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Sample records for acute phase gene

  1. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    Science.gov (United States)

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.

  2. Synergistic enhansons located within an acute phase responsive enhancer modulate glucocorticoid induction of angiotensinogen gene transcription.

    Science.gov (United States)

    Brasier, A R; Ron, D; Tate, J E; Habener, J F

    1990-12-01

    The hepatic transcription of the angiotensinogen gene is regulated by both glucocorticoids and cytokines generated as products of the acute phase reaction. We have identified a multimodular enhancer in the 5'-flanking region of the rat angiotensinogen gene that mediates these responses and consists of an acute phase response element (APRE) flanked on both sides by adjacent glucocorticoid response element consensus motifs (GREs). Induction of transcription by the cytokine interleukin-1 (IL-1) is glucocorticoid dependent and mediated through the APRE. The APRE binds in a mutually exclusive manner a cytokine/phorbol ester-inducible protein (BPi), indistinguishable from nuclear factor kB, and a family of constitutive liver proteins (BPcs) related to the heat-stable transcription factor C/EBP. Using mutated 5'-flanking sequences of the angiotensinogen gene fused to a firefly luciferase reporter gene transfected into hepatoblastoma (HepG2) cells, we have mapped enhanson sequences required for the transcriptional response to glucocorticoids. Two functionally distinct GREs are identified by deletion and site-directed mutagenesis, both of which mediate glucocorticoid-stimulated transcription in vivo. Glucocorticoid-induced transcription mediated by the angiotensinogen gene enhancer is, furthermore, dependent on the occupancy of the APRE by either the BPi or a member of the BPc family because a mutant APRE that binds neither BPi nor BPc exhibits an attenuated glucocorticoid responsiveness. Mutant APREs that permit exclusive binding of either BPi or BPc synergistically transmit the glucocorticoid response mediated by one or the other of the adjacent GREs. Thus, the induction of angiotensinogen gene transcription involves interaction between the glucocorticoid receptor and either one of the APRE-binding proteins: either the cytokine-inducible NFkB or the constitutive family of C/EBP-like proteins, bound to adjacent enhansons in a mutually synergistic enhancer complex.

  3. The effect of transport stress on turkey (Meleagris gallopavo) liver acute phase proteins gene expression.

    Science.gov (United States)

    Marques, Andreia Tomás; Lecchi, Cristina; Grilli, Guido; Giudice, Chiara; Nodari, Sara Rota; Vinco, Leonardo J; Ceciliani, Fabrizio

    2016-02-01

    The aim of this study was to investigate the effects of transport-related stress on the liver gene expression of four acute phase proteins (APP), namely α1-acid glycoprotein (AGP), C-Reactive Protein (CRP), Serum Amyloid A (SAA) and PIT54, in turkeys (Meleagris gallopavo). A group of seven BUT BIG 6 commercial hens was subjected to a two-hour long road transportation and the quantitative gene expression of APP in the liver was compared to that of a non transported control group. The expression of AGP and CRP mRNA was found to be increased in animals slaughtered after road transport. The presence of AGP protein was also confirmed by immunohistochemistry and Western blotting. The results of this study showed that road-transport may induce the mRNA expression of immune related proteins. The finding that AGP and CRP can be upregulated during transport could suggest their use as for the assessment of turkey welfare during transport.

  4. Gene expression profiling of porcine skeletal muscle in the early recovery phase following acute physical activity

    DEFF Research Database (Denmark)

    Hansen, Jeanette; Conley, Lene; Hedegaard, Jakob

    2012-01-01

    of unaccustomed exercise on global transcriptional profiles in porcine skeletal muscles. Using a combined microarray and candidate gene approach, we identified a suite of genes that are differentially expressed in muscles during postexercise recovery. Several members of the heat shock protein family and proteins...... of adenosine-to-inosine edited mRNAs in the ribonucleoprotein bodies called paraspeckles. These findings expand the complexity of pathways affected by acute contractile activity of skeletal muscle, contributing to a better understanding of the molecular processes that occur in muscle tissue in the recovery...

  5. The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.

    Directory of Open Access Journals (Sweden)

    Sara Lopes dos Santos

    Full Text Available BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas disease, a debilitating illness that affects millions of people in the Americas. A major finding of the T. cruzi genome project was the discovery of a novel multigene family composed of approximately 1,300 genes that encode mucin-associated surface proteins (MASPs. The high level of polymorphism of the MASP family associated with its localization at the surface of infective forms of the parasite suggests that MASP participates in host-parasite interactions. We speculate that the large repertoire of MASP sequences may contribute to the ability of T. cruzi to infect several host cell types and/or participate in host immune evasion mechanisms. METHODS: By sequencing seven cDNA libraries, we analyzed the MASP expression profile in trypomastigotes derived from distinct host cells and after sequential passages in acutely infected mice. Additionally, to investigate the MASP antigenic profile, we performed B-cell epitope prediction on MASP proteins and designed a MASP-specific peptide array with 110 putative epitopes, which was screened with sera from acutely infected mice. FINDINGS AND CONCLUSIONS: We observed differential expression of a few MASP genes between trypomastigotes derived from epithelial and myoblast cell lines. The more pronounced MASP expression changes were observed between bloodstream and tissue-culture trypomastigotes and between bloodstream forms from sequential passages in acutely infected mice. Moreover, we demonstrated that different MASP members were expressed during the acute T. cruzi infection and constitute parasite antigens that are recognized by IgG and IgM antibodies. We also found that distinct MASP peptides could trigger different antibody responses and that the antibody level against a given peptide may vary after sequential passages in mice. We speculate that changes in the large repertoire of MASP antigenic peptides during an infection may contribute to

  6. Significance and mechanism of CYP7a1 gene regulation during the acute phase of liver regeneration.

    Science.gov (United States)

    Zhang, Lisheng; Huang, Xiongfei; Meng, Zhipeng; Dong, Bingning; Shiah, Steven; Moore, David D; Huang, Wendong

    2009-02-01

    Cholesterol 7alpha-hydroxylase (CYP7a1) is the rate-limiting enzyme in the classic pathway of bile acid synthesis. Expression of CYP7a1 is regulated by a negative feedback pathway of bile acid signaling. Previous studies have suggested that bile acid signaling is also required for normal liver regeneration, and CYP7a1 expression is strongly repressed after 70% partial hepatectomy (PH). Both the effect of CYP7a1 suppression on liver regrowth and the mechanism by which 70% PH suppresses CYP7a1 expression are unknown. Here we show that liver-specific overexpression of an exogenous CYP7a1 gene impaired liver regeneration after 70% PH, which was accompanied by increased hepatocyte apoptosis and liver injury. CYP7a1 expression was initially suppressed after 70% PH in an farnesoid X receptor/ small heterodimer partner-independent manner; however, both farnesoid X receptor and small heterodimer partner were required to regulate CYP7a1 expression at the later stage of liver regeneration. c-Jun N-terminus kinase and hepatocyte growth factor signaling pathways are activated during the acute phase of liver regeneration. We determined that hepatocyte growth factor and c-Jun N-terminus kinase pathways were involved in the suppressing of the CYP7a1 expression in the acute phase of live regeneration. Taken together, our results provide the significance that CYP7a1 suppression is required for liver protection after 70% PH and there are two distinct phases of CYP7a1 gene regulation during liver regeneration.

  7. Endometrial gene expression of acute phase extracellular matrix components following estrogen disruption of pregnancy in pigs.

    Science.gov (United States)

    Ashworth, Morgan D; Ross, Jason W; Stein, Daniel; White, Frank; Geisert, Rodney D

    2010-12-01

    In pigs, administration of estrogen to gilts on Days 9 and 10 of pregnancy causes conceptus fragmentation and death between Days 15 and 18 of gestation. Conceptus degeneration is associated with breakdown of the microvilli surface glycocalyx on the lumenal epithelium (LE). We previously identified endometrial expression of inter-α-trypsin inhibitor (ITI) and hyaluronic acid (HA), which are key components of extracellular matrix (ECM), during the period of conceptus attachment to the uterine surface in the pig. Tumor necrosis factor-α-inducible protein-6 (TNFAIP6) serves as a linker for ECM expansion and is stimulated by prostaglandin E (PGE). We hypothesized that early estrogen administration alters the normal ECM components forming glycocalyx on the LE. Bred gilts (4 gilts/trt/day) were treated with either 5mg estradiol cypionate (E) or corn oil (CO) on Days 9 and 10 of gestation. The uterus was surgically removed on either Days 10, 12, 13, 15 and 17 of gestation and endometrial tissue snap frozen in liquid nitrogen. Endometrial tumor necrosis factor-α (TNF), TNFAIP6, interleukin 6 (IL6), and inter-α-trypsin inhibitor heavy chains (ITIH) were detected during early pregnancy thereby indicating all components for maintenance of the extracellular glycocalyx are present in the endometrium of pigs. However, only gene expression of ITIH2 was suppressed by E-treatment. TNFAIP6 protein was detected across all days of gestation but was not affected by E-treatment. The present study demonstrates that while the pig endometrium expresses key components of ECM only ITIH2 gene expression was altered by E-treatment. A decrease in ITIH2 could lead to the possible loss of the uterine glycocalyx leading to conceptus degeneration; however, other factors may be involved with the loss of glycocalyx during implantation in the pig following E-treatment.

  8. Cytokine and acute phase protein gene expression in liver biopsies from dairy cows with a lipopolysaccharide - induced mastitis

    DEFF Research Database (Denmark)

    Vels, J; Røntved, Christine M.; Bjerring, Martin

    2009-01-01

    - ), IL-1β, IL-6, and IL-10, and the acute phase proteins serum amyloid A isoform 3 (SAA3), haptoglobin (Hp), and 1-acid glycoprotein (AGP) were determined by real-time reverse transcription-PCR. Fourteen primiparous cows in mid lactation were challenged with 200 µg of LPS (n = 8) or NaCl solution (n = 6...

  9. Review: Acute phase reaction and acute phase proteins

    Institute of Scientific and Technical Information of China (English)

    GRUYS E.; TOUSSAINT M.J.M.; NIEWOLD T.A.; KOOPMANS S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes,negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants,they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached.Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need;and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations.

  10. Isoforms of human C4b-binding protein. II. Differential modulation of the C4BPA and C4BPB genes by acute phase cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, O.C.; Sanchez-Corral, P.; Rodriguez de Cordoba, S. [Center for Biological Investigations (CSIC), Velazquez, Madrid (Spain)

    1995-10-15

    Human C4b-binding protein (C4BP) controls activation of the complement system and inactivates the anticoagulant vitamin K-dependent protein S using two distinct polypeptides known as C4BP{alpha} and C4BP{beta}, respectively. C4BP presents three isoforms, {alpha}7{beta}1, {alpha}7{beta}0, and {alpha}6{beta}1, the proportion of which depends on the relative levels of C4BP{alpha} and C4BP{beta}. To better understand the regulation of C4BP during the acute phase response we analyzed the C4BP isoforms in 23 serial samples of acute phase patients and characterized the effect of various acute phase cytokines on the expression of the C4BPA and C4BPB genes using Hep3B cells. We show that the elevation of C4BP during acute phase response leads to changes in the proportion of the C4BP isoforms. However, there are striking differences among acute phase individuals. Some of them present a pattern of induction that primarily affects the {alpha}7{beta}0 isoform, whereas others present the opposite situation, increasing the C4BP{beta}-containing isoforms. In vitro studies demonstrate that IL-6, IL-1{beta}, and INF-{gamma} increase the levels of both C4BP{alpha} and C4BP{beta}-mRNAs, whereas TNF-{alpha} down-regulates these mRNAs. INF-{gamma} shows, in addition, a differential effect on the C4BP{alpha} and C4BP{beta}-mRNAs. Differential modulation of the C4BPA and C4BPB genes has been postulated as an efficient mechanism to maintain steady concentrations of C4BP{beta} when C4BP is induced. A synergistic 10-fold induction of C4BP{alpha}-mRNA, but a marginal increase of C4BP{beta}-mRNA, was observed when INF-{gamma} was used together with TNF-{alpha}, suggesting that association of these cytokines is critical to avoid elevation of C4BP{beta} during the acute phase induction of C4BP. 33 refs., 6 figs.

  11. Pharm GKB: Acute-Phase Reaction [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Phase Reaction; Acute Phase State; Acute-Phase Response; Acute...-Phase State; Reaction, Acute Phase; Reaction, Acute-Phase; Response, Acute Phase; Response, Acute...-Phase; State, Acute-Phase PharmGKB Accession Id: PA443262 External Vocabularies MeSH: Acute-Phase ...Reaction (D000210) UMLS: Acute-Phase Reaction [Disease/Finding] (C0001349) NDFRT: Acute...-Phase Reaction [Disease/Finding] (N0000000303) Common Searches Search Medline Plus Search CTD Pharm GKB: Acute-Phase Reaction ...

  12. Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Moesgaard, S. G.;

    2014-01-01

    The usefulness of Göttingen minipigs as models for obesity and obesity-related pathologies is well established. The low-grade inflammation associated with obesity involves a range of innate immune factors; however, to our knowledge, the impact of obesity on innate immune factor expression has...... between adipose tissues and a decreased tissue-specific expression of cytokines and chemokines. In contrast to obese humans, no changes in serum concentrations of haptoglobin, C-reactive protein, serum amyloid A, tumor necrosis factor-α and interleukin 6 were found in obese Göttingen minipigs....... not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine...

  13. A functional interaction of E7 with B-Myb-MuvB complex promotes acute cooperative transcriptional activation of both S- and M-phase genes. (129 c).

    Science.gov (United States)

    Pang, C L; Toh, S Y; He, P; Teissier, S; Ben Khalifa, Y; Xue, Y; Thierry, F

    2014-07-31

    High-risk human papillomaviruses are causative agents of cervical cancer. Viral protein E7 is required to establish and maintain the pro-oncogenic phenotype in infected cells, but the molecular mechanisms by which E7 promotes carcinogenesis are only partially understood. Our transcriptome analyses in primary human fibroblasts transduced with the viral protein revealed that E7 activates a group of mitotic genes via the activator B-Myb-MuvB complex. We show that E7 interacts with the B-Myb, FoxM1 and LIN9 components of this activator complex, leading to cooperative transcriptional activation of mitotic genes in primary cells and E7 recruitment to the corresponding promoters. E7 interaction with LIN9 and FoxM1 depended on the LXCXE motif, which is also required for pocket protein interaction and degradation. Using E7 mutants for the degradation of pocket proteins but intact for the LXCXE motif, we demonstrate that E7 functional interaction with the B-Myb-MuvB complex and pocket protein degradation are two discrete functions of the viral protein that cooperate to promote acute transcriptional activation of mitotic genes. Transcriptional level of E7 in patient's cervical lesions at different stages of progression was shown to correlate with those of B-Myb and FoxM1 as well as other mitotic gene transcripts, thereby linking E7 with cellular proliferation and progression in cervical cancer in vivo. E7 thus can directly activate the transcriptional levels of cell cycle genes independently of pocket protein stability.

  14. Management of pemphigus vulgaris during acute phase

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    Kar P

    2003-03-01

    Full Text Available We present our experience with 21 patients of pemphigus vulgaris seen over a period of 10 years managed in service hospitals during acute phase of the disease. Age groups of patients ranged from 25-45 years. Eighteen (85.7% were young adults, 30-40 years of age. Fifteen (71.4% were men and 6(28.6% were women. All the cases were hospitalized in ICU, till the acute phase of the disease subsided. Complete hematological profile, urinalysis, serum biochemistry and repeated bacterial cultures from the skin were carried out in all patients at the time of admission and thereafter weekly. The treatment comprised of potassium permanganate lotion bath (1:10000 and 1 framycetin gauze dressing of the denuded areas, maintenance of fluid and electrolyte balance. All suspected infections and septicemia were treated with appropriate antibiotics. The corticosteroids were usually administered as a single dose of prednisolone 1 mg/kg/day. Cyclophosphamide was given at an initial dose of 50mg/day and the dose was escalated to 100mg/day. Once the bulk of the lesions were healed, the dose of corticosteroids was gradually lowered by approximately 50% every two weeks and cyclophosphamide was continued till patients were symptomfree. Out of 21 patients receiving corticosteroids, cyclophosphamide and other supportive therapy, 20(95% had undergone clinical resolution of the disease. During follow up study 15(71.4% patients remained symptom-free and undergone clinical remission. Five patients (23.8% had relapse, out of which 4(19% remained symptom free, after subsequent treatment. There was one death (4.7% in our study.

  15. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  16. Neuropsychological intervention in the acute phase

    DEFF Research Database (Denmark)

    Norup, Anne; Siert, Lars; Mortensen, Erik Lykke

    2013-01-01

    This pilot study investigated the effects of acute neuropsychological intervention for relatives of patients with severe brain injury. Participants were enrolled in an intervention group comprising 39 relatives, and a control group comprising 47 relatives. The intervention consisted of supportive.......0100.30), but also significantly lower Role Emotional scores (= 2.12 = 0.043, = 0.40). In the sub-acute setting, an analysis of covariance model showed a borderline significant difference between the intervention and the control group on the anxiety scale (= 0.066 = 0.59). Any effects of the acute neuropsychological...

  17. Neuropsychological intervention in the acute phase

    DEFF Research Database (Denmark)

    Norup, Anne; Siert, Lars; Mortensen, Erik Lykke

    2013-01-01

    Objective: This pilot study investigated the effects of acute neuropsychological intervention for relatives of patients with severe brain injury. Methods: Participants were enrolled in an intervention group comprising 39 relatives, and a control group comprising 47 relatives. The intervention...... = 0.59). Conclusion: Any effects of the acute neuropsychological intervention were limited. Further research is needed to explore the effects of different interventions in more homogenous and larger groups of relatives....

  18. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Lipoprotein lipase gene variants: Association with acute myocardial infarction and lipid profiles. ... Therefore, genes involved in lipid and lipoprotein metabolism pathways such as lipoprotein lipase (LPL), are proper candidates ... Article Metrics.

  19. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

    DEFF Research Database (Denmark)

    Kristensen, Lena; Buhl, Rikke; Nostell, Katarina

    2014-01-01

    The purpose of the study was to investigate whether acute strenuous exercise (1600- to 2500-m race) would elicit an acute phase response (APR) in Standardbred trotters. Blood levels of several inflammatory markers [serum amyloid A (SAA), haptoglobin, fibrinogen, white blood cell count (WBC......), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts......, and iron levels were decreased 2 and/or 7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered in response to racing. Acute strenuous exercise did not elicit an acute phase reaction. The observed acute increase in hemoglobin levels and decreases in haptoglobin and iron levels may...

  20. Murine heart gene expression during acute Chagasic myocarditis

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    Andrés F. Henao-Martínez

    2015-06-01

    Full Text Available Chagas disease is transmitted by the parasite, Trypanosoma cruzi. Acute infection is characterized by acute myocarditis, although it is largely asymptomatic. Initial cardiac insult could be a determinant to the posterior development of chronic Chagasic cardiomyopathy, usually after 10 years in only approximately 30% of chronically infected patients. Herein, we characterized the acute gene expression profiling in heart tissue of two strains of mice infected with T. cruzi (tulahuen strain at 4 weeks and their respective controls. Gene sequence data are available at NCBI under GEO accession number: GSE63847. The output of the genes expression suggests differences in involvement of protein kinase B (AKT, NCAM1, HLA-DRA, and ubiquitin C genes networks. These gene activation differences may correlate with myocardial contractility during the acute infection.

  1. Application of acute phase protein measurements in veterinary clinical chemistry

    DEFF Research Database (Denmark)

    Petersen, Henning; Nielsen, J. P.; Heegaard, Peter M. H.

    2004-01-01

    The body's early defence in response to trauma, inflammation or infection, the acute phase response, is a complex set of systemic reactions seen shortly after exposure to a triggering event. One of the many components is an acute phase protein response in which increased hepatic synthesis leads t...... A and their possible use as non-specific indicators of health in large animal veterinary medicine such as in the health status surveillance of pigs at the herd level, for the detection of mastitis in dairy cattle and for the prognosis of respiratory diseases in horses....

  2. Application of acute phase protein measurements in veterinary clinical chemistry

    DEFF Research Database (Denmark)

    Petersen, Henning; Nielsen, J. P.; Heegaard, Peter M. H.

    2004-01-01

    The body's early defence in response to trauma, inflammation or infection, the acute phase response, is a complex set of systemic reactions seen shortly after exposure to a triggering event. One of the many components is an acute phase protein response in which increased hepatic synthesis leads t...... A and their possible use as non-specific indicators of health in large animal veterinary medicine such as in the health status surveillance of pigs at the herd level, for the detection of mastitis in dairy cattle and for the prognosis of respiratory diseases in horses....

  3. Acute phase proteins as diagnostic markers in horses with colic

    DEFF Research Database (Denmark)

    Pihl, Tina; Scheepers, Elrien; Sanz, Macarena

    2016-01-01

    colic. Design – Prospective observational multicenter study. Setting – Two university referral hospitals. Animals – Horses referred for severe acute abdominal pain to Hospital 1 (n = 148) or Hospital 2 (n = 78). Intervention – Blood and PF samples collected at admission were used for acute-phase protein...... revealed that only WBC and SAA and fibrinogen concentrations improved the model. With SAA included in the model no additional blood parameters improved the model, and the final model had an area under the curve of 90%. Addition of PF parameters (hemolysis, total protein concentration, WBC, SAA, or Hp......Objective – To investigate the diagnostic potential of the concentrations of acute-phase proteins serum amyloid A (SAA), haptoglobin (Hp), and fibrinogen in blood and peritoneal fluid (PF) for differentiating horses within flammatory colic (entero-colitis and peritonitis) from those with surgical...

  4. Gene expression profiling and endothelin in acute experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Helieh S Oz; Ying Lu; Louis P Vera-Portocarrero; Pei Ge; Ada Silos-Santiago; Karin N Westlund

    2012-01-01

    AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS:Dibutyltin dichloride (DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia (DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin (ET) receptor antagonists [ET-A (BQ123) and ET-B BQ788)].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies (edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors (cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory; extracellular matrix; structural; channel/receptor/transporter; signaling transduction; transcription/translation-related; antioxidants/chaperones/heat shock; pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in

  5. Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

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    Marek Kiliszek

    Full Text Available BACKGROUND: Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients. METHODS AND RESULTS: Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI were included. The blood was collected on the 1(st day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05 were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor, IL-10 and IL-6 (interleukin 10 and 6. CONCLUSIONS: In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.

  6. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

    de Jonge, H. J. M.; Huls, G.; de Bont, E. S. J. M.

    Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on

  7. Methylation of Gene CHFR Promoter in Acute Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    GONG Hui; LIU Wengli; ZHOU Jianfeng; XU Huizhen

    2005-01-01

    Summary: In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt-4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myelocytic leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.

  8. CDX2 gene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hanaa H. Arnaoaut

    2014-06-01

    Full Text Available CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  9. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

    Directory of Open Access Journals (Sweden)

    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  10. Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

    Science.gov (United States)

    Bernal, Luis; Feser, Mariane; Martínez-Subiela, Silvia; García-Martínez, Juan D; Cerón, José J; Tecles, Fernando

    2011-10-01

    We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus.

  11. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    Science.gov (United States)

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  12. Elimination Half-Lives of Acute Phase Proteins in Rats and Beagle Dogs During Acute Inflammation.

    Science.gov (United States)

    Kuribayashi, Takashi; Seita, Tetsuro; Momotani, Eiichi; Yamazaki, Shunsuke; Hagimori, Kohei; Yamamoto, Shizuo

    2015-08-01

    The half-lives of typical acute phase proteins in rats and beagle dogs during acute inflammation were investigated. Acute inflammation was induced by injection of turpentine oil in rats and administration of indomethacin in beagle dogs. Serum concentrations of α2-macroglobulin (α2M) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay and α1-acid glycoprotein (AAG) was measured by single radial immunodiffusion. Half-life was calculated as 0.693/elimination rate constant (K). The mean half-lives in the terminal elimination phase of α2M and AAG were 68.1 and 164.8 h, respectively. The half-life of AAG was significantly longer than that of α2M. Mean half-lives in the terminal elimination phase of CRP and AAG were 161.9 and 304.4 h, respectively. The half-life of AAG was significantly longer than that of CRP in beagle dogs. No significant differences in the half-life of AAG were observed between rats and beagle dogs. Furthermore, serum concentrations in the terminal elimination phase could be simulated with the K data acquired in this study.

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

    OpenAIRE

    Noriko Takeuchi; Daisuke Ekuni; Takaaki Tomofuji; Manabu Morita

    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 periodonta...

  14. Acute cholecystitis: two-phase spiral CT finding

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Eung Young; Yoon, Myung Hwan; Yang, Dal Mo; Chun Seok; Bae, Jun Gi; Kim, Hak Soo; Kim, Hyung Sik [Chungang Ghil Hospital, Incheon (Korea, Republic of)

    1998-07-01

    To describe the two-phase spiral CT findings of acute cholecystitis. Materials and Methods : CT scans of nine patients with surgically-proven acute cholecystitis were retrospectively reviewed for wall thickening, enhancement pattern of the wall, attenuation of the liver adjacent to the gallbladder, gallstones,gallbladder distension, gas collection within the gallbladder, pericholecystic fluid and infiltration of pericholecystic fat. Results : In all cases, wall thickening of the gallbladder was seen, though this was more distinct on delayed images, Using high-low-high attenuation, one layer was seen in five cases, nd three layers in four. On arterial images, eight cases showed transient focal increased attenuation of the liver adjacent to the gall bladder;four of these showed curvilinear attenuation and four showed subsegmental attenuation. One case showed curvilinear decreased attenuation between increased attenuation of the liver and the gallbladder, and during surgery, severe adhesion between the liver and gallbladder was confirmed. Additional CT findings were infiltration of pericholecystic fat (n=9), gallstones (n=7), gallbladder distension (n=6), pericholecystic fluid(n=3), and gas collection within the gallbladder (n=2). Conclusion : In patients with acute cholecystitis,two-phase spiral CT revealed wall thickening in one or three layers ; on delayed images this was more distinct. In many cases, arterial images showed transient focal increased attenuation of the liver adjacent to the gallbladder.

  15. Early phase of acute pancreatitis: Assessment and management

    Institute of Scientific and Technical Information of China (English)

    Veit; Phillip; Jrg; M; Steiner; Hana; Algül

    2014-01-01

    Acute pancreatitis(AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis.

  16. [Bradyarrhythmias in the acute phase of myocardial infarct].

    Science.gov (United States)

    Maroto Montero, J M; Lemus, J M; Marín-Huerta, E; Gorodezky, M; Cárdenas, M

    1975-01-01

    The functioning of the Intensive Care Units has permitted a better study and treatment of the arrhythmias which complicate the acute phase of myocardial infarction. 1,100 charts of patients admitted to the Coronary Unit of the National Institute of Cardiology of Mexico were reviewed. Acute myocardial infarction was demonstrated in 819 of them by the usual methods. The frequency and characteristics of the following bradiarrhythmias were studied: sinus bradicardia, sinus stoppage, seno-atrial block, migration of the atrial pacing, union rhythm and slow ventricular tachycardia. Sinus bradicardia was presented in 23.7% of the infarctions, sinus stoppage in 2.4%, migration of the atrial pacing in 9.4%, nodal rhythm in 7.2% and slow ventricular tachycardia in 7.8%. Bradiarrhythmias, generally considered as "lesser" arrhythmias, favor the appearance of lethal arrhythmias, regardless of the degree of mechanical failure, and thus should be treated actively.

  17. Gene Expression Profiling on Acute Rejected Transplant Kidneys with Microarray

    Institute of Scientific and Technical Information of China (English)

    Deping LI; Kang WANG; Yong DAI; Tianyu LV

    2008-01-01

    To investigate the gene expression profiles in acute allograft rejection of renal trans- plantation, and identify the markers for the early diagnosis of acute rejection, heterotopic kidney transplantation was performed by using F344 or Lewis donors and Lewis recipients. No immunosup- pressant was used. Renal grafts were harvested on days 3, 7, and 14. A commercial microarray was used to measure gene expression levels in day-7 grafts. The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control, and interferon-y-induced GTPase gene was most significantly up-regulated in allografts. It is concluded that a variety of pathways are involved in organ transplant rejection which is dynamic and non-balanced. IFN-inducible genes, such as IGTP, may play an important role in the rejection. A lot of important factors involved in acute re- jection are unnecessary but sufficient conditions for the rejection. We are led to conclude that it is virtually impossible to make an early diagnosis based on a single gene marker, but it could he achieved on the basis of a set of markers.

  18. Functional diets modulate the acute phase protein response in Oncorhynchus mykiss subjected to chronic stress and challenged with Vibrio anguillarum.

    Science.gov (United States)

    Castro-Osses, Darlyng; Carrera-Naipil, Crisleri; Gallardo-Escárate, Cristian; Gonçalves, Ana Teresa

    2017-07-01

    The acute phase response to pathogens alters the production of proinflammatory cytokines that, in turn, activate the synthesis of acute phase proteins. These proteins neutralize, prevent, and indicate tissue damage, thereby influencing the specific immune response and allowing the organism to regain homeostasis. Functional diets based in pre- and probiotics are used in aquaculture to improve fish health and resistance to diseases, but there is an information gap on the mechanisms involved in these effects and if these diets are efficient when fish are raised under high stocking densities. This study aimed an evaluation of the acute phase response in Oncorhynchus mykiss fed functional diets supplemented with pre- and probiotics (i.e. mannan-oligosaccharides and Saccharomyces cerevisiae, respectively) and challenged by either Vibrio anguillarum or chronic stress via maintenance under high stocking densities. For this, the relative expression of acute phase response related genes in liver, and of inflammatory response related genes in head kidney was evaluated by RT-qPCR. The supplemented diets differentially modulated the acute phase protein response to the assessed challenge conditions, specifically evidencing an overexpression of the genes HAPT, SAA, LECT2, and IL-1β under chronic stress and of HAPT, IL-1β, IL8, and LECT2 at 24 h post-challenge with V. anguillarum. The observed early-stage regulation of acute phase proteins and of the immune response by the probiotic S. cerevisiae and by prebiotic mannan-oligosaccharides suggests that both supplements have high immunostimulatory potentials for fish farmed under high stocking densities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia cell line Jurkat].

    Science.gov (United States)

    Wang, Chi-Juan; Xu, Hua; Zhang, Hai-Rui; Wang, Jian; Lin, Ya-Ni; Pang, Tian-Xiang; Li, Qing-Hua

    2014-08-01

    This study was purpose to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA-Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat.

  20. The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Adriana M. C. Canavaci

    2014-01-01

    Full Text Available In the present work we examine the contribution of 5-lipoxygenase- (5-LO- derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/− mice and wild-type (WT mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

  1. Physical anhedonia in the acute phase of schizophrenia

    Directory of Open Access Journals (Sweden)

    Petridou Eleni

    2006-01-01

    Full Text Available Abstract Background The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. Method Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS, the Positive and Negative Syndrome Scale (PANSS, the Rating Scale for Extrapyramidal Side-Effects (EPSE, the Barnes Akathisia Rating Scale (BARS and the Abnormal Involuntary Movement Scale (AIMS. Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. Results Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. Conclusion According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

  2. Microheterogeneity of acute phase proteins in patients with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Marian Grzymis(l)awski; Katarzyna Derc; Magdalena Sobieska; Krzysztof Wiktorowicz

    2006-01-01

    AIM: To estimate the serum α1-antichymotrypsin (ACT),α1-acid glycoprotein (AGP) and transferrin (Tf) concentrations and to evaluate the microheterogeneity of these acute phase proteins in patients with ulcerative colitis. METHODS: Twenty-seven patients with ulcerative colitis (UC) and 17 healthy control subjects were studied. The patients were categorised as severe (n = 9), moderate (n = 10) and mild groups (n = 8) using Truelove and Witts'classification of ulcerative colitis. Microheterogeneity of ACT, AGP and Tf was analysed by crossed immunoaffinity electrophoresis (CIAE) with concanavalin A. In all serum samples standard electrophoresis of serum proteins was performed, iron (Fe) concentration, total iron binding capacity (TIBC) and C-reactive protein (CRP) were also measured.RESULTS: Our patients suffering from ulcerative colitis had significantly higher serum ACT and AGP concentrations and lower serum transferrin concentration in comparison to healthy subjects. Changes in concentrationsof acute phase proteins were dependent on the activityof the inflammatory process. The glycosylation patterns of transferrin were related to the inflammation status. We also observed the correlation between ACT and AGP concentrations, patterns of transferrin glycosylation and changes in standard protein electrophoresis or blood cell count.CONCLUSION: The glycosylation patterns of transferrin obtained from patients suffering from ulcerative colitis are highly branched and sialylated compared with those obtained from healthy subjects. In contrast, the glycosylation patterns of transferrin do not differ according to the activity index of ulcerative colitis. The microheterogeneity patterns of AGP and ACT are similar in ulcerative colitis patients and healthy subjects.

  3. Acute phase response in cattle infected with Anaplasma marginale.

    Science.gov (United States)

    Nazifi, S; Razavi, S M; Kaviani, F; Rakhshandehroo, E

    2012-03-23

    This study was undertaken to evaluate the acute phase responses via the assessment of the concentration of serum sialic acids (total, lipid bound and protein bound), inflammatory mediators (IFN-γ and TNF-α) and acute phase proteins (Hp and SAA) in 20 adult crossbred cattle naturally infected by Anaplasma marginale. The infected animals were divided into 2 subgroups on the basis of parasitemia rate (20%). Also, as a control group, 10 clinically healthy cattle from the same farms were sampled. Our data revealed significant decreases in red blood cell count (RBC), hematocrite (PCV) and hemoglobine (Hb) in infected cattle compared to healthy ones. Conversely, the concentrations of Hp, SAA, ceruloplasmin, fibrinogen, serum sialic acids and the circulatory IFN-γ and TNF-α were increased in the diseased cattle (P<0.05). In addition, it was evident that the progression of parasitemia in infected cattle did not induce any significant alterations in the hematological indices (RBCs, PCV and Hb) and the concentrations of Hp, SAA, ceruloplasmin and fibrinogen. SAA was the most sensitive factor to change in the diseased cattle. Therefore, increase in SAA concentration may be a good indicator of inflammatory process in cattle naturally infected with Anaplasma marginale.

  4. RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, J.W.G.; Steenvoorden, A.C.M.; Lyons, J.; Anger, B.; Boehlke, J.U.; Bos, J.L.; Seliger, H.; Bartram, C.R.

    1987-12-01

    The authors report on investigations aimed at detecting mutated RAS genes in a variety of preleukemic disorders and leukemias of myeloid origin. DNA transfection analyses (tumorigenicity assay) and hybridization to mutation-specific oligonucleotide probes established NRAS mutations in codon 12 or 61 of 4/9 acute myelocytic leukemias (AML) and three AML lines. Leukemic cells of another AML patient showed HRAS gene activation. By using a rapid and sensitive dot-blot screening procedure based on the combination of in vitro amplification of RAS-specific sequences and oligonucleotide hybridization they additionally screened 15 myelodysplastic syndromes, 26 Philadelphia chromosome-positive chronic myelocytic leukemias in chronic or acute phase, and 19 other chronic myeloproliferative disorders. A mutation within NRAS codon 12 could thus be demonstrated in a patient with idiopathic myelofibrosis and in another with chronic myelomonocytic leukemia. Moreover, mutated NRAS sequences were detected in lymphocytes, in granulocytes, as well as in monocytes/macrophages of the latter case.

  5. Acute phase proteins in cattle after exposure to complex stress

    DEFF Research Database (Denmark)

    Lomborg, S. R.; Nielsen, L. R.; Heegaard, Peter M. H.

    2008-01-01

    Abstract Stressors such as weaning, mixing and transportation have been shown to lead to increased blood concentrations of acute phase proteins (APP), including serum amyloid A (SAA) and haptoglobin, in calves. This study was therefore undertaken to assess whether SAA and haptoglobin levels...... in blood mirror stress in adult cattle. Six clinically healthy Holstein cows and two Holstein heifers were transported for four to six hours to a research facility, where each animal was housed in solitary tie stalls. Blood samples for evaluation of leukocyte counts and serum SAA and haptoglobin...... concentrations were obtained before (0-sample) and at 8, 24 and 48 hours after the start of transportation. Upon arrival the animals gave the impression of being anxious, and they appeared to have difficulty coping with isolation and with being tied on the slippery floors of the research stable. Serum...

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

    Science.gov (United States)

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

    2015-08-05

    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 chronic periodontitis.

  7. Gp130-dependent release of acute phase proteins is linked to the activation of innate immune signaling pathways.

    Directory of Open Access Journals (Sweden)

    Maren Luchtefeld

    Full Text Available BACKGROUND: Elevated levels of acute phase proteins (APP are often found in patients with cardiovascular diseases. In a previous study, we demonstrated the importance of the IL-6-gp130 axis -as a key regulator of inflammatory acute phase signaling in hepatocytes-for the development of atherosclerosis. BACKGROUND/PRINCIPAL FINDINGS: Gp130-dependent gene expression was analyzed in a previously established hepatocyte-specific gp130 knockout mouse model. We performed whole transcriptome analysis in isolated hepatocytes to measure tissue specific responses after proinflammatory stimulus with IL-6 across different time points. Our analyses revealed an unexpected small gene cluster that requires IL-6 stimulus for early activation. Several of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response. Furthermore, we identified a potential biomarker Lipocalin (LCN 2 for the gp130 dependent early inflammatory response. CONCLUSIONS/SIGNIFICANCE: Our findings suggest a complex network of tightly linked genes involved in the early activation of different parts of the innate immune response including acute phase proteins, complement and coagulation cascade.

  8. Gene mutations of acute myeloid leukemia in the genome era.

    Science.gov (United States)

    Naoe, Tomoki; Kiyoi, Hitoshi

    2013-02-01

    Ten years ago, gene mutations found in acute myeloid leukemia (AML) were conceptually grouped into class I mutation, which causes constitutive activation of intracellular signals that contribute to the growth and survival, and class II mutation, which blocks differentiation and/or enhance self-renewal by altered transcription factors. A cooperative model between two classes of mutations has been suggested by murine experiments and partly supported by epidemiological findings. In the last 5 years, comprehensive genomic analysis proceeded to find new gene mutations, which are found in the epigenome-associated enzymes and the molecules never noticed so far. These new mutations apparently increase the complexity and heterogeneity of AML. Although a long list of gene mutations might have been compiled, the entire picture of molecular pathogenesis in AML remains to be elucidated because gene rearrangement, gene copy number, DNA methylation and expression profiles are not fully studied in conjunction with gene mutations. Comprehensive genome research will deepen the understanding of AML to promote the development of new classification and treatment. This review focuses on gene mutations that were recently discovered by genome sequencing.

  9. Alteration of immunologic responses on peripheral blood in the acute phase of ischemic stroke: blood genomic profiling study.

    Science.gov (United States)

    Oh, Seung-Hun; Kim, Ok-Joon; Shin, Dong-Ah; Song, Jihwan; Yoo, Hanna; Kim, Yu-Kyung; Kim, Jin-Kyeoung

    2012-08-15

    Peripheral blood cells and inflammatory mediators have a detrimental effect on brain during cerebral ischemia. We investigated the immunologic changes on peripheral blood in the acute phase of ischemic stroke using RNA microarray. mRNA microarray and real time-polymerase chain reaction (RT-PCR) for genes of interest in microarray data were analyzed in 12 stroke patients and 12 controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured in 120 stroke patients and 82 controls. In microarray analysis, a total of 11 genes of interest showed different expression in patients with ischemic stroke. The three most highly expressed genes were C19orf59 (chromosome 19 open reading frame 59), MMP9 and IL18RAP (interleukin-18 receptor accessory protein), whereas gene with the lowest expression was GNLY (granulysin). The expression patterns of three selected genes (MMP9, IL18RAP and GNLY) were validated by RT-PCR. The plasma concentration of MMP-9 was significantly elevated in the stroke patients, and showed a weakly positive correlation with infarct volume. Gene set enrichment analysis (GSEA) showed that gene sets related to immunity and defense, signal transduction, transport and cell adhesion were significant in acute ischemic stroke. In the peripheral blood, numerous genes of inflammatory mediators, including MMP9, IL18RAP and GNLY, are altered in the acute phase of ischemic stroke. This stroke-specific gene expression profiling provides valuable information about the role of peripheral inflammation to the pathophysiological mechanism of ischemic stroke. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Carvedilol versus metoprolol in the acute phase of myocardial infarction:.

    Science.gov (United States)

    Bonnemeier, Hendrik; Ortak, Jasmin; Tölg, Ralph; Witt, Maren; Schmidt, Jörg; Wiegand, Uwe K H; Bode, Frank; Schunkert, Heribert; Richardt, Gert

    2005-01-01

    antiadrenergic therapy on autonomic reflexes in the acute phase of AMI.

  11. The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Tegtmeier, C.; Andresen, Lars Ole;

    2006-01-01

    and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic, infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p...... the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1-12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1-2 days p.i. No clear pattern of changes...... signs and no arthritic lesions showed an APP response comparable to that of the other, clinically affected pigs. Thus, both acute clinical and subclinical S. suis infection could be revealed by the measurement of one or more of the APPs CRP, SAA, Hp, pig-MAP and Apo A-I. The combined measurement of two...

  12. T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin

    Directory of Open Access Journals (Sweden)

    Boris M. Baranovski

    2015-01-01

    Full Text Available The traditional model of T helper differentiation describes the naïve T cell as choosing one of several subsets upon stimulation and an added reciprocal inhibition aimed at maintaining the chosen subset. However, to date, evidence is mounting to support the presence of subset plasticity. This is, presumably, aimed at fine-tuning adaptive immune responses according to local signals. Reprograming of cell phenotype is made possible by changes in activation of master transcription factors, employing epigenetic modifications that preserve a flexible mode, permitting a shift between activation and silencing of genes. The acute phase response represents an example of peripheral changes that are critical in modulating T cell responses. α1-antitrypsin (AAT belongs to the acute phase responses and has recently surfaced as a tolerogenic agent in the context of adaptive immune responses. Nonetheless, AAT does not inhibit T cell responses, nor does it shutdown inflammation per se; rather, it appears that AAT targets non-T cell immunocytes towards changing the cytokine environment of T cells, thus promoting a regulatory T cell profile. The present review focuses on this intriguing two-way communication between innate and adaptive entities, a crosstalk that holds important implications on potential therapies for a multitude of immune disorders.

  13. Acute phase proteins response to feed deprivation in broiler chickens.

    Science.gov (United States)

    Najafi, P; Zulkifli, I; Soleimani, A F; Goh, Y M

    2016-04-01

    Feed deprivation in poultry farming imposes some degree of stress to the birds, and adversely affects their well -being. Serum levels of acute phase proteins (APP) are potential physiological indicators of stress attributed to feed deprivation. However, it has not been determined how long it takes for a measurable APP response to stressors to occur in avian species. An experiment was designed to delineate the APP and circulating levels of corticosterone responses in commercial broiler chickens to feed deprivation for 30 h. It was hypothesized that feed deprivation would elicit both APP and corticosterone (CORT) reactions within 30 h that is probably associated with stress of hunger. Twenty-one day old birds were subjected to one of 5 feed deprivation periods: 0 (ad libitum, AL), 6, 12, 18, 24, and 30 h. Upon completion of the deprivation period, blood samples were collected to determine serum CORT, ovotransferrin (OVT), α1-acid glycoprotein (AGP), and ceruloplasmin (CP) concentrations. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT (P=0.002 and Pstressful condition than CORT response in assessing the well-being of broiler chickens.

  14. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum.

    Science.gov (United States)

    Tobias, P S; Soldau, K; Ulevitch, R J

    1986-09-01

    This report describes the purification of an acute phase reactant from acute phase rabbit serum, which endows normal serum with the properties of acute phase serum, insofar as LPS is concerned. The acute phase reactant is referred to as LPS-binding protein, or LBP. LBP was purified approximately 2,000-fold by chromatography of acute phase serum on Bio-Rex 70 and Mono-Q resins. The resulting preparation consisted of two glycoproteins having molecular weights of 60,500 and 58,000; the two were obtained in a variable ratio, usually near 10:1, respectively. After separation by SDS-PAGE, the N-terminal 36 amino acid sequences of the two proteins were identical. From the N-terminal sequence, as well as other properties of LBP, LBP appears to be unrelated to any known acute phase reactants. The direct interaction of LPS and LBP was inferred from two types of evidence: first, immunoprecipitation of [3H]LPS from APRS by anti-LBP sera; and second, by the 125I-labeling of LBP when APRS-containing 125I-labeled 2-(p-azidosalicylamido)ethyl 1,3'-dithiopropionyl-LPS was photolysed. The data presented here support the concept that the 60-kD glycoprotein we have termed LBP is a newly recognized acute phase reactant that may modulate the biochemical and biologic properties of LPS in vivo.

  15. Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases

    Science.gov (United States)

    Hernández, Carolina; Cucunubá, Zulma; Flórez, Carolina; Olivera, Mario; Valencia, Carlos; Zambrano, Pilar; León, Cielo; Ramírez, Juan David

    2016-01-01

    Background The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases. Methodology/Principal Findings Samples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml). Conclusions/Significance The molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic

  16. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    Science.gov (United States)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  17. Acute phase proteins in the diagnosis of bovine subclinical mastitis.

    Science.gov (United States)

    Safi, Shahabeddin; Khoshvaghti, Ameneh; Jafarzadeh, Seyed Reza; Bolourchi, Mahmoud; Nowrouzian, Iradj

    2009-12-01

    The California mastitis test (CMT) and somatic cell count (SCC) are commonly used for diagnosis of subclinical mastitis in cattle. Acute phase proteins (APPs), as alternative biomarkers of mastitis, may increase in concentration in the absence of macroscopic changes in the milk, or may precede the onset of clinical signs. The aim of this study was to compare the accuracy of APPs measured in milk and in serum with bacterial culture for the diagnosis of bovine subclinical mastitis. One hundred and seventy-five Holstein cows were randomly selected from 7 dairy farms. Quarter milk and serum samples were taken from all cows. Milk samples were analyzed using a CMT and SCC, and for haptoglobin (MHp) and amyloid A (MAA) concentrations, and were also submitted for bacterial culture. Serum samples obtained concurrently were analyzed for haptoglobin (SHp) and amyloid A (SAA). Two-sample Wilcoxon (Mann-Whitney) test was used to compare SCC, MAA, MHp, SAA, and SHp concentrations between culture-positive and culture-negative animals. Receiver-operating characteristic analysis was used to assess the performance of each test using bacterial culture as the reference method. MAA concentration was the most accurate of the 5 tests, with a sensitivity of 90.6% and specificity of 98.3% at concentrations >16.4 mg/L. MAA and MHp had significantly larger areas under the curve than the respective serum proteins, SAA and SHp. The results suggest that measuring haptoglobin and amyloid A in milk is more accurate than serum analysis for the diagnosis of subclinical mastitis in Holstein cows.

  18. [Management of coronary artery disease at the acute phase].

    Science.gov (United States)

    Chatot, Marion; Schiele, François

    2015-03-01

    In patients with acute coronary syndrome (ACS), early management is of prime importance. However, the median time taken by the patient to call the emergency services is often very long, up to 2 hours. The presence of a physician as first responder ensures good quality resuscitation in case of cardiac arrest, and allows recording of a first ECG, which can be very informative, especially in ACS without ST segment elevation. Treatment at this stage is limited to sublingual nitroglycerin and aspirin. If the first ECG shows ST segment elevation, the patient should be immediately oriented for reperfusion, usually by percutaneous coronary intervention. in the absence of ST segment elevation, the diagnosis of ACS remains unconfirmed. This does not imply that the risk is lesser, but rather that the risk cannot be evaluated accurately in the pre-hospital setting. The use of risk scores can guide the choice of management towards an invasive strategy, including coronary angiography (immediately, or within 24-72 hours). Low-risk patients are candidates for an invasive strategy, provided non-invasive tests demonstrate the presence of ischemia. During the hospital phase, antiplatelet treatment should be initiated and must be adapted to the patient bleeding and thrombotic risk. Clopidogrel is recommended only in patients who are not amenable to prasugrel or ticagrelor. Statin therapy should be initiated from day one, regardless of the initial cholesterol level, preferably with 80 mg atorvastatin. Angiotensin-converting enzyme inhibitors and beta-blockers should also be prescribed to complete the medical prescription both in-hospital and in the long term.

  19. Conserved gene regulation during acute inflammation between zebrafish and mammals

    Science.gov (United States)

    Forn-Cuní, G.; Varela, M.; Pereiro, P.; Novoa, B.; Figueras, A.

    2017-01-01

    Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress. We provide evidence that immune signaling pathways and single gene expression is well conserved throughout evolution and that the zebrafish and mammal acute genomic responses after lipopolysaccharide stimulation are highly correlated despite the differential susceptibility between species to that compound. Therefore, we formally confirm that zebrafish inflammatory models are suited to study the basic mechanisms of inflammation in human inflammatory diseases, with great translational impact potential. PMID:28157230

  20. Acute-phase reactants in periodontal disease: current concepts and future implications.

    Science.gov (United States)

    Archana, Vilasan; Ambili, Ranjith; Nisha, Krishnavilasam Jayakumary; Seba, Abraham; Preeja, Chandran

    2015-05-01

    Periodontal disease has been linked to adverse cardiovascular events by unknown mechanisms. C-reactive protein is a systemic marker released during the acute phase of an inflammatory response and is a prognostic marker for cardiovascular disease, with elevated serum levels being reported during periodontal disease. Studies also reported elevated levels of various other acute-phase reactants in periodontal disease. It has been reported extensively in the literature that treatment of periodontal infections can significantly lower serum levels of C-reactive protein. Therefore, an understanding of the relationship between acute-phase response and the progression of periodontal disease and other systemic health complications would have a profound effect on the periodontal treatment strategies. In view of this fact, the present review highlights an overview of acute-phase reactants and their role in periodontal disease. © 2014 Wiley Publishing Asia Pty Ltd.

  1. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

    Science.gov (United States)

    Kobayashi, Masatake; Nanri, Kazunori; Taguchi, Takeshi; Ishiko, Tomoko; Yoshida, Masaharu; Yoshikawa, Noriko; Sugisaki, Kentaro; Tanaka, Nobuyuki

    2015-02-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

  2. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  3. Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis

    DEFF Research Database (Denmark)

    Vogel, Asmus; Elberling, Tina V; Hørding, Merete

    2007-01-01

    In the acute phase of Graves' thyrotoxicosis patients often have subjective cognitive complaints. Continuing controversy exists about the nature of these symptoms and whether they persist after treatment. This prospective study included 31 consecutively referred, newly diagnosed, and untreated pa...

  4. Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response

    NARCIS (Netherlands)

    van den Goor, J.; Nieuwland, R.; van den Brink, A.; van Oeveren, W.; Rutten, 27818; Tijssen, J.; Eijsman, L.; Rutten, P

    2004-01-01

    Objective: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated-

  5. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling

    NARCIS (Netherlands)

    R.G.W. Verhaak (Roel); B.J. Wouters (Bas); C.A.J. Erpelinck (Claudia); S. Abbas (Saman); H.B. Beverloo (Berna); S. Lugthart (Sanne); B. Löwenberg (Bob); H.R. Delwel (Ruud); P.J.M. Valk (Peter)

    2009-01-01

    textabstractWe examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific mol

  6. Air pollutants, genes and early childhood acute bronchitis.

    Science.gov (United States)

    Ghosh, Rakesh; Topinka, Jan; Joad, Jesse P; Dostal, Miroslav; Sram, Radim J; Hertz-Picciotto, Irva

    2013-09-01

    Studies have reported gene-by-environment interaction for chronic respiratory conditions but none on acute illnesses in children. We investigated, longitudinally, whether genotype modifies the relationship of environmental exposures (second-hand tobacco smoke, polycyclic aromatic hydrocarbons, particulate matter bronchitis in children below two years. A random sample of 1133 children, born between 1994 and 1998, in two districts of the Czech Republic, was followed-up from birth, of which 793 were genotyped. Pediatric records were abstracted for respiratory illnesses. Second-hand tobacco smoke exposure from household members was obtained through questionnaires and verified using urine cotinine. Air monitoring provided estimates of ambient polycyclic aromatic hydrocarbons and PM2.5. Additionally, we collected information on a range of potential confounders including breastfeeding history, indoor fuel use, other children in household, maternal characteristics, ambient temperature etc. DNA was extracted from tissues taken from the middle of the placenta, opposite the umbilical cord. We examined six single nucleotide polymorphisms (GSTM1, GSTP1, GSTT1, CYP1A1 MspI, EPHX1 exon 3 and 4) and one (EPHX1) diplotype. To investigate effect measure modification we constructed logistic regression models using generalized estimating equations (for repeated observations) stratified by genotypes. The EPHX1 low activity diplotype consistently imparts greater susceptibility to bronchitis from second-hand tobacco smoke, polyclic aromatic hydrocarbons (PAH) and PM2.5. Each of these three classes of exposure also showed elevated risk for bronchitis in the presence of either one or two histidines at exon 3 and exon 4 of EPHX1. Additional effect modifiers include CYP1A1 and GSTT1. Several xenobiotic metabolizing genes may modify the impact of second-hand tobacco smoke and ambient air pollutants, polycyclic aromatic hydrocarbons and PM2.5, on acute bronchitis in preschool children

  7. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    OpenAIRE

    López-González, Miguel A.; Antonio Abrante; Carmen López-Lorente; Antonio Gómez; Emilio Domínguez; Francisco Esteban

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deaf...

  8. Local and disseminated acute phase response during bacterial respiratory infection in pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Heegaard, Peter M. H.

    2010-01-01

    The acute phase response is playing an important role, aiming to restore the healthy state after tissue injury, inflammation and infection. The biological function of this response and its interplay with other parts of innate defense reactions remain somewhat elusive. Expression of acute phase pr......-types in the organism are involved in production of APP and further supports that extrahepatic APP might be important players of the innate defence system....

  9. Physical anhedonia in the acute phase of schizophrenia

    OpenAIRE

    Petridou Eleni; Stamouli Sophia S; Margariti Maria M; Havaki-Kontaxaki Beata J; Kollias Costas T; Kontaxakis Vassilis P; Christodoulou George N.

    2006-01-01

    Abstract Background The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. Method Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were inv...

  10. Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute phase of a natural infection in pigs

    Science.gov (United States)

    2010-01-01

    Background Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed in vivo during a natural infection, we undertook transcript profiling experiments with an A. pleuropneumoniae DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length. Results Transcriptional profiling of A. pleuropneumoniae recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed in vivo during the acute phase of the infection. Our results indicate that, for example, gene apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879) were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively) or lipoproteins (gene APL_0920). Only 4 of 72 up-regulated genes

  11. Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute phase of a natural infection in pigs

    Directory of Open Access Journals (Sweden)

    Harel Josée

    2010-02-01

    Full Text Available Abstract Background Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed in vivo during a natural infection, we undertook transcript profiling experiments with an A. pleuropneumoniae DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length. Results Transcriptional profiling of A. pleuropneumoniae recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed in vivo during the acute phase of the infection. Our results indicate that, for example, gene apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879 were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively or lipoproteins (gene APL_0920. Only 4

  12. Phase analysis of circadian-related genes in two tissues

    Directory of Open Access Journals (Sweden)

    Li Leping

    2006-02-01

    Full Text Available Abstract Background Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4–8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues. Results We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model. Conclusion We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. 2, and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can

  13. Acute light exposure suppresses circadian rhythms in clock gene expression.

    Science.gov (United States)

    Grone, Brian P; Chang, Doris; Bourgin, Patrice; Cao, Vinh; Fernald, Russell D; Heller, H Craig; Ruby, Norman F

    2011-02-01

    Light can induce arrhythmia in circadian systems by several weeks of constant light or by a brief light stimulus given at the transition point of the phase response curve. In the present study, a novel light treatment consisting of phase advance and phase delay photic stimuli given on 2 successive nights was used to induce circadian arrhythmia in the Siberian hamster ( Phodopus sungorus). We therefore investigated whether loss of rhythms in behavior was due to arrhythmia within the suprachiasmatic nucleus (SCN). SCN tissue samples were obtained at 6 time points across 24 h in constant darkness from entrained and arrhythmic hamsters, and per1, per2 , bmal1, and cry1 mRNA were measured by quantitative RT-PCR. The light treatment eliminated circadian expression of clock genes within the SCN, and the overall expression of these genes was reduced by 18% to 40% of entrained values. Arrhythmia in per1, per2, and bmal1 was due to reductions in the amplitudes of their oscillations. We suggest that these data are compatible with an amplitude suppression model in which light induces singularity in the molecular circadian pacemaker.

  14. The porcine acute phase response to infection with Actinobacillus pleuropneumoniae. Haptoglobin, C-reactive protein, major acute phase protein and serum amyloid a protein are sensitive indicators of infection

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Klausen, Joan; Nielsen, J.P.

    1998-01-01

    In an experimental infection model mimicking acute Actinobacillus pleuropneumoniae (Ap) infection in swine (Sus scrofa) by aerosol inoculation, the development of a number of typical clinical signs was accompanied by a prototypic acute phase reaction encompassing fever and an acute phase protein ...

  15. Feeding cues and injected nutrients induce acute expression of multiple clock genes in the mouse liver.

    Directory of Open Access Journals (Sweden)

    Hideaki Oike

    Full Text Available The circadian clock is closely associated with energy metabolism. The liver clock can rapidly adapt to a new feeding cycle within a few days, whereas the lung clock is gradually entrained over one week. However, the mechanism underlying tissue-specific clock resetting is not fully understood. To characterize the rapid response to feeding cues in the liver clock, we examined the effects of a single time-delayed feeding on circadian rhythms in the liver and lungs of Per2::Luc reporter knockin mice. After adapting to a night-time restricted feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule on the last day. The phase of the liver clock was delayed in all groups with delayed feeding, whereas the lung clock remained unaffected. We then examined the acute response of clock and metabolism-related genes in the liver using focused DNA-microarrays. Clock mutant mice were bred under constant light to attenuate the endogenous circadian rhythm, and gene expression profiles were determined during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed a similarly acute response in hepatic clock gene expression caused by feeding wild type mice after an overnight fast. In addition to Per2 and Dec1, the expression of Per1 increased, and that of Rev-erbα decreased in the liver within 1 h of feeding after fasting, whereas none of these clock genes were affected in the lung. Moreover, an intraperitoneal injection of glucose combined with amino acids, but not either alone, reproduced a similar hepatic response. Our findings show that multiple clock genes respond to nutritional cues within 1 h in the liver but not in the lung.

  16. Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy.

    Science.gov (United States)

    Nader, G A; von Walden, F; Liu, C; Lindvall, J; Gutmann, L; Pistilli, E E; Gordon, P M

    2014-03-15

    We sought to determine whether acute resistance exercise (RE)-induced gene expression is modified by RE training. We studied the expression patterns of a select group of genes following an acute bout of RE in naïve and hypertrophying muscle. Thirteen untrained subjects underwent supervised RE training for 12 wk of the nondominant arm and performed an acute bout of RE 1 wk after the last bout of the training program (training+acute). The dominant arm was either unexercised (control) or subjected to the same acute exercise bout as the trained arm (acute RE). Following training, men (14.8 ± 2.8%; P muscle hypertrophy with increases in dynamic strength in the trained arm (48.2 ± 5.4% and 72.1 ± 9.1%, respectively; P training resulted in attenuated anabolic signaling as reflected by a reduction in rpS6 phosphorylation following acute RE. Changes in mRNA levels of genes involved in hypertrophic growth, protein degradation, angiogenesis, and metabolism commonly expressed in both men and women was determined 4 h following acute RE. We show that RE training can modify acute RE-induced gene expression in a divergent and gene-specific manner even in genes belonging to the same ontology. Changes in gene expression following acute RE are multidimensional, and may not necessarily reflect the actual adaptive response taking place during the training process. Thus RE training can selectively modify the acute response to RE, thereby challenging the use of gene expression as a marker of exercise-induced adaptations.

  17. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie's Disease.

    Science.gov (United States)

    Nguyen, Hoang Minh Tue; Anaissie, James; DeLay, Kenneth J; Yafi, Faysal A; Sikka, Suresh C; Hellstrom, Wayne J G

    2017-09-02

    Peyronie's disease (PD), defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis, is a chronic condition that afflicts 3% to 13% of the US male population; there is no current research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD. To examine the efficacy and safety of CCH in the treatment of acute-phase PD. We retrospectively reviewed the records for all patients treated with CCH for PD from April 2014 through April 2017. Patients who reported penile pain and duration of PD no longer than 12 months at presentation qualified as being in the acute phase of PD. The primary outcomes of interest were final changes in curvature after CCH treatment regardless of the number of CCH cycles received and frequency of treatment-related adverse events. Parameters of efficacy and safety were compared between acute- and stable-phase PD. A total of 162 patients were included in the study, of which 36 (22%) qualified as having acute-phase PD (group 1) and the remaining 126 (78%) qualified as having stable-phase PD (group 2). Median duration of PD was 8.5 months (range = 1-12) for group 1 and 18 months (range = 1-492) for group 2. There was no significant difference in final change in curvature between the acute and stable phases of PD (16.7° vs 15.6°; P = .654). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12 patients, 10%; P = .778). CCH therapy is as safe and efficacious in acute-phase PD as it is in stable-phase PD. This is the first report that assesses the safety and efficacy of CCH therapy focusing on acute-phase PD. This study was composed of a large cohort of patients receiving CCH therapy in acute- and stable-phase PD. Limitations include bias associated with retrospective studies, a small sample, and a single-center setting. Although CCH is not clearly

  18. Intensive treadmill training in the acute phase after ischemic stroke

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2016-01-01

    The aim of the study was to (a) assess the feasibility of intensive treadmill training in patients with acute ischemic stroke, (b) test whether physical activity of the legs during training increases with time, and (c) evaluate to what extent training sessions contribute toward the overall physical...... activity of these patients. Twenty hospitalized patients with acute ischemic stroke trained on a treadmill twice daily for 30 min for 5 days and on day 30. Physical activity was measured as activity counts (AC) from accelerometers. A total of 196 of 224 initiated training sessions were completed. Training...... with increasing number of days, with the median AC being 133% higher on day 5 than on day 1. AC in the paretic leg during 60 min of training constituted median 53% of the daytime AC. Early intensive treadmill training in acute ischemic stroke patients is thus feasible and contributes considerably toward...

  19. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  20. Palliative care in the acute phase after a severe stroke: experiences of relatives.

    NARCIS (Netherlands)

    Boer, M.E. de; Depla, M.; Woijtkwiak, J.; Francke, A.; Visser, M.C.; Widdershoven, G.; Hertogh, C.M.P.M.

    2013-01-01

    Aims: Palliative care has potentially a lot to offer to patients in the acute phase after a severe stroke, but its deliberation and decisions towards palliative care are limited in this phase. This study aims at providing insight into the experiences of relatives of stroke patients with the care

  1. Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes.

    Directory of Open Access Journals (Sweden)

    Maxwell A Ruby

    Full Text Available Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1. Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP, perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251 and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control, IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2, which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50% the majority (303 of 533 of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and

  2. Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Kristian Løkke Funck; Dalsgaard, Jens; Grove, Erik Lerkevang

    2013-01-01

    fraction, and immature platelet count) were increased in the acute phase of STEMI compared to 3 months after PPCI (p-values STEMI despite dual antiplatelet treatment with aspirin and clopidogrel. Increased platelet......Newly produced platelets are present in the acute phase of ST-elevation myocardial infarction (STEMI). This may influence the antiplatelet effect of aspirin and clopidogrel administered prior to primary percutaneous coronary intervention (PPCI). The aims of this study were to investigate...... the antiplatelet effect of aspirin and clopidogrel and evaluate platelet turnover in the acute phase of STEMI compared to a stable phase 3 months later. In this observational follow-up study on 48 STEMI patients transferred for PPCI, loading doses of aspirin (300 mg) and clopidogrel (600 mg) were given orally...

  3. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    Directory of Open Access Journals (Sweden)

    Williams Andrew

    2009-04-01

    Full Text Available Abstract Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP and serum amyloid A (SAA in humans. In this study we test the hypothesis that diesel exhaust particles (DEP – or carbon black (CB-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005 177–182. As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap (the murine homologue of Crp and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3 responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT

  4. Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations.

    Science.gov (United States)

    Ryotokuji, Takeshi; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kurosawa, Saiko; Kobayashi, Yutaka; Kawata, Eri; Tajika, Kenji; Gomi, Seiji; Kanda, Junya; Kobayashi, Anna; Omori, Ikuko; Marumo, Atsushi; Fujiwara, Yusuke; Yui, Shunsuke; Terada, Kazuki; Fukunaga, Keiko; Hirakawa, Tsuneaki; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Tamai, Hayato; Nakayama, Kazutaka; Wakita, Satoshi; Fukuda, Takahiro; Inokuchi, Koiti

    2016-09-01

    In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (Pgene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.

  5. [cerebral Hemometabolism: Variability In The Acute Phase Of Traumatic Coma].

    OpenAIRE

    Falcão,A. L.; Araújo, S; Dragosavac, D; Terzi, R G; Thiesen, R A; Cintra, E A; Sardinha, L A; Capone Neto, A; Dantas Filho, V P; Quagliato, E M

    2015-01-01

    to evaluate the interrelationships between cerebral and systemic hemometabolic alterations in patients with severe traumatic brain injury managed according to a standardized therapeutic protocol. prospective, interventional study in patients with traumatic coma. a general Intensive Care Unit in a teaching hospital. twenty-seven patients (21M e 6F), aging 14 - 58 years, with severe acute brain trauma, presenting with three to eight points on the Glasgow Coma Scale, were prospectively evaluated...

  6. The role of the acute phase protein PTX3 in the ventilator-induced lung injury

    Directory of Open Access Journals (Sweden)

    JM Real

    2008-06-01

    Full Text Available The pentraxin 3 (PTX3 is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI, representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group were ventilated (45ml·kg–1 until respiratory system Elastance increased 50% (Ers150%, an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225. We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.

  7. Effects of anabolic steroids on acute phase responses in intra-abdominal sepsis

    Directory of Open Access Journals (Sweden)

    K. Mealy

    1997-01-01

    Full Text Available The acute phase response is an important adaptive response to sepsis and injury. As anabolic steroids increase protein synthesis we postulated that these agents might also increase hepatic acute phase protein synthesis. Male Wistar rats were pretreated with testosterone or danazol for 48 h prior to caecal ligation and puncture (CLP. Thirty-six h following surgery the animals were killed and blood taken for full blood count, total protein, albumin, α, β and γ globulin fractions on serum electrophoresis, complement C3 and transferrin levels. Danazol increased the α1, α2 and β1 globulin serum protein fractions in comparison with no surgery and CLP alone groups. These results indicate that danazol increases plasma acute phase proteins, as measured by electrophoresis, in this model of intra-abdominal sepsis.

  8. Diagnostical meaning acute phase proteins in cerebrospinal liquid in children with neuroinfections

    Directory of Open Access Journals (Sweden)

    L. A. Alekseeva

    2010-01-01

    Full Text Available In the article presented results of the examination of acute phase proteins in cerebrospinal liquid in 237 children with meningitis and encephalitis viral and bacterial etiology. The dependence between the level of acute phase proteins in cerebrospinal liquid and etiology of neuroinfectional process, the severity of brain damage and the process stage was determined. Diagnostic and prognostic efficiency of the acute phase proteins (C-reactive protein, albumin, alpha-1-antitripsin, alpha-2-macroglobulin, gaptoglobin examination in children with neuroinfections was specified. Developed method of express diagnostics of the severity of inflammatory damage of the brain in bacterial meningitis in children by determination in cerebrospinal liquid alpha-2-macroglobulin is described.

  9. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  10. Whole blood viscosity assessment issues IV: Prevalence in acute phase inflammation

    Directory of Open Access Journals (Sweden)

    Ezekiel Uba Nwose

    2010-08-01

    Full Text Available Background: Hyperviscosity syndrome has been suggested as not simply an acute reaction. Yet, erythrocyte sedimentation rate is associated with whole blood viscosity and it is an indirect acute phase inflammation marker. Aims: This work investigates the prevalence of hyperviscosity in acute phase inflammation. Materials and Methods: Archived clinical pathology data for the period of 1999 to 2008 were utilized. 40,632-cases tested for C-reactive protein and/or erythrocyte sedimentation rate from five alternate years, which were concomitantly tested for haematocrit and total proteins, were extracted. The prevalence of abnormal viscosity associated with positive results of C-reactive protein and erythrocyte sedimentation rate were evaluated. Results: Hyperviscosity is infrequently associated with positive C-reactive protein (2.9% and erythrocyte sedimentation rate (2.7% sub-populations, and are not statistically different from their respective negative sub-populations. Normoviscosity is significantly more prevalent in the positive sub-populations (p < 0.01. Further analyses indicate that prevalence of acute phase inflammation is statistically significantly less in hyperviscosity compared to normoviscosity sub-population (p < 0.00001. Actual blood viscosity level increases with level of inflammation though. Conclusion: The study demonstrates that although blood viscosity level may increase with inflammation, hyperviscosity is not frequent in, or sensitive to acute phase inflammation. It portends that whole blood viscosity is not unspecific as acute phase inflammation markers. It calls for clinicians to consider utilizing whole blood viscosity in disease conditions where stasis is implicated, in which it is specific and valuable. It would also benefit to establish whether hyperviscosity is a chronic phase inflammation marker.

  11. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl.

    Science.gov (United States)

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-07-01

    Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients.

  12. Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research

    Science.gov (United States)

    Reis, Cesar; Akyol, Onat; Ho, Wing Mann; Araujo, Camila; Huang, Lei; Applegate II, Richard

    2017-01-01

    Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments. PMID:28286764

  13. Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

    Science.gov (United States)

    Reis, Cesar; Akyol, Onat; Ho, Wing Mann; Araujo, Camila; Huang, Lei; Applegate, Richard; Zhang, John H

    2017-01-01

    Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments.

  14. Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research

    Directory of Open Access Journals (Sweden)

    Cesar Reis

    2017-01-01

    Full Text Available Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments.

  15. Acute phase reactants, challenge in the near future of animal production and veterinary medicine

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The future of acute phase proteins (APPs) in science is discussed in this paper. Many functions and associated pathological processes of APPs are unknown. Extrahepatic formation in local tissues needs attention. Local serum amyloid A (SAA) formation may be involved in deposition of AA-amyloid induced by conformational change of SAA resulting in amyloid formation, having tremendous food safety implications. Amyloidogenesis is enhanced in mouse fed beta pleated sheet-rich proteins. The local amyloid in joints of chicken and mammary corpora amylacea is discussed. Differences in glycosylation of glycoproteins among the APPs, as has been shown for α1-acid glycoprotein, have to be considered. More knowledge on the reactivity patterns may lead to implication of APPs in the diagnostics and staging of a disease. Calculation of an index from values of several acute phase variables increases the power of APPs in monitoring unhealthy individuals in animal populations.Vaccinations, just as infections in eliciting acute phase response seem to limit the profitability of vaccines because acute phase reactions are contraproductive in view of muscle anabolism. Interest is focused on amino acid patterns and vitamins in view of dietary nutrition effect on sick and convalescing animals.When inexpensive methodology such as liquid phase methods (nephelometry, turbidimetry) or protein array technology for rapid APPs measurement is available, APPs have a future in routine diagnostics. Specific groups of patients may be screened or populations monitored by using APPs.

  16. Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

    OpenAIRE

    2003-01-01

    The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component...

  17. Regulation of urea synthesis during the acute phase response in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Jessen, Niels; Buch Møller, Andreas

    2013-01-01

    of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral...... regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained...

  18. [Application of stroke rehabilitation unit in municipal hospitals during the acute phase of cerebral infarction].

    Science.gov (United States)

    Wang, Zhi-min; Wang, Peng; Chen, Jie; Luo, Dan-hong; Shen, Wang-ming

    2008-07-01

    To evaluate the efficacy of stroke rehabilitation unit in municipal hospitals during the acute phase of cerebral infarction. 77 acute cerebral infarction patients were randomly assigned to stroke rehabilitation unit group and 73 to ordinary group. The NIH stroke scale (NIHSS), activities of daily living (ADL) Barthel index and average hospitalized time were compared in two groups before and after the treatment. The average NIHSS in two groups before treatment were 9.26 and 9.12 respectively (P > 0.05) but became 2.62 and 7.64 after treatment (P 0.05) but 87.26 and 64.20 after the treatment (P stroke rehabilitation unit being applied in the acute phase of cerebral infarction, it showed positive results in the following aspects as: improving the neurological function, capabilities of managing daily life, and also shortening the days of hospitalization.

  19. Perfusion Computed Tomography in the Acute Phase of Mild Head Injury : Regional Dysfunction and Prognostic Value

    NARCIS (Netherlands)

    Metting, Zwany; Rodiger, Lars A.; Stewart, Roy E.; Oudkerk, Matthijs; De Keyser, Jacques; van der Naalt, Joukje

    2009-01-01

    Objective: Traumatic brain injury is a major Cause of disability and death. Most patients sustain a mild head injury with a subgroup that experiences disabling symptoms interfering with return to work. Brain imaging in the acute phase is not predictive of outcome, as 20% of noncontrast computed tomo

  20. Identification of Acute Phase Proteins and Assays Applicable in Nondomesticated Mammals

    DEFF Research Database (Denmark)

    Bertelsen, M. F.; Kjelgaard-Hansen, M.; Grøndahl, C.

    2009-01-01

    The serum concentration of acute phase proteins (APPs) increases dramatically in response to inflammation and tissue injury. APPs are clinically useful in a range of domesticated mammals; however, knowledge is limited in nondomesticated mammals. The detective ability of two assays for each of thr...

  1. Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

    2014-01-01

    Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this specie...

  2. In Utero Exposure to Lipopolysaccharide Alters the Postnatal Acute Phase Response in Beef Heifers

    Science.gov (United States)

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

  3. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  4. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov

    2016-01-01

    AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg/...... the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.......AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg....../kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein α-2-macroglobulin (α-2-M) 24 h after LPS. Also...

  5. Is visuospatial hemineglect really a determinant of postural control following stroke? An acute-phase study.

    NARCIS (Netherlands)

    Nes, I.J.W. van; Linden, S. van der; Hendricks, H.T.; Kuijk, A.A. van; Rulkens, M.; Verhagen, W.I.; Geurts, A.C.H.

    2009-01-01

    OBJECTIVE: The purpose of this study was to determine the independent contribution of visuospatial hemineglect to impaired postural control in the acute phase (<2 weeks) of stroke compared with other possible clinical and biological determinants. METHODS: This study was conducted in 4 hospitals i

  6. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

    NARCIS (Netherlands)

    Ruger, M; Gordijn, MCM; Beersma, DGM; de Vries, B; Daan, S

    2003-01-01

    Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to

  7. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Science.gov (United States)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  8. Renal infarct volume and renal function decline in acute and chronic phases.

    Science.gov (United States)

    Kagaya, Saeko; Yoshie, Ojima; Fukami, Hirotaka; Sato, Hiroyuki; Saito, Ayako; Takeuchi, Yoichi; Matsuda, Ken; Nagasawa, Tasuku

    2017-03-10

    Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p function decline in ARI. Therefore, assessment of infarct volume in ARI is important.

  9. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro

    NARCIS (Netherlands)

    Nijsten, MWN; Olinga, P; The, TH; de Vries, EGE; Groothuis, GMM; Limburg, PC; ten Duis, HJ; Moshage, H; Hoekstra, HJ; Bijzet, J; Zwaveling, JH; Schraffordt Koops, H.

    2000-01-01

    Objectives: Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states, PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive prote

  10. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.

    Science.gov (United States)

    Bouquet, Jerome; Soloski, Mark J; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N; Chiu, Charles Y

    2016-02-12

    Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the "window period" of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the

  11. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  12. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours

  13. Expression level of CDX2 gene in acute myeloid leukemia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    陆瀆

    2012-01-01

    Objective To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2(CDX2) gene in acute myeloid leukemia (AML) patients. Methods Real time quantitative PCR(RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features

  14. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours o

  15. The effects of grain-induced subactue ruminal acidosis on interleukin-6 and acute phase response in dairy cows

    DEFF Research Database (Denmark)

    Li, Shucong; Danscher, Anne Mette; Andersen, Pia Haubro

    2014-01-01

    Subacute ruminal acidosis (SARA) resulting from excessive grain feeding to dairy cows is accompanied by an acute phase response. Interleukin 6 (IL-6) has been proposed as a mediator of this response. We tested if the acute phase response associated with grain-induced SARA is mediated by IL-6. Six...

  16. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  17. Changes of Platelet Indices in Juvenile Idiopathic Arthritis in Acute Phase and After Two Months Treatment

    Directory of Open Access Journals (Sweden)

    Marjan Vakili

    2016-05-01

    Full Text Available Background Various indices have been raised as predictors of activity and severity of juvenile idiopathic arthritis. Objectives This study was conducted to investigate the changes of platelet indices in acute phase and two months after treatment in these patients. Patients and Methods In a cohort study, platelet count, mean platelet volume (MPV, platelet distribution width (PDW, plateletcrit (PCT were evaluated in children referred to children’s medical center, Tehran due to juvenile idiopathic arthritis from March 2013 to March 2014 during the acute phase and two months after standard treatment. The statistical data were analyzed by SPSS 19 software, and the significance level was set as P < 0.05. Results In this study, 55 children (24 boys and 31 girls with mean ± SD age of 7.50 ± 3.35 years were studied. The mean ± SD value of platelet count was 441872.7 ± 151836.9 in the acute phase and reached 395418.2 ± 119601.6 two months after treatment (P = 0.01. The mean ± SD PCT in the acute phase of various subtypes of the disease was 0.32 ± 0.11, which reached 0.29 ± 0.10 after treatment (P = 0.09. However, the PDW range in different subtypes of the disease reached 13.4 ± 8.0 from 13.9 ± 2.9 and MPV reached 8.7 ± 0.9 from 8.8 ± 1.1 after treatment, but they were not significantly different from the results in the acute phase (P = 0.5. Conclusions Platelet count is one of the most remarkable indices in JIA. Evaluation of PCT can also help determine the severity of the inflammatory process in the follow-up and treatment process.

  18. Muscle Contraction Induces Acute Hydroxymethylation of the Exercise-Responsive Gene Nr4a3

    DEFF Research Database (Denmark)

    Pattamaprapanont, Pattarawan; Garde, Christian; Fabre, Odile

    2016-01-01

    promoters. Exercise induces dynamic DNA demethylation at gene promoters; however, the contribution of the demethylation precursor hydroxymethylcytosine is unknown. Given the evanescent nature of hydroxymethylcytosine, a muscle contraction model that allows for the collection of samples that are repeatedly...... stimulated over time is required to determine whether contraction-induced demethylation is preceded by changes in the hydroxymethylcytosine level. Here, we established an acute skeletal muscle contraction model to mimic the effects of acute exercise on gene expression. We used this model to investigate...... the effect of muscle contraction on DNA demethylation and hydroxymethylation. First, we performed an acute exercise study in healthy humans to identify an exercise-responsive gene that we could study in culture. We identified the nuclear receptor subfamily 4 group A member 3 (Nr4a3) gene with the highest...

  19. 儿童过敏性紫瘢急性期FOXP3表达及其意义分析%The FOXP3 gene expression in children with Henoch-Schonlein purpura during acute phase and analysis of its significance

    Institute of Scientific and Technical Information of China (English)

    马继军; 宋力; 胡坚

    2011-01-01

    Objective This study aimed to explore the relationship between the gene expression of FOXP3 and the pathogenesis of Henoch-Schonlein purpura in children during the acute phase. Methods The mRNA expression of FOXP3 in the peripheral blood determined in 50 HSP children(HSP group) ,34 KD children(KD group and 50 children who would receive tonsilleetomy with normal physical examination (control group) respectively. Results Altogether 44 cases were included in the final statistical anaylsis, 17 in HSP group, 14 in KD group and 13 in control group. The mRNA expression of FOXP3 in patients with HSP was remarkably decreased compared to the healthy controls, and there was significant difference between the two groups (P 0.05). Conclusion The decrease of FOXP3 expression might be the indication of immune imsbalance of systematic vasculitis in children, not the specific manifestation of HSP.%目的 探讨过敏性紫瘢(HSP)患儿急性期外周血白细胞转录因子FOXP3基因表达情况及其与发病机制间的关系.方法 2008年11月至2009年4月在天津市儿童医院风湿免疫科住院的HSP患儿(HSP组)50例、KD患儿(KD组)34例及门诊择期行扁桃体切除术体检无异常儿童(对照组)50例,检测其外周血白细胞FOXP3 mRNA表达(别除非特异性扩增标本).结果 3组共计44例最终进入统计学分析,其中HSP组17例,KD组14例,对照组13例.HSP组急性期外周血白细胞FOXP3 mRNA的表达与对照组比较显著降低,差异有统计学意义(P 0.05).结论 FOXP3表达减低可能为导致儿童期系统性血管炎免疫失衡的共同原因,但并非HSP的特异性改变.

  20. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling.

    Science.gov (United States)

    Verhaak, Roel G W; Wouters, Bas J; Erpelinck, Claudia A J; Abbas, Saman; Beverloo, H Berna; Lugthart, Sanne; Löwenberg, Bob; Delwel, Ruud; Valk, Peter J M

    2009-01-01

    We examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific molecular subtypes. The favorable cytogenetic acute myeloid leukemia subtypes, i.e., acute myeloid leukemia with t(8;21), t(15;17) or inv(16), were predicted with maximum accuracy (positive and negative predictive value: 100%). Mutations in NPM1 and CEBPA were predicted less accurately (positive predictive value: 66% and 100%, and negative predictive value: 99% and 97% respectively). Various other characteristic molecular acute myeloid leukemia subtypes, i.e., mutant FLT3 and RAS, abnormalities involving 11q23, -5/5q-, -7/7q-, abnormalities involving 3q (abn3q) and t(9;22), could not be correctly predicted using gene expression profiling. In conclusion, gene expression profiling allows accurate prediction of certain acute myeloid leukemia subtypes, e.g. those characterized by expression of chimeric transcription factors. However, detection of mutations affecting signaling molecules and numerical abnormalities still requires alternative molecular methods.

  1. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  2. A potentially novel overlapping gene in the genomes of Israeli acute paralysis virus and its relatives

    Directory of Open Access Journals (Sweden)

    Price Nicholas

    2009-09-01

    Full Text Available Abstract The Israeli acute paralysis virus (IAPV is a honeybee-infecting virus that was found to be associated with colony collapse disorder. The IAPV genome contains two genes encoding a structural and a nonstructural polyprotein. We applied a recently developed method for the estimation of selection in overlapping genes to detect purifying selection and, hence, functionality. We provide evolutionary evidence for the existence of a functional overlapping gene, which is translated in the +1 reading frame of the structural polyprotein gene. Conserved orthologs of this putative gene, which we provisionally call pog (predicted overlapping gene, were also found in the genomes of a monophyletic clade of dicistroviruses that includes IAPV, acute bee paralysis virus, Kashmir bee virus, and Solenopsis invicta (red imported fire ant virus 1.

  3. Aripiprazole in the acute and maintenance phase of bipolar I disorder.

    Science.gov (United States)

    Zupancic, Melanie; Gonzalez, Misty L

    2012-01-01

    Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents.

  4. Development of gene expression markers of acute heat-light stress in reef-building corals of the genus Porites.

    Directory of Open Access Journals (Sweden)

    Carly D Kenkel

    Full Text Available Coral reefs are declining worldwide due to increased incidence of climate-induced coral bleaching, which will have widespread biodiversity and economic impacts. A simple method to measure the sub-bleaching level of heat-light stress experienced by corals would greatly inform reef management practices by making it possible to assess the distribution of bleaching risks among individual reef sites. Gene expression analysis based on quantitative PCR (qPCR can be used as a diagnostic tool to determine coral condition in situ. We evaluated the expression of 13 candidate genes during heat-light stress in a common Caribbean coral Porites astreoides, and observed strong and consistent changes in gene expression in two independent experiments. Furthermore, we found that the apparent return to baseline expression levels during a recovery phase was rapid, despite visible signs of colony bleaching. We show that the response to acute heat-light stress in P. astreoides can be monitored by measuring the difference in expression of only two genes: Hsp16 and actin. We demonstrate that this assay discriminates between corals sampled from two field sites experiencing different temperatures. We also show that the assay is applicable to an Indo-Pacific congener, P. lobata, and therefore could potentially be used to diagnose acute heat-light stress on coral reefs worldwide.

  5. Acute toxicity study of a simian immunodeficiency virus-based lentiviral vector for retinal gene transfer in nonhuman primates.

    Science.gov (United States)

    Ikeda, Yasuhiro; Yonemitsu, Yoshikazu; Miyazaki, Masanori; Kohno, Ri-ichiro; Murakami, Yusuke; Murata, Toshinori; Goto, Yoshinobu; Tabata, Toshiaki; Ueda, Yasuji; Ono, Fumiko; Suzuki, Toshimichi; Ageyama, Naohide; Terao, Keiji; Hasegawa, Mamoru; Sueishi, Katsuo; Ishibashi, Tatsuro

    2009-09-01

    A phase 1 clinical trial evaluating the safety of gene therapy for patients with wet age-related macular degeneration (AMD) or retinoblastoma has been completed without problems. The efficacy of gene therapy for Leber's congenital amaurosis (LCA) was reported by three groups. Gene therapy may thus hold promise as a therapeutic method for the treatment of intractable ocular diseases. However, it will first be important to precisely evaluate the efficiency and safety of alternative gene transfer vectors in a preclinical study using large animals. In the present study, we evaluated the acute local (ophthalmic) and systemic toxicity of our simian immunodeficiency virus from African green monkeys (SIVagm)-based lentiviral vectors carrying human pigment epithelium-derived factor (SIV-hPEDF) for transferring genes into nonhuman primate retinas. Transient inflammation and elevation of intraocular pressure were observed in some animals, but these effects were not dose dependent. Electroretinograms (ERGs), including multifocal ERGs, revealed no remarkable change in retinal function. Histopathologically, SIV-hPEDF administration resulted in a certain degree of inflammatory reaction and no apparent structural destruction in retinal tissue. Regarding systemic toxicity, none of the animals died, and none showed any serious side effects during the experimental course. No vector leakage was detected in serum or urine samples. We thus propose that SIVagm-mediated stable gene transfer might be useful and safe for ocular gene transfer in a clinical setting.

  6. The acute phase protein Serum Amyloid A induces lipolysis and inflammation in human adipocytes through distinct pathways.

    Directory of Open Access Journals (Sweden)

    Aurélie Faty

    Full Text Available BACKGROUND: The acute phase response (APR is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA is an acute phase protein mainly associated with High Density Lipoproteins (HDL. We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: In vitro differentiated human adipocytes (hMADS were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARγ2, C/EBPα and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-κB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes. CONCLUSIONS/SIGNIFICANCE: Besides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insulin resistant states.

  7. Combined use of transmyocardial stents with gene therapy in the treatment of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    王永武

    2006-01-01

    Objective To determine the efficacy of combined use of transmyocardial stent with gene therapy to treat acute myocardial infarction in porcine model. Methods 24 Chinese mini swines have been devided into 4 groups randomly: group myocardial infarction (group MI n1 = 6), group transmyocardial stent (group ST n2 = 6) , group vascular endothelial growth factor (group VEGF n3 = 6) , group transmyocardial stent and VEGF (group ST + VEGF n4 = 6). In group MI,acute myocardial infarc-

  8. PROGNOSTIC VALUE OF BRAIN AND ACUTE LEUKEMIA CYTOPLASMIC GENE EXPRESSION IN EGYPTIAN CHILDREN WITH ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    adel abd elhaleim hagag

    2015-04-01

    Full Text Available Abstract      Background: Acute myeloid leukemia (AML accounts for 25%-35% of the acute leukemia in children. BAALC (Brain and Acute Leukemia, Cytoplasmic gene is a recently identified gene on chromosome 8q22.3 that has prognostic significance in AML.  The aim of this work was to study the impact of BAALC gene expression on prognosis of AML in Egyptian children. Patients and methods: This study was conducted on 40 patients of newly diagnosed AML who were subjected to the following: Full history taking, clinical examination, laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry and immunophenotyping, assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results: BAALC gene expression showed positive expression in 24 cases (60% and negative expression in 16 cases (40%. Patients who showed positive BAALC gene expression included 10 patients achieved complete remission, 8 patients died and 6 relapsed patients, while patients who showed negative expression include 12 patients achieved complete remission, 1 relapsed patient and 3 patients died. There was significant association between BAALC gene expression and FAB classification of patients of AML patientsas positive BAALC expression is predominantly seen in FAB subtypes M1 and M2 compared with negative BAALC gene expression that was found more in M3 and M4 (8 cases with M1, 12 cases with M2, 1 case with M3 and 3 cases with M4 in positive BAALC expression versus 2 cases with M1, 3 cases with M2, 4 cases with M3 and 7 cases with M4 in BAALC gene negative expression group with significant difference regarding FAB subtypes. As regard age, sex, splenomegaly, lymphadenopathy, pallor, purpura, platelets count, WBCs count, and percentage of blast cells in BM, the present study showed no significant association with BAALC. Conclusion: BAALC expression is an important prognostic factor in AML

  9. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    Directory of Open Access Journals (Sweden)

    Saatsi Johanna

    2008-06-01

    Full Text Available Abstract Background Acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary

  10. Age- and sex-associated effects on acute-phase proteins in Göttingen minipigs

    DEFF Research Database (Denmark)

    Christoffersen, Berit Ø.; Jensen, Søren Juel; Ludvigsen, Trine P.;

    2015-01-01

    Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP......, haptoglobin and PAGP and a decrease in albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP was unchanged and albumin decreased. Obese pigs with and without diabetes showed increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were unchanged. PMAP was increased only...... and interpreting studies including aspects of inflammation. In addition, an APP response was verified after both acute and chronic stimuli....

  11. Age- and Sex-Associated Effects on Acute-Phase Proteins in Göttingen Minipigs

    DEFF Research Database (Denmark)

    Christoffersen, Berit Ø; Jensen, Søren J.; Ludvigsen, Trine P;

    2015-01-01

    Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP......, haptoglobin and PAGP and a decrease in albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP was unchanged and albumin decreased. Obese pigs with and without diabetes showed increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were unchanged. PMAP was increased only...... and interpreting studies including aspects of inflammation. In addition, an APP response was verified after both acute and chronic stimuli....

  12. Aripiprazole in the acute and maintenance phase of bipolar I disorder

    Directory of Open Access Journals (Sweden)

    Zupancic M

    2012-01-01

    Full Text Available Melanie Zupancic1, Misty L Gonzalez2,31Southern Illinois University School of Medicine, 2Division of Medicine Psychiatry, Southern Illinois University School of Medicine, 3Southern Illinois University Edwardsville School of Pharmacy, Southern Illinois University Edwardsville, Springfield, IL, USAAbstract: Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents.Keywords: aripiprazole, bipolar disorder, acute treatment, maintenance treatment

  13. Phase transitions in the evolution of gene regulatory networks

    Science.gov (United States)

    Skanata, Antun; Kussell, Edo

    The role of gene regulatory networks is to respond to environmental conditions and optimize growth of the cell. A typical example is found in bacteria, where metabolic genes are activated in response to nutrient availability, and are subsequently turned off to conserve energy when their specific substrates are depleted. However, in fluctuating environmental conditions, regulatory networks could experience strong evolutionary pressures not only to turn the right genes on and off, but also to respond optimally under a wide spectrum of fluctuation timescales. The outcome of evolution is predicted by the long-term growth rate, which differentiates between optimal strategies. Here we present an analytic computation of the long-term growth rate in randomly fluctuating environments, by using mean-field and higher order expansion in the environmental history. We find that optimal strategies correspond to distinct regions in the phase space of fluctuations, separated by first and second order phase transitions. The statistics of environmental randomness are shown to dictate the possible evolutionary modes, which either change the structure of the regulatory network abruptly, or gradually modify and tune the interactions between its components.

  14. Caerulin-induced pancreatitis in rats: Histological and genetic expression changes from acute phase to recuperation

    Institute of Scientific and Technical Information of China (English)

    Javier Maga(n)a-Gómez; Guillermo López-Cervantes; Ana María Calderón de la Barca

    2006-01-01

    AIM: To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats.METHODS: Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histologicai and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema (E), polymorphonuclear neutrophil (PMN) infiltration, cytoplasmic vacuolization (V), zymogen granule depletion (ZD) and acinar disorganization (AD) were microscopically evaluated. Accumulation of pancreatitisassociated protein (PAP) and L13A mRNAs were quantifled by real-time PCR.RESULTS: The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d.CONCLUSION: From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pancreas occur and PAP expression is exclusively an acute response of pancreatitis.

  15. Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma.

    Directory of Open Access Journals (Sweden)

    Jason D Christie

    Full Text Available Acute Lung Injury (ALI is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1, we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs at p<0.01 to a replication phase (Phase 2 comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3 using expression quantitative trait loci (eQTL analyses in stimulated B-lymphoblastoid cell lines (B-LCL in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021. PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.

  16. Serotonin, calcitonin and calcitonin gene-related peptide in acute pancreatitis

    DEFF Research Database (Denmark)

    Wahlstrøm, Kirsten Lykke; Novovic, Srdan; Ersbøll, Annette Kjær

    2017-01-01

    OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients with alco......OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients...... dysfunction. We hypothesize that serotonin plays a pathogenic role in the compromised pancreatic microcirculation, and calcitonin a role as a biomarker of severity in AP....

  17. Optimal combinations of acute phase proteins for detecting infectious disease in pigs

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Stockmarr, Anders; Piñeiro, Matilde

    2011-01-01

    gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative......The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect...... for single APPs and for APP combinations. Combinations of APPs allowed the detection of disease more sensitively than any individual APP and the best three-protein combinations were CRP, apoA1, pigMAP and CRP, apoA1, Hp, respectively, closely followed by the two-protein combinations CRP, pigMAP and apoA1...

  18. Age- and Sex-Associated Effects on Acute-Phase Proteins in Göttingen Minipigs

    DEFF Research Database (Denmark)

    Christoffersen, Berit Ø; Jensen, Søren J.; Ludvigsen, Trine P

    2015-01-01

    Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP...... in Göttingen minipigs and to investigate the effects of age, sex, and various stimuli on these ranges. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, pig major acute-phase protein (PMAP), albumin, and porcine α-1 acid glycoprotein (PAGP) were evaluated in 4 age groups (6...... in obese pigs without diabetes. In conclusion, reference values for CRP, PMAP, haptoglobin, SAA, PAGP and albumin were established for male and female Göttingen minipigs of different ages. These APP were influenced by age and sex, underlining the importance of considering these factors when designing...

  19. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis

    DEFF Research Database (Denmark)

    Eckersall, P D; Young, F J; Nolan, A M

    2006-01-01

    The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp...... and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M......-SAA3 in mammary tissues was determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring 3 d after infusion of the bacteria. The increase of acute phase proteins in milk (15 h) preceded the increase...

  20. The bovine acute phase response to endotoxin and Gram-negative bacteria

    DEFF Research Database (Denmark)

    Jacobsen, Stine

    The overall aims of the work presented in this thesis were to characterize bovine cytokine and acute phase protein (APP) responses to lipopolysaccharide (LPS) and to investigate how LPS-induced clinical and immunoinflammatory responses differed between individual cows. Two kinds of experimental...... from the udder. APP measurements in milk may therefore have great potential as mastitis diagnostics. Milk and plasma SAA concentrations seemed to be higher in cows with severe mastitis than in cows with moderate or mild mastitis, which suggests that SAA levels reflect severity of udder infection (Paper...... the pathogenesis of bovine acute phase response and the biologically relevant functions of central reactants such as cytokines and APPs. Cytokines are known to induce pathophysiological changes and SAA and haptoglobin have also been suggested to be important modulators of the inflammatory response. Success...

  1. 'Living a life in shades of grey': experiencing depressive symptoms in the acute phase after stroke.

    Science.gov (United States)

    Kouwenhoven, Siren E; Kirkevold, Marit; Engedal, Knut; Kim, Hesook S

    2012-08-01

    The aim of the present study was to describe the lived experience of stroke survivors suffering from depressive symptoms in the acute phase; addressing the following questions: (a) what is the nature of depression as experienced by post-stroke patients in the acute phase? (b) what is it like to live with depression within the first weeks following stroke? Post-stroke depression occurs in at least one quarter of stroke survivors and is linked to poorer outcomes. This qualitative study is methodologically grounded in hermeneutic phenomenology, influenced by van Manen and Ricoeur. A descriptive, qualitative design was used applying in-depth interviews as the method of data collection with nine participants. The data collection took place in 2008. The material revealed two main themes that generate the feeling and description of 'living a life in shades of grey': (a) being trapped and (b) losing oneself. 'Shades of grey' could be understood as being confined in a new life-world and losing oneself as the person one knew. The participants confirmed suffering from depressive symptoms, but depression was not seen as meaningful on its own. They related their experiences of post-stroke depression in the acute phase to the losses they experienced. Nurses ought to take into account the depth of the life changes that stroke survivors may experience. There is a need for continued empirical research on how nurses may help and support stroke survivors dealing with depressive symptoms in the acute phase after stroke and how depressive symptoms develop over time. © 2011 Blackwell Publishing Ltd.

  2. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

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    Wittwer Matthias

    2006-06-01

    Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential

  3. Temporal gene expression profile after acute electroconvulsive stimulation in the rat.

    Science.gov (United States)

    Dyrvig, Mads; Christiansen, Søren H; Woldbye, David P D; Lichota, Jacek

    2014-04-10

    Electroconvulsive therapy (ECT) remains one of the most effective treatments of major depression. It has been suggested that the mechanisms of action involve gene expression. In recent decades there have been several investigations of gene expression following both acute and chronic electroconvulsive stimulation (ECS). These studies have focused on several distinct gene targets but have generally included only few time points after ECS for measuring gene expression. Here we measured gene expression of three types of genes: Immediate early genes, synaptic proteins, and neuropeptides at six time points following an acute ECS. We find significant increases for c-Fos, Egr1, Neuritin 1 (Nrn 1), Bdnf, Snap29, Synaptotagmin III (Syt 3), Synapsin I (Syn 1), and Psd95 at differing time points after ECS. For some genes these changes are prolonged whereas for others they are transient. Npy expression significantly increases whereas the gene expression of its receptors Npy1r, Npy2r, and Npy5r initially decreases. These decreases are followed by a significant increase for Npy2r, suggesting anticonvulsive adaptations following seizures. In summary, we find distinct changes in mRNA quantities that are characteristic for each gene. Considering the observed transitory and inverse changes in expression patterns, these data underline the importance of conducting measurements at several time points post-ECS.

  4. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

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    Waller K Persson

    2004-06-01

    Full Text Available Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP haptoglobin, serum amyloid A (SAA and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I 250 D. viviparus infective third stage larvae (L3 once daily for 2 consecutive days, II 100 D. viviparus L3 once daily for 5 consecutive days, and III 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals.

  5. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    Directory of Open Access Journals (Sweden)

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  6. Acute-phase inflammatory response in idiopathic sudden deafness: pathogenic implications.

    Science.gov (United States)

    López-González, Miguel A; Abrante, Antonio; López-Lorente, Carmen; Gómez, Antonio; Domínguez, Emilio; Esteban, Francisco

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48-72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  7. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    Directory of Open Access Journals (Sweden)

    Miguel A. López-González

    2012-01-01

    Full Text Available The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  8. Presence of an acute phase response in sheep with clinical classical scrapie

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    Meling Siv

    2012-07-01

    Full Text Available Abstract Background Work with experimental scrapie in sheep has been performed on-site for many years including studies on PrPSc dissemination and histopathology of organs and tissues both at preclinical and clinical stages. In this work serum was sampled at regular intervals from lambs which were infected immediately after birth and from parallel healthy controls, and examined for acute phase proteins. In contrast to earlier experiments, which extensively studied PrPSc dissemination and histopathology in peripheral tissues and brain, this experiment is focusing on examination of serum for non-PrPSc markers that discriminates the two groups, and give insight into other on-going processes detectable in serum samples. Results There was clear evidence of an acute phase response in sheep with clinical scrapie, both experimental and natural. All the three proteins, ceruloplasmin, haptoglobin and serum amyloid A, were increased at the clinical stage of scrapie. Conclusion There was evidence of a systemic measurable acute phase response at the clinical terminal end-stage of classical scrapie.

  9. Correlation of oral health of children with acute leukemia during the induction phase

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    Kanchan P. Dholam

    2014-01-01

    Full Text Available Background: Treatment of acute leukemia′s- a common childhood malignancy, involves intensive and powerful multi-drug chemotherapeutic regime. Oral lesions are a common complication in these patients affecting oral health status. Aim: This study was conducted to evaluate and assess the oral health status of newly diagnosed leukemic pediatric patients during induction phase and its correlation to outcome of induction therapy. Material Methods: Oral examinations was done in 33 children between the age group of 5-15 years with acute lymphoblastic leukemia (ALL and acute myloblastic leukemia (AML, who were undergoing chemotherapy. Oral Hygiene Index- Simplified, (OHI-S decayed missing filled teeth index (def/DMFT, Loe and Sillness index for gingiva, and complete blood count at first and fourth week of induction phase were recorded for each patient. The changes in the oral health status were analyzed with Wilcoxon signed rank test. Results: During an induction phase it was observed that level of OHI-S (P = 0.002, Loe and Sillness index (P = 0.003, def/DMFT index (P = 0.076, platelet count (P = 0.00 increased significantly and no significant difference was noted in hemoglobin (P = 0.4 and total leucocytes count (P = 0.11. Conclusion: It was observed that, although oral health status had significantly worsened, the induction outcome was not affected.

  10. The effect of lunar phases on the occurrence of acute cardiovascular diseases

    Science.gov (United States)

    Chertoprud, V. E.; Gurfinkel', Yu. I.; Goncharova, E. E.; Ivanov-Kholodnyi, G. S.; Kanonidi, H. D.; Mitrofanova, T. A.; Trubina, M. A.

    2012-12-01

    This paper analyzes the possible impact of lunar phases on the dynamics of acute cardiovascular diseases: acute myocardial infarctions (MIs) and acute brain strokes (BSs) at different levels of heliogeomagnetic activity. The superposed epoch analysis (SEA) has been applied with dates of the new moon and full moon used as reference days. A statistical analysis of a 14-year-long (1992 to 2005) series of everyday medical data from the Central Clinical Hospital no. 1 of Russian Railways (Moscow) and the parameters of heliogeomagnetic activity was carried out. It was found that daily occurrences of MIs and BSs vary with the phase of the moon. These variations are significant; they continue at different levels of heliogeomagnetic activity and are not related to the variations in geomagnetic activity identified by the same method. The effect of lunar phases on MIs and BSs is quite different. New moons and full moons have qualitatively the same effect on MIs; however, there are significant differences in the incidence of BSs during new moons and full moons.

  11. Manifestation of Latent Left Ventricular Outflow Tract Obstruction in the Acute Phase of Takotsubo Cardiomyopathy

    Science.gov (United States)

    Ozaki, Kazuyuki; Okubo, Takeshi; Tanaka, Komei; Hosaka, Yukio; Tsuchida, Keiichi; Takahashi, Kazuyoshi; Oda, Hirotaka; Minamino, Tohru

    2016-01-01

    Objective Left ventricular outflow tract (LVOT) obstruction is a complication in 15-25% of patients with Takotsubo cardiomyopathy and sometimes leads to catastrophic outcomes, such as cardiogenic shock or cardiac rupture. However, the underlying mechanisms have not been clarified. Methods and Results We experienced 22 cases of Takotsubo cardiomyopathy during 3 years, and 4 of these 22 cases were complicated with LVOT obstruction in the acute phase (mean age 79±5 years, 1 man, 21 women). The LVOT pressure gradient in the acute phase was 100±17 mmHg. Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy (LVH) in one case and sigmoid-shaped septum without LVH in three cases. The complete resolution of the LVOT obstruction was achieved in a few days with normalization of the left ventricular wall motion following administration of beta-blockers. A dobutamine provocation test after normalization of the left ventricular wall motion reproduced the LVOT obstruction in all cases and revealed the presence of latent LVOT obstruction. Conclusion The manifestation of latent LVOT obstruction in the acute phase of Takotsubo cardiomyopathy is one potential reason for the complication of LVOT obstruction with Takotsubo cardiomyopathy. PMID:27904102

  12. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD.

    Science.gov (United States)

    Socié, Gérard; Vigouroux, Stéphane; Yakoub-Agha, Ibrahim; Bay, Jacques-Olivier; Fürst, Sabine; Bilger, Karin; Suarez, Felipe; Michallet, Mauricette; Bron, Dominique; Gard, Philippe; Medeghri, Zakaria; Lehert, Philippe; Lai, Chinglin; Corn, Tim; Vernant, Jean-Paul

    2017-02-02

    Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.

  13. Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

    Science.gov (United States)

    Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

    2017-04-01

    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

  14. In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile.

    Directory of Open Access Journals (Sweden)

    Michael J Sorich

    2008-04-01

    Full Text Available Childhood acute lymphoblastic leukemia (ALL is the most common cancer in children, and can now be cured in approximately 80% of patients. Nevertheless, drug resistance is the major cause of treatment failure in children with ALL. The drug methotrexate (MTX, which is widely used to treat many human cancers, is used in essentially all treatment protocols worldwide for newly diagnosed ALL. Although MTX has been extensively studied for many years, relatively little is known about mechanisms of de novo resistance in primary cancer cells, including leukemia cells. This lack of knowledge is due in part to the fact that existing in vitro methods are not sufficiently reliable to permit assessment of MTX resistance in primary ALL cells. Therefore, we measured the in vivo antileukemic effects of MTX and identified genes whose expression differed significantly in patients with a good versus poor response to MTX.We utilized measures of decreased circulating leukemia cells of 293 newly diagnosed children after initial "up-front" in vivo MTX treatment (1 g/m(2 to elucidate interpatient differences in the antileukemic effects of MTX. To identify genomic determinants of these effects, we performed a genome-wide assessment of gene expression in primary ALL cells from 161 of these newly diagnosed children (1-18 y. We identified 48 genes and two cDNA clones whose expression was significantly related to the reduction of circulating leukemia cells after initial in vivo treatment with MTX. This finding was validated in an independent cohort of children with ALL. Furthermore, this measure of initial MTX in vivo response and the associated gene expression pattern were predictive of long-term disease-free survival (p < 0.001, p = 0.02.Together, these data provide new insights into the genomic basis of MTX resistance and interpatient differences in MTX response, pointing to new strategies to overcome MTX resistance in childhood ALL.Total XV, Therapy for Newly Diagnosed

  15. Maternal acute lymphoctic leukemia with rearrangement of the mixed lineage leukemia gene occurring during pregnancy.

    Science.gov (United States)

    Aljurf, Mahmoud; Nassar, Amr; Saleh, Abu J; Almhareb, Fahed; Alzahrani, Hazzaa; Walter, Claudia; Bakr, Mohammad; Ahmed, Syed Osman; Chaudhri, Naeem

    2009-01-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases.

  16. Modulation of Gene Expression Networks underlying Realgar-Induced Differentiation of Acute Promyelocytic Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    王怀宇; 刘陕西

    2002-01-01

    Objective: To elucidate the molecular mechanism of the differentiation of acute promyelocytic leukemia (APL) cell line NB4 induced by realgar. Methods: The response of NB4 cell to realgar was explored with a cDNA microarray representing 1003 different human genes. Results: The analysis of gene expression profiles indicated that 8 genes were up-regulated and 33 genes were down-regulated 48 hrs after realgar treatment. Among the 8 up-regulated genes, 2 genes were involved in ubiquitin proteasome degradation pathway. Some genes related to RNA processing, protein synthesis and signal transduction were down-regulated. Conclusion: The ubiquitin-proteasome degradation pathway may play an important role in the degradation of PML/RAR α fusion protein and the differentiation of NB4 cells.

  17. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    OpenAIRE

    Idalia Garza-Veloz; Margarita L. Martinez-Fierro; Jose Carlos Jaime-Perez; Karol Carrillo-Sanchez; Maria Guadalupe Ramos-Del Hoyo; Angel Lugo-Trampe; Augusto Rojas-Martinez; Cesar Homero Gutierrez-Aguirre; Oscar Gonzalez-Llano; Rosario Salazar-Riojas; Alfredo Hidalgo-Miranda; David Gomez-Almaguer; Rocio Ortiz-Lopez

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by...

  18. Exploring the molecular mechanism of acute heat stress exposure in broiler chickens using gene expression profiling.

    Science.gov (United States)

    Luo, Q B; Song, X Y; Ji, C L; Zhang, X Q; Zhang, D X

    2014-08-10

    The process of heat regulation is complex and its exact molecular mechanism is not fully understood. In this study, to investigate the global gene regulation response to acute heat exposure, gene microarrays were exploited to analyze the effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow broiler chicken (Gallus gallus). We detected 166 differentially expressed genes (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these genes were differentially expressed in all three tissues and were validated by qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1) and the hunger and energy metabolism related gene (PDK). All these genes might be important factors in chickens suffering from heat stress. We constructed gene co-expression networks using the DEGs of the brain, leg muscle and liver and two, four and two gene co-expression modules were identified in these tissues, respectively. Functional enrichment of these gene modules revealed that various functional clusters were related to the effects of heat stress, including those for cytoskeleton, extracellular space, ion binding and energy metabolism. We concluded that these genes and functional clusters might be important factors in chickens under acute heat stress. Further in-depth research on the newly discovered heat-related genes and functional clusters is required to fully understand their molecular functions in thermoregulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Trajectories of sleep changes during the acute phase of traumatic brain injury: A 7-day actigraphy study

    Directory of Open Access Journals (Sweden)

    Hsiao-Yean Chiu

    2013-09-01

    Conclusion: Poor sleep efficiency and longer sleep duration are common symptoms in acute TBI patients. Both head injury severity and age predicted the trajectories of daytime and 24-hour sleep duration during the acute phase of TBI, whereas gender predicted the trajectories of 24-hour sleep duration in the mild TBI subgroup.

  20. Oncogenes, protooncogenes, and tumor suppressor genes in acute myelogenous leukemia.

    Science.gov (United States)

    Hijiya, N; Gewirtz, A M

    1995-05-01

    In recent years, our understanding of normal human hematopoiesis has expanded greatly. We have increased our knowledge of regulatory growth factors, the receptors through which they act, and the secondary messengers involved in transducing the growth/differentiation signals from the cytoplasmic membrane to the nucleus. This knowledge has revealed potential mechanisms for inducing the neoplastic transformation of hematopoietic cells. This applies in particular to the role of viral oncogenes and cellular protooncogenes and, more recently, to the role of tumor suppressor genes. Protooncogenes are intimately involved in the processes of cell proliferation and differentiation. Therefore, any amplification, mutation, structural alteration, or change in transcriptional regulation of protooncogenes might lead to or be associated with induction of the malignant phenotype. Based on the importance of these genes in leukemogenesis and the maintenance of the malignant phenotype, it seems reasonable to hypothesize that targeted disruption of leukemogenic genes may be of therapeutic value.

  1. [Research Advances of IDH2 Gene Mutation in Acute Myeloid Leukemia].

    Science.gov (United States)

    Zhao, Yan-Xia; Shen, Xu-Liang

    2016-04-01

    Acute myeloid leukemia (AML) is a malignant clonal hematologic disease from hematopoietic stem and progenitor cells. The isocitrate dehychogenase 2 (IDH2) gene mutation has been recently found, which may be associated with the course of AML. The incidence of IDH2 gene mutation in the patients with acute myeloid leukemia is high, especially in the AML patients with normal karyotype. Different subtypes of IDH2 mutation, or companing other molecular biology, will make different influence on clinical features and progress of patients with AML. IDH2 mutation is stable, which can be used as the test sign of AML and minimal residual disease (MRD), and for guiding the clinical treatment and predicting the progress. In this article, the research progress of IDH2 mutation in acute myeloid leukemia is reviewed.

  2. Comparative Analyses of Signature Genes in Acute Rejection and Operational Tolerance.

    Science.gov (United States)

    Choi, Jeong-Woo; Kim, Yong-Hee; Oh, Ji Won

    2017-08-01

    Using biomarkers as prediction tools or therapeutic targets can be a valuable strategy in transplantation. Recent studies identified biomarkers of acute rejection (AR) and operational tolerance (TOL) through the application of meta-analysis. In this study, we comparatively analyzed the signature genes in acute rejection and operational tolerance seen in human allogeneic transplantations using massive bioinformatical meta-analysis. To identify the signature genes in opposite immunological conditions, AR and TOL, we first collected the 1,252 gene expression data specifically intended for those circumstances. Then we excluded based on biological cut-values, Principal Component Analysis (PCA) as well as Multi-Dimensional Scaling (MDS). Using differentially expressed genes (DEGs) from meta-analysis, we then applied a ranked scoring system to identify the signature genes of AR and TOL. We identified 53 up-regulated and 32 down-regulated signature genes in acute rejection condition. Among them, ISG20, CXCL9, CXCL10, CCL19, FCER1G, PMSE1, UBD are highly expressed in AR condition. In operational tolerance, we identified 110 up-regulated and 48 down-regulated signature genes. TCL1A, BLNK, MS4A1, EBF1, IGHM are up-regulated in TOL condition. These genes are highly representative of AR or TOL across the different organs such as liver, kidney and heart. Since immune response is the sum of complex biological and molecular dynamics, these signature genes as well as pathway analysis using a systems biology approach could be used to catch the insights of the certain pathways that would be overlooked with the conventional gene-level comparative analysis.

  3. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  4. Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    冯广迅

    2013-01-01

    Objective To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes(CYP2C19,ABCB1 and PON1) in Chinese patients with acute coronary syndrome(ACS) by genotype analysis. Methods Genetic analysis was performed in patients admitted to

  5. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Mahyar Bahrami

    2015-05-13

    May 13, 2015 ... morphism (rs320) is located in position 495 of LPL gene's intron 8th. In this ... a control group, 203 age-matched individuals with normal coronary .... motifs for Ascl2 and NHLH1 transcription factor binding sites. (Fig 1) [29].

  6. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    DEFF Research Database (Denmark)

    Saber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction...... epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk...

  7. Acute phase proteins in dogs naturally infected with the Giant Kidney Worm (Dioctophyme renale)

    DEFF Research Database (Denmark)

    Schmidt, Elizabeth M. S.; Kjelgaard-Hansen, Mads; Thomas, Funmilola

    2016-01-01

    Background: Dioctophyme renale is a nematode parasite of dogs, usually found in the right kidney, causing severe damage to the renal parenchyma. Objectives: The objective was to evaluate the acute phase response in dogs naturally infected with this Giant Kidney Worm and the possible effects of ne...... of parasites and APP concentrations. Conclusion: There is a particular acute phase response profile in dogs with kidney worm infection. Nephrectomy induced a short-term inflammatory process....

  8. Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

    Directory of Open Access Journals (Sweden)

    Intskirveli Nino

    2011-03-01

    Full Text Available Abstract Background Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage. Methods Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0. Results At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P Conclusion According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.

  9. [Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy].

    Science.gov (United States)

    de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

    2014-12-01

    The aim of this study was to assess the pulmonary function of children with acute leukemia. Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(®) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(®)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Are there differences in acute phase inflammation markers regarding the type of heart failure?

    Directory of Open Access Journals (Sweden)

    Jaime Agüero-Ramón-Llin

    2011-09-01

    Full Text Available This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, Creactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001, presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001, and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01. No significant differences were observed in the inflammation markers analyzed among SHF and HFPSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

  11. Acute phase protein response in an experimental model of ovine caseous lymphadenitis

    Directory of Open Access Journals (Sweden)

    Lang Tamara L

    2007-12-01

    Full Text Available Abstract Background Caseous lymphadenitis (CLA is a disease of small ruminants caused by Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP such as haptoglobin (Hp serum amyloid A (SAA and α1 acid glycoprotein (AGP are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles. Results The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 105 cells of C. pseudotuberculosis showed significant increases (P C. pseudotuberculosis became detectable at 11 days p.i. and continued to rise throughout the experiment. Conclusion The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.

  12. Predictors of longitudinal outcomes after unstable response to acute-phase cognitive therapy for major depressive disorder.

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2015-06-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT, double-blinded fluoxetine, or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT.

  13. Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

    Directory of Open Access Journals (Sweden)

    Rodrigo Nunes Rodrigues-da-Silva

    2014-04-01

    Full Text Available Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

  14. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    Science.gov (United States)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  15. An accurate two-phase approximate solution to the acute viral infection model

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  16. Are the unenhanced and excretory CT phases necessary for the evaluation of acute pyelonephritis?

    Science.gov (United States)

    Taniguchi, Lincoln S; Torres, Ulysses S; Souza, Saulo M; Torres, Lucas R; D'Ippolito, Giuseppe

    2017-05-01

    Background The most widely accepted computed tomography (CT) protocol for diagnosis of acute pyelonephritis (APN) includes at least a pre- and post-contrast scan, which may expose patients to higher doses of ionizing radiation. Purpose To establish the accuracy, reproducibility, and degree of confidence in CT diagnosis of acute pyelonephritis (APN) and urolithiasis using only images obtained during the nephrographic phase. Material and Methods A retrospective study of 100 consecutive patients (88 women; age range, 19-70 years) with clinical and laboratory suspicion of APN and who underwent triphasic abdominal CT scans (non-contrast, nephrographic, and excretory phases) was performed. Two readers first evaluated independently only the nephrographic phase of scans, and, in a second session, the entire study. The diagnostic reference standard was settled by a third experienced radiologist who reviewed all triphasic scans and clinical data. Results The accuracy of only nephrographic phase for diagnosis of APN and urolithiasis was in the range of 90.3-91.78% and 96.27-99.25%, respectively. There was no significant difference in comparison with the triphasic reading (z: -0.4 - 0.2; P = 0.34-0.83). The average degree of confidence for APN also showed no significant variation for both readers ( P = 0.4 and 0.08). Almost perfect inter-observer agreements for the diagnosis of APN (k = 0.86, P < 0.001) and for urolithiasis (k = 0.84, P < 0.001) were observed when considering only the nephrographic phase. Conclusion CT assessment of APN and urolithiasis can be accurately performed using only the late nephrographic phase, with consequent dose reduction.

  17. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Milène Catoire

    Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

  18. Serum acute phase proteins in cows with SARA (Subacute Ruminal Acidosis suspect

    Directory of Open Access Journals (Sweden)

    C. Cannizzo

    2012-02-01

    Full Text Available The aim of this study was to evaluate the variations of Acute Phase Proteins (APPs and other blood constituents during the onset of the sub-acute ruminal acidosis (SARA pathological status. A total of 108 cows from 12 dairy herds were randomly selected and divided into three Groups of 36 animals each. All animals were subjected to a rumenocentesis. Group A was composed by subjects with a rumen pH>5.8, Group B was composed by subjects with a rumen pH ≤5.5≤5.8 and Group C was composed by subjects with a rumen pH<5.5. Blood samples were collected by jugular venipuncture and Haptoglobin (Hp, Serum Amyloid A (SAA, Total Proteins, Albumin and White Blood Cells (WBC were determined. One-way ANOVA showed a statistical significance on Rumen pH, Hp, SAA. SARA seems not stimulate the APPs production from liver.

  19. Risk factors for and impact of respiratory failure on mortality in the early phase of acute pancreatitis

    DEFF Research Database (Denmark)

    Dombernowsky, Tilde; Kristensen, Marlene Østermark; Rysgaard, Sisse

    2016-01-01

    : Retrospective cohort study including 359 patients admitted with acute pancreatitis. Information was gathered from electronic patient records. We defined respiratory failure based on the modified Marshall scoring system in the revised Atlanta criteria. Predictors of respiratory failure were evaluated......, or pneumonia may develop respiratory failure, suggests that acute lung injury, possibly associated with systemic inflammation, may be important.......BACKGROUND: The incidence of respiratory failure and other respiratory complications in the early phase of acute pancreatitis (AP) is not well investigated. OBJECTIVE: To evaluate the incidence and risk factors of respiratory failure, and its impact on mortality in the early phase AP. METHODS...

  20. Association of interleukin-10 gene promoter polymorphisms with susceptibility to acute pyelonephritis in children.

    Science.gov (United States)

    Javor, Juraj; Králinský, Karol; Sádová, Eva; Červeňová, Oľga; Bucová, Mária; Olejárová, Michaela; Buc, Milan; Liptáková, Adriana

    2014-07-01

    Interleukin-10 (IL-10) is a potent inhibitor of leukocyte chemotaxis, bacterial killing in phagocytes and synthesis of pro-inflammatory cytokines and chemokines, and recent studies have suggested an important role for this immunoregulatory cytokine in the pathogenesis of urinary tract infections (UTIs). Therefore, the gene encoding IL-10 (IL10) is an attractive candidate for association studies attempting to identify susceptibility genes conferring risk of UTIs. In this case-control study, we aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter region of IL10 with acute pyelonephritis in the Slovak population. Polymerase chain reaction with sequence-specific primers was used to analyse IL10 -1082A/G (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) SNPs in 147 children with acute pyelonephritis and 215 healthy controls. Comparison of patients with healthy controls using the logistic regression analysis revealed significantly increased risk of developing recurrent attacks of acute pyelonephritis for -1082 G allele in a dominant genetic model GG (GG + AG vs. AA, P = 0.019, odds ratio (OR) = 2.26). A similar tendency was also found when the recurrent acute pyelonephritis subgroup was compared to episodic pyelonephritis cases (GG + AG vs. AA, P = 0.009, OR = 3.38). In conclusion, our results suggest that IL10 -1082 A/G SNP is a susceptibility factor for development of recurrent attacks of acute pyelonephritis.

  1. Lactoferrin acute-phase protein and proteinase inhibitors in blood of patients with Q-wave myocardial infraction complicated by acute heart failure

    Directory of Open Access Journals (Sweden)

    K. P. Belokoneva

    2012-01-01

    Full Text Available 153 patients with Q-wave noncomplicated and complicated myocardial infraction have been examined. Blood serum was studied for acute-phase proteins (alfa-2-macroglobulin (MG, alfa-1-antitrypsin (ATr, and lactoferrin (LF in 97 patients ((57.9 ± 1.06 years old. Blood was sampled at the 1st, 7th, and 14th days after myocardial infraction. The decrease of MG in acute phase was observed in patients with cardiogenic shock. Increased concentrations of LF and unchanged MG level at the 1—7 days were observed at pulmonary edema.

  2. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  3. Multiplex high-throughput gene mutation analysis in acute myeloid leukemia.

    Science.gov (United States)

    Dunlap, Jennifer; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Fleming, William H; Loriaux, Marc; Heinrich, Michael C; Kovacsovics, Tibor; Kelemen, Katalin; Leeborg, Nicky; Gatter, Ken; Braziel, Rita M; Press, Richard; Corless, Christopher L; Fan, Guang

    2012-12-01

    Classification of acute myeloid leukemia increasingly depends on genetic analysis. However, the number of known mutations in acute myeloid leukemia is expanding rapidly. Therefore, we tested a high-throughput screening method for acute myeloid leukemia mutation analysis using a multiplex mass spectrometry-based approach. To our knowledge, this is the first reported application of this approach to genotype leukemias in a clinical setting. One hundred seven acute myeloid leukemia cases were screened for mutations using a panel that covers 344 point mutations across 31 genes known to be associated with leukemia. The analysis was performed by multiplex polymerase chain reaction for mutations in genes of interest followed by primer extension reactions. Products were analyzed on a Sequenom MassARRAY system (San Diego, CA). The multiplex panel yielded mutations in 58% of acute myeloid leukemia cases with normal cytogenetics and 21% of cases with abnormal cytogenetics. Cytogenetics and routine polymerase chain reaction-based screening of NPM1, CEBPA, FLT3-ITD, and KIT was also performed on a subset of cases. When combined with the results of these standard polymerase chain reaction-based tests, the mutation frequency reached 78% in cases with normal cytogenetics. Of these, 42% harbored multiple mutations primarily involving NPM1 with NRAS, KRAS, CEBPA, PTPN11, IDH1, or FLT3. In contrast, cases with abnormal cytogenetics rarely harbored more than 1 mutation (1.5%), suggesting different underlying biology. This study demonstrates the feasibility and utility of broad-based mutation profiling of acute myeloid leukemia in a clinical setting. This approach will be helpful in defining prognostic subgroups of acute myeloid leukemia and contribute to the selection of patients for enrollment into trials with novel inhibitors.

  4. Growth phase-dependent gene regulation in vivo in Sulfolobus solfataricus

    NARCIS (Netherlands)

    DeYoung, M.; Oost, van der J.

    2011-01-01

    Ribosomal genes are strongly regulated dependent on growth phase in all organisms, but this regulation is poorly understood in Archaea. Moreover, very little is known about growth phase-dependent gene regulation in Archaea. SSV1-based lacS reporter gene constructs containing the Sulfolobus 16S/23S r

  5. PROGNOSTIC IMPACT OF WT-1 GENE EXPRESSION IN EGYPTIAN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Adel Abd Elhaleim Hagag

    2016-01-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common childhood cancer representing 23% of pediatric cancers. Wilms' tumor -1 gene has is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work: The aim of this work was to study the impact of WT-1 gene expression in prognosis of Egyptian children with ALL. Patients and methods: This study was conducted on 40 children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, assessment of WT-1 Gene by real time PCR in BM samples at time of diagnosis. Results: Positive WT-1 gene expression was found in 22 cases (55% and negative expression in 18 cases (45%. Positive WT-1 gene expression group (n=22 includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18 includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping. There were significantly higher relapse and death rates and lower rates of CR, DFS and OAS in negativeWT-1 gene expression group.MRD at end of induction therapy was found in 14 cases out of 40 patients. There was

  6. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  7. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  8. Determinants of fatigue after first-ever ischemic stroke during acute phase.

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    Shan-Shan Wang

    Full Text Available Fatigue after stroke is common and has a negative impact on rehabilitation and survival. However, its pathogenesis and contributing factors remain unclear. The purpose of this study was to identify factors influencing the occurrence of fatigue after first-ever ischemic stroke in acute phase.We examined 265 consecutive patients with first-ever ischemic stroke during acute phase (within 2 weeks in two tertiary stroke care hospitals in Henan, China. We documented patients' demographic and clinical characteristics through face-to-face interviews using structured questionnaires and reviews of medical records. Post-stroke fatigue was defined as a score of ≥4 using the Fatigue Severity Scale. Multivariate logistic regression was used to examine post-stroke fatigue in relation to socio-demographic, lifestyle, clinical characteristics and family function.About 40% first-ever ischemic stroke patients experienced post-stroke fatigue in acute phase. Post-stroke fatigue was associated with lack of exercise before stroke (adjusted odds ratio 4.01, 95% CI 1.95-8.24, family dysfunction (2.63, 1.20-5.80, depression (2.39, 1.02-5.58, the presence of pre-stroke fatigue (4.89, 2.13-11.21, use of sedative medications (4.14, 1.58-10.88, coronary heart disease (3.38, 1.46-7.79 and more severe Modified Rankin Scale (2.55, 1.65-3.95.The causes of post-stroke fatigue are multifaceted. More physical exercise, improving family function, reducing depression and appropriate use of sedative medications may be helpful in preventing post-stroke fatigue.

  9. Value of dynamic susceptibility contrast perfusion MRI in the acute phase of transient global amnesia.

    Directory of Open Access Journals (Sweden)

    Alex Förster

    Full Text Available Transient global amnesia (TGA is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET or single-photon emission computed tomography (SPECT. In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI in TGA in the acute phase.From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF and volume (CBV were generated and analyzed by use of Signal Processing In NMR-Software (SPIN. CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB Software Library (FSL.Five TGA patients were included (2 men, 3 women. On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI

  10. Hypocortisolism in noncomatose patients during the acute phase of subarachnoid hemorrhage.

    Science.gov (United States)

    Lanterna, Luigi A; Spreafico, Veronica; Gritti, Paolo; Prodam, Flavia; Signorelli, Antonio; Biroli, Francesco; Aimaretti, Gianluca

    2013-10-01

    Hypopituitarism represents a common long-term complication of subarachnoid hemorrhage (SAH). The incidence of hypocortisolism may be higher during the acute phase of SAH. Although hypocortisolism may be harmful in critically ill SAH patients, data are still lacking. The primary objective of this study was to investigate the incidence of hypocortisolism during the acute phase of SAH (15 days). Secondary objectives included an analysis of the relationship between hypocortisolism and outcome and the computation of the cortisol-time secretion curve. Clinical data of a consecutive series of 26 noncomatose patients with aneurysmal SAH were collected prospectively. The sample size was calculated considering an expected proportion of hypocortisolism of 30%, a confidence level of 95%, and a total width of confidence interval of 0.35. The definition of hypocortisolism (as taken from a statement from the critical care medicine task forces) includes random total cortisol Hypocortisolism was diagnosed in 11 patients (42.3%). Cortisol increment after stimulation test was always >9 μg/dl, suggesting a hypothalamic-pituitary impairment. Hypocortisolism was independently associated with a higher risk of poor outcome (P = .046) even after adjusting for age and Hunt and Hess grade. The cortisol-time secretion curve showed a peak at day 5 and a minimum at day 8. The peak at day 5 correlated with the risk of delayed cerebral ischemia (P = .001), and the cortisol concentration slope between days 1 and 8 correlated with the risk of poor outcome (P = .033). Patients with SAH are at high risk of secondary hypocortisolism during the first 15 days after bleeding. Hypocortisolism independently increases the risk of poor outcome. The acute phase of hypothalamo-pituitary dysfunction, as reflected by an abnormal day-by-day cortisol secretion pattern, may affect the risk of delayed cerebral ischemia. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Effect of blonanserin on cognitive and social function in acute phase Japanese schizophrenia compared with risperidone

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    Hori H

    2014-03-01

    Full Text Available Hikaru Hori, Kenji Yamada, Dan Kamada, Yuka Shibata, Asuka Katsuki, Reiji Yoshimura, Jun NakamuraDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, JapanBackground: This study aims to determine the effectiveness of blonanserin (BNS on the cognitive and social functions of patients with schizophrenia compared with risperidone (RIS during acute-phase (8-week treatment.Methods: A total of 39 schizophrenia inpatients were included in this study. The subjects received either BNS (N=20 or RIS (N=19, and the clinical responses were evaluated periodically. The concomitant use of mood stabilizers was not allowed. Efficacy was assessed with the Positive and Negative Syndrome Scale for schizophrenia. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version. Social function was assessed using the Life Assessment Scale for the Mentally Ill.Results: For both groups, each assessment exhibited a decrease in the mean change from baseline on the Positive and Negative Syndrome Scale. The depression subscale was significantly improved in the BNS group compared with the RIS group at 8 weeks after administration. BNS improved verbal fluency and executive function (cognitive function and daily living and work skills (social function. Compared with the RIS group, BNS was observed to improve daily living.Conclusion: BNS may improve psychotic symptoms, cognitive function, and daily living in patients with acute-phase schizophrenia. BNS may be superior to RIS in the improvement of daily living.Keywords: risperidone, blonanserin, schizophrenia, cognitive function, social function, acute-phase

  12. Thromboembolism in the Sub-Acute Phase of Spinal Cord Injury: A Systematic Review of the Literature

    Science.gov (United States)

    Belci, Maurizio; Van Middendorp, Joost J; Al Halabi, Ahmed; Meagher, Tom M

    2016-01-01

    To review the evidence of thromboembolism incidence and prophylaxis in the sub-acute phase of spinal cord injury (SCI) 3–6 months post injury. All observational and experimental studies with any length of follow-up and no limitations on language or publication status published up to March 2015 were included. Two review authors independently selected trials for inclusion and extracted data. Outcomes studied were incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in the sub-acute phase of SCI. The secondary outcome was type of thromboprophylaxis. Our search identified 4305 references and seven articles that met the inclusion criteria. Five papers reported PE events and three papers reported DVT events in the sub-acute phase of SCI. Studies were heterogeneous in populations, design and outcome reporting, therefore a meta-analysis was not performed. The included studies report a PE incidence of 0.5%–6.0% and DVT incidence of 2.0%–8.0% in the sub-acute phase of SCI. Thromboprophylaxis was poorly reported. Spinal patients continue to have a significant risk of PE and DVT after the acute period of their injury. Clinicians are advised to have a low threshold for suspecting venous thromboembolism in the sub-acute phase of SCI and to continue prophylactic anticoagulation therapy for a longer period of time.

  13. [Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

    Science.gov (United States)

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

    2014-01-01

    To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

  14. Control of lipopolysaccharide-high density lipoprotein binding by acute phase protein(s).

    Science.gov (United States)

    Tobias, P S; Ulevitch, R J

    1983-10-01

    When Salmonella minnesota R595 lipopolysaccharide (LPS) is mixed with serum, the LPS eventually forms a complex with high density lipoprotein (HDL). Complex formation is conveniently followed by CsCl equilibrium density gradient centrifugation. When mixing 10 micrograms LPS with normal rabbit serum (NRS) at 37 degrees C in the presence of 20 mM EDTA, the half-life for LPS binding to HDL is typically 2 to 3 min. When the same experiment is performed with the use of acute phase rabbit serum (APRS; collected 24 hr post-induction with silver nitrate), the half-life for LPS binding to HDL is typically 40 to 100 min. Thus LPS binding to HDL occurs some 20- to 40-fold slower in APRS than in NRS. Two other phenomena have been found, the time dependencies of which correlate well with the time dependency of LPS binding to HDL in APRS. If LPS-APRS reaction mixtures are cooled to 4 degrees C shortly after mixing and are dialyzed against 2.5 mM HEPES, 15 mM NaCl, pH 7.4 buffer, LPS is recovered in the washed precipitates ("euglobulin precipitate") if, and only if, the LPS-HDL binding reaction is not complete. The amount of LPS in the precipitate correlates well with the amount of LPS that has not bound to HDL. The second phenomenon we observe is that the LPS-containing euglobulin precipitate prepared from LPS-acute phase serum reaction mixtures shortly after mixing also contains a protein, gp60, the concentration of which in the euglobulin precipitate correlates well with the amount of LPS in the precipitate. Thus three phenomena are kinetically well correlated in APRS: the degree of binding of LPS to HDL, the degree of appearance of LPS in a euglobulin fraction, and the concentration of protein gp60 in the euglobulin fraction. We were unable to precipitate gp60 from APRS in the absence of LPS, from APRS after the LPS has fully bound to HDL, or from normal serum in the presence or absence of LPS. The known properties of gp60 are not reminiscent of any other known acute phase

  15. Dose dependency and individual variability of the lipopolysaccharide-induced bovine acute phase protein response

    DEFF Research Database (Denmark)

    Jacobsen, S.; Andersen, P.H.; Tølbøll, T.

    2004-01-01

    In order to investigate the dose dependency and the individual variability of the lipopolysaccharide (LPS)-induced acute phase protein response in cattle, 8 nonlactating, nonpregnant Danish Holstein cows were challenged 3 times each by intravenous injection of increasing doses (10, 100, and 1000 ng...... for several days after each LPS injection, and their increase or decrease was significantly related to LPS dose. In addition to dose dependency, the response was also dependent on the individual, as APP concentrations differed significantly among cows. To compare APP production in 2 consecutive challenges...

  16. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    OpenAIRE

    Okino, Alessandra M; Cristiani Bürger; Cardoso, Jefferson R.; Edson L. Lavado; Lotufo, Paulo A; Ana Campa

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount f...

  17. Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation

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    Nicola Mario

    2001-11-01

    Full Text Available Abstract Background The NUP98 gene is involved in multiple rearrangements in haematological malignancy. The leukemic cells in an acute myeloid leukemia (AML patient with a t(9;11(p22;p15 were recently shown to have a fusion between the NUP98 gene and the LEDGF gene but it was not demonstrated that this fusion was recurrent in other leukaemia patients with the same translocation. Results We used RT-PCR to analyse the leukemic cells from an AML patient who presented with a cytogenetically identical translocation as the sole chromosomal abnormality. A NUP98-LEDGF fusion transcript was observed and confirmed by sequencing. The reciprocal transcript was also observed. The fusion transcript was not detectable during remission and recurred at relapse. The breakpoints in the NUP98 and LEDGF genes were different to those previously reported. The NUP98 breakpoint occurs in the intron between exons 8 and 9. It is the most 5' breakpoint reported in a translocation involving the NUP98 gene. All of the LEDGF gene is included in the fusion except for exon 1 which codes for the first 24 amino terminal amino acids. Conclusions Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.

  18. Acute ozone-induced differential gene expression profiles in rat lung.

    Science.gov (United States)

    Nadadur, Srikanth S; Costa, Daniel L; Slade, Ralph; Silbjoris, Robert; Hatch, Gary E

    2005-12-01

    Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-beta receptor c-erb-A-beta; and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.

  19. Differential gene expressions in testes of L2 strain Taiwan country chicken in response to acute heat stress.

    Science.gov (United States)

    Wang, Shih-Han; Cheng, Chuen-Yu; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Huang, San-Yuan

    2013-01-15

    Acute heat stress affects genes involved in spermatogenesis in mammals. However, there is apparently no elaborate research on the effects of acute heat stress on gene expression in avian testes. The purpose of this study was to investigate global gene expression in testes of the L2 strain of Taiwan country chicken after acute heat stress. Twelve roosters, 45 weeks old, were allocated into four groups, including control roosters kept at 25 °C, roosters subjected to 38 °C acute heat stress for 4 hours without recovery, with 2-hour recovery, and with 6-hour recovery, respectively. Testis samples were collected for RNA isolation and microarray analysis. Based on gene expression profiles, 169 genes were upregulated and 140 genes were downregulated after heat stress using a cutoff value of twofold or greater change. Based on gene ontology analysis, differentially expressed genes were mainly related to response to stress, transport, signal transduction, and metabolism. A functional network analysis displayed that heat shock protein genes and related chaperones were the major upregulated groups in chicken testes after acute heat stress. A quantitative real-time polymerase chain reaction analysis of mRNA expressions of HSP70, HSP90AA1, BAG3, SERPINB2, HSP25, DNAJA4, CYP3A80, CIRBP, and TAGLN confirmed the results of the microarray analysis. Because the HSP genes (HSP25, HSP70, and HSP90AA1) and the antiapoptotic BAG3 gene were dramatically altered in heat-stressed chicken testes, we concluded that these genes were important factors in the avian testes under acute heat stress. Whether these genes could be candidate genes for thermotolerance in roosters requires further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Integrative meta-analysis of differential gene expression in acute myeloid leukemia.

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    Brady G Miller

    Full Text Available BACKGROUND: Acute myeloid leukemia (AML is a heterogeneous disease with an overall poor prognosis. Gene expression profiling studies of patients with AML has provided key insights into disease pathogenesis while exposing potential diagnostic and prognostic markers and therapeutic targets. A systematic comparison of the large body of gene expression profiling studies in AML has the potential to test the extensibility of conclusions based on single studies and provide further insights into AML. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we systematically compared 25 published reports of gene expression profiling in AML. There were a total of 4,918 reported genes of which one third were reported in more than one study. We found that only a minority of reported prognostically-associated genes (9.6% were replicated in at least one other study. In a combined analysis, we comprehensively identified both gene sets and functional gene categories and pathways that exhibited significant differential regulation in distinct prognostic categories, including many previously unreported associations. CONCLUSIONS/SIGNIFICANCE: We developed a novel approach for granular, cross-study analysis of gene-by-gene data and their relationships with established prognostic features and patient outcome. We identified many robust novel prognostic molecular features in AML that were undetected in prior studies, and which provide insights into AML pathogenesis with potential diagnostic, prognostic, and therapeutic implications. Our database and integrative analysis are available online (http://gat.stamlab.org.

  1. Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.

    Directory of Open Access Journals (Sweden)

    Aaron R Wolen

    Full Text Available Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain across a highly diverse family of 27 isogenic mouse strains (BXD panel before and after treatment with ethanol.Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol

  2. Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications

    Science.gov (United States)

    Wolen, Aaron R.; Phillips, Charles A.; Langston, Michael A.; Putman, Alex H.; Vorster, Paul J.; Bruce, Nathan A.; York, Timothy P.; Williams, Robert W.; Miles, Michael F.

    2012-01-01

    Background Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol. Results Acute ethanol altered the expression of ∼2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2. Conclusions The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence

  3. Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis.

    Science.gov (United States)

    Virtaneva, Kimmo; Graham, Morag R; Porcella, Stephen F; Hoe, Nancy P; Su, Hua; Graviss, Edward A; Gardner, Tracie J; Allison, James E; Lemon, William J; Bailey, John R; Parnell, Michael J; Musser, James M

    2003-04-01

    The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

  4. Same-strand overlapping genes in bacteria: compositional determinants of phase bias

    Directory of Open Access Journals (Sweden)

    Landan Giddy

    2008-08-01

    Full Text Available Abstract Background Same-strand overlapping genes may occur in frameshifts of one (phase 1 or two nucleotides (phase 2. In previous studies of bacterial genomes, long phase-1 overlaps were found to be more numerous than long phase-2 overlaps. This bias was explained by either genomic location or an unspecified selection advantage. Models that focused on the ability of the two genes to evolve independently did not predict this phase bias. Here, we propose that a purely compositional model explains the phase bias in a more parsimonious manner. Same-strand overlapping genes may arise through either a mutation at the termination codon of the upstream gene or a mutation at the initiation codon of the downstream gene. We hypothesized that given these two scenarios, the frequencies of initiation and termination codons in the two phases may determine the number for overlapping genes. Results We examined the frequencies of initiation- and termination-codons in the two phases, and found that termination codons do not significantly differ between the two phases, whereas initiation codons are more abundant in phase 1. We found that the primary factors explaining the phase inequality are the frequencies of amino acids whose codons may combine to form start codons in the two phases. We show that the frequencies of start codons in each of the two phases, and, hence, the potential for the creation of overlapping genes, are determined by a universal amino-acid frequency and species-specific codon usage, leading to a correlation between long phase-1 overlaps and genomic GC content. Conclusion Our model explains the phase bias in same-strand overlapping genes by compositional factors without invoking selection. Therefore, it can be used as a null model of neutral evolution to test selection hypotheses concerning the evolution of overlapping genes. Reviewers This article was reviewed by Bill Martin, Itai Yanai, and Mikhail Gelfand.

  5. A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning

    Directory of Open Access Journals (Sweden)

    Karunatilake Harindra

    2009-08-01

    Full Text Available Abstract Background An estimated 2–3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion. Methods This study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours. Results The baseline characteristics of both groups were similar. The trial was stopped after completion of the 3rd dosing level. At the 1st and 2nd dosing level there were no reported adverse drug reactions. At the 3rd dosing level 5 patients (42% developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels. Conclusion Our findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning. Trial registration Current Controlled Trial ISRCTN89917816.

  6. Effects of acute heat stress on gene expression of brain-gut neuropeptides in broiler chickens.

    Science.gov (United States)

    Lei, L; Hepeng, L; Xianlei, L; Hongchao, J; Hai, L; Sheikhahmadi, A; Yufeng, W; Zhigang, S

    2013-11-01

    Heat stress-induced reduction in feed intake is an annoyance of the poultry industry. Feed intake is regulated by complex mechanisms in which brain-gut neuropeptides are involved, but the changes in such neuropeptides in broiler chickens during heat exposure remain unclear. In this study, we investigated the effects of acute heat stress (35°C, 6 h, and 65% relative humidity) on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of broiler chickens at 42 d of age. The hypothalamic mRNA levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, melanocortin 4 receptor, melanin-concentrating hormone, prepro-orexin, cholecystokinin (CCK), and ghrelin did not significantly change (P>0.05) in the heat-exposed broiler chickens. However, the mRNA levels of ghrelin in the glandular stomach, duodenum, and jejunum significantly increased and the mRNA level of CCK in the duodenum significantly decreased. The results indicate that acute heat stress had no effect on the gene expression of central appetite-regulating peptides under current experimental conditions; however, some gastrointestinal tract peptides (e.g., ghrelin and CCK) might play a role in the regulation of appetite in acute heat-exposed broiler chickens. Furthermore, ghrelin in the glandular stomach, duodenum, and jejunum might be the main regulative target of acute heat stress induced anorexia.

  7. FLT3 Gene Mutation in Childhood Acute Leukemia: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Zefarina Zulkafli

    2014-01-01

    Full Text Available Introduction. FLT3 is a tyrosine kinase receptor involved in the proliferation and differentiation of hematopoietic stem cells. There are two types of common FLT3 gene mutation, internal tandem duplication and the D835 mutation, which are known to be associated with a poor clinical outcome in acute leukemia patients. Methods. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD in 38 pediatric patients diagnosed with acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML in Hospital Universiti Sains Malaysia. DNA extraction was done from archive bone marrow samples to determine FLT3-ITD mutations using polymerase chain reaction. Results. In this pediatric series, the age ranges were 2–14 years. However, no FLT3-ITD mutations were detected in any of the samples. Conclusion. This preliminary study suggested that the incidence of FLT3 gene mutation most probably was very low in pediatrics patients diagnosed with acute leukemia. A further study with larger number of patient samples is necessary to confirm the findings and to further appreciate the prognostic value of FLT3-ITD mutation among pediatrics patients.

  8. ACUTE PHASE PROTEIN AND ELECTROPHORESIS PROTEIN FRACTION VALUES FOR CAPTIVE AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    Science.gov (United States)

    Delk, Katie W; Wack, Raymund F; Burgdorf-Moisuk, Anne; Kass, Philip H; Cray, Carolyn

    2015-12-01

    Protein electrophoresis has recognized applications in determining the health status of various species. While reference intervals for electrophoresis have been determined for psittacine and raptor species, there are none reported for Phoenicopteriformes species. Reference intervals for haptoglobin and protein fractions obtained by electrophoresis were determined for the American flamingo (Phoenicopterus ruber) based on plasma samples from 39 captive birds. The reference intervals were as follows: haptoglobin, 0.17-0.8 mg/ml; total protein, 3.65-6.38 g/dl; prealbumin, 0.26-1.9 g/dl; albumin, 1.51-3.12 g/dl; α-1 globulin, 0.06-0.38 g/dl; α-2 globulin, 0.17-0.67 g/dl; β globulin, 0.38-1.33 g/dl; γ globulin, 0.26-0.68 g/dl; albumin : globulin ratio, 0.93-2.17. As captive flamingos often suffer from pododermatitis, feet of all flamingos were scored to determine if pododermatitis would be reflected in the acute phase proteins. Spearman rank correlation was performed on each of the protein fractions and pododermatitis scores, and only albumin had a significant correlation. This indicates that albumin, as a negative acute phase protein, may be a marker for this disease process.

  9. Enhanced depth imaging OCT (EDI-OCT) findings in acute phase of sympathetic ophthalmia.

    Science.gov (United States)

    Behdad, Bahareh; Rahmani, Safa; Montahaei, Talieh; Soheilian, Roham; Soheilian, Masoud

    2015-06-01

    The purpose of this study was to describe the EDI-OCT findings in an acute phase of sympathetic ophthalmia (SO). A 24-year-old gentleman was referred to clinic complaining of progressive blurry vision of his right eye within last 3 days. He had a history of repaired corneoscleral laceration in his left eye followed by lensectomy and anterior vitrectomy approximately 1 month before his recent right eye discomfort. Physical examination revealed a granulomatous uveitis with an exudative RD of the right eye consistent with SO. EDI-OCT was done at initial exam and repeated 1 and 15 months after therapy. EDI-OCT 1 month following therapy showed significant improvement in choroidal thickening and outer retinal cell layers. The choroidal thickness in the right sympathizing eye decreased from 617 to 568 μm and in the left exciting eye from 539 to 521 μm. After 15 month follow-up, choroidal thickness that is reported in EDI-OCT is 436 μm in the right and 382 μm in the left eye. SO should be added to the list of choroidopathies that cause an increase in choroidal thickness in acute phase of disorder with subsequent decrease after therapy, so help us in assessing and estimation of response to treatment.

  10. Acute phase protein expression during elephant endotheliotropic herpesvirus-1 viremia in Asian elephants (Elephas maximus).

    Science.gov (United States)

    Stanton, Jeffrey J; Cray, Carolyn; Rodriguez, Marilyn; Arheart, Kristopher L; Ling, Paul D; Herron, Alan

    2013-09-01

    Infection of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can be associated with rapid, lethal hemorrhagic disease and has been documented in elephant herds in human care and in the wild. Recent reports describe real-time quantitative polymerase chain reaction (qPCR) assays used to monitor clinically ill elephants and also to detect subclinical EEHV1 infection in apparently healthy Asian elephants. Acute phase proteins have been demonstrated to increase with a variety of infectious etiologies in domesticated mammals but have not yet been described in elephants. In addition, the immune response of Asian elephants to EEHV1 infection has not been described. In this study, whole blood and trunk wash samples representing repeated measures from eight elephants were examined for the presence of EEHV1 using a qPCR assay. Elephants were classified into groups, as follows: whole blood negative and positive and trunk wash negative and positive. Serum amyloid A (SAA) and haptoglobin (HP) levels were compared between these groups. A significant difference in SAA was observed with nearly a threefold higher mean value during periods of viremia (P=0.011). Higher values of SAA were associated with >10,000 virus genome copies/ml EEHV1 in whole blood. There were no significant differences in HP levels, although some individual animals did exhibit increased levels with infection. These data indicate that an inflammatory process is stimulated during EEHV1 viremia. Acute phase protein quantitation may aid in monitoring the health status of Asian elephants.

  11. Effect of blonanserin on cognitive and social function in acute phase Japanese schizophrenia compared with risperidone.

    Science.gov (United States)

    Hori, Hikaru; Yamada, Kenji; Kamada, Dan; Shibata, Yuka; Katsuki, Asuka; Yoshimura, Reiji; Nakamura, Jun

    2014-01-01

    This study aims to determine the effectiveness of blonanserin (BNS) on the cognitive and social functions of patients with schizophrenia compared with risperidone (RIS) during acute-phase (8-week) treatment. A total of 39 schizophrenia inpatients were included in this study. The subjects received either BNS (N=20) or RIS (N=19), and the clinical responses were evaluated periodically. The concomitant use of mood stabilizers was not allowed. Efficacy was assessed with the Positive and Negative Syndrome Scale for schizophrenia. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version. Social function was assessed using the Life Assessment Scale for the Mentally Ill. For both groups, each assessment exhibited a decrease in the mean change from baseline on the Positive and Negative Syndrome Scale. The depression subscale was significantly improved in the BNS group compared with the RIS group at 8 weeks after administration. BNS improved verbal fluency and executive function (cognitive function) and daily living and work skills (social function). Compared with the RIS group, BNS was observed to improve daily living. BNS may improve psychotic symptoms, cognitive function, and daily living in patients with acute-phase schizophrenia. BNS may be superior to RIS in the improvement of daily living.

  12. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins

    Energy Technology Data Exchange (ETDEWEB)

    Miller, L.L.

    1976-01-01

    The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs--Ringer bicarbonate buffer containing 3% bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, ..cap alpha../sub 2/-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 ..mu..g) used was insufficient to induce synthesis of ..cap alpha../sub 2/-acute phase globulin, net syntheses of albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and ..cap alpha../sub 1/-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.

  13. Association between clinical condition and F-waves changes in the acute phase of stroke

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    Gustavo José Luvizutto

    Full Text Available ABSTRACT Objective To relate F-waves with clinical and laboratory exams in the acute phase of stroke. Methods Inclusion criteria for this cross-sectional study were: hemiplegia, absence of previous cranial trauma, myopathy, diabetes, alcoholism or other known causes of peripheral neuropathy, and normal sensory and motor conduction. The National Institutes of Health Stroke Scale (NIHSS score, glycemia, glucosilate hemoglobin, and CPK were obtained at admission by routine blood exams. After hospital admission, the F-wave latencies and persistence were obtained from the deep peroneal nerve using symmetrical techniques. Results Evaluation of 20 individuals – mean age 66 years, 50% male and 85% Caucasian – showed association of F-wave persistence with glycemia (r = 0.71; p < 0.001 and NIHSS categorized (NIHSS 1-7 = 65.0 x NIHSS 9-23 = 100; p = 0.004. Multivariate analysis found only association of F-wave persistence with glycemia β = 0.59 (0.44–0.74; p < 0.001. Conclusion The increase in the persistence of F-waves are associated with hyperglycemia in the acute phase of stroke.

  14. Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

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    Chen Chien-Ju

    2009-01-01

    Full Text Available Abstract Background Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3 in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout (ASIC3-/- or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation. Results Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3-/- mice induced by complete Freund's adjuvant (CFA or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3+/+ controls, ASIC3-/- mice showed normal thermal and mechanical hyperalgesia with acute (4-h intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3-/- or ASIC3+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3-/- mice, as previously described. However, ASIC3-/- mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3+/+ mice. Conclusion We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.

  15. Localized gene transfer into organotypic hippocampal slice cultures and acute hippocampal slices

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Shen, H;

    1993-01-01

    Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and express genes into fully differentiated, post-mitotic neurons. These vectors also transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter quantities of a virus stock of HSVlac, an HSV vector...... or hippocampal slices. The rapid expression of beta-gal by HSVlac allowed efficient transduction of acute hippocampal slices. Many genes have been transduced and expressed using HSV vectors; therefore, this microapplication method can be applied to many neurobiological questions....

  16. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  17. Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

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    Tai Dessmon

    2005-01-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs derived from SARS patients, and compared with healthy controls. Results The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. Conclusions This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.

  18. Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury

    Science.gov (United States)

    Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

    2011-01-01

    Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5(mu or u)g MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of pgenes were up-regulated and 76 genes were down-regulated in response to MeHg exposure. Individual genes exhibiting altered expression in response to MeHg exposure implicate effects on glutathione metabolism in the mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched among altered genes included protein folding, cell redox homeostasis, and steroid biosynthetic process. The most affected biological functions were related to nervous system development and function, as well as lipid metabolism and molecular transport. These results support the involvement of oxidative stress and effects on protein structure in the mechanism of action of MeHg in the female brain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and will investigate responsive genes as potential biomarkers of MeHg exposure.

  19. Lineage switch in relapse of acute leukemia with rearrangement of MLL gene (KMT2A. literature review and case reports

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    E. A. Zerkalenkova

    2016-01-01

    Full Text Available Lineage switch is a rare phenomenon in which a transition from lymphoid to myeloid was observed in relapse of acute leukemia, or vice versa. This paper presents the four clinical case reports of acute lymphoblastic leukemia with MLL gene rearrangement (KMT2A with myeloid phenotype in relapse.

  20. Gene expression analyses reveal metabolic specifications in acute O2 -sensing chemoreceptor cells.

    Science.gov (United States)

    Gao, Lin; Bonilla-Henao, Victoria; García-Flores, Paula; Arias-Mayenco, Ignacio; Ortega-Sáenz, Patricia; López-Barneo, José

    2017-07-17

    Glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM) are essential for reflex cardiorespiratory adaptation to hypoxia. However, the mechanisms whereby these cells detect changes in O2 tension are poorly understood. The metabolic properties of acute O2 -sensing cells have been investigated by comparing the transcriptomes of CB and AM cells, which are O2 -sensitive, with superior cervical ganglion neurons, which are practically O2 -insensitive. In O2 -sensitive cells, we found a characteristic prolyl hydroxylase 3 down-regulation and hypoxia inducible factor 2α up-regulation, as well as overexpression of genes coding for three atypical mitochondrial electron transport subunits and pyruvate carboxylase, an enzyme that replenishes tricarboxylic acid cycle intermediates. In agreement with this observation, the inhibition of succinate dehydrogenase impairs CB acute O2 sensing. The responsiveness of peripheral chemoreceptor cells to acute hypoxia depends on a 'signature metabolic profile'. Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2 -sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia. These signals alter membrane ion channel activity. To investigate the metabolic profile characteristic of acute O2 -sensing cells, we used adult mice to compare the transcriptomes of three cell types derived from common sympathoadrenal progenitors, but exhibiting variable

  1. Assessing the utility of the ventilation phase in ventilation-perfusion imaging for acute pulmonary embolism.

    Science.gov (United States)

    Grimm, Lars J; Coleman, Ralph E

    2013-01-01

    This study aims to identify patient characteristics that allow the exclusion of the ventilation phase in ventilation-perfusion imaging for the evaluation of acute pulmonary embolism (PE). A total of 500 consecutive ventilation-perfusion reports with an indication for possible acute PE were retrospectively reviewed. Information on ventilation abnormalities, perfusion defects, PIOPED classification, age, sex, chest radiograph results, and presence of respiratory disease was recorded. Patients with moderate and large perfusion defects were analyzed to assess the utility of the ventilation phase on the final PIOPED classification. Moderate (n=39) or large (n=26) perfusion defects were seen in 65 (13%) studies. Of these, 46 studies (70.8%) had defects unmatched on ventilation and three (4.6%) had triple-match defects, resulting in 49 reports (75.4%) classified as intermediate (n=28) or high (n=21) probability for PE. There was a statistically significant association between unmatched defects and a clear chest radiograph (P=0.03) and an association approaching statistical significance with younger age (P=0.05). There was a strong association with respiratory disease (P=0.12) and no association with patient sex (P=0.82). The percentage of studies with unmatched defects increased from 70.8 to 76.7% (33/43, P=0.39) if patients with respiratory disease were excluded, to 82.4% (28/34, P=0.14) if abnormal chest radiographs were excluded, and to 95.7% (22/23, P=0.01) if both were excluded. There may be a subset of patients - younger patients with clear chest radiographs and no respiratory disease - for whom the ventilation phase can be excluded and the determination of a PE is based solely on perfusion abnormalities.

  2. Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

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    J.F. Mata

    2006-11-01

    Full Text Available Infant acute lymphoblastic leukemia (IALL is characterized by mixed lineage leukemia (MLL gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively. Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

  3. Prognostic implication of N-RAS gene mutations in Egyptian adult acute myeloid leukemia.

    Science.gov (United States)

    Elghannam, Doaa M; Abousamra, Nashwa Khayrat; Shahin, Doaa A; Goda, Enas F; Azzam, Hanan; Azmy, Emad; El-Din, Manal Salah; El-Refaei, Mohamed F

    2009-01-01

    The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). The aim of the present work is to study the frequency and prognostic significance of N-RAS gene mutations (N-RASmut) in de novo Egyptian adult AML. Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for N-RAS mutations. In 12.7% (19/150) AML cases, N-RAS gene mutations were found and were observed more frequently in the FAB subtype M4eo (P = 0.028) and with codon 12, 13 (14 of 19; 73.7%). Patients with N-RAS mutation had a significant lower peripheral and marrow blasts (P = 0.004, P = 0.03) and clinical outcome did not improve more than in patients without mutation. In patients with N-RAS gene mutation vs. those without, complete remission rate was (63.2% vs. 56.5%; P = 0.46), resistant disease (15.8% vs. 23.6%; P = 0.51), three years overall survival (44% vs 42%; P= 0.85) and disease free survival (42.1% vs. 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = 0.002), followed by cytogenetics (P = 0.004). FAB types, N-RAS mutation and leukocytosis were the least important. In conclusion, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML.

  4. Differential expression of 114 oxidative stressrelated genes in peripheral blood mononuclear cells of acute cerebral infarction patients A gene microarray experiment

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Fei Zhong; Mingshan Ren; Jiangming Zhao

    2010-01-01

    Previous studies have focused on the analysis of single or several function-related genes in oxidative stress;however,little information is available regarding altered expression of oxidative stress-related genes in the process of ischemia-reperfusion injury from microarray experiments.The aim of the present study was to investigate the changes in cell oxidative stress-and toxicity-related gene expression utilizing microarray screening in patients with acute cerebral infarction during cerebral ischemia-reperfusion injury.Of the included 114 genes,expression was significantly upregulated in eight genes,including three heat shock protein-related genes,one oxidative and metabolic stress-related gene,one cell growth arrest/senescence related gene,two apoptosis signal-related genes,and one DNA damage and repair related gene.Expression was significantly downregulated in four genes,including one cell proliferation/cancer related gene,two oxidative and metabolic stress-related genes and one DNA damage and repair related gene.The results demonstrated that cerebral ischemia-reperfusion injury in patients with acute cerebral infarction was affected by many genes including oxidative stress-,heat shock-,DNA damage and repair-,and apoptosis signal-related genes.Therefore,it could be suggested that cerebral ischemia-reperfusion injury may be subjected to complex genetic regulation mechanisms.

  5. Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.

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    Mikihiko Arikawa

    Full Text Available BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI. In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9. In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.

  6. Connective tissue growth factor reacts as an IL-6/STAT3-regulated hepatic negative acute phase protein

    Institute of Scientific and Technical Information of China (English)

    Olav A Gressner; Ieva Peredniene; Axel M Gressner

    2011-01-01

    AIM: To investigate the mechanisms involved in a possible modulator role of interleukin (IL)-6 signalling on CYR61-CTGF-NOV (CCN) 2/connective tissue growth factor (CTGF) expression in hepatocytes (PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation.METHODS: Expression of CCN2/CTGF, p-STAT3, p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting, electrophoretic mobility shift assay (EMSA), reporter-gene-assays and reversetranscriptase polymerase chain reaction.RESULTS: IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC, enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients' sera. The inhibition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2 (and Smad1/3)signalling. However, the STAT3 SH2 domain binding peptide, a selective inhibitor of STAT3 DNA binding activity, counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate, an inhibitor primarily of STAT3 phosphorylation. An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2 /CTGF promoter.CONCLUSION: CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.

  7. Virtual histology study of atherosclerotic plaque composition in patients with stable angina and acute phase of acute coronary syndromes without ST segment elevation

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    Ivanović Miloš

    2013-01-01

    Full Text Available Introduction. Rupture of vulnerable atherosclerotic plaques is the cause of most acute coronary syndromes (ACS. Postmortem studies which compared stable coronary lesions and atherosclerotic plaques in patients who have died because of ACS indicated high lipid-core content as one of the major determinants of plaque vulnerability. Objective. Our primary goal was to assess the potential relations of plaque composition determined by IVUS-VH (Intravascular Ultrasound - Virtual Histology in patients with stable angina and subjects in acute phase of ACS without ST segment elevation. Methods. The study comprised of 40 patients who underwent preintervention IVUS examination. Tissue maps were reconstructed from radio frequency data using IVUS-VH software. Results. We analyzed 53 lesions in 40 patients. Stable angina was diagnosed in 24 patients (29 lesions, while acute phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions. In the patients in acute phase of ACS without ST segment elevation IVUS-VH examination showed a significantly larger area of the necrotic core at the site of minimal lumen area and a larger mean of the necrotic core volume in the entire lesion comparing to stable angina subjects (1.84±0.90 mm2 vs. 0.96±0.69 mm2; p<0.001 and 20.94±15.79 mm3 vs. 11.54±14.15 mm3; p<0.05 respectively. Conclusion. IVUS-VH detected that the necrotic core was significantly larger in atherosclerotic lesions in patients in acute phase of ACS without ST elevation comparing to the stable angina subjects and that it could be considered as a marker of plaque vulnerability.

  8. Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

    Directory of Open Access Journals (Sweden)

    van der Meijde Jolanda

    2007-08-01

    Full Text Available Abstract Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1 and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1. Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2, formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1, or for secretion of cholesterol (Abca1 and Abcg8. Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a increased oxidation of fat and xenobiotics, b increased cholesterol secretion, c increased susceptibility to electrophilic stressors, and d reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance

  9. Pig α1-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Miller, Ingrid; Sørensen, Nanna Skall;

    2013-01-01

    concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative...... acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase...

  10. Analyzing the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays

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    Yan-Fang Tao

    2012-09-01

    Full Text Available Abstract Background The Real-time PCR Array System is the ideal tool for analyzing the expression of a focused panel of genes. In this study, we will analyze the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays. Methods Real-time PCR array was designed and tested firstly. Then gene expression profile of 11 pediatric AML and 10 normal controls was analyzed with real-time PCR arrays. We analyzed the expression data with MEV (Multi Experiment View cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool. Results We designed and tested 88 real-time PCR primer pairs for a quantitative gene expression analysis of key genes involved in pediatric AML. The gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. To investigate possible biological interactions of differently regulated genes, datasets representing genes with altered expression profile were imported into the Ingenuity Pathway Analysis Tool. The results revealed 12 significant networks. Of these networks, Cellular Development, Cellular Growth and Proliferation, Tumor Morphology was the highest rated network with 36 focus molecules and the significance score of 41. The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to hematological disease, cell death, cell growth and hematological system development. In the top canonical pathways, p53 and Huntington’s disease signaling came out to be the top two most significant pathways with a p value of 1.5E-8 and2.95E-7, respectively. Conclusions The present study demonstrates the gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. We

  11. GENE RESPONSE OF THE GASTROCNEMIUS AND SOLEUS MUSCLES TO AN ACUTE AEROBIC RUN IN RATS

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    Michael J. McKenzie

    2011-06-01

    Full Text Available Genes can be activated or inhibited by signals within the tissues in response to an acute bout of exercise. It is unclear how a particular aerobic exercise bout may influence two muscles with similar actions to the activity. Therefore, the purposes of this investigation was to determine the gene response of selected genes involved in the "stress" response of the gastrocnemius (fast-twitch and soleus (slow-twitch muscles to a single two hour aerobic exercise bout in female Sprague-Dawley Rats at the 1 hour time point after the exercise. Exercised rats were run (n=8 for 2 hours at 20 m.min-1 and one hour after the completion of the bout had their soleus (S and gastrocnemius (G muscles removed. Age and timed matched sedentary control rats had both S and G muscles removed also. RNA was isolated from all muscles. Real-time PCR analysis was performed on the following genes: NFκB, TNFα, and Atf3. GAPDH was used as the housekeeping gene for both muscles. S muscle showed more genes altered (n = 52 vs G (n = 26. NFκB gene expression was 0.83 ± 0.14 in the exercised S but was + 1.36 ± 0.58 in the exercised G and was not significantly different between the muscles. TNFα was altered 1.30 ± 0. 34 in the exercised S and 1.36 ± 0.71 in the exercised G and was not significantly different between the muscles. The gene Atf3 was significantly altered at 4.97 ± 1.01 in the exercised S, while it was not significantly altered in the exercised G (0.70 ± 0.55. This study demonstrates that an acute bout of aerobic exercise can alter gene expression to a different extent in both the S and G muscles. It is highly likely that muscle recruitment was a factor which influenced the gene expression in theses muscles. It is interesting to note that some genes were similarly activated in these two muscles but other genes may demonstrate a varied response to the same exercise bout depending on the type of muscle

  12. Association analysis of genetic variants in the myosin IXB gene in acute pancreatitis.

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    Rian M Nijmeijer

    Full Text Available INTRODUCTION: Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis. METHODS: Five single nucleotide polymorphisms (SNPs in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls. RESULTS: Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05. Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR 1.94, 95% confidence interval (95% CI 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53. SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology. CONCLUSION: Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.

  13. ACCURACY OF RAPID TEST OF STORED ACUTE PHASE SERUM FOR DIAGNOSE JAPANESE ENCEPHALITIS

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    Ida Bagus Subanada

    2013-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE Japanese encephalitis (JE is common viral encephalitis with high sequele and mortality. With some limitations, there are several diagnostic tool to diagnose of JE. The objecive of this study was to know the accuracy of rapid test of stored acute phase serum for diagnose of JE. We conducted diagnostic test of stored acute phase serum of encephalitis patients with MAC ELISA of cerebrospinal fluid as a gold standard. Sensitivity, specificity, positive predictive value (PPV, negative predictive value NPV, positive likelihood ratio (PLR, negative likelihood ratio (NLR, and post-test probability were calculated. This study found the prevalence of JE was 42.1%, sensitivity 15.7 % (95% CI 9.2 to 22.2%, specificity 95.7% (95% CI 92.1 to 99.3%, PPV 72.7% (95% CI 64.8 to 80.6%, NPV 60.9% (95% CI 52.2 to 69.6%, PLR 3.7, NLR 0.9, and post-test probability was 0.73. We concluded that rapid test of acute phase stored serum was insensitive but specific to diagnose of JE. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  14. Serum amyloid A: an acute phase apolipoprotein and precursor of AA amyloid.

    Science.gov (United States)

    Marhaug, G; Dowton, S B

    1994-08-01

    Serum amyloid A is an acute phase protein complexed to HDL as an apoprotein. The molecular weight is 11.4-12.5 kDa in different species and the protein has from 104 to 112 amino acids, without or with an insertion of eight amino acids at position 72. The protein is very well conserved throughout evolution, indicating an important biological function. The N-terminal part of the molecule is hydrophobic and probably responsible for the lipid binding properties. The most conserved part is from position 38 to 52 and this part is therefore believed to be responsible for the until now unknown biological function. The protein is coded on chromosome 11p in man, and chromosome 7 in mice, and found in all mammals until now investigated, and also in the Peking duck. In the rat a truncated SAA mRNA has been demonstrated, but no equivalent serum protein has been reported. Acute phase SAA is first of all produced in hepatocytes after induction by cytokines, but extrahepatic expression of both acute phase and constitutive SAA proteins have been demonstrated. Several cytokines, first of all IL-1, IL-6 and TNF are involved in the induction of SAA synthesis, but the mutual importance of these cytokines seems to be cell-type specific and to vary in various experimental settings. The role of corticosteroids in SAA induction is somewhat confusing. In most in vitro studies corticosteroids show an enhancing or synergistic effect with cytokines on SAA production in cultured cell. However, in clinical studies and in vivo studies in animals an inhibitory effect of corticosteroids is evident, probably due to the all over anti-inflammatory effect of the drug. Until now no drug has been found that selectively inhibits SAA production by hepatocytes. Effective anti-inflammatory or antibacterial treatment is the only tool for reducing SAA concentration in serum and reducing the risk of developing secondary amyloidosis. The function of SAA is still unclear. Interesting theories, based on current

  15. Acute phase response of selenium status and glutathione peroxidase activity in blood plasma before and after total knee arthroplasty surgery.

    Science.gov (United States)

    Defi, Irma Ruslina; Yamazaki, Chiho; Kameo, Satomi; Kobayashi, Kenji; Nakazawa, Minato; Shinya, Yanagisawa; Sato, Naoki; Wada, Naoki; Shirakura, Kenji; Koyama, Hiroshi

    2011-12-01

    Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.

  16. Multidetector row computed tomography of acute pancreatitis: Utility of single portal phase CT scan in short-term follow up

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Yongwonn [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of); Park, Hee Sun, E-mail: heesun.park@gmail.com [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of); Kim, Young Jun; Jung, Sung Il; Jeon, Hae Jeong [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of)

    2012-08-15

    Objective: The purpose of this study is to evaluate the question of whether nonenhanced CT or contrast enhanced portal phase CT can replace multiphasic pancreas protocol CT in short term monitoring in patients with acute pancreatitis. Materials and methods: This retrospective study was approved by the Institutional Review Board. From April 2006 to May 2010, a total of 52 patients having acute pancreatitis who underwent initial dual phase multidetector row CT (unenhanced, arterial, and portal phase) at admission and a short term (within 30 days) follow up dual phase CT (mean interval 10.3 days, range 3-28 days) were included. Two abdominal radiologists performed an independent review of three sets of follow up CT images (nonenhanced scan, single portal phase scan, and dual phase scan). Interpretation of each image set was done with at least 2-week interval. Radiologists evaluated severity of acute pancreatitis with regard to pancreatic inflammation, pancreatic necrosis, and extrapancreatic complication, based on the modified CT severity index. Scores of each image set were compared using a paired t-test and interobserver agreement was evaluated using intraclass correlation coefficient statistics. Results: Mean scores of sum of CT severity index on nonenhanced scan, portal phase scan, and dual phase scan were 5.7, 6.6, and 6.5 for radiologist 1, and 5.0, 5.6, and 5.8 for radiologist 2, respectively. In both radiologists, contrast enhanced scan (portal phase scan and dual phase scan) showed significantly higher severity score compared with that of unenhanced scan (P < 0.05), while portal phase and dual phase scan showed no significant difference each other. The trend was similar regarding pancreatic inflammation and extrapancreatic complications, in which contrast enhanced scans showed significantly higher score compared with those of unenhanced scan, while no significant difference was observed between portal phase scan and dual phase scan. In pancreatic necrosis

  17. [Extramedullary onset of mixed phenotype acute leukemia with MLL gene rearrangement].

    Science.gov (United States)

    Kawashima, Ichiro; Shobu, Yuki; Yamamoto, Takeo; Hamanaka, Satoshi; Nozaki, Yumi; Nakajima, Kei; Mitsumori, Toru; Kirito, Keita

    2013-03-01

    Rearrangements of the mixed lineage leukemia MLL gene at chromosome 11q23 are common chromosomal abnormalities in human leukemia. MLL fused with numerous partner genes causes different leukemia phenotypes that depend on the function of partner genes. MLLT3-MLL is generated by translocation t(9;11), which primarily induces acute myeloid leukemia in humans, whereas MLLT3-MLL induces ALL or biphenotypic leukemia in mice. The microenvironment that surrounds leukemia cells plays a central role in this process. We report a patient with mixed phenotype acute leukemia with MLLT3-MLL. This patient, a 44-year-old woman, initially exhibited extramedullary leukemia with multiple tumors and subsequently developed bone marrow disease. The leukemia cells exhibited myeloid (CD13 and MPO) and B cell (CD19 and CD79a) phenotypes. Chromosomal analysis and RT-PCR assay revealed tumor cells with the MLLT3-MLL fusion gene. We treated this patient with a drug regimen for AML (Ara-C plus anthracycline), and complete remission was obtained. This report describes the fourth case of mixed phenotypic leukemia with extramedullary disease. The extramedullary circumstance may underlie the biphenotypic features of these patients.

  18. ADAMTS2 gene dysregulation in T/myeloid mixed phenotype acute leukemia.

    Science.gov (United States)

    Tota, Giuseppina; Coccaro, Nicoletta; Zagaria, Antonella; Anelli, Luisa; Casieri, Paola; Cellamare, Angelo; Minervini, Angela; Minervini, Crescenzio Francesco; Brunetti, Claudia; Impera, Luciana; Carluccio, Paola; Cumbo, Cosimo; Specchia, Giorgina; Albano, Francesco

    2014-12-16

    Mixed phenotype acute leukemias (MPAL) include acute leukemias with blasts that express antigens of more than one lineage, with no clear evidence of myeloid or lymphoid lineage differentiation. T/myeloid (T/My) MPAL not otherwise specified (NOS) is a rare leukemia that expresses both T and myeloid antigens, accounting for less than 1% of all leukemias but 89% of T/My MPAL. From a molecular point of view, very limited data are available on T/My MPAL NOS. In this report we describe a T/My MPAL NOS case with a complex rearrangement involving chromosomes 5 and 14, resulting in overexpression of the ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2) gene due to its juxtaposition to the T cell receptor delta (TRD) gene segment. Detailed molecular cytogenetic characterization of the complex rearrangement in the reported T/My MPAL case allowed us to observe ADAMTS2 gene overexpression, identifying a molecular marker that may be useful for monitoring minimal residual disease. To our knowledge, this is the first evidence of gene dysregulation due to a chromosomal rearrangement in T/My MPAL NOS.

  19. Significance of murine retroviral mutagenesis for identification of disease genes in human acute myeloid leukemia.

    Science.gov (United States)

    Erkeland, Stefan J; Verhaak, Roel G W; Valk, Peter J M; Delwel, Ruud; Löwenberg, Bob; Touw, Ivo P

    2006-01-15

    Retroviral insertion mutagenesis is considered a powerful tool to identify cancer genes in mice, but its significance for human cancer has remained elusive. Moreover, it has recently been debated whether common virus integrations are always a hallmark of tumor cells and contribute to the oncogenic process. Acute myeloid leukemia (AML) is a heterogeneous disease with a variable response to treatment. Recurrent cytogenetic defects and acquired mutations in regulatory genes are associated with AML subtypes and prognosis. Recently, gene expression profiling (GEP) has been applied to further risk stratify AML. Here, we show that mouse leukemia genes identified by retroviral insertion mutagenesis are more frequently differentially expressed in distinct subclasses of adult and pediatric AML than randomly selected genes or genes located more distantly from a virus integration site. The candidate proto-oncogenes showing discriminative expression in primary AML could be placed in regulatory networks mainly involved in signal transduction and transcriptional control. Our data support the validity of retroviral insertion mutagenesis in mice for human disease and indicate that combining these murine screens for potential proto-oncogenes with GEP in human AML may help to identify critical disease genes and novel pathogenetic networks in leukemia.

  20. Vaccination-induced noncytolytic effects in the acute phase of SHIV infection.

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    Janka Petravic

    Full Text Available Many studies have shown that vaccines inducing CD8+ T cell responses can reduce viral loads and preserve CD4+ T cell numbers in monkey models of HIV infection. The mechanism of viral control by the vaccine-induced CD8+ T cells is usually assumed to be cytolysis of infected cells. However, in addition to cytolysis of infected cells, CD8+ T cells secrete a range of soluble factors that suppress viral replication. We have studied the dynamics of virus and CD4+ T cells in a successful vaccination-challenge model of SHIV infection. We find that better viral control in the acute phase of infection is associated with slower decay of peak viral load. Comparing viral and CD4+ T cell dynamics in acute infection, we find that a cytolytic mode of viral control with direct killing of infected cells is inconsistent with the observed trends. On the other hand, comparison of the predicted effects of noncytolytic CD8+ effector function with the experimental data shows that non-cytolytic control provides a better explanation of the experimental results. Our analysis suggests that vaccine-induced CD8+ T cells control SHIV infection by non-cytolytic means.

  1. Global aphasia as a predictor of mortality in the acute phase of a first stroke

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    F F Oliveira

    2011-01-01

    Full Text Available OBJECTIVE: To establish whether vascular aphasic syndromes can predict stroke outcomes. METHOD: Thirty-seven adults were evaluated for speech and language within 72 hours after a single first-ever ischemic brain lesion, in blind association to CT and/or MR. RESULTS: Speech or language disabilities were found in seven (87.5% of the eight deceased patients and twenty-six (89.7% of the twenty-nine survivors. Global aphasia was identified in eleven patients, all with left hemisphere lesions (nine mute; five deceased, consisting on a risk factor for death in the acute stroke phase (ρ=0.022. Age (z=1.65; ρ>0.09, thrombolysis (ρ=0.591, infarct size (ρ=0.076 and side (ρ=0.649 did not significantly influence survival. Absence of aphasia did not predict a better evolution, regardless of the affected hemisphere. Prevalence of cardiovascular risk factors was similar for all patient groups. CONCLUSION: Global aphasia in acute stroke can adversely affect prognosis, translated into impairment of dominant perisylvian vascular territories, with mutism as an important semiological element.

  2. [Glycosylation profile of selected acute phase proteins in children with chronic tonsillitis and allergic symptoms].

    Science.gov (United States)

    Sobieska, Magdalena; Steiner, Iwona; Pucher, Beata; Grzegorowski, Michał; Samborski, Włodzimierz

    2006-01-01

    Acute phase proteins may be regarded as laboratory markers of inflammatory processes of various origin, but they also play several important biological roles. As majority of them are glycoproteins alterations in glycosylations profiles form additional sign of disturbances in the cytokines network during inflammation and allow to distinguish between acute and chronic inflammatory conditions. A group of 25 children, aged from 6 to 13 years, admitted due to tonsillectomy was examined using skin tests towards specific allergens. Fifteen children out of the whole group showed reaction to pollens, whereas in ten children no allergen was detected despite clear allergic symptoms. In sera samples from every child concentrations of C-reactive protein, alpha1-acid glycoprotein (AGP) and alpha1-antichymotrypsin (ACT) were measured using rocket immunoelectrophoresis acc. to Laurell, and glycosylations profiles of AGP and ACT were determined, using crossed affino-immunoelectrophoresis acc. to Bøg-Hansen. Lower concentration of AGP and higher of ACT was shown for children allergic to pollens. Glycosylation profile of both proteins was altered towards higher reactivity with ConA for children allergic to pollens, whereas rather chronic image was observed in children allergic to unknown allergen. The latter image was similar to previously described in children with food allergies. The presence of allergic reaction may alter the cytokine network activity in children, thus affecting also the immune status, independently from chronic inflammatory process in tonsillitis.

  3. [Myocardial infarct after the acute phase--the risk of arrhythmia].

    Science.gov (United States)

    de Azevedo, S G

    1989-03-01

    Upon the development, divulgation and improvement of the Ambulatory Electrocardiographic Monitoring (AEM) techniques, the problem of the arrhythmias after an acute myocardial infarction (AMI) has acquired a new acuteness. Its importance becomes clearly evident from the fact today recognized that about 10% of the patients die within the first year after AMI and that the great majority of them dies suddenly. The prognostic value of certain types of ventricular arrhythmias is now well proved to be an independent risk factor respecting to the late complications of AMI, namely the sudden death issue. In this paper, after referring the prognostic criteria for the ventricular arrhythmias, the Author proposes an AEM execution calendar for the AMI patients, since the late hospital phase (hospital discharge). Afterwards, the controversial therapeutic problem of the ventricular arrhythmias is approached, quoting the pharmacological set-backs and pointing out the AEM limitations in regard to the selection and efficacy confirmation of the anti-arrhythmic drugs. At last, a few conclusions of the "Cardiac Arrhythmia Pilot Study" (CAPS, 1986) are mentioned and an other ongoing multicenter study is referred, whose conclusions will be of capital importance to define the anti-arrhythmic therapy utility in the setting of the post-AMI patients.

  4. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    Science.gov (United States)

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF.

  5. Effect of insulin on the inflammatory and acute phase response after burn injury.

    Science.gov (United States)

    Jeschke, Marc G; Boehning, Darren F; Finnerty, Celeste C; Herndon, David N

    2007-09-01

    After a severe burn, the liver plays a pivotal role by modulating inflammatory processes, metabolic pathways, immune functions, and the acute phase response. Therefore, liver integrity and function are important for recovery. A thermal injury, however, causes hepatic damage by inducing hepatic edema, fatty infiltration, hepatocyte apoptosis, and metabolic derangements associated with insulin resistance and impaired insulin signaling. In preliminary studies, we found that these pathophysiological processes are related to hepatic inflammation, altered intracellular signaling, and mitochondrial dysfunction. We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients. Insulin administration improves survival and decreases the rate of infections in severely burned and critically ill patients. Here, we show that insulin administration decreases the synthesis of proinflammatory cytokines and signal transcription factors and improves hepatic structure and function after a severe burn injury; insulin also restores hepatic homeostasis and improves hepatic dysfunction postburn via alterations in the signaling cascade.

  6. Use of escitalopram to prevent depression and cognitive impairments in the acute phase of stroke

    Directory of Open Access Journals (Sweden)

    Dina Rustemovna Khasanova

    2013-01-01

    Full Text Available The purpose of the study was to comparatively analyze the rate of post-stroke depression and cognitive impairments in escitalopram (cipralex-treated and untreated (control patients. Emotional and affective cognitive symptoms, neurological deficit, and day-to-day activity were evaluated over time 1, 3, and 6 months after treatment. The results of the study indicated that escitalopram used to prevent depression in the acute phase of stroke provided a good effect. This drug caused a prompter recovery of cognitive impairments and reduced the pace of development of neurodegenerative disorders underlying the post-stroke 2D (depression and dementia syndrome. The study group was recorded to have more favorable functional outcomes of stroke and patient mobility indicators associated with lower disability rates.

  7. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    Science.gov (United States)

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  8. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

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    Rosana Macher Teodori

    2011-01-01

    Full Text Available There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1, those that began to swim 14 days after injury (CS14, injured rats not submitted to swimming (C, and uninjured rats submitted to swimming (S. After 30 days the number of axons in CS1 and CS14 was lower than in C (P0.05. Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury.

  9. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    Science.gov (United States)

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection.

  10. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov;

    2016-01-01

    /kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein α-2-macroglobulin (α-2-M) 24 h after LPS. Also...... μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver mRNA or serum levels of α-2-M. Also, the conjugate reduced TNF-α (7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6 (15685 ± 3779 pg/mL vs 25715...

  11. Pig-MAP, porcine acute phase proteins and standardisation of assays in Europe

    DEFF Research Database (Denmark)

    Alava, M.A.; Gonzalez-Ramon, N.; Heegaard, Peter M. H.;

    1997-01-01

    reactive protein (CRP) and haptoglobin (Hp) increase 5-7 times 48 h after the injection. Porcine Alb, alpha-lipoprotein, fetuin and transferrin were negative APP. Finally, the concentration of alpha(1)-acid glycoprotein and alpha(1)-protease inhibitor (alpha(1)-antitrypsin) did not change significantly......The pattern of plasma proteins changes greatly following infection, inflammation or tissue injury. The concentration of some proteins referred to as acute phase proteins (APPs) significantly increases within hours or days after the onset of these processes. In contrast, the concentration of other...... for the presence of infectious, inflammatory and pathological lesions in animals. The ability to monitor the APP concentration in serum of pigs will improve the quality and safety of the meat produced as well as provide important diagnostic information for animal health and welfare. The serum concentration of APP...

  12. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    Science.gov (United States)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  13. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    Science.gov (United States)

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; Montebelo, Maria Imaculada de Lima

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. PMID:21876821

  14. Genome-wide gene expression profiling of acute metal exposures in male zebrafish

    Directory of Open Access Journals (Sweden)

    Christine E. Baer

    2014-12-01

    Full Text Available To capture global responses to metal poisoning and mechanistic insights into metal toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate at concentrations corresponding to their respective 96 h LC20, LC40 and LC60 (i.e. 96 h concentrations at which 20%, 40% and 60% lethality is expected, respectively. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal exposure. Here we describe in detail the contents and quality controls for the gene expression and other data associated with the study published by Hussainzada and colleagues in BMC Pharmacology and Toxicology (Hussainzada et al., 2014 with the data uploaded to Gene Expression Omnibus (accession number GSE50648.

  15. Genome-wide gene expression profiling of acute metal exposures in male zebrafish

    Science.gov (United States)

    Baer, Christine E.; Ippolito, Danielle L.; Hussainzada, Naissan; Lewis, John A.; Jackson, David A.; Stallings, Jonathan D.

    2014-01-01

    To capture global responses to metal poisoning and mechanistic insights into metal toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate at concentrations corresponding to their respective 96 h LC20, LC40 and LC60 (i.e. 96 h concentrations at which 20%, 40% and 60% lethality is expected, respectively). Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal exposure. Here we describe in detail the contents and quality controls for the gene expression and other data associated with the study published by Hussainzada and colleagues in BMC Pharmacology and Toxicology (Hussainzada et al., 2014) with the data uploaded to Gene Expression Omnibus (accession number GSE50648). PMID:26484131

  16. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    Science.gov (United States)

    Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

    2017-01-01

    Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening PMID:28217503

  17. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    Directory of Open Access Journals (Sweden)

    Pradip P Dalwadi

    2017-01-01

    Full Text Available Introduction: Traumatic brain injury (TBI is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3 and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening

  18. Optimal combinations of acute phase proteins for detecting infectious disease in pigs

    Directory of Open Access Journals (Sweden)

    Heegaard Peter MH

    2011-03-01

    Full Text Available Abstract The acute phase protein (APP response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect any disease with an inflammatory component seven porcine APPs were analysed in serum sampled at regular intervals in six different experimental challenge groups of pigs, including three bacterial (Actinobacillus pleuropneumoniae, Streptococcus suis, Mycoplasma hyosynoviae, one parasitic (Toxoplasma gondii and one viral (porcine respiratory and reproductive syndrome virus infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP, haptoglobin (Hp, pig major acute phase protein (pigMAP and serum amyloid A (SAA and three negative (albumin, transthyretin, and apolipoprotein A1 (apoA1 were performed in the more than 400 serum samples constituting the serum panel. This was followed by advanced statistical treatment of the data using a multi-step procedure which included defining cut-off values and calculating detection probabilities for single APPs and for APP combinations. Combinations of APPs allowed the detection of disease more sensitively than any individual APP and the best three-protein combinations were CRP, apoA1, pigMAP and CRP, apoA1, Hp, respectively, closely followed by the two-protein combinations CRP, pigMAP and apoA1, pigMAP, respectively. For the practical use of such combinations, methodology is described for establishing individual APP threshold values, above which, for any APP in the combination, ongoing infection/inflammation is indicated.

  19. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    Science.gov (United States)

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  20. An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Taskesen, E.; Staal, F.J.T.; Reinders, M.J.T.

    2015-01-01

    Background The wingless-Int (WNT) pathway has an essential role in cell regulation of hematopoietic stem cells (HSC). For Acute Myeloid Leukemia (AML), the malignant counterpart of HSC, currently only a selective number of genes of the WNT pathway are analyzed by using either gene expression or DNA-

  1. Defined symptom-change trajectories during acute-phase cognitive therapy for depression predict better longitudinal outcomes.

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2016-12-01

    Acute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD), but responders experience varying post-acute outcomes (e.g., relapse vs. recovery). Responders' symptom-change trajectories during response to acute-phase CT may predict longer term outcomes. We studied adult outpatients (N = 220) with recurrent MDD who responded to CT but had residual symptoms. Responders with linear (steady improvement), log-linear (quicker improvement earlier and slower later), one-step (a single, relatively large, stable improvement between adjacent assessments), or undefined (not linear, log-linear, or one-step) symptom trajectories were assessed every 4 months for 32 additional months. Defined (linear, log-linear, one-step) versus undefined acute-phase trajectories predicted lower depressive symptoms (d = 0.36), lower weekly probability of being in a major depressive episode (OR = 0.46), higher weekly probabilities of remission (OR = 1.93) and recovery (OR = 2.35), less hopelessness (d = 0.41), fewer dysfunctional attitudes (d = 0.31), and better social adjustment (d = 0.32) for 32 months after acute-phase CT. Differences among defined trajectory groups were nonsignificant. Responding to acute-phase CT with a defined trajectory (orderly pattern) of symptom reduction predicts better longer term outcomes, but which defined trajectory (linear, log-linear, or one-step) appears unimportant. Frequent measurement of depressive symptoms to identify un/defined CT response trajectories may clarify need for continued clinical monitoring and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Gene mutation patterns in patients with minimally differentiated acute myeloid leukemia.

    Science.gov (United States)

    Kao, Hsiao-Wen; Liang, Der-Cherng; Wu, Jin-Hou; Kuo, Ming-Chung; Wang, Po-Nan; Yang, Chao-Ping; Shih, Yu-Shu; Lin, Tung-Huei; Huang, Yu-Hui; Shih, Lee-Yung

    2014-06-01

    Minimally differentiated acute myeloid leukemia (AML-M0) is a rare subtype of AML with poor prognosis. Although genetic alterations are increasingly reported in AML, the gene mutations have not been comprehensively studied in AML-M0. We aimed to examine a wide spectrum of gene mutations in patients with AML-M0 to determine their clinical relevance. Twenty gene mutations including class I, class II, class III of epigenetic regulators (IDH1, IDH2, TET2, DNMT3A, MLL-PTD, ASXL1, and EZH2), and class IV (tumor suppressor genes) were analyzed in 67 patients with AML-M0. Mutational analysis was performed with polymerase chain reaction-based assays followed by direct sequencing. The most frequent gene mutations from our data were FLT3-ITD/FLT3-TKD (28.4%), followed by mutations in IDH1/IDH2 (28.8%), RUNX1 (23.9%), N-RAS/K-RAS (12.3%), TET2 (8.2%), DNMT3A (8.1%), MLL-PTD (7.8%), and ASXL1 (6.3%). Seventy-nine percent (53/67) of patients had at least one gene mutation. Class I genes (49.3%) were the most common mutated genes, which were mutually exclusive. Class III genes of epigenetic regulators were also frequent (43.9%). In multivariate analysis, old age [hazard ratio (HR) 1.029, 95% confidence interval (CI) 1.013-1.044, P=.001) was the independent adverse factor for overall survival, and RUNX1 mutation (HR 2.326, 95% CI 0.978-5.533, P=.056) had a trend toward inferior survival. In conclusion, our study showed a high frequency of FLT3, RUNX1, and IDH mutations in AML-M0, suggesting that these mutations played a role in the pathogenesis and served as potential therapeutic targets in this rare and unfavorable subtype of AML.

  3. DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE

    Directory of Open Access Journals (Sweden)

    A. V. Vinogradov

    2015-01-01

    Full Text Available Aim: to estimate the frequency of DNMT3A gene exons 18–26 point mutations in acute myeloid leukemia (AML patients (pts using target automatic sequencing technique.Material and Methods. Bone marrow and peripheral blood samples were obtained from 34 AML pts aged 21 to 64, who were treated in Sverdlovsk Regional Hematological Centre (Ekaterinburg during the period 2012–2014. Distribution of the pts according to FAB-classification was as follows: AML M0 – 3, M1 – 1, M2 – 12, M3 – 3, M4 – 10, M5 – 2, M6 – 1, M7 – 1, blastic plasmacytoid dendritic cell neoplasm – 1. Total RNA was extracted from leukemic cells and subjected to reverse transcription. DNMT3A gene exons 18–26 were amplified by PCR. Detection of mutations in DNMT3A gene was performed by direct sequencing. Sequencing was realized using an automatic genetic analyzer ABI Prism 310.Results. The average frequency of functionally significant point mutations in DNMT3A gene exons 18– 26 among the treated AML pts was 5.9%. They were detected in morphological subgroups M2 and M4(according to WHO classification. The average frequency of DNMT3A gene exons 18–26 point mutations among the AML M2 and M4 pts without chromosomal aberrations and TP53 gene point mutations was 14.3%. In both cases there were samples in which DNMT3A gene mutations were accompanied by molecular lesions of NPM1, KRAS and WT1 genes. AML pts with DNMT3A gene exons 18–26 point mutations characterized by poor response to standard chemotherapeutic regimens and unfavorable prognosis.

  4. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    ) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...

  5. Improved oxygen uptake efficiency slope in acute myocardial infarction patients after early phase I cardiac rehabilitation.

    Science.gov (United States)

    Tsai, Yun-Jeng; Li, Min-Hui; Chen, Chia-Hsin; Tuan, Sheng-Hui; Chen, Yi-Jen; Lin, Ko-Long

    2017-09-01

    A predischarge submaximal exercise test is often recommended after acute myocardial infarction (AMI) as part of phase I cardiac rehabilitation. In this study, a submaximal exercise parameter, oxygen uptake efficiency slope (OUES), was used to monitor the benefit of early mobilization within 48 h after AMI. An early mobilization protocol within 48 h after AMI has been initiated since 1 September 2012 in our center. Patients with onset time of AMI within 1 year before and 1 year after initiation of the early mobilization protocol were recruited for comparisons. Sixty patients were analyzed on the basis of this criterion, and were subjected to predischarge submaximal exercise tests. The OUES calculated with 100% exercise duration (OUES100) and calculated with the first 50% of exercise duration (OUES50) were obtained and analyzed. Both OUES100 and OUES50 of the AMI patients with early mobilization were significantly higher than those without early mobilization (P=0.025 and 0.007, respectively). The OUES100 and OUES50 were also highly correlated (r=0.891, P<0.001). The subgroup analysis using patients within 3 months before and 3 months after initiation of the protocol also showed a significant difference. OUES could be used to measure the exercise capacity and monitor the effect of phase I cardiac rehabilitation in patients soon after AMI. Early mobilization within 48 h following AMI significantly enhanced the patient's exercise capacity.

  6. Gene expression profiling of acute type A aortic dissection combined with in vitroassessment†.

    Science.gov (United States)

    Kimura, Naoyuki; Futamura, Kyoko; Arakawa, Mamoru; Okada, Naoko; Emrich, Fabian; Okamura, Homare; Sato, Tetsuya; Shudo, Yasuhiro; Koyano, Tiffany K; Yamaguchi, Atsushi; Adachi, Hideo; Matsuda, Akio; Kawahito, Koji; Matsumoto, Kenji; Fischbein, Michael P

    2017-04-11

    The mechanisms underlying aortic dissection remain to be fully elucidated. We aimed to identify key molecules driving dissection through gene expression profiling achieved by microarray analysis and subsequent in vitro experiments using human aortic endothelial cells (HAECs) and aortic vascular smooth muscle cells (AoSMCs). Total RNA, including microRNA (miRNA), was isolated from the intima-media layer of dissected ascending aorta obtained intraoperatively from acute type A aortic dissection (ATAAD) patients without familial thoracic aortic disease ( n  = 8) and that of non-dissected ascending aorta obtained from transplant donors ( n  = 9). Gene expression profiling was performed with mRNA and miRNA microarrays, and results were confirmed by quantitative polymerase chain reaction (qPCR). Target genes and miRNA were identified by gene ontology analysis and a literature search. To reproduce the in silico results, HAECs and AoSMCs were stimulated in vitro by upstream cytokines, and expression of target genes was assessed by qPCR. Microarray analysis revealed 1536 genes (3.6%, 1536/42 545 probes) and 41 miRNAs (3.0%, 41/1368 probes) that were differentially expressed in the ATAAD group (versus donor group). The top 15 related pathways included regulation of inflammatory response, growth factor activity and extracellular matrix. Gene ontology analysis identified JAK2 (regulation of inflammatory response), PDGFA, TGFB1, VEGFA (growth factor activity) and TIMP3 , TIMP4, SERPINE1 (extracellular matrix) as the target genes and miR-21-5p, a TIMP3 repressor, as target miRNA that interacts with the target genes. Validation qPCR confirmed the altered expression of all 7 target genes and miR-21-5p in dissected aorta specimens (all genes, P  < 0.05). Ingenuity pathway analysis showed TNF-α and TGF-β to be upstream cytokines for the target genes. In vitro experiments showed these cytokines inhibit TIMP3 expression ( P  < 0.05) and enhance VEGFA expression ( P

  7. Serum protein capillary electrophoresis and measurement of acute phase proteins in a captive cheetah (Acinonyx jubatus) population.

    Science.gov (United States)

    Depauw, Sarah; Delanghe, Joris; Whitehouse-Tedd, Katherine; Kjelgaard-Hansen, Mads; Christensen, Michelle; Hesta, Myriam; Tugirimana, Pierrot; Budd, Jane; Dermauw, Veronique; Janssens, Geert P J

    2014-09-01

    Renal and gastrointestinal pathologies are widespread in the captive cheetah (Acinonyx jubatus) population but are often diagnosed at a late stage, because diagnostic tools are limited to the evaluation of clinical signs or general blood examination. Presently, no data are available on serum proteins and acute-phase proteins in cheetahs during health or disease, although they might be important to improve health monitoring. This study aimed to quantify serum proteins by capillary electrophoresis in 80 serum samples from captive cheetahs, categorized according to health status and disease type. Moreover, serum amyloid A concentrations were measured via a turbidimetric immunoassay validated in domestic cats, whereas haptoglobin and C-reactive protein were determined by non-species-specific functional tests. Cheetahs classified as healthy had serum protein and acute phase protein concentrations within reference ranges for healthy domestic cats. In contrast, unhealthy cheetahs had higher (P cheetahs suffering from chronic kidney disease were significantly greater compared to the reportedly healthy cheetahs. Our study indicates that serum proteins in the cheetah can be analyzed by routine capillary electrophoresis, whereas acute-phase proteins can be measured using available immunoassays or non-species-specific techniques, which are also likely to be applicable in other exotic felids. Moreover, results suggest that serum amyloid A and haptoglobin are important acute-phase proteins in the diseased cheetah and highlight the need to evaluate their role as early-onset markers for disease.

  8. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    Science.gov (United States)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  9. Prenatal transportation alters the acute phase response (APR) of bull calves exposed to a lipopolysaccharide (LPS) challenge

    Science.gov (United States)

    This study was designed to determine if prenatal transportation influences the acute phase response (APR) to a postnatal Lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day...

  10. The effects of grain-induced subactue ruminal acidosis on interleukin-6 and acute phase response in dairy cows

    DEFF Research Database (Denmark)

    Li, Shucong; Danscher, Anne Mette; Andersen, Pia Haubro

    2014-01-01

    Subacute ruminal acidosis (SARA) resulting from excessive grain feeding to dairy cows is accompanied by an acute phase response. Interleukin 6 (IL-6) has been proposed as a mediator of this response. We tested if the acute phase response associated with grain-induced SARA is mediated by IL-6. Six...... 5, and d 3 before SARA induction and during three SARA days. ELISA kits were used for measurement of IL-6, and the acute phase proteins haptoglobin (Hp), LPS binding protein (LBP), and serum amyloid A (SAA). The SARA challenge tended to increase LBP (7.54 vs. 10.23 mg/L, P = 0.10), and increased...... the SAA (4.24 vs. 11.60 mg/L, P = 0.04) and Hp (3.57 vs. 22.09 mg/L, P = 0.04) in blood plasma, confirming that the challenge caused an acute phase response. Concentrations of IL-6 were not affected by the SARA challenge, and averaged 5.06 ng/mL across treatments. Our data do not confirm that IL-6...

  11. The effect of yeast cell wall supplementation on the physiological and acute phase responses of crossbred heifers to endotoxin challenge

    Science.gov (United States)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to endotoxin (lipopolysaccharide; LPS) challenge. Heifers (n=24; 218.9+/-2.4 kg) were obtained from commercial sale barns and tra...

  12. Yeast cell wall supplementation alters the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Science.gov (United States)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to an endotoxin challenge. Heifers (n = 24; 219 ± 2.4 kg) were separated into treatment groups receiving a Control diet (n = 8), ...

  13. Dried citrus pulp modulates the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Science.gov (United States)

    This study examined the effect of feeding dried citrus pulp (CP) pellets on the physiological and acute phase responses (APR) of newly-received crossbred heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Heifers (n=24; 218.3±2.4 kg) were obtained from commercial sale barns and transported...

  14. Supplementation of Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in pigs.

    Science.gov (United States)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kilograms body weight) were housed individually in pens with ad libi...

  15. CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase.

    Science.gov (United States)

    Mehde, Atheer Awad; Yusof, Faridah; Adel Mehdi, Wesen; Zainulabdeen, Jwan Abdulmohsin

    2015-01-01

    ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

  16. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    Science.gov (United States)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  17. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Idalia Garza-Veloz

    2015-01-01

    Full Text Available Background. Acute lymphoblastic leukemia type B (B-ALL is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05. There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27. The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05. Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

  18. [Identification of novel pathogenic gene mutations in pediatric acute myeloid leukemia by whole-exome resequencing].

    Science.gov (United States)

    Shiba, Norio

    2015-12-01

    A new class of gene mutations, identified in the pathogenesis of adult acute myeloid leukemia (AML), includes DNMT3A, IDH1/2, TET2 and EZH2. However, these mutations are rare in pediatric AML cases, indicating that pathogeneses differ between adult and pediatric forms of AML. Meanwhile, the recent development of massively parallel sequencing technologies has provided a new opportunity to discover genetic changes across entire genomes or proteincoding sequences. In order to reveal a complete registry of gene mutations, we performed whole exome resequencing of paired tumor-normal specimens from 19 pediatric AML cases using Illumina HiSeq 2000. In total, 80 somatic mutations or 4.2 mutations per sample were identified. Many of the recurrent mutations identified in this study involved previously reported targets in AML, such as FLT3, CEBPA, KIT, CBL, NRAS, WT1 and EZH2. On the other hand, several genes were newly identified in the current study, including BCORL1 and major cohesin components such as SMC3 and RAD21. Whole exome resequencing revealed a complex array of gene mutations in pediatric AML genomes. Our results indicate that a subset of pediatric AML represents a discrete entity that could be discriminated from its adult counterpart, in terms of the spectrum of gene mutations.

  19. Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    GUO ChunYu; YIN HuiJun; JIANG YueRong; XUE Mei; SHI DaZhuo

    2008-01-01

    To determine the differential genes in ischemic myocardium of Wistar rats with acute myocardial in-farction (AMI),we constructed two differential gone expression profiles.AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats.Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point at the 8th day after the operation.Dif-ferential gone expression profiles of the two samples were constructed by using long serial analysis of gone expression (LongSAGE).Real time fluorescence quantitative PCR (Q-PCR) was used to confirm the expression changes of partial target genes.The main results were as follows:a total of 15966 tags were screened from the normal and the ischemic LongSAGE maps,and 9646 tags in the normal tissue and 9563 tags in the ischemic tissue were obtained.Among them,7665 novel tags were identified by NCBI BLAST search.In the ischemic tissue,142 genes significantly changed compared to those in the normal tissue (P<0.05).These differentially expressed genes may play important roles in the pathways of oxidation and phosphoryiation,ATP synthesis and glycolysis and so on.Partial genes identified by the LongSAGE were confirmed by Q-PCR.The results show that AMI causes a series of gone expres-sion changes in the regulation of the pathways related to energy metabolism.

  20. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Jaime-Perez, Jose Carlos; Carrillo-Sanchez, Karol; Ramos-Del Hoyo, Maria Guadalupe; Lugo-Trampe, Angel; Gutierrez-Aguirre, Cesar Homero; Gonzalez-Llano, Oscar; Salazar-Riojas, Rosario; Hidalgo-Miranda, Alfredo; Gomez-Almaguer, David

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. PMID:25802479

  1. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    NARCIS (Netherlands)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.; Niewold, T.A.; Heegaard, P.M.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were highe

  2. Value of oral glucose tolerance test in the acute phase of myocardial infarction

    Directory of Open Access Journals (Sweden)

    Grabczewska Zofia

    2011-03-01

    Full Text Available Abstract Background Although European guidelines advise oral glucose tolerance test (OGTT in patients with acute myocardial infarction (AMI before or shortly after hospital discharge, data supporting this recommendation are inconclusive. We aimed to analyze whether disturbances in glucose metabolism diagnosed before hospital discharge in AMI patients represents a latent pre-existing condition or rather temporary finding. Additionally, we planned to investigate the value of pre-selected glycemic control parameters as predictors of long-term glucometabolic state. Methods We assessed admission glycemia, glycated hemoglobin, mean blood glucose concentration on days 1 and 2 in 200 patients with a first AMI but without overt disturbances of glucose metabolism. We also performed OGTT at discharge and 3 months after discharge. Results The prevalence of disturbances in glucose metabolism (as assessed by OGTT at 3 months was significantly lower than at discharge (29% vs. 48%, p = 0.0001. Disturbances in glucose metabolism were not confirmed in 63% of patients with impaired glucose tolerance and in 36% of patients with diabetes mellitus diagnosed during the acute phase of AMI. Age >77 years, glucose ≥12.06 mmol/l at 120 minutes during OGTT before discharge and mean blood glucose level on day 2 >7.5 mmol/l were identified as independent predictors of disturbances in glucose metabolism at the 3-month follow-up. Conclusions Disturbances in glucose metabolism observed in patients with a first AMI are predominantly transient. Elderly age, high plasma glucose concentration at 120 minutes during OGTT at discharge and elevated mean blood glucose level on day 2 were associated with sustained disturbances in glucose metabolism.

  3. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    Science.gov (United States)

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  4. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

    Science.gov (United States)

    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

  5. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Science.gov (United States)

    Mithal, Leena B; Palac, Hannah L; Yogev, Ram; Ernst, Linda M; Mestan, Karen K

    2017-01-01

    Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  6. Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population.

    Science.gov (United States)

    Iqbal, Mohammad Perwaiz; Iqbal, Khalida; Tareen, Asal Khan; Parveen, Siddiqa; Mehboobali, Naseema; Haider, Ghulam; Iqbal, Saleem Perwaiz

    2016-11-01

    High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.

  7. Drosophila highwire gene modulates acute ethanol sensitivity in the nervous system

    Institute of Scientific and Technical Information of China (English)

    Awoyemi A.AWOFALA

    2011-01-01

    Animals exhibit behavioral differences in their sensitivity to ethanol,a trait that is at least in part due to genetic predispositions.This study has implicated a large neuronal protein involving Highwire,a Drosophila E3 ubiquitin ligase (Hiw,a homolog of Pam,a protein associated with Myc found in humans) in acute sensitivity to ethanol sedation.Flies lacking Hiw were hypersensitive to the sedating effect of ethanol whereas those overexpressing Hiw showed decreased sensitivity to ethanol.Furthermore,RNAi functional knockdown of Hiw in adult neurons or ellipsoid body neurons showed increased sensitivity to ethanol sedation.None of these manipulations of the hiw gene caused changes in the rate of ethanol absorption and/or metabolism.These results suggest a previously unknown role for this highly conserved gene in regulating the behavioral responses to an addictive drug.

  8. The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.;

    2000-01-01

    respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7-8 days after inoculation of BRSV, while no response...... was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response......The ability of a pure virus infection to induce an acute phase protein response is of interest as viral infections are normally considered to be less efficient in inducing an acute phase protein response than bacterial infections. This was studied in a bovine model for infection with bovine...

  9. Insertional oncogenesis by non-acute retroviruses: implications for gene therapy.

    Science.gov (United States)

    Fan, Hung; Johnson, Chassidy

    2011-04-01

    Retroviruses cause cancers in a variety of animals and humans. Research on retroviruses has provided important insights into mechanisms of oncogenesis in humans, including the discovery of viral oncogenes and cellular proto-oncogenes. The subject of this review is the mechanisms by which retroviruses that do not carry oncogenes (non-acute retroviruses) cause cancers. The common theme is that these tumors result from insertional activation of cellular proto-oncogenes by integration of viral DNA. Early research on insertional activation of proto-oncogenes in virus-induced tumors is reviewed. Research on non-acute retroviruses has led to the discovery of new proto-oncogenes through searches for common insertion sites (CISs) in virus-induced tumors. Cooperation between different proto-oncogenes in development of tumors has been elucidated through the study of retrovirus-induced tumors, and retroviral infection of genetically susceptible mice (retroviral tagging) has been used to identify cellular proto-oncogenes active in specific oncogenic pathways. The pace of proto-oncogene discovery has been accelerated by technical advances including PCR cloning of viral integration sites, the availability of the mouse genome sequence, and high throughput DNA sequencing. Insertional activation has proven to be a significant risk in gene therapy trials to correct genetic defects with retroviral vectors. Studies on non-acute retroviral oncogenesis provide insight into the potential risks, and the mechanisms of oncogenesis.

  10. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Energy Technology Data Exchange (ETDEWEB)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  11. Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

    Science.gov (United States)

    Gofshteyn, Jacqueline S; Wilfong, Angus; Devinsky, Orrin; Bluvstein, Judith; Charuta, Joshi; Ciliberto, Michael A; Laux, Linda; Marsh, Eric D

    2017-01-01

    Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

  12. Association of two polymorphisms of tumor necrosis factor gene with acute biliary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Dian-Liang Zhang; Jie-Shou Li; Zhi-Wei Jiang; Bao-Jun Yu; Xing-Ming Tang; Hong-Mei Zheng

    2003-01-01

    AIM: To investigate TNF-α-308 and TNFB polymorphisms in acute biliary pancreatitis (ABP) and to related them to the plasma TNF-α levels.METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients (n=127) and healthy controls (n=-102)using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Reading the size of digested bands from polyacrylamide gel demonstrated the two alleles TNF1 and TNF2, or the two alleles TNFB1and TNFB2.RESULTS: The frequencies of TNF2 polymorphism and TNFB2 polymorphism were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. Patients with septic shock showed a significantly higher prevalence of the TNF2 than those without. No significant differences were found in the genotype distribution of TNF-α-308 and TNFB among different groups. Plasma TNF-α levels did not differ significantly in ASBP patients displaying different alleles of the TNF gene studied.CONCLUSION: Results indicate that TNF gene polymorphisms studied play no part in determination of disease severity or susceptibility to acute biliary pancreatitis; however, TNF2polymorphism is associated with septic shock from ASBP.Genetic factors are not important in determining plasma TNF-α levels in ASBP.

  13. FMS-LIKE TYROSINE KINASE (FLT3 GENE ITD MUTATION IN ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Rajko Kusec

    2004-12-01

    Full Text Available Background. FLT3 is a class III receptor tyrosine kinase expressed in normal stem cells and blasts of myeloid leukemia. Internal tandem duplication (ITD of the FLT3 gene affecting the exons 14 and 15 leads to ligand-independent FLT3 dimerization and constitutive activation. This stimulates proliferation and induces inhibition of apoptosis which contributes to leukemogenesis. We have screened a panel of acute myeloid leukemia (AML patients for the occurrence of FLT3/ITD mutation and correlated this mutation to patients’ survival and basic hematological parameters.Methods. RT-PCR for ITD in exons 14 and 15 of FLT3 gene was done on bone marrow samples of 67 AML patients at diagnosis.Results. There was a 16.4% incidence of FLT3/ITD mutation in the cohort of examined patients. By cytognetic subgroups there were 2/6 t(15;17 and 1 of 4 t(8;21 positive patients. The rest had normal and 2 had complex karyotype. Majority were of FAB M2 or M4 phenotype. For a subset of patients taken into comparative survival analysis there was a clear disadvantage for FLT3/ITD patients. No difference was found for basic hematological parameters between two groups.Conclusions. As it is evident today that FLT3/ITD is the single most common genetic abnormality in AML that also presents unfavorable clinical prognostic marker, it should be included in molecular diagnostic testing of acute myeloid leukemia.

  14. Promotion of acute-phase skin wound healing by Pseudomonas aeruginosa C4 -HSL.

    Science.gov (United States)

    Kanno, Emi; Kawakami, Kazuyoshi; Miyairi, Shinichi; Tanno, Hiromasa; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Gotoh, Naomasa; Maruyama, Ryoko; Tachi, Masahiro

    2016-12-01

    A Pseudomonas aeruginosa quorum-sensing system, which produces N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12 -HSL) and N-butanoyl-l-homoserine lactone (C4 -HSL), regulates the virulence factors. In our previous study, 3-oxo-C12 -HSL, encoded by lasI gene, was shown to promote wound healing. However, the effect of C4 -HSL, encoded by rhlI gene, remains to be elucidated. We addressed the effect of C4 -HSL on wounds in P. aeruginosa infection. Wounds were created on the backs of Sprague-Dawley SD rats, and P. aeruginosa PAO1 (PAO1) or its rhlI deletion mutant (ΔrhlI) or lasI deletion mutant (ΔlasI) was inoculated onto the wound. Rats were injected intraperitoneally with anti-C4 -HSL antiserum or treated with C4 -HSL at the wound surface. PAO1 inoculation led to significant acceleration of wound healing, which was associated with neutrophil infiltration and TNF-α synthesis. These responses were reversed, except for TNF-α production, when ΔrhlI was inoculated instead of PAO1 or when rats were co-treated with PAO1 and anti-C4 -HSL antiserum. In contrast, the healing process and neutrophil infiltration, but not TNF-α synthesis, were accelerated when C4 -HSL was administered in the absence of PAO1. This acceleration was not affected by anti-TNF-α antibody. These results suggest that C4 -HSL may be involved in the acceleration of acute wound healing in P. aeruginosa infection by modifying the neutrophilic inflammation. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  15. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML with normal cytogenetics.

    Directory of Open Access Journals (Sweden)

    Marta Fernandez-Mercado

    Full Text Available Acute myeloid leukemia patients with normal cytogenetics (CN-AML account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8% and FLT3 (50.0%, and in secondary cases ASXL1 (48.5% and TET2 (30.3%. We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  16. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics.

    Science.gov (United States)

    Fernandez-Mercado, Marta; Yip, Bon Ham; Pellagatti, Andrea; Davies, Carwyn; Larrayoz, María José; Kondo, Toshinori; Pérez, Cristina; Killick, Sally; McDonald, Emma-Jane; Odero, María Dolores; Agirre, Xabier; Prósper, Felipe; Calasanz, María José; Wainscoat, James S; Boultwood, Jacqueline

    2012-01-01

    Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  17. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.

    Science.gov (United States)

    von Bergh, Anne R M; Beverloo, H Berna; Rombout, Paul; van Wering, Elisabeth R; van Weel, Margreet H; Beverstock, Geoffrey C; Kluin, Philip M; Slater, Rosalyn M; Schuuring, Ed

    2002-09-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia.

  18. Effects of balneotherapy on the reactants of acute inflammation phase in Ankylosing spondylitis

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    Stamenković Bojana

    2009-01-01

    Full Text Available Introduction. Ankylosing spondylitis (AS is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. Objective. The aim of the research was to establish serum concentrations of C-reactive protein (CRP, α 1-acid glycoprotein (α 1-AGP, ceruloplasmine (CP and erythrocyte sedimentation rate (SE before and after the balneotherapy in ankylosing spondylitis. Methods. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute 'Niška Banja'. All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy; the serum concentrations of CRP, α1-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. Results. After dosed balneotherapy, a significant decrease in the concentrations of CP (p<0.05, α1-AGP (p<0.01 and CRP (p<0.05 was registered in the serums of AS patients. ESR was not significantly reduced. Conclusion. The research proved that α 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

  19. Relationship of Acute Phase Reactants and Fat Accumulation during Treatment for Tuberculosis

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    Alejandro Sanchez

    2011-01-01

    Full Text Available Background. Tuberculosis causes inflammation and muscle wasting. We investigated how attenuation of inflammation relates to repletion of body composition during treatment in an underserved population. Design. Twenty-four patients (23 to 79 years old with pulmonary tuberculosis and inflammation (pretreatment albumin =2.96±0.13 g/dL, C-reactive protein [CRP] =6.71±1.34 μg/dL, and beta-2-microglobulin =1.68±0.10 μg/L were evaluated and had BIA over 24 weeks. Results. Weight increased by 3.02±0.81 kg (5.5%; =0.007 at week 4 and by 8.59±0.97 kg (15.6%; <0.0001 at week 24. Repletion of body mass was primarily fat, which increased by 2.09±0.52 kg at week 4 and 5.05±0.56 kg at week 24 (=0.004 and <0.0001 versus baseline. Fat-free mass (FFM, body cell mass (BCM, and phase angle did not increase until study week 8. Albumin rose to 3.65±0.14 g/dL by week 4 (<0.001 and slowly increased thereafter. CRP levels declined by ~50% at each interval visit. Conclusions. During the initial treatment, acute phase reactants returned towards normal. The predominant accrual of fat mass probably reflects ongoing, low levels of inflammation.

  20. Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

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    Kosan, C. [Department of Pediatric Nephrology, Faculty of Medicine, Ataturk University, Erzurum (Turkey); Cayir, A.; Turan, M.I. [Department of Pediatrics, Faculty of Medicine, Ataturk University, Erzurum (Turkey)

    2013-09-18

    Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity.

  1. Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

    Science.gov (United States)

    Kosan, C.; Cayir, A.; Turan, M.I.

    2013-01-01

    Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity. PMID:24141617

  2. Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

    Directory of Open Access Journals (Sweden)

    C. Kosan

    2013-09-01

    Full Text Available Familial Mediterranean fever (FMF is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity.

  3. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    Science.gov (United States)

    Okino, Alessandra M.; Bürger, Cristiani; Cardoso, Jefferson R.; Lavado, Edson L.; Lotufo, Paulo A.; Campa, Ana

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 ± 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 ± 0.37 and 0.68 ± 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764;p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8–360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates. PMID:16864904

  4. Acute-phase protein behavior in dairy cattle herd naturally infected with Trypanosoma vivax.

    Science.gov (United States)

    Sampaio, Paulo Henrique; Fidelis Junior, Otavio Luiz; Marques, Luiz Carlos; Machado, Rosangela Zacarias; Barnabé, Patrícia de Athayde; André, Marcos Rogério; Balbuena, Tiago Santana; Cadioli, Fabiano Antonio

    2015-07-30

    Trypanosoma vivax is a hemoprotozoon that causes disease in cattle and is difficult to diagnose. The host-parasite relationship in cattle that are infected by T. vivax has only been poorly studied. In the present study, a total of 429 serum proteinograms were produced from naturally infected animals (NIF) and were compared with 50 samples from control animals (C). The total protein, IgA band, complement C3 β chain band, albumin band, antitrypsin band, IgG band, haptoglobin band, complement C3c α chain band and protein HP-20 band presented higher levels in the serum proteinograms of the NIF group. Inter-alpha-trypsin inhibitor heavy chain H4, α2-macroglobulin, complement C6, ceruloplasmin, transferrin band and apolipoprotein A1 band presented lower levels in this group. There was no significant difference (pNIF and C groups. Acute phase proteins may be useful for understanding the host-parasite relationship, since the antitrypsin band was only present in the NIF group. This can be used as an indicator for infection in cattle that are naturally infected by T. vivax.

  5. Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention.

    Science.gov (United States)

    Rahel, Braim M; Visseren, Frank L J; Suttorp, Maarten-Jan; Plokker, Thijs H W; Kelder, Johannes C; de Jongh, Bartelt M; Bouter, K Paul; Diepersloot, Rob J A

    2003-10-15

    In this study we evaluate the value of baseline concentrations of acute-phase reactants on prognosis after percutaneous coronary intervention (PCI). Blood samples were drawn immediately before PCI to measure baseline concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), lipoprotein(a) (Lp(a)), and fibrinogen. Follow-up data were collected at 8 months. Repeat PCI, CABG, myocardial infarction, and death were recorded as major adverse clinical events (MACE). Furthermore the recurrence of angina pectoris was noted. The study included 600 consecutive patients after a successful PCI. Sixty-four percent of the patients were stented. The mean age was 61.6 years and 68.9% were male. CRP levels were significantly higher in patients who were to have repeat angina as compared with those who were not (P=0.0322). IL-6 levels were not correlated with angina or MACE. Lp(a) and fibrinogen concentrations were both significantly related to MACE (P=0.0337 and P=0.0253, respectively). Our study clearly supports the role of inflammation in restenosis after PCI as measured in statistically higher levels of Lp(a) and fibrinogen in patients with MACE and CRP in patients with repeat angina.

  6. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    Science.gov (United States)

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  7. Determination of ceruloplasmin, some other acute phase proteins, and biochemical parameters in cows with endometritis

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    S. Kaya

    2016-10-01

    Full Text Available Aim: The aim of this study is to determine serum ceruloplasmin levels in cows with endometritis of varying degrees of severity and to establish whether or not there is a correlation between acute phase protein (APP levels and biochemical parameters. Material and Methods: The study was conducted with 100 Brown Swiss cows (3-8 years of age on days 28-32 postpartum. Cows were divided into endometritis (mild, moderate, and severe endometriosis and healthy groups based on ultrasonography, vaginoscopy, and cytological examination. Blood samples were collected from all cows. Levels of haptoglobin (Hp, serum amyloid A (SAA, ceruloplasmin, albumin, and some biochemical parameters were analyzed. Results: Hp, SAA, and ceruloplasmin levels were higher in cows with endometritis than in healthy cows (p=0.001, and the levels of these APPs increased as endometritis became more severe (p=0.001. Some significant correlations were found between APPs and the biochemical parameters that were analyzed. In conclusion, it was determined that ceruloplasmin levels increase significantly in the presence of endometritis and proportionate to the severity of endometritis. A significant correlation was found between ceruloplasmin levels and Hp and SAA levels. Conclusion: It was concluded that ceruloplasmin levels can be used in the diagnosis of endometritis as an alternative to Hp and SAA levels.

  8. Acute phase proteins response in cats naturally infected with Hepatozoon felis and Babesia vogeli.

    Science.gov (United States)

    Vilhena, Hugo; Tvarijonaviciute, Asta; Cerón, José J; Vieira, Lisete; Pastor, Josep; Silvestre-Ferreira, Ana C

    2017-03-01

    The measurement of acute phase proteins (APP) is being increasingly used in human and veterinary medicine in diagnosis, prognosis, treatment monitoring, and in general health screening. However, information about the APP response in cats infected with agents of vector-borne diseases is lacking. The purpose of the study was to investigate the concentrations of serum amyloid A (SAA), haptoglobin (Hp), and paraoxonase-1 (PON1) in cats naturally infected with Hepatozoon felis and Babesia vogeli. Serum concentrations of SAA, Hp, and PON1 were determined in 19 cats naturally infected with H felis and in 11 cats naturally infected with B vogeli, and compared to concentrations in 10 healthy control cats. Serum Hp concentrations were significantly increased, and PON1 concentrations significantly decreased in symptomatic and asymptomatic cats infected with H felis and B vogeli when compared with healthy noninfected cats. In the H felis-infected population, concentrations of SAA and Hp were significantly increased in symptomatic cats when compared with asymptomatic animals. This study demonstrated differences in APP concentrations in cats infected with H felis and B vogeli. Therefore, Hp and PON1 concentrations could be helpful in discriminating healthy cats from cats with asymptomatic or symptomatic infection by these agents. © 2017 American Society for Veterinary Clinical Pathology.

  9. Acute phase response and oxidative stress status in familial Mediterranean fever (FMF).

    Science.gov (United States)

    Guzel, Savas; Andican, Gulnur; Seven, Arzu; Aslan, Mahmure; Bolayirli, Murat; Guzel, Eda Celik; Hamuryudan, Vedat

    2012-06-01

    We aimed to determine acute phase response (APR) and oxidative stress in patients with familial Mediterranean fever (FMF) and compare these characteristics with those in healthy controls; 20 patients with FMF and 15 healthy controls were enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, and leukocyte levels were determined as markers of APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl group and thiol (T-SH) levels were analyzed to determine the oxidative damage to proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were measured as markers of antioxidant status. Conjugated diene (p FMF patients compared with controls. FMF patients in the attack period (n = 8) had significantly higher CRP, ESR, fibrinogen, and leukocyte levels (p FMF patients in the attack period. The findings revealed upregulated APR during the attack period in FMF patients and enhanced oxidative stress in the FMF patients as compared to controls.

  10. Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction.

    Science.gov (United States)

    Zimetti, Francesca; De Vuono, Stefano; Gomaraschi, Monica; Adorni, Maria Pia; Favari, Elda; Ronda, Nicoletta; Ricci, Maria Anastasia; Veglia, Fabrizio; Calabresi, Laura; Lupattelli, Graziana

    2017-10-01

    Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition, and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes, or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44.8%, respectively) and of medium-sized HDL (-10.5%) occurred in APR. Total HDL CEC was impaired in APR subjects (-18%). Evaluating specific CEC pathways, we found significant reductions in CEC by aqueous diffusion and by the transporters scavenger receptor B-I and ABCG1 (-25.5, -41.1 and -30.4%, respectively). ABCA1-mediated CEC was not affected. Analyses adjusted for age and gender provided similar results. In addition, correcting for HDL-cholesterol (HDL-C) levels, the differences in aqueous diffusion total and ABCG1-CEC remained significant. APR subjects displayed higher levels of HDL serum amyloid A (+20-folds; P = 0.003). In conclusion, APR does not associate with cholesterol synthesis and absorption changes but with alterations of HDL composition and a marked impairment of HDL CEC, partly independent of HDL-C serum level reduction. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  11. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA, in comparison with C reactive protein (CRP and total protein (TP, can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic and in 12 transudates (9 pleural and 3 ascitic. CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10 % of the amount found in serum, that is, the exudate/serum ratio (E/S was 0.10 ± 0.13 . For comparison, the exudate/serum ratio for CRP and TP was 0.39 ± 0.37 and 0.68 ± 0.15 , respectively. There was a strong positive correlation between serum and exudate SAA concentration ( r = 0.764 ; p < 0.0001 . The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8–360.5un g/mL. SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates

  12. The acute-phase proteins serum amyloid A and C reactive protein in transudates and exudates.

    Science.gov (United States)

    Okino, Alessandra M; Bürger, Cristiani; Cardoso, Jefferson R; Lavado, Edson L; Lotufo, Paulo A; Campa, Ana

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 +/- 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 +/- 0.37 and 0.68 +/- 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764; p transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8-360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates.

  13. Adiponectin gene polymorphisms and acute respiratory distress syndrome susceptibility and mortality.

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    Amy M Ahasic

    Full Text Available RATIONALE: Adiponectin is an anti-inflammatory adipokine that is the most abundant gene product of adipose tissue. Lower levels have been observed in obesity, insulin resistance, and in critical illness. However, elevated levels early in acute respiratory failure have been associated with mortality. Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2 have been examined for relationships with obesity, insulin resistance and diabetes, cardiovascular disease, and to circulating adipokine levels, but many gaps in knowledge remain. The current study aims to assess the association between potentially functional polymorphisms in adiponectin-related genes with acute respiratory distress syndrome (ARDS risk and mortality. METHODS: Consecutive patients with risk factors for ARDS admitted to the ICU were enrolled and followed prospectively for development of ARDS. ARDS cases were followed through day 60 for all-cause mortality. 2067 patients were successfully genotyped using the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed ARDS. Forty-four single nucleotide polymorphisms (SNPs on ADIPOQ, ADIPOR1 and ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be functional based on their location (promoter, exon, or 3' untranslated region. These 9 SNPs were analyzed for association with ARDS case status and mortality among ARDS cases. RESULTS: After multivariable analysis and adjustment for multiple comparisons, no SNPs were significantly associated with ARDS case status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36-5.00, p = 0.0039 after adjustment for significant covariates. The significance of this association persisted after adjustment for multiple comparisons (FDR_q = 0.029. CONCLUSIONS: A common and potentially functional polymorphism in ADIPOQ may impact survival in ARDS. Further

  14. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

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    de Carvalho Tatiana

    2010-07-01

    Full Text Available Abstract Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P 2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min were also increased during the course of the disease (P Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities.

  15. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

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    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  16. Elements of style: consent form language and the therapeutic misconception in phase 1 gene transfer trials.

    Science.gov (United States)

    Kimmelman, Jonathan; Levenstadt, Aaron

    2005-04-01

    The therapeutic misconception arises wherever human subjects misinterpret the primary purpose of a clinical trial as therapeutic. Such misconceptions are particularly prevalent in trials involving severely ill subjects or novel and well-publicized investigational agents. In order to identify possible sources of the therapeutic misconception in gene transfer trials, 286 phase 1 human gene transfer consent documents were analyzed for their description of purpose, alternatives, and their use of the term gene transfer. We report that 20% of trials fail to explain their purpose as safety and dosage, only 41% of oncology trials identify comfort care as an alternative to participation, and that the term gene therapy is used with twice the frequency of the term gene transfer. Trends and coherence in consent form language were analyzed as well. Our results indicate that consent forms used in gene transfer phase 1 trials often contain language that promotes, or does little to deter, therapeutic misconceptions.

  17. Gene Mutation Patterns in Patients with Minimally Differentiated Acute Myeloid Leukemia

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    Hsiao-Wen Kao

    2014-06-01

    Full Text Available Minimally differentiated acute myeloid leukemia (AML-M0 is a rare subtype of AML with poor prognosis. Although genetic alterations are increasingly reported in AML, the gene mutations have not been comprehensively studied in AML-M0. We aimed to examine a wide spectrum of gene mutations in patients with AML-M0 to determine their clinical relevance. Twenty gene mutations including class I, class II, class III of epigenetic regulators (IDH1, IDH2, TET2, DNMT3A, MLL-PTD, ASXL1, and EZH2, and class IV (tumor suppressor genes were analyzed in 67 patients with AML-M0. Mutational analysis was performed with polymerase chain reaction–based assays followed by direct sequencing. The most frequent gene mutations from our data were FLT3-ITD/FLT3-TKD (28.4%, followed by mutations in IDH1/IDH2 (28.8%, RUNX1 (23.9%, N-RAS/K-RAS (12.3%, TET2 (8.2%, DNMT3A (8.1%, MLL-PTD (7.8%, and ASXL1 (6.3%. Seventy-nine percent (53/67 of patients had at least one gene mutation. Class I genes (49.3% were the most common mutated genes, which were mutually exclusive. Class III genes of epigenetic regulators were also frequent (43.9%. In multivariate analysis, old age [hazard ratio (HR 1.029, 95% confidence interval (CI 1.013-1.044, P = .001 was the independent adverse factor for overall survival, and RUNX1 mutation (HR 2.326, 95% CI 0.978-5.533, P = .056 had a trend toward inferior survival. In conclusion, our study showed a high frequency of FLT3, RUNX1, and IDH mutations in AML-M0, suggesting that these mutations played a role in the pathogenesis and served as potential therapeutic targets in this rare and unfavorable subtype of AML.

  18. Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas' disease in rats.

    Science.gov (United States)

    Caetano, Leony Cristina; Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado, José Clóvis

    2009-03-01

    The effect of repetitive stress during acute infection with Trypanosoma cruzi (T. cruzi) on the chronic phase of ensuing Chagas' disease was the focus of this investigation. The aim of this study was to evaluate in Wistar rats the influence of repetitive stress during the acute phase of infection (7 days) with the Y strain of T. cruzi on the chronic phase of the infection (at 180 days). Exposure to ether vapor for 1 min twice a day was used as a stressor. Repetitive stress enhanced the number of circulating parasites and cardiac tissue disorganization, from a moderate to a severe diffuse mononuclear inflammatory process and the presence of amastigote burden in the cardiac fibers. Immunological parameters revealed that repetitive stress triggered a reduced concanavalin A induced splenocyte proliferation in vitro with major effects on the late chronic phase. Serum interleukin-12 concentration decreased in both stressed and infected rats in the early phase of infection although it was higher on 180 days post-infection. These results suggest that repetitive stress can markedly impair the host's immune system and enhance the pathological process during the chronic phase of Chagas' disease.

  19. Global analysis of phase locking in gene expression during cell cycle: the potential in network modeling

    Directory of Open Access Journals (Sweden)

    Hessner Martin J

    2010-12-01

    Full Text Available Abstract Background In nonlinear dynamic systems, synchrony through oscillation and frequency modulation is a general control strategy to coordinate multiple modules in response to external signals. Conversely, the synchrony information can be utilized to infer interaction. Increasing evidence suggests that frequency modulation is also common in transcription regulation. Results In this study, we investigate the potential of phase locking analysis, a technique to study the synchrony patterns, in the transcription network modeling of time course gene expression data. Using the yeast cell cycle data, we show that significant phase locking exists between transcription factors and their targets, between gene pairs with prior evidence of physical or genetic interactions, and among cell cycle genes. When compared with simple correlation we found that the phase locking metric can identify gene pairs that interact with each other more efficiently. In addition, it can automatically address issues of arbitrary time lags or different dynamic time scales in different genes, without the need for alignment. Interestingly, many of the phase locked gene pairs exhibit higher order than 1:1 locking, and significant phase lags with respect to each other. Based on these findings we propose a new phase locking metric for network reconstruction using time course gene expression data. We show that it is efficient at identifying network modules of focused biological themes that are important to cell cycle regulation. Conclusions Our result demonstrates the potential of phase locking analysis in transcription network modeling. It also suggests the importance of understanding the dynamics underlying the gene expression patterns.

  20. Growth Phase dependent gene regulation in Bordetella bronchiseptica

    Science.gov (United States)

    Bordetellae are Gram negative bacterial respiratory pathogens. Bordetella pertussis, the causative agent of whooping cough, is a human-restricted variant of Bordetella bronchiseptica, which infects a broad range of mammals causing chronic and often asymptomatic infections. Growth phase dependent gen...

  1. Mapping acute systemic effects of inhaled particulate matter and ozone: multiorgan gene expression and glucocorticoid activity.

    Science.gov (United States)

    Thomson, Errol M; Vladisavljevic, Djordje; Mohottalage, Susantha; Kumarathasan, Prem; Vincent, Renaud

    2013-09-01

    Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g., neurodegenerative disease, cognitive decline, depression, and suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24h after a 4-h exposure by inhalation to particulate matter (0, 5, and 50mg/m(3) EHC-93 urban particles) and ozone (0, 0.4, and 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some interorgan and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis are associated with adverse neurobehavioral, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes and suggest a mechanism through which such health effects may be induced.

  2. Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus.

    Science.gov (United States)

    Mifsud, Karen R; Reul, Johannes M H M

    2016-10-04

    A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1 Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand-receptor interactions.

  3. Proteomic approach for acute-phase proteins of hemolymph and muscles in Scylla serrata challenged by a pathogenic bactedum

    Institute of Scientific and Technical Information of China (English)

    LIU Wenjie; SU Jing; WANG Guizhong; WANG Sanying

    2006-01-01

    Acute-phase response is documented to be a significant mechanism of innate immunity in vertebrates and invertebrates.In this study,proteomic methodologies were applied for different protein expressions in hemolymph of Scylla serrata challenged by Vibrio parahaemolyticus after immunization,and in muscles of the crabs separately challenged by V.parahaemolyticus.V.anguillarum and Aeromonas hydrophila.Up-regulated cryptocyanin is documented in the hemolymph and up-regulated calexcitin,wingless(fragment)and tachykinin-related peptide in the muscle as acute-phase proteins.All the four altered proteins were responsible for bacterial stress,but cryptocyanin seemed to be a memory response protein against the challenge by a live bacterium after immunization of the live cells.These up-regulated proteins can be indicative of an understanding of immunity of a crab.

  4. Reference intervals for acute phase protein and serum protein electrophoresis values in captive Asian elephants (Elephas maximus).

    Science.gov (United States)

    Isaza, Ramiro; Wiedner, Ellen; Hiser, Sarah; Cray, Carolyn

    2014-09-01

    Acute phase protein (APP) immunoassays and serum protein electrophoresis (SPEP) are assays for evaluating the inflammatory response and have use as diagnostic tools in a variety of species. Acute phase proteins are markers of inflammation that are highly conserved across different species while SPEP separates and quantifies serum protein fractions based on their physical properties. In the current study, serum samples from 35 clinically healthy Asian elephants (Elephas maximus) were analyzed using automated assays for C-reactive protein, serum amyloid A, and haptoglobin and SPEP. Robust methods were used to generate reference intervals for the APPs: C-reactive protein (1.3-12.8 mg/l), serum amyloid A (0-47.5 mg/l), and haptoglobin (0-1.10 mg/ml). In addition, SPEP was performed on these samples to establish reference intervals for each protein fraction. A combination of APPs and SPEP measurements are valuable adjunctive diagnostic tools in elephant health care.

  5. Plasma-exchange as a "rescue therapy" for dermato/polymyositis in acute phase. Experience in three young patients.

    Science.gov (United States)

    Cozzi, Franco; Marson, Piero; Pigatto, Erika; Tison, Tiziana; Polito, Pamela; Galozzi, Paola; De Silvestro, Giustina; Punzi, Leonardo

    2015-12-01

    There are few data in the literature supporting the efficacy of plasma-exchange in dermato/polymyositis. The authors report three cases of patients with acute disease phase showing severe pharyngo-esophageal muscle weakness unresponsive to conventional therapy (corticosteroids and immunosuppressant agents) who were treated with plasma-exchange. As the patients were at high risk of "aspiration pneumonia", tracheostomy and PEG tubes were placed. The patients underwent a series of plasma-exchange for a mean of 15 weeks, during which time they progressively recovered muscle strength, their serum muscle enzyme values returned to normal levels, and MRI showed resolution of muscle edema. The tracheostomy and PEG tubes could be removed. Our findings suggest that plasma-exchange in association with immunosuppressant agents could play a relevant role in the management of dermato/polymyositis in acute phase. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Hyperhomocysteinemia, a biochemical tool for differentiating ischemic and nonischemic central retinal vein occlusion during the early acute phase.

    Science.gov (United States)

    Lahiri, Kapil Deb; Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-04-01

    The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p 0.1). Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population.

  7. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    DEFF Research Database (Denmark)

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K

    2009-01-01

    BACKGROUND: Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute...... analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E...

  8. A selected reaction monitoring-based analysis of acute phase proteins in interstitial fluids from experimental equine wounds healing by secondary intention

    DEFF Research Database (Denmark)

    Bundgaard, Louise; Bendixen, Emøke; Sørensen, Mette Aa

    2016-01-01

    In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate...... levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification...... five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media...

  9. Paediatric Dengue Fever diagnosed through parents' epidemiologic report and preventive strategy during the acute phase of infection.

    Science.gov (United States)

    Poddighe, Dimitri; Bonomelli, Irene; Giardinetti, Silvia; Nedbal, Marco; Bruni, Paola

    2016-01-01

    In Europe, Dengue Fever is one of the most frequent imported diseases and also autochthonous cases occurred in areas where the insect vector is present. Here, we describe a child returning from Philippines and diagnosed with Dengue Fever, through the information provided by parents about an ongoing outbreak in their municipality. An appropriate clinical management in the hospital was established to monitor the occurrence of complications and to cancel the risk of dengue virus transmission in the acute phase of infection.

  10. Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Anne Thoustrup Saber

    Full Text Available BACKGROUND: Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk. METHODS: We analysed the mRNA expression of Serum Amyloid A (Saa3 in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes, diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. RESULTS: Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. CONCLUSIONS: Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease.

  11. Control of lipopolysaccharide-high-density lipoprotein interactions by an acute-phase reactant in human serum.

    Science.gov (United States)

    Tobias, P S; McAdam, K P; Soldau, K; Ulevitch, R J

    1985-10-01

    We have recently described several phenomena involving the interactions of lipopolysaccharides (LPS) from Salmonella minnesota Re595 (Re595-LPS) with rabbit serum, which are different in and unique to acute-phase serum as compared with normal serum (P.S. Tobias and R.J. Ulevitch, J. Immunol. 131:1913-1916, 1983). To determine whether these phenomena could also be observed in acute-phase human serum (APHS), we used APHS obtained from volunteers injected with etiocholanolone. As observed in acute-phase rabbit serum, we found that (i) in APHS, Re595-LPS forms a protein complex with a density of 1.3 g/cm3 which does not form in normal human serum (NHS), (ii) in APHS, the t1/2 for LPS-high-density lipoprotein (HDL) complexation is at least a factor of 10 slower than the t1/2 for LPS-HDL complexation in NHS, (iii) when Re595-LPS serum mixtures are dialyzed against a low salt buffer, Re595-LPS precipitates in less soluble form from APHS than from NHS, and (iv) the precipitate from Re595-LPS-APHS mixtures includes a protein with a molecular weight of approximately 60,000 which does not precipitate from Re595-LPS-NHS mixtures or from NHS or APHS alone. These indications of an altered status of LPS in NHS and APHS suggest that one or more acute-phase reactants interact with Re595-LPS to modify its rate of binding to HDL.

  12. Influence of disease process and duration on acute phase proteins in serum and peritoneal fluid of horses with colic

    OpenAIRE

    Pihl, Tina; Scheepers, E.; Sanz, M.; Goddard, A.; Page, P.; Toft, Nils; Andersen, Pia Haubro; Jacobsen, Stine

    2015-01-01

    Background: The acute phase proteins (APP) serum amyloid A (SAA), haptoglobin, and fibrinogen are valuable blood bi-omarkers in equine inflammatory diseases, but knowledge of factors influencing their concentrations in blood and peritonealfluid (PF) of horses with colic is needed.Objectives: The objective of this study was to investigate the influence of demographics (age, sex, breed), disease process (sim-ple obstruction, strangulating obstruction, inflammatory), disease location, disease duration...

  13. Epidemiological and clinical studies on aseptic meningitis in 377 cases, 3. A study on brain CT scan in acute phase

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Masaaki; Kondo, Tomio; Takashima, Akira; Kono, Shinya; Yamashina, Manabu (Ogaki Shimin Hospital, Gifu (Japan))

    1984-02-01

    Brain CT scan performed in the acute phase of aseptic meningitis in 88 cases revealed abnormal findings in 5 consisting of 2 of cerebral edema, 2 of subdural hygroma and one of cerebral atrophy. Clinical findings showed no particular relation to the age, but cerebral edema was observed in the cases of possible cephalomeningitis diagnosed on the basis of accompanying convulsion and disturbance of consciousness. Abnormal findings were associated with 25% of symptoms diagnosed more than 4 days after onset.

  14. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress.

    Science.gov (United States)

    Unternaehrer, E; Luers, P; Mill, J; Dempster, E; Meyer, A H; Staehli, S; Lieb, R; Hellhammer, D H; Meinlschmidt, G

    2012-08-14

    Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61-67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (POXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR-which may in part reflect changes in blood cell composition-but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders.

  15. Prothrombotic gene variants as risk factors of acute myocardial infarction in young women

    Directory of Open Access Journals (Sweden)

    Tomaiuolo Rossella

    2012-11-01

    Full Text Available Abstract Background Acute myocardial infarction (AMI in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. Methods We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females and in 698 AMI (245 females patients. The data were compared to those obtained in 909 unrelated subjects (458 females from the general population of the same geographical area (southern Italy. Results In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; p Discussion and conclusion Our data confirm that young AMI in females is a peculiar phenotype with specific risk factors as the increased plasma procoagulant activity of FV and FII. On the contrary, the homozygous state for the 677T MTHFR variant may cause increased levels of homocysteine and/or an altered folate status and thus an increased risk for AMI, particularly in males. The knowledge of such risk factors (that may be easily identified by molecular analysis may help to improve prevention strategies for acute coronary diseases in specific risk-group subjects.

  16. PLASMA PROTEIN ELECTROPHORESIS AND SELECT ACUTE PHASE PROTEINS IN HEALTHY BONNETHEAD SHARKS (SPHYRNA TIBURO) UNDER MANAGED CARE.

    Science.gov (United States)

    Hyatt, Michael W; Field, Cara L; Clauss, Tonya M; Arheart, Kristopher L; Cray, Carolyn

    2016-12-01

    Preventative health care of elasmobranchs is an important but understudied field of aquatic veterinary medicine. Evaluation of inflammation through the acute phase response is a valuable tool in health assessments. To better assess the health of bonnethead sharks ( Sphyrna tiburo ) under managed care, normal reference intervals of protein electrophoresis (EPH) and the acute phase proteins, C-reactive protein (CRP) and haptoglobin (HP), were established. Blood was collected from wild caught, captive raised bonnethead sharks housed at public aquaria. Lithium heparinized plasma was either submitted fresh or stored at -80°C prior to submission. Electrophoresis identified protein fractions with migration characteristics similar to other animals with albumin, α-1 globulin, α-2 globulin, β globulin, and γ globulin. These fractions were classified as fractions 1-5 as fractional contents are unknown in this species. Commercial reagents for CRP and HP were validated for use in bonnethead sharks. Reference intervals were established using the robust method recommended by the American Society for Veterinary Clinical Pathology for the calculation of 90% reference intervals. Once established, the diagnostic and clinical applicability of these reference intervals was used to assess blood from individuals with known infectious diseases that resulted in systemic inflammation and eventual death. Unhealthy bonnethead sharks had significantly decreased fraction 2, fraction 3, and fraction 3:4 ratio and significantly increased fraction 5, CRP, and HP. These findings advance our understanding of elasmobranch acute phase inflammatory response and health and aid clinicians in the diagnosis of inflammatory disease in bonnethead sharks.

  17. ACUTE PHASE PROTEIN RESPONSES IN MICE INFECTED WITH RIVER WATER CONTAMINATED BY PASTEURELLA MULTOCIDA TYPE B: 2

    Directory of Open Access Journals (Sweden)

    Mohammed Muqdad Khaleel

    2013-01-01

    Full Text Available Animals are predisposed to infections through varieties of ways which activate the innate immune systems at the initial phase of acute infections. Hemorrhagic Septicemia (HS is a devastating septicemic disease of cattle and buffaloes caused by a particular serotypes of Pasteurella multocida and serotype B: 2 is the most important cause of the disease in Asia. Therefore, the present study aims to investigate on acute phase protein responses in mice infected with river water contaminated by Pasteurella multocida type B: 2. Five infected mice were placed in each tank containing river water for 24, 48 and 72 h. The groups comprise of five mice each made up of the control, intraperitoneal, oral and the aerosol routes. There were increased concentrations of Haptoglobin (Hp in the mice inoculated with infected river water kept for 24 h intraperitoneally (p<0.0454 relative to the control, oral and the aerosol routes. There was significant increased concentration of Serum Amyloid A (SAA in the mice that were inoculated with infected river water kept for 72 h intraperitoneally (p<0.0020 compared to control, orally and the aerosol routes. The intraperitoneal route though most effective in response but practically not feasible for vaccine administration in larger animals and the oral routes was inadequate in eliciting acute phase response in the present study of mice model. Therefore, the aerosol routes could perhaps be a readily available route for effective vaccine administration and heightened immunity in animals considering the progressive responses of APPs through this route.

  18. Impact of Diet Supplemented by Coconut Milk on Corticosterone and Acute Phase Protein Level under High Stocking Density

    Directory of Open Access Journals (Sweden)

    Majid SHAKERI

    2016-05-01

    Full Text Available The purpose of this study was to investigate effects of coconut milk supplementation on corticosterone and acute phase protein level under high stocking density. A total 300 Cobb 500 male chicks were placed in cages and stocked as 10 birds/cage (normal stocking density and 15 birds/cage (high stocking density. The treatments were as (i control diet and stocked at 10 and 15 birds/cage (ii control diet + 3% coconut milk from 1-42 day and stocked at 10 and 15 birds/cage (iii control diet + 5% coconut milk from 1-42 day and stocked at 10 and 15 birds/cage. On day 42, 20 birds per treatment were slaughtered to collect blood samples. The results showed higher level of corticosterone and acute phase protein level in control diet compare to other supplemented diets with coconut milk. In conclusion, coconut milk decreased the level of corticosterone and acute phase protein when chicks were subjected to high stocking density.

  19. Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline.

    Science.gov (United States)

    Kilby, J Michael; Lee, Ha Youn; Hazelwood, J Darren; Bansal, Anju; Bucy, R Patterson; Saag, Michael S; Shaw, George M; Acosta, Edward P; Johnson, Victoria A; Perelson, Alan S; Goepfert, Paul A

    2008-05-11

    Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen. Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression. We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations. There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence. Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum.

  20. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

    Science.gov (United States)

    Vreugdenhil, A C; Dentener, M A; Snoek, A M; Greve, J W; Buurman, W A

    1999-09-01

    The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.

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

    Science.gov (United States)

    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.

  2. [Types of Care for Adult Patients Diagnosed With Acute and Maintenance Phase Schizophrenia].

    Science.gov (United States)

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; Oviedo Lugo, Gabriel Fernando; de la Hoz Bradford, Ana María; Castro Díaz, Sergio Mario; García Valencia, Jenny; Jaramillo González, Luis Eduardo; Ávila-Guerra, Mauricio

    2014-01-01

    To assist the clinician in making decisions about the types of care available for adults with schizophrenia. To determine which are the modalities of treatment associated with better outcomes in adults with schizophrenia. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. Patients who were in Assertive community treatment had a lower risk of new hospitalizations. For the intensive case management, the results favored this intervention in the outcomes: medium term readmissions, social functioning and satisfaction with services. The crisis resolution teams was associated with better outcomes on outcomes of readmissions, social functioning and service satisfaction in comparison with standard care. The use of different modalities of care leads to the need of a comprehensive approach to patients to reduce the overall disability associated with the disease. Evidence shows overall benefit for most outcomes studied without encountering hazards for health of patients. This evaluation is recommended to use the professional ways of providing health services that are community-based and have a multidisciplinary group. It is not recommended the modality "day hospital" during the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  3. Comparison of the outcome of burn patients using acute-phase plasma base deficit.

    Science.gov (United States)

    Salehi, S H; As'adi, K; Mousavi, J

    2011-12-31

    Background. In recent years, plasma base deficit has been used as a marker to determine the status of tissue perfusion in trauma patients and also to predict the outcome of these patients. This study was performed to investigate the effect of plasma base deficit in predicting burn patient outcome. Methods. This prospective cohort study was performed from October 2009 to October 2010 in the acute phase of burn patients who were admitted within 6 h post-injury to Motahari Burn Hospital in Iran. The patients were divided into two groups based on the plasma base deficit in the first 24 h post-injury: group A, in which the mean plasma base deficit was less than or equal to -6 (more negative), and group B, in which the mean plasma base deficit greater than -6. Statistical analysis was performed using SPSS v.16 software. Results. Thirty-eight patients were enrolled in each group. The mean plasma base deficit in group A (-7.76 ± 2.18 mmol) was significantly less than that in group B (-1.19 ± 2.82) mmol (p 0.05) and despite removal of interfering factors, there were significant differences between the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome score and the percentage of sepsis between the two groups (p 0.05). Conclusion. The plasma base deficit can be used as a valuable marker in the resuscitation of burn patients, along with clinical criteria. Physiological indicators (burn percentage, age, and mucosal burns) are not sufficient to predict mortality and morbidity in burn patients, and it is necessary to investigate the role of biochemical markers such as base deficit in determining the final outcome of burn patients.

  4. ACUTE PHASE PROTEINS, LIPID PROFILE AND PROINFLAMMATORY CYTOKINES IN HEALTHY AND BRONCHOPNEUMONIC WATER BUFFALO CALVES

    Directory of Open Access Journals (Sweden)

    Sabry M. El-Bahr

    2013-01-01

    Full Text Available The aim of the present study was to evaluate the diagnostic value of Acute Phase Proteins (APP, lipid profiles and proinflammatory cytokines in healthy and bronchopneumonic water buffalo calves. Therefore, sixty water buffalo calves (9±1 month old, 175±15 kg were divided into two equal groups, the first group represented healthy, control, calves whereas calves of the second group were affected with bronchopneumonia. Total leukocytic and differential counts were determined. Serum total protein, albumin, Triacylglyceol (TAG, low density lipoprotein cholesterol (LDL-c, High Density Lipoprotein cholesterol (HDL-c, Total cholesterol, Alanine Amino Transferase (ALT, Aspartate Amino Transferase (AST, Alkaline Phosphatase (ALP, Fibrinogen (Fb, Haptaglobin (Hp, Serum Amyloid A (SAA, Tumor Necrosis Factor-alpha (TNF-α, Interleukins (IL1β, IL-12 and Interferon-gamma (IFN-γ were also determined. In addition, Bronchoalveolar Lavage (BAL was collected and analyzed. The present findings indicated that, total leukocytic and neutrophils counts were significantly (p<0.05 higher in pneumonic water buffalo calves compare with control. The examined biochemical parameters were significantly (p<0.05 increased in pneumonic calves except for total protein, albumin, cholesterol and HDL-c which were significantly (p<0.05 lower compare with control. Serum concentrations of investigated APP and proinflammatory cytokines were significantly (p<0.05 higher in pneumonic water buffalo calves than those of control. The present study demonstrated that, APP, lipid profile and proinflammatory cytokines perhaps served as biomarkers of bronchopneumonia in water buffalo calves. However, future studies with higher baseline sampling are still needed to establish and validate reference values for APP and cytokines in water buffalo calves.

  5. Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

    Science.gov (United States)

    Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-09-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

  6. Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications.

    Science.gov (United States)

    Tsiouris, J A; Mehta, P D; Patti, P J; Madrid, R E; Raguthu, S; Barshatzky, M R; Cohen, I L; Sersen, E

    2000-12-01

    Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha2 macroglobulin (alpha2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha2M, and the AP proteins c-reactive protein (CRP), alpha1 antitrypsin (alpha1AT), ceruloplasmin (Cp), beta2 Macroglobulin (beta2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha2M and CRP were significantly different in the depressed versus non-depressed groups. The alpha2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.

  7. Acute heat stress induces differential gene expressions in the testes of a broiler-type strain of Taiwan country chickens.

    Directory of Open Access Journals (Sweden)

    Shih-Han Wang

    Full Text Available The expression of testicular genes following acute heat stress has been reported in layer-type roosters, but few similar studies have been conducted on broilers. This study investigated the effect of acute heat stress on the gene expression in the testes of a broiler-type strain of Taiwan country chickens. Roosters were subjected to acute heat stress (38°C for 4 h, and then exposed to 25°C, with testes collected 0, 2, and 6 h after the cessation of heat stress, using non-heat-stressed roosters as controls (n = 3 roosters per group. The body temperature and respiratory rate increased significantly (p<0.05 during the heat stress. The numbers of apoptotic cells increased 2 h after the acute heat stress (79 ± 7 vs. 322 ± 192, control vs. heat stress; p<0.05, which was earlier than the time of increase in layer-type roosters. Based on a chicken 44 K oligo microarray, 163 genes were found to be expressed significantly different in the testes of the heat-stressed chickens from those of the controls, including genes involved in the response to stimulus, protein metabolism, signal transduction, cell adhesion, transcription, and apoptosis. The mRNA expressions of upregulated genes, including HSP25, HSP90AA1, HSPA2, and LPAR2, and of downregulated genes, including CDH5, CTNNA3, EHF, CIRBP, SLA, and NTF3, were confirmed through quantitative real-time polymerase chain reaction (qRT-PCR. Moreover, numerous transcripts in the testes exhibited distinct expressions between the heat-stressed broiler-type and layer-type chickens. We concluded that the transcriptional responses of testes to acute heat stress may differ between the broiler-type and layer-type roosters. Whether the differential expression patterns associate with the heat-tolerance in the strains require a further exploration.

  8. Acute heat stress induces differential gene expressions in the testes of a broiler-type strain of Taiwan country chickens.

    Science.gov (United States)

    Wang, Shih-Han; Cheng, Chuen-Yu; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Huang, San-Yuan

    2015-01-01

    The expression of testicular genes following acute heat stress has been reported in layer-type roosters, but few similar studies have been conducted on broilers. This study investigated the effect of acute heat stress on the gene expression in the testes of a broiler-type strain of Taiwan country chickens. Roosters were subjected to acute heat stress (38°C) for 4 h, and then exposed to 25°C, with testes collected 0, 2, and 6 h after the cessation of heat stress, using non-heat-stressed roosters as controls (n = 3 roosters per group). The body temperature and respiratory rate increased significantly (pheat stress. The numbers of apoptotic cells increased 2 h after the acute heat stress (79 ± 7 vs. 322 ± 192, control vs. heat stress; pchicken 44 K oligo microarray, 163 genes were found to be expressed significantly different in the testes of the heat-stressed chickens from those of the controls, including genes involved in the response to stimulus, protein metabolism, signal transduction, cell adhesion, transcription, and apoptosis. The mRNA expressions of upregulated genes, including HSP25, HSP90AA1, HSPA2, and LPAR2, and of downregulated genes, including CDH5, CTNNA3, EHF, CIRBP, SLA, and NTF3, were confirmed through quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, numerous transcripts in the testes exhibited distinct expressions between the heat-stressed broiler-type and layer-type chickens. We concluded that the transcriptional responses of testes to acute heat stress may differ between the broiler-type and layer-type roosters. Whether the differential expression patterns associate with the heat-tolerance in the strains require a further exploration.

  9. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia.

    Science.gov (United States)

    Karp, Judith E; Vener, Tatiana I; Raponi, Mitch; Ritchie, Ellen K; Smith, B Douglas; Gore, Steven D; Morris, Lawrence E; Feldman, Eric J; Greer, Jacqueline M; Malek, Sami; Carraway, Hetty E; Ironside, Valerie; Galkin, Steven; Levis, Mark J; McDevitt, Michael A; Roboz, Gail R; Gocke, Christopher D; Derecho, Carlo; Palma, John; Wang, Yixin; Kaufmann, Scott H; Wright, John J; Garret-Mayer, Elizabeth

    2012-01-05

    Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.

  10. Influence of lesion ratio on diagnostic performance of in-phase/opposed-phase imaging and apparent diffusion coefficient for differentiating acute benign vertebral fractures and metastases

    Institute of Scientific and Technical Information of China (English)

    LIN Fan; LEI Yi; LI Yang-bin

    2009-01-01

    Background The usefulness of in-phase/opposed-phase imaging and diffusion weighted imaging (DWI) in differentiating benign and neoplastic vertebral fractures has been described. In this study, we aimed to evaluate the influence of the severity of vertebral damage on the diagnostic performance of these two technologies.Methods Totally 59 patients with 68 acute benign vertebral fractures and 43 patients with 79 vertebral metastases were included in this study. The MR protocol included DWls and sagittal in-phase/opposed-phase gradient recalled sequence.The severity of vertebral damage was expressed by lesion ratio (LR, the ratio of lesion area to vertebral area on the slices of largest abnormal signal area in the T1-weighted sequence). Quantitative (signal intensity ratio (SIR) defined as signal intensity (SI) on opposed-phase gradient recalled echo (GRE) images divided by SI on in-phase; apparent diffusion coefficient (ADC) value derived from DWI analysis was performed, the relationships between LR and the measurements of these two technologies were analyzed using linear regression. The covariate-specific receiver operating characteristic (ROC) curves were also fitted to evaluate the influence of LR on the diagnostic performance of ADC and SIR. Results The difference in both SIR and ADC for vertebral metastasis and acute benign vertebral fractures was significant (P 0.05). More severe cases were associated with increased AUC for SIR.Conclusions LR is capable of affecting the diagnostic performances of chemical shift imaging. Thus, when applying these tests to make diagnoses on vertebral fractures, the severity of the vertebral damage should be taken into account.The covariate-specific ROC model is recommended because it substantially improves the ability to avoid bias when evaluating tests.

  11. Frequent epigenetic inactivation of the SLIT2 gene in chronic and acute lymphocytic leukemia.

    Science.gov (United States)

    Dunwell, Thomas L; Dickinson, Rachel E; Stankovic, Tatjana; Dallol, Ashraf; Weston, Victoria; Austen, Belinda; Catchpoole, Daniel; Maher, Eamonn R; Latif, Farida

    2009-05-16

    Recently a mouse model of T/natural killer acute lymphoblastic leukemia was used to assess global promoter methylation across the mouse genome using the restriction landmark genomic scanning technique. One of the methylated mouse genes identified in this way was Slit2. There are three mammalian SLIT genes (SLIT1, SLIT2, SLIT3), that belong to a highly conserved family of axon guidance molecules. We have previously demonstrated that SLIT2 is frequently inactivated in lung, breast, colorectal and glioma tumors by hypermethylation of a CpG island in its promoter region, whilst inactivating somatic mutations are rare. Furthermore, we demonstrated that SLIT2 acts as a tumor suppressor gene in breast and colorectal cancer cells. In this report we determined the methylation status of the SLIT2 gene in leukemias (CLL and ALL). SLIT2 was methylated in all ten leukemia cell lines analyzed (eight completely and two partially methylated). SLIT2 expression was restored after treating ALL lines with 5-aza-2dC. In primary ALL and CLL samples, SLIT2 was also frequently methylated, 58% (30/52) B-ALL; 83% (10/12) T-ALL and in 80% (24/30) CLL. Whilst DNA from peripheral blood and bone marrow from healthy control samples showed no SLIT2 methylation. Methylation results in leukemia cell lines and ALL and CLL primary samples were confirmed by direct sequencing of bisulfite modified DNA. Our results demonstrate that methylation of the SLIT2 5' CpG island is conserved between mice and humans, and therefore is likely to be of functional importance.

  12. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.;

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

  13. [The influence of ITGB3 gene polymorphism on the frequency of arterial hypertension in patients with acute coronary syndrome].

    Science.gov (United States)

    Zotova, T Iu; Miandina, G I; Frolov, V A; Komarova, A G; Zotov, A K

    2013-01-01

    PLA polymorphism of platelet integrin receptor, GpIIIa glycoprotein, (PLA polymorphism of the ITGB3 gene) is associated with the risk of myocardial infarction and CHD especially in young subjects. We analyzed ITGB3 gene polymorphism in patients with acute coronary insufficiency. It was shown that increased AP and altered blood lipid spectrum in the acute period of disease in carriers of the PLA allele (PLA1/PLA2 and PLA2/PLA2 genotypes) can be regarded as manifestations of stress reaction. The data obtained indicate that the PLA2 allele is a predictor of complications of acute coronary insufficiency. This observation is of importance for the choice of adequate therapy for the patients with this disorder.

  14. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    DEFF Research Database (Denmark)

    Bengtson, Stefan; Knudsen, KB; Kyjovska, ZO

    2017-01-01

    the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90...... without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

  15. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  16. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Gregers, J; Gréen, H; Christensen, I J

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...

  17. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media

    NARCIS (Netherlands)

    Emonts, Marieke; Veenhoven, Reinier H.; Wiertsema, Selma P.; Houwing-Duistermaat, Jeanine J.; Walraven, Vanessa; de Groot, Ronald; Hermans, Peter W. M.; Sanders, Elisabeth A. M.

    2007-01-01

    OBJECTIVE. Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS. DNA samples from

  18. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media.

    NARCIS (Netherlands)

    Emonts, M.; Veenhoven, R.H.; Wiertsema, S.P.; Houwing-Duistermaat, J.J.; Walraven, V.; Groot, R. de; Hermans, P.W.M.; Sanders, E.A.M.

    2007-01-01

    OBJECTIVE: Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS: DNA samples from

  19. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media

    NARCIS (Netherlands)

    Emonts, Marieke; Veenhoven, Reinier H.; Wiertsema, Selma P.; Houwing-Duistermaat, Jeanine J.; Walraven, Vanessa; de Groot, Ronald; Hermans, Peter W. M.; Sanders, Elisabeth A. M.

    2007-01-01

    OBJECTIVE. Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS. DNA samples from

  20. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media.

    NARCIS (Netherlands)

    Emonts, M.; Veenhoven, R.H.; Wiertsema, S.P.; Houwing-Duistermaat, J.J.; Walraven, V.; Groot, R. de; Hermans, P.W.M.; Sanders, E.A.M.

    2007-01-01

    OBJECTIVE: Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS: DNA samples from

  1. [The influence of GPIIIA gene polymorphism on the variability of standard electrocardiogram in patients with acute coronary syndrome].

    Science.gov (United States)

    Komarova, A G; Zotova, T Iu; Miandina, G I; Kasapova, E N; Zotov, A K; Tarasova, E S; Frolov, V A

    2010-01-01

    The authors analyse effect of GPIIIA gene (PI a allele) polymorphism on the frequency of complicated coronary heart disease in patients with dyslipidemia and hypertensive disease. Specific features of ventricular repolarization (T-wave variability) in patients with acute coronary syndrome are described.

  2. Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Plasschaert, S.L.A.; Groninger, E.; Boezen, M.; Kema, I.P.; Vries, E.G.F. de; Uges, D.R.A.; Veerman, A.J.P.; Kamps, W.A.; Vellenga, E.; Graaf, S.S.N. de; Bont, E.S. de

    2004-01-01

    OBJECTIVE: Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P-glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia. METHODS: From 52 of 70 children who participated in a previous study on vincris

  3. Restriction of histone gene transcription to S phase by phosphorylation of a chromatin boundary protein.

    Science.gov (United States)

    Kurat, Christoph F; Lambert, Jean-Philippe; van Dyk, Dewald; Tsui, Kyle; van Bakel, Harm; Kaluarachchi, Supipi; Friesen, Helena; Kainth, Pinay; Nislow, Corey; Figeys, Daniel; Fillingham, Jeffrey; Andrews, Brenda J

    2011-12-01

    The cell cycle-regulated expression of core histone genes is required for DNA replication and proper cell cycle progression in eukaryotic cells. Although some factors involved in histone gene transcription are known, the molecular mechanisms that ensure proper induction of histone gene expression during S phase remain enigmatic. Here we demonstrate that S-phase transcription of the model histone gene HTA1 in yeast is regulated by a novel attach-release mechanism involving phosphorylation of the conserved chromatin boundary protein Yta7 by both cyclin-dependent kinase 1 (Cdk1) and casein kinase 2 (CK2). Outside S phase, integrity of the AAA-ATPase domain is required for Yta7 boundary function, as defined by correct positioning of the histone chaperone Rtt106 and the chromatin remodeling complex RSC. Conversely, in S phase, Yta7 is hyperphosphorylated, causing its release from HTA1 chromatin and productive transcription. Most importantly, abrogation of Yta7 phosphorylation results in constitutive attachment of Yta7 to HTA1 chromatin, preventing efficient transcription post-recruitment of RNA polymerase II (RNAPII). Our study identified the chromatin boundary protein Yta7 as a key regulator that links S-phase kinases with RNAPII function at cell cycle-regulated histone gene promoters.

  4. Modulation of the acute phase response following a lipopolysaccharide challenge in pigs supplemented with an all-natural Saccharomyces cerevisiae fermentation product

    Science.gov (United States)

    This study was designed to determine if feeding a Saccharomyces cerevisiae fermentation product to weaned pigs would reduce the stress and acute phase responses (APR) following an acute lipopolysaccharide (LPS) challenge. Pigs (n = 20; 6.4 +/- 0.2 kg body weight) were obtained and transported to an ...

  5. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes

    Directory of Open Access Journals (Sweden)

    Chang Hung

    2012-02-01

    Full Text Available Abstract Concurrent hematologic malignancies are relatively rare. We encountered a case of concurrent acute myeloid leukemia (AML and T lymphoblastic lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(5;12(q33;p13, which indicated presence of PDGFRB gene translocations. Therefore, this disease belongs to the new WHO category of myeloid and lymphoid neoplasms with abnormalities in PDGFRA, PDGFRB and FGFR1 genes. Although such genetic mutations are prone to multi-lineage differentiation, the present case is in fact the first report of concurrent AML and T lymphoblastic lymphoma involving PDGFRB mutations. The patient was treated with cytarabine and daunomycin in combination with high dose dexamethasone. Allogeneic stem cell transplantation was performed after successful remission induction for both entities. The patient eventually died of chronic graft-versus-host-disease related infection. Based on such an experience, we suggest the decision of stem cell transplantation should be weighed carefully against the risks, especially when tyrosine kinase inhibitors are safe and potentially effective in dealing with such entities.

  6. Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.

    Directory of Open Access Journals (Sweden)

    Michael S Madejczyk

    Full Text Available U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na(2Cr(2O(7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH, resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.

  7. Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

    Science.gov (United States)

    Madejczyk, Michael S.; Baer, Christine E.; Dennis, William E.; Minarchick, Valerie C.; Leonard, Stephen S.; Jackson, David A.; Stallings, Jonathan D.; Lewis, John A.

    2015-01-01

    U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers. PMID:25993096

  8. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  9. Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

    Science.gov (United States)

    Alcalay, M; Zangrilli, D; Fagioli, M; Pandolfi, P P; Mencarelli, A; Lo Coco, F; Biondi, A; Grignani, F; Pelicci, P G

    1992-01-01

    Two chimeric genes, PML-RAR alpha and RAR alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR alpha-PML mRNA junctions (RAR alpha exon 2/PML exon 4 or RAR alpha exon 2/PML exon 7) that maintain the RAR alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR alpha-PML transcript was present in most, but not all, APL patients. Images PMID:1317574

  10. Protein-Energy Malnutrition Developing after Global Brain Ischemia Induces an Atypical Acute-Phase Response and Hinders Expression of GAP-43: e107570

    National Research Council Canada - National Science Library

    Shari E Smith; Sarah A Figley; David J Schreyer; Phyllis G Paterson

    2014-01-01

      Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia...

  11. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43

    National Research Council Canada - National Science Library

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia...

  12. Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Matsuda Akihisa

    2012-08-01

    Full Text Available Abstract Background A previous meta-analysis reported a positive association between an insertion/deletion (I/D polymorphism in the angiotensin-converting enzyme gene (ACE and the risk of acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. Methods We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. Results The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( Pallele Pdominant = 0.001, Precessive = 0.002. This finding remained significant after correction for multiple comparisons. Conclusions There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.

  13. Serum levels of chicken mannan-binding lectin (MBL) during virus infections; indication that chicken MBL is an acute phase reactant

    DEFF Research Database (Denmark)

    Nielsen, O.L.; Jensenius, J. C.; Jørgensen, Poul Henrik

    1999-01-01

    Mannan-binding lectin (MBL) is a serum collectin which is believed to be an opsonin of the innate immune defence against various microorganisms. MBL is a minor acute phase reactant in man. We investigated the concentration of serum MBL in chickens infected with infectious bronchitis virus (IBV...... levels returned to normal values 6-10 days after infection. The results indicated that MBL is a minor acute phase reactant in chickens....

  14. Exocrine pancreatic function during the early recovery phase of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Raffaele Pezzilli; Patrizia Simoni; Riccardo Casadei; Antonio M. Morselli-Labate

    2009-01-01

    BACKGROUND: Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis, but the data are scarce and conlficting. This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding. METHODS: Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their ifrst episode of the disease. They were 75 patients including 60 (80.0%) patients with mild acute pancreatitis and 15 (20.0%) patients with severe acute pancreatitis. Etiologically 61 patients (81.3%) had biliary disease, 1 (1.3%) had alcoholic disease and 3 (4.0%) had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients (13.3%). The mean (±SD) refeeding time after the attack of acute panereatitis was 11.2±10.2 days. RESULTS: Pathological values of FE-1 were found in 9 of the 75 patients (12.0%): 7 (9.3%) patients with mild pancreatitis and 2 (2.7%) patients with severe pancreatitis (P=1.000). The frequency of the pathological values of fecal elastase-1 was signiifcantly different from that of various etiologies of the disease (P=0.030). It was signiifcantly lower in patients with biliary pancreatitis (9.8%;P=0.035) than in one patient with alcoholic pancreatitis (P=0.126), one patient with hypertriglyceridemia-induced pancreatitis (33.3%;P=0.708), and one patient with idiopathic pancreatitis (10.0%;P=0.227). Pathological fecal elastase-1 was not signiifcantly related to sex, age or day of refeeding.CONCLUSION: Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.

  15. Computational identification and structural analysis of deleterious functional SNPs in MLL gene causing acute leukemia.

    Science.gov (United States)

    George Priya Doss, C; Rajasekaran, R; Sethumadhavan, Rao

    2010-09-01

    A promising application of the huge amounts of data from the Human Genome Project currently available offers new opportunities for identifying the genetic predisposition and developing a better understanding of complex diseases such as cancers. The main focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations does not only provide insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. In this study, we evaluated the Single Nucleotide Polymorphisms (SNPs) that can alter the expression and the function in MLL gene through computational methods. We applied an evolutionary perspective to screen the SNPs using a sequence homologybased SIFT tool, suggested that 10 non-synonymous SNPs (nsSNPs) (50%) were found to be deleterious. Structure based approach PolyPhen server suggested that 5 nsSNPS (25%) may disrupt protein function and structure. PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutations that occurred in the native protein coded by MLL gene is at amino acid positions Q1198P and K1203Q. The solvent accessibility results showed that 7 residues changed from exposed state in the native type protein to buried state in Q1198P mutant protein and remained unchanged in the case of K1203Q. From the overall results obtained, nsSNP with id (rs1784246) at the amino acid position Q1198P could be considered as deleterious mutation in the acute leukemia caused by MLL gene.

  16. A 17-gene stemness score for rapid determination of risk in acute leukaemia.

    Science.gov (United States)

    Ng, Stanley W K; Mitchell, Amanda; Kennedy, James A; Chen, Weihsu C; McLeod, Jessica; Ibrahimova, Narmin; Arruda, Andrea; Popescu, Andreea; Gupta, Vikas; Schimmer, Aaron D; Schuh, Andre C; Yee, Karen W; Bullinger, Lars; Herold, Tobias; Görlich, Dennis; Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Cheok, Meyling; Preudhomme, Claude; Dombret, Herve; Metzeler, Klaus; Buske, Christian; Löwenberg, Bob; Valk, Peter J M; Zandstra, Peter W; Minden, Mark D; Dick, John E; Wang, Jean C Y

    2016-12-15

    Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials. The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance. Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC(+) and 89 LSC(-) cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.

  17. Prognostic Impact of Nucleophosmin 1 (NPM1 Gene Mutations in Egyptian Acute Myeloid Leukemia Patients

    Directory of Open Access Journals (Sweden)

    Magda Zidan

    2013-06-01

    Full Text Available OBJECTIVE: Somatic mutations of the nucleophosmin gene (NPM1, which alter the subcellular localization of the product, are the most frequent mutations in patients with acute myeloid leukemia. The aim of the study was to assess the prevalence and prognostic impact of NPM1 gene mutations in adult AML patients. METHODS: Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP were used to screen 55 AML patients for mutations of NPM1 gene. RESULTS: NPM1 mutations were found in 12 (21.8% of 55 patients, significantly associated with higher total leukocytie count, marrow blast percentage (p=0.03 and p=0.02, respectively, and M5 subtype (p<0.001. Patients with NPM1 mutations had significantly higher complete remission rates (p=0.003 and a trend to lower rates of mortality, relapse and refractory disease (p=0.28, p=0.45 and p=0.08, respectively. Survival analysis showed significantly longer disease-free survival (mean 18.635±1.229 versus 11.041±1.250 months, p=0.044 and overall survival (mean 19.810±1.624 versus 12.063±1.244 months, p=0.041 in patients with NPM1 mutations compared with those without. Multivariate analyses confirmed NPM1 mutation as a significant independent predictor for disease-free survival (HR=0.066, p=0.001 and overall survival (HR=0.125, p=0.002. CONCLUSION: NPM1 mutation is a prognostic factor for a favorable outcome in Egyptian population. This finding is of major clinical importance since it strongly suggests that NPM1 mutations may allow one to divide the heterogeneous patient group of AML into prognostically different subgroups.

  18. [The importance of transcranial Doppler (TDC) in the assessment of cerebrovascular hemodynamics of the acute phase of ischemic stroke].

    Science.gov (United States)

    Wojczal, Joanna; Szerej, Anna Szczepańska; Belniak, Ewa; Blaszkowska, Anna; Stelmasiak, Zbigniew

    2003-01-01

    Most recent studies on transcranial Doppler (TCD) in the acute phase of ischemic stroke are reviewed in this paper. TCD is a highly sensitive and specific method of quick, bedside assessment of cerebrovascular circulation hemodynamics in the acute phase of ischemic stroke. The following issues are discussed in the paper: a new classification of ultrasound pathological changes associated with intracranial arteries occlusion or stenosis, the frequency of spontaneous re-canalisation by TCD, a comparison of TCD results with findings obtained by means of other vascular imaging techniques (e.g. DSA, CTA and MRA), relationship between TCD baseline assessment of primary blood flow changes and thrombolysis efficacy (the so-called TIBI classification, Thrombolysis in Brain Ischemia), and prognostic significance of TCD in the acute ischemic stroke. Moreover, first clinical reports on an additive effect of TCD on thrombolytic therapy are presented. The main limitations of TCD include the lack of sufficient bone window in 5-15% of patients and the lack of sufficiently trained staff capable of performing the examination a 24 h duty, since results of the examination to a large degree depend on the examiner's skills.

  19. Serum acute phase proteins as biomarkers of pleuritis and cranio-ventral pulmonary consolidation in slaughter-aged pigs.

    Science.gov (United States)

    Saco, Yolanda; Fraile, Lorenzo; Giménez, Mercè; Alegre, Ana; López-Jimenez, Rosa; Cortey, Martí; Segalés, Joaquim; Bassols, Anna

    2011-08-01

    The purpose of this study was to investigate the relationship between the existence of lung lesions in pigs at slaughter and the concentration of the serum acute phase proteins (APP), haptoglobin (Hp), pig-major acute protein (Pig-MAP) and C-reactive protein (CRP). A total of 24 pig farms were selected out of a larger farm database previously screened to study risk factors associated with pleuritis and cranio-ventral pulmonary consolidation (CVPC) lesions at slaughter-aged pigs in Spain. The farms were classified as "pleuritis negative (P-) or positive (P+)" and as "CVPC negative (M-) or positive (M+)" and divided into four groups according to a 2X2 factorial design (P-M-, P-M+, P+M-, P+M+). Also at slaughter, blood from 20 randomly selected pigs from each farm was collected. Obtained serum samples were used to measure acute phase proteins. All APP concentrations were significantly higher for M+ farms than for M- ones. However, only Hp and Pig-MAP showed significantly higher concentrations for P+ farms than for P- ones. Pig-MAP was the most sensitive biomarker since it was able to clearly discriminate between P-/P+ and M-/M+ groups (ppleuritis and good for CVPC lesions. CRP was able to discriminate for CVPC lesions but not for pleuritis. The present results indicate that Pig-MAP and, possibly Hp, may be used as potential markers to characterise and discriminate respiratory lesions in swine herds at slaughter.

  20. Acute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task.

    Science.gov (United States)

    Glienke, Katharina; Piefke, Martina

    2016-09-01

    Successful execution of intentions, but also the failure to recall are common phenomena in everyday life. The planning, retention, and realization of intentions are often framed as the scientific concept of prospective memory. The current study aimed to examine the influence of acute stress on key dimensions of complex "real life" prospective memory. To this end, we applied a prospective memory task that involved the planning, retention, and performance of intentions during a fictional holiday week. Forty healthy males participated in the study. Half of the subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions, and the other half of the participants underwent a control procedure at the same time. Salivary cortisol was used to measure the effectiveness of the SECPT stress induction. Stressed participants did not differ from controls in planning accuracy. However, when we compared stressed participants with controls during prospective memory retrieval, we found statistically significant differences in PM across the performance phase. Participants treated with the SECPT procedure before the planning phase showed improved prospective memory retrieval over time, while performance of controls declined. Particularly, there was a significant difference between the stress and control group for the last two days of the holiday week. Interestingly, control participants showed significantly better performance for early than later learned items, which could be an indicator of a primacy effect. This differential effect of stress on performance was also found in time- and event-dependent prospective memory. Our results demonstrate for the first time, that acute stress induced before the planning phase may improve prospective memory over the time course of the performance phase in time- and event-dependent prospective memory. Our data thus indicate that prospective memory can be enhanced by acute stress.

  1. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Holger B Kramer

    2010-05-01

    Full Text Available The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, beta-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA occurred as early as 5-7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT, termed virus inhibitory peptide (VIRIP, was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

  2. Systemic acute phase proteins response in calves experimentally infected with Eimeria zuernii.

    Science.gov (United States)

    Lassen, Brian; Bangoura, Berit; Lepik, Triin; Orro, Toomas

    2015-09-15

    Acute phase proteins (APPs) have been demonstrated to be useful in evaluating general health stress and diseases in cattle. Serum amyloid A (SAA) and haptoglobin (Hp) are APPs that are produced during inflammation, and likely play a role in host immunological defence against Eimeria infection and the associated intestinal tissue damage. We investigated the involvement of SAA and HP in an experimental study, including three groups of calves: a control group (group 0, n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were monitored for 28 days and data was collected on oocyst excretion, faecal score, animal weight, and SAA and Hp serum concentrations. Generalized linear mixed models showed that the clinical symptoms, indicated by an increase in the number of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1 and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to be a more sensitive marker than SAA, and differences between groups 1 and 2 were observed only for Hp. Linear regression models showed a negative association between weight gain and Hp concentrations, calculated as the area under the curve (AUC) during the overall experimental period and the patency period. A similar result was seen for SAA only during the patency period. This result supports the assumption that reduced weight gain due to E. zuernii infection is an immunologically driven process that involves an increase in APPs. A random intercept regression model of oocyst shedding groups showed that calves shedding 1-500 oocysts had reduced concentrations of Hp, indicating that a different immunological reaction occurs during mild shedding of E. zuernii oocysts than during more intensive shedding. A similar model was used to examine associations between faecal scores and Hp concentrations for each group. Group 2 calves with haemorrhagic diarrhoea displayed

  3. Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol.

    Science.gov (United States)

    Bolli, Niccolò; Manes, Nicla; McKerrell, Thomas; Chi, Jianxiang; Park, Naomi; Gundem, Gunes; Quail, Michael A; Sathiaseelan, Vijitha; Herman, Bram; Crawley, Charles; Craig, Jenny I O; Conte, Natalie; Grove, Carolyn; Papaemmanuil, Elli; Campbell, Peter J; Varela, Ignacio; Costeas, Paul; Vassiliou, George S

    2015-02-01

    Prognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype. Read depth varied between and within genes for the same sample, but was predictable and highly consistent across samples. Consequently, we were able to detect copy number changes, such as an interstitial deletion of BCOR, three MLL partial tandem duplications, and a novel KRAS amplification. With regards to coding mutations, we identified likely oncogenic variants in 41 of 42 samples. NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1 and FLT3 indels were reported with good efficiency. We also showed that DNMT3A mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and relapse, we were able to delineate the dynamics of tumor evolution and give insights into order of acquisition of variants. HaloPlex is a quick and reliable target enrichment method that can aid diagnosis and prognostic stratification of acute myeloid leukemia patients.

  4. RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Bret S. E. Heale

    2012-04-01

    Full Text Available We describe the first report of RNA sequencing of 5' capped (Pol II RNAs isolated from acutely hepatitis C virus (HCV infected Huh 7.5 cells that provides a general approach to identifying differentially expressed annotated and unannotated genes that participate in viral-host interactions. We identified 100, 684, and 1,844 significantly differentially expressed annotated genes in acutely infected proliferative Huh 7.5 cells at 6, 48, and 72 hours, respectively (fold change ≥ 1.5 and Bonferroni adjusted p-values < 0.05. Most of the differentially expressed genes (>80% and biological pathways (such as adipocytokine, Notch, Hedgehog and NOD-like receptor signaling were not identified by previous gene array studies. These genes are critical components of host immune, inflammatory and oncogenic pathways and provide new information regarding changes that may benefit the virus or mediate HCV induced pathology. RNAi knockdown studies of newly identified highly upregulated FUT1 and KLHDC7B genes provide evidence that their gene products regulate and facilitate HCV replication in hepatocytes. Our approach also identified novel Pol II unannotated transcripts that were upregulated. Results further identify new pathways that regulate HCV replication in hepatocytes and suggest that our approach will have general applications in studying viral-host interactions in model systems and clinical biospecimens.

  5. Beneficial Effects of Delayed Opening the Infarct -related Artery on Late Phase Left Ventricular Function in Acute Anterior Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Ma Likun; Yu Hua; Huang Xiangyang; Chu Jun; Feng Kefu; Ding Xiaomei; Yan Ji; Gu Tongyuan

    2004-01-01

    Objectives To assess the effect of delayed opening the infarct - related artery(IRA) by percutanous coronary intervention (PCI) on the late phase left ventricular function after acute anterior myocardial infarction. Methods 64 patients with initial Q -wave anterior myocardial infarction and the infarct- related arteries were total occluded conformed by angiogram at 2 to 14 days after onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re - opened). 2 - DE was performed at early phase ( about 3 weeks) , 2 and 6months after onset of AMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. Results VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end - diastolic and end-systolic volume indices (LVEDVI and LVDSVI)were similar in 2 groups at early phase and 2 months.There were no differences between early phase and 2months in each group too. VWMA scores and LVEF did not changed at 6 months in each group compared with the early phase and 2 months (P > 0.05 ). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than in the control group (P <0.01,P < 0. 05 ). The congestive heart failure events were taken place in 19% of patients in control group compared with 2% in successful PCI group ( P > 0.05 ).Conclusions Although the infarct size does not changed, delayed opening the IRA has beneficial effect to the late phase left ventricular dilatation after acute anterior myocardial infarction.

  6. Amplification of thermostable lipase genes fragment from thermogenic phase of domestic waste composting process

    Science.gov (United States)

    Nurhasanah, Nurbaiti, Santi; Madayanti, Fida; Akhmaloka

    2015-09-01

    Lipases are lipolytic enzymes, catalyze the hydrolysis of fatty acid ester bonds of triglycerides to produce free fatty acids and glycerol. The enzyme is widely used in various fields of biotechnological industry. Hence, lipases with unique properties (e.g.thermostable lipase) are still being explored by variation methods. One of the strategy is by using metagenomic approach to amplify the gene directly from environmental sample. This research was focused on amplification of lipase gene fragment directly from the thermogenic phase of domestic waste composting in aerated trenches. We used domestic waste compost from waste treatment at SABUGA, ITB for the sample. Total chromosomal DNA were directly extracted from several stages at thermogenic phase of compost. The DNA was then directly used as a template for amplification of thermostable lipase gene fragments using a set of internal primers namely Flip-1a and Rlip-1a that has been affixed with a GC clamp in reverse primer. The results showed that the primers amplified the gene from four stages of thermogenic phase with the size of lipase gene fragment of approximately 570 base pairs (bp). These results were further used for Denaturing Gradient Gel Electrophoresis (DGGE) analysis to determine diversity of thermostable lipase gene fragments.

  7. Genetic Variants Of Cytochrome b-245, Alpha Polypeptide Gene And Premature Acute Myocardial Infarction Risk In An Iranian Population

    Directory of Open Access Journals (Sweden)

    Amin Fatemeh

    2015-10-01

    Full Text Available Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD and hence acute myocardial infarction (AMI. The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673 and premature acute myocardial infarction risk in an Iranian population.

  8. Detection of the acute phase of abdominal angiostrongyliasis with a parasite-specific IgG enzyme linked immunosorbent assay

    Directory of Open Access Journals (Sweden)

    Geiger Stefan Michael

    2001-01-01

    Full Text Available Angiostrongylus costaricensis may cause intestinal lesions of varied severity when it accidentally infects man in Central and South America. First-stage larvae have never been detected in stools. Therefore, a parasite-specific IgG ELISA was evaluated for the determination of the acute phase of infection. The specificity and the sensitivity of the immunoassay was shown to be 76.2% and 91.1%, respectively. Eight serum samples taken from patients with histopathological diagnosis, at different time points (3 to 15 months after surgical treatment, showed a sharp and early decline in antibody reactivity. The titration of anti-A. costaricensis antibodies has proved to be a useful method for the diagnosis of acute abdominal angiostrongyliasis.

  9. ADAMTS2 gene dysregulation in T/myeloid mixed phenotype acute leukemia

    National Research Council Canada - National Science Library

    Tota, Giuseppina; Coccaro, Nicoletta; Zagaria, Antonella; Anelli, Luisa; Casieri, Paola; Cellamare, Angelo; Minervini, Angela; Minervini, Crescenzio Francesco; Brunetti, Claudia; Impera, Luciana; Carluccio, Paola; Cumbo, Cosimo; Specchia, Giorgina; Albano, Francesco

    2014-01-01

    Mixed phenotype acute leukemias (MPAL) include acute leukemias with blasts that express antigens of more than one lineage, with no clear evidence of myeloid or lymphoid lineage differentiation. T/myeloid (T/My...

  10. Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

    Science.gov (United States)

    Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

    2016-01-01

    Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings.

  11. Multi-modal magnetic resonance imaging in the acute and sub-acute phase of mild traumatic brain injury: can we see the difference?

    Science.gov (United States)

    Toth, Arnold; Kovacs, Noemi; Perlaki, Gabor; Orsi, Gergely; Aradi, Mihaly; Komaromy, Hedvig; Ezer, Erzsebet; Bukovics, Peter; Farkas, Orsolya; Janszky, Jozsef; Doczi, Tamas; Buki, Andras; Schwarcz, Attila

    2013-01-01

    Advanced magnetic resonance imaging (MRI) methods were shown to be able to detect the subtle structural consequences of mild traumatic brain injury (mTBI). The objective of this study was to investigate the acute structural alterations and recovery after mTBI, using diffusion tensor imaging (DTI) to reveal axonal pathology, volumetric analysis, and susceptibility weighted imaging (SWI) to detect microhemorrhage. Fourteen patients with mTBI who had computed tomography with negative results underwent MRI within 3 days and 1 month after injury. High resolution T1-weighted imaging, DTI, and SWI, were performed at both time points. A control group of 14 matched volunteers were also examined following the same imaging protocol and time interval. Tract-Based Spatial Statistics (TBSS) were performed on DTI data to reveal group differences. T1-weighted images were fed into Freesurfer volumetric analysis. TBSS showed fractional anisotropy (FA) to be significantly (corrected p<0.05) lower, and mean diffusivity (MD) to be higher in the mTBI group in several white matter tracts (FA=40,737; MD=39,078 voxels) compared with controls at 72 hours after injury and still 1month later for FA. Longitudinal analysis revealed significant change (i.e., normalization) of FA and MD over 1 month dominantly in the left hemisphere (FA=3408; MD=7450 voxels). A significant (p<0.05) decrease in cortical volumes (mean 1%) and increase in ventricular volumes (mean 3.4%) appeared at 1 month after injury in the mTBI group. SWI did not reveal microhemorrhage in our patients. Our findings present dynamic micro- and macrostructural changes occurring in the acute to sub-acute phase in mTBI, in very mildly injured patients lacking microhemorrhage detectable by SWI. These results underscore the importance of strictly defined image acquisition time points when performing MRI studies on patients with mTBI.

  12. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  13. Rapid loss of both CD4+ and CD8+ T lymphocyte subsets during the acute phase of severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    李太生; 邱志峰; 韩扬; 王仲; 范宏伟; 吕玮; 谢静; 马小军; 王爱霞

    2003-01-01

    Objective To study the alteration of peripheral lymphocyte subsets in severe acute respiratory syndrome (SARS) patients and to help improve the early diagnosis of the disease. Methods Anti-coagulating blood samples from 98 SARS patients in the acute phase, 56 normal healthy blood donors, and from patients infected by HIV, CMV and EBV were collected. The T lymphocyte subsets were counted by flow cytometry using fluorescence-labeled specific monoclonal antibodies. Results A significant decrease was observed in all SARS patients in their peripheral CD4+ and CD8+ T lymphocyte absolute counts [256(104)×106/L and 256 (117)×106/L, respectively], which were also lower than those of the patients infected with HIV, CMV and EBV. All patients infected with HIV, CMV and EBV had significantly higher CD8+ T lymphocyte counts in comparison with normal controls. Conclusions Decrease of both CD4+ and CD8+ T lymphocytes of patients is related to onset of SARS. T lymphocyte subset analysis would help improve the early diagnosis of the disease.

  14. Early treatment with intravenous metoprolol for suspected acute myocardial infarction: a phase IV United States trial. Phase IV Metoprolol in Myocardial Infarction Study Group.

    Science.gov (United States)

    Antman, E M; Dupont, W D; Bonalsky, J; Califf, R M; Corwin, S; Fink, L; Hansen, D E; Kawanishi, D T; Kronenberg, M W; McKay, C R

    1989-05-01

    Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

  15. Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium.

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    Sheila K Patterson

    Full Text Available Salmonella enterica serovar Typhimurium strain 798 has previously been shown to undergo phenotypic phase variation. One of the phenotypes expresses virulence traits such as adhesion, while the other phenotype does not. Phenotypic phase variation appears to correlate with the ability of this strain to cause persistent, asymptomatic infections of swine. A new method to detect cells in either phenotypic phase was developed using Evans Blue-Uranine agar plates. Using this new assay, rates of phenotypic phase variation were obtained. The rate of phase variation from non-adhesive to adhesive phenotype was approximately 10(-4 per cell per generation while phase variation from the adhesive to the non-adhesive phenotype was approximately 10(-6 per cell per generation. Two highly virulent S. Typhimurium strains, SL1344 and ATCC 14028, were also shown to undergo phase variation. However, while the rate from adhesive to non-adhesive phenotype was approximately the same as for strain 798, the non-adhesive to adhesive phenotype shift was 37-fold higher. Differential gene expression was measured using RNA-Seq. Eighty-three genes were more highly expressed by 798 cells in the adhesive phenotype compared to the non-adhesive cells. Most of the up-regulated genes were in virulence genes and in particular all genes in the Salmonella pathogenicity island 1 were up-regulated. When compared to the virulent strain SL1344, expression of the virulence genes was approximately equal to those up-regulated in the adhesive phenotype of strain 798. A comparison of invasive ability demonstrated that strain SL1344 was the most invasive followed by the adhesive phenotype of strain 798, then the non-adhesive phenotype of strain 798. The least invasive strain was ATCC 14028. The genome of strain 798 was sequenced and compared to SL1344. Both strains had very similar genome sequences and gene deletions could not readily explain differences in the rates of phase variation from non

  16. Evaluation of the prevalence of stress and its phases in acute myocardial infarction in patients active in the labor market

    Directory of Open Access Journals (Sweden)

    Luciane Boreki Lucinda

    2015-02-01

    Full Text Available Introduction: Acute myocardial infarction is a social health problem of epidemiological relevance, with high levels of morbidity and mortality. Stress is one of the modifiable risk factors that triggers acute myocardial infarction. Stress is a result of a set of physiological reactions, which when exaggerated in intensity or duration can lead to imbalances in one's organism, resulting in vulnerability to diseases. Objective: To identify the presence of stress and its phases in hospitalized and active labor market patients with unstable myocardial infarction and observe its correlation with the life of this population with stress. Methods: The methodology used was a quantitative, descriptive and transversal research approach conducted with a total of 43 patients, who were still active in the labor market, presenting or not morbidities. Data collection occurred on the fourth day of their hospitalization and patients responded to Lipp's Stress Symptom Inventory for adults. Results: Thirty-one patients (72.1% presented stress and twelve (27.8% did not. In patients with stress, the identified phases were: alert - one patient (3.2%; resistance -twenty-two patients (71.0%; quasi-exhaustion - six patients (19.4% and exhaustion - two patients (6.5%. All women researched presented stress. Conclusion: The results suggest a high level of stress, especially in the resistance phase, in the male infarcted population, hospitalized and active in the labor market.

  17. Intron phase correlations and the evolution of the intron/exon structure of genes.

    Science.gov (United States)

    Long, M; Rosenberg, C; Gilbert, W

    1995-01-01

    Two issues in the evolution of the intron/exon structure of genes are the role of exon shuffling and the origin of introns. Using a large data base of eukaryotic intron-containing genes, we have found that there are correlations between intron phases leading to an excess of symmetric exons and symmetric exon sets. We interpret these excesses as manifestations of exon shuffling and make a conservative estimate that at least 19% of the exons in the data base were involved in exon shuffling, suggesting an important role for exon shuffling in evolution. Furthermore, these excesses of symmetric exons appear also in those regions of eukaryotic genes that are homologous to prokaryotic genes: the ancient conserved regions. This last fact cannot be explained in terms of the insertional theory of introns but rather supports the concept that some of the introns were ancient, the exon theory of genes. PMID:8618928

  18. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    Science.gov (United States)

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-03

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

  19. Activation of type I interferon signaling in the parotid and exorbital lachrymal glands during the acute phase of encephalomyocarditis (EMC) virus infection in mice.

    Science.gov (United States)

    Ohguchi, Atsuko; Yamauchi, Hirofumi; Doi, Kunio; Nakayama, Hiroyuki

    2016-06-01

    The present study was carried out to clarify the mechanisms of EMC virus-induced sialodacryoadenitis in mice during the acute phase infection focusing on the activation of type I interferon (IFN) signaling in the parotid and exorbital lachrymal glands. In the parotid gland, a few apoptotic acinar cells were detected at 2days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4DPI. On the other hand, in the exorbital lachrymal gland, apoptosis of acinar cells and infiltration of inflammatory cells mainly composed of mononuclear cells started at 3DPI, and prominent acinar cell damage developed at 4DPI. Viral RNA was detected at 3 and 4DPI in both glands and the expression level was higher in the exorbital lachrymal gland than in the parotid gland. The up-regulation of IFN-stimulated genes (ISGs), such as Irf7, Pkr and Oas, was quickly induced at 2DPI in the parotid gland, and this probably contributed to suppress viral replication and to eliminate affected cells by apoptosis. In the exorbital lachrymal gland, the expression levels of ISGs mRNAs were not elevated at 2DPI, suggesting no induction of an effective anti-viral response such as apoptosis at this time point. In the exorbital lachrymal gland, the mRNA expression of IFN beta and IFN alpha (type I IFNs) was weak- to strong-positive at 1DPI, and became negative at 2DPI. The weak- to strong-positive expression of IFNs at 1DPI is likely related to the abrupt viral replication and pathological changes in the exorbital lachrymal gland through activating the negative feedback regulation that depressed the IFN signaling cascade at 2DPI. In conclusion, the present study showed the changes in factors involved in the activation of type I IFN signaling cascade in the parotid and exorbital lachrymal glands and their differences between the two glands during the acute phase of EMC virus infection in mice.

  20. Acute-phase protein α1-antitrypsin--a novel regulator of angiopoietin-like protein 4 transcription and secretion.

    Science.gov (United States)

    Frenzel, Eileen; Wrenger, Sabine; Immenschuh, Stephan; Koczulla, Rembert; Mahadeva, Ravi; Deeg, H Joachim; Dinarello, Charles A; Welte, Tobias; Marcondes, A Mario Q; Janciauskiene, Sabina

    2014-06-01

    The angiopoietin-like protein 4 (angptl4, also known as peroxisome proliferator-activated receptor [PPAR]γ-induced angiopoietin-related protein) is a multifunctional protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5-154.6] versus 76.8 [54.8-98.8], respectively, p = 0.045) and correlated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase protein A1AT is a physiological regulator of angptl4, another acute-phase protein.

  1. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn (Poland); Wu, Dongmei, E-mail: dongmei.wu@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

  2. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  3. PROGNOSTIC SIGNIFICANCE OF NRAS GENE MUTATIONS IN CHILDREN WITH ACUTE MYELOGENOUS LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Rabab Aly

    2011-11-01

    Full Text Available Background: NRAS mutations are the most commonly detected molecular abnormalities  in hematologic malignancies, especially in those of myeloid origin. Objective: We aimed to determine the frequency of NRAS (NRAS mutation; and its prognostic significance in Egyptian children with acute myelogenous leukemia (AML. Subject and methods: Peripheral blood and bone marrow (BM samples were taken from  39 de novo pediatric AML patients. Twenty subjects with matched age and sex were  selected as a control group. Samples from patients and control were analyzed for Exons 1, 2 of NRAS gene using genomic PCR-SSCP method. Results: NRAS mutations at the time of diagnosis was found in 6/39 (15.4% AML  cases.  Patients with NRAS   had no significant  improved clinical  outcome than patients without mutation. Patients with NRAS  had similar complete remission (CR rates compared with non mutated patients (66.7% vs. 69.5%, P=0.43.  Those in CR had a similar relapse rate regardless of the presence ofNRAS  (RR 33.4% vs. 30.2%, P=0.26.  However, an adverse prognosis for 3 year overall survival (OS was associated with the presence of NRAS mutations. This adverse prognosis associated with NRAS mutations was also observed in terms  of disease-free survival (DFS  (P=0.007. Univariate analysis showed that unfavorable prognostic factors for DFS were cytogenetic data (P = 0.005 and the NRAS gene mutation (P = 0.002.  Conclusion: NRAS  did not contribute to increase the disease recurrence, however NRAS  was found to be a poor prognostic factor for children with AML. Further studies to confirm these findings are required because of the small number of patients with NRAS mutation.

  4. PROGNOSTIC SIGNIFICANCE OF NRAS GENE MUTATIONS IN CHILDREN WITH ACUTE MYELOGENOUS LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Adel A. Hagag

    2011-01-01

    Full Text Available Background: NRAS mutations are the most commonly detected molecular abnormalities  in hematologic malignancies, especially in those of myeloid origin. Objective: We aimed to determine the frequency of NRAS (NRAS mutation; and its prognostic significance in Egyptian children with acute myelogenous leukemia (AML. Subject and methods: Peripheral blood and bone marrow (BM samples were taken from  39 de novo pediatric AML patients. Twenty subjects with matched age and sex were  selected as a control group. Samples from patients and control were analyzed for Exons 1, 2 of NRAS gene using genomic PCR-SSCP method. Results: NRAS mutations at the time of diagnosis was found in 6/39 (15.4% AML  cases.  Patients with NRAS   had no significant  improved clinical  outcome than patients without mutation. Patients with NRAS  had similar complete remission (CR rates compared with non mutated patients (66.7% vs. 69.5%, P=0.43.  Those in CR had a similar relapse rate regardless of the presence ofNRAS  (RR 33.4% vs. 30.2%, P=0.26.  However, an adverse prognosis for 3 year overall survival (OS was associated with the presence of NRAS mutations. This adverse prognosis associated with NRAS mutations was also observed in terms  of disease-free survival (DFS  (P=0.007. Univariate analysis showed that unfavorable prognostic factors for DFS were cytogenetic data (P = 0.005 and the NRAS gene mutation (P = 0.002.  Conclusion: NRAS  did not contribute to increase the disease recurrence, however NRAS  was found to be a poor prognostic factor for children with AML. Further
    studies to confirm these findings are required because of the small number of patients with NRAS mutation.

  5. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia.

    Science.gov (United States)

    Stam, Ronald W; den Boer, Monique L; Schneider, Pauline; Nollau, Peter; Horstmann, Martin; Beverloo, H Berna; van der Voort, Ella; Valsecchi, Maria G; de Lorenzo, Paola; Sallan, Stephen E; Armstrong, Scott A; Pieters, Rob

    2005-10-01

    Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment outcome. Therefore, novel therapeutic strategies are needed to improve prognosis. Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL). Here we demonstrate FLT3 expression in infants with MLL (n = 41) to be significantly higher compared to both infant (n = 8; P < .001) and noninfant patients with ALL (n = 23; P = .001) carrying germline MLL genes. Furthermore, leukemic cells from infants with MLL were significantly more sensitive to the Fms-like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than noninfant ALL cells, and at least as sensitive as internal tandem duplication-positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However, measuring FLT3 phosphorylation in infants with MLL expressing varying levels of wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand-independent FLT3 activation. This suggests that infant MLL cells displaying activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors such as PKC412. However, at concentrations of PKC412 minimally required to fully inhibit FLT3 phosphorylation, the cytotoxic effects were only fractional. Thus, PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of FLT3 inhibition alone but may involve inhibition of multiple other kinases by this drug.

  6. Analysis of gene expression during the transition to climacteric phase in carnation flowers (Dianthus caryophyllus L.).

    Science.gov (United States)

    In, Byung-Chun; Binder, Brad M; Falbel, Tanya G; Patterson, Sara E

    2013-11-01

    It has been generally thought that in ethylene-sensitive plants such as carnations, senescence proceeds irreversibly once the tissues have entered the climacteric phase. While pre-climacteric petal tissues have a lower sensitivity to ethylene, these tissues are converted to the climacteric phase at a critical point during flower development. In this study, it is demonstrated that the senescence process initiated by exogenous ethylene is reversible in carnation petals. Petals treated with ethylene for 12h showed sustained inrolling and senescence, while petals treated with ethylene for 10h showed inrolling followed by recovery from inrolling. Reverse transcription-PCR analysis revealed differential expression of genes involved in ethylene biosynthesis and ethylene signalling between 10h and 12h ethylene treatment. Ethylene treatment at or beyond 12h (threshold time) decreased the mRNA levels of the receptor genes (DcETR1, DcERS1, and DcERS2) and DcCTR genes, and increased the ethylene biosynthesis genes DcACS1 and DcACO1. In contrast, ethylene treatment under the threshold time caused a transient decrease in the receptor genes and DcCTR genes, and a transient increase in DcACS1 and DcACO1. Sustained DcACS1 accumulation is correlated with decreases in DcCTR genes and increase in DcEIL3 and indicates that tissues have entered the climacteric phase and that senescence proceeds irreversibly. Inhibition of ACS (1-aminocyclopropane-1-carboxylic acid synthase) prior to 12h ethylene exposure was not able to prevent reduction in transcripts of DcCTR genes, yet suppressed transcript of DcACS1 and DcACO1. This leads to the recovery from inrolling of the petals, indicating that DcACS1 may act as a signalling molecule in senescence of flowers.

  7. Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun

    2013-01-01

    at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar......, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. Conclusions Pulmonary acute phase response may constitute a direct link between particle inhalation and risk...

  8. Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

    Directory of Open Access Journals (Sweden)

    Laura Herrero

    Full Text Available The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT, brown adipose tissue (BAT and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

  9. Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Stordrange Laila

    2009-03-01

    Full Text Available Abstract Background The molecular changes in vivo in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response. Methods The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting. Results Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells. Conclusion Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy

  10. Prognostic importance of expression of the Wilms' tumor 1 gene in newly diagnosed acute promyelocytic leukemia.

    Science.gov (United States)

    Hecht, Anna; Nolte, Florian; Nowak, Daniel; Nowak, Verena; Reinwald, Mark; Hanfstein, Benjamin; Faldum, Andreas; Büchner, Thomas; Spiekermann, Karsten; Sauerland, Cristina; Weiss, Christel; Hofmann, Wolf-Karsten; Lengfelder, Eva

    2015-01-01

    Wilms' tumor 1 gene (WT1) is known to be highly expressed in acute promyelocytic leukemia (APL) but information on its impact on prognosis is lacking. WT1 expression was analyzed in bone marrow samples of 79 patients with APL at initial diagnosis. Patients had a differing outcome according to their level of WT1 expression. In patients who achieved a complete remission (CR), low or high WT1 expression was significantly associated with inferior overall survival (OS) compared to intermediate WT1 expression (49% for WT1high vs. 63% for WT1low vs. 93% for WT1int; p=0.008). Moreover, there were significant differences in relapse-free survival (RFS) between the three expression groups (42% for WT1high vs. 63% for WT1low vs. 83% for WT1int; p=0.047). In multivariable analysis WT1 expression showed an independent prognostic impact on OS of responders to induction therapy. In conclusion, the level of WT1 expression can add prognostic information in APL risk stratification.

  11. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...... Germany (600 mg) × 3/day/1 week) group (n = 13) in a double-blinded-fashion. Tendon biopsies were taken from the painful and a healthy region of the same tendon 2 h after 1 h running. Gene-expression of several targets was analysed in the sampled Achilles tendon biopsies. The mRNA for TGF-ß, collagen...

  12. p21 as a transcriptional co-repressor of S-phase and mitotic control genes.

    Directory of Open Access Journals (Sweden)

    Nuria Ferrándiz

    Full Text Available It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562 with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene. Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes.

  13. Value of the Doppler index of myocardial performance in the early phase of acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Jensen, S E; Tei, C

    2000-01-01

    Prospective assessment of a nongeometric Doppler-derived index of combined systolic and diastolic myocardial performance was performed in 64 patients with acute myocardial infarction (MI) within 1 hour after their arrival to the hospital and in 39 age-matched healthy subjects. The index is defined...

  14. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M;

    2000-01-01

    BACKGROUND: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human...

  15. Acute Heart Failure Clinical Drug Development : From Planning to Proof of Activity to Phase III

    NARCIS (Netherlands)

    Cotter, Gad; Voors, Adriaan A.; Weatherley, Beth Davison; Pang, Peter S.; Teerlink, John R.; Filippatos, Gerasimos; Ponikowski, Piotr; Milo-Cotter, Olga; Dittrich, Howard; Teichman, Sam L.; Adams, Kirkwood F.; Gheorghiade, Mihai; Metra, Marco

    2010-01-01

    Over the last decades, attempts to develop new therapies for acute heart failure (AHF) have largely failed. Limitations in understanding the pathophysiology of AHF, its natural history, the effects of current therapies, the properties of new agents, and, importantly, study designs and execution have

  16. Targeted proteomics as a tool for porcine acute phase proteins measurements

    DEFF Research Database (Denmark)

    Marco-Ramell, Anna; Bassols, Anna; Bislev, Stine Lønnerup

    2013-01-01

    ) and there is recent evidence that they can be also considered as welfare markers (Giannetto et al., 2011). During an acute stress situation, the levels of some interleukins (IL-1β, IL-6 and TNF-α) are increased (Elenkov and Chrousos, 2002) and consequently the concentration of the APPs varies dramatically. In pigs...

  17. Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene.

    Science.gov (United States)

    Milewicz, Dianna; Hostetler, Ellen; Wallace, Stephanie; Mellor-Crummey, Lauren; Gong, Limin; Pannu, Hariyadarshi; Guo, Dong-chuan; Regalado, Ellen

    2016-04-01

    Almost one-quarter of patients presenting with thoracic aortic aneurysms (TAAs) or acute aortic dissections (TAADs) have an underlying mutation in a specific gene. A subset of these patients will have systemic syndromic features, for example, skeletal features in patients with Marfan Syndrome. It is important to note that the majority of patients with thoracic aortic disease will not have these syndromic features but many will have a family history of the disease. The genes predisposing to these thoracic aortic diseases are inherited in an autosomal dominant manner, and thirteen genes have been identified to date. As the clinical phenotype associated with each specific gene is defined, the data indicate that the underlying gene dictates associated syndromic features. More importantly, the underlying gene also dictates the aortic disease presentation, the risk for dissection at a given range of aortic diameters, the risk for additional vascular diseases and what specific vascular diseases occur associated with the gene. These results lead to the recommendation that the medical and surgical management of these patients be dictated by the underlying gene, and for patients with mutations in ACTA2, the specific mutation in the gene.

  18. A 4-gene expression score associated with high levels of Wilms Tumor-1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia

    NARCIS (Netherlands)

    Niavarani, A. (Ahmadreza); Herold, T. (Tobias); Y. Reyal (Yasmin); M.C. Sauerland (Maria); T. Büchner (Thomas); W. Hiddemann (Wolfgang); S.K. Bohlander (Stefan); P.J.M. Valk (Peter); Bonnet, D. (Dominique)

    2016-01-01

    textabstractWilms Tumor-1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression p

  19. Neurological deterioration in the acute phase of minor ischemic stroke is an independent predictor of poor outcomes at 1 year: results from the China National Stroke Registry (CNSR)

    Institute of Scientific and Technical Information of China (English)

    JU Yi; ZHAO Xing-quan; WANG Chun-xue; WANG Yi-long; LIU Gai-fen; WANG Yong-jun

    2013-01-01

    Background The risk of clinical deterioration still exists in the acute phase despite the fact that patients with minor stroke may display less severe symptoms.The impact of this clinical deterioration on long-term outcomes is unknown.We characterized the clinical features of neurological deterioration (ND) in the acute phase of minor ischemic stroke (MIS) and investigated its impact on mid-and long-term outcomes.Methods This was a multi-centered,prospective clinical study involving patients with MIS (the National Institutes of Health Stroke Scale,NIHSS <3) recruited from the China National Stroke Registry.Patients were included who had been hospitalized within 24 hours of stroke onset.Baseline characteristics,complication rates during hospitalization,etiology of stroke,as well as 3-,6-,and 12-month post-stroke outcomes were compared between patients with and without ND during the acute phase.Results A number of 368 (15.2%) out of 2424 patients included in the study exhibited ND in the acute phase.Compared to patients without ND,patients with ND had longer hospital stay,increased rate of baseline diabetes,and multiple complications.Multivariate Logistic regression indicated that ND in acute phase was an independent factor predictive of increased dependence (adjusted odds ratio =5.20,95% Cl,3.51-7.70,P <0.001) at 12-month post-stroke.Conclusions The risk of ND in the acute phase is high in patients with MIS.ND in the acute phase is an independent predictor for poor outcomes at 12 months post-stroke onset.

  20. Positive autoregulation delays the expression phase of mammalian clock gene Per2.

    Directory of Open Access Journals (Sweden)

    Yukino Ogawa

    Full Text Available In mammals, cellular circadian rhythms are generated by a transcriptional-translational autoregulatory network that consists of clock genes that encode transcriptional regulators. Of these clock genes, Period1 (Per1 and Period2 (Per2 are essential for sustainable circadian rhythmicity and photic entrainment. Intriguingly, Per1 and Per2 mRNAs exhibit circadian oscillations with a 4-hour phase difference, but they are similarly transactivated by CLOCK-BMAL1. In this study, we investigated the mechanism underlying the phase difference between Per1 and Per2 through a combination of mathematical simulations and molecular experiments. Mathematical analyses of a model for the mammalian circadian oscillator demonstrated that the slow synthesis and fast degradation of mRNA tend to advance the oscillation phase of mRNA expression. However, the phase difference between Per1 and Per2 was not reproduced by the model, which implemented a 1.1-fold difference in degradation rates and a 3-fold difference in CLOCK-BMAL1 mediated inductions of Per1 and Per2 as estimated in cultured mammalian cells. Thus, we hypothesized the existence of a novel transcriptional activation of Per2 by PER1/2 such that the Per2 oscillation phase was delayed. Indeed, only the Per2 promoter, but not Per1, was strongly induced by both PER1 and PER2 in the presence of CLOCK-BMAL1 in a luciferase reporter assay. Moreover, a 3-hour advance was observed in the transcriptional oscillation of the delta-Per2 reporter gene lacking cis-elements required for the induction by PER1/2. These results indicate that the Per2 positive feedback regulation is a significant factor responsible for generating the phase difference between Per1 and Per2 gene expression.

  1. The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

    Science.gov (United States)

    Dziadkowiak, Edyta; Chojdak-Łukasiewicz, Justyna; Guziński, Maciej; Noga, Leszek; Paradowski, Bogusław

    2016-04-01

    Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.

  2. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

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    Satoru Moritoh

    Full Text Available BACKGROUND: Organotypic tissue culture of adult rodent retina with an acute gene transfer that enables the efficient introduction of variable transgenes would greatly facilitate studies into retinas of adult rodents as animal models. However, it has been a difficult challenge to culture adult rodent retina. The purpose of this present study was to develop organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We established an interphase organotypic tissue culture for adult rat retinas (>P35 of age which was optimized from that used for adult rabbit retinas. We implemented three optimizations: a greater volume of Ames' medium (>26 mL per retina, a higher speed (constant 55 rpm of agitation by rotary shaker, and a greater concentration (10% of horse serum in the medium. We also successfully applied this method to adult mouse retina (>P35 of age. The organotypic tissue culture allowed us to keep adult rodent retina morphologically and structurally intact for at least 4 days. However, mouse retinas showed less viability after 4-day culture. Electrophysiologically, ganglion cells in cultured rat retina were able to generate action potentials, but exhibited less reliable light responses. After transfection of EGFP plasmids by particle-mediated acute gene transfer, we observed EGFP-expressing retinal ganglion cells as early as 1 day of culture. We also introduced polarized-targeting fusion proteins such as PSD95-GFP and melanopsin-EYFP (hOPN4-EYFP into rat retinal ganglion cells. These fusion proteins were successfully transferred into appropriate locations on individual retinal neurons. CONCLUSIONS/SIGNIFICANCE: This organotypic culture method is largely applicable to rat retinas, but it can be also applied to mouse retinas with a caveat regarding cell viability. This method is quite flexible for use in acute gene transfection in adult rodent retina, replacing

  3. Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

    Science.gov (United States)

    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Hasani, Seyed-Shahab-Adin; Naderi, Majid; Sadeghi-Bojd, Simin; Taheri, Mohsen

    2017-03-04

    We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

  4. Preferentially Expressed Antigen of Melanoma (PRAME and Wilms’ Tumor 1 (WT 1 Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival

    Directory of Open Access Journals (Sweden)

    Engy El Khateeb

    2015-03-01

    CONCLUSION: It is concluded that the expression of PRAME and WT1 genes are indicators of favorable prognosis and can be useful tools for monitoring minimal residual disease (MRD in acute leukemia especially in patients without known genetic markers. Differential expression between acute leukemia patients and healthy volunteers suggests that the immunogenic antigens (PRAME and WT1 are potential candidates for immunotherapy in childhood acute leukemia.

  5. CORRELATION BETWEEN THE POLYMORPHISM OF GLYCOPROTEINⅠa GENE AND ACUTE CORONARY SYNDROME

    Institute of Scientific and Technical Information of China (English)

    赵永辉; 王燕妮; 祝家庆

    2004-01-01

    Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary collagen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associated with the 807 C/T polymorphism of GPⅠagene in American and Spanish Caucasian populations. This study investigated the correlation between acute coronary syndrome (ACS) and 807 C/T dimorphism of GPⅠa gene in Chinese of Han ethnicity. Methods A case-control study was carried out, including 75 patients with either acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and 65 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases. Genotypes of GPⅠa were checked by polymerase chain reaction-sequence specific primers (PCR-SSP) technique. Results The frequencies of both homozygotes and heterozygotes for T807 allele (TT+TC) were significantly higher in patients with AMI than in controls (62.16% vs 33.85%, P<0.01; odds ratio 3.21).The prevalence of (TT+TC) genotypes was also markedly higher in patients with UAP than in controls (65.79% vs 33.85%, P < 0.005; odds ratio 3.76). There was significant difference in the distribution of (TT+TC) genotypes not only between all patients and controls (64.00% vs 33.85%, P <0.005; odds ratio 3.47) but also between the two subgroups aged < 60 years (70.00% vs 38.24%, P <0.005; odds ratio 3.77). However, there was no significant difference in the distribution of (TT+TC) genotypes between patients with AMI and with UAP. Platelet GPⅠa T807 allele remained significantly associated with AMI and UAP by multiple logistic regression (odds ratio 4.94). Conclusion This study suggests a strong association between presence of GPⅠa T807 allele and ACS. T807 allele can be a marker of genetic susceptibility to ACS.

  6. A phase synchronization clustering algorithm for identifying interesting groups of genes from cell cycle expression data

    Directory of Open Access Journals (Sweden)

    Tcha Hong

    2008-01-01

    Full Text Available Abstract Background The previous studies of genome-wide expression patterns show that a certain percentage of genes are cell cycle regulated. The expression data has been analyzed in a number of different ways to identify cell cycle dependent genes. In this study, we pose the hypothesis that cell cycle dependent genes are considered as oscillating systems with a rhythm, i.e. systems producing response signals with period and frequency. Therefore, we are motivated to apply the theory of multivariate phase synchronization for clustering cell cycle specific genome-wide expression data. Results We propose the strategy to find groups of genes according to the specific biological process by analyzing cell cycle specific gene expression data. To evaluate the propose method, we use the modified Kuramoto model, which is a phase governing equation that provides the long-term dynamics of globally coupled oscillators. With this equation, we simulate two groups of expression signals, and the simulated signals from each group shares their own common rhythm. Then, the simulated expression data are mixed with randomly generated expression data to be used as input data set to the algorithm. Using these simulated expression data, it is shown that the algorithm is able to identify expression signals that are involved in the same oscillating process. We also evaluate the method with yeast cell cycle expression data. It is shown that the output clusters by the proposed algorithm include genes, which are closely associated with each other by sharing significant Gene Ontology terms of biological process and/or having relatively many known biological interactions. Therefore, the evaluation analysis indicates that the method is able to identify expression signals according to the specific biological process. Our evaluation analysis also indicates that some portion of output by the proposed algorithm is not obtainable by the traditional clustering algorithm with

  7. Do results from major clinical trials indicate a change in management in the acute phase of myocardial infarction?

    Science.gov (United States)

    Hjalmarson, A

    1987-01-01

    Since introduction of modern Coronary Care Units, hospital mortality has been reduced by about 50%. This is most likely due to a number of treatments that today are well established. Those include detection and treatment of serious arrhythmias with antiarrhythmic agents and electrical conversion, and more aggressive early treatment of congestive heart failure, of chest pain, and of atrioventricular (AV) block and bradyarrhythmias. The new goals in early management of suspected acute myocardial infarction must aim at prevention and limitation of ischemic damage. The use of beta-blockers has been widely studied. Data from 27 randomized trials with a total of about 27,000 patients have convincingly shown that early beta-blockade reduces mortality, prevents and limits infarct development and arrhythmias, and reduces infarct complications. Three large trials, the Göteborg and MIAMI Trials on metoprolol and the ISIS Trial on atenolol, have demonstrated significant beneficial effects and good tolerance. Thrombolytic therapy in patients with signs of acute myocardial infarction, mainly streptokinase, has demonstrated significant reduction of short-term mortality. The large Italian GISSI Trial, including almost 12,000 patients, showed very significant reduction in 21 day mortality by streptokinase, and the earlier treatment started, the better the reduction. Pooling all published studies in the literature also shows the same favorable effects on mortality. Early treatment with thrombolytic therapy might also prevent and limit infarct development and preserve myocardial function. Recent large scale studies have convincingly demonstrated the value of early beta-blockade and of thrombolytic therapy in selected patients with signs of acute myocardial infarction. It seems reasonable to change the management in the acute phase of myocardial infarction based upon recent major clinical trials.

  8. Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

    Institute of Scientific and Technical Information of China (English)

    Liliana Belmonte; Philippe Ducrotté; Pierre Déchelotte; Mo(i)se Co(e)ffier; Florence Le Pessot; Olga Miralles-Barrachina; Martine Hiron; Antony Leplingard; Jean-Fran(c)ois Lemeland; Bernadette Hecketsweiler; Maryvonne Daveau

    2007-01-01

    AIM:To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock.METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder.Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed.RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ±0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation.CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

  9. Latex-protein complexes from an acute phase recombinant antigen of Toxoplasma gondii for the diagnosis of recently acquired toxoplasmosis.

    Science.gov (United States)

    Peretti, Leandro E; Gonzalez, Verónica D G; Marcipar, Iván S; Gugliotta, Luis M

    2014-08-01

    The synthesis and characterization of latex-protein complexes (LPC), from the acute phase recombinant antigen P35 (P35Ag) of Toxoplasma gondii and "core-shell" carboxylated or polystyrene (PS) latexes (of different sizes and charge densities) are considered, with the aim of producing immunoagglutination reagents able to detect recently acquired toxoplasmosis. Physical adsorption (PA) and chemical coupling (CC) of P35Ag onto latex particles at different pH were investigated. Greater amounts of adsorbed protein were obtained on PS latexes than on carboxylated latexes, indicating that hydrophobic forces govern the interactions between the protein and the particle surface. In the CC experiments, the highest amount of bound protein was obtained at pH 6, near the isoelectric point of the protein (IP=6.27). At this pH, it decreased both the repulsion between particle surface and protein, and the repulsion between neighboring molecules. The LPC were characterized and the antigenicity of the P35Ag protein coupled on the particles surface was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results from ELISA showed that the P35Ag coupled to the latex particles surface was not affected during the particles sensitization by PA and CC and the produced LPC were able to recognize specific anti-P35Ag antibodies present in the acute phase of the disease.

  10. Acute phase response in the primiparous dairy cows after repeated percutaneous liver biopsy during the transition period.

    Science.gov (United States)

    Jawor, P; Brzozowska, A; Słoniewski, K; Kowalski, Z M; Stefaniak, T

    2016-01-01

    The aim of this study was to evaluate the acute phase response of dairy cows to repeated liver biopsy in order to estimate the safety of this procedure during the transition period. Liver biopsies (up to 1000 mg of liver tissue) were conducted twice a day, 7 days before expected parturition and 3 days after calving. The number of needle insertions for each biopsy was recorded and was dependent on the amount of obtained tissue. Blood samples were taken on day 7 before expected parturition, then on days 3, 4, 7 and 14 after calving. Body temperature was measured daily in all 30 cows from day 3 until day 14 after calving. The concentrations of haptoglobin, serum amyloid A, fibrinogen and interleukin-6 were determined in serum and plasma. In 16.7% of cows, the rectal body temperature rose by ≥ 0.5°C on the day after liver biopsy. Although the concentrations of haptoglobin, serum amyloid A and fibrinogen increased significantly after calving (pbiopsies on the acute phase reaction and repeated biopsy during the transition period had no effect on body temperature. Therefore, the procedure may be regarded as safe for cows during the transition period.

  11. The acute phase of mild traumatic brain injury is characterized by a distance-dependent neuronal hypoactivity.

    Science.gov (United States)

    Johnstone, Victoria P A; Shultz, Sandy R; Yan, Edwin B; O'Brien, Terence J; Rajan, Ramesh

    2014-11-15

    The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes.

  12. Acute phase protein response during subclinical infection of pigs with H1N1 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2012-10-12

    In the present study acute phase proteins (APPs) responses in pigs after subclinical infection with H1N1 swine influenza virus (SwH1N1) were evaluated. Fourteen 5 weeks old, seronegative piglets, both sexes were used. Ten of them were infected intranasally with SwH1N1. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP) concentrations in serum were measured using commercial ELISAs. No significant clinical signs were observed in any of the infected pigs, however, all infected animals developed specific antibodies against SwH1N1 and viral shedding was observed from 2 to 5 dpi. Only concentrations of Hp and SAA were significantly induced after infection, with mean maximum levels from days 1 to 2 post infection (dpi). The concentrations of CRP and Pig-MAP remained generally unchanged, however in half of infected pigs the concentration of CRP tended to increase at 1 dpi (but without statistical significance). The results of our study confirmed that monitoring of APPs may be useful for detection of subclinically infected pigs. The use of SAA or Hp and Pig-MAP may be a valuable in combination [i.e. Hp (increased concentration) and Pig-MAP (unchanged concentration)] to detect subclinically SIV infected pigs, or to identify pigs actually producing a large amount of virus. Additional studies need to be done in order to confirm these findings.

  13. Influence of systemic immune and cytokine responses during the acute phase of zoster on the development of postherpetic neuralgia

    Institute of Scientific and Technical Information of China (English)

    Sheng-mei ZHU; Yong-min LIU; Er-dan AN; Qing-lian CHEN

    2009-01-01

    Postherpetic neuralgia (PHN) is a severe sequela of herpes zoster (HZ). Until now, only age and pain severity were considered predisposing factors for the development of PHN. We evaluated 49 patients with acute phase HZ, 10 of whom developed PHN (Group A) and 39 of whom did not develop PHN (Group B). Twenty-five healthy volunteers similar in age and gender distribution to the study group were recruited as controls (Group C). Numbers of serum CD3+ (pan-T lymphocytes), CD4+ (helper/inducer), and CD8+ (suppressor/cytotoxic) lymphocytes were decreased significantly in Groups A and B relative to the control group, but there were no statistical differences between Groups A and B. Interleukin (IL)-1β IL-6, tumor necrosis factor (TNF)-α, IL-8, and IL-10 were significantly elevated in Groups A and B relative to Group C. IL-6 was significantly higher in Group A than in Group B, and was significantly positively correlated with pain severity scored on a visual analog scale. Therefore, we suggest that the inflammatory response, especially that of IL-6, in the acute phase of HZ may be associated with hyperalgesia and the development of PHN.

  14. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  15. Expression of the outcome predictor in acute leukemia 1 (OPAL1) gene is not an independent prognostic factor in patients treated according to COALL or St Jude protocols

    NARCIS (Netherlands)

    A. Holleman (Amy); C.H. Pui (Ching-Hon); W.E. Evans (William); R. Pieters (Rob); M.L. den Boer (Monique); M.H. Cheok (Meyling); K.M. Kazemier (Karin); D. Pei (Deqing); J.R. Downing (James); G.E. Janka-Schaub (Gritta); U. Göbel (Ulrich); U. Graubner (Ulrike)

    2006-01-01

    textabstractNew prognostic factors may result in better risk classification and improved treatment of children with acute lymphoblastic leukemia (ALL). Recently, high expression of a gene named OPAL1 (outcome predictor in acute leukemia) was reported to be associated with favorable prognosis in ALL.

  16. AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Kristensen, Caroline Maag;

    2015-01-01

    -induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I...

  17. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  18. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  19. Value of oral glucose tolerance test in the acute phase of myocardial infarction

    OpenAIRE

    Grabczewska Zofia; Bronisz Marek; Kubica Aldona; Sukiennik Adam; Swiatkiewicz Iwona; Gierach Joanna; Fabiszak Tomasz; Magielski Przemyslaw; Kozinski Marek; Bronisz Agata; Sinkiewicz Anna; Junik Roman; Kubica Jacek

    2011-01-01

    Abstract Background Although European guidelines advise oral glucose tolerance test (OGTT) in patients with acute myocardial infarction (AMI) before or shortly after hospital discharge, data supporting this recommendation are inconclusive. We aimed to analyze whether disturbances in glucose metabolism diagnosed before hospital discharge in AMI patients represents a latent pre-existing condition or rather temporary finding. Additionally, we planned to investigate the value of pre-selected glyc...

  20. Growth phase and ompR regulation of transcription of microcin B17 genes.

    Science.gov (United States)

    Hernández-Chico, C; San Millán, J L; Kolter, R; Moreno, F

    1986-09-01

    The synthesis of the peptide antibiotic microcin B17 was shown to occur as the cells entered the stationary phase of growth. This type of growth phase regulation is commonly observed in the production of a number of different bacterial products such as toxins and antibiotics. Microcin B17 synthesis is also dependent on the product of the ompR gene. To determine the role of transcription in this double regulation of microcin B17 production, operon fusions with Mu d1 (Ap lac) were constructed. Insertions were obtained in all four plasmid genes involved in production of microcin B17 (mcbA-D) and in the immunity region. Three classes of fusions were obtained. Fusions into mcbA, mcbB, and mcbC (first class) exhibited an increase in their transcription as the cells approached the stationary phase. These increases as well as basal levels of transcription were dependent on OmpR. Expression of fusions in mcbD and in the immunity region (second class) was also dependent on OmpR, but their expression remained constant throughout growth. One fusion in mcbC (third class) was obtained which was transcribed in the opposite direction than the others. It showed no growth phase regulation and no OmpR dependence. The implications of these results in terms of the transcriptional organization of the mbc genes are discussed.

  1. Lipid Phases Eye View to Lipofection. Cationic Phosphatidylcholine Derivatives as Efficient DNA Carriers for Gene Delivery

    Directory of Open Access Journals (Sweden)

    Rumiana Koynova

    2008-01-01

    Full Text Available Efficient delivery of genetic material to cells is needed for tasks of utmost importance in laboratory and clinic, such as gene transfection and gene silencing. Synthetic cationic lipids can be used as delivery vehicles for nucleic acids and are now considered the most promising non-viral gene carriers. They form complexes (lipoplexes with the polyanionic nucleic acids. A critical obstacle for clinical application of the lipid-mediated DNA delivery (lipofection is its unsatisfactory efficiency for many cell types. Understanding the mechanism of lipid-mediated DNA delivery is essential for their successful application, as well as for rational design and synthesis of novel cationic lipoid compounds for enhanced gene delivery. According to the current understanding, the critical factor in lipid-mediated transfection is the structural evolution of lipoplexes within the cell, upon interacting and mixing with cellular lipids. In particular, recent studies with cationic phospha- tidylcholine derivatives showed that the phase evolution of lipoplex lipids upon interaction and mixing with membrane lipids appears to be decisive for transfection success: specifically, lamellar lipoplex formulations, which were readily susceptible to undergoing lamellar-nonlamellar (precisely lamellar-cubic phase transition upon mixing with cellular lipids, were found rather consistently associated with superior transfection potency, presumably as a result of facilitated DNA release subsequent to lipoplex fusion with the cellular membranes. Further, hydrophobic moiety of the cationic phospholipids was found able to strongly modulate liposomal gene delivery into primary human umbilical artery endothelial cells; superior activity was found for cationic phosphatidylcholine derivatives with two 14-carbon atom monounsaturated hydrocarbon chains, able to induce formation of cubic phase in membranes. Thus, understanding the lipoplex structure and the phase changes upon interacting

  2. Brucella melitensis global gene expression study provides novel information on growth phase-specific gene regulation with potential insights for understanding Brucella:host initial interactions

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    Garner Harold R

    2009-05-01

    Full Text Available Abstract Background Brucella spp. are the etiological agents of brucellosis, a zoonotic infectious disease that causes abortion in animals and chronic debilitating illness in humans. Natural Brucella infections occur primarily through an incompletely defined mechanism of adhesion to and penetration of mucosal epithelium. In this study, we characterized changes in genome-wide transcript abundance of the most and the least invasive growth phases of B. melitensis cultures to HeLa cells, as a preliminary approach for identifying candidate pathogen genes involved in invasion of epithelial cells. Results B. melitensis at the late logarithmic phase of growth are more invasive to HeLa cells than mid-logarithmic or stationary growth phases. Microarray analysis of B. melitensis gene expression identified 414 up- and 40 down-regulated genes in late-log growth phase (the most invasive culture compared to the stationary growth phase (the least invasive culture. As expected, the majority of up-regulated genes in late-log phase cultures were those associated with growth, including DNA replication, transcription, translation, intermediate metabolism, energy production and conversion, membrane transport, and biogenesis of the cell envelope and outer membrane; while the down-regulated genes were distributed among several functional categories. Conclusion This Brucella global expression profile study provides novel information on growth phase-specific gene expression. Further characterization of some genes found differentially expressed in the most invasive culture will likely bring new insights into the initial molecular interactions between Brucella and its host.

  3. Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias.

    Science.gov (United States)

    Lee, Sung Hak; Jeong, Eun Goo; Yoo, Nam Jin; Lee, Sug Hyung

    2007-12-01

    NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). To see whether NOTCH1 mutation occurs in other malignancies, we analyzed NOTCH1 for the detection of somatic mutations in 334 malignancies, including 48 lung, 48 breast, 48 colorectal and 48 gastric carcinomas, and 142 acute leukemias (105 acute myelogenous leukemias, 32 B-ALLs and 4 T-ALLs) by single-strand conformation polymorphism assay. Also, to see whether other NOTCH genes harbor somatic mutations, we analyzed NOTCH2, NOTCH3 and NOTCH4 genes in the same tissue samples. Overall, we detected three NOTCH mutations in the cancers, which consisted of one NOTCH1 mutation in the T-ALLs (25.0%), one NOTCH2 mutation in the breast carcinomas (2.1%), and one NOTCH3 mutation in the colorectal carcinomas (2.0%). There was no NOTCH mutation in other malignancies analyzed. Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. Despite the importance of NOTCH activation in many types of human cancers, mutation of NOTCH genes, except for NOTCH1 mutation in T-ALL, may not play an important role in the tumorigenesis of common cancers.

  4. Absolute coronary blood flow measurement and microvascular resistance in ST-elevation myocardial infarction in the acute and subacute phase

    Energy Technology Data Exchange (ETDEWEB)

    Wijnbergen, Inge; Veer, Marcel van ' t [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands); Lammers, Jeroen; Ubachs, Joey [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Pijls, Nico H.J., E-mail: nico.pijls@cze.nl [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands)

    2016-03-15

    Background/Purpose: In a number of patients with acute myocardial infarction (AMI), myocardial hypoperfusion, known as the no-reflow phenomenon, persists after primary percutaneous intervention (PPCI). The aim of this study was to evaluate the feasibility and safety of a new quantitative method of measuring absolute blood flow and resistance within the perfusion bed of an infarct-related artery. Furthermore, we sought to study no-reflow by correlating these measurements to the index of microvascular resistance (IMR) and the area at risk (AR) as determined by cardiac magnetic resonance imaging (CMR). Methods: Measurements of absolute flow and myocardial resistance were performed in 20 patients with ST-segment elevation myocardial infarction (STEMI), first immediately following PPCI and then again after 3–5 days. These measurements used the technique of thermodilution during a continuous infusion of saline. Flow was expressed in ml/min per gram of tissue within the area at risk. Results: The average time needed for measurement of absolute flow, resistance and IMR was 20 min, and all measurements could be performed without complication. A higher flow supplying the AR correlated with a lower IMR in the acute phase. Absolute flow increased from 3.14 to 3.68 ml/min/g (p = 0.25) and absolute resistance decreased from 1317 to 1099 dyne.sec.cm-5/g (p = 0.40) between the first day and fifth day after STEMI. Conclusions: Measurement of absolute flow and microvascular resistance is safe and feasible in STEMI patients and may allow for a better understanding of microvascular (dys)function in the early phase of AMI. - Highlights: • We measured absolute coronary blood flow and microvascular resistance in STEMI patients in the acute phase and in the subacute phase, using the technique of thermodilution with low grade intracoronary continuous infusion of saline. • These measurements are safe and feasible during PPCI in STEMI patients. • In STEMI patients, absolute flow

  5. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  6. GeneLab Phase 2: Integrated Search Data Federation of Space Biology Experimental Data

    Science.gov (United States)

    Tran, P. B.; Berrios, D. C.; Gurram, M. M.; Hashim, J. C. M.; Raghunandan, S.; Lin, S. Y.; Le, T. Q.; Heher, D. M.; Thai, H. T.; Welch, J. D.; hide

    2016-01-01

    The GeneLab project is a science initiative to maximize the scientific return of omics data collected from spaceflight and from ground simulations of microgravity and radiation experiments, supported by a data system for a public bioinformatics repository and collaborative analysis tools for these data. The mission of GeneLab is to maximize the utilization of the valuable biological research resources aboard the ISS by collecting genomic, transcriptomic, proteomic and metabolomic (so-called omics) data to enable the exploration of the molecular network responses of terrestrial biology to space environments using a systems biology approach. All GeneLab data are made available to a worldwide network of researchers through its open-access data system. GeneLab is currently being developed by NASA to support Open Science biomedical research in order to enable the human exploration of space and improve life on earth. Open access to Phase 1 of the GeneLab Data Systems (GLDS) was implemented in April 2015. Download volumes have grown steadily, mirroring the growth in curated space biology research data sets (61 as of June 2016), now exceeding 10 TB/month, with over 10,000 file downloads since the start of Phase 1. For the period April 2015 to May 2016, most frequently downloaded were data from studies of Mus musculus (39) followed closely by Arabidopsis thaliana (30), with the remaining downloads roughly equally split across 12 other organisms (each 10 of total downloads). GLDS Phase 2 is focusing on interoperability, supporting data federation, including integrated search capabilities, of GLDS-housed data sets with external data sources, such as gene expression data from NIHNCBIs Gene Expression Omnibus (GEO), proteomic data from EBIs PRIDE system, and metagenomic data from Argonne National Laboratory's MG-RAST. GEO and MG-RAST employ specifications for investigation metadata that are different from those used by the GLDS and PRIDE (e.g., ISA-Tab). The GLDS Phase 2 system

  7. Identification of differentially expressed genes in parasitic phase Miamiensis avidus (Ciliophora: Scuticociliatia) using suppression subtractive hybridization.

    Science.gov (United States)

    Lee, Eun Hye; Kim, Ki Hong

    2011-04-06

    Miamiensis avidus, a causative agent of scuticociliatosis in cultured marine fish, can live not only in seawater as a free-living organism but also in fish as a parasite. In this study, a cDNA library of representative mRNAs more specific to parasitic phase M. avidus was generated using suppression subtractive hybridization (SSH), and 520 clones selected from the SSH library were single-run sequenced. The differential gene expression patterns were confirmed by semi-quantitative reverse-transcription PCR. Of the 510 SSH clones, 21 clones of 6 putative genes did not match sequences in the public database. The expectation values (E-values) of 117 clones encoding 9 putative genes were greater than 1 x 10(-5). The other 372 clones that met the criterion of E value <1 x 10-5 were matched to 26 known sequences in the database. Genes associated with signal transduction, cell proliferation, membrane transportation, protein translocation, and transcription regulation were preferentially expressed in parasitic phase M. avidus. The differential gene expression may be needed for the ciliates to survive in the host fish, and the corresponding proteins might be used as antigen candidates for development of scuticociliatosis vaccines.

  8. Silencing Mist1 Gene Expression Is Essential for Recovery from Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Anju Karki

    Full Text Available Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Because the synthesis of high levels of hydrolases is potentially dangerous, the pancreas is prone to acute pancreatitis (AP, a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM, inflammation and fibrosis-events that can transition into the earliest stages of pancreatic ductal adenocarcinoma. Despite a wealth of information concerning the broad phenotype associated with pancreatitis, little is understood regarding specific transcriptional regulatory networks that are susceptible to AP and the role these networks play in acinar cell and exocrine pancreas responses. In this study, we examined the importance of the acinar-specific maturation transcription factor MIST1 to AP damage and organ recovery. Analysis of wild-type and Mist1 conditional null mice revealed that Mist1 gene transcription and protein accumulation were dramatically reduced as acinar cells underwent ADM alterations during AP episodes. To test if loss of MIST1 function was primarily responsible for the damaged status of the organ, mice harboring a Cre-inducible Mist1 transgene (iMist1 were utilized to determine if sustained MIST1 activity could alleviate AP damage responses. Unexpectedly, constitutive iMist1 expression during AP led to a dramatic increase in organ damage followed by acinar cell death. We conclude that the transient silencing of Mist1 expression is critical for acinar cells to survive an AP episode, providing cells an opportunity to suppress their secretory function and regenerate damaged cells. The importance of MIST1 to these events suggests that modulating key pancreas transcription networks could ease clinical symptoms in patients diagnosed with pancreatitis and pancreatic cancer.

  9. Genome-wide transcriptional analysis of genes associated with acute desiccation stress in Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Mei-Hui Wang

    Full Text Available Malaria transmission in sub-Saharan Africa varies seasonally in intensity. Outbreaks of malaria occur after the beginning of the rainy season, whereas, during the dry season, reports of the disease are less frequent. Anopheles gambiae mosquitoes, the main malaria vector, are observed all year long but their densities are low during the dry season that generally lasts several months. Aestivation, seasonal migration, and local adaptation have been suggested as mechanisms that enable mosquito populations to persist through the dry season. Studies of chromosomal inversions have shown that inversions 2La, 2Rb, 2Rc, 2Rd, and 2Ru are associated with various physiological changes that confer aridity resistance. However, little is known about how phenotypic plasticity responds to seasonally dry conditions. This study examined the effects of desiccation stress on transcriptional regulation in An. gambiae. We exposed female An. gambiae G3 mosquitoes to acute desiccation and conducted a genome-wide analysis of their transcriptomes using the Affymetrix Plasmodium/Anopheles Genome Array. The transcription of 248 genes (1.7% of all transcripts was significantly affected in all experimental conditions, including 96 with increased expression and 152 with decreased expression. In general, the data indicate a reduction in the metabolic rate of mosquitoes exposed to desiccation. Transcripts accumulated at higher levels during desiccation are associated with oxygen radical detoxification, DNA repair and stress responses. The proportion of transcripts within 2La and 2Rs (2Rb, 2Rc, 2Rd, and 2Ru (67/248, or 27% is similar to the percentage of transcripts located within these inversions (31%. These data may be useful in efforts to elucidate the role of chromosomal inversions in aridity tolerance. The scope of application of the anopheline genome demonstrates that examining transcriptional activity in relation to genotypic adaptations greatly expands the number of

  10. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.

    Science.gov (United States)

    Umman, B; Cakmakoglu, B; Cincin, Z B; Kocaaga, M; Emet, S; Tamer, S; Gokkusu, C

    2015-12-10

    Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.

  11. Overexpression of Wilms tumor 1 gene as a negative prognostic indicator in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Xiaodong Lyu

    Full Text Available Chromosomal aberrations are useful in assessing treatment options and clinical outcomes of acute myeloid leukemia (AML patients. However, 40 ∼ 50% of the AML patients showed no chromosomal abnormalities, i.e., with normal cytogenetics aka the CN-AML patients. Testing of molecular aberrations such as FLT3 or NPM1 can help to define clinical outcomes in the CN-AML patients but with various successes. Goal of this study was to test the possibility of Wilms' tumor 1 (WT1 gene overexpression as an additional molecular biomarker. A total of 103 CN-AML patients, among which 28% had overexpressed WT1, were studied over a period of 38 months. Patient's response to induction chemotherapy as measured by the complete remission (CR rate, disease-free survival (DFS and overall survival (OS were measured. Our data suggested that WT1 overexpression correlated negatively with the CR rate, DFS and OS. Consistent with previous reports, CN-AML patients can be divided into three different risk subgroups based on the status of known molecular abnormalities, i.e., the favorable (NPM1(mt/no FLT3(ITD, the unfavorable (FLT3(ITD and the intermediate risk subgroups. The WT1 overexpression significantly reduced the CR, DFS and OS in both the favorable and unfavorable groups. As the results, patients with normal WT1 gene expression in the favorable risk group showed the best clinical outcomes and all survived with complete remission and disease-free survival over the 37 month study period; in contrast, patients with WT1 overexpression in the unfavorable risk group displayed the worst clinical outcomes. WT1 overexpression by itself is an independent and negative indicator for predicting CR rate, DFS and OS of the CN-AML patients; moreover, it increases the statistical power of predicting the same clinical outcomes when it is combined with the NPM1(mt or the FLT3(ITD genotypes that are the good or poor prognostic markers of CN-AML.

  12. Hh/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene

    Directory of Open Access Journals (Sweden)

    Riccardo Masetti

    2017-01-01

    Full Text Available Abstract Background CBFA2T3-GLIS2 is a fusion gene found in 17% of non-Down syndrome acute megakaryoblastic leukemia (non-DS AMKL, FAB M7 and in 8% of pediatric cytogenetically normal acute myeloid leukemia (CN-AML, in association with several French-American-British (FAB subtypes. Children with AML harboring this aberration have a poor outcome, regardless of the FAB subtype. This fusion gene drives a peculiar expression pattern and leads to overexpression of some of Hedgehog-related genes. GLI-similar protein 2 (GLIS2 is closely related to the GLI family, the final effectors of classic Hedgehog pathway. These observations lend compelling support to the application of GLI inhibitors in the treatment of AML with the aberration CBFA2T3-GLIS2. GANT61 is, nowadays, the most potent inhibitor of GLI family proteins. Methods We exposed to GANT61 AML cell lines and primary cells positive and negative for CBFA2T3-GLIS2 and analyzed the effect on cellular viability, induction of apoptosis, cell cycle, and expression profile. Results As compared to AML cells without GLIS2 fusion, GANT61 exposure resulted in higher sensitivity of both cell lines and primary AML cells carrying CBFA2T3-GLIS2 to undergo apoptosis and G1 cell cycle arrest. Remarkably, gene expression studies demonstrated downregulation of GLIS2-specific signature genes in both treated cell lines and primary cells, in comparison with untreated cells. Moreover, chromatin immunoprecipitation analysis revealed direct regulation by GLIS2 chimeric protein of DNMT1 and DNMT3B, two genes implicated in important epigenetic functions. Conclusions Our findings indicate that the GLI inhibitor GANT61 may be used to specifically target the CBFA2T3-GLIS2 fusion gene in pediatric AML.

  13. Endogenous Cortisol: Acute Modulation of Cytokine Gene Expression in Bovine PBMCs

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  14. Acute modulation of cytokine gene expression in bovine PBMCs by endogenous cortisol

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  15. Acute modulation of cytokine gene expression in bovine peripheral blood mononuclear cells (PBMCs) by endogenous cortisol

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar. 2009. Neuroimmunomod. 16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expr...

  16. HIV Replication Is Not Controlled by CD8+ T Cells during the Acute Phase of the Infection in Humanized Mice.

    Directory of Open Access Journals (Sweden)

    Nicolas Y Petit

    Full Text Available HIV replication follows a well-defined pattern during the acute phase of the infection in humans. After reaching a peak during the first few weeks after infection, viral replication resolves to a set-point thereafter. There are still uncertainties regarding the contribution of CD8(+ T cells in establishing this set-point. An alternative explanation, supported by in silico modeling, would imply that viral replication is limited by the number of available targets for infection, i.e. CD4(+CCR5(+ T cells. Here, we used NOD.SCID.gc(-/- mice bearing human CD4(+CCR5(+ and CD8(+ T cells derived from CD34(+ progenitors to investigate the relative contribution of both in viral control after the peak. Using low dose of a CCR5-tropic HIV virus, we observed an increase in viral replication followed by "spontaneous" resolution of the peak, similar to humans. To rule out any possible role for CD8(+ T cells in viral control, we infected mice in which CD8(+ T cells had been removed by a depleting antibody. Globally, viral replication was not affected by the absence of CD8(+ T cells. Strikingly, resolution of the viral peak was equally observed in mice with or without CD8(+ T cells, showing that CD8(+ T cells were not involved in viral control in the early phase of the infection. In contrast, a marked and specific loss of CCR5-expressing CD4(+ T cells was observed in the spleen and in the bone marrow, but not in the blood, of infected animals. Our results strongly suggest that viral replication during the acute phase of the infection in humanized mice is mainly constrained by the number of available targets in lymphoid tissues rather than by CD8(+ T cells.

  17. HIV Replication Is Not Controlled by CD8+ T Cells during the Acute Phase of the Infection in Humanized Mice.

    Science.gov (United States)

    Petit, Nicolas Y; Lambert-Niclot, Sidonie; Marcelin, Anne-Geneviève; Garcia, Sylvie; Marodon, Gilles

    2015-01-01

    HIV replication follows a well-defined pattern during the acute phase of the infection in humans. After reaching a peak during the first few weeks after infection, viral replication resolves to a set-point thereafter. There are still uncertainties regarding the contribution of CD8(+) T cells in establishing this set-point. An alternative explanation, supported by in silico modeling, would imply that viral replication is limited by the number of available targets for infection, i.e. CD4(+)CCR5(+) T cells. Here, we used NOD.SCID.gc(-/-) mice bearing human CD4(+)CCR5(+) and CD8(+) T cells derived from CD34(+) progenitors to investigate the relative contribution of both in viral control after the peak. Using low dose of a CCR5-tropic HIV virus, we observed an increase in viral replication followed by "spontaneous" resolution of the peak, similar to humans. To rule out any possible role for CD8(+) T cells in viral control, we infected mice in which CD8(+) T cells had been removed by a depleting antibody. Globally, viral replication was not affected by the absence of CD8(+) T cells. Strikingly, resolution of the viral peak was equally observed in mice with or without CD8(+) T cells, showing that CD8(+) T cells were not involved in viral control in the early phase of the infection. In contrast, a marked and specific loss of CCR5-expressing CD4(+) T cells was observed in the spleen and in the bone marrow, but not in the blood, of infected animals. Our results strongly suggest that viral replication during the acute phase of the infection in humanized mice is mainly constrained by the number of available targets in lymphoid tissues rather than by CD8(+) T cells.

  18. Bladder response to acute sacral neuromodulation while treating rats in different phases of complete spinal cord injury: a preliminary study

    Directory of Open Access Journals (Sweden)

    Ping Shi

    2015-12-01

    Full Text Available Background: Compared to conventional therapies, sacral neuromodulation (SNM may offer an alternative, non-destructive treatment for SCI patients with bladder dysfunction. Understanding bladder response to SNM treatment for SCI in different phases may yield new insights for innovative use of this promising technique. Materials and Methods: Female Sprague-Dawley rats were used in this study to examine the effects of acute SNM on bladder reflex in complete SCI rats. All rats were anesthetized and set up for continuous saline infusion. Acute SNM treatment was implemented for about 6 hours for each rat. Cystometric parameters, including time between contractions, contraction duration, bladder peak pressure, and number of uninhibited contractions, were analyzed and compared within rats before and after SNM treatment. Results: For the spinally transected rats during early phase (less than two weeks post spinalization, the time between contractions and contraction duration both increased after SNM treatments, yet the increased amplitude was about or less than 20%. For the spinally transected rats with a longer days survival (about two to four weeks post spinalization, the time between contractions and contraction duration substantially increased after SNM treatment and the changes for their average values were more than 90%. For the spinally transected rats with a much longer days survival (more than five weeks post spinalization, the time between contractions and contraction duration increased after SNM treatments, yet the magnitude of changes were less than 30%. Conclusion: The present study suggested that the significant effectiveness of SNM for complete SCI played its role after the spinal shock phase and prior to the development of detrusor overactivity. It indicated that the time point of SNM treatment is necessary to be paid attention.

  19. Effects of Partial and Acute Total Sleep Deprivation on Performance across Cognitive Domains, Individuals and Circadian Phase

    Science.gov (United States)

    Lo, June C.; Groeger, John A.; Santhi, Nayantara; Arbon, Emma L.; Lazar, Alpar S.; Hasan, Sibah; von Schantz, Malcolm; Archer, Simon N.; Dijk, Derk-Jan

    2012-01-01

    Background Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate. Methodology/Principal Findings We conducted a 2 × 12-day laboratory protocol to characterize the interaction of repeated partial and acute total sleep deprivation and circadian phase on performance across seven cognitive domains in 36 individuals (18 males; mean ± SD of age = 27.6±4.0 years). The sample was stratified for the rs57875989 polymorphism in PER3, which confers cognitive susceptibility to total sleep deprivation. We observed a deterioration of performance during both repeated partial and acute total sleep deprivation. Furthermore, prior partial sleep deprivation led to poorer cognitive performance in a subsequent total sleep deprivation period, but its effect was modulated by circadian phase such that it was virtually absent in the evening wake maintenance zone, and most prominent during early morning hours. A significant effect of PER3 genotype was observed for Subjective Alertness during partial sleep deprivation and on n-back tasks with a high executive load when assessed in the morning hours during total sleep deprivation after partial sleep loss. Overall, however, Subjective Alertness and Sustained Attention were more affected by both partial and total sleep deprivation than other cognitive domains and tasks including n-back tasks of Working Memory, even when implemented with a high executive load. Conclusions/Significance Sleep loss has a primary effect on Sleepiness and Sustained Attention with much smaller effects on challenging Working Memory tasks. These findings have implications for understanding how sleep debt and circadian rhythmicity

  20. Effects of partial and acute total sleep deprivation on performance across cognitive domains, individuals and circadian phase.

    Directory of Open Access Journals (Sweden)

    June C Lo

    Full Text Available BACKGROUND: Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a 2 × 12-day laboratory protocol to characterize the interaction of repeated partial and acute total sleep deprivation and circadian phase on performance across seven cognitive domains in 36 individuals (18 males; mean ± SD of age = 27.6 ± 4.0 years. The sample was stratified for the rs57875989 polymorphism in PER3, which confers cognitive susceptibility to total sleep deprivation. We observed a deterioration of performance during both repeated partial and acute total sleep deprivation. Furthermore, prior partial sleep deprivation led to poorer cognitive performance in a subsequent total sleep deprivation period, but its effect was modulated by circadian phase such that it was virtually absent in the evening wake maintenance zone, and most prominent during early morning hours. A significant effect of PER3 genotype was observed for Subjective Alertness during partial sleep deprivation and on n-back tasks with a high executive load when assessed in the morning hours during total sleep deprivation after partial sleep loss. Overall, however, Subjective Alertness and Sustained Attention were more affected by both partial and total sleep deprivation than other cognitive domains and tasks including n-back tasks of Working Memory, even when implemented with a high executive load. CONCLUSIONS/SIGNIFICANCE: Sleep loss has a primary effect on Sleepiness and Sustained Attention with much smaller effects on challenging Working Memory tasks. These findings have implications for understanding how sleep debt and

  1. Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations.

    Science.gov (United States)

    Abbas, Saman; Sanders, Mathijs A; Zeilemaker, Annelieke; Geertsma-Kleinekoort, Wendy M C; Koenders, Jasper E; Kavelaars, Francois G; Abbas, Zabiollah G; Mahamoud, Souad; Chu, Isabel W T; Hoogenboezem, Remco; Peeters, Justine K; van Drunen, Ellen; van Galen, Janneke; Beverloo, H Berna; Löwenberg, Bob; Valk, Peter J M

    2014-05-01

    Acute myeloid leukemia is a neoplasm characterized by recurrent molecular aberrations traditionally demonstrated by cytogenetic analyses. We used high density genome-wide genotyping and gene expression profiling to reveal acquired cryptic abnormalities in acute myeloid leukemia. By genome-wide genotyping of 137 cases of primary acute myeloid leukemia, we disclosed a recurrent focal amplification on chromosome 14q32, which included the genes BCL11B, CCNK, C14orf177 and SETD3, in two cases. In the affected cases, the BCL11B gene showed consistently high mRNA expression, whereas the expression of the other genes was unperturbed. Fluorescence in situ hybridization on 40 cases of acute myeloid leukemia with high BCL11B mRNA expression [2.5-fold above median; 40 out of 530 cases (7.5%)] revealed 14q32 abnormalities in two additional cases. In the four BCL11B-rearranged cases the 14q32 locus was fused to different partner chromosomes. In fact, in two cases, we demonstrated that the focal 14q32 amplifications were integrated into transcriptionally active loci. The translocations involving BCL11B result in increased expression of full-length BCL11B protein. The BCL11B-rearranged acute myeloid leukemias expressed both myeloid and T-cell markers. These biphenotypic acute leukemias all carried FLT3 internal tandem duplications, a characteristic marker of acute myeloid leukemia. BCL11B mRNA expression in acute myeloid leukemia appeared to be strongly associated with expression of other T-cell-specific genes. Myeloid 32D(GCSF-R) cells ectopically expressing Bcl11b showed decreased proliferation rate and less maturation. In conclusion, by an integrated approach involving high-throughput genome-wide genotyping and gene expression profiling we identified BCL11B as a candidate oncogene in acute myeloid leukemia.

  2. Delivery of glutamine synthetase gene by baculovirus vectors: a proof of concept for the treatment of acute hyperammonemia.

    Science.gov (United States)

    Torres-Vega, M A; Vargas-Jerónimo, R Y; Montiel-Martínez, A G; Muñoz-Fuentes, R M; Zamorano-Carrillo, A; Pastor, A R; Palomares, L A

    2015-01-01

    Hyperammonemia, a condition present in patients with urea cycle disorders (UCDs) or liver diseases, can cause neuropsychiatric complications, which in the worst cases result in brain damage, coma or death. Diverse treatments exist for the treatment of hyperammonemia, but they have limited efficacy, adverse effects and elevated cost. Gene therapy is a promising alternative that is explored here. A baculovirus, termed Bac-GS, containing the glutamine synthetase (GS) gene was constructed for the in vitro and in vivo treatment of hyperammonemia. Transduction of MA104 epithelial or L6 myoblast/myotubes cells with Bac-GS resulted in a high expression of the GS gene, an increase in GS concentration, and a reduction of almost half of exogenously added ammonia. When Bac-GS was tested in an acute hyperammonemia rat model by intramuscularly injecting the rear legs, the concentration of ammonia in blood decreased 351 μM, in comparison with controls. A high GS concentration was detected in gastrocnemius muscles from the rats transduced with Bac-GS. These results show that gene delivery for overexpressing GS in muscle tissue is a promising alternative for the treatment of hyperammonemia in patients with acute or chronic liver diseases and hepatic encephalopathy or UCD.

  3. Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver.

    Science.gov (United States)

    Peng, Lai; Piekos, Stephanie; Guo, Grace L; Zhong, Xiao-Bo

    2016-09-01

    The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation. Farnesoid X receptor (FXR) is critical for bile acid and lipid homeostasis in liver. However, the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control (C57BL/6) mouse livers during development. Liver samples of male C57BL/6 and Fxr-null mice at 6 different ages from prenatal to adult were used. The Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression, including cytochrome P450s at neonatal ages. Among the 185 phase-I genes from 12 different families, 136 were expressed, and differential expression during development occurred in genes from all 12 phase-I families, including hydrolysis: carboxylesterase (Ces), paraoxonase (Pon), and epoxide hydrolase (Ephx); reduction: aldoketo reductase (Akr), quinone oxidoreductase (Nqo), and dihydropyrimidine dehydrogenase (Dpyd); and oxidation: alcohol dehydrogenase (Adh), aldehyde dehydrogenase (Aldh), flavin monooxygenases (Fmo), molybdenum hydroxylase (Aox and Xdh), cytochrome P450 (P450), and cytochrome P450 oxidoreductase (Por). The data also suggested new phase-I genes potentially targeted by FXR. These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.

  4. Transplantation of human thioredoxin gene-modified hepatocytes for treatment of acute liver failure in rat model

    Institute of Scientific and Technical Information of China (English)

    LI Hua; JIANG Nan; ZHANG Jian; WANG Gen-shu; YANG Yang; CHEN Gui-hua

    2009-01-01

    Background Mostly because of the limited number and proliferative ability of the transplanted hepatocytes,hepatocyte transplantation offers only temporary support to the hepatic function with rather poor functional replacement of the damaged liver parenchyma.This study aimed to observe the therapeutic effect of human thioredoxin(hTrx)gene-modified hepatocytes on experimental acute liver failure in rats.Methods hTrx cDNA was obtained by reverse transcription-polymerase chain reaction(RT-PCR)from human osteosercoma 143(TK-)cells to construct the recombinant retrovirus vector pLEGFP/hTrx,which was packaged into PA317 cells to collect the recombinant retrovirus containing hTrx gene.After titration and characterization,the recombinant retrovirus was applied to primary cultured rat hepatocyte for infection to generate hTrx gene-modified rat hepatocytes,whose viability and antioxidative capacity were examined by immunohistochemistry and MIF assay,respectively.In a Sprague-Dawley(SD)rat model of acute liver failure,the modified hepatocytes were injected into the spleen,and the hepatic function and survival rate of the recipient rats were evaluated at different time points after the transplantation.Results NIH3T3 cells infected by the recombinant retrovirus were capable of expressing bioactive hTrx in the form of fusion proteins.Immunohistochemistry demonstrated normal function of the hTrx gene-modified hepatocytes,which possessed strong antioxidative capacity as shown by MTT assay.Transplantation of the modified hepatocytes in rats with acute liver failure resulted in significantly lowered serum alanine aminotransferase(ALT)and total bilirubin(TBIL)levels(P<0.05).The hepatocytes exhibited long-term survival and efficient proliferation after transplantation.Fourteen days after the operation,the rat models receiving hTrx gene-modified hepatocytes had significantly higher survival rate than those without the transplantation.Conclusion hTrx gene-modifled hepatocyte

  5. Effects of Acupuncture on mRNA Levels of Apoptotic Factors in Perihematomal Brain Tissue During the Acute Phase of Cerebral Hemorrhage

    Science.gov (United States)

    Li, Zuowei; Zheng, Xiaonan; Li, Ping; Itoua, Eudes Saturnin Régis; Moukassa, Donatien; Andely, Françoise Ndinga

    2017-01-01

    Background To explore the time-dependent effects of acupuncture on mRNA levels of the apoptotic factors BCL-2 and BAX in a rat cerebral hemorrhage model, slow injection of autologous blood to the caudate nucleus was used to generate the cerebral hemorrhage model. Material/Methods A sham surgery control group, groups with acupuncture applied 3, 9, 24, and 48 hours after model induction, and time-matched model-only control groups were used. In situ hybridization was used to detect BCL-2 and BAX mRNA expression, and semi-quantitative RT-PCR was used to measure the expression. Results The number of BCL-2 and BAX mRNA-positive cells significantly increased during the acute phase of cerebral hemorrhage. BCL-2 mRNA was significantly upregulated in acupuncture groups compared to other groups, whereas BAX mRNA levels in the acupuncture groups were lower in the other groups, except for the sham surgery group. Additionally, earlier acupuncture intervention was associated with a lower ratio of expression between the two genes. Changes in BCL-2 and BAX mRNA expression were consistent with changes in the number of cells positive for BCL-2 and BAX mRNA; however, the change in the expression ratio was consistent with the change in the number of cells positive for BCL-2 mRNA, but opposite to the change in the number of cells positive for BAX mRNA. Conclusions Acupuncture ameliorated changes in expression of apoptotic factors in the brain induced by acute cerebral hemorrhage and may thus protect the brain, with greater efficacy when the delay before acupuncture was minimized. PMID:28357997

  6. Effects of Acupuncture on mRNA Levels of Apoptotic Factors in Perihematomal Brain Tissue During the Acute Phase of Cerebral Hemorrhage.

    Science.gov (United States)

    Li, Zuowei; Zheng, Xiaonan; Li, Ping; Itoua, Eudes Saturnin Régis; Moukassa, Donatien; Ndinga Andely, Françoise

    2017-03-30

    BACKGROUND To explore the time-dependent effects of acupuncture on mRNA levels of the apoptotic factors BCL-2 and BAX in a rat cerebral hemorrhage model, slow injection of autologous blood to the caudate nucleus was used to generate the cerebral hemorrhage model. MATERIAL AND METHODS A sham surgery control group, groups with acupuncture applied 3, 9, 24, and 48 hours after model induction, and time-matched model-only control groups were used. In situ hybridization was used to detect BCL-2 and BAX mRNA expression, and semi-quantitative RT-PCR was used to measure the expression. RESULTS The number of BCL-2 and BAX mRNA-positive cells significantly increased during the acute phase of cerebral hemorrhage. BCL-2 mRNA was significantly upregulated in acupuncture groups compared to other groups, whereas BAX mRNA levels in the acupuncture groups were lower in the other groups, except for the sham surgery group. Additionally, earlier acupuncture intervention was associated with a lower ratio of expression between the two genes. Changes in BCL-2 and BAX mRNA expression were consistent with changes in the number of cells positive for BCL-2 and BAX mRNA; however, the change in the expression ratio was consistent with the change in the number of cells positive for BCL-2 mRNA, but opposite to the change in the number of cells positive for BAX mRNA. CONCLUSIONS Acupuncture ameliorated changes in expression of apoptotic factors in the brain induced by acute cerebral hemorrhage and may thus protect the brain, with greater efficacy when the delay before acupuncture was minimized.

  7. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    DEFF Research Database (Denmark)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were...... higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 mug/ml, but negligible concentrations in milk, indicating that a pathogen must be present...... in the mammary gland for serum amyloid A to accumulate in milk. The acute phase protein concentrations in milk increased significantly with increasing somatic cell count, suggesting that they may be indicators of the severity of an infection....

  8. Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial.

    Science.gov (United States)

    Kantarjian, Hagop M; Roboz, Gail J; Kropf, Patricia L; Yee, Karen W L; O'Connell, Casey L; Tibes, Raoul; Walsh, Katherine J; Podoltsev, Nikolai A; Griffiths, Elizabeth A; Jabbour, Elias; Garcia-Manero, Guillermo; Rizzieri, David; Stock, Wendy; Savona, Michael R; Rosenblat, Todd L; Berdeja, Jesus G; Ravandi, Farhad; Rock, Edwin P; Hao, Yong; Azab, Mohammad; Issa, Jean-Pierre J

    2017-08-24

    The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m(2) guadecitabine for 5 days as an effective treatment schedule. In this phase 2 study, we aimed to assess the safety and activity of two doses and schedules of guadecitabine in older (≥65 years) patients with treatment-naive acute myeloid leukaemia who were not candidates for intensive chemotherapy. We did a multicentre, randomised, open-label, phase 1/2 study of guadecitabine in cohorts of patients with treatment-naive acute myeloid leukaemia, relapsed or refractory acute myeloid leukaemia, and myelodysplastic syndromes; here we report the phase 2 results from the cohort of treatment-naive patients with acute myeloid leukaemia. We included patients aged at least 65 years from 14 US medical centres (hospitals and specialist cancer clinics) who were not candidates for intensive chemotherapy and randomly assigned them (1:1) using a computer algorithm (for dynamic randomisation) to guadecitabine 60 or 90 mg/m(2) on days 1-5 (5-day schedule) of a 28-day treatment cycle. Treatment allocation was not masked. We also assigned additional patients to guadecitabine 60 mg/m(2) in a 10-day schedule in a 28-day treatment cycle after a protocol amendment. The primary endpoint was composite complete response (complete response, complete response with incomplete platelet recovery, or complete response with incomplete neutrophil recovery regardless of platelets). Response was assessed in all patients (as-treated) who received at least one dose of guadecitabine. We present the final analysis, although at the time of the database lock

  9. Immunomodulatory properties of gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.

    Science.gov (United States)

    Plessers, Elke; Wyns, Heidi; Watteyn, Anneleen; Pardon, Bart; De Baere, Siegrid; Sys, Stanislas U; De Backer, Patrick; Croubels, Siska

    2016-03-01

    Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein-Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment (n=4) and a GAM (n=4), a KETO (n=4) and a GAM-KETO (n=4) group, rece