptotic cells between 3.88±1.43 and 19.58±4.29% (P<0.05). The expression levels of ROCK2, cyclin D1 and Bcl-2 were reduced by the downregulation of AMFR and enhanced by overexpression of AMFR-C. In conclusion, AMFR appears to be crucial for the proliferation of the THP-1 acute monocytic leukemia cell line. Therefore, AMFR may represent a potential target for the treatment of acute monocytic leukemia. PMID:26136223

  19. The effects of granulocyte colony-stimulating factor in preclinical models of infection and acute inflammation.

    PubMed

    Marshall, John C

    2005-12-01

    The cytokine granulocyte colony-stimulating factor (G-CSF) is a potent endogenous trigger for the release of neutrophils from bone marrow stores and for their activation for enhanced antimicrobial activity. G-CSF has been widely evaluated in preclinical models of acute illness, with generally promising though divergent results. A recombinant G-CSF molecule has recently undergone clinical trials to assess its efficacy as an adjuvant therapy in community-acquired and nosocomial pneumonia, however, these studies failed to provide convincing evidence of benefit. We undertook a systematic review of the published literature reporting the effects of modulation of G-CSF in preclinical in vivo models to determine whether evidence of differential efficacy might explain the disappointing results of human studies and point to disease states that might be more likely to benefit from G-CSF therapy. G-CSF has been evaluated in 86 such studies involving a variety of different models. The strongest evidence of benefit was seen in studies involving intraperitoneal challenge with live organisms; benefit was evident whether the agent was given before or after challenge. G-CSF demonstrates anti-inflammatory activity in models of systemic challenge with viable organisms or endotoxin, but only when the agent is given before challenge; evidence of benefit after challenge was minimal. Preclinical models of intrapulmonary challenge only show efficacy when the cytokine is administered before the infectious challenge, and suggested harm in gram-negative pneumonia resulting from challenge with Escherichia coli or Klebsiella. There is little evidence for therapeutic efficacy in noninfectious models of acute illness. We conclude that the most promising populations for evaluation of G-CSF are neutropenic patients with invasive infection and patients with intra-abdominal infection, particularly those with the syndrome of tertiary, or recurrent, peritonitis. Significant variability in the design

  20. 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.

  1. 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.

  2. The risk factors for thrombosis in children with acute lymphoblastic leukemia.

    PubMed

    Sivaslioglu, Selda; Gursel, Turkiz; Kocak, Ulker; Kaya, Zuhre

    2014-09-01

    We aimed to scrutinize the risk factors for thrombosis in children with acute lymphoblastic leukemia treated with the Berlin-Frankfurt-Münster 95 protocol. The study population was 82 children younger than 16 years of age. The children were followed up for 10 years until January 2007. Thrombosis occurred in 10 (12%) of 82 patients during the treatment course, mainly after the M protocol. The most common risk factor was factor V Leiden (FVL; 15.6%). This was followed by methyleneterahydrofolate reductase (MTHFR; 9.3%), elevated lipoprotein (1.5%), and prothrombin (PT) 20210A (1.5%) in descending order. The risk of thrombosis was found to be significantly high in patients with FVL mutation (odds ratio = 7.1, 95% confidence interval = 1.6-30.5). The risk of thrombosis was not significant in patients with MTHFR and PT20210A mutation (P = .2). Age, catheter usage, FVL mutation, and prednisolone treatment are significant risk factors for thromboemboli occurrence.

  3. 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

  4. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  5. 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

  6. 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

  7. BET bromodomain inhibition suppresses the functional output of hematopoietic transcription factors in acute myeloid leukemia

    PubMed Central

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

    2015-01-01

    Summary 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 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

  8. Factor IXa as a target for pharmacologic inhibition in acute coronary syndrome.

    PubMed

    Roser-Jones, Christopher; Chan, Mark; Howard, Emily L; Becker, Kristian C D; Rusconi, Christopher P; Becker, Richard C

    2011-08-01

    Anticoagulant therapy, combined with platelet-directed inhibitors, represents a standard-of-care in the management of patients with acute coronary syndrome, particularly those who require percutaneous coronary interventions. While a vast clinical experience, coupled with large clinical trials have collectively provided guidance, an optimal anticoagulant drug and applied strategy, defined as one that reduces thrombotic and hemorrhagic events consistently, with minimal off-target effects and active control of systemic anticoagulation according to patient and clinical-setting specific need, remains at large. An advancing knowledge of coagulation, hemostasis, and thrombosis suggests that factor IXa, a protease that governs thrombin generation in common thrombotic disorders may represent a prime target for pharmacologic inhibition.

  9. 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

  10. [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

  11. [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.

  12. 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

  13. 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

  14. Spectrum, antibiotic susceptibility and virulence factors of bacterial infections complicating severe acute pancreatitis.

    PubMed

    Israil, A M; Palade, R; Chifiriuc, M C; Vasile, D; Grigoriu, M; Voiculescu, D; Popa, D

    2011-01-01

    Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, their antibiotic susceptibility patterns and virulence features in patients with severe acute pancreatitis (SAP). A total of 19 patients with acute pancreatitis were consecutively selected from 153 clinical cases of septic abdominal surgical emergencies (age 29-80, 12 males, 7 females) admitted during 2009-2011, in the First Surgical Clinic of the University Emergency Hospital of Bucharest. All 19 SAP cases were submitted to pre-operatory antibiotic empiric treatment. Ten cases were culture negative, in spite of the positive microscopy registered in eight of them. The rest of nine cases were culture positive, 17 different bacterial strains being isolated and identified as belonging to eight aerobic and four anaerobic species. Polymicrobial infection was seen in six patients and the etiology was dominated by Gram-negative bacilli, followed by gut anaerobic bacteria, attesting their colonic origin. The susceptibility testing of the isolated strains confirmed in vitro in all cases the efficiency of the antibiotics that had been used in the empiric pre-operatory treatment. Out of 19 cases submitted to pre-operatory empiric treatment, 14 proved a favorable evolution and five a lethal outcome. The host depending factors (sepsis and other co-morbidities), as well as the aggressivity of the isolated microbial strains (mediated by the presence of different factors implicated in adherence, toxicity and invasion) were found to contribute to the unfavorable, even lethal clinical outcome of SAP cases. In spite of all theoretical controversies, the antibiotic therapy remains at present a very important therapeutic mean for the SAP treatment; although it cannot solve the septic necrotizing pancreatitis in 100% of cases, however

  15. Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype

    PubMed Central

    Jang, J E; Min, Y H; Yoon, J; Kim, I; Lee, J-H; Jung, C W; Shin, H-J; Lee, W S; Lee, J H; Hong, D-S; Kim, H-J; Kim, H-J; Park, S; Lee, K-H; Jang, J H; Chung, J S; Lee, S M; Park, J; Park, S K; Ahn, J-S; Min, W-S; Cheong, J-W

    2015-01-01

    Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated. PMID:26473530

  16. 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

  17. 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

  18. Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome.

    PubMed

    Gruss, E; Bernis, C; Tomas, J F; Garcia-Canton, C; Figuera, A; Motellón, J L; Paraiso, V; Traver, J A; Fernandez-Rañada, J M

    1995-01-01

    To assess the prevalence, risk factors, clinical causes and outcome of acute renal failure (ARF) following bone marrow transplantation (BMT), a retrospective analysis of 275 patients was undertaken. ARF was diagnosed in 72 patients (26%) and occurred in 81.9% within the first month. The three main clinical causes were multifactorial (36%), nephrotoxic (29%), and veno-occlusive disease of the liver (VOD) 15%. The prevalence was higher in allogeneic BMT (36%) than in autologous BMT (6.5%). Risk factors related to the development of ARF wee preexisting VOD and age older than 25 years. Logistic regression in allogeneic BMT confirmed this association (VOD, odds ratio 3.8; age offer than 25, odds ratio 1.9). Underlying disease, graft-versus-host disease, sepsis, conditioning therapy, and sex were not associated with ARF. Seventeen cases of ARF required hemodialysis (24%) mainly in association with VOD (70.5%). The overall morality from ARF was 45.8%, the dialyzed group having the highest mortality (88%). Survival in the ARF group was continuously worse up to 3 months and the actuarial survival at 10 years was 29.7 versus 53.2%. We conclude that ARF is a common complication mainly in allogeneic BMT and carries a grave prognosis. VOD and age were risk factors for ARF.

  19. 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

  20. 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.

  1. 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

  2. HES1 is an independent prognostic factor for acute myeloid leukemia

    PubMed Central

    Tian, Chen; Tang, Yingjun; Wang, Tengteng; Yu, Yong; Wang, Xiaofang; Wang, Yafei; Zhang, Yizhuo

    2015-01-01

    HES1 is the target of Notch signaling which is reported to affect cell differentiation and maintain the cells in G0 phase in various tissues including the hematopoietic tissue. HES1 expression appears to be an independent prognostic factor for survival in a heterogeneous group of acute myeloid leukemia (AML) patients. To better assess its significance, we analyzed HES1 expression in a group of non-core binding factor AML patients and correlated its expression with the overall survival and relapse-free survival of AML patients. First, we detected the messenger RNA expression of HES1 in 40 patients with AML by real-time polymerase chain reaction. The top 50% of AML cases with the high HES1 expression were compared with the rest of the AML cohort. Overall survival was calculated from the date of diagnosis until the date of death from any cause or until the date of final follow-up. Relapse-free survival was determined for responders from the time of diagnosis until relapse or death from any cause. We showed that the lower-expression group had a shorter overall survival time and shorter relapse-free survival time compared with those of the high-expression group (37.6±1.6 versus 54.0±1.3 months, 28.6±1.8 months versus 44.8±2.1 months, respectively, P<0.05), and Cox regression showed that HES1 was an independent prognostic factor. In all, we conclude that expression of HES1 is a useful prognostic factor for patients with non-core binding factor AML. PMID:25960660

  3. 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

  4. 14. (Credit CBF) The McNeil Street Pumping Station c1926, after ...

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

    14. (Credit CBF) The McNeil Street Pumping Station c1926, after substantial enlargement, from the front of the new combination main high service-low service pumping room. On the left, located over the old clear water well, is a circular building which housed both the laboratory and the chlorination room (it was added c1911). The tank above the lab-chlorination room is the filter wash water tank (new). From: South-West Waterworks Association Convention, Shreveport, Louisiana, October 1926, Souvenir Booklet, p.19) - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  5. 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

  6. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  7. Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

    PubMed

    Eisner, M D; Thompson, T; Hudson, L D; Luce, J M; Hayden, D; Schoenfeld, D; Matthay, M A

    2001-07-15

    In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

  8. Factors Associated with the Use of Preventive Care for Contrast-Induced Acute Kidney Injury

    PubMed Central

    Mor, Maria K.; Kim, Sunghee; Hartwig, Kathryn C.; Sonel, Ali F.; Palevsky, Paul M.; Fine, Michael J.

    2009-01-01

    BACKGROUND The factors that affect the implementation of preventive care for contrast-induced acute kidney injury (CIAKI) are unknown. OBJECTIVE To assess patient and provider factors associated with the use of preventive care for CIAKI. DESIGN Prospective cohort study. PARTICIPANTS Patients with kidney disease undergoing procedures with intravascular iodinated radiocontrast. MEASUREMENTS We recorded the use of preventive care defined as the administration of: (1) pre- and post-procedure isotonic intravenous (IV) fluid, (2) N-acetylcysteine, and (3) iso-osmolal radiocontrast. We surveyed patients’ providers to assess their knowledge, experience, and training on CIAKI and used multiple logistic regression to assess the independent associations of patient and provider factors with the use of these preventive interventions. RESULTS We enrolled 660 patients and 87 providers. Patient factors associated with use of IV fluid and N-acetylcysteine were higher baseline serum creatinine (OR 1.5 and 5.0, p < 0.05) and inpatient status (OR 3.0 and 6.3, p < 0.05), while higher baseline serum creatinine was associated with the use of iso-osmolal contrast (OR = 13.4, p < 0.01). The primary provider characteristics associated with the use of IV fluid and N-acetylcysteine were a greater degree of prior training on CIAKI (OR 1.9 and 2.8, p < 0.05) and higher number of prior patients with CIAKI (OR 2.7 and 2.6, p < 0.05). CONCLUSIONS Patient baseline kidney function and provider training and experience with CIAKI are independently associated with the use of preventive care. Efforts to increase and intensify the training providers receive on CIAKI may help decrease the incidence of this costly iatrogenic condition. PMID:19156472

  9. Factors affecting loss of tympanic membrane mobility in acute otitis media model of chinchilla.

    PubMed

    Guan, Xiying; Chen, Yongzheng; Gan, Rong Z

    2014-03-01

    Recently we reported that middle ear pressure (MEP), middle ear effusion (MEE), and ossicular changes each contribute to the loss of tympanic membrane (TM) mobility in a guinea pig model of acute otitis media (AOM) induced by Streptococcus pneumoniae (Guan and Gan, 2013). However, it is not clear how those factors vary along the course of the disease and whether those effects are reproducible in different species. In this study, a chinchilla AOM model was produced by transbullar injection of Haemophilus influenzae. Mobility of the TM at the umbo was measured by laser vibrometry in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent relatively early and later phases of AOM. In each group, the vibration of the umbo was measured at three experimental stages: unopened, pressure-released, and effusion-removed ears. The effects of MEP and MEE and middle ear structural changes were quantified in each group by comparing the TM mobility at one stage with that of the previous stage. Our findings show that the factors affecting TM mobility do change with the disease time course. The MEP was the dominant contributor to reduction of TM mobility in 4D AOM ears, but showed little effect in 8D ears when MEE filled the tympanic cavity. MEE was the primary factor affecting TM mobility loss in 8D ears, but affected the 4D ears only at high frequencies. After the release of MEP and removal of MEE, residual loss of TM mobility was seen mainly at low frequencies in both 4D and 8D ears, and was associated with middle ear structural changes. Our findings establish that the factors contributing to TM mobility loss in the chinchilla ear were similar to those we reported previously for the guinea pig ears with AOM. Outcomes did not appear to differ between the two major bacterial species causing AOM in these animal models.

  10. The role of tumor necrosis factor in increased airspace epithelial permeability in acute lung inflammation.

    PubMed

    Li, X Y; Donaldson, K; Brown, D; MacNee, W

    1995-08-01

    Increased airspace epithelial permeability is an early event in lung inflammation and injury. In this study, we have developed a rat model to study the mechanisms of the epithelial permeability to 125iodine-labeled bovine serum albumin (125I-BSA), instilled intratracheally during acute lung inflammation. Epithelial permeability was measured as the percentage of instilled 125I-BSA appearing in the blood. The increase in epithelial permeability induced by intratracheal instillation of heat-killed Corynebacterium parvum produced a peak influx of neutrophils into the bronchoalveolar space at 16 h, which occurred after the peak increase in epithelial permeability (8 h). The increased epithelial permeability induced by C. parvum did not appear to be protease- or oxidant-mediated. Depletion of peripheral blood neutrophils was achieved by an intravenous injection of anti-neutrophil polyclonal antibody. The consequent profound reduction in neutrophil and macrophage influx into the airspaces 8 h after instillation of C. parvum reduced the epithelial permeability to control values. Bronchoalveolar lavage (BAL) leukocytes from rats 8 h, but not 16 h, after treatment with C. parvum caused a modest increase in epithelial permeability when re-instilled intratracheally into control rat lungs. Separation of the leukocytes before re-instillation indicated that macrophages rather than neutrophils were predominantly responsible for the increased epithelial permeability. The presence of dramatically increased levels of tumor necrosis factor (TNF) in BAL 8 h in contrast to a slight increase in BAL 16 h after C. parvum, the release of TNF from 8 h macrophages, the increased epithelial permeability induced by TNF in epithelial monolayers in vitro, and the inhibition of C. parvum-induced epithelial permeability by TNF antibody support the premise that TNF is a major player in the increased epithelial permeability that occurs during C. parvum-induced acute alveolitis. PMID:7626286

  11. 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

  12. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka

    2013-01-01

    Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

  13. Are Intensive Care Factors Associated with Depressive Symptoms Six Months after Acute Lung Injury?

    PubMed Central

    Dowdy, David W.; Bienvenu, O. Joseph; Dinglas, Victor D.; Mendez-Tellez, Pedro A.; Sevransky, Jonathan; Shanholtz, Carl; Needham, Dale M.

    2009-01-01

    Objective To evaluate intensive care-related factors as predictors of depressive symptoms 6 months after acute lung injury (ALI) Design Prospective cohort study Setting Thirteen intensive care units (ICUs) in 4 hospitals in Baltimore, MD Patients Consecutive ALI survivors (n = 160; 71% from medical ICUs) screened for depressive symptoms at six months post-ALI Interventions None Measurements and Main Results We prospectively measured 12 features of critical illness and ICU care and used multivariable regression to evaluate associations with depressive symptoms as measured by the Hospital Anxiety and Depression (HAD) depression score. The prevalence of a positive screening for depression (score ≥8) at 6 months post-ALI was 26%. Depressive symptoms were significantly associated with surgical (versus medical or trauma) ICU admission (relative risk [RR] 2.2, 95% confidence interval [CI] 1.1 – 4.2), maximum daily Sequential Organ Failure Assessment score of >10 (RR 2.1, 95% CI 1.1 – 3.5), and mean daily ICU benzodiazepine dose of ≥75mg of midazolam-equivalent (RR 2.1, 95% CI 1.1 – 3.5). Conclusions Depressive symptoms at 6 months post-ALI are common and potentially associated with ICU-related factors. Mechanisms by which critical illness and intensive care management associate with depressive symptoms merit further investigation. PMID:19357507

  14. 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…

  15. 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

  16. 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...

  17. Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease.

    PubMed

    Siero, Jeroen C W; Hartkamp, Nolan S; Donahue, Manus J; Harteveld, Anita A; Compter, Annette; Petersen, Esben T; Hendrikse, Jeroen

    2015-01-15

    Blood-oxygenation-level-dependent (BOLD) MRI is widely used for inferring neuronal activation and is becoming increasingly popular for assessing cerebrovascular reactivity (CVR) when combined with a vasoactive stimulus. The BOLD signal contains changes in cerebral blood flow (CBF) and thus information regarding neurovascular coupling and CVR. The BOLD signal, however, is also modulated by changes in cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), as well as changes in the physiological baseline state. Here, we measured BOLD and CBF responses upon neuronal (visual) activation, before and after a vasodilatory challenge (acetazolamide, ACZ) in patients with vertebrobasilar steno-occlusive disease. After ACZ, the neuronal activation induced BOLD response was reduced or even negative (3 out of 8 subjects), whereas the CBF response remained similar. We show that BOLD alone cannot correctly assess the neuronal activation and underlying neurovascular coupling. The generally assumed positive relationship between BOLD and CBF responses may be severely compromised under changes in the physiological baseline state. Accompanying CBF measurements contain crucial information, and simulations suggest an altered flow-metabolism coupling in these patients.

  18. Uncoupling cognitive workload and prefrontal cortical physiology: a PET rCBF study.

    PubMed

    Goldberg, T E; Berman, K F; Fleming, K; Ostrem, J; Van Horn, J D; Esposito, G; Mattay, V S; Gold, J M; Weinberger, D R

    1998-05-01

    Working memory is a fundamental cognitive building block involved in the short-term maintenance and transformation of information. In neuropsychological studies, working memory has been shown to be of limited capacity; however, the neurophysiological concomitants of this capacity limitation have not been explored. In this study we used the [15O] water PET rCBF technique and statistical parametric mapping to examine normal subjects while they performed two cognitive tasks, both individually and simultaneously. One task was the Wisconsin Card Sorting Test, a complex reasoning task involving working memory, and the other was a rapidly paced auditory verbal shadowing task. When both tasks were performed simultaneously, there were significant decrements in performance compared with the individual task performance scores, indicating that cognitive workload had been increased. Analysis of the rCBF maps showed that when the two tasks were performed together, in contrast to when they were performed separately, there was less prefrontal activation. These results suggest that increases in cognitive workload do not necessarily recruit and then sustain cortical neurophysiological resources to a maximum, but rather may actually be accompanied by a diminution in cortical activity.

  19. Clinical course and prognostic factors in acute low back pain: an inception cohort study in primary care practice.

    PubMed Central

    Coste, J.; Delecoeuillerie, G.; Cohen de Lara, A.; Le Parc, J. M.; Paolaggi, J. B.

    1994-01-01

    OBJECTIVE--To describe the natural course of recent acute low back pain in terms of both morbidity (pain, disability) and absenteeism from work and to evaluate the prognostic factors for these outcomes. DESIGN--Inception cohort study. SETTING--Primary care. PATIENTS--103 patients with acute localised non-specific back pain lasting less than 72 hours. MAIN OUTCOME MEASURES--Complete recovery (disappearance of both pain and disability) and return to work. RESULTS--90% of patients recovered within two weeks and only two developed chronic low back pain. Only 49 of 100 patients for whom data were available had bed rest and 40% of 75 employed patients lost no time from work. Proportional hazards regression analysis showed that previous chronic episodes of low back pain, initial disability level, initial pain worse when standing, initial pain worse when lying, and compensation status were significantly associated with delayed episode recovery. These factors were also related to absenteeism from work. Absenteeism from work was also influenced by job satisfaction and gender. CONCLUSIONS--The recovery rate from acute low back pain was much higher than reported in other studies. Those studies, however, did not investigate groups of patients enrolled shortly after the onset of symptoms and often mixed acute low back pain patients with patients with exacerbations of chronic pain or sciatica. Several sociodemographic and clinical factors were of prognostic value in acute low back pain. Factors which influenced the outcome in terms of episode recovery (mainly physical severity factors) were only partly predictive of absenteeism from work. Time off work and return to work depended more on sociodemographic and job related influences. PMID:8148683

  20. Representing and Retrieving Patients' Falls Risk Factors and Risk for Falls among Adults in Acute Care through the Electronic Health Record

    ERIC Educational Resources Information Center

    Pfaff, Jann

    2013-01-01

    Defining fall risk factors and predicting fall risk status among patients in acute care has been a topic of research for decades. With increasing pressure on hospitals to provide quality care and prevent hospital-acquired conditions, the search for effective fall prevention interventions continues. Hundreds of risk factors for falls in acute care…

  1. The Relationship Between Risk Factors and Survival in Adult Acute Lymphoblastic Leukemia

    PubMed Central

    Allahyari, Abolghasem; Hashemi, Seyed-Mehdi; Nazemian, Fahimeh; Karimi, Mohammad; Kazemi, Mohammad-Reza; Sadeghi, Masoud

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is aggressive cancer, especially in adults as only 20-40% is cured with current treatment regimens. Objectives The aim of this study is to evaluate prognostic factors and their effects on survival in ALL patients in the Northeast of Iran. Methods In a descriptive and retrospective study from 2009 to 2015, 48 ALL patients referred to hematology-oncology clinic. Age, sex, fever, blood group, type of ALL and consumption of amphotericin B, forms of cytogenetic, survival in the patients, WBC, hemoglobin, and platelet were checked in the first referral for every patient. The mean follow-up was 27.3 months in which 28 patients (59.3%) died. overall survival (OS) was plotted by GraphPad Prism 5 and the Log-rank test was used for analysis of survival with risk factors. Results The mean age for all the ALL patients at diagnosis was 32.3 years (range, 15-71 years), and 81.3% were male. Of all patients, 62.5% had fever and 25% consumed amphotericin B. 1-, 2-, 3-, 4-, 5-year OS rates were 62.2%, 52.7%, 40.6%, 39.1%, 22.2%, respectively. 75%, 29.2% and 39.6% of patients had WBC < 20 × 103/μl, Hb < 7 g/dL and platelet < 30 × 103/μL, respectively. There was a significant difference in survival based on age (P = 0.000). Conclusions Based on the results, age > 35 years is the most prognostic factor in ALL patients. Also, patients who received amphotericin B had lower life expectancy because these patients were suffering from fungal infection or due to lack of response to antibacterial drugs, they have been treated with amphotericin B.

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

    PubMed Central

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

    2016-01-01

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

  3. Risk Factors for Death and Major Morbidity in Guatemalan Children with Acute Bacterial Meningitis

    PubMed Central

    Olson, Daniel; Lamb, Molly M.; Gaensbauer, James T.; Todd, James K.; Halsey, Neal A.; Asturias, Edwin J.

    2015-01-01

    Background Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries (LMICs). Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. Methods Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000-2007 was analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture; positive latex agglutination; or CSF WBC > 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd (HTS). Results Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity, and 192 (23.7%) died. Among 383 children with non-missing data, the most significant multivariate predictors for death or major morbidity were seizure (OR 101.5, p<0.001), CSF glucose < 20 mg/dL (OR 5.3, p = 0.0004), symptom duration > 3 days (OR 3.7, p=0.003), and coma (OR 6.3, p=0.004). Of 221 children with a HTS score > 5, 204 (92%) died or suffered major morbidity (OR 10.3, p<0.0001). Conclusion ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite Herson-Todd Score predicted death or major morbidity. These predictors could help clinicians in LMIC guide medical care for ABM, and could contribute to the public health impact assessment in preventing meningitis with vaccines. PMID:26069947

  4. Effects of different kinds of acute stress on nerve growth factor content in rat brain.

    PubMed

    von Richthofen, Sita; Lang, Undine E; Hellweg, Rainer

    2003-10-17

    Nerve growth factor (NGF) has several effects on the central nervous system; on the one hand NGF fosters survival and function of cholinergic neurons of the basal forebrain, on the other hand this protein is implicated in the stress response of the hypothalamic-pituitary-adrenocortical axis (HPAA). In this study we tested the influence of threatening and painful stress treatments in three different intensities as well as forced motoric activity on NGF content in different brain areas in adult rats. We found that threatening treatment with or without painful stimuli was followed by a significant decrease of NGF concentration in the amygdala (44.5%; P=0.03) and the frontal cortex (-45.5%; P=0.02). We also observed that after stress of forced motoric activity NGF content in the frontal cortex (-32%; P=0.01) and the hippocampus (-32%; P=0.006) was significantly reduced. Thus, NGF content in distinct brain regions is decreased, following different forms of acute stress. This might be relevant for the pathophysiological understanding of psychiatric diseases, such as depression, which are associated with stress.

  5. 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

  6. 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

  7. Von Willebrand factor and oxidative stress parameters in acute coronary syndromes.

    PubMed

    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-NO(2)-), superoxide anion radical (O(2)-), 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 NO(2)-, 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.

  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. 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

  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.

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

    PubMed Central

    Ding, Wenhui; Wang, Fang

    2015-01-01

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

  12. Factors Affecting Outcome in Acute Hypertriglyceridemic Pancreatitis Treated with Plasma Exchange: An Observational Cohort Study

    PubMed Central

    Gubensek, Jakob; Buturovic-Ponikvar, Jadranka; Romozi, Karmen; Ponikvar, Rafael

    2014-01-01

    Objectives The optimal therapy for hypertriglyceridemic acute pancreatitis, especially the role of plasma exchange (PE), is not entirely clear. The aim of our large, single-center, observational, cohort study was to analyze the factors affecting outcome in hypertriglyceridemic pancreatitis treated with PE. Methods We included 111 episodes of hypertriglyceridemic pancreatitis treated with PE, which occurred in 103 different patients. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, triglycerides, delay to first PE, and PE treatment details were retrospectively obtained from the patients’ records. The main outcome measures were length of hospitalization and in-hospital mortality. Results The patients were 47±9 years old and the median APACHE II score at first PE was 4 (inter-quartile range (IQR) 2–7). There was a seasonal variation in the incidence of hypertriglyceridemic pancreatitis, and the recurrence rate was 1.6% per year. Triglycerides at presentation did not correlate with APACHE II or influence the outcome. The mean reduction in triglycerides during PE was 59% (from 44±31 to 18±15 mmol/l), which was twice the reduction observed during conservative treatment (27% daily). The median hospital stay was 16 days (IQR 10–24) and in-hospital mortality was 5%. The median delay to first PE was 35 hours (IQR 24–52), and there was no difference in mortality in the early and late PE groups (7% vs. 6%, p = 0.79). The group with citrate anticoagulation during PE had a significantly lower mortality than the group with heparin anticoagulation (1% vs. 11%, p = 0.04), and citrate was an independent predictor also in the multivariate model (p = 0.049). Conclusions PE effectively reduced serum triglycerides faster than could be expected with conservative treatment. The delay in PE therapy did not influence survival. We found that citrate anticoagulation during PE was associated with reduced mortality, which should be confirmed in a

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

  15. Risk Factors, Pattern and Clinical Outcome of Acute Graft Versus Host Disease in Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplant.

    PubMed

    Gupta, Alok; Punatar, Sachin; Gawande, Jayant; Mathew, Libin; Bagal, Bhausaheb; Kannan, Sadhana; Khattry, Navin

    2015-12-01

    We sought to determine risk factors, pattern and outcome of acute graft versus host disease (aGVHD) in seventy-seven acute leukemia patients who underwent allogeneic stem cell transplant at our centre from January 2008 to March 2013. GVHD prophylaxis with cyclosporine-methotrexate or cyclosporine-mycophenolate mofetil was used. Patients were divided in 2 groups, grade II-IV aGVHD (group A) and grade 0-I aGVHD (group B). Incidence of any grade and grade II-IV aGVHD was 44 and 18 %, respectively. The most common site of aGVHD was gastro-intestinal tract (65 %) followed by skin (35 %). Higher total nucleated cell (TNC) dose infused was associated with increased incidence of grade II-IV aGVHD. Incidence of relapse and incidence of slippage of chimerism was 21 and 36 % in group A while 37 and 27 % in group B respectively. Transplant related mortality (TRM) was 21 % in group A and 13 % in group B. Probability of OS and RFS at 4 years was 63 and 34 % in group A compared with 40 and 38 % in group B, respectively. We conclude that higher TNC dose infused is a risk factor for grade II-IV aGVHD with gut being the commonest site. Grade II-IV aGVHD did not have a significant impact on incidence of relapse, TRM and OS.

  16. [Acute lung injury as a consequence of fresh frozen plasma administration in a patient with factor XII deficiency].

    PubMed

    San Juan-Álvarez, M; Sánchez-Zamora, P; de la Flor-Robledo, M

    2014-10-01

    Along with the complete blood count, the coagulation tests are those most demanded before a surgical procedure. The activated partial thromboplastin time (APPT) quantifies the intrinsic and common coagulation pathways, including factors XII, XI, IX, VIII, X, V and II. Factor XII deficiency is associated with a prolonged APPT and an increase in thromboembolic phenomena, without increasing the intraoperative bleeding risk. A 20 year old man with factor XII deficiency was receiving two units of fresh frozen plasma because of an APPT of 100 seconds, with the intention of normalizing it before an urgent surgery procedure, and the fear of intraoperative bleeding. An hour after starting the transfusion the patient developed an acute lung injury (ALI) compatible with the diagnosis of a transfusion related acute lung injury (TRALI). The surgery continued without complications, and the patient was admitted to the resuscitation unit for 72 h, needing respiratory support. If the APTT is prolonged in the absence of bleeding, the presence of a non-specific circulating anticoagulant, a deficiency of factor XI, XII and VIII (associated to Von Willebrand disease) must be ruled out. Therefore, in the case presented here, the administration of hemoderivatives was unnecessary and can have consequences as serious as the one that the patient presented, a transfusion related acute lung injury.

  17. PEBP2-β/CBF-β–dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis

    PubMed Central

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

    2008-01-01

    The heterodimeric transcription factor RUNX1/PEBP2-β (also known as AML1/CBF-β) is essential for definitive hematopoiesis. Here, we show that interaction with PEBP2-β leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser249, Ser273, and Thr276 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-β-SMMHC prevents RUNX1/p300 phosphorylation by sequestering HIPK2 to mislocalized RUNX1/β-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

  18. Restricted feeding entrains rhythms of inflammation-related factors without promoting an acute-phase response.

    PubMed

    Luna-Moreno, Dalia; Aguilar-Roblero, Raúl; Díaz-Muñoz, Mauricio

    2009-10-01

    A restricted schedule of food access promotes numerous metabolic and physiological adaptations to optimize the biochemical handling of nutrients. The restricted feeding activates responses in hypothalamic and midbrain areas, as well as in peripheral organs involved in energy metabolism. A restricted feeding schedule (RFS) is associated with marked behavioral arousal coincident with the food anticipatory activity (FAA) and extreme hyperphagia during food access. Food restriction is also accompanied by changes in an array of stress-related parameters, such as increase in corticosterone, slower rate in body weight gain, and reduction in retroperitoneal and epididymal adipose tissue. During RFS, the liver shows a diversity of biochemical and physiologically adaptations that are advantageous for food ingestion and processing, as well as for adequate nutrient distribution to other tissues. Taking into account the probable relationship between stressful conditions and the metabolic adaptations in the liver, we addressed whether an acute-phase response (APR), or a pro-inflammatory state, occurred after three weeks of 2 h food restriction. First, we compared the circulating levels of inflammation markers (interleukin-1alpha, interleukin-6, tumor necrosis factor-alpha), and APR proteins (C-reactive protein and fibrinogen) in rats under food restriction to those in rats treated with lipopolysacharide, a strong inducer of the APR. Second, the influence of RFS on the daily rhythms of systemic cytokines and APR proteins was characterized. Third, we tested if the feeding condition (22 h fasting and 2 h refeeding) influences these parameters. Finally, we assessed if a local stressed state was established in the liver associated with the restricted feeding by measuring the activation of the transcriptional factor NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells). The results showed that the following occurred during RFS: no APR was implemented; food

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

    PubMed Central

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

    2016-01-01

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

  20. Mutations in the Ca2+/H+ Transporter CAX1 Increase CBF/DREB1 Expression and the Cold-Acclimation Response in Arabidopsis

    PubMed Central

    Catalá, Rafael; Santos, Elisa; Alonso, José M.; Ecker, Joseph R.; Martínez-Zapater, José M.; Salinas, Julio

    2003-01-01

    Transient increases in cytosolic free calcium concentration ([Ca2+]cyt) are essential for plant responses to a variety of environmental stimuli, including low temperature. Subsequent reestablishment of [Ca2+]cyt to resting levels by Ca2+ pumps and C-REPEAT BINDING FACTOR/DEHYDRATION RESPONSIVE ELEMENT BINDING FACTOR 1 (Ca2+/H+) antiporters is required for the correct transduction of the signal. We have isolated a cDNA from Arabidopsis that corresponds to a new cold-inducible gene, RARE COLD INDUCIBLE4 (RCI4), which was identical to CALCIUM EXCHANGER 1 (CAX1), a gene that encodes a vacuolar Ca2+/H+ antiporter involved in the regulation of intracellular Ca2+ levels. The expression of CAX1 was induced in response to low temperature through an abscisic acid–independent pathway. To determine the function of CAX1 in Arabidopsis stress tolerance, we identified two T-DNA insertion mutants, cax1-3 and cax1-4, that display reduced tonoplast Ca2+/H+ antiport activity. The mutants showed no significant differences with respect to the wild type when analyzed for dehydration, high-salt, chilling, or constitutive freezing tolerance. However, they exhibited increased freezing tolerance after cold acclimation, demonstrating that CAX1 plays an important role in this adaptive response. This phenotype correlates with the enhanced expression of CBF/DREB1 genes and their corresponding targets in response to low temperature. Our results indicate that CAX1 ensures the accurate development of the cold-acclimation response in Arabidopsis by controlling the induction of CBF/DREB1 and downstream genes. PMID:14630965

  1. Functional connectivity in BOLD and CBF data: similarity and reliability of resting brain networks.

    PubMed

    Jann, Kay; Gee, Dylan G; Kilroy, Emily; Schwab, Simon; Smith, Robert X; Cannon, Tyrone D; Wang, Danny J J

    2015-02-01

    Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2 × 2 × 2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test-retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905 ± 0.033 between-sessions; 0.885 ± 0.052 between-scanners) than ASL (0.545 ± 0.048; 0.575 ± 0.059). Nevertheless, ASL provided highly reproducible (0.955 ± 0.021; 0.970 ± 0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.

  2. Draft Genome Sequence of Pseudomonas putida CBF10-2, a Soil Isolate with Bioremediation Potential in Agricultural and Industrial Environmental Settings

    PubMed Central

    Damania, Ashish

    2016-01-01

    Pseudomonas putida CBF10-2 is a microorganism isolated from farmland soil in Fairchild, TX, found to degrade high-impact xenobiotics, including organophosphate insecticides, petroleum hydrocarbons, and both monocyclic and polycyclic aromatics. The versatility of CBF10-2 makes it useful for multipurpose bioremediation of contaminated sites in agricultural and industrial environments. PMID:27417844

  3. Draft Genome Sequence of Pseudomonas putida CBF10-2, a Soil Isolate with Bioremediation Potential in Agricultural and Industrial Environmental Settings.

    PubMed

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Pseudomonas putida CBF10-2 is a microorganism isolated from farmland soil in Fairchild, TX, found to degrade high-impact xenobiotics, including organophosphate insecticides, petroleum hydrocarbons, and both monocyclic and polycyclic aromatics. The versatility of CBF10-2 makes it useful for multipurpose bioremediation of contaminated sites in agricultural and industrial environments. PMID:27417844

  4. Molecular dysfunctions in acute rejection after renal transplantation revealed by integrated analysis of transcription factor, microRNA and long noncoding RNA.

    PubMed

    Sui, Weiguo; Lin, Hua; Peng, Wujian; Huang, Yuanshuai; Chen, Jiejing; Zhang, Yue; Dai, Yong

    2013-10-01

    Acute rejection remains a problem in renal transplantation. To further illustrate the mechanism of rejection, we integrated protein array-based proteomics and RNA microarray-based genomics to investigate the transcription factor, microRNA and long noncoding RNA of biopsies of three patients with acute rejections and a control group. 99 transcription factors were identified in acute rejection biopsies compared to normal renal tissue. We correlated transcription factor data with microRNA and long noncoding RNA data sets and reported the expression of 5 transcription factors (AP-1, AP-4, STATx, c-Myc and p53), 12 miRNAs and 32 lncRNAs in acute rejection biopsies. Pathway analysis demonstrated that over-presentation of transcription factor pathway plays a critical role in acute rejection. This is the first study to comprehensively report the acute rejection transcription factor pathway. Integrative analysis of the transcription factor, microRNA and long noncoding RNA provided an expansive view of molecular signaling pathways in acute rejection after renal transplantation.

  5. The prevalence of and risk factors for acute mountain sickness in the Eastern and Western Alps.

    PubMed

    Mairer, Klemens; Wille, Maria; Burtscher, Martin

    2010-01-01

    Acute mountain sickness (AMS) is the most common condition of high altitude illnesses. Its prevalence varies between 15% and 80% depending on the speed of ascent, absolute altitude reached, and individual susceptibility. Additionally, we assumed that the more experienced mountaineers of the Western Alps are less susceptible to developing AMS than recreational mountaineers of the Eastern Alps or tourist populations. Therefore, the main goals of the present study were the collection of data regarding the AMS prevalence and triggers in both the Eastern and Western Alps using identical methods. A total of 162 mountaineers, 79 in the Eastern Alps (3454 m) and 83 in the Western Alps (3817 m) were studied on the morning after their first night at high altitude. A diagnosis of AMS was based on a Lake Louise Score (LLS) ≥4, the presence of headache, and at least one additional symptom. Thirty of 79 subjects (38.0%) suffered from AMS at 3454 m in the Eastern Alps as did 29 of 83 (34.9%) at 3817 m in the Western Alps. After adjustment for altitude, the prevalence in the Western Alps constituted 24.5%, which differed significantly (p = 0.04) from that found in the Eastern Alps. The lower mountaineering experience of mountaineers in the Eastern Alps turned out to be the only factor for explaining their higher AMS prevalence. Thus, expert advice by mountain guides or experienced colleagues could help to reduce the AMS risk in these subjects.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. The Cbf5-Nop10 Complex is a Molecular Bracket that Organizes Box H/ACA RNPs

    SciTech Connect

    Hamma, Tomoko; Reichow, Steve L.; Varani, Gabriele; Ferre-D'Amare, Adrian R.

    2005-12-01

    Box H/ACA ribonucleoprotein particles (RNPs) catalyze RNA pseudouridylation and direct processing of ribosomal RNA, and are essential architectural components of vertebrate telomerases. H/ACA RNPs comprise four proteins and a multihelical RNA. Two proteins, Cbf5 and Nop10, suffice for basal enzymatic activity in an archaeal in vitro system. We now report their cocrystal structure at 1.95-A resolution. We find that archaeal Cbf5 can assemble with yeast Nop10 and with human telomerase RNA, consistent with the high sequence identity of the RNP componenets between archaea and eukarya. Thus, the Cbf5-Nop10 architecture is phylogenetically conserved. The structure shows how Nop10 buttresses the active site of Cbf5, and it reveals two basic troughs that bidirectionally extend the active site cleft. Mutagenesis results implicate an adjacent basic patch in RNA binding. This tripartite RNA-binding surface may function as a molecular bracket that organizes the multihelical H/ACA and telomerase RNAs.

  9. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Use of a stress inducible promoter to drive ectopic AtCBF expression improves potato freezing tolerance while minimizing negative effects on tuber yield.

    PubMed

    Pino, María-Teresa; Skinner, Jeffrey S; Park, Eung-Jun; Jeknić, Zoran; Hayes, Patrick M; Thomashow, Michael F; Chen, Tony H H

    2007-09-01

    Solanum tuberosum is a frost-sensitive species incapable of cold acclimation. A brief exposure to frost can significantly reduce its yields, while hard frosts can completely destroy entire crops. Thus, gains in freezing tolerance of even a few degrees would be of considerable benefit relative to frost damage. The S. tuberosum cv. Umatilla was transformed with three Arabidopsis CBF genes (AtCBF1-3) driven by either a constitutive CaMV35S or a stress-inducible Arabidopsis rd29A promoter. AtCBF1 and AtCBF3 over-expression via the 35S promoter increased freezing tolerance about 2 degrees C, whereas AtCBF2 over-expression failed to increase freezing tolerance. Transgenic plants of AtCBF1 and AtCBF3 driven by the rd29A promoter reached the same level of freezing tolerance as the 35S versions within a few hours of exposure to low but non-freezing temperatures. Constitutive expression of AtCBF genes was associated with negative phenotypes, including smaller leaves, stunted plants, delayed flowering, and reduction or lack of tuber production. While imparting the same degree of freezing tolerance, control of AtCBF expression via the stress-inducible promoter ameliorated these negative phenotypic effects and restored tuber production to levels similar to wild-type plants. These results suggest that use of a stress-inducible promoter to direct CBF transgene expression can yield significant gains in freezing tolerance without negatively impacting agronomically important traits in potato.

  13. Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.

    PubMed

    Mullinger, K J; Mayhew, S D; Bagshaw, A P; Bowtell, R; Francis, S T

    2014-07-01

    Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR. PMID:24632092

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

    PubMed Central

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

    2013-01-01

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

  15. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in

  16. Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

    PubMed

    Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

    2012-01-01

    Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis.

  17. Inhibition of pulmonary nuclear factor kappa-B decreases the severity of acute Escherichia coli pneumonia but worsens prolonged pneumonia

    PubMed Central

    2013-01-01

    Introduction Nuclear factor (NF)-κB is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair. We wished to determine whether overexpression of the NF-κB inhibitor IκBα could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies. Methods Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 × 109 adenoassociated virus (AAV) vectors encoding the IκBα transgene (5 × 109 AAV-IκBα); (b) 1 × 1010 AAV-IκBα; (c) 5 × 1010 AAV-IκBα; or (d) vehicle alone. After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia). Additional experiments examined the effects of IκBα and null-gene overexpression on E. coli-induced and sham pneumonia. Results In acute pneumonia, IκBα dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1β concentrations. Benefit was maximal at the intermediate (1 × 1010) IκBα vector dose; however, efficacy was diminished at the higher (5 × 1010) IκBα vector dose. In contrast, IκBα worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response. Conclusions Inhibition of pulmonary NF-κB activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia. PMID:23622108

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

    PubMed Central

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

    1997-01-01

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

  19. Screening Household Members of Acute Brucellosis Cases in Endemic Areas and Risk Factors for Brucellosis.

    PubMed

    Deniz, Secil; Baykam, Nurcan; Celikbas, Aysel; Yilmaz, Sirin Menekse; Guzel, Tugba Cirkin; Dokuzoguz, Basak; Ergonul, Onder

    2015-08-01

    Early diagnosis and treatment of acute brucellosis cases were targeted by screening the household members of the index cases. We also aimed to describe the causal relations of brucellosis in an endemic region. A cross-sectional study was performed among household members (29 index cases, 113 household members). Brucellosis was diagnosed on the basis of clinical findings, serum agglutinin titer of ≥1/160 in standard tube agglutination test (STA), or a positive blood culture. Index cases were defined as patients who had been admitted to the clinic on suspicion of brucellosis and then confirmed as brucellosis cases. The people who lived in the same house as the index cases were defined as household members. The risk factors for seropositivity were studied by multivariate analysis. Independent variables of gender, consuming fresh cheese, blood groups, dealing with husbandry, and contact with the placenta of infected animals were included to the model. Backward and forward selections were performed. Nineteen out of 113 (17%) screened individuals had agglutination titers ≥1/160. The mean ages of index cases and household members were 43 years (standard deviation [SD] 18) and 29 years (SD 19), respectively. In multivariate analysis, consuming fresh cheese (odds ratio [OR]=3.1, confidence interval [CI] 1.07-9.68, p=0.049), blood group A (OR=2.6, CI 1.18-5.96, p=0.018), contact with the placenta of the infected animals (OR=3.7, CI 1.42-9.68, p=0.007), and age >30 years (OR=2.8, CI 1.25-6.51, p=0.13) were found to be associated with brucellosis. In univariate analysis, the individuals with blood group B were protected from brucella infection (p=0.013). In conclusion, screening of the people in brucellosis-endemic areas should be considered for early diagnosis and treatment. To our knowledge, blood groups were studied for the first time by this study. Higher prevalence of brucellosis among the individuals with blood group A and less prevalence among the individuals with

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

    PubMed Central

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

    2015-01-01

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

  1. Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution.

    PubMed

    Lee, Hee-Woo; Kim, Sung-Min; Shim, Na-Ri; Bae, Soo-Kyung; Jung, Il-Gun; Kwak, Jong-Young; Kim, Bong-Seon; Kim, Jae-Bong; Moon, Jeon-Ok; Chung, Joo-Seop; Yoon, Sik

    2007-06-01

    Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. Nerve growth factor (NGF) is increasingly recognized as a potent immunomodulator, promoting "cross-talk" between various types of immune system cells. The present study describes the expression of NGF during thymus regeneration following acute involution induced by cyclophosphamide in the rat. Immunohistochemical stain demonstrated not only the presence of NGF but also its upregulated expression mainly in the subcapsular, paraseptal, and perivascular epithelial cells, and medullary epithelial cells including Hassall's corpuscles in both the normal and regenerating thymus. Biochemical data obtained using Western blot and RT-PCR supported these results and showed that thymic extracts contain NGF protein and mRNA, at higher levels during thymus regeneration. Thus, our results suggest that NGF expressed in these thymic epithelial cells plays a role in the T lymphopoiesis associated with thymus regeneration during recovery from acute thymic involution.

  2. Limited Reliability of CT perfusion acute infarct volume measurements compared to DWI in anterior circulation stroke

    PubMed Central

    Schaefer, Pamela W.; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A.; Yoo, Albert J.; Kamalian, Shahmir; Gonzalez, R. Gilberto; Lev, Michael H.

    2015-01-01

    Background and Purpose DWI can reliably identify critically ischemic tissue (CIT) shortly after stroke onset. We tested if thresholded CT-CBF and CT-CBV maps are sufficiently accurate to substitute for DWI for estimating CIT volume. Methods Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation, and CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast-to-noise ratios (CNR) of ischemic regions on the DWI and CTP images were measured. Correlation and Bland-Altman analyses were used to assess reliability of CTP. Results Mean CNRs for DWI, CT-CBF and CT-CBV were 4.3, 0.9 and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R2=0.87 for CT-CBF; R2=0.83 for CT-CBV; p<0.001). Bland-Altman analyses revealed little systemic bias (−2.6 ml) but high measurement variability (95% CI ±56.7 ml) between mean CT-CBF and DWI lesion volumes, and systemic bias (−26 ml) and high measurement variability (95% CI ±64.0 ml) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. Conclusions The poor CNRs of CT-CBV and CT-CBF compared to DWI result in large measurement error making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than if DWI is used. PMID:25550366

  3. Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

    PubMed Central

    Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-01

    Background Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Methodology/Principal Findings Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. Conclusions This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies. PMID:18231608

  4. Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance

    PubMed Central

    Spada, E; Mele, A; Berton, A; Ruggeri, L; Ferrigno, L; Garbuglia, A R; Perrone, M P; Girelli, G; Del Porto, P; Piccolella, E; Mondelli, M U; Amoroso, P; Cortese, R; Nicosia, A; Vitelli, A; Folgori, A

    2004-01-01

    Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment. PMID:15479691

  5. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation

    PubMed Central

    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-01-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. PMID:20030669

  6. Heterogeneity of clonal expansion and maturation-linked mutation acquisition in hematopoietic progenitors in human acute myeloid leukemia.

    PubMed

    Walter, R B; Laszlo, G S; Lionberger, J M; Pollard, J A; Harrington, K H; Gudgeon, C J; Othus, M; Rafii, S; Meshinchi, S; Appelbaum, F R; Bernstein, I D

    2014-10-01

    Recent technological advances led to an appreciation of the genetic complexity of human acute myeloid leukemia (AML), but underlying progenitor cells remain poorly understood because their rarity precludes direct study. We developed a co-culture method integrating hypoxia, aryl hydrocarbon receptor inhibition and micro-environmental support via human endothelial cells to isolate these cells. X-chromosome inactivation studies of the least mature precursors derived following prolonged culture of CD34(+)/CD33(-) cells revealed polyclonal growth in highly curable AMLs, suggesting that mutations necessary for clonal expansion were acquired in more mature progenitors. Consistently, in core-binding factor (CBF) leukemias with known complementing mutations, immature precursors derived following prolonged culture of CD34(+)/CD33(-) cells harbored neither mutation or the CBF mutation alone, whereas more mature precursors often carried both mutations. These results were in contrast to those with leukemias with poor prognosis that showed clonal dominance in the least mature precursors. These data indicate heterogeneity among progenitors in human AML that may have prognostic and therapeutic implications.

  7. Burden of acute infections (except respiratory and diarrheal) and its risk factors among under-five children in India: A systematic review and meta-analysis

    PubMed Central

    Ganguly, Enakshi; Sharma, Pawan K; Bunker, Clareann H

    2016-01-01

    Context Acute infections of eyes, ears, skin, and others are a common cause of morbidity in under-five children. The overall burden of other infections and their risk factors is not known. Evidence Acquisition Available literature was searched comprehensively using PubMed for acute infections (except acute respiratory and diarrheal diseases) using the relevant medical subject heading terms. Extracted articles were independently reviewed against inclusion/exclusion criteria and rated for quality. 10 articles were abstracted and reviewed to identify the reported prevalence and risk factors for acute infections among children. Results The pooled prevalence of infections (not including acute respiratory and diarrhea) between 2002 and 2013 was 18.42 (95% confidence interval: 9.30–30.62), with reported range of 3.7–50.8%. The significantly positively associated factors reported in single studies were young age of the child, malnutrition, poor breastfeeding, low socio-economic status, animal rearing near household and mothers’ illiteracy for independent morbidities. Conclusion The evidence on risk factors including breastfeeding, vaccination, age, and sex that predispose under-five Indian children to different infections is inconclusive. There is a need to conduct more studies on acute infections other than acute respiratory and diarrhea, to establish their determinants in Indian children. PMID:27170943

  8. Systolic Blood Pressure Variability is a Novel Risk Factor for Rebleeding in Acute Subarachnoid Hemorrhage

    PubMed Central

    Lin, Qing-Song; Ping-Chen; Lin, Yuan-Xiang; Lin, Zhang-Ya; Yu, Liang-Hong; Dai, Lin-Sun; Kang, De-Zhi

    2016-01-01

    Abstract Rebleeding of an aneurysm is a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Whereas numerous studies have demonstrated predictors of rebleeding and effect of systolic blood pressure variability (SBPV) on stroke, few data on the association between SBPV and rebleeding. Here, we sought to identify the effect of SBPV on rebleeding in acute aneurysmal SAH. Case–control study. From January 2010 to June 2015, 612 patients with aneurysmal SAH were enrolled in our tertiary care medical center. Main outcome measures: Consecutive patients with acute (<3 days from ictus) aneurismal rebleeding or repair or death were retrospectively included. Antihypertensive therapy based on a predefined standardized protocol was prescribed to lower and maintain SBP between 120 and 160 mm Hg. SBP was measured hourly until a censoring event occurred. SBPV was determined as standard deviation (SD) and successive variation (SV). Binary logistic regression was used to assess the association between SBPV and rebleeding. Rebleeding occurred in 61 (10.0%) of the 612 patients. We identified 47 acute rebleeding as cases and 382 early repair or early death as controls. On binary logistic regression analysis, rebleeding was associated with the SD of SBP (odds ratio [OR], 1.254; 95% confidence interval [CI], 1.131–1.391; P < 0.001) and the SV of SBP (OR, 1.131; 95% CI, 1.039–1.231; P = 0.004). No significant difference was seen between rebleeding and mean systolic blood pressure (MSBP). SBPV is associated with increased rates of acute aneurysmal rebleeding. Further prospective research is warranted to confirm that SBP stability prevents acute aneurysm rebleeding. PMID:26986118

  9. Frequency of family history of acute myocardial infarction in patients with acute myocardial infarction. Argentine FRICAS (Factores de Riesgo Coronario en America del Sur) Investigators.

    PubMed

    Ciruzzi, M; Schargrodsky, H; Rozlosnik, J; Pramparo, P; Delmonte, H; Rudich, V; Piskorz, D; Negri, E; Soifer, S; La Vecchia, C

    1997-07-15

    The relation between family history of acute myocardial infarction (AMI) and the risk of AMI was analyzed using data of a case-control study conducted in Argentina between 1992 and 1994. Case patients were 1,060 subjects with AMI admitted to 35 coronary care units, and controls were 1,071 subjects admitted to the same network of hospitals where cases had been identified, for a wide spectrum of acute conditions unrelated to known or likely risk factors for AMI: 31% of cases versus 15% of controls reported > or = 1 first-degree relative with history of AMI. Compared with subjects without family history of AMI, the odds ratio (OR) of AMI, after allowance for age, sex, cholesterolemia, smoking, diabetes, hypertension, body mass index, education, social class, and physical exercise, was 2.18 (95% confidence interval [CI] 1.74 to 2.74) for those with family history of AMI. The OR was 2.04 (95% CI 1.60 to 2.60) for subjects with 1 relative, and 3.18 (95% C 1.86 to 5.44) for those reporting > or = 2 relatives with AMI. In women the OR for any family history of AMI was 2.83, and in men 2.01. The association was of similar magnitude if the mother (OR 1.98), the father (OR 2.13), or a sibling (OR 2.48) had had an AMI. The association with family history was stronger at a younger age because the OR for subjects reporting > or = 2 more relatives with a history of AMI was 4.42 for subjects aged < 55 years, and 3.00 for those aged > or = 55 years. The association between AMI and family history of AMI was consistent across separate strata of education, social class, smoking, and serum cholesterol, but was less strong in subjects with history of diabetes and hypertension. When the interaction of known risk factors with family history of AMI was analyzed, hypercholesterolemia, hypertension, and smoking had approximately multiplicative effects on the relative risk. The OR was 4.50 for subjects with family history and cholesterol > or = 240 ml/dl, 4.52 for those with hypertension, and

  10. Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation.

    PubMed

    Fan, Yu-Ting; Yin, Guo-Jian; Xiao, Wen-Qin; Qiu, Lei; Yu, Ge; Hu, Yan-Ling; Xing, Miao; Wu, De-Qing; Cang, Xiao-Feng; Wan, Rong; Wang, Xing-Peng; Hu, Guo-Yong

    2015-01-01

    Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 μ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits. PMID:26364660

  11. Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

    PubMed Central

    Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

    2014-01-01

    Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

  12. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  13. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury.

    PubMed

    Chihara, Hideo; Takagi, Yasushi; Nishino, Kazunari; Yoshida, Kazumichi; Arakawa, Yoshiki; Kikuchi, Takayuki; Takenobu, Yohei; Miyamoto, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either "with HAL suitability" or "without HAL suitability" based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL.

  14. Identifying youth at risk for difficulties following a traumatic event: pre-event factors are associated with acute symptomatology.

    PubMed

    Goslin, Megan C; Stover, Carla Smith; Berkowitz, Steven; Marans, Steven

    2013-08-01

    This study examined factors related to children's acute symptoms following a potentially traumatic event (PTE) to more clearly identify domains that should be included in screenings of youth exposed to a PTE. In particular, the authors examined whether trauma category (i.e., sexual abuse/disclosure of abuse, intentionally perpetrated traumas other than sexual abuse, and unintentional traumas) was related to symptoms after controlling for other relevant factors. Participants were 112 youth presenting for clinical evaluation within a month of a PTE and their nonoffending caregivers. Using data from baseline assessments collected as part of a randomized controlled trial of a secondary prevention program, the following factors were tested in 3 hierarchical regression models: index PTE category, history of traumatic exposure, preindex event functioning, and parenting behaviors. Prior trauma exposure, preindex event functioning, and hostile parenting were uniquely related to children's symptoms in the acute posttraumatic period after controlling for time since the event and child age, but trauma category was not. Implications for identifying and referring children at high risk for poor outcomes in the early aftermath of a PTE are discussed. An exclusive focus on the event is insufficient and more comprehensive understanding of the child and family is required. PMID:23861167

  15. [Research Progress on the Role of Chromatin Remodeling Factor BRG1 in Acute Myeloid Leukemia].

    PubMed

    Gao, Shuo; Xu, Xue-Jing; Zhang, Kui

    2016-06-01

    BRG1 (Brahma-related gene 1, BRG1) is the ATPase subunit of SWI/SNF chromatin remodeling complexes, which plays an important role in cell cycle regulation, DNA repair and tumor development. Unlike the evidence as tumor suppressor genes in the past reports, latest researches show that BRG1 plays an important role in sustaining the growth of leukemia cells in acute myeloid leukemia, and these effects on normal hematopoietic stem cells are dispensable. Further studies of the role and mechanism of BRG1 in acute myeloid leukemia will contribute to the development of a new and promising targeted therapy strategy. This article reviews the role of BRG1 on leukemia cells and leukemia stem cells in AML and discusses the related mechanism, which providing some reference for the targeted treatment strategy of AML. PMID:27342536

  16. Personal and situational factors that predict coping strategies for acute stress among basketball referees.

    PubMed

    Kaissidis-Rodafinos, A; Anshel, M H; Porter, A

    1997-08-01

    The aim of this study was to establish the ways in which coping style and situational appraisals are related to the consistency of using approach and avoidance coping strategies for skilled Australian basketball referees (n = 133) after three game-related stressful events. The events, 'making a mistake', 'aggressive reactions by coaches or players' and 'presence of important others', were determined from previous research on sources of acute stress among basketball officials. Our findings indicated that: referees exhibited consistent avoidance, but not approach, coping styles; they used more avoidance than approach strategies; and they perceived stress to be positively correlated with approach, and negatively associated with avoidance, coping strategies. These findings suggest that individual differences exist in perceptions of stress (i.e. situational appraisals), controllability and coping styles among moderately and highly skilled basketball referees. The implications for teaching cognitive and behavioural strategies for effective coping with acute stress in basketball officiating are discussed.

  17. Different Circulating Brain-Derived Neurotrophic Factor Responses to Acute Exercise Between Physically Active and Sedentary Subjects

    PubMed Central

    Nofuji, Yu; Suwa, Masataka; Sasaki, Haruka; Ichimiya, Atsushi; Nishichi, Reiko; Kumagai, Shuzo

    2012-01-01

    Although circulating brain-derived neurotrophic factor (BDNF) level is affected by both acute and chronic physical activity, the interaction of acute and chronic physical activity was still unclear. In this study, we compared the serum and plasma BDNF responses to maximal and submaximal acute exercises between physically active and sedentary subjects. Eight active and 8 sedentary female subjects participated in the present study. Both groups performed 3 exercise tests with different intensities, i.e. 100% (maximal), 60% (moderate) and 40% (low) of their peak oxygen uptake. In each exercise test, blood samples were taken at the baseline and immediately, 30 and 60 min after the test. The serum BDNF concentration was found to significantly increase immediately after maximal and moderate exercise tests in both groups. In maximal exercise test, the pattern of change in the serum BDNF concentration was different between the groups. While the serum BDNF level for the sedentary group returned to the baseline level during the recovery phase, the BDNF levels for the active group decreased below the baseline level after the maximal exercise test. No group differences were observed in the pattern of plasma BDNF change for all exercise tests. These findings suggest that regular exercise facilitates the utilization of circulating BDNF during and/or after acute exercise with maximal intensity. Key points In maximal exercise test, the pattern of change in the serum BDNF concentration was different between the groups. While the serum BDNF level for the sedentary group returned to the baseline level during the recovery phase, the BDNF levels for the active group decreased below the baseline level after the maximal exercise test. No group differences were observed in the pattern of serum BDNF change for moderate or low exercise tests. No group differences were observed in the pattern of plasma BDNF change for all exercise tests. PMID:24137066

  18. Fission Yeast CSL Transcription Factors: Mapping Their Target Genes and Biological Roles

    PubMed Central

    Převorovský, Martin; Oravcová, Martina; Tvarůžková, Jarmila; Zach, Róbert; Folk, Petr; Půta, František; Bähler, Jürg

    2015-01-01

    Background Cbf11 and Cbf12, the fission yeast CSL transcription factors, have been implicated in the regulation of cell-cycle progression, but no specific roles have been described and their target genes have been only partially mapped. Methodology/Principal Findings Using a combination of transcriptome profiling under various conditions and genome-wide analysis of CSL-DNA interactions, we identify genes regulated directly and indirectly by CSL proteins in fission yeast. We show that the expression of stress-response genes and genes that are expressed periodically during the cell cycle is deregulated upon genetic manipulation of cbf11 and/or cbf12. Accordingly, the coordination of mitosis and cytokinesis is perturbed in cells with genetically manipulated CSL protein levels, together with other specific defects in cell-cycle progression. Cbf11 activity is nutrient-dependent and Δcbf11-associated defects are mitigated by inactivation of the protein kinase A (Pka1) and stress-activated MAP kinase (Sty1p38) pathways. Furthermore, Cbf11 directly regulates a set of lipid metabolism genes and Δcbf11 cells feature a stark decrease in the number of storage lipid droplets. Conclusions/Significance Our results provide a framework for a more detailed understanding of the role of CSL proteins in the regulation of cell-cycle progression in fission yeast. PMID:26366556

  19. Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

    PubMed Central

    Holliday, Malcolm A.; Kalayci, M. N.; Harrah, Jean

    1968-01-01

    Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (NaE and ClE). The following observations are noted: Brain Cl content varies directly with ClE and brain Na content in the Cl space (Nae) varies directly with NaE, indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (Vi) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in Vi in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) NaE is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) Vi is osmotically active; and (d) there is no net gain or loss of solute from Vi. The validity of these assumptions is considered. When changes in osmolality are sustained, Vi is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in Vi observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon NaE describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in NaE by the freedom for Na and Cl to move from the Cl space, by Vi not changing acutely to the degree predicted from osmotic properties of cells in general, and by

  20. Improvement in Regional CBF by L-Serine Contributes to Its Neuroprotective Effect in Rats after Focal Cerebral Ischemia

    PubMed Central

    Jiang, Zheng-Lin; Wang, Guo-Hua; Sun, Li; Jiang, Rui; Zhao, Guang-Wei; Han, Le-Yang

    2013-01-01

    To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF). Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1) reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2) improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3) increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca2+-activated K+ channels on the cerebral blood vessel endothelium. PMID:23825613

  1. Cloning and characterization of Arabidopsis thaliana AtNAP57--a homologue of yeast pseudouridine synthase Cbf5p.

    PubMed

    Maceluch, J; Kmieciak, M; Szweykowska-Kulińska, Z; Jarmołowski, A

    2001-01-01

    Rat Nap57 and its yeast homologue Cbf5p are pseudouridine synthases involved in rRNA biogenesis, localized in the nucleolus. These proteins, together with H/ACA class of snoRNAs compose snoRNP particles, in which snoRNA guides the synthase to direct site-specific pseudouridylation of rRNA. In this paper we present an Arabidopsis thaliana protein that is highly homologous to Cbf5p (72% identity and 85% homology) and NAP57 (67% identity and 81% homology). Moreover, the plant protein has conserved structural motifs that are characteristic features of pseudouridine synthases of the TruB class. We have named the cloned and characterized protein AtNAP57 (Arabidopsis thaliana homologue of NAP57). AtNAP57 is a 565 amino-acid protein and its calculated molecular mass is 63 kDa. The protein is encoded by a single copy gene located on chromosome 3 of the A. thaliana genome. Interestingly, the AtNAP57 gene does not contain any introns. Mutations in the human DKC1 gene encoding dyskerin (human homologue of yeast Cbf5p and rat NAP57) cause dyskeratosis congenita a rare inherited bone marrow failure syndrome characterized by abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia.

  2. Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats.

    PubMed

    Demirel, Ulvi; Yalniz, Mehmet; Aygün, Cem; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Kazim; Ozercan, Ibrahim Hanifi; Bahçecioğlu, Ibrahim Halil

    2012-08-01

    Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

  3. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  4. Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction

    PubMed Central

    Yang, Qin; He, Yong-Ming; Cai, Dong-Ping; Yang, Xiang-Jun; Xu, Hai-Feng

    2016-01-01

    Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven’t been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle. PMID:27748452

  5. Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury

    PubMed Central

    Lu, Haiyan; Huang, Danping; Saederup, Noah; Charo, Israel F.; Ransohoff, Richard M.; Zhou, Lan

    2011-01-01

    CC chemokine receptor 2 (CCR2) is essential to acute skeletal muscle injury repair. We studied the subpopulation of inflammatory cells recruited via CCR2 signaling and their cellular functions with respect to muscle regeneration. Mobilization of monocytes/macrophages (MOs/MPs), but not lymphocytes or neutrophils, was impaired from bone marrow to blood and from blood to injured muscle in Ccr2−/− mice. While the Ly-6C+ but not the Ly-6C− subset of MOs/MPs was significantly reduced in blood, both subsets were drastically reduced in injured muscle of Ccr2−/− mice. Expression of insulin-like growth factor-1 (IGF-I) was markedly up-regulated in injured muscle of wild-type but not Ccr2−/− mice. IGF-I was strongly expressed by macrophages within injured muscle, more prominently by the Ly-6C− subset. A single injection of IGF-I, but not PBS, into injured muscle to replace IGF-I remarkably improved muscle regeneration in Ccr2−/− mice. CCR2 was not detected in myogenic cells or capillary endothelial cells in injured muscle to suggest its direct involvement in muscle regeneration or angiogenesis. We conclude that CCR2 is essential to acute skeletal muscle injury repair primarily by recruiting Ly-6C+ MOs/MPs. Within injured muscle, these cells conduct phagocytosis, contribute to accumulation of intramuscular Ly-6C− macrophages, and produce a high level of IGF-I to promote muscle regeneration.—Lu, H., Huang, D., Saederupm, N., Charo, I. F., Ransohoff, R. M., Zhou, L. Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. PMID:20889618

  6. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.

    PubMed

    Santos, M S Biagioni; Seguro, A C; Andrade, L

    2010-03-01

    The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm(3), 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

  7. Types, Risk Factors, Clinical symptoms and Diagnostic Tests of Acute Adult Meningitis in Northern Iran During 2006-2012

    PubMed Central

    Bagheri-Nesami, Masoumeh; Babamahmoodi, Farhang

    2015-01-01

    Background Acute bacterial meningitis is a medical emergency condition that requires prompt diagnosis and treatment and otherwise associated with serious morbidity and mortality. Aim The aim of this study was to assess types, risk factors, clinical symptoms and diagnostic tests of meningitis in hospitalized patients of Mazandaran University of medical sciences hospitals during 2006-2012. Matherials and Methods This is a retrospective descriptive study. Following approval of the ethics committee of Mazandaran University of Medical Sciences, records of adult patients diagnosed with acute meningitis from 2006 to 2012 were extracted from Mazandaran Provincial Health Center and patients attending hospitals affiliated to Mazandaran University of Medical Sciences. Statistical Analysis Data were analyzed with SPSS-16 using descriptive statistics (frequency, mean, standard deviation, and median). Results In this study, of the 137 patients with meningitis, 73 (53.9%) were viral, 61 (46%) bacterial, 1 (0.7%) fungal, and 2 (1.4%) unknown. The majority of risk factors in patients were head trauma, upper respiratory infection, and drug addiction. The most common clinical signs were headache, fever, nausea and vomiting, and stiff neck. Conclusion In this study, the incidence of meningitis was much lower than any other country. It could be due to geographic variation or incomplete recording of patient's data. It is recommended to perform a longitudinal study during the coming years on patients with meningitis. PMID:26155497

  8. Angiographic and Clinical Factors Related with Good Functional Outcome after Mechanical Thrombectomy in Acute Cerebral Artery Occlusion

    PubMed Central

    Park, Jong Hyuk; Han, Young Min; Jang, Kyeong Sool; Yoon, Wan Soo; Jang, Dong Kyu

    2015-01-01

    Objective The aim of this study is to investigate good prognostic factors for an acute occlusion of a major cerebral artery using mechanical thrombectomy. Methods Between January 2013 to December 2014, 37 consecutive patients with acute occlusion of a major cerebral artery treated by mechanical thrombectomy with stent retrievers were conducted. We analyzed clinical and angiographic factors retrospectively. The collateral flow and the result of recanalization were sorted by grading systems. Outcome was assessed by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 90 days. We compared the various parameters between good and poor angiographic and clinical results. Results Twenty seven patients demonstrated good recanalization [Thrombolysis in Cerebral Infarction (TICI) 2b or 3] after thrombectomy. At the 90-day follow up, 19 patients had good (mRS, 0-2), 14 had moderate (3-4) and four had poor outcomes (5-6). The mRS of older patients (≥75 years) were poor than younger patients. Early recanalization, high Thrombolysis in Myocardial Infarction risk score, and low baseline NIHSS were closely related to 90-day mRS, whereas high TICI was related to both mRS and the decrease in the NIHSS. Conclusion NIHSS decreased markedly only when recanalization was successful. A good mRS was related to low initial NIHSS, good collateral, and early successful recanalization. PMID:26539260

  9. Pharmacological stimulation of Hypoxia Inducible Factor-1α facilitates the corticosterone response to a mild acute stressor

    PubMed Central

    Harrell, Constance S.; Rowson, Sydney A.; Neigh, Gretchen N.

    2015-01-01

    While both glucocorticoids (the principal output of the hypothalamic-pituitary-adrenal axis) and oxidative stress have been implicated in outcomes due to an excessive or prolonged stress response, the precise mechanisms linking these two systems remain poorly elucidated. One potential mediator between the hypothalamic-pituitary-adrenal axis and oxidative stress is the Hypoxia Inducible Factor-1 (HIF-1) pathway. HIF-1 is an oxygen-responsive transcription factor with diverse effects including changes in cellular metabolism. The experiments in this manuscript sought to determine if pharmacological stimulation of HIF-1α via administration of dimethyloxalylglycine (DMOG) would facilitate the corticosterone response to a mild acute stressor. DMOG administration significantly increased plasma corticosterone five minutes after an acute airpuff without changing baseline plasma corticosterone or plasma corticosterone level two hours post-startle. DMOG administration also reduced hippocampal gene expression of the pro-translocation co-chaperone for the glucocorticoid receptor, FKBP4, two hours after airpuff startle. At this same two-hour time point, hippocampal expression of FKBP5, an anti-translocation co-chaperone of glucocorticoid receptor, in the DMOG-treated group was also positively correlated with plasma corticosterone levels. These data indicate that there is significant crosstalk between the hypothalamic-pituitary-axis and the HIF-1 pathway and extend the current knowledge of glucocorticoid and hypoxia interactions in an ethologically relevant stress model. PMID:26037418

  10. Optimization of methods for quantification of rCBF using high-resolution [15O]H2O PET images

    NASA Astrophysics Data System (ADS)

    Walker, M. D.; Feldmann, M.; Matthews, J. C.; Anton-Rodriguez, J. M.; Wang, S.; Koepp, M. J.; Asselin, M.-C.

    2012-04-01

    This study aimed to derive accurate estimates of regional cerebral blood flow (rCBF) from noisy dynamic [15O]H2O PET images acquired on the high-resolution research tomograph, while retaining as much as possible the high spatial resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET autoradiographic method and generalized linear least-squares (GLLS), with fixed or extended to include spatially variable estimates of the dispersion of the measured input function, were compared to nonlinear least-squares (NLLS) for rCBF estimation. Six healthy volunteers underwent two [15O]H2O PET scans with continuous arterial blood sampling. rCBF estimates were obtained from three image reconstruction methods (one analytic and two iterative, of which one includes a resolution model) to which a range of post-reconstruction filters (3D Gaussian: 2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to be around 11 MBq kg-1 (800 MBq) by extrapolation of patient-specific noise equivalent count rates. Whole-brain rCBF values were found to be relatively insensitive to the method of reconstruction and rCBF quantification. The grey and white matter rCBF for analytic reconstruction and NLLS were 0.44 ± 0.03 and 0.15 ± 0.03 mL min-1 cm-3, respectively, in agreement with literature values. Similar values were obtained from the other methods. For generation of parametric images using GLLS or the autoradiographic method, a filter of ⩾4 mm was required in order to suppress noise in the PET images which otherwise produced large biases in the rCBF estimates.

  11. Acute phase proteins, C9, factor B, and lysozyme in recurrent oral ulceration and Behçet's syndrome.

    PubMed Central

    Lehner, T; Adinolfi, M

    1980-01-01

    The concentrations and sequential changes of some acute phase proteins, factor B, and lysozyme have been assayed in recurrent oral ulceration and Behçet's syndrome. C9 was elevated in both groups of patients and was the sensitive index of disease activity; however, it failed to discriminate between the three types of recurrent oral ulcers and four types of Behçet's syndrome. The level of alpha 1 acid glycoprotein and lysozyme were significantly increased predominantly in the ocular type, whereas factor B was significantly increased especially in the neurological type of Behçet's syndrome. It is suggested that the changes in the concentrations of some plasma proteins may help our understanding of tissue involvement in Behçet's syndrome, as well as in the selection of therapeutic agents in this disease. PMID:6900632

  12. [Nature of the relation of acute appendicitis morbidity to meteorological and heliogeophysical factors].

    PubMed

    Khaavel', A A; Birkenfeldt, R R

    1978-04-01

    The authors analyzed 2009 appendicitis case records for the period from 1964 to 1973. In a sea climate region an evident season distribution of the apendicitis morbidity was found, with the rise of the incidence rate in January, March and April. The rise of the appendicitis incidence rate during the periods of vast fluctuations of air temperature, increase of air humidity and decrease of actual duration of sun radiance was established. The rise of the incidence of acute appendicitis was also noted during the months of a great and extremely great magnetic storms.

  13. Acute kidney injury: risk factors and management challenges in developing countries.

    PubMed

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  14. Acute kidney injury: risk factors and management challenges in developing countries

    PubMed Central

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  15. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  16. Nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias

    SciTech Connect

    Huebner, K.; Isobe, M.; Chao, M.; Bothwell, M.; Ross, A.H.; Finan, J.; Hoxie, J.A.; Sehgal, A.; Buck, C.R.; Lanahan, A.

    1986-03-01

    Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17q12-q22. Additionally, part, if not all, of the nerve growth factor receptor locus is present on the translocated portion of 17q (17q21-qter) from a poorly differential acute leukemia in which the chromosome 17 breakpoint was indistinguishable cytogenetically from the 17 breakpoint observed in the t(15;17)(q22;q21) translocation associated with acute promyelocytic leukemia. Thus the nerve growth factor receptor locus may be closely distal to the acute promyelocytic leukemia-associated chromosome 17 breakpoint at 17q21.

  17. Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in Peshawar, Pakistan.

    PubMed

    Zaidi, Saira H; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services' admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient's parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts.

  18. Factors affecting the estimated probabilistic acute dietary exposure to captan from apple consumption.

    PubMed

    Zentai, A; Sali, J; Szabó, I J; Szeitzné-Szabó, M; Ambrus, A; Vásárhelyi, A

    2013-01-01

    The effect of the number of pesticide residue values below the LOQ/LOD of analytical methods, the variability of residues in individual fruits, mass of fruit units and the number of bootstrap iterations was studied on the probabilistically estimated acute exposure of consumers. The 4720 daily apple consumption data and the results of 1239 apple sample analyses for captan residues, performed within the Hungarian monitoring programme between 2005 and 2011, were used in this study as model matrix. Up to about 95th percentile exposure (µg/(kg bw·day)), simply multiplying each residue in composite samples with each consumption value gave similar estimates to those obtained with the complex procedure taking also into account the mass of and residues in individual fruits. However, the exposure above the 95th percentile calculated with the complex procedure gradually increased with increasing percentile level compared to the simple procedure. Including the high number of non-detects reduced the estimated exposure, which was the highest when only the residues measured in treated fruits were taken into account. The number of bootstrap iterations between 100 and 10,000 did not significantly affect the calculated exposure. The 99.99th percentile exposure amounted to 17.9% of the acute reference dose of 300 µg/(kg bw·day) for women of childbearing age.

  19. Diapers in War Zones: Ethnomedical Factors in Acute Childhood Gastroenteritis in Peshawar, Pakistan

    PubMed Central

    Zaidi, Saira H.; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services’ admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient’s parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  20. Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in Peshawar, Pakistan.

    PubMed

    Zaidi, Saira H; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services' admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient's parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  1. Cell- and stage-specific chromatin structure across the Complement receptor 2 (CR2/CD21) promoter coincide with CBF1 and C/EBP-beta binding in B cells.

    PubMed

    Cruickshank, Mark N; Fenwick, Emily; Karimi, Mahdad; Abraham, Lawrence J; Ulgiati, Daniela

    2009-08-01

    Stringent developmental transcription requires multiple transcription factor (TF) binding sites, cell-specific expression of signaling molecules, TFs and co-regulators and appropriate chromatin structure. During B-lymphopoiesis, human Complement receptor 2 (CR2/CD21) is detected on immature and mature B cells but not on B cell precursors and plasma cells. We examined cell- and stage-specific human CR2 gene regulation using cell lines modeling B-lymphopoiesis. Chromatin accessibility assays revealed a region between -409 and -262 with enhanced accessibility in mature B cells and pre-B cells, compared to either non-lymphoid or plasma cell-types, however, accessibility near the transcription start site (TSS) was elevated only in CR2-expressing B cells. A correlation between histone acetylation and CR2 expression was observed, while histone H3K4 dimethylation was enriched near the TSS in both CR2-expressing B cells and non-expressing pre-B cells. Candidate sites within the CR2 promoter were identified which could regulate chromatin, including a matrix attachment region associated with CDP, SATB1/BRIGHT and CEBP-beta sites as well as two CBF1 sites. ChIP assays verified that both CBF1 and C/EBP-beta bind the CR2 promoter in B cells raising the possibility that these factors facilitate or respond to alterations in chromatin structure to control the timing and/or level of CR2 transcription.

  2. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol

    PubMed Central

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S.; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    Aims: With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. Background: DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. Methods/Design: A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting

  3. Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus.

    PubMed

    Scaini, Giselli; Mello-Santos, Lis Mairá; Furlanetto, Camila B; Jeremias, Isabela C; Mina, Francielle; Schuck, Patrícia F; Ferreira, Gustavo C; Kist, Luiza W; Pereira, Talita C B; Bogo, Maurício R; Streck, Emilio L

    2013-12-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase leading to accumulation of the branched-chain amino acids (BCAA) and their corresponding branched-chain α-keto acids. In this study, we examined the effects of acute and chronic administration of BCAA on protein levels and mRNA expression of nerve growth factor (NGF) considering that patients with MSUD present neurological dysfunction and cognitive impairment. Considering previous observations, it is suggested that oxidative stress may be involved in the pathophysiology of the neurological dysfunction of MSUD. We also investigated the influence of antioxidant treatment (N-acetylcysteine and deferoxamine) in order to verify the influence of oxidative stress in the modulation of NGF levels. Our results demonstrated decreased protein levels of NGF in the hippocampus after acute and chronic administration of BCAA. In addition, we showed a significant decrease in the expression of ngf in the hippocampus only following acute administration in 10-day-old rats. Interestingly, antioxidant treatment was able to prevent the decrease in NGF levels by increasing ngf expression. In conclusion, the results suggest that BCAA is involved in the regulation of NGF in the developing rat. Thus, it is possible that alteration of neurotrophin levels during brain maturation could be of pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the decrease in NGF levels was prevented by antioxidant treatment, reinforcing that the hypothesis of oxidative stress can be an important pathophysiological mechanism underlying the brain damage observed in MSUD. PMID:23559405

  4. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    PubMed

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain.

  5. Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

    PubMed Central

    Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

    2012-01-01

    Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

  6. Physical exercise and acute restraint stress differentially modulate hippocampal brain-derived neurotrophic factor transcripts and epigenetic mechanisms in mice.

    PubMed

    Ieraci, Alessandro; Mallei, Alessandra; Musazzi, Laura; Popoli, Maurizio

    2015-11-01

    Physical exercise and stressful experiences have been shown to exert opposite effects on behavioral functions and brain plasticity, partly by involving the action of brain-derived neurotrophic factor (BDNF). Although epigenetic modifications are known to play a pivotal role in the regulation of the different BDNF transcripts, it is poorly understood whether epigenetic mechanisms are also implied in the BDNF modulation induced by physical exercise and stress. Here, we show that total BDNF mRNA levels and BDNF transcripts 1, 2, 3, 4, 6, and 7 were reduced immediately after acute restraint stress (RS) in the hippocampus of mice, and returned to control levels 24 h after the stress session. On the contrary, exercise increased BDNF mRNA expression and counteracted the stress-induced decrease of BDNF transcripts. Physical exercise-induced up-regulation of BDNF transcripts was accounted for by increase in histone H3 acetylated levels at specific BDNF promoters, whereas the histone H3 trimethylated lysine 27 and dimethylated lysine 9 levels were unaffected. Acute RS did not change the levels of acetylated and methylated histone H3 at the BDNF promoters. Furthermore, we found that physical exercise and RS were able to differentially modulate the histone deacetylases mRNA levels. Finally, we report that a single treatment with histone deacetylase inhibitors, prior to acute stress exposure, prevented the down-regulation of total BDNF and BDNF transcripts 1, 2, 3, and 6, partially reproducing the effect of physical exercise. Overall, these results suggest that physical exercise and stress are able to differentially modulate the expression of BDNF transcripts by possible different epigenetic mechanisms.

  7. Effects of acute aerobic exercise on a task-switching protocol and brain-derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness.

    PubMed

    Tsai, Chia-Liang; Pan, Chien-Yu; Chen, Fu-Chen; Wang, Chun-Hao; Chou, Feng-Ying

    2016-07-01

    What is the central question of this study? Neurocognitive functions can be enhanced by acute aerobic exercise, which could be associated with changes in serum brain-derived neurotrophic factor (BDNF) concentrations. We aimed to explore acute exercise-induced changes in BDNF concentrations, neuropsychological and neurophysiological performances when individuals with different levels of cardiorespiratory fitness performed a cognitive task. What is the main finding and its importance? Only young adults with higher cardiorespiratory fitness could attain switching cost and neurophysiological benefits via acute aerobic exercise. The mechanisms might be fitness dependent. Although acute aerobic exercise could enhance serum BDNF concentrations, changes in peripheral BDNF concentrations could not be the potential factor involved in the beneficial effects on neurocognitive performance. This study investigated the effects of acute aerobic exercise on neuropsychological and neurophysiological performances in young adults with different cardiorespiratory fitness levels when performing a task-switching protocol and explored the potential associations between acute aerobic exercise-induced changes in serum brain-derived neurotrophic factor (BDNF) concentrations and various neurocognitive outcomes. Sixty young adults were categorized into one control group (i.e. non-exercise-intervention; n = 20) and two exercise-intervention (EI) groups [i.e. higher (EIH , n = 20) and lower (EIL , n = 20) cardiorespiratory fitness] according to their maximal oxygen consumption. At baseline and after either an acute bout of 30 min of moderate-intensity aerobic exercise or a control period, the neuropsychological and neurophysiological performances and serum BDNF concentrations were measured when the participants performed a task-switching protocol involving executive control and greater demands on working memory. The results revealed that although acute aerobic exercise decreased reaction

  8. Effects of acute aerobic exercise on a task-switching protocol and brain-derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness.

    PubMed

    Tsai, Chia-Liang; Pan, Chien-Yu; Chen, Fu-Chen; Wang, Chun-Hao; Chou, Feng-Ying

    2016-07-01

    What is the central question of this study? Neurocognitive functions can be enhanced by acute aerobic exercise, which could be associated with changes in serum brain-derived neurotrophic factor (BDNF) concentrations. We aimed to explore acute exercise-induced changes in BDNF concentrations, neuropsychological and neurophysiological performances when individuals with different levels of cardiorespiratory fitness performed a cognitive task. What is the main finding and its importance? Only young adults with higher cardiorespiratory fitness could attain switching cost and neurophysiological benefits via acute aerobic exercise. The mechanisms might be fitness dependent. Although acute aerobic exercise could enhance serum BDNF concentrations, changes in peripheral BDNF concentrations could not be the potential factor involved in the beneficial effects on neurocognitive performance. This study investigated the effects of acute aerobic exercise on neuropsychological and neurophysiological performances in young adults with different cardiorespiratory fitness levels when performing a task-switching protocol and explored the potential associations between acute aerobic exercise-induced changes in serum brain-derived neurotrophic factor (BDNF) concentrations and various neurocognitive outcomes. Sixty young adults were categorized into one control group (i.e. non-exercise-intervention; n = 20) and two exercise-intervention (EI) groups [i.e. higher (EIH , n = 20) and lower (EIL , n = 20) cardiorespiratory fitness] according to their maximal oxygen consumption. At baseline and after either an acute bout of 30 min of moderate-intensity aerobic exercise or a control period, the neuropsychological and neurophysiological performances and serum BDNF concentrations were measured when the participants performed a task-switching protocol involving executive control and greater demands on working memory. The results revealed that although acute aerobic exercise decreased reaction

  9. Factors Related to Successful Transition to Practice for Acute Care Nurse Practitioners.

    PubMed

    Dillon, Deborah L; Dolansky, Mary A; Casey, Kathy; Kelley, Carol

    2016-01-01

    The transition from student to acute care nurse practitioner (ACNP) has been recognized as a time of stress. The purpose of this descriptive, correlational-comparative design pilot study was to examine: (1) the relationships among personal resources, community resources, successful transition, and job retention; (2) the difference between ACNPs with 0 to 4 years and ACNPs with more than 4 years of prior experience as a registered nurse in an intensive care unit or emergency department; and (3) the skills/procedures that ACNPs found difficult to perform independently. Thirty-four participants were recruited from a social media site for nurse practitioners. Organizational support, communication, and leadership were the most important elements of successful transition into the ACNP role. This information can help ACNP faculty and hospital orientation/fellowship program educators to help ACNPs transition into their first position after graduation.

  10. Factors Related to Successful Transition to Practice for Acute Care Nurse Practitioners.

    PubMed

    Dillon, Deborah L; Dolansky, Mary A; Casey, Kathy; Kelley, Carol

    2016-01-01

    The transition from student to acute care nurse practitioner (ACNP) has been recognized as a time of stress. The purpose of this descriptive, correlational-comparative design pilot study was to examine: (1) the relationships among personal resources, community resources, successful transition, and job retention; (2) the difference between ACNPs with 0 to 4 years and ACNPs with more than 4 years of prior experience as a registered nurse in an intensive care unit or emergency department; and (3) the skills/procedures that ACNPs found difficult to perform independently. Thirty-four participants were recruited from a social media site for nurse practitioners. Organizational support, communication, and leadership were the most important elements of successful transition into the ACNP role. This information can help ACNP faculty and hospital orientation/fellowship program educators to help ACNPs transition into their first position after graduation. PMID:27153306

  11. Knowledge, attitude and practice factors in childhood acute respiratory infections in a peninsular Malaysia health district.

    PubMed

    Vasanthamala, A; Arokiasamy, J T

    1989-01-01

    This study compares the knowledge, attitudes and practice of mothers in two ethnic groups with regard to acute respiratory infections (ARI) in their child. Most had traditional beliefs as to the cause of ARI with only a minority knowing the causes. Most mothers were aware of the effect of frequent attacks of ARI on the health status of their child and of the importance of early treatment. Reasons for their becoming worried during an episode of ARI in their child indicated that problems of distance, transportation and arrangements for care of their other children predominate. A large proportion of the respondents felt that their present knowledge of ARI was inadequate and were thus interested in obtaining more information. PMID:2620023

  12. Knowledge, attitude and practice factors in childhood acute respiratory infections in a peninsular Malaysia health district.

    PubMed

    Vasanthamala, A; Arokiasamy, J T

    1989-01-01

    This study compares the knowledge, attitudes and practice of mothers in two ethnic groups with regard to acute respiratory infections (ARI) in their child. Most had traditional beliefs as to the cause of ARI with only a minority knowing the causes. Most mothers were aware of the effect of frequent attacks of ARI on the health status of their child and of the importance of early treatment. Reasons for their becoming worried during an episode of ARI in their child indicated that problems of distance, transportation and arrangements for care of their other children predominate. A large proportion of the respondents felt that their present knowledge of ARI was inadequate and were thus interested in obtaining more information.

  13. [Expression and clinical significance of caudal type homeobox transcription factor-2 in adult acute lymphocytic leukemia].

    PubMed

    Lu, Hai-Yan; Xia, Hai-Long; Chen, Xiao-Wen; Zhu, Li-Xin; Wang, Qing-Yi; Cheng, Xin

    2011-04-01

    This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.

  14. Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis

    PubMed Central

    Jackson, Stewart; Mathews, Kyle H.; Pulanić, Dražen; Falconer, Rachel; Rudan, Igor; Campbell, Harry; Nair, Harish

    2013-01-01

    Aim To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. Methods We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. Results We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). Conclusion This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia. PMID:23630139

  15. Nerve growth factor acutely reduces chemical transmission by means of postsynaptic TrkA-like receptors in squid giant synapse

    PubMed Central

    Moreno, Herman; Nadal, Marcela; Leznik, Elena; Sugimori, Mutsuyuki; Lax, Irit; Schlessinger, Joseph; Llinás, Rodolfo

    1998-01-01

    Tyrosine phosphorylation has been shown to be an important modulator of synaptic transmission in both vertebrates and invertebrates. Such findings hint toward the existence of extracellular ligands capable of activating this widely represented signaling mechanism at or close to the synapse. Examples of such ligands are the peptide growth factors which, on binding, activate receptor tyrosine kinases. To gain insight into the physiological consequences of receptor tyrosine kinase activation in squid giant synapse, a series of growth factors was tested in this preparation. Electrophysiological, pharmacological, and biochemical analysis demonstrated that nerve growth factor (NGF) triggers an acute and specific reduction of the postsynaptic potential amplitude, without affecting the presynaptic spike generation or presynaptic calcium current. The NGF target is localized at a postsynaptic site and involves a new TrkA-like receptor. The squid receptor crossreacts with antibodies generated against mammalian TrkA, is tyrosine phosphorylated in response to NGF stimulation, and is blocked by specific pharmacological inhibitors. The modulation described emphasizes the important role of growth factors on invertebrate synaptic transmission. PMID:9844004

  16. Nerve growth factor acutely reduces chemical transmission by means of postsynaptic TrkA-like receptors in squid giant synapse.

    PubMed

    Moreno, H; Nadal, M; Leznik, E; Sugimori, M; Lax, I; Schlessinger, J; Llinás, R

    1998-12-01

    Tyrosine phosphorylation has been shown to be an important modulator of synaptic transmission in both vertebrates and invertebrates. Such findings hint toward the existence of extracellular ligands capable of activating this widely represented signaling mechanism at or close to the synapse. Examples of such ligands are the peptide growth factors which, on binding, activate receptor tyrosine kinases. To gain insight into the physiological consequences of receptor tyrosine kinase activation in squid giant synapse, a series of growth factors was tested in this preparation. Electrophysiological, pharmacological, and biochemical analysis demonstrated that nerve growth factor (NGF) triggers an acute and specific reduction of the postsynaptic potential amplitude, without affecting the presynaptic spike generation or presynaptic calcium current. The NGF target is localized at a postsynaptic site and involves a new TrkA-like receptor. The squid receptor crossreacts with antibodies generated against mammalian TrkA, is tyrosine phosphorylated in response to NGF stimulation, and is blocked by specific pharmacological inhibitors. The modulation described emphasizes the important role of growth factors on invertebrate synaptic transmission.

  17. Effect of acute and chronic administration of L-tyrosine on nerve growth factor levels in rat brain.

    PubMed

    Ferreira, Gabriela K; Jeremias, Isabela C; Scaini, Giselli; Carvalho-Silva, Milena; Gomes, Lara M; Furlanetto, Camila B; Morais, Meline O; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2013-08-01

    Most inborn errors of tyrosine catabolism produce hypertyrosinemia. Neurological manifestations are variable and some patients are developmentally normal, while others show different degrees of developmental retardation. Considering that current data do not eliminate the possibility that elevated levels of tyrosine and/or its derivatives may have noxious effects on central nervous system development in some patients, the present study evaluated nerve growth factor (NGF) levels in hippocampus, striatum and posterior cortex of young rats. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal administration of L-tyrosine (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); the rats were killed 12 h after the last injection. NGF levels were then evaluated. Our findings showed that acute administration of L-tyrosine decreased NGF levels in striatum of 10-day-old rats. In the 30-day-old rats, NGF levels were decreased in hippocampus and posterior cortex. On the other hand, chronic administration of L-tyrosine increased NGF levels in posterior cortex. Decreased NGF may impair growth, differentiation, survival and maintenance of neurons. PMID:23690230

  18. Acute tubular injury in protocol biopsies of renal grafts: prevalence, associated factors and effect on long-term function.

    PubMed

    Gwinner, W; Hinzmann, K; Erdbruegger, U; Scheffner, I; Broecker, V; Vaske, B; Kreipe, H; Haller, H; Schwarz, A; Mengel, M

    2008-08-01

    Acute tubular injury (ATI) is commonly observed in renal allografts, especially early after transplantation. This study analyzes prevalence and associated clinical conditions of ATI in serial protocol biopsies (pBx) and indication biopsies (iBx), and its impact on long-term graft function. 612 pBx from 204 patients taken at 6 weeks, 3 and 6 months, and 151 iBx performed within the first year of transplantation were evaluated. Prevalence of ATI in pBx was 40% (6 weeks), 34% (3 months) and 37% (6 months), and 46% in iBx. ATI was associated with delayed graft function and prolonged cold ischemia time in pBx, and with acute rejections in iBx. The GFR at 1 and 2 years after transplantation correlated inversely with the frequency of ATI in both pBx and iBx (p < 0.001). Prevalence of chronic changes at 6 months was not significantly related to ATI (patients without ATI: 36%, patients with multiple ATI findings: 54%). ATI is linked to inferior long-term graft function. While this suggests lack of recovery from ATI with permanent allograft damage, the underlying molecular mechanisms need yet to be uncovered. Prevention of the potential pathogenetic factors identified in this study might be the key point to attain good long-term graft function.

  19. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    PubMed Central

    Hacioglu, Gulay; Senturk, Ayse; Ince, Imran; Alver, Ahmet

    2016-01-01

    Objective(s): Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain. PMID:27279982

  20. Use of Therapeutic Neuroscience Education to address psychosocial factors associated with acute low back pain: a case report.

    PubMed

    Zimney, Kory; Louw, Adriaan; Puentedura, Emilio J

    2014-04-01

    Acute low back pain (LBP) from injuries is prevalent in the work place. It has been shown that patients with psychosocial factors often progress with persistent pain and lead to significant workers compensation costs. Therapeutic Neuroscience Education (TNE) has been shown to be beneficial in changing a patient's cognition regarding their pain state, which may result in decrease fear, anxiety and catastrophization. A 19-year-old female who developed LBP from a work injury was the patient for this case report. A physical examination, Numeric Pain Rating Scale (NRPS), Oswestry Disability Index (ODI), Fear-Avoidance Beliefs Questionnaire (FABQ), Keele STarT Back Screening Tool (Keele SBST) and Acute Low Back Pain Screening (ALBPS) Questionnaires were assessed during initial physical therapy visit and discharge. Treatment consisted of use of TNE, manual therapy and exercises. She attended five total visits over a 2-week period prior to full discharge. During the initial visit the patient reported NRPS = 3/10, ODI = 36%, FABQ-PA = 23, FABQ-W = 30, Keele SBST = 4/9, ALBPS = 101. At discharge the patient reported a 0 on all outcome questionnaires with ability to return to full work and no pain complaints. PMID:24252071

  1. Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies.

    PubMed

    Lagraauw, H Maxime; Kuiper, Johan; Bot, Ilze

    2015-11-01

    Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. PMID:26256574

  2. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    PubMed

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations.

  3. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

    PubMed Central

    Qian, X; Samadani, U; Porcella, A; Costa, R H

    1995-01-01

    Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF-3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1-HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due

  4. Serum homocysteine as a risk factor for carotid intimal thickening in acute stroke: A cross sectional observational study

    PubMed Central

    Devasia, Anup J.; Joy, Binu; Tarey, Subhash D.

    2016-01-01

    Introduction: The present study aimed to analyse if there is a correlation between carotid intima medial thickening (CIMT) and Hcy in stroke patients. Methodology: We studied 100 consecutive cases of acute anterior circulation strokes at St. John's Medical College, Bangalore, India. Fasting serum samples for homocysteine were sent within 24 hours of admission and all patients underwent a carotid Doppler scan and carotid intima-medial thickness (CIMT) was estimated on both sides. Results: There was significant correlation between serum homocysteine levels and carotid intima-medial thickness (r = 0.409, p = 0.000). Also after controlling for other possible risk factors it was found that elevations in serum homocysteine levels would cause a variation of 60% in the carotid intima-medial thickening. Conclusion: Serum Hcy levels correlate well with CIMT and hence may predict atherothrombotic events. PMID:27011628

  5. Effect of simulated weightlessness on the expression of Cbfα1 induced by fluid shear stress in MG-63 osteosarcoma cells.

    NASA Astrophysics Data System (ADS)

    Yang, Z.; Zhang, S.; Wang, B.; Sun, X. Q.

    Objective The role of mechanical load in the functional regulation of osteoblasts becomes an emphasis in osseous biomechanical researches recently This study was aim to explore the effect of flow shear stress on the expression of Cbf alpha 1 in human osteosarcoma cells and to survey its functional alteration in simulated weightlessness Method After cultured for 72 h in two different gravitational environments i e 1G terrestrial gravitational condition and simulated weightlessness condition human osteosarcoma cells MG-63 were treated with 0 5 Pa or 1 5 Pa fluid shear stress FSS in a flow chamber for 15 30 60 min respectively The total RNA in cells was isolated Transcription PCR analysis was made to examine the gene expression of Cbf alpha 1 And the total protein of cells was extracted and the expression of Cbf alpha 1 protein was detected by means of Western Blotting Results MG-63 cultured in 1G condition reacted to FSS treatment with an enhanced expression of Cbf alpha 1 Compared with no FSS control group Cbf alpha 1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS P 0 01 And there was remarkable difference on the Cbf alpha 1 mRNA and protein expression between the treatments of 0 5 Pa and 1 5 Pa FSS at 30 min or 60 min P 0 01 As to the osteoblasts cultured in simulated weightlessness by using clinostat the expression of Cbf alpha 1 was significantly different between 1G and simulated weightlessness conditions at each test time P 0 05 Compared with no FSS

  6. Analyzing the Expression Profile of AREB/ABF and DREB/CBF Genes under Drought and Salinity Stresses in Grape (Vitis vinifera L.).

    PubMed

    Zandkarimi, Hana; Ebadi, Ali; Salami, Seyed Alireza; Alizade, Houshang; Baisakh, Niranjan

    2015-01-01

    Expression patterns of four candidate AREB/ABF genes and four DREB/CBF genes were evaluated in leaf and root tissues of five grape varieties ('Qalati', 'Kaj Angoor', 'Sabz Angoor', 'Siahe Zarghan', 'Bidane Safid') with differential response to drought stress. Among the AREB/ABF genes, AREB1 and ABF2 showed up-regulation in response to drought stress in leaf and root tissues of all varieties while AREB2 and ABF1 showed down-regulation in both leaf and root tissues of the sensitive variety 'Bidane Sefid' in response to drought and salt stress. Among the DREB/CBF genes, CBF4 was the most responsive to drought stress in both leaf and root tissues. CBF2 and CBF3 showed up-regulation in all varieties in response to drought stress in leaf except in 'Bidane Sefid'. Under salinity stress, AREB2 and ABF2 showed up-regulation in response to the increasing level of salinity in the leaf tissues but in the root tissues ABF2 was up-regulated in response to increasing NaCl concentration while AREB2 was down-regulated. Therefore, it seems AREB2 has tissue-specific response to salinity stress. All CBF genes were up-regulated in response to salinity stress in the leaf and root tissues. Expression data suggested that CBF2 is more responsive to NaCl stress. Among all four promising and stress tolerant varieties 'Siah Zarghan' and 'Kaj Angoor' were more tolerant than 'Qalati' and 'Sabz Angoor' to drought and salinity.

  7. Analyzing the Expression Profile of AREB/ABF and DREB/CBF Genes under Drought and Salinity Stresses in Grape (Vitis vinifera L.)

    PubMed Central

    Zandkarimi, Hana; Ebadi, Ali; Salami, Seyed Alireza; Alizade, Houshang; Baisakh, Niranjan

    2015-01-01

    Expression patterns of four candidate AREB/ABF genes and four DREB/CBF genes were evaluated in leaf and root tissues of five grape varieties (‘Qalati’, ‘Kaj Angoor’, ‘Sabz Angoor’, ‘Siahe Zarghan’, ‘Bidane Safid’) with differential response to drought stress. Among the AREB/ABF genes, AREB1 and ABF2 showed up-regulation in response to drought stress in leaf and root tissues of all varieties while AREB2 and ABF1 showed down-regulation in both leaf and root tissues of the sensitive variety ‘Bidane Sefid’ in response to drought and salt stress. Among the DREB/CBF genes, CBF4 was the most responsive to drought stress in both leaf and root tissues. CBF2 and CBF3 showed up-regulation in all varieties in response to drought stress in leaf except in ‘Bidane Sefid’. Under salinity stress, AREB2 and ABF2 showed up-regulation in response to the increasing level of salinity in the leaf tissues but in the root tissues ABF2 was up-regulated in response to increasing NaCl concentration while AREB2 was down-regulated. Therefore, it seems AREB2 has tissue-specific response to salinity stress. All CBF genes were up-regulated in response to salinity stress in the leaf and root tissues. Expression data suggested that CBF2 is more responsive to NaCl stress. Among all four promising and stress tolerant varieties ‘Siah Zarghan’ and ‘Kaj Angoor’ were more tolerant than ‘Qalati’ and ‘Sabz Angoor’ to drought and salinity. PMID:26230273

  8. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia

    PubMed Central

    Klein, Hans-Ulrich; Hascher, Antje; Isken, Fabienne; Tickenbrock, Lara; Thoennissen, Nils; Agrawal-Singh, Shuchi; Tschanter, Petra; Disselhoff, Christine; Wang, Yipeng; Becker, Anke; Thiede, Christian; Ehninger, Gerhard; zur Stadt, Udo; Koschmieder, Steffen; Seidl, Matthias; Müller, Frank U.; Schmitz, Wilhelm; Schlenke, Peter; McClelland, Michael; Berdel, Wolfgang E.; Dugas, Martin; Serve, Hubert

    2010-01-01

    Acute myeloid leukemia (AML) is commonly associated with alterations in transcription factors because of altered expression or gene mutations. These changes might induce leukemia-specific patterns of histone modifications. We used chromatin-immunoprecipitation on microarray to analyze histone 3 lysine 9 trimethylation (H3K9me3) patterns in primary AML (n = 108), acute lymphoid leukemia (n = 28), CD34+ cells (n = 21) and white blood cells (n = 15) specimens. Hundreds of promoter regions in AML showed significant alterations in H3K9me3 levels. H3K9me3 deregulation in AML occurred preferentially as a decrease in H3K9me3 levels at core promoter regions. The altered genomic regions showed an overrepresentation of cis-binding sites for ETS and cyclic adenosine monophosphate response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML-specific H3K9me3 patterns were not associated with known cytogenetic abnormalities. But a signature derived from H3K9me3 patterns predicted event-free survival in AML patients. When the H3K9me3 signature was combined with established clinical prognostic markers, it outperformed prognosis prediction based on clinical parameters alone. These findings demonstrate widespread changes of H3K9me3 levels at gene promoters in AML. Signatures of histone modification patterns are associated with patient prognosis in AML. PMID:20498303

  9. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection.

    PubMed

    Benfield, Camilla T O; Ren, Hongwei; Lucas, Stuart J; Bahsoun, Basma; Smith, Geoffrey L

    2013-07-01

    Vaccinia virus (VACV) encodes many proteins that antagonize the innate immune system including a family of intracellular proteins with a B-cell lymphoma (Bcl)-2-like structure. One of these Bcl-2 proteins called K7 binds Toll-like receptor-adaptor proteins and the DEAD-box RNA helicase DDX3 and thereby inhibits the activation of NF-κB and interferon regulatory factor 3. However, the contribution of K7 to virus virulence is not known. Here a VACV lacking the K7R gene (vΔK7) was constructed and compared with control viruses that included a plaque purified wt (vK7), a revertant with the K7R gene reinserted (vK7-rev) and a frame-shifted virus in which the translational initiation codon was mutated to prevent K7 protein expression (vK7-fs). Data presented show that loss of K7 does not affect virus replication in cell culture or in vivo; however, viruses lacking the K7 protein were less virulent than controls in murine intradermal (i.d.) and intranasal (i.n.) infection models and there was an altered acute immune response to infection. In the i.d. model, vΔK7 induced smaller lesions than controls, and after i.n. infection vΔK7 induced a reduced weight loss and signs of illness, and more rapid clearance of virus from infected tissue. Concomitantly, the intrapulmonary innate immune response to infection with vΔK7 showed increased infiltration of NK cells and CD8⁺ T-cells, enhanced MHC class II expression by macrophages, and enhanced cytolysis of target cells by NK cells and VACV-specific CD8⁺ T-cells. Thus protein K7 is a virulence factor that affects the acute immune response to infection.

  10. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

    PubMed

    Kornhauser, Carlos; Dubey, Luis-Antonio; Garay, M-Eugenia; Pérez-Luque, Elva-Leticia; Malacara, Juan-Manuel; Vargas-Origel, Arturo

    2002-05-01

    Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

  11. Short Door-to-Needle Times in Acute Ischemic Stroke and Prospective Identification of Its Delaying Factors

    PubMed Central

    Van Schaik, Sander M.; Scott, Saskia; de Lau, Lonneke M.L.; Van den Berg-Vos, Renske M.; Kruyt, Nyika D.

    2015-01-01

    Background The clinical benefit of intravenous thrombolysis (IVT) in acute ischemic stroke is time dependent. Several studies report a short median door-to-needle time (DNT; 20 min), mainly in large tertiary referral hospitals equipped with a level 1 emergency department, a dedicated stroke team available 24/7, and on-site neuroimaging facilities. Meanwhile, in daily practice, the majority of stroke patients are admitted to secondary care hospitals, and in practice, even the generous benchmark of the American Heart Association (a DNT of 60 min in >80% of the cases) is met for a minority of patients treated with IVT. The first objective of our study was to investigate if, in a secondary care teaching hospital rather than a tertiary referral hospital, similar short DNTs can be accomplished with an optimized IVT protocol. Our second objective was to prospectively identify factors that delay the DNT in this setting. Methods A multicenter, consecutive cohort study of patients treated with IVT in one of two secondary care teaching hospitals. In both hospitals, data of consecutive stroke patients as well as median DNTs and factors delaying this were prospectively assessed for each patient. Multivariable logistic regression analysis was used to evaluate associations between patient-related and logistic factors with a delayed (i.e. exceeding 30 min) DNT. Results In total, 1,756 patients were admitted for ischemic stroke during the study period. Out of these, 334 (19.0%) patients were treated with IVT. The median DNT was 25 min (interquartile range: 20-35). A total of 71% (n = 238) had a DNT below 30 min. In 63% of the patients treated with IVT the DNT was delayed by at least one factor. Patients without any delaying factor had a 10 min shorter median DNT compared to patients with at least one delaying factor (p < 0.001). The following factors were independently associated with a delayed DNT: uncertainty about symptom onset, uncontrolled blood pressure, fluctuating

  12. Factors Associated with Early Hospital Arrival in Patients with Acute Ischemic Stroke

    PubMed Central

    Song, Dongbeom; Tanaka, Eijirou; Lee, Kijeong; Sato, Shoichiro; Koga, Masatoshi; Kim, Young Dae; Nagatsuka, Kazuyuki; Toyoda, Kazunori

    2015-01-01

    Background and Purpose Factors associated with early arrival may vary according to the characteristics of the hospital. We investigated the factors associated with early hospital arrival in two different stroke centers located in Korea and Japan. Methods Consecutive patients with ischemic stroke arrived hospital within 48 hours of onset between January 2011 and December 2012 were identified and the clinical and time variables were retrieved from the prospective stroke registries of Severance Hospital of Yonsei University Health System (YUHS; Seoul, Korea) and National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan). Subjects were dichotomized into early (time from onset to arrival ≤4.5 hours) and late (>4.5 hours) arrival groups. Univariate and multivariate analyses were performed to evaluate factors associated with early hospital arrival. Results A total of 1,966 subjects (992 from YUHS; 974 from NCVC) were included in this study. The median time from onset to arrival was 6.1 hours [interquartile range, 1.7-17.8 hours]. In multivariate analysis, the factors associated with early arrival were atrial fibrillation (Odds ratio [OR], 1.505; 95% confidence interval [CI], [1.168-1.939]), higher initial National Institute of Health Stroke Scale scores (OR, 1.037; 95% CI [1.023-1.051]), onset during daytime (OR, 2.799; 95% CI [2.173-3.605]), and transport by an emergency medical service (OR, 2.127; 95% CI [1.700-2.661]). These factors were consistently associated with early arrival in both hospitals. Conclusions Despite differences between the hospitals, there were common factors related to early arrival. Efforts to identify and modify these factors may promote early hospital arrival and improve stroke outcome. PMID:26060803

  13. Potential factors associated with fruit and vegetable intake after premature acute coronary syndrome: a prospective cohort study.

    PubMed

    Leung Yinko, Sylvie S L; Pelletier, Roxanne; Behlouli, Hassan; Bacon, Simon L; Karp, Igor; Thanassoulis, George; Daskalopoulou, Stella S; Eisenberg, Mark J; Khan, Nadia A; Lavoie, Kim L; Pilote, Louise

    2015-01-01

    Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations.

  14. Potential factors associated with fruit and vegetable intake after premature acute coronary syndrome: a prospective cohort study.

    PubMed

    Leung Yinko, Sylvie S L; Pelletier, Roxanne; Behlouli, Hassan; Bacon, Simon L; Karp, Igor; Thanassoulis, George; Daskalopoulou, Stella S; Eisenberg, Mark J; Khan, Nadia A; Lavoie, Kim L; Pilote, Louise

    2015-01-01

    Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations. PMID:26529090

  15. The epidemiology and prognostic factors of mortality in critically ill children with acute kidney injury in Taiwan.

    PubMed

    Chang, Jei-Wen; Jeng, Mei-Jy; Yang, Ling-Yu; Chen, Tzeng-Ji; Chiang, Shu-Chiung; Soong, Wen-Jue; Wu, Keh-Gong; Lee, Yu-Sheng; Wang, Hsin-Hui; Yang, Chia-Feng; Tsai, Hsin-Lin

    2015-03-01

    The incidence of acute kidney injury (AKI) in critically ill children varies among countries. Here we used claims data from the Taiwanese National Health Insurance program from 2006 to 2010 to investigate the epidemiological features and identify factors that predispose individuals to developing AKI and mortality in critically ill children with AKI. Of 60,338 children in this nationwide cohort, AKI was identified in 850, yielding an average incidence rate of 1.4%. Significant independent risk factors for AKI were the use of extracorporeal membrane oxygenation, mechanical ventilation or vasopressors, intrinsic renal diseases, sepsis, and age more than 1 year. Overall, of the AKI cases, 46.5% were due to sepsis, 36.1% underwent renal replacement therapy, and the mortality rate was 44.2%. Multivariate analysis showed that the use of vasopressors, mechanical ventilation, and hemato-oncological disorders were independent predictors of mortality in AKI patients. Thirty-two of the 474 patients who survived had progression to chronic kidney disease or end-stage renal disease. Thus, although not common, AKI in critically ill children still has a high mortality rate associated with a variety of factors. Long-term close follow-up to prevent progressive chronic kidney disease in survivors of critical illnesses with AKI is mandatory. PMID:25252027

  16. Angiogenic factors are associated with development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Nie, Di-min; Wu, Qiu-ling; Zhu, Xia-xia; Zhang, Ran; Zheng, Peng; Fang, Jun; You, Yong; Zhong, Zhao-dong; Xia, Ling-hui; Hong, Mei

    2015-10-01

    Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD. PMID:26489624

  17. Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke

    PubMed Central

    Wicking, Manon; Bellebaum, Christian; Hermann, Dirk M.

    2016-01-01

    Background Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described. Methods We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years), whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group. Results In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030), but not the acquisition phase (F[2,30] = 1.01; p = 0.376) and the acquired equivalence (F[2,30] = 1.04; p = 0.367) tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012), but not acquisition learning (r = -0.20, p = 0.121) or acquired equivalence (r = -0.22, p = 0.096). Conclusions The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies. PMID:27163585

  18. Factors affecting outcome of coronary reperfusion with intracoronary streptokinase in acute myocardial infarction.

    PubMed

    Smalling, R W; Fuentes, F; Matthews, M W; Kuhn, J; Nishikawa, A; Walker, W E; Adams, P R; Gould, K L

    1987-03-01

    Aggressive interventional therapy in acute myocardial infarction (AMI) is expensive, time-consuming and not without significant risk. To determine which patients are most likely to benefit from such therapy, the effects of patient age, reperfusion success, admission left ventricular (LV) function, infarct location, admission clinical class, time from onset of pain to reperfusion and admission electrocardiographic findings on the outcome of coronary reperfusion in AMI were assessed in 292 prospectively studied, sequential patients from August 1980 to January 1984. Two hundred ten patients received intracoronary streptokinase (SK) therapy on admission and 82 patients, who either refused the protocol or met exclusion criteria, served as control subjects. Patients older than 65 years showed little improvement in 1-year mortality risk and no significant improvement in LV function during hospitalization after treatment with intracoronary SK. The remaining patients, 178 treated with SK and 48 control, were well matched and served as the basis for further comparisons. In this subgroup of patients, reperfusion success was associated with improved survival and LV function (mortality rate 3%, vs 17% in control subjects; increase in ejection fraction [EF] 18% vs 4%). Patients with an EF of less than 45% on admission showed a 21 +/- 30% increase in EF, compared with an increase in control subjects of 8 +/- 19%, and a lower 1-year mortality rate than controls (6% vs 21%, p = 0.01). Patients with anterior AMI had a significant increase in EF in the SK group (22 +/- 31%) and lower mortality compared with control subjects (5% vs 25%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Reliability comparison of spontaneous brain activities between BOLD and CBF contrasts in eyes-open and eyes-closed resting states.

    PubMed

    Zou, Qihong; Miao, Xinyuan; Liu, Dapeng; Wang, Danny J J; Zhuo, Yan; Gao, Jia-Hong

    2015-11-01

    Blood oxygenation level dependent (BOLD) and arterial spin labeling (ASL) are two predominant resting-state fMRI techniques in mapping spontaneous brain activities. At single voxel level, cerebral blood flow (CBF) measured by ASL and amplitude of low frequency fluctuations (ALFF) of BOLD have been recognized as useful indices to characterize brain function in health and disease. However, no study has directly compared the test-retest reliability between BOLD and CBF contrasts on the same group of subjects at single voxel level. Moreover, both eyes-open and eyes-closed conditions have been employed as resting states, but it is still not clear which state is more reliable. Here we collected BOLD and ASL data during eyes-open and eyes-closed states across three scanning visits on twenty-two healthy young subjects. CBF-mean, BOLD- and CBF-ALFF were computed to characterize corresponding brain activities at single voxel level. Seed-based functional connectivity (FC) with the posterior cingulate cortex (PCC) was further calculated for both BOLD and CBF data. Intra-class correlation was used as the index of long-term reliability between visits 1 and 2 (two months apart) and short-term reliability between visits 2 and 3 (on the same day). Both short- and long-term reliabilities for CBF-mean and BOLD-ALFF were high, but were lower for CBF-ALFF, BOLD- and CBF-FC in both eyes-open and eyes-closed states. Direct comparisons showed that brain regions with the highest reliability of CBF-mean were mainly in the gray matter. The reliability of CBF-ALFF and BOLD-FC was lower than that of BOLD-ALFF, and the reliability of CBF-FC was lower than those of both CBF-ALFF and BOLD-FC. Furthermore, we observed that reliabilities of the eyes-open state were higher than those of the eyes-closed state for both imaging contrasts, though the effect size was small. Voxel-wise comparisons demonstrated that the long-term reliability of BOLD-ALFF was significantly higher with eyes open in the

  20. HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients.

    PubMed

    Zou, Jing; Guo, Qiang; Chi, Jiachang; Wu, Huawei; Bao, Chunde

    2015-04-01

    The aim of this study is to evaluate the factors associated to 1-year mortality in clinically amyopathic dermatomyositis (CADM) patients with acute interstitial lung disease (ILD). A single center of 37 cases of Chinese patients with CADM was reviewed retrospectively in Renji hospital. All CADM patients were diagnosed with ILD; there were 24 cases of acute interstitial pneumonia (AIP) and 13 cases of acute exacerbation of non-acute interstitial pneumonia non-AIP. The clinical features, including blood tests, chest high-resolution computed tomography (HRCT) score, and lung function, were analyzed, respectively. Neutrophil lymphocyte ratio (NLR), serum ferritin level, serum lactate dehydrogenase (LDH) level, and HRCT score were statistically significant factors on univariate analysis. Multivariate analysis revealed that the overall HRCT score (HR 1.134, 95 % confidence interval 1.009-1.275, P = 0.017) and serum ferritin level (HR 1.001, 95 % confidence interval 1.002-1.007, P = 0.010) were independently significant factors of 1-year mortality. C statistic value of HRCT score (c statistic value 0.867, P < 0.0001) and serum ferritin level (c statistic value 0.808, P = 0.002) were statistically significant in the classification of non-survivors. Patients with calcineurin inhibitor presented a better outcome than those without calcineurin inhibitor (log-rank test, P = 0.006). HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute ILD in CADM patients. Calcineurin inhibitor might improve the outcome of CADM patients with acute ILD.

  1. Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

    PubMed

    Daniel, Maria; Ekenbäck, Christina; Agewall, Stefan; Brolin, Elin B; Caidahl, Kenneth; Cederlund, Kerstin; Collste, Olov; Eurenius, Lars; Frick, Mats; Younis-Hassan, Shams; Henareh, Loghman; Jernberg, Tomas; Malmqvist, Karin; Spaak, Jonas; Sörensson, Peder; Hofman-Bang, Claes; Tornvall, Per

    2015-09-15

    Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA. PMID:26251000

  2. Factors Affecting Trial Without Catheter for First Spontaneous Acute Urinary Retention

    PubMed Central

    Vaddi, Surya Prakash; Godala, Chandra-Mohan; Reddy, V. Vijaya Kumar; Sambar, Venkat Krishna

    2013-01-01

    Purpose To find the association of trial without catheter (TWOC) outcome for first spontaneous acute urinary retention (AUR) in benign prostatic obstruction with age, prior lower urinary tract symptoms (LUTS), retention volume at catheterization (RV), and size of prostate. Methods Our prospective observational analytical (interventional) study enrolled 77 cases of spontaneous AUR over 24 months. After clinical evaluation, digital rectal examination, and transabdominal ultrasonography, all patients were catheterized per urethra and their RV was recorded. TWOC was administered after 2 or 3 doses of 0.4 mg tamsulosin-oral absorption control system and after 48-72 hours had passed. A successful endpoint was defined as a maximum flow-rate, >5 mL/sec; voided volume, >100 mL; postvoid residue, <200 mL; and voiding within 6 hours of catheter removal. Data obtained from 58 patients were analyzed after excluding the cases lost to follow-up and secondary exclusion. Age, RV, duration of LUTS, and prostate volume on examination and ultrasonography (PUSG) were recorded and statistically analyzed. Prostate-specific antigen levels were obtained on follow-up and cases of cancer, as seen on transrectal ultrasound-guided biopsy, were secondarily excluded. Results The patients had a mean age of 65.89±8.67 years. Prior LUTS was seen in 35 patients (2.07±2.91 months). The mean PUSG and RV were 46.81±20.58 mL and 854.8±36.26 mL, respectively. Thirty patients underwent a successful TWOC; a mean age of 63.13±8.58 years (mean±standard deviation; unpaired t-test; P=0.0053) and a PUSG of ≤45 mL (Pearson chi-square test; P=0.0427) were significantly associated with a successful outcome. Conclusions There is a significant association between TWOC outcome, age (P=0.0053), and PUSG (P=0.0427). PMID:24143290

  3. Prehospitalization Risk Factors for Acute Kidney Injury during Hospitalization for Serious Infections in the REGARDS Cohort

    PubMed Central

    Wang, Henry E.; Powell, T. Clark; Gutiérrez, Orlando M.; Griffin, Russell; Safford, Monika M.

    2015-01-01

    Background/Aims Acute kidney injury (AKI) frequently occurs in hospitalized patients. In this study, we determined prehospitalization characteristics associated with AKI in community-dwelling adults hospitalized for a serious infection. Methods We used prospective data from 30,239 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of community-dwelling adults ≥45 years old. We identified serious infection hospitalizations between 2003 and 2012. Using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, we defined AKI as an increase in serum creatinine (sCr) ≥0.3 mg/dl from the first inpatient sCr measurement during the first 7 hospitalization days. We excluded individuals with a history of renal transplant or preexisting end-stage renal disease as well as individuals with <2 sCr measurements. We identified baseline characteristics (sociodemographics, health behaviors, chronic medical conditions, biomarkers, and nonsteroidal anti-inflammatory, statin, or antihypertensive medication use) independently associated with AKI events using multivariable generalized estimating equations. Results Over a median follow-up of 4.5 years (interquartile range 2.4-6.3), we included 2,074 serious infection hospitalizations among 1,543 individuals. AKI occurred in 296 of 2,074 hospitalizations (16.5%). On multivariable analysis, prehospitalization characteristics independently associated with AKI among individuals hospitalized for a serious infection included a history of diabetes [odds ratio (OR) 1.38; 95% CI 1.02-1.89], increased cystatin C (OR 1.73 per SD; 95% CI 1.20-2.50), and increased albumin-to-creatinine ratio (OR 1.19 per SD; 95% CI 1.007-1.40). Sex, race, hypertension, myocardial infarction, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and the use of nonsteroidal anti-inflammatory, statin, or antihypertensive medications were not associated with AKI. Conclusions

  4. Risk factors and clinical characteristics of in-hospital death in acute myocardial infarction with IABP support

    PubMed Central

    Cao, Jianing; Liu, Wenxian; Zhu, Jiajia; Zhao, Han

    2015-01-01

    Background: Despite the widespread use of the intra-aortic balloon pump (IABP) in acute myocardial infarction (AMI), there were few clinical trials regarding the deceased’s feature. Therefore, we conducted a study to investigate the clinical characteristics and risk factor led to in-hospital deaths among AMI patients with IABP support. Objective: To investigate the clinical characteristics and risk factors of in-hospital death with IABP support in AMI patients. Methods: The clinical data of 572 consecutive IABP supported patients with AMI within 72 hours from symptom onset from July 2005 to July 2013 were retrospectively analyzed. The evolution of the risk factors of in-hospital death and clinical characteristics was compared in 81 non-survivors and the survivors. Results: Non-survivors had a more severe clinical profile at admission. Fewer patients were treated with emergency reperfusion therapy in the non-survivors group. Cardiogenic shock, Mechanical complications, ventricular tachycardia/fibrillation and MODS were much common in non-survivors (P<0.001). Multivariate logistic regression analysis showed advanced age (>65 years), prolonged time from symptom onset to first medical contact (FMC), Killip class III/IV, renal dysfunction(GFR <60 ml/min/1.73 m2), and left ventricular ejection fraction (LVEF) <30% were risk factors associated with higher in-hospital mortality. Conclusions: IABP support may be more effective combined with revascularization for AMI patients whose hemodynamics is compromised. Patients accompanied with cardiogenic shock and other life-threatening complications are often uselesswith IABP support. Meanwhile, patient whose hemodynamics parameters have significant response to IABP may get benefits with IABP to improve in-hospital survival. PMID:26221368

  5. Clinical Characteristics and Risk Factors of Left Ventricular Thrombus after Acute Myocardial Infarction: A Matched Case-control Study

    PubMed Central

    Jiang, Yue-Xin; Jing, Lin-De; Jia, You-Hong

    2015-01-01

    Background: Left ventricular thrombus (LVT) is reported to be a common complication in acute myocardial infarction (AMI) patients. And it has the potential to cause systemic embolism. This retrospective study was to present the current situation of LVT in clinical practice, as well as to evaluate the clinical characteristics and the risk factors of LVT after AMI. Methods: LVT cases (n = 96) were identified from 13,732 AMI (non-ST elevation myocardial infarction was excluded) patients in Fuwai Hospital's electronic medical records system from January 2003 to January 2013. The controls (n = 192) were gender- and age-matched AMI patients without LVT during this period. A conditional logistic regression (fitted by the Cox model) was performed to identify the independent risk factors. Results: The incidence of LVT after AMI was 0.7%. Univariate analysis indicated that the anterior myocardial infarction (especially extensive anterior myocardial infarction), lower left ventricular ejection fraction (LVEF), LVEF ≤40%, severe regional wall motion abnormalities (RWMA), pericardial effusion, and left ventricular aneurysm were all related to LVT after AMI. The independent risk factors obtained from the conditional logistic regression analysis were lower LVEF (odds ratio (OR) = 0.891, 95% confidence interval (CI): 0.828–0.960), extensive anterior myocardial infarction (OR = 6.403, 95% CI: 1.769–23.169), severe RWMA (OR = 7.348, 95% CI: 1.323–40.819), and left ventricular aneurysm (OR = 6.955, 95% CI: 1.673–28.921). Conclusions: This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice. PMID:26365955

  6. Risk Factors for Acute Stroke among South Asians Compared to Other Racial/Ethnic Groups

    PubMed Central

    Gezmu, Tefera; Schneider, Dona; Demissie, Kitaw; Lin, Yong; Gizzi, Martin S.

    2014-01-01

    Background Studies of racial/ethnic variations in stroke rarely consider the South Asian population, one of the fastest growing sub-groups in the United States. This study compared risk factors for stroke among South Asians with those for whites, African-Americans, and Hispanics. Methods Data on 3290 stroke patients were analyzed to examine risk differences among the four racial/ethnic groups. Data on 3290 patients admitted to a regional stroke center were analyzed to examine risk differences for ischemic stroke (including subtypes of small and large vessel disease) among South Asians, whites, African Americans and Hispanics. Results South Asians were younger and had higher rates of diabetes mellitus, blood pressure, and fasting blood glucose levels than other race/ethnicities. Prevalence of diabetic and antiplatelet medication use, as well as the incidence of small-artery occlusion ischemic stroke was also higher among South Asians. South Asians were almost a decade younger and had comparable socioeconomic levels as whites; however, their stroke risk factors were comparable to that of African Americans and Hispanics. Discussion Observed differences in stroke may be explained by dietary and life style choices of South Asian-Americans, risk factors that are potentially modifiable. Future population and epidemiologic studies should consider growing ethnic minority groups in the examination of the nature, outcome, and medical care profiles of stroke. PMID:25268987

  7. Risk factors for development of left ventricular thrombus after first acute anterior myocardial infarction-association with anticardiolipin antibodies

    PubMed Central

    2010-01-01

    Background Left ventricular thrombus(LVT] formation is a frequent complication in patients with acute anterior myocardial infarction(MI). LVT is associated with increased risk of embolism and higher mortality rates after acute MI. Anticardiolipin antibodies (ACA) are immunoglobulins that react with phospholipid-binding proteins interfering with the prothrombin activator complex. The effects of phospholipids on pathophysiology of cardiovascular thrombotic events are well known. In this study, we aimed to evaluate the importance of clinical and biochemical parameters including anticardiolipin antibodies on left ventricular thrombus formation after acute anterior MI. Methods and Results Seventy patients with a first anterior AMI were prospectively and consecutively enrolled. Patients with previous MI, autoimmune disease, collagen vascular disease and arterial or venous thrombosis history were excluded from this study. At the time of hospitalization, key demographic and clinical characteristics were collected including age, gender, ethanol intake and presence of traditional risk factors for atherosclerosis (hypertension, diabetes, smoking, hyperlipidemia, positive family history). Patients were evaluated for echocardiographic data, blood chemistry and ACA. Two-dimensional and Doppler echocardiographic examinations were performed in all patients within the first week and at 14 days after MI. LV thrombus was detected in 30 (42.8%) patients. ACA IgM levels were significantly higher in the patient group with LV thrombus than in the group without thrombus (12.44 ±4.12 vs. 7.69 ± 4.25 mpl, p = 0,01). ACA IgG levels were also found higher in the group with LV thrombus (24.2 ± 7.5 vs.17.98 ± 6.45 gpl, p = 0.02). Multivariate analyses revealed diabetes mellitus, higher WMSI, lower MDT and higher ACA IgM and higher ACA IgG levels as independent predictors of left ventricular thrombus formation. Conclusions Our data demonstrate that beside the low ejection fraction, lower MDT

  8. Heparin-binding epidermal growth factor–like growth factor attenuates acute lung injury and multiorgan dysfunction after scald burn

    PubMed Central

    Lutmer, Jeffrey; Watkins, Daniel; Chen, Chun-Liang; Velten, Markus; Besner, Gail

    2013-01-01

    Background Impaired gut barrier function and acute lung injury (ALI) are significant components of the multiorgan dysfunction syndrome that accompanies severe burns. Heparin-binding epidermal growth factor–like growth factor (HB-EGF) has been shown to reduce inflammation, preserve gut barrier function, and protect the lungs from acute injury in several models of intestinal injury; however, comparable effects of HB-EGF after burn injury have never been investigated. The present studies were based on the hypothesis that HB-EGF would reduce the severity of ALI and multiorgan dysfunction after scald burns in mice. Materials and methods Mice were randomized to sham, burn (25% of total body surface area with full thickness dorsal scald), and burn + HB-EGF groups. The HB-EGF group was pre-treated with two enteral doses of HB-EGF (1200 μg/kg/dose). Mice were resuscitated after injury and sacrificed at 8 h later. Their lungs were harvested for determination of pulmonary myeloperoxidase activity, wet:dry ratios, and terminal deoxynucleotidyl transferase dUTP nick end label and cleaved caspase 3 immunohistochemistry. Lung function was assessed using the SCIREQ Flexivent. Splenic apoptosis was quantified by Western blot for cleaved caspase 3, and intestinal permeability was measured using the everted gut sac method. Results Mice subjected to scald burn injury had increased lung myeloperoxidase levels, increased pulmonary and splenic apoptosis, elevated airway resistance and bronchial reactivity, and increased intestinal permeability compared with sham mice. These abnormalities were significantly attenuated in mice that were subjected to scald burn injury but treated with enteral HB-EGF. Conclusions These data suggest that HB-EGF protects mice from ALI after scald burn and attenuates the severity of postburn multiorgan dysfunction. PMID:23777985

  9. Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21.

    PubMed

    Muise, Eric S; Souza, Sandra; Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-Yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P; Hendrickson, Ronald C; Thompson, John R; Mu, James; Berger, Joel P; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation.

  10. Downstream Signaling Pathways in Mouse Adipose Tissues Following Acute In Vivo Administration of Fibroblast Growth Factor 21

    PubMed Central

    Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P.; Hendrickson, Ronald C.; Thompson, John R.; Mu, James; Berger, Joel P.; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation. PMID:24039848

  11. Acute Respiratory Tract Infection Visits of Veterans With Spinal Cord Injuries and Disorders: Rates, Trends, and Risk Factors

    PubMed Central

    Smith, Bridget M; Evans, Charlesnika T; Kurichi, Jibby E; Weaver, Frances M; Patel, Nayna; Burns, Stephen P

    2007-01-01

    Background/Objectives: Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. Methods: This was a longitudinal (fiscal years 1998–2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. Results: Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; CI = 0.51–0.67). Conclusions: Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds. PMID:17853657

  12. Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.

    PubMed

    Chavez-Tapia, Norberto C; Mendiola-Pastrana, Indira; Ornelas-Arroyo, Victoria J; Noreña-Herrera, Camilo; Vidaña-Perez, Desiree; Delgado-Sanchez, Guadalupe; Uribe, Misael; Barrientos-Gutierrez, Tonatiuh

    2015-01-01

    Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.

  13. Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia.

    PubMed

    Wakita, S; Yamaguchi, H; Ueki, T; Usuki, K; Kurosawa, S; Kobayashi, Y; Kawata, E; Tajika, K; Gomi, S; Koizumi, M; Fujiwara, Y; Yui, S; Fukunaga, K; Ryotokuji, T; Hirakawa, T; Arai, K; Kitano, T; Kosaka, F; Tamai, H; Nakayama, K; Fukuda, T; Inokuchi, K

    2016-03-01

    We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.

  14. Intraoperative hypotension - a neglected causative factor in hospital-acquired acute kidney injury; a Mayo Clinic Health System experience revisited.

    PubMed

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma

    2015-01-01

    Acute kidney injury (AKI) is a relatively common complication of cardiothoracic surgery and has both short- and long-term survival implications, even when AKI does not progress to severe renal failure. Given that currently, there are no active effective treatments for AKI, other than renal replacement therapy when indicated, the focus of clinicians ought to be on prevention and risk factor management. In the AKI-surgery literature, there exists this general consensus that intraoperative hypotension (IH) following hypotensive anesthesia (HA) or controlled hypotension (CH) in the operating room has no significant short-term and long-term impacts on renal function. In this review, we examine the basis for this consensus, exposing some of the flaws of the clinical study data upon which this prevailing consensus is based. We then describe our experiences in the last decade at the Mayo Clinic Health System, Eau Claire, in Northwestern Wisconsin, USA, with two selected case presentations to highlight the contribution of IH as a potent yet preventable cause of post-operative AKI. We further highlight the causative although neglected role of IH in precipitating postoperative AKI in chronic kidney disease (CKD) patients. We show additional risk factors associated with this syndrome and further make a strong case for the elimination of IH as an achievable mechanism to reduce overall, the incidence of hospital acquired AKI. We finally posit that as the old saying goes, prevention is indeed better than cure. PMID:26468476

  15. Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

    PubMed Central

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-01-01

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  16. Aberrant nuclear factor-kappa B activity in acute myeloid leukemia: from molecular pathogenesis to therapeutic target.

    PubMed

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-03-20

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  17. Intraoperative hypotension - a neglected causative factor in hospital-acquired acute kidney injury; a Mayo Clinic Health System experience revisited

    PubMed Central

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma

    2015-01-01

    Acute kidney injury (AKI) is a relatively common complication of cardiothoracic surgery and has both short- and long-term survival implications, even when AKI does not progress to severe renal failure. Given that currently, there are no active effective treatments for AKI, other than renal replacement therapy when indicated, the focus of clinicians ought to be on prevention and risk factor management. In the AKI-surgery literature, there exists this general consensus that intraoperative hypotension (IH) following hypotensive anesthesia (HA) or controlled hypotension (CH) in the operating room has no significant short-term and long-term impacts on renal function. In this review, we examine the basis for this consensus, exposing some of the flaws of the clinical study data upon which this prevailing consensus is based. We then describe our experiences in the last decade at the Mayo Clinic Health System, Eau Claire, in Northwestern Wisconsin, USA, with two selected case presentations to highlight the contribution of IH as a potent yet preventable cause of post-operative AKI. We further highlight the causative although neglected role of IH in precipitating postoperative AKI in chronic kidney disease (CKD) patients. We show additional risk factors associated with this syndrome and further make a strong case for the elimination of IH as an achievable mechanism to reduce overall, the incidence of hospital acquired AKI. We finally posit that as the old saying goes, prevention is indeed better than cure. PMID:26468476

  18. Risk factors of acute diarrhoea in summer--a nation-wide French case-control study.

    PubMed Central

    Yazdanpanah, Y.; Beaugerie, L.; Boëlle, P. Y.; Letrilliart, L.; Desenclos, J. C.; Flahault, A.

    2000-01-01

    The aim of this study was to identify risk factors for acute diarrhoea (AD) during the summer in France. A matched case-control study was conducted at a national level among patients of 500 general practitioners (GPs). From July to September 1996, 468 case-control pairs were included. Cases were more likely than controls (i) to live away from their main residence (OR 3.0; 95% CI 1.6-5.7), (ii) to have returned from a country at high risk of AD (OR 4.6; CI 0.9-23.1), and (iii) to have been in contact with a case of AD (OR 2.0; CI 1.3-3.1). A significantly decreased risk of AD was found for consumption of well-cooked chicken (OR 0.5; CI 0.3-0.8) and raw or undercooked home-made egg-containing products (OR 0.6; CI 0.4-0.8). These findings suggest that travel to high-risk areas, or travel within France, and being in contact with a case of AD, are risk factors for the occurrence of AD in summer in France. PMID:10982064

  19. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury.

    PubMed

    Marzec, Jacqui M; Christie, Jason D; Reddy, Sekhar P; Jedlicka, Anne E; Vuong, Hue; Lanken, Paul N; Aplenc, Richard; Yamamoto, Tae; Yamamoto, Masayuki; Cho, Hye-Youn; Kleeberger, Steven R

    2007-07-01

    We recently used positional cloning to identify the transcription factor Nrf2 (NF-E2 related factor 2) as a susceptibility gene in a murine model of oxidant-induced acute lung injury (ALI). NRF2 binds to antioxidant response elements (ARE) and up-regulates protective detoxifying enzymes in response to oxidative stress. This led us to investigate NRF2 as a candidate susceptibility gene for risk of development of ALI in humans. We identified multiple single nucleotide polymorphisms (SNPs) by resequencing NRF2 in ethnically diverse subjects, and one (-617 C/A) significantly (P<0.001) diminished luciferase activity of promoter constructs containing the SNP and significantly decreased the binding affinity (P<0.001) relative to the wild type at this locus (-617 CC). In a nested case-control study, patients with the -617 A SNP had a significantly higher risk for developing ALI after major trauma (OR 6.44; 95% CI 1.34, 30.8; P=0.021) relative to patients with the wild type (-617 CC). This translational investigation provides novel insight into the molecular mechanisms of susceptibility to ALI and may help to identify patients who are predisposed to develop ALI under at risk conditions, such as trauma and sepsis. Furthermore, these findings may have important implications in other oxidative stress related illnesses.

  20. Altered nuclear co-factor switching in retinoic resistant variants of the PML-RARα oncoprotein of acute promyelocytic leukemia†

    PubMed Central

    Farris, Mindy; Lague, Astrid; Manuelyan, Zara; Statnekov, Jacob; Francklyn, Christopher

    2011-01-01

    Acute Promyelocytic Leukemia (APL) results from a reciprocal translocation that fuses the gene for the PML tumor suppressor to that encoding the retinoic acid receptor alpha (RARα). The resulting PML-RARα oncogene product interferes with multiple regulatory pathways associated with myeloid differentiation, including normal PML and RARα functions. The standard treatment for APL includes anthracycline-based chemotherapeutic agents plus the RARα agonist all-trans retinoic acid (ATRA). Relapse, which is often accompanied by ATRA resistance, occurs in an appreciable frequency of treated patients. One potential mechanism suggested by model experiments featuring the selection of ATRA resistant APL cell lines involves ATRA resistant versions of the PML-RARα oncogene, where the relevant mutations localize to the RARα ligand-binding domain (LBD). Such mutations may act by compromising agonist binding, but other mechanisms are possible. Here, we studied the molecular consequence of ATRA resistance by use of circular dichroism, protease resistance, and fluorescence anisotropy assays employing peptides derived from the NCOR nuclear co-repressor and the ACTR nuclear co-activator. The consequences of the mutations on global structure and co-factor interaction functions were assessed quantitatively, providing insights into the basis of agonist resistance. Attenuated co-factor switching and increased protease resistance represent features of the LBDs of ATRA-resistant PML-RARα, and these properties may be recapitulated in the full-length oncoproteins. PMID:22228505

  1. Clinical factors associated with early readmission among acutely decompensated heart failure patients

    PubMed Central

    Pierre-Louis, Bredy; Rodriques, Shareen; Gorospe, Vanessa; Guddati, Achuta K.; Ahn, Chul; Wright, Maurice

    2016-01-01

    Introduction Congestive heart failure (CHF) is a common cause of hospital readmission. Material and methods A retrospective study was conducted at Harlem Hospital in New York City. Data were collected for 685 consecutive adult patients admitted for decompensated CHF from March, 2009 to December, 2012. Variables including patient demographics, comorbidities, laboratory studies, and medical therapy were compared between CHF patient admissions resulting in early CHF readmission and not resulting in early CHF readmission. Results Clinical factors found to be independently significant for early CHF readmission included chronic obstructive pulmonary disease (odds ratio (OR) = 6.4), HIV infection (OR = 3.4), African-American ethnicity (OR = 2.2), systolic heart failure (OR = 1.9), atrial fibrillation (OR = 2.3), renal disease with glomerular filtration rate < 30 ml/min (OR = 2.7), evidence of substance abuse (OR = 1.7), and absence of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy after discharge (OR = 1.8). The ORs were used to develop a scoring system regarding the risk for early readmission. Conclusions Identifying patients with clinical factors associated with early CHF readmission after an index hospitalization for CHF using the proposed scoring system would allow for an early CHF readmission risk stratification protocol to target particularly high-risk patients. PMID:27279845

  2. Factors Associated With Severe Acute Esophagitis From Hyperfractionated Radiotherapy With Concurrent Chemotherapy for Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Watkins, John M.; Wahlquist, Amy E. M.S.; Shirai, Keisuke; Garrett-Mayer, Elizabeth; Aguero, Eric G.; Fortney, John A.; Sherman, Carol A.; Sharma, Anand K.

    2009-07-15

    Purpose: To describe incidence and identify factors associated with development of severe acute esophagitis during hyperfractionated radiotherapy with concurrent chemotherapy (BID-CRT) in patients with limited-stage small-cell lung cancer (SCLC). Methods and Materials: Retrospective cohort analysis of patient-, tumor-, and treatment-related variables was performed to identify factors associated with Radiation Therapy Oncology Group (RTOG) Grade 3 acute esophagitis. Twice-daily chemoradiotherapy (BID-CRT) involved 45 Gy at 1.5 Gy per fraction, treated twice daily with concurrent platinum-based chemotherapy. Logistic regression analyses were used to identify factors associated with esophagitis. Results: Between June 1999 and June 2007, 48 patients underwent curative intent BID-CRT for SCLC and were included in the analysis. Median radiotherapy dose was 45 Gy (range, 42-51 Gy) delivered with a median 4 cycles of chemotherapy (range, 2-6). RTOG Grade 3 acute esophagitis developed in 11 patients. No patient developed Grade 4 or 5 esophagitis. Simple logistic regression analyses demonstrated a highly significant association between Grade 3 acute esophagitis and mean esophageal dose (p = 0.002) as well as relative volume dosimetric area under curve (RV-AUC; p = 0.004). Using multiple regression analysis, RV-AUC was identified as the only factor associated with Grade 3 esophagitis (p = 0.004). The most strongly associated dosimetric volume was the V15 (Grade 3 esophagitis rates of 15% vs. 64% for V15 <60% versus {>=}60%, respectively). Conclusions: RV-AUC is the factor most associated with development of Grade 3 acute esophagitis in limited stage SCLC patients receiving BID-CRT.

  3. Correlation between vascular endothelial growth factor and long-term prognosis in patients with acute myocardial infarction

    PubMed Central

    NIU, JIAMIN; HAN, XIA; QI, HUAXIN; YIN, JIE; ZHANG, ZHIQIANG; ZHANG, ZENGTANG

    2016-01-01

    The aim of the present study was to investigate the correlation between plasma the levels of vascular endothelial growth factor (VEGF) and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). A total of 124 patients with AMI undergoing emergency percutaneous coronary intervention (PCI) were selected, and plasma VEGF levels were measured 7 days after the onset of AMI using an enzyme-linked immunosorbent assay. The patients were divided into the L (≤190 pg/ml VEGF) and H (>190 pg/ml VEGF) groups, and were followed up every 2 months for an average of 12 months. MACE were recorded during follow-up. On the basis of these results, the patients were further divided into the MACE and non-MACE (N-MACE) groups, and the serum VEGF concentration was compared between the two groups. At the 6-month follow-up, the incidence of MACE in the H group was found to be significantly reduced compared with the L group. The serum VEGF concentration in the N-MACE group was significantly higher compared with the MACE group. Multinomial logistic regression revealed that reduced VEGF levels (β=1.243; 95% CI, 1.018–1.326; P=0.026) were independent risk factors for MACE. In conclusion, high plasma VEGF levels at 7 days after AMI onset facilitate the long-term prognosis in the same infarct zone in patients with AMI, while low plasma VEGF levels are independent risk factors for MACE. PMID:27347081

  4. CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY

    PubMed Central

    LUNA, Leonardo Duarte Sobreira; SOARES, Douglas de Sousa; JUNIOR, Geraldo Bezerra da SILVA; CAVALCANTE, Malena Gadelha; MALVEIRA, Lara Raissa Cavalcante; MENESES, Gdayllon Cavalcante; PEREIRA, Eanes Delgado Barros; DAHER, Elizabeth De Francesco

    2016-01-01

    SUMMARY Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001). Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death. PMID:27410912

  5. Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty

    PubMed Central

    Lindberg, Maren Falch; Miaskowski, Christine; Rustøen, Tone; Rosseland, Leiv Arne; Paul, Steven M.

    2016-01-01

    Objectives Unrelieved postoperative pain after total knee arthroplasty (TKA) is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA. Methods Prior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD) 0 to 4. Clinical data were extracted from medical records. Results Several factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA) were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery. Discussion Patients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients’ perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes. PMID:27583551

  6. Apolipoprotein B versus Non- High Density Lipoprotein Cholesterol as a Discriminating Factor for Acute Coronary Syndrome in Young People.

    PubMed

    Aditya, G P; Bari, M A

    2016-07-01

    This study aimed to compare Apolipoprotein B(Apo B) with non-HDL-C as a predictor and discriminating factor of acute coronary syndrome (ACS). This is a case control study among 50 cases of first attack of ACS among 18-45 years of age of both sex, admitted in coronary care unit of Mymensingh Medical College Hospital, Bangladesh from June 2009 to May 2010. Data was recently reanalyzed. Apo B is more sensitive than non-HDL C (84% vs. 62%) as well with more negative predictive value (NPV) (76.5% vs. 62.7%) but with similar positive predictive value (PPV) (63%). Specificity was more for non HDL C than Apo B (64% vs. 52%). Highest specificity and PPV observed for HDL- C, 88% and 71.4% respectively but with low sensitivity (30%). In this study diagnostic value of LDL-C, TC and TG was low. Apo B was a more discriminating factor as well predictor for ACS cases than non-HDL-C (OR: 5.678, 95% CI 2.227 - 14.528, P=0.001) vs. (OR: 2.901, 95% CI 1.288 - 6.534, P=0.01). Area under the Receiver Operating Characteristic (ROC) curve was greater for Apo B than non-HDL-C (0.680 vs. 0.630). Though ApoB and non-HDL-C theoretically often equally reflects the atherogenic burden, Apo B was a more discriminating factor for ACS cases than non-HDL-C. PMID:27612891

  7. Prognostic value of early response to treatment combined with conventional risk factors in pediatric acute lymphoblastic leukemia.

    PubMed

    Morimoto, Akira; Kuriyama, Kikuko; Hibi, Shigeyoshi; Todo, Shinjiro; Yoshihara, Takao; Kuroda, Hiroshi; Imashuku, Shibsaku

    2005-04-01

    To determine useful prognostic factors in treating childhood acute lymphoblastic leukemia (ALL), we correlated conventional risk factors and bone marrow response 14 days after induction chemotherapy. Our study included 116 precursor B-cell (n = 104) and T-cell (n = 12) ALL patients treated with our protocol between 1988 and 1999. The patients were classified into 3 initial risk groups on the basis of conventional risk factors (56 in the low-risk, 33 in the high-risk, and 27 in the very high-risk groups). All patients received similar systemic chemotherapy regimens before the evaluation of their bone marrow on day 14. We evaluated the marrow of 69 patients as M1 (less than 5% blasts), 25 as M2 (5%-25% blasts), and 22 as M3 (more than 25% blasts). Although all patients attained an initial complete remission (CR), relapse was noted in 33 of the 116 patients, and 15 patients died. All of the M1 marrow patients, irrespective of the initial risk group, showed the best event-free survival rate (85.1% +/- 3 4.4%), the lowest relapse rate (14.5%), and the highest attainment of a second CR (100%); they were defined as the new R1 prognostic group. The low-risk patients with M2 or M3 marrow (R2 group) had a relatively high relapse rate, but all of these relapsed patients were treated successfully with subsequent therapy. High- or very high-risk patients with M2 or M3 marrow (R3 group) had the worst prognosis. Our new prognostic definition (R1, R2, R3) incorporating day 14 marrow findings is useful to tailor early-phase treatments for better therapeutic results in childhood ALL.

  8. Recombinant human tumor necrosis factor induces acute reductions in food intake and body weight in mice

    PubMed Central

    1988-01-01

    We examined the effects of treatment with rHuTNF on food consumption and body weight in C3H/HeJ mice. rHuTNF was administered intraperitoneally either by injections of 3, 12, or 24 micrograms twice a day or by implantation of osmotic pumps that released 0.75, 3, or 12 micrograms per day. Dose-dependent reductions in both food intake and weight were induced by rHuTNF. However, in spite of continued exposure to rHuTNF, the mice developed a resistance to rHuTNF and resumed their pretreatment food intake and weight. Non-immunological factors may play a role in the development of this tolerance, since it developed rapidly and faded within 2 wk of cessation of exposure to rHuTNF. PMID:3385359

  9. Etiology and Risk Factors of Acute Gastroenteritis in a Taipei Emergency Department: Clinical Features for Bacterial Gastroenteritis

    PubMed Central

    Lai, Chao-Chih; Ji, Dar-Der; Wu, Fang-Tzy; Mu, Jung-Jung; Yang, Ji-Rong; Jiang, Donald Dah-Shyong; Lin, Wen-Yun; Chen, Wei-Ting; Yen, Muh-Yong; Wu, Ho-Sheng; Chen, Tony Hsiu-Hsi

    2016-01-01

    Background The causative pathogen is rarely identified in the emergency department (ED), since the results of cultures are usually unavailable. As a result, antimicrobial treatment may be overused. The aim of our study was to investigate the pathogens, risk factors of acute gastroenteritis, and predictors of acute bacterial gastroenteritis in the ED. Methods We conducted a matched case-control study of 627 stool samples and 612 matched pairs. Results Viruses (41.3%) were the leading cause of gastroenteritis, with noroviruses (32.2%) being the most prevalent, followed by bacteria (26.8%) and Giardia lamblia (12.4%). Taking antacids (adjusted odds ratio [aOR] 4.10; 95% confidence interval [CI], 2.57–6.53), household members/classmates with gastroenteritis (aOR 4.69; 95% CI, 2.76–7.96), attending a banquet (aOR 2.29; 95% CI, 1.64–3.20), dining out (aOR 1.70; 95% CI, 1.13–2.54), and eating raw oysters (aOR 3.10; 95% CI, 1.61–5.94) were highly associated with gastroenteritis. Elders (aOR 1.04; 05% CI, 1.02–1.05), those with CRP >10 mg/L (aOR 2.04; 95% CI, 1.15–3.62), or those who were positive for fecal leukocytes (aOR 2.04; 95% CI, 1.15–3.62) or fecal occult blood (aOR 1.97; 95% CI, 1.03–3.77) were more likely to be hospitalized in ED. In addition, presence of fecal leukocytes (time ratio [TR] 1.22; 95% CI, 1.06–1.41), abdominal pain (TR 1.20; 95% CI, 1.07–1.41), and frequency of vomiting (TR 0.79; 95% CI, 0.64–0.98) were significantly associated with the duration of acute gastroenteritis. Presence of fecal leukocytes (aOR 2.08; 95% CI, 1.42–3.05), winter season (aOR 0.45; 95% CI, 0.28–0.74), frequency of diarrhea (aOR 1.69; 95% CI, 1.01–2.83), and eating shrimp or crab (aOR 1.53; 95% CI, 1.05–2.23) were highly associated with bacterial gastroenteritis. The area under the receiver operating characteristic curve of the final model was 0.68 (95% CI, 0.55–0.63). Conclusions Acute bacterial gastroenteritis was highly associated with season

  10. The risk factors and prognostic implication of acute pulmonary edema in resuscitated cardiac arrest patients

    PubMed Central

    Kang, Dae-hyun; Kim, Joonghee; Rhee, Joong Eui; Kim, Taeyun; Kim, Kyuseok; Jo, You Hwan; Lee, Jin Hee; Lee, Jae Hyuk; Kim, Yu Jin; Hwang, Seung Sik

    2015-01-01

    Objective Pulmonary edema is frequently observed after a successful resuscitation in out-of-hospital cardiac arrest (OHCA) patients. Currently, its risk factors and prognostic implications are mostly unknown. Methods Adult OHCA patients with a presumed cardiac etiology who achieved sustained return of spontaneous circulation (ROSC) in emergency department were retrospectively analyzed. The patients were grouped according to the severity of consolidation on their initial chest X-ray (group I, no consolidation; group II, patchy consolidations; group III, consolidation involving an entire lobe; group IV, total white-out of any lung). The primary objective was to identify the risk factors of developing severe pulmonary edema (group III or IV). The secondary objective was to evaluate the association between long-term prognosis and the severity of pulmonary edema. Results One hundred and seven patients were included. Total duration of cardiopulmonary resuscitation (CPR) and initial pCO2 level were both independent predictors of developing severe pulmonary edema with their odds ratio (OR) being 1.02 (95% confidence interval [CI], 1.00 to 1.04; per 1 minute) and 1.04 (95% CI, 1.01 to 1.07; per 1 mmHg), respectively. The long term prognosis was significantly poor in patients with severe pulmonary edema with a OR for good outcome (6-month cerebral performance category 1 or 2) being 0.22 (95% CI, 0.06 to 0.79) in group III and 0.16 (95% CI, 0.04 to 0.63) in group IV compared to group I. Conclusion The duration of CPR and initial pCO2 level were both independent predictors for the development of severe pulmonary edema after resuscitation in emergency department. The severity of the pulmonary edema was significantly associated with long-term outcome.

  11. Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

    PubMed Central

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F.; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A.; Mensa, Josep

    2013-01-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a Cmin determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low Cmin. A total of 29.5% of patients had a Cmin < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy. PMID:23403416

  12. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  13. The ‘Perfect Storm’ and Acute Coronary Syndrome Onset: Do Psychosocial Factors Play a Role?

    PubMed Central

    Burg, Matthew M.; Edmondson, Donald; Shimbo, Daichi; Shaffer, Jonathan; Kronish, Ian M.; Whang, William; Alcántara, Carmela; Schwartz, Joseph E.; Muntner, Paul; Davidson, Karina W.

    2013-01-01

    The revolution in cardiac care over the past two decades, characterized by emergent revascularization, drug eluting stents, anti-platelet medications, and advanced imaging has had little impact on overall ACS recurrence, or ACS prevention. The “Perfect Storm” refers to a confluence of events and processes, including atherosclerotic plaque, coronary flow dynamics, hemostatic and fibrinolytic function, metabolic and inflammatory conditions, neurohormonal dysregulation, and environmental events that give rise to, and result in an ACS event. In this article we illustrate the limits of the traditional main effect research model, giving a brief description of the current state of knowledge regarding the development of atherosclerotic plaque and the rupturing of these plaques that defines an ACS event. We then apply the Perfect Storm conceptualization to describe a program of research concerning a psychosocial vulnerability factor that contributes to increased risk of recurrent ACS and early mortality, and that has defied our efforts to identify underlying pathophysiology and successfully mount efforts to fully mitigate this risk. PMID:23621970

  14. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    PubMed

    Poo, Yee Suan; Rudd, Penny A; Gardner, Joy; Wilson, Jane A C; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T; Nakaya, Helder I; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A; Khromykh, Alexander A; Lopez, José A; Suhrbier, Andreas

    2014-12-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  15. Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute Pancreatitis and Blunts Atrial Natriuretic Factor's Beneficial Effect in Rats: Role of MRP4 (ABCC4).

    PubMed

    Ventimiglia, María Silvia; Najenson, Ana Clara; Perazzo, Juan Carlos; Carozzo, Alejandro; Vatta, Marcelo S; Davio, Carlos A; Bianciotti, Liliana G

    2015-01-06

    We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflux through multidrug resistance-associated protein 4 (MRP4) in the exocrine pancreas. Here we sought to establish in vivo whether this mechanism was involved in acute pancreatitis onset in the rat. Rats pretreated with or without probenecid (MRPs general inhibitor) were infused with secretin alone or with ANF. A set of these animals were given repetitive cerulein injections to induce acute pancreatitis. Plasma amylase and intrapancreatic trypsin activities were measured and histological examination of the pancreas performed. Secretin alone activated trypsinogen but induced no pancreatic histological changes. Blockade by probenecid in secretin-treated rats increased trypsin and also induced vacuolization, a hallmark of acute pancreatitis. ANF prevented the secretin response but in the absence of probenecid. In rats with acute pancreatitis, pretreatment with secretin aggravated the disease, but ANF prevented secretin-induced changes. Blockade of MRPs in rats with acute pancreatitis induced trypsinogen activation and larger cytoplasmic vacuoles as well as larger areas of necrosis and edema that were aggravated by secretin but not prevented by ANF. The temporal resolution of intracellular cAMP levels seems critical in the onset of acute pancreatitis, since secretin-evoked cAMP in a context of MRP inhibition makes the pancreas prone to injury in normal rats and aggravates the onset of acute pancreatitis. Present findings support a protective role for ANF mediated by cAMP extrusion through MRP4 and further suggest that the regulation of MRP4 by ANF would be relevant to maintain pancreatic acinar cell homeostasis.

  16. Randomized Trial of Two Dosages of Prophylactic Granulocyte Colony-Stimulating Factor after Induction Chemotherapy in Pediatric Acute Myeloid Leukemia

    PubMed Central

    Inaba, Hiroto; Cao, Xueyuan; Pounds, Stanley; Pui, Ching-Hon; Rubnit, Jeffrey E.; Ribeiro, Raul C.; Razzouk, Bassem I.

    2010-01-01

    Background Granulocyte colony-stimulating factor (G-CSF) is effective in accelerating neutrophil recovery after intensive chemotherapy for acute myeloid leukemia (AML). However, the optimal G-CSF dosage for patients with AML has not been determined. To our knowledge, G-CSF dosages have not been compared in a randomized AML study. Methods Patients enrolled on the St. Jude AML97 protocol who remained on study after window therapy were eligible to participate. The effect of the dosage of G-CSF given after induction chemotherapy courses 1 and 2 was analyzed in 46 patients randomly assigned in a double-blinded manner to receive 5 or 10 μg/kg/day of G-CSF. The number of days of G-CSF treatment, neutropenia (absolute neutrophil count < 0.5 × 109/L), and hospitalization; the number of episodes of febrile neutropenia, grade 2-4 infection, and antimicrobial therapy; transfusion requirements; the cost of supportive care; and survival were compared between the two study arms. Results We found no statistically significant difference between the two arms in any of the endpoints measured. Conclusions The higher G-CSF dosage (10 μg/kg/day) offers no greater benefit than the lower dosage (5 μg/kg/day) in patients undergoing intensive chemotherapy for AML. PMID:21381017

  17. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

    PubMed Central

    Xie, Jieshi; Yang, Le; Tian, Lei; Li, Weiyang; Yang, Lin; Li, Liying

    2016-01-01

    Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID:27273604

  18. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  19. Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

    PubMed

    Seo, Joo Youn; Choi, Bo Youl; Ki, Moran; Jang, Hye Lim; Park, Hee Suk; Son, Hyun Jin; Bae, Si Hyun; Kang, Jin Han; Jun, Dae Won; Lee, Jin-Woo; Hong, Young Jin; Kim, Young Seok; Kim, Chang-Hwi; Chang, U Im; Kim, Jong-Hyun; Yang, Hyeon Woong; Kim, Hong Soo; Park, Kyeong Bae; Hwang, Jae Seok; Heo, Jeong; Kim, In Hee; Kim, Jung Soo; Cheon, Gab Jin

    2013-06-01

    This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.

  20. Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice

    PubMed Central

    Wu, Dongdong; Pan, Pinhua; Su, Xiaoli; Zhang, Lemeng; Qin, Qingwu; Tan, Hongyi; Huang, Li; Li, Yuanyuan

    2016-01-01

    ABSTRACT Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation. PMID:26939040

  1. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure.

    PubMed

    Lee, Ing-Kit; Liu, Jien-Wei; Yang, Kuender D

    2009-04-01

    In a retrospective study, acute renal failure (ARF) was found in 10 (3.3%) among 304 hospitalized adults with dengue hemorrhagic fever (DHF), and 6 (60%) of the 10 patients with ARF died, whereas all 294 patients without ARF (controls) survived (P < 0.001). Compared with the controls, DHF patients with ARF were found to be significantly older (P = 0.002) and male predominant (P < 0.001) and to have higher frequency of previous stroke (P = 0.005), chronic renal insufficiency (P = 0.046), dengue shock syndrome (DSS; P < 0.001), gastrointestinal bleeding (P < 0.001), and concurrent bacteremia (P = 0.009), lower hemoglobin (P = 0.003) and serum albumin levels (P = 0.003), and higher incidences of prolonged prothrombin time (P < 0.001), elevated aspartate aminotransferase (P < 0.001), and alanine aminotransferase levels (P < 0.001). Multivariate analysis showed DSS (odd ratio = 220.0; P < 0.001) was an independent risk factor for development of ARF in DHF patients. The high fatality rate in DHF patients complicated with ARF in our series underscore the importance of clinicians' alertness to this potentially fatal complication so that initiation of timely appropriate treatment is possible.

  2. An Epstein-Barr Virus Encoded Inhibitor of Colony Stimulating Factor-1 Signaling Is an Important Determinant for Acute and Persistent EBV Infection

    PubMed Central

    Ohashi, Makoto; Fogg, Mark H.; Orlova, Nina; Quink, Carol; Wang, Fred

    2012-01-01

    Acute Epstein-Barr virus (EBV) infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1) signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV), naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1). Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection. PMID:23300447

  3. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program

    PubMed Central

    Mengesha, Melkamu Merid; Deyessa, Negussie; Tegegne, Balewgizie Sileshi; Dessie, Yadeta

    2016-01-01

    Background The outpatient therapeutic care program (OTP) of children with severe acute malnutrition (SAM) has been decentralized to health post level in Ethiopia since 2008–2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. Objective This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. Design Health facility–based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. Result 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97)]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56)]. However, children who gained Mid-Upper Arm Circumference (MUAC) ≥ 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06)]. Conclusions Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome. PMID:27396484

  4. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

    PubMed

    Karol, Seth E; Mattano, Leonard A; Yang, Wenjian; Maloney, Kelly W; Smith, Colton; Liu, ChengCheng; Ramsey, Laura B; Fernandez, Christian A; Chang, Tamara Y; Neale, Geoffrey; Cheng, Cheng; Mardis, Elaine; Fulton, Robert; Scheet, Paul; San Lucas, F Anthony; Larsen, Eric C; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Devidas, Meenakshi; Relling, Mary V

    2016-02-01

    Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children <10 years incompletely understood. Here, we perform the first evaluation of genetic risk factors for osteonecrosis in children <10 years. The discovery cohort comprised 82 cases of osteonecrosis and 287 controls treated on Children's Oncology Group (COG) standard-risk ALL protocol AALL0331 (NCT00103285, https://clinicaltrials.gov/ct2/show/NCT00103285), with results tested for replication in 817 children <10 years treated on COG protocol AALL0232 (NCT00075725, https://clinicaltrials.gov/ct2/show/NCT00075725). The top replicated single nucleotide polymorphisms (SNPs) were near bone morphogenic protein 7 [BMP7: rs75161997, P = 5.34 × 10(-8) (odds ratio [OR] 15.0) and P = .0498 (OR 8.44) in the discovery and replication cohorts, respectively] and PROX1-antisense RNA1 (PROX1-AS1: rs1891059, P = 2.28 × 10(-7) [OR 6.48] and P = .0077 [OR 3.78] for the discovery and replication cohorts, respectively). The top replicated nonsynonymous SNP, rs34144324, was in a glutamate receptor gene (GRID2, P = 8.65 × 10(-6) [OR 3.46] and P = .0136 [OR 10.8] in the discovery and replication cohorts, respectively). In a meta-analysis, the BMP7 and PROX1-AS1 variants (rs75161997 and rs1891059, respectively) met the significance threshold of <5 × 10(-8). Top replicated SNPs were enriched in enhancers active in mesenchymal stem cells, and analysis of annotated genes demonstrated enrichment in glutamate receptor and adipogenesis pathways. These data may provide new insights into the pathophysiology of osteonecrosis. PMID:26590194

  5. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces antiapoptotic and proapoptotic signals in acute myeloid leukemia.

    PubMed

    Faderl, Stefan; Harris, David; Van, Quin; Kantarjian, Hagop M; Talpaz, Moshe; Estrov, Zeev

    2003-07-15

    High levels of cytokines are associated with a poor prognosis in acute myeloid leukemia (AML). However, cytokines may induce, on one hand, survival factor expression and cell proliferation and, on the other hand, expression of inhibitory signals such as up-regulation of suppressors of cytokine signaling (SOCS) and induce apoptotic cell death. Because blasts from patients with AML express high procaspase protein levels, we asked whether granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances procaspase protein production in AML cells. In the GM-CSF-responsive OCIM2 AML cell line, GM-CSF induced signal transducer and activator of transcription 5 (Stat 5) phosphorylation, up-regulated cyclin D2, and stimulated cell cycle progression. Concurrently, GM-CSF stimulated expression of SOCS-2 and -3 and of procaspases 2 and 3 and induced caspase 3 activation, poly(ADP[adenosine 5'-diphosphate]-ribose) polymerase (PARP) cleavage, and apoptotic cell death. The Janus kinase (Jak)-Stat inhibitor AG490 abrogated GM-CSF-induced expression of procaspase 3 and activation of caspase 3. Under the same conditions GM-CSF up-regulated production of BAX as well as Bcl-2, Bcl-XL, survivin, and XIAP. GM-CSF also increased procaspase 3 protein levels in OCI/AML3 and Mo7e cells, suggesting that this phenomenon is not restricted to a single leukemia cell line. Our data suggest that GM-CSF exerts a dual effect: it stimulates cell division but contemporaneously up-regulates Jak-Stat-dependent proapoptotic proteins. Up-regulation of procaspase levels in AML is thus a beacon for an ongoing growth-stimulatory signal.

  6. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

    PubMed

    Karol, Seth E; Mattano, Leonard A; Yang, Wenjian; Maloney, Kelly W; Smith, Colton; Liu, ChengCheng; Ramsey, Laura B; Fernandez, Christian A; Chang, Tamara Y; Neale, Geoffrey; Cheng, Cheng; Mardis, Elaine; Fulton, Robert; Scheet, Paul; San Lucas, F Anthony; Larsen, Eric C; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Devidas, Meenakshi; Relling, Mary V

    2016-02-01

    Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children <10 years incompletely understood. Here, we perform the first evaluation of genetic risk factors for osteonecrosis in children <10 years. The discovery cohort comprised 82 cases of osteonecrosis and 287 controls treated on Children's Oncology Group (COG) standard-risk ALL protocol AALL0331 (NCT00103285, https://clinicaltrials.gov/ct2/show/NCT00103285), with results tested for replication in 817 children <10 years treated on COG protocol AALL0232 (NCT00075725, https://clinicaltrials.gov/ct2/show/NCT00075725). The top replicated single nucleotide polymorphisms (SNPs) were near bone morphogenic protein 7 [BMP7: rs75161997, P = 5.34 × 10(-8) (odds ratio [OR] 15.0) and P = .0498 (OR 8.44) in the discovery and replication cohorts, respectively] and PROX1-antisense RNA1 (PROX1-AS1: rs1891059, P = 2.28 × 10(-7) [OR 6.48] and P = .0077 [OR 3.78] for the discovery and replication cohorts, respectively). The top replicated nonsynonymous SNP, rs34144324, was in a glutamate receptor gene (GRID2, P = 8.65 × 10(-6) [OR 3.46] and P = .0136 [OR 10.8] in the discovery and replication cohorts, respectively). In a meta-analysis, the BMP7 and PROX1-AS1 variants (rs75161997 and rs1891059, respectively) met the significance threshold of <5 × 10(-8). Top replicated SNPs were enriched in enhancers active in mesenchymal stem cells, and analysis of annotated genes demonstrated enrichment in glutamate receptor and adipogenesis pathways. These data may provide new insights into the pathophysiology of osteonecrosis.

  7. Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI)

    PubMed Central

    2012-01-01

    Introduction Critical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms. Methods Twenty-eight sheep were randomised into two groups, receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (Day 1) or stored (Day 42) non-leucoreduced human packed red blood cells (PRBC) or an infusion of saline. TRALI was defined by hypoxaemia during or within two hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study, using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro. Results TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however, there was no difference to neutrophil priming in vitro. Conclusions In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS

  8. Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

    PubMed Central

    2014-01-01

    Background To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy. Methods Seventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE. Results Seventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, OR = 1.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; OR = 9.686) and V50 (p<0.001; OR = 1.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (p = 0.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC. Conclusions Concomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to

  9. Hospital Performance Indicators and Their Associated Factors in Acute Child Poisoning at a Single Poison Center, Central Saudi Arabia.

    PubMed

    Alanazi, Menyfah Q; Al-Jeriasy, Majed I; Al-Assiri, Mohammed H; Afesh, Lara Y; Alhammad, Fahad; Salam, Mahmoud

    2015-12-01

    Admission rate and length of stay (LOS) are two hospital performance indicators that affect the quality of care, patients' satisfaction, bed turnover, and health cost expenditures. The aim of the study was to identify factors associated with higher admission rates and extended average LOS among acutely poisoned children at a single poison center, central Saudi Arabia.This is a cross-sectional, poison and medical chart review between 2009 and 2011. Exposures were child characteristics, that is, gender, age, body mass index (BMI), health history, and Canadian 5-level triage scale. Poison incident characteristics were, that is, type, exposure route, amount, form, home remedy, and arrival time to center. Admission status and LOS were obtained from records. Chronic poisoning, plant allergies, and venomous bites were excluded. Bivariate and regression analyses were applied. Significance at P < 0.05.Of the 315 eligible cases, (72%) were toddlers with equal gender distribution, (58%) had normal BMI, and (77%) were previously healthy. Poison substances were pharmaceutical drugs (63%) versus chemical products (37%). Main exposure route was oral (98%). Home remedy was observed in (21.9%), which were fluids, solutes, and/or gag-induced vomiting. Almost (52%) arrived to center >1 h. Triage levels: non-urgent cases (58%), less urgent (11%), urgent (18%), emergency (12%), resuscitative (1%). Admission rate was (20.6%) whereas av. LOS was 13 ± 22 h. After adjusting and controlling for confounders, older children (adj.OR = 1.19) and more critical triage levels (adj.OR = 1.35) were significantly associated with higher admission rates compared to younger children and less critical triage levels (adj.P = 0.006) and (adj.P = 0.042) respectively. Home remedy prior arrival was significantly associated with higher av. LOS (Beta = 9.48, t = 2.99), compared to those who directly visited the center, adj.P = 0.003.Hospital administrators are cautioned

  10. Hospital Performance Indicators and Their Associated Factors in Acute Child Poisoning at a Single Poison Center, Central Saudi Arabia.

    PubMed

    Alanazi, Menyfah Q; Al-Jeriasy, Majed I; Al-Assiri, Mohammed H; Afesh, Lara Y; Alhammad, Fahad; Salam, Mahmoud

    2015-12-01

    Admission rate and length of stay (LOS) are two hospital performance indicators that affect the quality of care, patients' satisfaction, bed turnover, and health cost expenditures. The aim of the study was to identify factors associated with higher admission rates and extended average LOS among acutely poisoned children at a single poison center, central Saudi Arabia.This is a cross-sectional, poison and medical chart review between 2009 and 2011. Exposures were child characteristics, that is, gender, age, body mass index (BMI), health history, and Canadian 5-level triage scale. Poison incident characteristics were, that is, type, exposure route, amount, form, home remedy, and arrival time to center. Admission status and LOS were obtained from records. Chronic poisoning, plant allergies, and venomous bites were excluded. Bivariate and regression analyses were applied. Significance at P < 0.05.Of the 315 eligible cases, (72%) were toddlers with equal gender distribution, (58%) had normal BMI, and (77%) were previously healthy. Poison substances were pharmaceutical drugs (63%) versus chemical products (37%). Main exposure route was oral (98%). Home remedy was observed in (21.9%), which were fluids, solutes, and/or gag-induced vomiting. Almost (52%) arrived to center >1 h. Triage levels: non-urgent cases (58%), less urgent (11%), urgent (18%), emergency (12%), resuscitative (1%). Admission rate was (20.6%) whereas av. LOS was 13 ± 22 h. After adjusting and controlling for confounders, older children (adj.OR = 1.19) and more critical triage levels (adj.OR = 1.35) were significantly associated with higher admission rates compared to younger children and less critical triage levels (adj.P = 0.006) and (adj.P = 0.042) respectively. Home remedy prior arrival was significantly associated with higher av. LOS (Beta = 9.48, t = 2.99), compared to those who directly visited the center, adj.P = 0.003.Hospital administrators are cautioned

  11. Cathelicidin-BF suppresses intestinal inflammation by inhibiting the nuclear factor-κB signaling pathway and enhancing the phagocytosis of immune cells via STAT-1 in weanling piglets.

    PubMed

    Yi, Hongbo; Yu, Caihua; Zhang, Haiwen; Song, Deguang; Jiang, Denghu; Du, Huahua; Wang, Yizhen

    2015-09-01

    The severity of intestinal inflammation in mammals can be profoundly impacted by weaning stress. Cathelicidins protect intestinal homeostasis by not only directly killing bacteria but also immune regulators. Here, we investigated the effects of cathelicidin-BF (C-BF) derived from the snake venoms of Bungarus fasciatus on weaning stress and intestinal inflammation and examined the mechanisms by which C-BF modulates intestinal immune responses in weanling piglets. We found that C-BF treatment significantly increased performance and reduced the diarrheal index in weanling piglets. Serum IL-6, IL-22 and TNF-α production was decreased by C-BF treatment. We demonstrated that C-BF inhibited the expression of the inflammatory cytokines TNF-α, IL-6 and IL-8 but increased the expression of the anti-inflammatory cytokine IL-10 in the intestine. We also demonstrated that C-BF suppressed inflammation by down-regulating the nuclear factor-κB (NF-κB) signaling pathway in the intestine and in LPS-induced macrophages in vitro. However, C-BF significantly induced the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) to enhance the phagocytosis of macrophages when inflammation was suppressed. In summary, our study demonstrated that C-BF suppressed intestinal inflammation by down-regulating the NF-κB signaling pathway and enhancing the phagocytosis of immune cells by activating STAT-1 during weaning.

  12. Extended Daily Dialysis in Acute Kidney Injury Patients: Metabolic and Fluid Control and Risk Factors for Death

    PubMed Central

    Ponce, Daniela; Abrão, Juliana Maria Gera; Albino, Bianca Ballarin; Balbi, André Luis

    2013-01-01

    Intermittent hemodialysis (IHD) and continuous renal replacement therapies (CRRT) are used as Acute Kidney Injury (AKI) therapy and have certain advantages and disadvantages. Extended daily dialysis (EDD) has emerged as an alternative to CRRT in the management of hemodynamically unstable AKI patients, mainly in developed countries. Objectives We hypothesized that EDD is a safe option for AKI treatment and aimed to describe metabolic and fluid control of AKI patients undergoing EDD and identify complications and risk factors associated with death. Study Selection This is an observational and retrospective study describing introduction of EDD at our institution. A total of 231 hemodynamically unstable AKI patients (noradrenalin dose between 0.3 and 1.0 ucg/kg/min) were assigned to 1367 EDD session. EDD consisted of 6–8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 300 ml/min. Data Synthesis Mean age was 60.6±15.8 years, 97.4% of patients were in the intensive care unit, and sepsis was the main etiology of AKI (76.2). BUN and creatinine levels stabilized after four sessions at around 38 and 2.4 mg/dl, respectively. Fluid balance decreased progressively and stabilized around zero after five sessions. Weekly delivered Kt/V was 5.94±0.7. Hypotension and filter clotting occurred in 47.5 and 12.4% of treatment session, respectively. Regarding AKI outcome, 22.5% of patients presented renal function recovery, 5.6% of patients remained on dialysis after 30 days, and 71.9% of patients died. Age and focus abdominal sepsis were identified as risk factors for death. Urine output and negative fluid balance were identified as protective factors. Conclusions EDD is effective for AKI patients, allowing adequate metabolic and fluid control. Age, focus abdominal sepsis, and lower urine output as well as positive fluid balance after two EDD sessions were associated significantly with death. PMID:24349114

  13. Ectopic AtCBF1 over-expression enhances freezing tolerance and induces cold acclimation-associated physiological modifications in potato.

    PubMed

    Pino, María-Teresa; Skinner, Jeffrey S; Jeknić, Zoran; Hayes, Patrick M; Soeldner, Alfred H; Thomashow, Michael F; Chen, Tony H H

    2008-04-01

    We studied the effect of ectopic AtCBF over-expression on physiological alterations that occur during cold exposure in frost-sensitive Solanum tuberosum and frost-tolerant Solanum commersonii. Relative to wild-type plants, ectopic AtCBF1 over-expression induced expression of COR genes without a cold stimulus in both species, and imparted a significant freezing tolerance gain in both species: 2 degrees C in S. tuberosum and up to 4 degrees C in S. commersonii. Transgenic S. commersonii displayed improved cold acclimation potential, whereas transgenic S. tuberosum was still incapable of cold acclimation. During cold treatment, leaves of wild-type S. commersonii showed significant thickening resulting from palisade cell lengthening and intercellular space enlargement, whereas those of S. tuberosum did not. Ectopic AtCBF1 activity induced these same leaf alterations in the absence of cold in both species. In transgenic S. commersonii, AtCBF1 activity also mimicked cold treatment by increasing proline and total sugar contents in the absence of cold. Relative to wild type, transgenic S. commersonii leaves were darker green, had higher chlorophyll and lower anthocyanin levels, greater stomatal numbers, and displayed greater photosynthetic capacity, suggesting higher productivity potential. These results suggest an endogenous CBFpathway is involved in many of the structural, biochemical and physiological alterations associated with cold acclimation in these Solanum species.

  14. Draft Genome Sequence of Stenotrophomonas maltophilia CBF10-1, an Organophosphate-Degrading Bacterium Isolated from Ranch Soil in Fairchilds, Texas

    PubMed Central

    Damania, Ashish

    2016-01-01

    Stenotrophomonas maltophilia CBF10-1 was isolated from a ranch in Fairchilds, Texas, USA. Its genome reveals a highly adaptable microorganism with a large complement of antibiotic and heavy metal resistance genes, efflux pumps, multidrug transporters, and xenobiotic degradation pathways. PMID:27174285

  15. The antimicrobial activity of Cbf-K16 against MRSA was enhanced by β-lactamantibiotics through cell wall non-integrity.

    PubMed

    Li, Bo; Kang, Wei; Liu, Hanhan; Wang, Yanrong; Yu, Changzhong; Zhu, Xinyi; Dou, Jie; Cai, Haibo; Zhou, Changlin

    2016-07-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important pathogens both in health care and in community-onset infections. Cbf-K16, a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous studies. We evaluated the potential for synergy of Cbf-K16 with ceftazidime/ampicilin against MRSA, which was resistant to these two antibiotics with the minimum inhibitory concentration more than 64 μg/ml. The combinations showed a synergistic effect by a checkerboard assay with a fractional inhibitory concentration index ≤0.5. The killing curves of the combination treatment against MRSA showed that CFU counts decreased rapidly within 4 h by almost five logs, while single medication groups and the control group exhibited little inhibitory effect. In addition, in a mice bacteremia model, studies indicated that the combination treatment significantly prolonged the survival time of mice infected with MRSA, with a death protection rate of 80 %. Flow cytometry analysis and transmission electron microscopy indicated that combination-treated MRSA was completely ruptured with the cellular contents leaked out. The synergistic effect showed that Cbf-K16 selectively killed cells with non-integrity induced by cell wall inhibition antibiotics, suggesting that Cbf-K16 is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy. PMID:27287456

  16. Differential expression of heat shock transcription factors and heat shock proteins after acute and chronic heat stress in laying chickens (Gallus gallus).

    PubMed

    Xie, Jingjing; Tang, Li; Lu, Lin; Zhang, Liyang; Xi, Lin; Liu, Hsiao-Ching; Odle, Jack; Luo, Xugang

    2014-01-01

    Heat stress due to high environmental temperature negatively influences animal performances. To better understand the biological impact of heat stress, laying broiler breeder chickens were subjected either to acute (step-wisely increasing temperature from 21 to 35°C within 24 hours) or chronic (32°C for 8 weeks) high temperature exposure. High temperature challenges significantly elevated body temperature of experimental birds (P<0.05). However, oxidation status of lipid and protein and expression of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) 70 and 90 were differently affected by acute and chronic treatment. Tissue-specific responses to thermal challenge were also found among heart, liver and muscle. In the heart, acute heat challenge affected lipid oxidation (P = 0.05) and gene expression of all 4 HSF gene expression was upregulated (P<0.05). During chronic heat treatment, the HSP 70 mRNA level was increased (P<0.05) and HSP 90 mRNA (P<0.05) was decreased. In the liver, oxidation of protein was alleviated during acute heat challenge (P<0.05), however, gene expression HSF2, 3 and 4 and HSP 70 were highly induced (P<0.05). HSP90 expression was increased by chronic thermal treatment (P<0.05). In the muscle, both types of heat stress increased protein oxidation, but HSFs and HSPs gene expression remained unaltered. Only tendencies to increase were observed in HSP 70 (P = 0.052) and 90 (P = 0.054) gene expression after acute heat stress. The differential expressions of HSF and HSP genes in different tissues of laying broiler breeder chickens suggested that anti-heat stress mechanisms might be provoked more profoundly in the heart, by which the muscle was least protected during heat stress. In addition to HSP, HSFs gene expression could be used as a marker during acute heat stress.

  17. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  18. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    PubMed

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  19. Long-Term Effects of Autologous Bone Marrow Stem Cell Treatment in Acute Myocardial Infarction: Factors That May Influence Outcomes

    PubMed Central

    Clifford, David M.; Fisher, Sheila A.; Brunskill, Susan J.; Doree, Carolyn; Mathur, Anthony; Clarke, Mike J.; Watt, Suzanne M.; Martin-Rendon, Enca

    2012-01-01

    Aims To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. Methods and Results MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005–2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 108 cells and to patients with more severe heart dysfunction. Conclusions Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials. PMID:22655042

  20. Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome.

    PubMed

    Goldstein, Sidney; Bates, Eric R; Bhatt, Deepak L; Cao, Charlie; Holmes, David; Kupfer, Stuart; Martinez, Felipe; Spaeder, Jeffrey; Weitz, Jeffrey I; Ye, Zhan; Zannad, Faiez

    2014-06-01

    TAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose-dependent effect of TAK-442 on major bleeding when added to standard treatment in stabilised patients with acute coronary syndrome (ACS). In this phase II double-blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition to usual care using a three-stage adaptive design. Patients were randomised to placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was started 36 hours after emergent treatment of ACS and within seven days of admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding incidence was low, but higher with the pooled TAK-442 doses than with placebo (17 [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor dose-dependent. However, a dose response was evident when using the modified ISTH scale. The incidence of cardiovascular events was similar among TAK-442 dose groups and placebo. When administered over a wide range of doses after an ACS event, TAK-442 treatment did not result in a dose-dependent increase in TIMI major bleeding, but increased bleeding was observed when a more sensitive bleeding scale was used. There was no evidence for efficacy.

  1. SOLID FUEL USE IS A MAJOR RISK FACTOR FOR ACUTE CORONARY SYNDROMES AMONG RURAL WOMEN: A MATCHED CASE CONTROL STUDY

    PubMed Central

    Fatmi, Z.; Coggon, D.; Kazi, A.; Naeem, I.; Azam, I.; Kadir, M.M.; Sathiakumar, N.

    2014-01-01

    Objectives Almost half of the world’s population uses solid fuel for cooking, exposing women to high levels of particulate pollution in indoor air. We assessed the risk of acute coronary syndrome (ACS) among rural women, according to their use of solid fuel. Study design Matched case control study. Methods Data were collected at a public tertiary care hospital in a rural district of Pakistan. Seventy-three women with ACS were compared with controls, individually matched for sex and age (±5years), who were admitted to hospital for other reasons. Fuels used for cooking and exposures to potentially confounding variables were ascertained through a questionnaire administered at interview and measurement of height and weight. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (95% CIs). Results After adjustment for potential confounding factors, current use of solid fuel was strongly associated with ACS ( OR 4.8, 95% CI: 1.5 to 14.8), and risk was lowest in women who had last used solid fuel more than 15 years earlier. The population attributable fraction for ACS in relation to current use of solid fuel was 49.0% (95% CI: 41.3% - 57.4%). Conclusions These findings support the hypothesis that indoor air pollution from use of solid fuel is an important cause of ACS. Our study demonstrates the feasibility of case-control studies in rural populations of women to address this question, and is an encouragement to larger and statistically more powerful investigations. PMID:24342134

  2. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  3. The study for loss of bcl-xs expression as a prognostic factor in acute myeloid leukemia.

    PubMed

    Yamaguchi, Hiroki; Inokuchi, Koiti; Dan, Kazuo

    2002-12-01

    We reported here abnormal expression profile of the bcl-x gene is associated with the recurrence in acute myelogenous leukemia (AML).The bcl-x gene product exists in two forms, bcl-xl and bcl-xs. The bcl-xl, similar to bcl-2, inhibits apoptosis, whereas bcl-xs counters the effects of bcl-2 and bcl-xl. Mononuclear cells of bone marrow cells were obtained from 50 patients with recurrent AML at diagnosis prior to treatment and during relapse. We investigated the expression of the two isoforms of the bcl-x gene, bcl-xl and bcl-xs. The bcl-xl transcript was detected in all patients at both stages, but the bcl-xs transcript was not detected in six cases at both stages and in seven other cases at relapse (bcl-xs (-) group, n=13). The duration of relapse-free survival (RFS) and overall survival (OS) of the bcl-xs (-) group were significantly shorter than those of the bcl-xs (+) group (RFS: P=0.04; OS: P=0.02). Subsequently, mutation of the bcl-x gene was investigated. No mutation of the bcl-x gene was detected in all patients of both stages. Some refractory leukemic cells which escape chemotherapy-induced apoptosis due to loss of the bcl-xs transcript may continue to proliferate, resulting in the relapse of chemotherapy-resistant leukemia. The examination of the expression status of the bcl-x gene could facilitate the prediction of chemotherapy resistance and the prognosis of patients with refractory AML. The future large study will confirm the present data about loss of bcl-xs gene expression as prognostic factor.

  4. Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

    PubMed Central

    Conger, J D; Robinette, J B; Schrier, R W

    1988-01-01

    Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels. PMID:3261301

  5. Increased susceptibility to acute kidney injury due to endoplasmic reticulum stress in mice lacking tumor necrosis factor-α and its receptor 1.

    PubMed

    Huang, Lianghu; Zhang, Ruihua; Wu, Jin; Chen, Jian; Grosjean, Fabrizio; Satlin, Lisa H; Klein, Janet D; Sands, Jeffrey M; Striker, Gary E; Tan, Jianming; Zheng, Feng

    2011-03-01

    Endoplasmic reticulum (ER) stress is actively involved in acute organ injury. Since tumor necrosis factor α (TNFα) plays a role in acute kidney injury, and induces ER stress and cell death in vitro, we examined the contribution of TNFα to acute kidney ER stress induced by tunicamycin. Contrary to expectation, tunicamycin caused much more severe kidney injury in TNFα-/- than in wild-type mice. The major site of kidney injury in TNFα-/- mice was proximal tubules, which showed extensive cell vacuolation, lipid accumulation, and apoptosis. Reconstitution of TNFα-/- mice with TNFα 24 h before tunicamycin injection reversed the susceptibility. When TNFα-receptor-deficient mice were treated with tunicamycin, severe renal injury developed in TNFR1-/- but not TNFR2-/- mice, suggesting this aspect of TNFα action was through TNF receptor-1 (TNFR1). In response to tunicamycin-induced acute ER stress, kidneys from neither TNFα-/- nor TNFR1-/- mice showed a significant increase in phosphorylated eukaryotic translation initiation factor 2α (eIF2α), a key step in ER stress regulation. Moreover, proximal tubular cells from TNFR1-/- mice did not show increased eIF2α phosphorylation in response to tunicamycin and were susceptible to ER stress-induced cell death. Finally, treatment of proximal tubule cells isolated from TNFR1-/- mice with an inhibitor of eIF2α phosphatase increased the levels of phosphorylated eIF2α and substantially reduced tunicamycin-induced cell death. Thus, disruption of TNFR1 signaling leads to dysregulation of eIF2α and increased susceptibility to acute ER stress injury in the kidney.

  6. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis.

    PubMed

    Zhong, Weibin; Geng, Na; Wang, Pengfei; Li, Zhenguang; Cao, Lili

    2016-08-01

    Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge.

  7. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis.

    PubMed

    Zhong, Weibin; Geng, Na; Wang, Pengfei; Li, Zhenguang; Cao, Lili

    2016-08-01

    Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge. PMID:27129874

  8. Cloning and characterization of cold, salt and drought inducible C-repeat binding factor gene from a highly cold adapted ecotype of Lepidium latifolium L.

    PubMed

    Akhtar, M; Jaiswal, A; Jaiswal, J P; Qureshi, M I; Tufchi, M; Singh, N K

    2013-04-01

    The dehydration-responsive element-binding (DREB) protein/C-Repeat Binding Factors (CBFs) belongs to APETALA2 (AP2) family transcription factors that binds to DRE/CRT cis-element in cold-responsive (COR) genes and induce COR genes. CBFs have been isolated and characterized from evolutionarily diverse plant species. CBF pathway is conserved by CBF regulon and the size or the number and kind of target genes vary among freezing sensitive and tolerant plants. Hence, cloning of CBFs from highly freezing tolerant plants such as Lepidium latifolium L. will be useful in understanding the freezing tolerance of this species. In this study, LlCBF, a CBF1 family gene from L. Latifolium L., was cloned using RT-PCR and RACE-PCR. The full length mRNA of LlCBF is 948 bp with an open reading frame of 642 bp, encoding a protein of 213 amino acids with a molecular weight of 23.92 kDa and a theoretical isoelectric point of 4.80. Amino acid sequence analysis showed that LlCBF has an AP2 DNA binding domain, a potential CBF type nuclear localization signal (NLS) and C-terminal acidic domain. Semi-quantitative RT-PCR analysis of LlCBF revealed that this gene is up-regulated by high salt, dehydration and low temperature stresses. The investigation is therefore successful in cloning of a gene having strong homology with CBF transcription factors and responsive to low temperature, high salt and dehydration conditions.

  9. Factors Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke: Lessons from China.

    PubMed

    Huang, Qiang; Ma, Qing-feng; Feng, Juan; Cheng, Wei-yang; Jia, Jian-ping; Song, Hai-qing; Chang, Hong; Wu, Jian

    2015-01-01

    In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60 min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135 min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay

  10. Study of differences in presentation, risk factors and management in diabetic and nondiabetic patients with acute coronary syndrome

    PubMed Central

    Sharma, Krishna Kumar; Mathur, Mukul; Lodha, Sailesh; Sharma, Surendra Kumar; Sharma, Niharika; Gupta, Rajeev

    2016-01-01

    Objectives: To compare clinical characteristics, treatment, and utilization of evidence-based medicines at discharge from hospital in acute coronary syndrome (ACS) patients with or without diabetes at a tertiary care cardiac center in India. Methods: We performed an observational study in consecutive patients discharged following management of ACS. We obtained demographic details, comorbid conditions, and cardiovascular risk factors, physical and biochemical parameters, and management. Descriptive statistics are reported. Results: We enrolled 100 patients (diabetics = 28) with mean age of 59.0 ± 10.8 years (diabetics 59.3 ± 11.6, nondiabetics 58.9 ± 8.5). Forty-nine patients had ST-elevation myocardial infarction (STEMI) (diabetics = 14, 28.7%) while 51 had nonSTEMI/unstable angina (diabetics = 14, 27.4%) (P = nonsignificant). Among diabetics versus nondiabetics there was greater prevalence (%) of hypertension (78.6% vs. 44.4%), obesity (25.0% vs. 8.3%), abdominal obesity (85.7% vs. 69.4%) and sedentary activity (89.2% vs. 77.8%), and lower prevalence of smoking/tobacco use (10.7% vs. 25.0%) (P < 0.05). In STEMI patients 28 (57.1%) were thrombolysed (diabetes 17.8% vs. 31.9%), percutaneous coronary interventions (PCI) was in 67.8% diabetics versus 84.7% nondiabetics and coronary bypass surgery in 21.4% versus 8.3%. At discharge, in diabetics versus nondiabetics, there was similar use of angiotensin converting enzyme inhibitors (67.9% vs. 69.4%) and statins (100.0% vs. 98.6%) while use of dual antiplatelet therapy (85.7% vs. 95.8%) and beta-blockers (64.3% vs. 73.6%) was lower (P < 0.05). Conclusions: Diabetic patients with ACS have greater prevalence of cardiometabolic risk factors (obesity, abdominal obesity, and hypertension) as compared to nondiabetic patients. Less diabetic patients undergo PCIs and receive lesser dual anti-platelet therapy and beta-blockers. PMID:27186553

  11. Multifunctional Centromere Binding Factor 1 Is Essential for Chromosome Segregation in the Human Pathogenic Yeast Candida glabrata

    PubMed Central

    Stoyan, Tanja; Gloeckner, Gernot; Diekmann, Stephan; Carbon, John

    2001-01-01

    The CBF1 (centromere binding factor 1) gene of Candida glabrata was cloned by functional complementation of the methionine biosynthesis defect of a Saccharomyces cerevisiae cbf1 deletion mutant. The C. glabrata-coded protein, CgCbf1, contains a basic-helix-loop-helix leucine zipper domain and has features similar to those of other budding yeast Cbf1 proteins. CgCbf1p binds in vitro to the centromere DNA element I (CDEI) sequence GTCACATG with high affinity (0.9 × 109 M−1). Bandshift experiments revealed a pattern of protein-DNA complexes on CgCEN DNA different from that known for S. cerevisiae. We examined the effect of altering the CDEI binding site on CEN plasmid segregation, using a newly developed colony-sectoring assay. Internal deletion of the CDEI binding site led only to a fivefold increase in rates of plasmid loss, indicating that direct binding of Cbf1p to the centromere DNA is not required for full function. Additional deletion of sequences to the left of CDEI, however, led to a 70-fold increase in plasmid loss rates. Deletion of the CBF1 gene proved to be lethal in C. glabrata. C. glabrata cells containing the CBF1 gene under the influence of a shutdown promoter (tetO-ScHOP) arrested their growth after 5 h of cultivation in the presence of the reactive drug doxycycline. DAPI (4′,6′-diamidino-2-phenylindole) staining of the arrested cells revealed a significant increase in the number of large-budded cells with single nuclei, 2C DNA content, and short spindles, indicating a defect in the G2/M transition of the cell cycle. Thus, we conclude that Cbf1p is required for chromosome segregation in C. glabrata. PMID:11438645

  12. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  13. Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia

    PubMed Central

    Cheng, Chi Keung; Chan, Natalie P. H.; Wan, Thomas S. K.; Lam, Lai Ying; Cheung, Coty H. Y.; Wong, Terry H. Y.; Ip, Rosalina K. L.; Wong, Raymond S. M.; Ng, Margaret H. L.

    2016-01-01

    Helicase-like transcription factor is a SWI/SNF chromatin remodeling factor involved in various biological processes. However, little is known about its role in hematopoiesis. In this study, we measured helicase-like transcription factor mRNA expression in the bone marrow of 204 adult patients with de novo acute myeloid leukemia. Patients were dichotomized into low and high expression groups at the median level for clinicopathological correlations. Helicase-like transcription factor levels were dramatically reduced in the low expression patient group compared to those in the normal controls (n=40) (P<0.0001). Low helicase-like transcription factor expression correlated positively with French-American-British M4/M5 subtypes (P<0.0001) and complex cytogenetic abnormalities (P=0.02 for ≥3 abnormalities; P=0.004 for ≥5 abnormalities) but negatively with CEBPA double mutations (P=0.012). Also, low expression correlated with poorer overall (P=0.005) and event-free (P=0.006) survival in the intermediate-risk cytogenetic subgroup. Consistent with the more aggressive disease associated with low expression, helicase-like transcription factor knockdown in leukemic cells promoted proliferation and chromosomal instability that was accompanied by downregulation of mitotic regulators and impaired DNA damage response. The significance of helicase-like transcription factor in genome maintenance was further indicated by its markedly elevated expression in normal human CD34+ hematopoietic stem cells. We further demonstrated that helicase-like transcription factor was a RUNX1 target and transcriptionally repressed by RUNX1-ETO and site-specific DNA methylation through a duplicated RUNX1 binding site in its promoter. Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia. PMID:26802049

  14. Myelodysplastic syndrome and acute myeloid leukemia following adjuvant chemotherapy with and without granulocyte colony-stimulating factors for breast cancer.

    PubMed

    Calip, Gregory S; Malmgren, Judith A; Lee, Wan-Ju; Schwartz, Stephen M; Kaplan, Henry G

    2015-11-01

    Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for MDS/AML risk. Among 56,251 breast cancer cases, 1.2 % developed MDS/AML during median follow-up of 3.2 years. 47.1 % of women received radiation and 14.3 % received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR = 1.38, 95 %-CI 0.98-1.93) and chemotherapy/radiation (HR = 1.77, 95 %-CI 1.25-2.51) had increased risk of MDS/AML, but not radiation alone (HR = 1.08, 95 % CI 0.86-1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR = 1.86, 95 %-CI 1.33-2.61) and filgrastim (HR = 1.47, 95 %-CI 1.05-2.06), but not pegfilgrastim (HR = 1.10, 95 %-CI 0.73-1.66). We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients.

  15. Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

    PubMed Central

    Park, Chul Soo; Chung, Woo Baek; Choi, Yun Seok; Kim, Pum Joon; Lee, Jong Min; Baek, Ki-Hyun; Kim, Hee Yeol; Yoo, Ki Dong; Song, Ki-Ho; Chung, Wook Sung; Seung, Ki Bae; Lee, Man Young; Kwon, Hyuk-Sang

    2015-01-01

    Objective To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors. Methods We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates. Results The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups. Conclusions AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities. PMID:26295946

  16. Conventional Risk Factors and Acute Coronary Syndrome during a Period of Socioeconomic Transition: Population-based Case-control Study in Tirana, Albania

    PubMed Central

    Burazeri, Genc; Goda, Artan; Sulo, Gerhard; Stefa, Jonida; Roshi, Enver; Kark, Jeremy D.

    2007-01-01

    Aim To assess the association between conventional risk factors and acute coronary syndrome in Albania, a transitional country in Southeast Europe. Methods A population-based case-control study was conducted in Tirana in 2003-2006. A total of 467 consecutive patients with nonfatal acute coronary syndrome were recruited. There were 370 men with mean ± standard deviation (SD) age of 59.1 ± 8.7 years and 97 women with mean±SD age of 63.3 ± 7.1 years. The control group comprised a population-representative sample of Tirana residents. In the control group, there were 469 men with mean±SD age of 53.1 ± 10.4 years and 268 women aged 54.0 ± 10.9 years. A structured questionnaire on demographic, socioeconomic, psychosocial factors, and health behaviors was administered. Physical measurements included anthropometrics and blood pressure. Venous blood and adipose tissue aspirations from the gluteal region were frozen-stored for future analysis. Multivariable-adjusted logistic regression was used to assess the independent associations of conventional risk factors with acute coronary syndrome. Results Upon adjustment for covariates, family history of coronary heart disease was found to be a strong predictor of acute coronary syndrome in both men (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.58-5.30) and women (OR, 4.53; 2.40-8.57). Waist-to-hip ratio in men (OR, 4.03; 2.83-5.73) and obesity in women (OR, 3.31; 1.54-7.14) were strongly associated with acute coronary syndrome. In men, but not in women, there was a significant association with hypertension and current smoking (P = 0.011 and P<0.001, respectively). Diabetes was not significantly independently associated in either sex. Conclusion Classical risk factors predicted coronary heart disease in Albania, similarly as in the rest of the world, although associations with family history and anthropometric indices were stronger. These findings are resulting largely from the heterogeneous

  17. Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle.

    PubMed

    Kivelä, Riikka; Silvennoinen, Mika; Lehti, Maarit; Kainulainen, Heikki; Vihko, Veikko

    2007-10-01

    Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was >10-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01). Increased immunohistochemical staining of VEGF-D was found in degenerative muscle fibers in the diabetic mice. In conclusion, the results suggest that acute exercise or exercise training does not significantly affect lymphangiogenesis in skeletal muscle. Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage.

  18. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  19. Factors involved in the antinatriuretic effects of acute constriction of the thoracic and abdominal inferior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.

    1971-01-01

    Study of the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction in the absence of alterations in renal perfusion pressure. A comparison is made of the effects of equivalent degrees of TIVC and abdominal inferior vena cava constriction on arterial pressure, renal hemodynamics, and electrolyte excretion.

  20. In-Hospital Mortality among Rural Medicare Patients with Acute Myocardial Infarction: The Influence of Demographics, Transfer, and Health Factors

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Knudson, Alana D.; Klug, Marilyn G.; Wynne, Joshua

    2011-01-01

    Context/Purpose: Most rural hospitals can provide medical care to acute myocardial infarction (AMI) patients, but a need for advanced cardiac care requires timely transfer to a tertiary hospital. There is little information on AMI in-hospital mortality predictors among rural transfer patients. Methods: Cross-sectional retrospective analyses on…

  1. Prevalence of factors associated with malnutrition among acute geriatric patients in Norway: a cross-sectional study

    PubMed Central

    Jacobsen, Ellisiv Lærum; Brovold, Therese; Bergland, Astrid; Bye, Asta

    2016-01-01

    Objectives Data on acute geriatric patients' nutritional status are lacking, and the associations among physical function, sarcopenia, health status and nutritional status are not sufficiently investigated in this population. The aims of this study are to investigate (1) nutritional status and sarcopenia in a group of acute geriatric patients, (2) the association between nutritional status, physical function and sarcopenia in acute geriatric patients, controlling for health status. Design A cross-sectional study. Setting Two acute geriatric hospital wards in Norway. Participants This study included 120 patients with a mean age of 82.6