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Sample records for acute phase gene

  1. Heterogeneous lobular distribution of hepatocytes expressing acute- phase genes during the acute inflammatory reaction

    OpenAIRE

    1989-01-01

    Functional heterogeneity in the lobule with regard to plasma protein synthesis is still debated. Therefore, we have localized in liver sections from normal rats and from rats with turpentine-induced AIR the mRNA and protein products of three genes with different alterations in their hepatic expression during an AIR: alpha 2M and alpha 1PI, two positively reacting acute-phase genes, and alpha 1I3, a negative acute- phase reactant. In normal liver, all hepatocytes expressed alpha 2M and alpha 1...

  2. Induction of acute phase gene expression by brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Ji-Hong [UCLA School of Medicine, Los Angeles, CA (United States)]|[Chang Gung Memorial Hospital, Taipei (Taiwan, Province of China); Sun, Ji-Rong; Withers, H.R. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  3. Post-transcriptional control of negative acute phase genes by transforming growth factor beta.

    OpenAIRE

    Morrone, G; Cortese, R; Sorrentino, V

    1989-01-01

    During the acute phase (AP) reaction the expression of a series of liver-specific genes coding for secretory proteins is either stimulated or suppressed by different cytokines released by activated monocytes. Transforming growth factor beta (TGF-beta) is a cytokine that, first identified for its ability to regulate cellular growth, has been gradually recognized to modulate several other functions. We have investigated the effect of TGF-beta on the expression of acute phase genes in liver cell...

  4. Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes.

    OpenAIRE

    Varley, A.W.; Coulthard, M G; Meidell, R S; Gerard, R D; Munford, R S

    1995-01-01

    We report that promoters for two murine acute-phase protein (APP) genes, complement factor 3 (C3) and serum amyloid A3 (SAA3), can increase recombinant protein expression in response to inflammatory stimuli in vivo. To deliver APP promoter-luciferase reporter gene constructs to the liver, where most endogenous APP synthesis occurs, we introduced them into a nonreplicating adenovirus vector and injected the purified viruses intravenously into mice. When compared with the low levels of basal lu...

  5. Interleukin 6 induces a liver-specific nuclear protein that binds to the promoter of acute-phase genes.

    OpenAIRE

    Poli, V.; Cortese, R

    1989-01-01

    Interleukin 6 (IL-6) is responsible for a variety of biological effects related to the activation of defenses against infection or inflammation, including the immune response and the acute-phase reaction. Its mechanism of action is unknown. It has recently been shown to induce transcription of several genes encoding acute-phase proteins. Here we describe the identification of an IL-6 responsive element (IL-6RE) present in the promoter of the human hemopexin gene. This element is necessary and...

  6. 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.

  7. 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. PMID:26850544

  8. 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

    Acute physical activity elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. In the present time-course study, pigs were submitted to an acute bout of treadmill running until near exhaustion to determine the impact...... detected an upregulation of genes that are associated with muscle cell proliferation and differentiation, including MUSTN1, ASB5 and CSRP3, possibly reflecting activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression...... 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...

  9. Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene.

    OpenAIRE

    Hattori, M; Abraham, L J; Northemann, W; Fey, G H

    1990-01-01

    Interleukin 6 (IL-6) was established as a transcriptional inducer of the rat alpha 2-macroglobulin gene, a prototype liver acute-phase gene. Maximum induction occurred when the 5' flanking sequences of this gene (position -209 to -43) directed expression from the gene's own TATA box and transcription start site. Removal of the hexanucleotide CTGGGA (position -164 to -159) abolished 60-70% of the hormonal induction in FAO1 rat hepatoma cells. This hexanucleotide was defined as the IL-6 respons...

  10. Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes.

    OpenAIRE

    Campos, S P; Baumann, H

    1992-01-01

    Several endocrine hormones which influence liver metabolism are known to increase in activity during the acute phase of injury or inflammation. We determined whether these hormones have the potential to influence acute-phase protein production in human and rat hepatoma cells. Catecholamines, glucagon, growth hormone, triiodothyronine, and cyclic nucleotides individually or in combination did not modulate the basal or the interleukin-1 (IL-1)-, IL-6-, and dexamethasone-stimulated levels of acu...

  11. INFLAMMATION AND ACUTE PHASE RESPONSE

    Directory of Open Access Journals (Sweden)

    Farah Aziz Khan

    2010-10-01

    Full Text Available Inflammation caused by infection takes place by the cooperative cascade of cytokines and leukocytes. Tumor necrosis factor, interlukin-1, and interlukin-6 play important roles as proinflammatory cytokines to mediate local inflammation and activate other inflammatory cells e.g. neutrophils, monocytes, and macrophages. At least 15 different low molecular weight cytokine are secreted by activated leukocytes and are responsible for triggering acute phase response in the form of fever, leukocytosis, increased secretion of adreno corticotropic hormones, and production of acute phase proteins. Acute phase proteins are produced in liver under the influence of cytokines, which through blood stream passes to the site of inflammation and kill the pathogens by opsonization and activating complement pathways. The changes in the concentrations of positive acute-phase proteins and negative acute-phase proteins are due to the changes in their production by liver. Three of the best known acute phase proteins are C-reactive protein, serum anyloid A, and haptoglobin. Some disease states are casually related to acute phase proteins. C-reactive protein mediated compliment activation has a key role in some forms of tissue alteration such as cardiac infarction. Elevated S amyloid A levels are seen in chronic arthritis and tuberculosis. Other acute phase proteins show more moderate rise, usually less than fivefold.

  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

    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...... receptor antagonist (up-regulated) with interleukin 1 receptor antagonist being the most highly regulated gene in both VAT and RPAT. Looking at patterns of expression across the three types of adipose tissues, obesity was associated with an increased number of acute phase proteins differentially expressed...... 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....

  13. 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.

  14. 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.

  15. 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

    A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor (TN......, a minimally invasive liver biopsy technique can be used for studying the hepatic APR in diseased cattle. Lipopolysaccharide-induced mastitis resulted in a time-dependent production of inflammatory cytokines and SAA and Hp in the liver of dairy cows.......A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor (TNF...

  16. Cytokines and the hepatic acute phase response

    NARCIS (Netherlands)

    Moshage, H

    1997-01-01

    The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncont

  17. INFLAMMATION AND ACUTE PHASE RESPONSE

    OpenAIRE

    Farah Aziz Khan; Mohd Fareed Khan

    2010-01-01

    Inflammation caused by infection takes place by the cooperative cascade of cytokines and leukocytes. Tumor necrosis factor, interlukin-1, and interlukin-6 play important roles as proinflammatory cytokines to mediate local inflammation and activate other inflammatory cells e.g. neutrophils, monocytes, and macrophages. At least 15 different low molecular weight cytokine are secreted by activated leukocytes and are responsible for triggering acute phase response in the form of fever, leukocytosi...

  18. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    Science.gov (United States)

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  19. Acute Phase Response in Animals: A Review

    OpenAIRE

    Cray, Carolyn; Zaias, Julia; Altman, Norman H

    2009-01-01

    The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins, an integral part of the acute phase response, have been a focus...

  20. Comparison of changes in gene expression of transferrin receptor-1 and other iron-regulatory proteins in rat liver and brain during acute-phase response

    OpenAIRE

    Malik, Ihtzaz; Naz, Naila; Sheikh, Nadeem; Khan, Sajjad; Moriconi, Federico; Blaschke, Martina; Ramadori, Giuliano

    2011-01-01

    The “acute phase” is clinically characterized by homeostatic alterations such as somnolence, adinamia, fever, muscular weakness, and leukocytosis. Dramatic changes in iron metabolism are observed under acute-phase conditions. Rats were administered turpentine oil (TO) intramuscularly to induce a sterile abscess and killed at various time points. Tissue iron content in the liver and brain increased progressively after TO administration. Immunohistology revealed an abundant expression of transf...

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

    OpenAIRE

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

    1995-01-01

    Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in...

  2. The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins.

    OpenAIRE

    Schumann, R.R.; Kirschning, C.J.; Unbehaun, A; Aberle, H P; Knope, H P; Lamping, N; Ulevitch, R J; Herrmann, F.

    1996-01-01

    Acute-phase reactants (APRs) are proteins synthesized in the liver following induction by interleukin-1 (IL-1), IL-6, and glucocorticoids, involving transcriptional gene activation. Lipopolysaccharide-binding protein (LBP) is a recently identified hepatic secretory protein potentially involved in the pathogenesis of sepsis, capable of binding the bacterial cell wall product endotoxin and directing it to its cellular receptor, CD14. In order to examine the transcriptional induction mechanisms ...

  3. Acute Phase Proteins and Their Role in Periodontitis: A Review

    OpenAIRE

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- l...

  4. Effects of Hepatocyte Nuclear Factor-4α on the Regulation of the Hepatic Acute Phase Response

    OpenAIRE

    Wang, Zhongyan; Burke, Peter A.

    2007-01-01

    Following injury, a large number of hepatic acute phase genes are rapidly modulated at the transcriptional level to restore metabolic homeostasis an limit tissue damage. Hepatocyte nuclear factor 4α (HNF-4α) is a liver-enriched transcription factor that controls embryonic liver development and regulates tissue specific gene expression in adult liver cells. Many genes encoding acute phase proteins contain HNF-4α binding sites in their promoter regions and are transcriptionally regulated by HNF...

  5. Liver-specific gene expression: A-activator-binding site, a promoter module present in vitellogenin and acute-phase genes.

    OpenAIRE

    Kaling, M; Kugler, W.; Ross, K.; Zoidl, C.; Ryffel, G U

    1991-01-01

    The A2 vitellogenin gene of Xenopus laevis, which is expressed liver specifically, contains an A-activator-binding site (AABS) that mediates high in vitro transcriptional activity in rat liver nuclear extracts. Footprint experiments with DNase I and gel retardation assays revealed the binding of several proteins to AABS. Using binding sites of known DNA-binding proteins as competitors in the gel retardation assay, we found that the transcription factor C/EBP and/or one of its "iso-binders" as...

  6. 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.

  7. Acute phase serum proteins in diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Rema M

    1996-01-01

    Full Text Available The serum concentration of various acute phase reactants were studied in patients with non-insulin dependent diabetes mellitus with and without retinopathy and in control subjects. The serum levels of haptoglobin was elevated in diabetics with retinopathy and the levels were highest in those with proliferative diabetic retinopathy. The levels of serum albumin, alpha-1 acid glycoprotein, alpha-1 antitrypsin and caeruloplasmin were not significantly different between the patients with retinopathy and controls. Haptoglobin increases serum viscosity and this could be the mechanism by which it plays a role in pathogenesis of diabetic retinopathy. These preliminary observations need to be confirmed by studies based on larger number of patients. Longitudinal studies on acute phase reactants in various stages of development of diabetic retinopathy would also provide valuable information.

  8. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    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...... genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query...

  9. Acute Phase Proteins and Their Role in Periodontitis: A Review.

    Science.gov (United States)

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-11-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  10. BCL11A expression in acute phase chronic myeloid leukemia.

    Science.gov (United States)

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  11. Management of pemphigus vulgaris during acute phase

    Directory of Open Access Journals (Sweden)

    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.

  12. 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...... proteins (APP) outside the liver is increasingly recognized, still little is known of extra-hepatic production of APP in pigs. 14-18 h after experimental infection with Actinobacillus pleuropneumoniae, causing acute pleuropneumonia in pigs, we studied local APP gene expression changes in different...... differentially expressed between infected and control animals. We demonstrated that acute pleuropneumonia caused by A. pleuropneumoniae leads to a rapid disseminated local intra-lung APP response, also in apparently unaffected areas of the infected lung. Further extrahepatic expression of several acute-phase...

  13. Monitoring health by values of acute phase proteins

    NARCIS (Netherlands)

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.; Dijk, van E.; Meloen, R.H.

    2006-01-01

    A systemic acute phase reaction may develop during infection and inflammation, due to the action of peripherally liberated proinflammatory cytokines. Hepatic metabolism changes, and negative and positive acute phase proteins (APPs) can be measured in the blood: the APPs therefore represent appropria

  14. 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...

  15. 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...

  16. 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....

  17. Acute phase response in Wistar rats after controlled hemorrhage

    OpenAIRE

    Stepanović Predrag; Maličević Ž.; Andrić N.; Nikolovski-Stefanović Zorica

    2011-01-01

    After injury the acute-phase response of the organism activates mechanisms which imply the release of cytokines, stress hormones, and mediators of pain and inflammation. The main function of the acutephase response is to hinder further damage of the injured tissue by activating reparative processes. The increase in the concentration of acute phase proteins and the concurrent decrease in albumins and prealbumins indicate that there is a strong link between t...

  18. Presence of acute phase response in coal workers' pneumoconiosis.

    OpenAIRE

    Fernandez Rego, G; Ocio Achaerandio, G; González Cuervo, V; Rodríquez Menéndez, C; Martínez Gonezález, C; Alvarez Alvarez, C

    1991-01-01

    To evaluate the role of personal factors in pneumoconiosis, several acute phase proteins were studied in 62 coal miners without acute illnesses and classified as having no pneumoconiosis (n = 19), simple pneumoconiosis (n = 23), or complicated pneumoconiosis with progressive massive fibrosis (n = 20). Groups were similar for age, years of work at high risk jobs, chronic bronchitis, and forced expiratory volume in one second (FEV1). C-reactive protein concentration was significantly higher in ...

  19. 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

  20. EXPRESSION AND CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE AND MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN GENE IN ACUTE LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    LAI Yong-rong; MA Jie; LU Yu-ying; NU Wei-lin; XIANG Zhi-fu

    1999-01-01

    Objective: To evaluate the expression and clinical significance of multidrug resistance gene (mdr1) and multidrug resistance-associated protein (MRP) gene in acute leukemia. Methods: The expression of mdr1 and MRP assay in 55 patients with acute leukemia (AL) by reverse transcription polymerase chain reaction (RT-PCR).Results: The mdr1 and MRP gene expression levels in the relapsed AL and the blastic plastic phases of CML were significantly higher than those in the newly diagnostic AL and controls. The mdr1 and MRP gene expression levels in the clinical drug-resistant group were significantly higher than those in the non-drug-resistant group. The complete remission (CR) rate in patients with high mdr1 expression (14.3%) was significantly lower than that with low mdr1 expression (57.5%); similarly the CR rate in patients with high MRP level was also lower than that with low MRP level. Using both high expression of mdr1 and MRP gene as the indicator for evaluating multidrug resistance (MDR),the positive predictive value and accuracy increased in comparison with single gene high expression. Conclusion:Elevated level of mdr1 or MRP gene expression might be unfavorable prognostic factors for AL patient and may be used as an important index for predicting drug-resistance and relapse in AL patient. Measuring both mdr1 and MRP gene expression would increase accuracy and sensibility of evaluating MDR in acute leukemia.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

    ), 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...

  3. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

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

    2011-01-01

    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 morpholog

  4. 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.

  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...

  6. Avian acute phase protein ovotransferrin modulates phagocyte function

    Science.gov (United States)

    Acute phase proteins (APP) are serum proteins elevated in response to a variety of physiological injuries including infection and inflammation. These pathogen nonspecific proteins are predominantly synthesized in the liver and serve as a humoral component of innate immunity by way of recognizing and...

  7. 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.

  8. 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

  9. The Use of Dermal Substitutes in Burn Surgery: Acute Phase

    OpenAIRE

    Shahrokhi, Shahriar; Anna, Arno; Marc G. Jeschke

    2014-01-01

    Dermal substitutes are increasingly becoming an essential part of the burn care strategy. During the acute phase of burn treatment, dermal substitutes improve functional and cosmetic results long-term and thus increase quality of life. In the chronic wound setting, dermal substitutes are used to reconstruct and improve burn scars and other defects. Despite some successes in the use of dermal substitutes there are more needs and requirements to further improve outcomes and hence further resear...

  10. Extrahepatic production of acute phase serum amyloid A

    OpenAIRE

    Upragarin, N.; Landman, W.J.M.; Gaastra, W; Gruys, E.

    2005-01-01

    Amyloidosis is a group of diseases characterized by the extracellular deposition of protein that contains non-branching, straight fibrils on electron microscopy (amyloid fibrils) that have a high content of ß-pleated sheet conformation. Various biochemically distinct proteins can undergo transformation into amyloid fibrils. The precursor protein of amyloid protein A (AA) is the acute phase protein serum amyloid A (SAA). The concentration of SAA in plasma increa...

  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. 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.

  13. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis

    OpenAIRE

    Windsor, A; Kanwar, S; Li, A.; Barnes, E.; Guthrie, J; Spark, J; Welsh, F.; Guillou, P; Reynolds, J

    1998-01-01

    Background—In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. 
Aims—To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with ac...

  14. 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.

  15. Hyperglycemia in nondiabetic patients during the acute phase of stroke

    Directory of Open Access Journals (Sweden)

    Daniel Agustin Godoy

    2012-02-01

    Full Text Available OBJECTIVE: To determine patterns of hyperglycemic (HG control in acute stroke. METHODS: Anonymous survey through Internet questionnaire. Participants included Latin-American physicians specialized in neurocritical care. RESULTS: The response rate was 74%. HG definition varied widely. Fifty per cent considered it when values were >140 mg/dL (7.8 mmol/L. Intravenous (IV regular insulin was the drug of choice for HG correction. One fifth of the respondents expressed adherence to a protocol. Intensive insulin therapy (IIT was used by 23%. Glucose levels were measured in all participants at admission. Routine laboratory test was the preferred method for monitoring. Reactive strips were more frequently used when monitoring was intensive. Most practitioners (56.7% monitored glucose more than two times daily throughout the Intensive Care Unit stay. CONCLUSIONS: There is considerable variability and heterogeneity in the management of elevated blood glucose during acute phase of stroke by the surveyed Latin-American physicians.

  16. Serum acute phase proteins and swine health status

    OpenAIRE

    Chen, Hsin-Hsin; Lin, Jyh-Hung; Fung, Hang-Pong; Ho, Lin-Lin; Yang, Ping-Chin; Lee, Wen-Chuan; Lee, Yan-Pai; Chu, Rea-Min

    2003-01-01

    The purpose of this study was to investigate the relationship between swine health status and the concentration of the serum acute phase proteins, haptoglobin (HP), and C-reactive protein (CRP). A total of 378 clinically healthy pigs from farms A and B, plus 20 pigs culled from farm A due to poor growth, were used in this experiment. Each pig was examined and blood samples were collected during slaughter. The HP concentration was measured by using an HP-hemoglobin binding assay. The CRP conce...

  17. 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.

  18. 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.

  19. Acute phase proteins in experimentally induced pregnancy toxemia in goats.

    Science.gov (United States)

    González, Félix H D; Hernández, Fuensanta; Madrid, Josefa; Martínez-Subiela, Silvia; Tvarijonaviciute, Asta; Cerón, José J; Tecles, Fernando

    2011-01-01

    The present work aimed to study the behavior of acute phase proteins (haptoglobin, serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin) in fasting-induced pregnancy toxemia in goats and their relationship with classical indicators of this disorder such as beta-hydroxybutyrate and nonesterified fatty acids in the blood and decreased urine pH and ketonuria. Twelve adult Murciano-Granadina goats at the final stage of gestation were used in this experiment. Pregnancy toxemia was induced in 6 goats by fasting for 72 hr. The other 6 animals were used as control group. Ketonuria was present in 4 out of 5 fasting animals at 24 hr and in all fasting animals at 48 hr of fasting. Serum nonesterified fatty acids were significantly increased at 24, 48, and 72 hr of fasting. Beta-hydroxybutyrate and haptoglobin achieved significantly increased concentrations at 48 hr and 72 hr, respectively, remaining increased during the entire study. Serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin were not affected by fasting. In conclusion, acute phase proteins (including haptoglobin) seemed not to have an advantage over traditional markers in diagnosis of fasting-induced pregnancy toxemia in goats. PMID:21217028

  20. 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.

  1. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia.

    Directory of Open Access Journals (Sweden)

    Andrea Bonetto

    Full Text Available BACKGROUND: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6, and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26-carcinoma cachexia. METHODOLOGY/PRINCIPAL FINDINGS: Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. CONCLUSIONS/SIGNIFICANCE: These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and

  2. 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...

  3. 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

    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...

  4. The negative acute phase response of serum transthyretin following Streptococcus suis infection in the pig

    DEFF Research Database (Denmark)

    Campbell, F.M.; Waterston, M.; Andresen, Lars Ole;

    2005-01-01

    Transthyretin (TTR) is a serum protein which is a negative acute phase reactant in humans and levels of TTR are routinely measured as an indicator of health status. Such tests have yet to be established for the pig. In order to measure serum TTR in the pig during an acute phase response an assay...... in three different age groups from 10 to 25 weeks. Following Streptococcus suis type 2 infection transthyretin showed a negative acute phase response with serum concentrations reaching a significantly lower level at two days following infection....

  5. 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

  6. Early post parturient changes in milk acute phase proteins.

    Science.gov (United States)

    Thomas, Funmilola C; Waterston, Mary; Hastie, Peter; Haining, Hayley; Eckersall, P David

    2016-08-01

    The periparturient period is one of the most critical periods in the productive life of a dairy cow, and is the period when dairy cows are most susceptible to developing new intramammary infections (IMI) leading to mastitis. Acute phase proteins (APP) such as haptoglobin (Hp), mammary associated serum amyloid A3 (M-SAA3) and C-reactive protein (CRP) have been detected in milk during mastitis but their presence in colostrum and milk in the immediate postpartum period has had limited investigation. The hypothesis was tested that APP are a constituent of colostrum and milk during this period. Enzyme linked immunosorbent assays (ELISAs) were used to determine each APP's concentration in colostrum and milk collected daily from the first to tenth day following calving in 22 Holstein-Friesian dairy cows. Haptoglobin was assessed in individual quarters and composite milk samples while M-SAA3 and CRP concentration were determined in composite milk samples. Change in Hp in relation to the high abundance proteins during the transition from colostrum to milk were evaluated by 1 and 2 dimension electrophoresis and western blot. In 80% of the cows all APPs were detected in colostrum on the first day following parturition at moderately high levels but gradually decreased to minimal values in the milk by the 6th day after calving. The remaining cows (20%) showed different patterns in the daily milk APP concentrations and when an elevated level is detected could reflect the presence of IMI. Demonstration that APP are present in colostrum and milk following parturition but fall to low levels within 4 days means that elevated APP after this time could be biomarkers of post parturient mastitis allowing early intervention to reduce disease on dairy farms. PMID:27600971

  7. 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.

  8. 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.

  9. 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.

  10. The analysis of the acute phase response during the course of Trypanosoma carassii infection in the goldfish (Carassius auratus L.).

    Science.gov (United States)

    Kovacevic, Nikolina; Hagen, Mariel O; Xie, Jiasong; Belosevic, Miodrag

    2015-11-01

    The expression of genes encoding the acute phase proteins (APP) during the course of Trypanasoma carassii infection in the goldfish was determined using quantitative PCR. Significant changes in the mRNA levels of ceruloplasmin (Cp), C-reactive protein (CRP), transferrin (Tf), hemopexin (Hx) and serum amyloid A (SAA) were observed in the kidney, liver and spleen at various days post infection (dpi). Of the five acute phase protein genes examined, CRP and SAA exhibited the highest expression in the tissues during the acute infection. Cp and Tf were up-regulated throughout the acute course of infection in the liver. During the chronic phase of the infection, APP expression in the liver was similar to that in the non-infected control fish. At 7 dpi, Cp, Tf and Hx were down-regulated in the spleen, and Cp and Tf kidney, but their mRNA levels gradually returned to those of control non-infected fish. In contrast, during the chronic phase of the infection, there was an up-regulation of Cp, Hx and Tf in the spleen, and Tf and SAA in the kidney. The goldfish CRP was cloned and functionally characterized. CRP was differentially expressed in normal goldfish immune cells, with highest expression in monocytes and lowest expression in mature macrophages. A recombinant goldfish CRP (rgfCRP) was generated using prokaryotic expression. rgfCRP enhanced complement-mediated killing of trypanosomes in vitro, and the lysis increased after addition of immune serum. rgfCRP did not affect the production of reactive oxygen and nitrogen intermediates by monocytes and macrophages, respectively. PMID:26116443

  11. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile

    OpenAIRE

    WANG Min; Yan, Jingjun; He, Xingxing; Zhong, Qiang; Zhan, Chengye; Li, Shusheng

    2016-01-01

    Background Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways asso...

  12. 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.

  13. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette;

    2009-01-01

    infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented......The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  14. The role of HOX genes in normal hematopoiesis and acute leukemia

    OpenAIRE

    Alharbi, RA; Pettengell, R; Pandha, HS; Morgan, R

    2013-01-01

    The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overex...

  15. Synthesis of acute phase proteins in rats with cirrhosis exposed to lipopolysaccharide

    OpenAIRE

    Nielsen, Susanne Schouw; Grøfte, Thorbjørn; Tygstrup, Niels; Vilstrup, Hendrik

    2006-01-01

    Background In patients with cirrhosis, infection is frequent and a leading cause of death. This is secondary to various immunologic abnormalities in both the innate and the adaptive immune system. However, it remains unclear whether cirrhosis affects the inflammatory systemic component of the innate immunity, 'the acute phase response', mostly effectuated by the liver itself. We hypothesized that rats with cirrhosis raise a reduced acute phase response induced by lipopolysaccharide (LPS). Res...

  16. Acute phase proteins: a review of their function, behaviour and measurement in chickens

    OpenAIRE

    O'Reilly, E.L.; Eckersall, P.D.

    2014-01-01

    This review brings together and consolidates the large amount of research on acute phase proteins (APPs) that has been undertaken in chickens. Acute phase proteins are secreted from the liver as a result of inflammation or infection that can be measured in plasma. They have been well-characterised in other farm animal species and have been measured in a wide variety of poultry research areas. The acceleration in chicken APP research is in response to increased interest in ways the immune resp...

  17. Mechanisms of the Hepatic Acute-Phase Response during Bacterial Pneumonia▿

    OpenAIRE

    Quinton, Lee J.; Jones, Matthew R.; Robson, Bryanne E.; Mizgerd, Joseph P.

    2009-01-01

    The acute-phase response is characterized by increased circulating levels of acute-phase proteins (APPs) generated by the liver. During bacterial pneumonia, APPs correlate with the severity of disease, serve as biomarkers, and are functionally significant. The kinetics and regulatory mechanisms of APP induction in the liver during lung infection have yet to be defined. Here we show that APP mRNA transcription is induced in the livers of mice whose lungs are infected with either Escherichia co...

  18. Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response

    OpenAIRE

    Ahyi, Ayele-Nati N.; Quinton, Lee J.; Jones, Matthew R.; Ferrari, Joseph D.; Pepper-Cunningham, Zachary A.; Mella, Juan R.; Remick, Daniel G.; Mizgerd, Joseph P.

    2013-01-01

    The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-κB, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including t...

  19. RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level.

    Directory of Open Access Journals (Sweden)

    Kenian Chen

    Full Text Available Spinal cord injury (SCI is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology. The top enriched functional categories include "inflammation response," "neurological disease," "cell death and survival" and "nervous system development." The top enriched pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc. Furthermore, we developed a systems-based analysis framework in order to identify key determinants in the global gene networks of the acute and sub-acute phases. Some candidate genes that we identified have been shown to play important roles in SCI, which demonstrates the validity of our approach. There are also many genes whose functions in SCI have not been well studied and can be further investigated by future experiments. We have also incorporated pharmacogenomic information into our analyses. Among the genes identified, the ones with existing drug information can be readily tested in SCI animal models. Therefore, in this study we have described an example of how global gene profiling can be translated to identifying genes of interest for functional tests in the future and generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform identification and the estimation of expression levels, thus providing useful information for increasing the specificity of drug design and reducing potential side effect. In summary, these results provide a valuable reference data resource for a better understanding of the SCI process in the acute and sub-acute phases.

  20. 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

  1. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

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

    DEFF Research Database (Denmark)

    Strømmen, Anna M; 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...

  3. 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

    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...

  4. 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

  5. Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection

    OpenAIRE

    Ayala, Pedro; Meneses, Manuel; Olmos, Pablo; Montalva, Rebeca; Droguett, Karla; Ríos, Mariana; Borzone, Gisella

    2016-01-01

    Background Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality. Although aspiration-induced local lung inflammation has been studied in animal models, little is known about extrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric fluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins having antiprotease activity. Met...

  6. 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

  7. Altered Gene Expression Pattern in Peripheral Blood Mononuclear Cells in Patients with Acute Myocardial Infarction

    OpenAIRE

    Marek Kiliszek; Beata Burzynska; Marcin Michalak; Monika Gora; Aleksandra Winkler; Agata Maciejak; Agata Leszczynska; Ewa Gajda; Janusz Kochanowski; Grzegorz Opolski

    2012-01-01

    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: Twe...

  8. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene 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 the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, tho...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases...... 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...

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

    OpenAIRE

    JM Real; MM. Marques; GMGT Spilborghs; EM Negri; MM Matzuk; RP Moura; AA Camargo; Deheinzelin, D; AAM Dias

    2008-01-01

    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 obje...

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

    OpenAIRE

    Intskirveli Nino; Shakarishvili1 Roman; Sanikidze Tamar; Beridze Maia; Bornstein Natan M

    2011-01-01

    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 Ind...

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

    OpenAIRE

    Lang Tamara L; Waterston Mary M; Bence Laura; Lawson Fraser P; Eckersall Peter D; Donachie William; Fontaine Michael C

    2007-01-01

    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 CL...

  13. 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.

  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...... response peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP), and major acute phase protein (MAP) responded with large increases in serum levels, preceding the development of specific antibodies by 4-5 days. Serum amyloid A protein (SAA) was also strongly induced. The increase......, kinetics of induction and normalization were different between these proteins. It is concluded that experimental Ap-infection by the aerosol route induces a typical acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major acute phase reactants. These findings indicate the possibility...

  15. 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.

  16. 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....../kg, consecutively) of Escherichia coli LPS with 3-wk intervals. All 3 LPS doses resulted in a rapid increase in serum concentrations of haptoglobin and serum amyloid A (SAA) and a decrease in serum concentrations of albumin in all 8 cows. Serum concentrations of acute phase proteins (APP) remained altered...... and haptoglobin concentrations in either of the challenges, which suggests that the synthesis of haptoglobin and SAA are regulated in different ways. In conclusion, cattle are highly susceptible to LPS, as very low doses of LPS elicited acute phase albumin, SAA, and haptoglobin responses. Concentrations of APP...

  17. 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.

  18. 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.

  19. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    Science.gov (United States)

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

  20. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    Science.gov (United States)

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  1. [The prognostic value of content of acute phase proteins in development of puerperal endometritis].

    Science.gov (United States)

    Anokhova, L I; Pateiuk, A V; Zagorodnaia, E D

    2012-07-01

    The analysis was made of the content of proteins in inflammation acute phase in 100 healthy puerperants and 157 women with endometritis after cesarean section. The established disproportion in protein concentration during acute phase in healthy puerperants is considered as a female organism adaptive reaction to pregnancy and delivery. As for patients with endometritis, this condition testifies the compensatory resources stress, development of pathophysiological reactions of organism and intensity of local damages. The concentration of C-reactive protein and prealbumin in patients with endometritis provides an opportunity to forecast the degree of severity of course of disease. PMID:22988794

  2. Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice

    OpenAIRE

    Pini, Maria; Rhodes, Davina H.; Fantuzzi, Giamila

    2011-01-01

    Obesity is associated with chronic inflammation and elevated levels of IL-6. The role of IL-6 in induction of acute-phase proteins and modulation of haematological responses has been demonstrated in models of inflammation and aging, but not in obesity. We hypothesized that IL-6 is necessary to regulate the acute-phase response and hematological changes associated with diet-induced obesity (DIO) in mice. Feeding a 60% kcal/fat diet for 13 weeks to C57BL6 WT male mice induced a significant incr...

  3. 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

  4. 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

  5. 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.

  6. Metabolic changes in concussed American football players during the acute and chronic post-injury phases

    Directory of Open Access Journals (Sweden)

    Ellemberg Dave

    2011-08-01

    Full Text Available Abstract Background Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations. Methods The present study investigated the effects of sports concussion on brain metabolism using 1H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years and education (mean: 16 years within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI. Results Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1 cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase. Conclusions These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.

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

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    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.

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

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    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.

  9. Heterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes

    OpenAIRE

    Mar, Daniel; Gharib, Sina A; Zager, Richard A.; Johnson, Ali; Denisenko, Oleg; Bomsztyk, Karol

    2015-01-01

    Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). Since epigenetic processes control gene expression in a cell- and environment-defined manner, understanding the epigenetic pathways that regulate genes altered by AKI may open vital new insights into the complexities of disease pathogenesis and identify possible therapeutic targets. Here we used matrix chromatin immunoprecipitation and integrative analysis to study twenty key permissive and repressive epigenetic hi...

  10. Early weaning alters the acute phase immune response to an endotoxin challenge in beef cattle

    Science.gov (United States)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  11. Early weaning alters the acute phase response to an endotoxin challenge in beef calves

    Science.gov (United States)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  12. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis.

    Science.gov (United States)

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  13. 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

  14. 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/...

  15. 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

  16. 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...

  17. 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...

  18. C-reactive protein and the acute phase reaction in geriatric patients.

    Science.gov (United States)

    Bertsch, Thomas; Triebel, Jakob; Bollheimer, Cornelius; Christ, Michael; Sieber, Cornel; Fassbender, Klaus; Heppner, Hans Jürgen

    2015-10-01

    The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations. PMID:26334841

  19. 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

  20. Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants

    NARCIS (Netherlands)

    Wieringa, F.T.; Dijkhuizen, M.A.; West, C.E.; Northrop-Clewes, C.A.; Muhilal,

    2002-01-01

    Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), α1-antichymotrypsin (ACT) and α1-acid glycoprotein (AGP), and indicato

  1. The acute-phase response and serum amyloid a inhibit the inflammatory response to Acinetobacter baumannii pneumonia

    NARCIS (Netherlands)

    R. Renckens; J.J.T.H. Roelofs; S. Knapp; A.F. de Vos; S. Florquin; T. van der Poll

    2006-01-01

    Background. Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and post-surgical patients display a profound acute-phase protein response and are susceptible to pneumonia. Methods. To study the way in which the acute-phase response induced by sterile tissue injury influe

  2. 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.

  3. 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-

  4. 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

  5. Early phase combined therapeutic management of acute ischaemic stroke.

    Science.gov (United States)

    Bassi, P; Lattuada, P; Tonietti, S

    2005-05-01

    An adequate treatment of ischaemic stroke in the early phase (28-48 h) is the most important factor for a better outcome. Thrombolysis with rTPA (within 3 h) and oral ASA 300 mg/days are the first therapeutic misures. Continuous monitoring of cardiological and haemodinamic parameters allows early detection of cardiac disturbances. Treatment of hypertension, low haematic oxigenation, hyperglicaemia, seizures and hypertermia is basic to improve outcome. Pharmacological therapy is only one of the components of effective multidisciplinary integrated management of ischaemic stroke; we remind also the precocity of rehabilitation procedures and an accurate psychological assessment. PMID:15883687

  6. 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

  7. 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.

  8. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 ± 139 ng/mL for the stable phase of IPF, 645 ± 247 ng/mL for early phase of acute exacerbation of IPF, 534 ± 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 ± 42 for chronic obstructive pulmonary disease, and 150 ± 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM-1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers. PMID:26543791

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

    OpenAIRE

    C. Cannizzo; Gianesella, M.; Giudice, E.; Messina, V; G. Piccione; M. Morgante

    2012-01-01

    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 subj...

  10. 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. PMID:24518690

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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

  13. 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....

  14. 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....

  15. 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

  16. ACUTE PHASE REACTANCTS IN PERICARDIAL FLUID ARE INDICATORS OF CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Yılmaz Mehmet Ali

    2012-12-01

    Full Text Available Inflammation in formation of atherosclerosis, and acute phase reactants in the site of inflammation have major functions. Thus, do the acute phase reactants constitute the biggest risk factor for coronary artery disease? 55 patients are included in the study. Patients with coronary artery bypass surgery are included in Group I (38 patients and patients with valve operation are included in Group II (17 patients. CABG patients are further divided into two sub-groups as on-pump and off-pump. In both groups, homocystein, high sensitivity C reactive protein, ceruloplasmin, lipoprotein A and serum amyloid A protein levels are analyzed from blood and pericardial fluid. In patients with coronary artery disease, the measured high specific C- reactive protein levels from blood and pericardial fluid are found to be significantly high compared to patients with valve operation.Homocystein levels of pericardial fluids of patients with CABG are found to be higher than patients with valve operation and it is confirmed that the situation is correlated with blood homocystein levels. Although there are lots studies expressing the relation between coronary artery disease and lipoprotein A, ceruloplasmin and serum amyloid A protein levels; no significant difference for those parameters was obtained in our study. We determined that other phase reactants are higher in patients with coronary artery disease, in accordance with the literature. We aimed to state that acute phase reactants not only increase as a result of disease, but their levels are also elevated beforehand, as an indicator of the disease.

  17. 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.

  18. Chromosomal translocation involving the beta T cell receptor gene in acute leukemia

    OpenAIRE

    1988-01-01

    DNA spanning a t(7;19) chromosomal translocation breakpoint was isolated from the human T cell line SUP-T7 established from an acute lymphoblastic leukemia. Nucleotide sequence analysis showed that the point of crossover on chromosome 7 occurred immediately adjacent to joining segment J beta 1.1 within the TCR-beta gene, suggesting that this translocation resulted from an error in TCR gene rearrangement. On chromosome 19, the translocation occurred within a previously uncharacterized transcri...

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

    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...... 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...... 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...

  4. 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.

  5. Evaluation of the Effects of Honey on Acute-Phase Deep Burn Wounds

    OpenAIRE

    Nakajima, Yukari; Mukai, Kanae; Nasruddin; kOMATSU, Emi; Iuchi, Terumi; Kitayama, Yukie; Sugama, Junko; Nakatani, Toshio

    2013-01-01

    This study aimed to clarify the effects of honey on acute-phase deep burn wounds. Two deep burn wounds were created on mice which were divided into four groups: no treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound sizes were calculated as expanded wound areas and sampled 30 minutes and 1–4 days after wounding for histological observation. The wound sections were subjected to hematoxylin and eosin and immunohistological staining to detect necrotic cells, apoptotic ...

  6. ACUTE PHASE PROTEINS, LIPID PROFILE AND PROINFLAMMATORY CYTOKINES IN HEALTHY AND BRONCHOPNEUMONIC WATER BUFFALO CALVES

    OpenAIRE

    El-Bahr, Sabry M.; Wael M. EL-Deeb

    2013-01-01

    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 pr...

  7. Markers of acute-phase response in the treatment of pulmonary tuberculosis

    OpenAIRE

    Cristiane Martins; Antônio Carlos de Castro Gama; Daniela Valcarenghi; Anna Paula de Borba Batschauer

    2014-01-01

    Introduction:Tuberculosis promotes an acute phase response with an increase of blood reactants, such as C-reactive protein (CRP), among others, which are associated with increased erythrocyte sedimentation rate (ESR).Objective:Evaluate the ESR and the CRP as markers for diagnosis and monitoring cases of pulmonary tuberculosis.Method:Research on patients with clinical, laboratory, and imaging diagnosis of pulmonary tuberculosis, from Itajaí-SC; in which CRP and ESR were analyzed in three diffe...

  8. Acute Phase Response of Rabbit to HgCl2 and CdCl2

    Institute of Scientific and Technical Information of China (English)

    NinaGHOSH; SHELLEYBHATTACHARYA

    1993-01-01

    A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein,C-reactive protein in the serum and significant reduction in the serum titres of albumin and acetylcholinesterase.The phospholipid profile is postively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit.Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change.

  9. An Explanation for the Paradoxical Induction and Suppression of an Acute Phase Response by Ethanol

    OpenAIRE

    Pruett, Brandon S.; Pruett, Stephen B

    2006-01-01

    Binge ethanol (EtOH) consumption suppresses inflammatory responses and resistance to infection, but paradoxically it is associated with increased levels of acute phase proteins (which are indicators of inflammation) and an increased risk of inflammation mediated pathologies such as cardiovascular disease and cirrhosis of the liver. The latter effect may be mediated by increased translocation of bacteria leading to activation of toll-like receptor 4 (TLR4). In this study, the dose-response and...

  10. Ethionine-dependent inhibition of acute-phase plasma protein synthesis in the rat.

    OpenAIRE

    Kasperczyk, H.; Koj, A

    1983-01-01

    Ethionine administered intraperitoneally to rats suffering from turpentine-induced inflammation preferentially reduced incorporation of 14C-leucine into fibrinogen, haptoglobin and other acute-phase proteins. The inhibitory effect was observed both in vivo and in liver slices obtained from ethionine-treated donors, while addition of ethionine to liver slices in vitro led to general reduction of synthesis of all liver and plasma proteins, including albumin. For comparison, the effects of galac...

  11. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    OpenAIRE

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    International audience The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we st...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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...... of cognitive deficits) had decreased significantly, with further normalisation 1-year after treatment initiation. In conclusion, patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis but comprehensive neuropsychological testing revealed no cognitive impairment....... Reports of cognitive dysfunction may reflect affective and somatic manifestations of thyrotoxicosis and in most patients these symptoms disappear after treatment of Graves' thyrotoxicosis....

  16. Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

    OpenAIRE

    Mario Pirisi; Carlo Fabris; Maria Piera Panozzo; Giorgio Soardo; Pierluigi Toniutto; Ettore Bartou

    1993-01-01

    Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P

  17. 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. PMID:25685944

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

    International Nuclear Information System (INIS)

    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. (paper)

  19. Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol.

    Science.gov (United States)

    Osechkina, N S; Ivanov, M B; Nazarov, G V; Batotsyrenova, E G; Lapina, N V; Babkin, A V; Berdinskikh, I S; Melekhova, A S; Voitsekhovich, K O; Lisitskii, D S; Kashina, T V

    2016-02-01

    Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3. PMID:26902358

  20. 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.

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

    OpenAIRE

    Yan-Fang Tao; Dong Wu; Li Pang; Wen-Li Zhao; Jun Lu; Na Wang; Jian Wang; Xing Feng; Yan-Hong Li; Jian Ni; Jian Pan

    2012-01-01

    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 so...

  2. Dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of Legionnaires' disease.

    Directory of Open Access Journals (Sweden)

    Cornelis P C de Jager

    Full Text Available STUDY OBJECTIVE: Absolute lymphocytopenia is recognised as an important hallmark of the immune response to severe infection and observed in patients with Legionnaires' disease. To explore the immune response, we studied the dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of LD. METHODS AND RESULTS: EDTA-anticoagulated blood was obtained from eight patients on the day the diagnosis was made through detection of L. pneumophila serogroup 1 antigen in urine. A second blood sample was obtained in the subacute phase. Multiparametric flow cytometry was used to calculate lymphocyte counts and values for B-cells, T-cells, NK cells, CD4+ and CD8+ T-cells. Expression of activation markers was analysed. The values obtained in the subacute phase were compared with an age and gender matched control group. Absolute lymphocyte count (×10⁹/l, median and range significantly increased from 0.8 (0.4-1.6 in the acute phase to 1.4 (0.8-3.4 in the subacute phase. B-cell count showed no significant change, while T-cell count (×10⁶/l, median and range significantly increased in the subacute phase (495 (182-1024 versus 979 (507-2708, p = 0.012 as a result of significant increases in both CD4+ and CD8+ T-cell counts (374 (146-629 versus 763 (400-1507, p = 0.012 and 119 (29-328 versus 224 (107-862, p = 0.012. In the subacute phase of LD, significant increases were observed in absolute counts of activated CD4+ T-cells, naïve CD4+ T-cells and memory CD4+ T-cells. In the CD8+ T-cell compartment, activated CD8+ T-cells, naïve CD8+ T-cell and memory CD8+ T-cells were significantly increased (p<0.05. CONCLUSION: The acute phase of LD is characterized by absolute lymphocytopenia, which recovers in the subacute phase with an increase in absolute T-cells and re-emergence of activated CD4+ and CD8+ T cells. These observations are in line with the suggested role for T-cell activation in the immune response to LD.

  3. 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

  4. 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...

  5. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    OpenAIRE

    Andrea Bonetto; Tufan Aydogdu; Noelia Kunzevitzky; Guttridge, Denis C.; Sawsan Khuri; Koniaris, Leonidas G.; Teresa A Zimmers

    2011-01-01

    BACKGROUND: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the i...

  6. Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice.

    OpenAIRE

    Vogels, M.T.E.; L. Cantoni; Carelli, M.; Sironi, M; Ghezzi, P; van der Meer, J. W M

    1993-01-01

    Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge of granulocytopenic and normal mice enhances nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins, liver proteins which possess several detoxifying effects, we investigated the role of these proteins in the IL-1-induced protection. Inhibition of liver protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1-induced synthesis of acute-phase...

  7. 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.

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

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    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

  9. 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.

  10. 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.

  11. 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.

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

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    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.

  13. 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.

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

    International Nuclear Information System (INIS)

    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

  15. 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

  16. Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

    Energy Technology Data Exchange (ETDEWEB)

    Trout, D.R.

    1987-01-01

    Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed for parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia.

    OpenAIRE

    Felix, C A; Nau, M M; Takahashi, T.; Mitsudomi, T.; Chiba, I.; Poplack, D G; Reaman, G H; Cole, D E; Letterio, J J; Whang-Peng, J

    1992-01-01

    The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. ...

  3. Risk stratification of intermediate-risk acute myeloid leukemia: Integrative analysis of a multitude of gene mutation and gene expression markers

    NARCIS (Netherlands)

    V. Rockova (Veronika); S. Abbas (Saman); B.J. Wouters (Bas); C.A.J. Erpelinck (Claudia); H.B. Beverloo (Berna); H.R. Delwel (Ruud); W.L.J. van Putten (Wim); B. Löwenberg (Bob); P.J.M. Valk (Peter)

    2011-01-01

    textabstractNumerous molecular markers have been recently discovered as potential prognostic factors in acute myeloid leukemia (AML). It has become of critical importance to thoroughly evaluate their interrelationships and relative prognostic importance. Gene expression profiling was conducted in a

  4. ACUTE PHASE PROTEINS AS A MARKER OF RESPIRATORY INFLAMMATION IN PRZEWALSKI'S HORSE (EQUUS FERUS PRZEWALSKII).

    Science.gov (United States)

    Sander, Samantha J; Joyner, Priscilla H; Cray, Carolyn; Rotstein, David S; Aitken-Palmer, Copper

    2016-06-01

    Acute phase proteins are sensitive markers of inflammation, which are highly conserved across taxa. Although the utility of these proteins are becoming well defined in human and domestic animal medical fields, their role in nondomestic species remains unclear. In this communication, a 20-yr-old Przewalski's horse was presented for unresolving aspiration pneumonia, which cultured a unique Actinomyces-like bacteria. Despite waxing and waning clinical signs and minimal changes on baseline hematologic analysis, protein electrophoresis, serum amyloid A, and surfactant protein D serum concentrations showed changes that more accurately reflected the clinical severity of this case. PMID:27468045

  5. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis

    OpenAIRE

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other inte...

  6. 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...

  7. Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR and with cytomegalovirus (CMV infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37%  = AR and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.

  8. 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.

  9. DOSE-RELATED GENE EXPRESSION CHANGES IN FOREBRAIN FOLLOWING ACUTE, LOW-LEVEL CHLORPYRIFOS EXPOSURE IN NEONATAL RATS

    OpenAIRE

    Ray, Anamika; Liu, Jing; Ayoubi, Patricia; Pope, Carey

    2010-01-01

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 hr following acute CPF exposure in seven day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following e...

  10. Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase.

    Science.gov (United States)

    Tappe, Dennis; Pérez-Girón, José Vicente; Zammarchi, Lorenzo; Rissland, Jürgen; Ferreira, Davis F; Jaenisch, Thomas; Gómez-Medina, Sergio; Günther, Stephan; Bartoloni, Alessandro; Muñoz-Fontela, César; Schmidt-Chanasit, Jonas

    2016-06-01

    Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase.

  11. Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase.

    Science.gov (United States)

    Tappe, Dennis; Pérez-Girón, José Vicente; Zammarchi, Lorenzo; Rissland, Jürgen; Ferreira, Davis F; Jaenisch, Thomas; Gómez-Medina, Sergio; Günther, Stephan; Bartoloni, Alessandro; Muñoz-Fontela, César; Schmidt-Chanasit, Jonas

    2016-06-01

    Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase. PMID:26702627

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. Acute phase proteins as biomarkers of urinary tract infection in dairy cows: diagnostic and prognostic accuracy.

    Science.gov (United States)

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-02-01

    The aims of this study were to investigate the level of acute phase proteins in dairy cows with urinary tract infection (UTI) and to evaluate their diagnostic and prognostic value. Eighty-four lactating cows with clinical and laboratory evidence of UTI and 15 healthy controls were included in this study. Serum samples were evaluated for the levels of Haptoglobin (Hp), serum amyloid A (SAA), fibrinogen (Fb), α1-Acid glycoprotein (AGP), total protein, and globulin. The diagnostic and prognostic performance of each parameter was evaluated by estimating the area under receiver operating characteristics curve (AUROC). Escherichia coli and Corynebacterium spp. were the primary bacteria associated with UTI. The levels of serum Hp, SAA, Fb, AGP, total protein, and globulin were significantly higher in UTI cows. Successfully treated cows (n = 51) had lower levels of Hp, SAA, AGP, total protein, and globulin than non-responsive cows. Overall, Hp, SAA, Fb, and AGP showed comparable diagnostic accuracy (AUROC ranged from 0.93 to 0.98). Both Hp and SAA showed high accuracy in predicting treatment response (AUROC > 0.95), whereas Fb level was of no prognostic value (AUROC = 0.48). From this study, acute phase proteins levels can be used as markers for UTI in cows and higher levels of Hp, SAA and AGP are related to poor treatment response. PMID:27348889

  15. 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.

  16. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    Science.gov (United States)

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment. PMID:26472721

  17. Tail biting induces a strong acute phase response and tail-end inflammation in finishing pigs.

    Science.gov (United States)

    Heinonen, Mari; Orro, Toomas; Kokkonen, Teija; Munsterhjelm, Camilla; Peltoniemi, Olli; Valros, Anna

    2010-06-01

    The extent of inflammation associated with tail biting in finishing pigs was evaluated. Tail histopathology, carcass condemnation and the concentration of three acute phase proteins (APPs), C-reactive protein (CRP), serum amyloid-A (SAA) and haptoglobin (Hp), were examined in 12 tail-bitten and 13 control pigs. The median concentrations of APPs were higher (Ppigs (CRP 65.7mg/L, 28.4-180.4; SAA 6.2mg/L, 6.2-21.4; Hp 1.2g/L, 0.9-1.5). There was a tendency for APP concentrations to rise with the histopathological score but the differences were only statistically significant between some of the scores. Five (42%) bitten cases and one (8%) control pig had partial carcass condemnations owing to abscesses (P=0.07). The results show that tail biting induces an inflammatory response in the tail end leading to an acute phase response and formation of carcass abscesses. PMID:19398209

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. THE CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE (mdr1) EXPRESSION IN ACUTE LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    Dong Zuoren; Cong Bin; Luo Jianmin; Xu Wenxin; Wang Fuxu; Guo Xiaonan; Zhang Xuejun; Yao Ergu; Xu Shirong; Ren Jinhai

    1998-01-01

    Objective: To study the clinical significance of multidrug resistance gene expression in acute leukemia.Methods: The relationships between drug resistance of leukemia cells and prognosis, multidrug resistance gene (mdr1) were examined in 85 patients with acute leukemia and 20 normal controls by reverse transcriptase polymerase chain reaction (RT-PCR). Results: The mdr1 positive rate in untreated group was 44.7 %. The complete remission (CR) rate of mdr1 positive patients (23.9 %) was significantly lower than that of mdr1 negative patients(88.5 %) (P<0.005). The mdr1 expression level in relapsedrefractory group was higher than that of CR group. A gradually increased mdr1 mRNA level in CR patients indicated early relapse. Conclusion: The mdr1 positive rate in normal control and long-term survival patients was very low. The mdr1 expression was correlated with French-American-British Cooperative Group (FAB)classification. The mdr1 expression level was correlated with chemotherapeutic effect and prognosis. It is an unfavorable prognostic factor for patients with acute leukemia.

  2. 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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. 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...... 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....

  7. Relation between raised concentrations of fucose, sialic acid, and acute phase proteins in serum from patients with cancer: choosing suitable serum glycoprotein markers.

    OpenAIRE

    Turner, G A; Skillen, A W; Buamah, P; Guthrie, D.; Welsh, J; Harrison, J; Kowalski, A.

    1985-01-01

    Serum concentrations of fucose, sialic acid, and eight acute phase proteins were measured in single specimens from patients with cancer in order to determine whether the raised concentrations of protein bound sugars commonly found in cancer correlate with increased concentrations of the acute phase proteins. Strong positive correlations were found only with alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobins. Changes in protein bound sugars and acute phase proteins were also exam...

  8. 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.

  9. Heterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes.

    Science.gov (United States)

    Mar, Daniel; Gharib, Sina A; Zager, Richard A; Johnson, Ali; Denisenko, Oleg; Bomsztyk, Karol

    2015-10-01

    Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). As epigenetic processes control gene expression in a cell- and environment-defined manner, understanding the epigenetic pathways that regulate genes altered by AKI may open vital new insights into the complexities of disease pathogenesis and identify possible therapeutic targets. Here we used matrix chromatin immunoprecipitation and integrative analysis to study 20 key permissive and repressive epigenetic histone marks at transcriptionally induced Tnf, Ngal, Kim-1, and Icam-1 genes in mouse models of AKI; unilateral renal ischemia/reperfusion, lipopolysaccharide (LPS), and their synergistically injurious combination. Results revealed unexpected heterogeneity of transcriptional and epigenetic responses. Tnf and Ngal were transcriptionally upregulated in response to both treatments individually, and to combination treatment. Kim-1 was induced by ischemia/reperfusion and Icam-1 by LPS only. Epigenetic alterations at these genes exhibited distinct time-dependent changes that shared some similarities, such as reduction in repressive histone modifications, and also had major ischemia/reperfusion versus endotoxin differences. Thus, diversity of changes at AKI genes in response to different insults indicates involvement of several epigenetic pathways. This could be exploited pharmacologically through rational-drug design to alter the course and improve clinical outcomes of this syndrome. PMID:26061546

  10. Revealing the acute asthma ignorome: characterization and validation of uninvestigated gene networks.

    Science.gov (United States)

    Riba, Michela; Garcia Manteiga, Jose Manuel; Bošnjak, Berislav; Cittaro, Davide; Mikolka, Pavol; Le, Connie; Epstein, Michelle M; Stupka, Elia

    2016-01-01

    Systems biology provides opportunities to fully understand the genes and pathways in disease pathogenesis. We used literature knowledge and unbiased multiple data meta-analysis paradigms to analyze microarray datasets across different mouse strains and acute allergic asthma models. Our combined gene-driven and pathway-driven strategies generated a stringent signature list totaling 933 genes with 41% (440) asthma-annotated genes and 59% (493) ignorome genes, not previously associated with asthma. Within the list, we identified inflammation, circadian rhythm, lung-specific insult response, stem cell proliferation domains, hubs, peripheral genes, and super-connectors that link the biological domains (Il6, Il1ß, Cd4, Cd44, Stat1, Traf6, Rela, Cadm1, Nr3c1, Prkcd, Vwf, Erbb2). In conclusion, this novel bioinformatics approach will be a powerful strategy for clinical and across species data analysis that allows for the validation of experimental models and might lead to the discovery of novel mechanistic insights in asthma. PMID:27097888

  11. Reduced natriuretic response to acute sodium loading in COMT Gene deleted mice

    Directory of Open Access Journals (Sweden)

    Uhlén Staffan

    2002-08-01

    Full Text Available Abstract Background The intrarenal natriuretic hormone dopamine (DA is metabolised by catechol-O-methyltransferase (COMT and monoamine oxidase (MAO. Inhibition of COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The present study in anaesthetized homozygous and heterozygous COMT gene deleted mice attempted to further elucidate the importance of COMT in renal DA and sodium handling. After acute intravenous isotonic sodium loading, renal function was followed. Results COMT activity in heterozygous mice was about half of that in wild type mice and was zero in the homozygous mice. MAO activity did not differ between the genotypes. Urinary sodium excretion increased 10-fold after sodium loading in wild type mice. In heterozygous and homozygous mice, the natriuretic effects of sodium loading were only 29 % and 39 %, respectively, of that in wild type mice. Arterial pressure and glomerular filtration rate did not differ between genotypes. Baseline norepinephrine and DA excretions in urine were elevated in the homozygous, but not in heterozygous, COMT gene deleted mice. Urinary DA excretion increased after isotonic sodium loading in the wild type mice but not in the COMT gene deleted mice. Conclusions Mice with reduced or absent COMT activity have altered metabolism of catecholamines and are unable to increase renal DA activity and produce normal natriuresis in response to acute sodium loading. The results support the hypothesis that COMT has an important role in the DA-mediated regulation of renal sodium excretion.

  12. Analysis of genes that influence sheep follicular development by different nutrition levels during the luteal phase using expression profiling.

    Science.gov (United States)

    Luo, F; Jia, R; Ying, S; Wang, Z; Wang, F

    2016-06-01

    Nutrition is an important factor that regulates reproductive performance of sheep and affects follicle development. However, the correlation between nutrition and follicle development is poorly understood at the molecular level. To study its possible molecular mechanisms, we performed expression profiling of granulosa cells isolated from sheep that were fed different levels of nutrition levels during the luteal phase. To do this, ewes received a maintenance diet (M), and their estrus was synchronized by intravaginal progestogen sponges for 12 days. Ewes were randomly divided into the short-term dietary-restricted group (R; 0.5 × M) and the nutrient-supplemented group (S; 1.5 × M). RNA samples were extracted from granulosa cells. Transcriptome libraries from each group were constructed by Illumina sequencing. Among 18 468 detected genes, 170 genes were significantly differentially expressed, of which 140 genes were upregulated and 30 genes were downregulated in group S relative to group R. These genes could be candidates regulating follicular development in sheep. Gene Ontology, KEGG and clustering analyses were performed. Genes related to oocyte meiosis, such as ADCY7, were upregulated. We identified two important groups of related genes that were upregulated with improved nutrition: one group comprising the genes PTGS2, UCP2 and steroidogenic acute regulatory protein and the other group comprising interleukin-1A and interleukin-1B. The genes within each group showed similar expression patterns. Additionally, all five genes are involved in the reproduction process. Quantitative real-time PCR was performed to validate the results of expression profiling. These data in our study are an abundant genomic resource to expand the understanding of the molecular and cellular events underlying follicle development. PMID:26970339

  13. The Effect of Oxandrolone on the Endocrinologic, Inflammatory, and Hypermetabolic Responses During the Acute Phase Postburn

    Science.gov (United States)

    Jeschke, Marc G.; Finnerty, Celeste C.; Suman, Oscar E.; Kulp, Gabriela; Mlcak, Ronald P.; Herndon, David N.

    2007-01-01

    Objective and Summary Background Data: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT. PMID:17717439

  14. Procalcitonin and other acute phase reactants in patients with chronic obstructive pulmonary disease exacerbation

    Directory of Open Access Journals (Sweden)

    Cemil Civelek

    2011-06-01

    Full Text Available The aim of this study was to investigate the correlation between procalcitonin and other acute phase reactants, and also analyze their relationship with clinical situation in chronic obstructive pulmonary disease (COPD acute exacerbations.Materials and methods: The study was made with 122 acute COPD exacerbated patients, who were admitted to emergency service. Patients with below 0.25 ng/ml PCT value included Group 1, and the patients with PCT values ≥ 0.25 ng/ml Group 2. Serum procalcitonin levels, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP values and white blood cell (WBC counts were measured. Also, patients hospitalization time and mortality rates were recorded and compared with PCT.Results: Patients were divided in 3 groups according to their clinical diagnosis; Pneumonia (n=27, Mycoplasma-Chlamydia pneumonia (n=11 and the patients with only COPD exacerbation(n=84. Mean PCT values according to the groups were 9.47 ± 8.1 ng/ml, 0.41 ± 0.2 ng/ml, and 0.21 ± 0.05 ng/ml respectively. The relationship between PCT with CRP and white blood cell has been found between significiant (p=0.001, p=0.005 respectively, whereas the relationship between PCT and ESR was nonsignificant (p=0.55. Procalcitonin and CRP had a positive correlation with the hospitalization time (p=0.034, p=0.022 respectively. The mean ± standard error of PCT for the patients who died was 28.3 ± 27.5 ng/ml, and the difference between patients who died or were discharged was statistically significant (p= 0.012.Conclusion: PCT can be a useful indicator for morbidity and prognosis in COPD patients.

  15. Acute phase IL-10 plasma concentration associates with the high risk sources of cardiogenic stroke.

    Directory of Open Access Journals (Sweden)

    Otso Arponen

    Full Text Available Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10 associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.A total of 141 patients (97 males; mean age 61±11 years with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE. IL-10 was measured on admission to the hospital and on a three month follow-up visit.Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01. In patients with no risk sources (n = 104, the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3-16.3 ng/L, with one risk source (n = 26 3.7±5.5 ng/L (0.3-23.6 ng/L, with two risk sources (n = 10 7.0±10.0 ng/L (1.29-34.8 ng/L and with three risk sources (n = 1 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. A robust quantitative solid phase immunoassay for the acute phase protein C-reactive protein (CRP) based on cytidine 5 '-diphosphocholine coupled dendrimers

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Pedersen, H. G.; Jensen, A. L.;

    2009-01-01

    C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP...

  6. 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.

  7. Effects of NANOG gene down-regulation on the apoptosis of T-cell acute lymphoblastic leukemia cells

    Institute of Scientific and Technical Information of China (English)

    曹江

    2014-01-01

    Objective To explore gene expression of NANOG in T-cell acute lymphoblastic leukemia(T-ALL)cell lines and the effects of NANOG gene down-regulation on apoptosis of leukemia cells.Methods Real-time PCR(RtPCR)and Western blot were used to detect the expression level of NANOG gene and protein in MOLT-4,CCRF-HSB2 and Jurkat cells.

  8. 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.

  9. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

    International Nuclear Information System (INIS)

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  10. 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.

  11. 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...... effective and rapid. The titer of the HSVlac stocks was determined on NIH3T3 cells. Eighty-three percent of the beta-gal forming units successfully transduced beta-gal after microapplication to slice cultures. beta-Gal expression was detected as rapidly as 4 h after transduction into cultures of fibroblasts...... 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....

  12. 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

  13. 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

  14. Regulatory and Ethical Issues for Phase I In Utero Gene Transfer Studies

    OpenAIRE

    Strong, Carson

    2011-01-01

    Clinical gene transfer research has involved adult and child subjects, and it is expected that gene transfer in fetal subjects will occur in the future. Some genetic diseases have serious adverse effects on the fetus before birth, and there is hope that prenatal gene therapy could prevent such disease progression. Research in animal models of prenatal gene transfer is actively being pursued. The prospect of human phase I in utero gene transfer studies raises important regulatory and ethical i...

  15. Influence of disease process and duration on acute phase proteins in serum and peritoneal fluid of horses with colic

    DEFF Research Database (Denmark)

    Pihl, Tina; Scheepers, E.; Sanz, M.;

    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...

  16. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    Science.gov (United States)

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  17. 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...

  18. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

    NARCIS (Netherlands)

    Sander, L.E.; Sackett, S.D.; Dierssen, U.; Beraza, N.; Linke, R.; Müller, M.R.; Blander, J.M.; Tacke, F.; Trautwein, C.

    2010-01-01

    Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Us

  19. 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

  20. 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 pdevelopment 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.

  1. Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Amaia Vilas-Zornoza

    Full Text Available Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL. Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48. We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-2'-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001 and mortality (p<0.001 rate being an independent prognostic factor for disease-free survival (DFS (p = 0.006 and overall survival (OS (p = 0.005 in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.

  2. 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

  3. Detection of CEBPA double mutants in acute myeloid leukemia using a custom gene expression array.

    Science.gov (United States)

    van Vliet, Martin H; Burgmer, Pia; de Quartel, Linda; Brand, Jaap P L; de Best, Leonie C M; Viëtor, Henk; Löwenberg, Bob; Valk, Peter J M; van Beers, Erik H

    2013-05-01

    Double (bi-allelic) mutations in the gene encoding the CCAAT/enhancer-binding protein-alpha (CEBPA) transcription factor have a favorable prognostic impact in acute myeloid leukemia (AML). Double mutations in CEBPA can be detected using various techniques, but it is a notoriously difficult gene to sequence due to its high GC-content. Here we developed a two-step gene expression classifier for accurate and standardized detection of CEBPA double mutations. The key feature of the two-step classifier is that it explicitly removes cases with low CEBPA expression, thereby excluding CEBPA hypermethylated cases that have similar gene expression profiles as a CEBPA double mutant, which would result in false-positive predictions. In the second step, we have developed a 55 gene signature to identity the true CEBPA double-mutation cases. This two-step classifier was tested on a cohort of 505 unselected AML cases, including 26 CEBPA double mutants, 12 CEBPA single mutants, and seven CEBPA promoter hypermethylated cases, on which its performance was estimated by a double-loop cross-validation protocol. The two-step classifier achieves a sensitivity of 96.2% (95% confidence interval [CI] 81.1 to 99.3) and specificity of 100.0% (95% CI 99.2 to 100.0). There are no false-positive detections. This two-step CEBPA double-mutation classifier has been incorporated on a microarray platform that can simultaneously detect other relevant molecular biomarkers, which allows for a standardized comprehensive diagnostic assay. In conclusion, gene expression profiling provides a reliable method for CEBPA double-mutation detection in patients with AML for clinical use. PMID:23485358

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

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    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.

  5. Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms in Egyptian patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Aml S Nasr

    2015-01-01

    Full Text Available BACKGROUND: The super family of glutathione S-transferases (GSTs is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment. AIM OF WORK: To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment. PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML, as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and conventional polymerase chain reaction (PCR, respectively. RESULTS: For GSTP1 313 A → G (GSTP1 Ile105Val polymorphism, It was found that the wild genotype (AA was significantly higher among control subjects (P value = 0.0277, while the frequency of heteromutant genotype (AG and mutant G allele (AG + GG was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively. For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005. CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

  6. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  8. Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

    International Nuclear Information System (INIS)

    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. 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. 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. 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 response. Therapy-induced gene expression reflects the complex

  9. 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.

  10. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia.

    Science.gov (United States)

    Konopleva, Marina; Thall, Peter F; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R; Melink, Teresa J; Gutheil, John C; Andreeff, Michael; Estey, Elihu H; Kantarjian, Hagop

    2015-07-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m(2). The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m(2) or 4 g/m(2) had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Exposure of Lactating Dairy Cows to Acute Pre-Ovulatory Heat Stress Affects Granulosa Cell-Specific Gene Expression Profiles in Dominant Follicles.

    Science.gov (United States)

    Vanselow, Jens; Vernunft, Andreas; Koczan, Dirk; Spitschak, Marion; Kuhla, Björn

    2016-01-01

    High environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28°C) or thermoneutral conditions (15°C) with pair-feeding for four days. After hormonal heat induction growth of the respective dominant follicles was monitored by ultrasonography for two days, then an ovulatory GnRH dose was given and follicular steroid hormones and granulosa cell-specific gene expression profiles were determined 23 hrs thereafter. The data showed that the pre-ovulatory growth of dominant follicles and the estradiol, but not the progesterone concentrations tended to be slightly affected. mRNA microarray and hierarchical cluster analysis revealed distinct expression profiles in granulosa cells derived from heat stressed compared to pair-fed animals. Among the 255 affected genes heatstress-, stress- or apoptosis associated genes were not present. But instead, we found up-regulation of genes essentially involved in G-protein coupled signaling pathways, extracellular matrix composition, and several members of the solute carrier family as well as up-regulation of FST encoding follistatin. In summary, the data of the present study show that acute pre-ovulatory heat stress can specifically alter gene expression profiles in granulosa cells, however without inducing stress related genes and pathways and suggestively can impair follicular growth due to affecting the activin-inhibin-follistatin system. PMID:27532452

  13. 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.

  14. 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.

  15. Strain-specific differences in Neisseria gonorrhoeae associated with the phase variable gene repertoire

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    Saunders Nigel J

    2005-04-01

    Full Text Available Abstract Background There are several differences associated with the behaviour of the four main experimental Neisseria gonorrhoeae strains, FA1090, FA19, MS11, and F62. Although there is data concerning the gene complements of these strains, the reasons for the behavioural differences are currently unknown. Phase variation is a mechanism that occurs commonly within the Neisseria spp. and leads to switching of genes ON and OFF. This mechanism may provide a means for strains to express different combinations of genes, and differences in the strain-specific repertoire of phase variable genes may underlie the strain differences. Results By genome comparison of the four publicly available neisserial genomes a revised list of 64 genes was created that have the potential to be phase variable in N. gonorrhoeae, excluding the opa and pilC genes. Amplification and sequencing of the repeat-containing regions of these genes allowed determination of the presence of the potentially unstable repeats and the ON/OFF expression state of these genes. 35 of the 64 genes show differences in the composition or length of the repeats, of which 28 are likely to be associated with phase variation. Two genes were expressed differentially between strains causing disseminated infection and uncomplicated gonorrhoea. Further study of one of these in a range of clinical isolates showed this association to be due to sample size and is not maintained in a larger sample. Conclusion The results provide us with more evidence as to which genes identified through comparative genomics are indeed phase variable. The study indicates that there are large differences between these four N. gonorrhoeae strains in terms of gene expression during in vitro growth. It does not, however, identify any clear patterns by which previously reported behavioural differences can be correlated with the phase variable gene repertoire.

  16. 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

  17. 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

    2016-01-01

    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. PMID:27323085

  18. 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. PMID:8521602

  19. Evaluation of the Effects of Honey on Acute-Phase Deep Burn Wounds

    Directory of Open Access Journals (Sweden)

    Yukari Nakajima

    2013-01-01

    Full Text Available This study aimed to clarify the effects of honey on acute-phase deep burn wounds. Two deep burn wounds were created on mice which were divided into four groups: no treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound sizes were calculated as expanded wound areas and sampled 30 minutes and 1–4 days after wounding for histological observation. The wound sections were subjected to hematoxylin and eosin and immunohistological staining to detect necrotic cells, apoptotic cells, neutrophils, and macrophages. The no treatment group formed a scar. The redness around the wound edges in the silver sulfadiazine group was the most intense. All groups exhibited increased wound areas after wounding. The proportions of necrotic cells and the numbers of neutrophils in the manuka and acacia honey groups were lower than those in the no treatment and silver sulfadiazine groups until day 3; however, there were no significant differences between all groups on day 4. These results show that honey treatment on deep burn wounds cannot prevent wound progression. Moreover, comparing our observations with those of Jackson, there are some differences between humans and animals in this regard, and the zone of hyperemia and its surrounding area fall into necrosis, which contributes to burn wound progression.

  20. 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

  1. The autophagy associated gene, ULK1, promotes tolerance to chronic and acute hypoxia

    International Nuclear Information System (INIS)

    Background and purpose: Tumor hypoxia is associated with therapy resistance and malignancy. Previously we demonstrated that activation of autophagy and the unfolded protein response (UPR) promote hypoxia tolerance. Here we explored the importance of ULK1 in hypoxia tolerance, autophagy induction and its prognostic value for recurrence after treatment. Material and methods: Hypoxic regulation of ULK1 mRNA and protein was assessed in vitro and in primary human head and neck squamous cell carcinoma (HNSCC) xenografts. Its importance in autophagy induction, mitochondrial homeostasis and tolerance to chronic and acute hypoxia was evaluated in ULK1 knockdown cells. The prognostic value of ULK1 mRNA expression was assessed in 82 HNSCC patients. Results: ULK1 enrichment was observed in hypoxic tumor regions. High enrichment was associated with a high hypoxic fraction. In line with these findings, high ULK1 expression in HNSCC patients appeared associated with poor local control. Exposure of cells to hypoxia induced ULK1 mRNA in a UPR and HIF1α dependent manner. ULK1 knockdown decreased autophagy activation, increased mitochondrial mass and ROS exposure and sensitized cells to acute and chronic hypoxia. Conclusions: We demonstrate that ULK1 is a hypoxia regulated gene and is associated with hypoxia tolerance and a worse clinical outcome

  2. 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.

  3. Polymorphisms of CYP1A1*4 and GST as Susceptibility and Prognostic Genes for Acute Myeloid Leukemia

    OpenAIRE

    Sheriff, E.; Ahmed, A.; Heba, M

    2010-01-01

    Associations between polymorphisms for genes encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the study is to investigate the influence of cytochromes P450 (CYP1A1*4) and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to acute myeloid leukemia (AML) as well as their prognostic role for the treatment outcome in AML patients. Material and Methods: This study incl...

  4. GENE CONTROL OF PROGRAMMED MYOCARDIAL CELL DEATH IN ACUTE MYOCARDIAL INFARCTION, ITS DYNAMICS IN TREATMENT AND PROSPECTS FOR THERAPY

    OpenAIRE

    Belousov S.S.; Kuznetsov А.N.; Eroshevskaya N.V.; Novikov D.V.; Novikov V.V.

    2014-01-01

    The aim of the investigation was to study gene regulation of apoptosis in acute myocardial infarction and during the treatment, and assess the effect of levocarnitine (Elcar) on gene expression of Fas-dependent apoptosis. Materials and Methods. We examined 28 patients with Q-myocardial infarction included in the study within the first 24 h of the disease and followed up during the treatment course. The patients were divided into two groups: group 1 (n=10) consisted of patients with standa...

  5. Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors.

    Science.gov (United States)

    Gunerka, Pawel; Dymek, Barbara; Stanczak, Aleksandra; Bujak, Anna; Grygielewicz, Paulina; Turowski, Pawel; Dzwonek, Karolina; Lamparska-Przybysz, Monika; Pietrucha, Tadeusz; Wieczorek, Maciej

    2015-10-15

    Janus kinase (JAK) inhibitors are a promising treatment strategy in several hematological malignancies and autoimmune diseases. A number of inhibitors are in clinical development, and two have already reached the market. Unfortunately, all of them are burdened with different toxicity profiles. To check if the JAK inhibitors of different selectivity evoke different responses on JAK2-dependent and independent cells, we have used three acute myeloid leukemia cell lines with confirmed JAK2 mutation status. We have found that JAK inhibitors exert distinct effect on the expression of BCLXL, CCND1 and c-MYC genes, regulated by JAK pathway, in JAK2 wild type cells in comparison to JAK2 V617F-positive cell lines. Moreover, cell cycle analysis showed that inhibitors alter the cycle by arresting cells in different phases. Our results suggest that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. PMID:26300391

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

    Directory of Open Access Journals (Sweden)

    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.

  7. The rat acute-phase protein {alpha}{sub 2}-macroglobulin plays a central role in amifostine-mediated radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Mirjana, Mihailovic; Goran, Poznanovic; Nevena, Grdovic; Melita, Vidakovic; Svetlana, Dinic; Ilijana, Grigorov; Desanka, Bogojevic, E-mail: mista@ibiss.bg.ac.r [Department of Molecular Biology, Institute for Biological Research ' Sinisa Stankovic' , University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade (Serbia)

    2010-09-15

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD{sub 50/30}) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in {alpha}{sub 2}M in the circulation led us to hypothesise that {alpha}{sub 2}M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of {alpha}{sub 2}M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the {alpha}{sub 2}M gene in amifostine-pretreated animals. In both {alpha}{sub 2}M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of {alpha}{sub 2}M plays a central role in amifostine-provided radioprotection.

  8. Dexamethasone acutely down-regulates genes involved in steroidogenesis in stallion testes.

    Science.gov (United States)

    Ing, Nancy H; Forrest, David W; Riggs, Penny K; Loux, Shavahn; Love, Charlie C; Brinsko, Steven P; Varner, Dickson D; Welsh, Thomas H

    2014-09-01

    In rodents, livestock and primate species, a single dose of the synthetic glucocorticoid dexamethasone acutely lowers testosterone biosynthesis. To determine the mechanism of decreased testosterone biosynthesis, stallions were treated with 0.1mg/kg dexamethasone 12h prior to castration. Dexamethasone decreased serum concentrations of testosterone by 60% compared to saline-treated control stallions. Transcriptome analyses (microarrays, northern blots and quantitative PCR) of testes discovered that dexamethasone treatment decreased concentrations of glucocorticoid receptor alpha (NR3C1), alpha actinin 4 (ACTN4), luteinizing hormone receptor (LHCGR), squalene epoxidase (SQLE), 24-dehydrocholesterol reductase (DHCR24), glutathione S-transferase A3 (GSTA3) and aromatase (CYP19A1) mRNAs. Dexamethasone increased concentrations of NFkB inhibitor A (NFKBIA) mRNA in testes. SQLE, DHCR24 and GSTA3 mRNAs were predominantly expressed by Leydig cells. In man and livestock, the GSTA3 protein provides a major 3-ketosteroid isomerase activity: conversion of Δ(5)-androstenedione to Δ(4)-androstenedione, the immediate precursor of testosterone. Consistent with the decrease in GSTA3 mRNA, dexamethasone decreased the 3-ketosteroid isomerase activity in testicular extracts. In conclusion, dexamethasone acutely decreased the expression of genes involved in hormone signaling (NR3C1, ACTN4 and LHCGR), cholesterol synthesis (SQLE and DHCR24) and steroidogenesis (GSTA3 and CYP19A1) along with testosterone production. This is the first report of dexamethasone down-regulating expression of the GSTA3 gene and a very late step in testosterone biosynthesis. Elucidation of the molecular mechanisms involved may lead to new approaches to modulate androgen regulation of the physiology of humans and livestock in health and disease. PMID:25010478

  9. Time for the new approach in management of early phase of severe acute pancreatitis?

    Institute of Scientific and Technical Information of China (English)

    Darko Zdravkovic; Dragoljub Bilanovi(c); Tomislav Randjelovic; Borislav Toskovic

    2010-01-01

    @@ To the Editor: We read with a great interest the recent article by Dr. Yang et al, in which they summarized the surgical treatment of patients with fulminant acute pancreatitis in their hospital. This is a very interesting paper on treating severe acute panceratitis (SAP) since the management of acute pancreatitis has been controversial over the past decades, varying between a conservative medical approach on the one hand and aggressive surgical approach on the other.

  10. 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 e...

  11. 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…

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    Science.gov (United States)

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  17. Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

    Directory of Open Access Journals (Sweden)

    Mario Pirisi

    1993-01-01

    Full Text Available Phospholipase A2 (PLA2 modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P<0.001; Bonferroni’s test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (p<0.0 I and mild chronic liver disease (p<0.0S J. Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reacti ve protein, alkaline phosphatase and al-fetoprotein as predictor variables was significant (multiple R= 0.7056, multiple R2= 0.4978, F= 15.36, P= <0.0001. The standardized regression coefficients found to be significant were those of Creactive protein, blood urea nitrogen and al-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2 activity increases parallel to disease severity and accompanies the expression of proteins of the acute phase response that. like PLA2 activity, increase in serum while liver synthesis declines.

  18. 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.

  19. 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...... 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...

  20. 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

    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...... 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...

  1. Acute phase and transport protein synthesis in simulated infection in undernourished men using uniformly labelled Spirulina Platensis

    International Nuclear Information System (INIS)

    Although it has been known for many years that injury and infection lead to body nitrogen loss, the reason has remained obscure. In this paper, we develop the argument that the processes that are activated during infection demand the provision of specific amino acids which have to be supplied from body protein. In particular, we show that the positive acute phase proteins are very rich in the aromatic amino acids and the exaggerated use of these amino acids (phenylalanine, tryptophan and tyrosine) in acute phase protein synthesis lead to an endogenous ''amino acid imbalance'' which restricts the use of other amino acids for tissue protein synthesis. Minimally invasive protocols, involving the administration of 15N and 13C-labelled amino acids for studying whole body nitrogen turnover, amino acid oxidation and plasma protein synthesis are described. (author). 22 refs, 3 tabs

  2. 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 Aamand;

    2016-01-01

    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...... supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin...

  3. 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.

  4. 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.

  5. 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.

  6. HIV Replication Is Not Controlled by CD8+ T Cells during the Acute Phase of the Infection in Humanized Mice

    OpenAIRE

    Petit, Nicolas Y.; Lambert-Niclot, Sidonie; Marcelin, Anne-Geneviève; Garcia, Sylvie; Marodon, Gilles

    2015-01-01

    International audience 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 i...

  7. Early Diagnosis of Congenital Trypanosoma cruzi Infection, Using Shed Acute Phase Antigen, in Ushuaia, Tierra del Fuego, Argentina

    OpenAIRE

    Mallimaci, María Cristina; Sosa-Estani, Sergio; Russomando, Graciela; Sanchez, Zunilda; Sijvarger, Carina; Alvarez, Isabel Marcela; Barrionuevo, Lola; Lopez, Carlos; Segura, Elsa Leonor

    2010-01-01

    Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital i...

  8. The serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis

    OpenAIRE

    Johnsen, Erik; Fathian, Farivar; Kroken, Rune A.; Vidar M Steen; Jørgensen, Hugo A; Gjestad, Rolf; Løberg, Else-Marie

    2016-01-01

    Background Inflammatory processes have been implicated in the etiology of schizophrenia and related psychoses, in which cognitive deficits represent core symptoms. The aim of the present study was to investigate possible associations between the level of the inflammation marker C-reactive protein (CRP) and cognitive performance in patients through the acute phase of psychosis. Methods A total of 124 patients were assessed at admittance to hospital and 62 patients were retested at discharge or...

  9. The influence of supplemental chromium and vaccines on the acute phase response of newly arrived feeder calves.

    OpenAIRE

    Wright, A. J.; Mallard, B A; Mowat, D N

    1995-01-01

    The acute phase response as indicated by serum haptoglobin and total haemolytic complement activity (CH50) was measured in 72 cross-bred steer calves purchased at sales in Ontario. During the 28 day (d) trial, 18 steers were randomly assigned to each of the following groups: 1) control; 2) vaccinated (Infectious Bovine Rhinotracheitis, Parainfluenza-3, Bovine Viral Diarrhea, Bovine Respiratory Synctial Virus vaccine plus Pasteurella haemolytica vaccine); 3) supplemental chelated Cr (0.14 mg/k...

  10. Evaluation of Sialic Acid and Acute Phase Proteins (Haptoglobin and Serum Amyloid A) in Clinical and Subclinical Bovine Mastitis

    OpenAIRE

    S. Nazifi*, M. Haghkhah1, Z. Asadi, M. Ansari-Lari2, M. R. Tabandeh3, Z. Esmailnezhad and M. Aghamiri

    2011-01-01

    The present study was conducted to evaluate the concentrations of sialic acids (total, lipid bound and protein bound) and their correlation with acute phase proteins (haptoglobin and serum amyloid A) in clinical and subclinical mastitis of cattle. Thirty subclinical mastitic cows with positive California mastitis test (CMT) test and no clinical signs of mastitis, 10 clinical mastitic cows and 10 healthy cows with negative CMT test and normal somatic cell count were selected. Milk and blood sa...

  11. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.;

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...... than the initial values, were observed at 2 to 4 days. It is concluded that ApoA-I is a negative acute-phase protein in pigs....

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

    OpenAIRE

    Williams Andrew; Møller Peter; Boisen Anne; Bornholdt Jette; Folkmann Janne K; Halappanavar Sabina; Saber Anne T; Yauk Carole; Vogel Ulla; Loft Steffen; Wallin Håkan

    2009-01-01

    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)-induc...

  13. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

    OpenAIRE

    Sander, L.E.; Sackett, S.D.; Dierssen, U.; Beraza, N.; Linke, R.; Müller, M.R.; Blander, J.M.; Tacke, F; Trautwein, C

    2010-01-01

    Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increase...

  14. 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.

  15. 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.

  16. 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

  17. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    Science.gov (United States)

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  18. 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.

  19. 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.

  20. 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.

  1. Synthesis of acute-phase alpha 2-macroglobulin during inflammation and pregnancy.

    Science.gov (United States)

    Panrucker, D E; Lorscheider, F L

    1983-01-01

    A recent investigation of acute-phase alpha 2-macroglobulin (AP alpha 2M) concentration in the rat during pregnancy demonstrated a bimodal distribution, for which we suggested a maternal source of AP alpha 2M in early gestation and a fetal source in late gestation. This interpretation was supported by the findings of the present study, which employed organ culture techniques, incorporation of [35S]methionine, immunoprecipitation of radioactivity, and fluorography to measure synthesis of AP alpha 2M in specific fetal, adult, and maternal tissues. Preliminary results indicated that in adult male rats treated with croton oil (compared with nontreated males), AP alpha 2M was synthesized in kidney, spleen, thymus, and lymphocytes by 48 hr post induction, but synthesis in the liver was not evident. In the pregnant rat from 12 to 16 days (compared with nonpregnant females), synthesis of AP alpha 2M was high in metrial gland, moderate in spleen, thymus and lymphocytes, and absent in liver; at 21 days, synthesis of AP alpha 2M in these four maternal tissues had declined. Fetal synthesis of AP alpha 2M in yolk sac (12 to 16 days) and in liver (15 to 16 days) was significantly elevated, and at 21 days fetal liver still displayed marked synthesis. These data are consistent with the interpretation that an early maternal source of AP alpha 2M synthesis is the metrial gland and that in the fetus both yolk sac and liver are major sources of AP alpha 2M, the latter tissue continuing synthesis into late gestation. Lymphopoietic and lymph-containing tissues appear to be major sites of AP alpha 2M synthesis during inflammation and pregnancy. PMID:6200027

  2. 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.

  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. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    Science.gov (United States)

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P x time interaction (P

  5. Acute intermittent porphyria: A single-base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide

    Energy Technology Data Exchange (ETDEWEB)

    Lee, G.L.; Astrin, K.H.; Desnick, R.J. [Mount Sinai School of Medicine, New York, NY (United States)

    1995-08-28

    Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, since the life-threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solid-phase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. 29 refs., 2 figs.

  6. 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)

    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

    2012-01-01

    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. PMID:22001391

  7. 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

    2012-01-01

    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.

  8. Nucleophosmin (NPM1) gene variants in Egyptian patients with acute myeloid leukemia

    International Nuclear Information System (INIS)

    To the editor Kassem et al. [1] described a novel mutational deletion [del 1178 (A)] in the 30 untranslated region of NPM1 gene detected in a heterozygous form in seven de novo acute myeloid leukemia (AML) patients of their study population. The described nucleotide deletion is an NPM1 gene polymorphism recorded in db SNP database (rs34351976; g28027: Genbank accession number NG016018.1) (http://www.ncbi.nlm.nih.gov/projects/SNP/) and was described previously by Do hner et al. [2] and Chou et al. [3]. This variant accounted for 60-70% of AML patients with normal karyotype [2]. The putative deletion was also identified in healthy volunteers and persisted at complete remission and also at relapse of AML patients [3]. This deletion had no effect on the predicted amino acid sequence and is not in linkage disequilibrium with any previously identified NPM1 mutations [2,3]. Analysis of RNA folding at the region surrounding the rs34351976 in the presence or absence of the deletion using Mfold analysis software (http://www.mfold.rna.albany.edu) revealed no RNA folding change that may alter RNA splicing and subsequently gene expression. Furthermore, splicing motifs analysis using Human Splicing Finder software version 2.4.1 showed that the presence of the deletion does not abolish any recognition site of exonic or intronic enhancers or silencer motifs. In general, it seems that the impact of NMP1 polymorphisms on the molecular pathogenesis of AML is not clear yet and needs further investigation. Kassem et al. [1] describes the molecular aspect of de novo AML in the Egyptian population. The previously known NPM1 mutations mentioned in their study are less frequent compared to the figures recorded worldwide. Moreover, the authors wondered whether the NPM1 variants identified in their patients may confer a better outcome of AML. According to the previously mentioned data, one can speculate that the presence of NPM1 gene polymorphism (rs34351976) should not be mistaken as being

  9. 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.

  10. Myeloperoxidase and serum amyloid A contribute to impaired in vivo reverse cholesterol transport during the acute phase response but not group IIA secretory phospholipase A(2)

    NARCIS (Netherlands)

    Annema, Wijtske; Nijstad, Niels; Toelle, Markus; de Boer, Jan Freark; Buijs, Ruben V. C.; Heeringa, Peter; van der Giet, Markus; Tietge, Uwe J. F.

    2010-01-01

    Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse cholesterol transport (RCT). The present study aimed to test the impact of acute inflammation as well as selected acute phase proteins on RCT wit

  11. 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.

  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. 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.

  14. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury

    OpenAIRE

    Borlak, Jürgen; Chatterji, Bijon; Londhe, Kishor B; Watkins, Paul B

    2013-01-01

    Background Acetaminophen (APAP) is a commonly used analgesic. However, its use is associated with drug-induced liver injury (DILI). It is a prominent cause of acute liver failure, with APAP hepatotoxicity far exceeding other causes of acute liver failure in the United States. In order to improve its safe use this study aimed to identify individuals at risk for DILI prior to drug treatment by searching for non-genetic serum markers in healthy subjects susceptible to APAP-induced liver injury (...

  15. 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...

  16. Arterial stiffness during acute and recovery phases of children with rheumatic fever.

    Science.gov (United States)

    Ibrahim, N N I N; Jaafar, H; Rasool, A H; Wong, A R

    2016-02-01

    Acute rheumatic fever (ARF) is associated with systemic inflammation and arterial stiffness during the acute stage. It has not been reported if arterial stiffness remains after recovery. The aim of this study was to determine the arterial stiffness during acute stage and 6 months after recovery from ARF. Arterial stiffness was assessed by carotid femoral pulse wave velocity (PWV) in 23 ARF patients during the acute stage of ARF and 6 months later. Simultaneously, erythrocyte sedimentation rate (ESR) and other anthropometric measurements were taken during both stages. There was a significant reduction in PWV; 6.5 (6.0, 7.45) m/s to 5.9 (5.38, 6.48) m/s, p=0.003 6 months after the acute stage of ARF. Similarly, ESR was also significantly reduced from 92.0 (37.5, 110.50) mm/hr to 7.0 (5.0, 16.0) mm/hr, p=0.001. In conclusion, arterial stiffness improved 6 months after the acute stage with routine aspirin treatment; this correlates well with the reduction in systemic inflammation. PMID:27130739

  17. 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....

  18. Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease

    OpenAIRE

    Cunningham, Colm; Wilcockson, David C.; Boche, Delphine; Perry, V. Hugh

    2005-01-01

    Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory...

  19. Role of mga in growth phase regulation of virulence genes of the group A streptococcus.

    OpenAIRE

    McIver, K S; J. R. Scott

    1997-01-01

    To determine whether growth phase affects the expression of mga and other virulence-associated genes in the group A streptococcus (GAS), total RNA was isolated from the serotype M6 GAS strain JRS4 at different phases of growth and transcript levels were quantitated by hybridization with radiolabeled DNA probes. Expression of mga (which encodes a multiple gene regulator) and the Mga-regulated genes emm (which encodes M protein) and scpA (which encodes a complement C5a peptidase) was found to b...

  20. 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.

  1. 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.

  2. 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. PMID:27370532

  3. Cytotoxic T lymphocyte antigen 4 gene polymorphism associated with ST-segment elevation acute myocardial infarction

    International Nuclear Information System (INIS)

    Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a particularly important molecule in down-regulating T-cell expansion and cytokine production. The purpose of the present study was to determine the frequency distribution of an A/G single nucleotide polymorphism at position 49 in exon 1 of the CTLA-4 gene, which may be a functional related-genetic risk marker for the development of ST-segment elevation (ST-se) acute myocardial infarction (AMI). A total of 503 consecutive patients, consisting of 250 ST-se AMI patients undergoing primary coronary angioplasty (group 1), 203 angina pectoris patients undergoing elective coronary angioplasty (group 2) and 50 patients with chest pain and normal coronary angiographic findings (group 3), were enrolled in the present study. The frequency of the G/G genotype was significantly higher in group 1 (53.2%) than in groups 2 (33.0%) and 3 (36.0%) (p=0.0005). In group 1, patients with a G/G genotype had significantly higher levels of high-sensitivity C-reactive protein and white blood cell counts, and much higher incidences of multi-vessel disease, greater lesion lengths, advanced congestive heart failure (≥class 3) and 30-day mortality, than patients with G/A or A/A genotypes (p values<0.05 in all cases). Multivariate analysis of the enrolled baseline variables (age, gender, diabetes mellitus, smoking, hypertension and hypercholesterolemia) and the genotypes (G/G, A/G and A/A) demonstrated that G/G genotype is the only independent predictor of development of AMI (p<0.0001). The G/G genotype polymorphism of the CTLA-4 gene is associated with increased risk of AMI. (author)

  4. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    Science.gov (United States)

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  5. 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.

  6. 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.

  7. 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. PMID:26837258

  8. 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

    2014-07-01

    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.

  9. Gene Control of Programmed Myocardial Cell Death in Acute Myocardial Infarction, Its Dynamics in Treatment and Prospects for Therapy

    Directory of Open Access Journals (Sweden)

    Belousov S.S.

    2014-12-01

    Full Text Available The aim of the investigation was to study gene regulation of apoptosis in acute myocardial infarction and during the treatment, and assess the effect of levocarnitine (Elcar on gene expression of Fas-dependent apoptosis. Materials and Methods. We examined 28 patients with Q-myocardial infarction included in the study within the first 24 h of the disease and followed up during the treatment course. The patients were divided into two groups: group 1 (n=10 consisted of patients with standard treatment (anti-aggregants, ACE inhibitors, and anti-anginal agents — if indicated; group 2 (n=18 — those patients, who received standard treatment with Elcar (levocarnitine intravenously, in 5% glucose normal saline, at the dose of 3.0 g a day for three days. For the following 7 days the patients were given Elcar per os, 4.0 g a day. A control group (group 3 (n=18 consisted of healthy subjects. All patients underwent general examination, ECG, echocardiography, genetic research: we determined mRNA gene expression of mFas and sFas using real-time polymerase chain reaction thrice in each patient — on admission, after 1 week treatment, and at the end of the second week of treatment. Results. Apoptotic gene expression in patients with Q-infarction was found to be increased compared to the norm, the increase lasting for a longer period than acute myocardial infarction itself. This fact enables to explain the cause of prolonged apoptosis by the sustained activity of apoptosis-inducing genes. The use of levocarnitine promotes the normalization of an increased level of gene expression, and has a cardioprotective effect that is important in acute myocardial infarction treatment.

  10. 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.

  11. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

    Directory of Open Access Journals (Sweden)

    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

  12. ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection

    DEFF Research Database (Denmark)

    Pineiro, M.; Andres, M.; Iturralde, M.;

    2004-01-01

    We have isolated from calf serum a protein with an apparent M, of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4,....... Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle......., and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease...

  13. Molecular characterization of two immunity-related acute-phase proteins: Haptoglobin and serum amyloid A from black rockfish (Sebastes schlegeli).

    Science.gov (United States)

    Jayasinghe, J D H E; Elvitigala, Don Anushka Sandaruwan; Whang, Ilson; Nam, Bo-Hye; Lee, Jehee

    2015-08-01

    Haptoglobin (Hp) and serum amyloid A (SAA) are two vital proteins involved in inflammatory reactions and are classified as acute-phase proteins. They are released from hepatocytes under inflammatory conditions to protect healthy cells from being damaged by pathogens or from self-destructive mechanisms. In this study, a previously constructed black rockfish (Sebastes schlegeli) cDNA library was used to identify the full-length cDNA sequences of Hp and SAA homologs (RfHp and RfSAA, respectively) and characterize them at the molecular level. As expected, in silico analysis of these homologs showed the typical domain architectures of their known counterparts. Open reading frames of RfHp and RfSAA consisted of 942-bp and 313-bp DNA sequences, respectively. The derived polypeptide sequence of RfHp was composed of 313 amino acids (aa) with a predicted molecular weight of 34 kD, whereas RfSAA had a 121-amino acid sequence with a molecular weight of 13 kD. Phylogenetic analysis as well as pairwise sequence alignment results showed that RfHp was more closely related to Oreochromis mossambicus from an evolutionary perspective while RfSAA was closely related to the Epinephelus coioides ortholog. Although both genes were expressed ubiquitously in the tissues analyzed, they were particularly expressed in liver tissue, suggesting their origin in hepatocytes. Quantitative real-time PCR analysis indicated that both RfHp and RfSAA were significantly up-regulated by both bacterial and viral stimulation in liver tissue, affirming their putative importance in the acute phase of first-line host immune defenses. PMID:25989623

  14. Regulatory and ethical issues for phase I in utero gene transfer studies.

    Science.gov (United States)

    Strong, Carson

    2011-11-01

    Clinical gene transfer research has involved adult and child subjects, and it is expected that gene transfer in fetal subjects will occur in the future. Some genetic diseases have serious adverse effects on the fetus before birth, and there is hope that prenatal gene therapy could prevent such disease progression. Research in animal models of prenatal gene transfer is actively being pursued. The prospect of human phase I in utero gene transfer studies raises important regulatory and ethical issues. One issue not previously addressed arises in applying U.S. research regulations to such studies. Specifically, current regulations state that research involving greater than minimal risk to the fetus and no prospect of direct benefit to the fetus or pregnant woman is not permitted. Phase I studies will involve interventions such as needle insertions through the uterus, which carry risks to the fetus including spontaneous abortion and preterm birth. It is possible that these risks will be regarded as exceeding minimal. Also, some regard the probability of therapeutic benefit in phase I studies to be so low that these studies do not satisfy the regulatory requirement that they "hold out the prospect of direct benefit" to subjects. On the basis of these considerations, investigators and institutional review boards might reasonably conclude that some phase I in utero studies are not to be permitted. This paper identifies considerations that are relevant to such judgments and explores ethically acceptable ways in which phase I studies can be designed so that they are permitted by the regulations. PMID:21846200

  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. 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

  17. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    International Nuclear Information System (INIS)

    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 (CNTSmall, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNTLarge, 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 CNTLarge 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 different, the two

  18. Phase I Study of Oral Clofarabine Consolidation in Adults Aged 60 and Older with Acute Myeloid Leukemia

    OpenAIRE

    Jacoby, Meagan A.; Michael G. Martin; Uy, Geoffrey L.; Westervelt, Peter; DiPersio, John F.; Cashen, Amanda; Stockerl-Goldstein, Keith; Vij, Ravi; Luo, Jingqin; Reineck, Teresa; Bernabe, Noel; Abboud, Camille N.

    2014-01-01

    Clofarabine has shown activity and tolerability in older patients with acute myeloid leukemia (AML). We investigated the safety and tolerability of an oral formulation of clofarabine for consolidation therapy of patients aged 60 and older with AML. In this phase I study, twenty-two patients older than 60 years with AML in first complete remission were treated once daily with oral clofarabine for 14 or 21 days of a 28 day cycle, for up to 5 cycles. Dose escalation from 1 mg to 6 mg daily using...

  19. Investigation of the solubility and the potentials for purification of serum amyloid A (SAA) from equine acute phase serum

    DEFF Research Database (Denmark)

    Christensen, Michelle Brønniche; Sørensen, Jens Christian; Jacobsen, Stine;

    2013-01-01

    for purification of equine SAA based on biochemical properties.Freeze dried equine acute phase serum was dissolved in 70% 2-propanol, 8 M urea, and milli-Q water, respectively. Supercritical fluid extraction (SFE), size-exclusive chromatography (FPLC-SEC), and preparative isoelectric focusing (IEF) were performed...... in the attempt to purify. Immunostaining of IEF blots were used for isoform-specific detection of SAA in the preparations and purity was assessed by silverstained SDS-PAGE. FINDINGS: SAA was soluble in 70% 2-propanol, 8 M urea and Milli-Q water. SAA was not separated in the lipophilic or ampipathic fractions...

  20. Early prognosis of survival or death after a recent stroke by blood levels of acute-phase proteins.

    Science.gov (United States)

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Ghiţescu, M

    1991-01-01

    From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.

  1. Regulation of major acute-phase plasma proteins by hepatocyte- stimulating factors of human squamous carcinoma cells

    OpenAIRE

    1986-01-01

    Human squamous carcinoma (COLO-16) cells release factors which specifically stimulate the synthesis of major acute-phase plasma proteins in human and rodent hepatic cells. Anion exchange, hydroxyapatite, lectin, and gel chromatography of conditioned medium of COLO-16 cells result in separation into three distinct forms of hepatocyte-stimulating factors (designated HSF-I, HSF-II, and HSF-III) with apparent molecular weights of 30,000, 50,000 and 70,000, respectively. None of the preparations c...

  2. Genetic effects on acute phase protein response to the stresses of weaning and transportation in beef calves.

    Science.gov (United States)

    Qiu, X; Arthington, J D; Riley, D G; Chase, C C; Phillips, W A; Coleman, S W; Olson, T A

    2007-10-01

    The objective herein was to estimate heterosis and breed effects in purebred and crossbred Romosinuano, Brahman, and Angus calves on acute phase protein response to weaning and transportation. Calves (n = 1,032) were weaned in September of 2002, 2003, and 2004 at approximately 7 mo of age. Approximately 28 d after weaning, steer calves (n = 482) were transported 1,800 km (20 h) to Oklahoma. Concentrations of 3 acute phase proteins (ceruloplasmin, fibrinogen, and haptoglobin) were measured in blood samples. Calves (steers and heifers) were sampled at weaning, and 24 and 72 h postweaning. For separate analyses, steers sent to Oklahoma were sampled before shipment, upon arrival, and 24 and 72 h after arrival. Combinations of the following fixed effects were investigated: sire breed, dam breed, sampling time, birth location, calf sex (weaning only), year, cow age, and interactions. Effects of special interest were sire breed x dam breed as an indication of breed group of calf, and the interaction of sire and dam breeds with sampling time. Weaning age and BW were investigated as linear and quadratic covariates. Sire of calf within sire breed was a random term. The correlation structure of repeated measures was determined by comparison of information criterion values for different structures within each analysis. In general, plasma acute phase protein concentrations in weaned calves increased with sampling time. Concentrations in the transported steers increased through sampling at 24 h after arrival, and were lower at 72 h. Significant estimates of heterosis were detected for Brahman-Angus haptoglobin concentrations at weaning (0.38 +/- 0.14 mg/dL x 100; 44%), and for Romosinuano-Angus fibrinogen concentrations at weaning (11.4 +/- 5.5 mg/dL; 10%) and in transported steers (22.5 +/- 8.4 mg/dL; 20%). The direct effect of Romosinuano was to increase (P Angus was to lower ceruloplasmin concentrations in weaned calves (-3.9 +/- 1.2; P = 0.001). Significant maternal effects

  3. 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...

  4. Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

    OpenAIRE

    Huh, Hee Jin; Park, Chan-Jeoung; Jang, Seongsoo; Seo, Eul-Ju; Chi, Hyun-Sook; Lee, Je-Hwan; Lee, Kyoo-Hyung; Seo, Jong Jin; Moon, Hyung Nam; Ghim, Thad

    2006-01-01

    The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of the...

  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. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

    Directory of Open Access Journals (Sweden)

    Li Xinran

    2015-04-01

    Full Text Available The study was conducted on 24 Mongolian horses, with oligofructose-induced equine laminitis (10 g/kg b.w.. The objective of the study was to investigate the relationships among matrix metalloproteinase 2 (MMP-2, P38 mitogen-activated protein kinases (P38 MAPK, tissue inhibitor of metalloproteinase 2 (TIMP-2, lipopolysaccharides (LPS, and tumour necrosis factor-α (TNF-α during acute developmental phase of laminitis, and to determine whether there are any characteristic tendencies. Moreover, plasma concentrations of LPS and TNF-α were measured in order to determine the time of leukocytes’ activation. Eleven of the 12 horses showed clinical signs of laminitis. The contents of MMP-2 and P38 MAPK increased significantly from 8 h to 64 h, and the content of TIMP-2 decreased significantly at the same time. Plasma LPS concentrations increased significantly between 8 h and 20 h and reached a peak of 0.024 ± 0.009 EU/mL (equivalent to 3.04 ± 1.19 pg/mL at 12 h. TNF-α concentration increased between 20 h and 36 h. This data indicates that MMP-2 plays an important role during the early acute developmental phase of oligofructose-induced equine laminitis.

  15. 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. PMID:27487515

  16. The influence of supplemental chromium and vaccines on the acute phase response of newly arrived feeder calves.

    Science.gov (United States)

    Wright, A J; Mallard, B A; Mowat, D N

    1995-01-01

    The acute phase response as indicated by serum haptoglobin and total haemolytic complement activity (CH50) was measured in 72 cross-bred steer calves purchased at sales in Ontario. During the 28 day (d) trial, 18 steers were randomly assigned to each of the following groups: 1) control; 2) vaccinated (Infectious Bovine Rhinotracheitis, Parainfluenza-3, Bovine Viral Diarrhea, Bovine Respiratory Synctial Virus vaccine plus Pasteurella haemolytica vaccine); 3) supplemental chelated Cr (0.14 mg/kg); and 4) Cr plus vaccines. Haptoglobin concentrations were low at arrival, increased (P 0.05) by day 14. Supplemental Cr reduced (P 0.05) than in healthy calves. Complement activity was lowest on day 7 (P 0.10). Complement activity did not increase on day 14 (P > 0.05) with Cr supplementation as in other treatments. Morbid calves had lower (P < 0.05) CH50 activity than healthy calves on day 14. Following antibiotic treatment, the Cr-supplemented group had higher (P < 0.05) CH50 than during morbidity. In general, chromium supplementation reduced the acute phase response in newly arrived feeder calves. PMID:8548694

  17. 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.

  18. 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.

  19. Chediak-Higashi syndrome in accelerated phase masquerading as severe acute malnutrition

    OpenAIRE

    Karande, Sunil; Agarwal, Shruti; Gandhi, Bhaumik; Muranjan, Mamta

    2014-01-01

    A toddler presented with poor appetite, weight loss and frequent respiratory tract infections for the past 6 months, fever and increasing paleness for the past 2 months and bilateral pedal oedema for the past 1 month. Anthropometry confirmed severe acute malnutrition. Clinical and laboratory evaluation revealed that the child also had hypopigmented hair and skin, splenohepatomegaly, pancytopenia and hypoalbuminaemia. The coexistence of hypopigmentation and suspected low immunity prompted us t...

  20. 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.

  1. 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.

  2. Potentially reversible factors during the very acute phase of stroke and their impact on the prognosis

    DEFF Research Database (Denmark)

    Jørgensen, H S; Reith, J; Nakayama, H;

    2001-01-01

    In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with 'good' prognostic parameters (body...... in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5-56; p

  3. A PROSPECTIVE STUDY OF IN HOSPITAL OUTCOME OF ACUTE PHASE OF STEMI WITH HYPONATREMIA

    OpenAIRE

    Suresh; Akshaya; Syed

    2014-01-01

    BACKGROUND AND OBJECTIVE: In acute STEMI, due to activation of the Baro receptors, there is activation of the sympathetic nervous system. This leads to release of hormones like vasopressin and also activation of renin angiotensin system. Magnitude of this neurohormonal change is related to the severity of the myocardial damage. Hyponatremia is a reflection of these hormonal changes. So serum Na+ level may be an indicator of the severity of ST elevation MI (STEMI). The aim ...

  4. Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria.

    OpenAIRE

    Gillespie, S H; C. DOW; Raynes, J G; Behrens, R. H.; Chiodini, P L; McAdam, K P

    1991-01-01

    Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/...

  5. Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

    Institute of Scientific and Technical Information of China (English)

    Wei-ming YAN; Jia-quan HUANG; Xiao-ping LUO; Qin NING

    2007-01-01

    To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

  6. Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Patterson, Sheila K; Borewicz, Klaudyna; Johnson, Timothy; Xu, Wayne; Isaacson, Richard E

    2012-01-01

    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-adhesive to the

  7. Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium.

    Directory of Open Access Journals (Sweden)

    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

  8. Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia

    Science.gov (United States)

    Huang, Sai; Jiang, Meng-Meng; Chen, Guo-Feng; Qian, Kun; Gao, Hong-Hao; Guan, Wei; Shi, Jin-Long; Liu, An-Qi; Liu, Jing; Wang, Bian-Hong; Li, Yong-Hui; Yu, Li

    2016-01-01

    Background: The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML. Methods: Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay. Results: EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively. Conclusions: Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target

  9. Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    Sai Huang; Meng-Meng Jiang; Guo-Feng Chen; Kun Qian; Hong-Hao Gao; Wei Guan; Jin-Long Shi

    2016-01-01

    Background:The acute myeloid leukemia 1 (AML 1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML.By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells,we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML.Methods:Qualitative polymerase chain reaction (PCR),quantitative reverse transcription PCR (RT-PCR),and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines.Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4.Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4.Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region.The influence of EYA4 gene in the cell proliferation,apoptosis,and cell clone-forming ability was detected by the technique of Cell Counting Kit-8,flow cytometry,and clonogenic assay.Results:EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells,compared to HL-60 and SKNO-1-siA/E cells,respectively.We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases.Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines.We also found EYA4 transfection increased apoptosis ofKasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control,respectively.Conclusions:Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene.In addition,we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate

  10. 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.

  11. Phase 1 Dose- Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukaemias

    OpenAIRE

    Zeidan, Amer M.; Ricklis, Rebecca M.; Carraway, Hetty E.; Yun, Hyun D.; Greer, Jacqueline M.; Smith, B. Douglas; Levis, Mark J.; McDevitt, Michael A.; Pratz, Keith W.; Showel, Margaret M.; Gladstone, Douglas E; Gore, Steven D.; Judith E Karp

    2012-01-01

    The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enrolled (28 acute myeloid leukaemia [AML], 12 acute lymphoblastic leukaemia [ALL]) in this Phase 1 dose-escalation trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for 4 consecutive days (CLO-CYx4). The median age was 48.5 years. The median number of prior regimens was 2 (range 1–5), and 6/40 patients (15%) had prior allogeneic haematopoietic ste...

  12. RCSD1-ABL1 Translocation Associated with IKZF1 Gene Deletion in B-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Shawana Kamran

    2015-01-01

    Full Text Available The RCSD1 gene has recently been identified as a novel gene fusion partner of the ABL1 gene in cases of B-cell Acute Lymphoblastic Leukemia (B-ALL. The RCSD1 gene is located at 1q23 and ABL1 is located at 9q34, so that the RCSD1-ABL1 fusion typically arises through a rare reciprocal translocation t(1;9(q23;q34. Only a small number of RCSD1-ABL1 positive cases of B-ALL have been described in the literature, and the full spectrum of clinical, morphological, immunophenotypic, and molecular features associated with this genetic abnormality has not been defined. We describe extensive genetic characterization of a case of B-ALL with RCSD1-ABL1 fusion, by using conventional cytogenetic analysis, Fluorescence In Situ Hybridization (FISH studies, and Chromosomal Microarray Analysis (CMA. The use of CMA resulted in detection of an approximately 70 kb deletion at 7p12.2, which caused a disruption of the IKZF1 gene. Deletions and mutations of IKZF1 are recurring abnormalities in B-ALL and are associated with a poor prognosis. Our findings highlight the association of the deletion of IKZF1 gene with the t(1;9(q24;q34 and illustrate the importance of comprehensive cytogenetic and molecular evaluation for accurate prediction of prognosis in patients with B-cell ALL.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. A PROSPECTIVE STUDY OF IN HOSPITAL OUTCOME OF ACUTE PHASE OF STEMI WITH HYPONATREMIA

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    Suresh

    2014-12-01

    Full Text Available BACKGROUND AND OBJECTIVE: In acute STEMI, due to activation of the Baro receptors, there is activation of the sympathetic nervous system. This leads to release of hormones like vasopressin and also activation of renin angiotensin system. Magnitude of this neurohormonal change is related to the severity of the myocardial damage. Hyponatremia is a reflection of these hormonal changes. So serum Na+ level may be an indicator of the severity of ST elevation MI (STEMI. The aim of this study is to evaluate in hospital prognosis of acute ST segment elevation myocardial infarction with Hyponatremia. MATERIAL AND METHODS: This prospective observational study was conducted in patients presenting with acute ST-elevation myocardial infarction admitted in ICCU, Basaveshwar Teaching and General Hospital, Gulbarga attached to Mahadevappa Rampure Medical College during the period of Jan 2013 to July 2014.Qualifying patients underwent detailed history and clinical examination. Plasma sodium concentrations were obtained on admission and at 24, 48 and 72 hours thereafter. Study population were grouped into two groups, 50 patients with hyponatraemia were included in Group-I and 50 patients with normal plasma sodium level were in Group-II. Hyponatremia defined as plasma sodium level less than 135 mmol/L. In hospital outcome of these two groups of patients were evaluated and compared. RESULTS: The hypo and normo natremic groups were comparable with respect to baseline characteristics and in-hospital management. There was no statistically significant difference between the two groups regarding the incidence of risk factors of IHD. Hyponatremics had higher rates of in-hospital mortality (24%vs 6%p<0.01 composite of death, heart failure (72% vs. 36%, p=0.05 and arrhythmias (30% vs 6% p<0.01 Anterior myocardial infarction was more frequent in patients with hyponatremia, who showed advanced Killip class. After adjustment for covariates, hyponatremia was independently

  18. Pig major acute-phase protein and haptoglobin serum concentrations correlate with PCV2 viremia and the clinical course of postweaning multisystemic wasting syndrome

    DEFF Research Database (Denmark)

    Grau-Roma, Llorenc; Heegaard, Peter M. H.; Hjulsager, Charlotte Kristiane;

    2009-01-01

    The aim of the present longitudinal study was to assess the evolution of two acute phase proteins (APPs), pig-major acute phase protein (pig-MAP) and haptoglobin (HPT), in serum from pigs that developed postweaning multisystemic wasting syndrome (PMWS) in comparison to healthy and wasted non...... and both pig-MAP (R=0.487 to 0.602, p>0.001) and HPT (R=0.326 to 0.550, p>0.05 to 0.0001) concentrations in serum of PMWS affected pigs, indicating that the acute phase response in PMWS affected pigs occurred concomitantly to PCV2 viremia. No other pathogen, apart from PCV2, was consistently related...

  19. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background Ciguatoxins (CTXs are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  20. β1-Na(+),K(+)-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Lin, X; Barravecchia, M; Kothari, P; Young, J L; Dean, D A

    2016-06-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with diverse disorders and characterized by disruption of the alveolar-capillary barrier, leakage of edema fluid into the lung, and substantial inflammation leading to acute respiratory failure. Gene therapy is a potentially powerful approach to treat ALI/ARDS through repair of alveolar epithelial function. Herein, we show that delivery of a plasmid expressing β1-subunit of the Na(+),K(+)-ATPase (β1-Na(+),K(+)-ATPase) alone or in combination with epithelial sodium channel (ENaC) α1-subunit using electroporation not only protected from subsequent lipopolysaccharide (LPS)-mediated lung injury, but also treated injured lungs. However, transfer of α1-subunit of ENaC (α1-ENaC) alone only provided protection benefit rather than treatment benefit although alveolar fluid clearance had been remarkably enhanced. Gene transfer of β1-Na(+),K(+)-ATPase, but not α1-ENaC, not only enhanced expression of tight junction protein zona occludins-1 (ZO-1) and occludin both in cultured cells and in mouse lungs, but also reduced pre-existing increase of lung permeability in vivo. These results demonstrate that gene transfer of β1-Na(+),K(+)-ATPase upregulates tight junction formation and therefore treats lungs with existing injury, whereas delivery of α1-ENaC only maintains pre-existing tight junction but not for generation. This indicates that the restoration of epithelial/endothelial barrier function may provide better treatment of ALI/ARDS. PMID:26910760

  1. Phase II study of profiromycin vs mitomycin-C utilizing acute intermittent schedules.

    Science.gov (United States)

    Baker, L H; Izbicki, R M; Vaitkevicius, V K

    1976-01-01

    A randomized prosective study of Mitomycin-C and its N-methyl derivative, Porfiromycin, was conducted. Thirty-two patients with disseminated gastrointestinal cancer or other disseminated abdominal adenocarcinoma were treated with Mitomycin-C; 31 patients received Porfiromycin. Both drugs were given by acute intermittent bolus schedule (Mitomucin-C , 22.5 mg/M2 or Porfiromycin, 75 mg/M2 every 6--8 weeks as a single bolus i.v. injection). Eleven patients (34%) who received Mitomycin-C entered into partial remission. In 10 of the 31 patients (32%) receiving Porfiromycin, partial remission occured. Analysis by tumor type demonstrated that in the Mitomycin-C treated group responses occured in 4 of 12 patients with colorectal carcinoma, in 4 of 9 with upper GI cancers, and in 3 of 11 with ovarian cancer. Correspondingly in Porfiromycin group responses occured in 2 of 12 colorectal carcinoma patients, in 3 of 7 upper GI cancer patients, and in 5 of 12 ovarian cancer patients. Both drugs produced significant myelosuppression; however, Porfiromycin toxicity appeared more cumulative. Further clinical trial of Mitomycin in an acute intermittent bolus schedule appears justified. PMID:958162

  2. Effects of traditional Chinese medicine on intestinal mucosal permeability in early phase of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong; LI Fei; JIA Jian-guo; DIAO Yong-peng; LI Zong-xin; SUN Jia-bang

    2010-01-01

    Background Traditional Chinese medicine has been used widely for many years in China to treat acute pancreatitis.We have investigated the effects of Dachengqi decoction on intestinal mucosal permeability and outcome in patients with severe acute pancreatitis (SAP).Methods Forty patients with sustained SAP that required admission to the surgical intensive care unit were enrolled prospectively in the study. All of these patients were divided randomly into the Dachengqi decoction group (n=20) and control group (n=20) on admission. Intestinal permeability was assessed by measuring absorption of two metabolically inert markers, lactulose (L) and mannitol (M), which were administered orally. Serum concentrations of endotoxin (lipopolysaccharide, LPS) and the ratio of lactulose to mannitol in urine (L/M) were detected in all patients.Results Compared with those in the control group, urinary L/M ratio decreased significantly in the Dachengqi decoction group on the 7th day after admission (P=0.001). Also, serum concentrations of LPS were reduced on the 5th and 7th day after admission (P=0.006, P=0.008, respectively). Incidence of multiple organ dysfunction syndrome (MODS) and pancreatic infection was significantly lower in the Dachengqi decoction group compared with those in the control group (P=0.038, P=0.025, respectively).Conclusion Dachengqi decoction may promote the recovery of intestinal mucosal permeability and decrease the incidence of MODS and pancreatic infection in patients with SAP.

  3. Positive autoregulation delays the expression phase of mammalian clock gene Per2.

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    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.

  4. Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes

    NARCIS (Netherlands)

    Santos, Joana; Cerveira, Nuno; Bizarro, Susana; Ribeiro, Franclim R.; Correia, Cecilia; Torres, Lurdes; Lisboa, Susana; Vieira, Joana; Mariz, Jose M.; Norton, Lucilia; Snijder, Simone; Mellink, Clemens H.; Buijs, Arjan; Shih, Lee-Yung; Strehl, Sabine; Micci, Francesca; Heim, Sverre; Teixeira, Manuel R.

    2010-01-01

    Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have r

  5. Functional analyses of Src-like adaptor (SLA), a glucocorticoid-regulated gene in acute lymphoblastic leukemia.

    Science.gov (United States)

    Mansha, Muhammad; Carlet, Michela; Ploner, Christian; Gruber, Georg; Wasim, Muhammad; Wiegers, Gerrit Jan; Rainer, Johannes; Geley, Stephan; Kofler, Reinhard

    2010-04-01

    Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and are used in the therapy of lymphoid malignancies. SLA (Src-like-adaptor), an inhibitor of T- and B-cell receptor signaling, is a promising candidate derived from expression profiling analyses in children with acute lymphoblastic leukemia (ALL). Over-expression and knock-down experiments in ALL in vitro model revealed that transgenic SLA alone had no effect on survival or cell cycle progression, nor did it affect sensitivity to, or kinetics of, GC-induced apoptosis. Although SLA is a prominent GC response gene, it does not seem to contribute to the anti-leukemic effects of GC.

  6. Genetic variants within telomere-associated genes, leukocyte telomere length and the risk of acute coronary syndrome in Czech women.

    Science.gov (United States)

    Dlouha, Dana; Pitha, Jan; Mesanyova, Jana; Mrazkova, Jolana; Fellnerova, Adela; Stanek, Vladimir; Lanska, Vera; Hubacek, Jaroslav A

    2016-02-15

    The association between leukocyte telomere length (LTL) and cardiovascular disease (CVD) has been published in many reports, although almost exclusively in men. In our study we analysed the association between LTL and five selected variants within three candidate genes (TERC rs12696304; TERF2IP rs3784929 and rs8053257; UCP2 rs659366 and rs622064), which are not only involved in telomere-length maintenance but also potentially associated with higher risk of acute coronary syndrome (ACS) in Czech women (505 cases and 642 controls). We detected significantly shorter LTL in women with ACS (Ptelomere length or ACS risk in Czech females.

  7. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

    Science.gov (United States)

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection.

  8. 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

  9. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

    Science.gov (United States)

    Camargo, Carolina de Quadros; Borges, Dayanne da Silva; de Oliveira, Paula Fernanda; Chagas, Thayz Rodrigues; Del Moral, Joanita Angela Gonzaga; Durigon, Giovanna Steffanello; Dias, Bruno Vieira; Vieira, André Guedes; Gaspareto, Patrick; Trindade, Erasmo Benício Santos de Moraes; Nunes, Everson Araújo

    2015-01-01

    Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

  10. Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.

    Science.gov (United States)

    Kumar De, Ujjwal; Mukherjee, Reena; Nandi, Sukdeb; Patel, Bhimnere Hanumatnagouda Manjunatha; Dimri, Umesh; Ravishankar, Chintu; Verma, Ashok Kumar

    2014-10-01

    Rotaviral enteritis has emerged as a major cause of morbidity and mortality in piglets during their post-natal life. The present study was carried out to examine high-mobility group box 1 (HMGB1) protein, acute phase response and oxidative stress indices in the serum of suckling piglets suffering from enteritis with or without association of porcine group A rotavirus infection. The present investigation utilized 23 clinical cases with signs of acute enteritis and 12 more healthy piglets of a similar age group as control animals. Out of 23 enteritis cases, 12 cases were found to be positive for porcine group A rotavirus infection as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for group A rotavirus, and the rest were found negative. The acute enteritis cases in piglets were associated with an elevated level of HMGB1 protein and serum haptoglobin and ceruloplasmin suggestive of an acute phase response. Among the oxidative stress indices, the concentrations of malondialdehyde (MDA) and nitric oxide (NO) in serum were significantly increased. A pronounced drop of total antioxidant capacity and the activity of antioxidant enzymes such as catalase and superoxide dismutase in the serum of piglets suffering from acute enteritis compared to healthy ones were also noticed. The alterations in HMGB1 protein, acute phase response and oxidative stress indices were more pronounced in cases with the involvement of porcine rotavirus as compared to rotavirus-negative cases. It is concluded that HMGB1 protein, markers of oxidative stress and acute phase proteins might play an important role in the aetiopathogenesis of porcine diarrhoea caused by rotavirus and might be true markers in diagnosing the conditions leading to the extension of the prompt and effective therapeutic care.

  11. Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego, Argentina.

    Science.gov (United States)

    Mallimaci, María Cristina; Sosa-Estani, Sergio; Russomando, Graciela; Sanchez, Zunilda; Sijvarger, Carina; Alvarez, Isabel Marcela; Barrionuevo, Lola; Lopez, Carlos; Segura, Elsa Leonor

    2010-01-01

    Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital infection among children in the study was 4.4% (3/68). Our results show that for infants younger than 30 days of age, matched blood samples from mother and infant were capable of identifying congenital transmission of infection using an enzyme-linked immunosorbent assay with SAPA. For infants older than 3 months, congenital infection could be ruled out using the same procedure. PMID:20064996

  12. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Arellano

    1995-01-01

    Full Text Available Hydrolytic enzymes are the major constituents of alveolar macrophages (AM and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs. An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF protein concentration, BALF LDH and BALF alkaline phosphatase activities. All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease.

  13. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation

    DEFF Research Database (Denmark)

    Johansson, P I; Ostrowski, S R

    2010-01-01

    Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the...... circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally...... evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant...

  14. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    Science.gov (United States)

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  15. 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.

  16. 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

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

    OpenAIRE

    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

    Background 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. Case presentation In this re...

  18. GENE EXPRESSION OF NOVEL RETROVIRUS ASSOCIATED WITH HUMAN ACUTE MULOID LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    许晓华; 徐荣臻; 王世炯; 郑树; 朱宁希; 周旋

    2003-01-01

    Objective: To explore the potentiality of retroviral etiology in human acute myeloid leukemia(AML). Methods: The expression of clone 6#11 in leukemic cell samples from 19 AML cases and peripheral blood mononuclear cells (PBMNCs) from 20 controls was studied by means of Northern blot and reversal transcription polymerase chain reaction (RT-PCR). Results: Northern blot and RT-PCR analyses showed that the expression level of clone 6#11 was significantly higher in AML patients than that in control. Conclusion: Northern blot and RT-PCR analyses revealed that the expression of novel retrovirus were associated with acute myeloid leukemia.

  19. Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound

    Institute of Scientific and Technical Information of China (English)

    HUANG Jiaquan; XIAO Fei; YU Haijing; HUANG Tiejun; HUANG Haiyan; NING Qin

    2007-01-01

    Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure in- fected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% re- spectively 48 h after intrapefitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oli- gonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fg12, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

  20. REM sleep deprivation of rats induces acute phase response in liver.

    Science.gov (United States)

    Pandey, Atul Kumar; Kar, Santosh Kumar

    2011-07-01

    REM sleep is essential for maintenance of body physiology and its deprivation is fatal. We observed that the levels of ALT and AST enzymes and pro-inflammatory cytokines like IL-1 β, IL-6 and IL-12 circulating in the blood of REM sleep deprived rats increased in proportion to the extent of sleep loss. But in contrast the levels of IFN-γ and a ∼200 kDa protein, identified by N-terminal sequencing to be alpha-1-inhibitor-3(A1I3), decreased significantly. Quantitative PCR analysis confirmed that REM sleep deprivation down regulates AII3 gene and up regulates IL1 β, IL6 and their respective receptors gene expression in the liver initiating its inflammation.

  1. Time-Course Changes of Steroidogenic Gene Expression and Steroidogenesis of Rat Leydig Cells after Acute Immobilization Stress

    Directory of Open Access Journals (Sweden)

    Han Lin

    2014-11-01

    Full Text Available Leydig cells secrete testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid (corticosterone, CORT; in rats, which decreases circulating testosterone levels in part through a direct action by binding to the glucocorticoid receptors (NR3C1 in Leydig cells. The intratesticular CORT level is dependent on oxidative inactivation of glucocorticoid by 11β-hydroxysteroid dehydrogenase 1 (HSD11B1 in Leydig cells. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute immobilization stress in rats. The plasma CORT levels were significantly increased 0.5, 1, 3 and 6 h after immobilization stress, while plasma testosterone levels were significantly reduced 3 and 6 h, after stress and luteinizing hormone (LH did not change. Immobilization stress caused the down-regulation of Scarb1, Star and Cyp17a1 expression levels in the rat testis starting at the first hour of stress, ahead of the significant decreases of plasma testosterone levels. Other mRNA levels, including Cyp11a1, Hsd3b1 and Hsd17b3, began to decline after 3 h. Hsd11b1 and Nos2 mRNA levels did not change during the course of stress. Administration of glucocorticoid antagonist RU486 significantly restored plasma testosterone levels. In conclusion, Scarb1, Star and Cyp17a1 expression levels are more sensitive to acute stress, and acute immobilization stress causes the decline of the steroidogenic pathway via elevating the levels of glucocorticoid, which binds to NR3C1 in Leydig cells to inhibit steroidogenic gene expression.

  2. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment

    NARCIS (Netherlands)

    A. Holleman (Amy); C. Cheng (Cheng); C.H. Pui (Ching-Hon); W.E. Evans (William); M.V. Relling (Mary); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); M.H. Cheok (Meyling); M.L. den Boer (Monique); W. Yang; A.J. Veerman; K.M. Kazemier (Karin); D. Pei (Deqing)

    2004-01-01

    textabstractBACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173

  3. Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    Balgobind, Brian V.; Van den Heuvel-Eibrink, Marry M.; De Menezes, Renee X.; Reinhardt, Dirk; Hollink, Iris H. I. M.; Arentsen-Peters, Susan T. J. C. M.; van Wering, Elisabeth R.; Kaspers, Gertjan J. L.; Cloos, Jacqueline; de Bont, Evelien S. J. M.; Cayuela, Jean-Michel; Baruchel, Andre; Meyer, Claus; Marschalek, Rolf; Trka, Jan; Stary, Jan; Beverloo, H. Berna; Pieters, Rob; Zwaan, C. Michel; den Boer, Monique L.

    2011-01-01

    Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the

  4. Local interleukin-12 gene transfer promotes conversion of an acute arthritis to a chronic destructive arthritis.

    NARCIS (Netherlands)

    Joosten, L.A.B.; Heuvelmans-Jacobs, M.; Lubberts, G.J.H.; Loo, F.A.J. van de; Bakker, A.C.; Helsen, M.M.A.; Richards, C.D.; Berg, W.B. van den

    2002-01-01

    OBJECTIVE: To determine whether local overexpression of interleukin-12 (IL-12), a pleiotropic cytokine that promotes the development of naive T cells into Th1 cells, could aggravate murine streptococcal cell wall (SCW)-induced arthritis, a model of acute arthritis. METHODS: C57BL/6 mice were injecte

  5. INHALATION OF OZONE AND DIESEL EXHAUST PARTICLES (DEP) INDUCES ACUTE AND REVERSIBLE CARDIAC GENE EXPRESSION CHANGES

    Science.gov (United States)

    We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...

  6. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    Science.gov (United States)

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  7. 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...

  8. Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Micci, Francesca; Thorsen, Jim;

    2013-01-01

    Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT...

  9. The acute phase reactant orosomucoid-1 is a bimodal regulator of angiogenesis with time- and context-dependent inhibitory and stimulatory properties.

    Directory of Open Access Journals (Sweden)

    Giovanni Ligresti

    Full Text Available BACKGROUND: Tissues respond to injury by releasing acute phase reaction (APR proteins which regulate inflammation and angiogenesis. Among the genes upregulated in wounded tissues are tumor necrosis factor-alpha (TNFα and the acute phase reactant orosomucoid-1 (ORM1. ORM1 has been shown to modulate the response of immune cells to TNFα, but its role on injury- and TNFα-induced angiogenesis has not been investigated. This study was designed to characterize the role of ORM1 in the angiogenic response to injury and TNFα. METHODS AND RESULTS: Angiogenesis was studied with in vitro, ex vivo, and in vivo angiogenesis assays. Injured rat aortic rings cultured in collagen gels produced an angiogenic response driven by macrophage-derived TNFα. Microarray analysis and qRT-PCR showed that TNFα and ORM1 were upregulated prior to angiogenic sprouting. Exogenous ORM1 delayed the angiogenic response to injury and inhibited the proangiogenic effect of TNFα in cultures of aortic rings or isolated endothelial cells, but stimulated aortic angiogenesis over time while promoting VEGF production and activity. ORM1 inhibited injury- and TNFα-induced phosphorylation of MEK1/2 and p38 MAPK in aortic rings, but not of NFκB. This effect was injury/TNFα-specific since ORM1 did not inhibit VEGF-induced signaling, and cell-specific since ORM1 inhibited TNFα-induced phosphorylation of MEK1/2 and p38 MAPK in macrophages and endothelial cells, but not mural cells. Experiments with specific inhibitors demonstrated that the MEK/ERK pathway was required for angiogenesis. ORM1 inhibited angiogenesis in a subcutaneous in vivo assay of aortic ring-induced angiogenesis, but stimulated developmental angiogenesis in the chorioallantoic membrane (CAM assay. CONCLUSION: ORM1 regulates injury-induced angiogenesis in a time- and context-dependent manner by sequentially dampening the initial TNFα-induced angiogenic response and promoting the downstream stimulation of the angiogenic

  10. Effects of Salmonella typhimurium Challenge on Swine Growth, Nitrogen Balance, Insulin-like Growth Factor-I, and Acute Phase Proteins

    Directory of Open Access Journals (Sweden)

    J. A. Loughmiller

    2007-01-01

    Full Text Available Growing barrows were used to determine the effects of an en teric disease challenge on nutrient balance, growth, acute phase proteins, and IGF-I. Pigs were challenged on d 0 with Salmonella typhimurium (S; N=21, or unchallenged and fed ad libitum (A; n=6, or unchallenged and pair-fed the same amount of feed as a challenged pig (P; n=8. Blood was collected on d -3, 1, 5, 9, and 15. A disease challenge  time interaction was observed for serum haptoglobin (P typhimurium challenge (P > 0.20. Results indicate that 66% of the short-term reductions in average daily gain from an acute S. typhimurium disease challenge are due to reductions in feed intake. The remaining differences are due to the acute phase immune response.

  11. Phase analysis of platelet aggregation in acute disturbances of cerebral circulation.

    Science.gov (United States)

    Petrova, T R; Pavlishchuk, S A; Grigoriev, G I

    1975-01-01

    In 120 patients with atherosclerosis, complicated in 43 patients by a haemorrhagic, in 47 patients by an ischaemic, and in 30 patients by a transient cerebral insult, phase analysis of platelet aggregation was performed by the turbidimetric method according to Born with graphic recording according to O'Brien. An increase in the platelet activity was found in ischaemic insult, manifesting itself by the occurrence of spontaneous aggregationin 60% of the cases, an acceleration of ADP-induced aggregation, and the second aggregation phase in all patients examined. A direct correlation was revealed between the secondary aggregation and the intensity of spontaneous and of ADP-induced aggregation, and the possibility of a transformation of the spontaneous into the secondary aggregation of platelets was demonstrated. Haemorrhagic insults were characterized by the absence of spontaneous and secondary aggregation and by the suppression of ADP-induced aggregation. In a transient insult, the mean values of the aggregatogram items did differ from normal. In vitro, the role of increased permeability of platelet membranes in the mechanism triggering off spontaneous aggregation and the second phase of ADP-induced aggregation was documented.

  12. Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain.

    Science.gov (United States)

    Jha, Mithilesh Kumar; Rahman, Md Habibur; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Lee, Won-Ha; Suk, Kyoungho

    2016-09-01

    Pyruvate dehydrogenase (PDH) kinases (PDKs) 1-4, expressed in peripheral and central tissues, regulate the activity of the PDH complex (PDC). The PDC is an important mitochondrial gatekeeping enzyme that controls cellular metabolism. The role of PDKs in diverse neurological disorders, including neurometabolic aberrations and neurodegeneration, has been described. Implications for a role of PDKs in inflammation and neurometabolic coupling led us to investigate the effect of genetic ablation of PDK2/4 on nociception in a mouse model of acute inflammatory pain. Deficiency in Pdk2 and/or Pdk4 in mice led to attenuation of formalin-induced nociceptive behaviors (flinching, licking, biting, or lifting of the injected paw). Likewise, the pharmacological inhibition of PDKs substantially diminished the nociceptive responses in the second phase of the formalin test. Furthermore, formalin-provoked paw edema formation and mechanical and thermal hypersensitivities were significantly reduced in Pdk2/4-deficient mice. Formalin-driven neutrophil recruitment at the site of inflammation, spinal glial activation, and neuronal sensitization were substantially lessened in the second or late phase of the formalin test in Pdk2/4-deficient animals. Overall, our results suggest that PDK2/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain. © 2016 Wiley Periodicals, Inc. PMID:26931482

  13. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Andreas Pohlmann

    Full Text Available Ischemia/reperfusion (I/R injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI. There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  14. Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia.

    Science.gov (United States)

    Jacoby, Meagan A; Martin, Michael G; Uy, Geoffrey L; Westervelt, Peter; Dipersio, John F; Cashen, Amanda; Stockerl-Goldstein, Keith; Vij, Ravi; Luo, Jingqin; Reineck, Teresa; Bernabe, Noel; Abboud, Camille N

    2014-05-01

    Clofarabine has shown activity and tolerability in older patients with acute myeloid leukemia (AML). We investigated the safety and tolerability of an oral formulation of clofarabine for consolidation therapy of patients aged 60 and older with AML. In this phase I study, twenty-two patients older than 60 years with AML in first complete remission were treated once daily with oral clofarabine for 14 or 21 days of a 28-day cycle, for up to five cycles. Dose escalation from 1 mg to 6 mg daily using a 3 + 3 design was used to determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and tolerability of oral clofarabine. No DLTs or Grade 3-4 nonhematologic toxicities were observed. The primary toxicities were hematologic, including uncomplicated grade 3-4 neutropenia (50%) and thrombocytopenia (50%). Given that myelosuppression necessitating dose delays/reductions was observed more commonly at higher doses, the recommended phase II dose is 2 mg daily for 21 of 28 days. At doses equal to or greater than 2 mg, the median relapse-free survival was 28.35 months. Oral clofarabine was well-tolerated with encouraging activity in patients older than 60 years. Further investigation of oral clofarabine as a consolidation and/or maintenance therapy in AML for older individuals is warranted. (ClinicalTrials.gov:NCT00727766). PMID:24415560

  15. Differences Between Women and Men in Phase I Cardiac Rehabilitation After Acute Myocardial Infarction: A Nationwide Population-Based Analysis.

    Science.gov (United States)

    Lin, Wen-Chih; Ho, Chung-Han; Tung, Li-Chen; Ho, Chi-Che; Chou, Willy; Wang, Chun-Hou

    2016-01-01

    Although numerous studies have investigated gender-related differences in patients who have had an acute myocardial infarction (AMI), few studies have examined the gender-related differences among inpatients receiving Phase I inpatient cardiac rehabilitation following AMI.Using data from the Taiwan National Health Insurance Research Database, this study analyzed 6713 adult patients who received inpatient cardiac rehabilitation following AMI between 2002 and 2011. The differences in comorbidity, medical service use, and prognosis between the male and female patients were analyzed to determine whether the comorbidities affecting their prognoses differed.Female patients accounted for 23.18% of the sample, had a higher average age, and exhibited severe comorbidities; furthermore, they had significantly more days of hospitalization and days in an intensive care unit than did male patients. The gender-related differences in hospital mortality rate and 30-day mortality rate were nonsignificant, but female patients exhibited a significantly higher 1-year mortality rate. Moreover, the risk for 1-year mortality was higher among female patients with moderate or severe renal disease (odds ratio: 1.94, 95% confidence interval: 1.29-2.92) than among their male counterparts. However, the 1-year mortality rate for the female patients did not increase after all risk factors were adjusted.Gender-related differences in age, comorbidity, and prognosis were confirmed in AMI patients receiving Phase I inpatient cardiac rehabilitation. In addition, gender-related differences were observed in the comorbidity risk factors affecting prognosis. However, being female did not affect the prognosis.

  16. Perfusion and diffusion MRI study detecting CBF disturbance and edema formation in the acute phase of cerebral contusion

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, Tatsuro; Aoyama, Naoki; Mori, Tatsuro; Maeda, Takeshi; Katayama, Yoichi [Nihon Univ., Tokyo (Japan). School of Medicine

    1998-12-01

    In order to clarify the mechanisms underlying cerebral contusion-induced CBF disturbance and edema formation, echoplanar diffusion and perfusion images were obtained in the patients with cerebral contusion. In the acute phase within 48 hours post-trauma, the apparent diffusion coefficient (ADC) showed various levels with a tendency to increase in the central area of contusion (ADC ratio=1.06{+-}0.21). In contrast, the ADC was significantly reduced in the peripheral area of contusion (ADC ratio=0.87{+-}0.16). The ADC at 2 weeks post-trauma increased both in the central (ADC ratio=1.16{+-}0.26) and the peripheral area of contusion (ADC ratio=1.10{+-}0.26, p<0.05), as compared to those within 48 hours post-trauma. The perfusion images showed a wide spread CBF depression extending beyond the area of contusion observed on the T1 and T2 weighted images. These results indicate that; in the early phase of contusion-induced edema formation, cytotoxic edema is predominant, especially in the peripheral area of contusion, and vasogenic edema appears thereafter. The CBF depression may contribute such cytotoxic edema formation in the surrounding area of cerebral contusion. It is concluded that echo-planar diffusion and perfusion images are excellent technique to investigate the evolution of CBF disturbance and edema formation following traumatic brain injury. (author)

  17. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.

    2012-01-01

    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with

  18. ACUTE TOXICITY PROFILE AND COMPLIANCE TO ACCELERATED RADIOTHERAPY PLUS CARBOGEN AND NICOTINAMIDE FOR CLINICAL STAGE T2-4 LARYNGEAL CANCER : RESULTS OF A PHASE III RANDOMIZED TRIAL

    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  19. Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

    NARCIS (Netherlands)

    de Vries, Heleen A. H.; Ponds, Fraukje A. M.; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2013-01-01

    Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Ma

  20. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.;

    2015-01-01

    We investigated the inflammatory response, acute phase response and genotoxic effect of diesel exhaust particles (DEPs, NIST1650b) following a single intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 µg/mouse and were killed 1, 3 and 28 days post-exposure. Vehicle controls...

  1. The Effectiveness of Inpatient Rehabilitation in the Acute Postoperative Phase of Care After Transtibial or Transfemoral Amputation: Study of an Integrated Health Care Delivery System

    OpenAIRE

    Stineman, Margaret G.; Kwong, Pui L.; Kurichi, Jibby E.; Prvu-Bettger, Janet A.; Vogel, W. Bruce; Maislin, Greg; Bates, Barbara E.; Reker, Dean M.

    2008-01-01

    Stineman MG, Kwong PL, Kurichi JE, Prvu-Bettger JA, Vogel WB, Maislin G, Bates BE, Reker DM. The effectiveness of inpatient rehabilitation in the acute postoperative phase of care after transtibial or transfemoral amputation: study of an integrated health care delivery system. Arch Phys Med Rehabil 2008;89:1863-72.

  2. Phorbol Ester Modulates Interleukin 6- and Interleukin 1-regulated Expression of Acute Phase Plasma Proteins in Hepatoma Cells*

    OpenAIRE

    Baumann, Heinz; Isseroff, Hadar; Latimer, Jean J.; Jahreis, Gerald P.

    1988-01-01

    Interleukin 6 (IL 6) and interleukin 1 (IL-1) regulate the expression of actue phase plasma proteins in rat and human hepatoma cells. Phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), partially mimics the stimulatory effect of IL-6 but reduces that effect of IL-1. TPA and IL-6 act synergistically. These regulatory properties of TPA are also manifested in HepG2 cells transiently transfected with an indicator gene construct carrying the IL-1/IL-6 regulatory enhancer element of the rat ...

  3. Management of poor grade subarachnoid hemorrhage. Unsolved problems in the ultra-acute phase

    International Nuclear Information System (INIS)

    We evaluated the management of patients with subarachnoid hemorrhage (SAH) after arrival for surgical intervention in the ultra-acute stage. Immediately after brief neurological and systemic examination, patients were deeply sedated to prevent aneurysmal rerupture. Principally they were intubated with intensive control of systolic blood pressure below 120 mmHg by radial arterial monitoring. Buprenorphine, midazolam, and vecuronium were routinely intravenously administered; and propofol, barbiturate, nicardipine, or prostaglandin was added to lower blood pressure if necessary. A total of 163 consecutive patients with SAH (59 men and 104 women, mean age of 61.1 years) arrived between 2003 and 2005 were enrolled. The majority of patients were in poor grade: 26 with Grade IV, 54 with Grade V by grading scale of the World Federation of Neurological Society, and 32 with cardiopulmonary arrest. Eighty-seven patients (53%) arrived within 1 hour after onset of SAH and 127 patients (78%) arrived within 3 hours. Most of the poor-grade patients were intubated before initial brain CT scan. Mean systolic blood pressure was around 170 mmHg at the time of arrival, which was controlled around 120 mmHg or less during resuscitation and angiography. A total of 117 patients had DSA, 111 of them (68%) within 3 hours, and 111 patients underwent surgery, 81 of them (85%) within 6 hours. Despite intensive resuscitation, 36 episodes of rebleeding were detected in 32 patients, 24 before and 12 after arrival. Extravasation of contrast media was seen in 6 patients during cerebral angiography. Favorable outcome (good recovery and moderate disability) was obtained in 69% of Grade IV and 24% of the Grade V patients. The risk of ultra-early rebleeding is highest for patients with poor grades. Deep sedation and strict blood pressure control followed by urgent obliteration of the ruptured aneurysm have a strong rationale to prevent rerupture and to achieve better overall outcome. (author)

  4. The prehospital phase of acute myocardial infarction in the era of thrombolysis.

    Science.gov (United States)

    Schmidt, S B; Borsch, M A

    1990-06-15

    To evaluate the factors affecting the time between symptom onset and hospital arrival in patients with acute myocardial infarction (AMI), we gave a detailed questionnaire to all who were admitted or transferred with AMI from January 1988 to February 1989. In these 126 patients (94 men, 32 women) the mean prehospital time was 5.9 +/- 11.0 hours (median 2.0, range 0.4 to 69.0). The time between symptom onset and reaching a decision that medical care should be sought was 62% of the mean prehospital time. In 100 (79%) patients, the prehospital time was less than or equal to 6 hours; of these, 61 (61%) were retrospectively judged to have been optimal candidates for lytic therapy. Stepwise multiple regression selected the following 4 variables as independent predictors of prehospital time: slow symptom progression; low income; female gender; and advanced age. All of these variables are predictive (p less than 0.03) of increased prehospital time; absence of prior AMI was of borderline additional significance (p = 0.053). Similarly, logistic regression analysis selected slow symptom progression, female gender and low income as significant (p less than or equal to 0.02) independent predictors of prehospital time greater than 6 hours. The logistic regression model incorporating these 3 variables had a sensitivity of 54%, a specificity of 95% and a positive predictive value of 72% in identifying patients with prehospital time greater than 6 hours. Thus, these data indicate it is possible to characterize patients likely to experience undue prehospital delay during AMI, which may be of importance to future public education efforts. PMID:2353644

  5. Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial

    NARCIS (Netherlands)

    D.W.J. Dippel (Diederik); E.J. van Breda (Eric); H.M.A. van Gemert (Maarten); H.B. van der Worp (Bart); R.J. Meijer (Ron); L.J. Kappelle (Jaap); P.J. Koudstaal (Peter Jan)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially w

  6. The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase, is caused by a deletion in the VRN1 gene

    International Nuclear Information System (INIS)

    The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase (mvp), was induced by nitrogen ion-beam treatment and was identified by its inability to transit from the vegetative to reproductive phase. In our previous study, we showed that WAP1 (wheat APETALA1) is a key gene in the regulatory pathway that controls phase transition from vegetative to reproductive growth in common wheat. WAP1 is an ortholog of the VRN1 gene that is responsible for vernalization insensitivity in einkorn wheat. The mvp mutation resulted from deletion of the VRN1 coding and promoter regions, demonstrating that WAP1/VRN1 is an indispensable gene for phase transition in wheat. Expression analysis of flowering-related genes in mvp plants indicated that wheat GIGANTIA (GI), CONSTANS (CO) and SUPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) genes either act upstream of or in a different pathway to WAP1/VRN1

  7. Internal tandem duplications in the Flt3-gene in human acute myeloid leukemia

    NARCIS (Netherlands)

    W.J.C. Rombouts

    2004-01-01

    textabstractIn the process of hematopoietic development errors may occur, resulting in the aber¬rant activation of (proto-)oncogenes and inactivation of tumor-suppressor genes. This aberrant gene expression may finally result in leukemia, a neoplastic disorder in which immature hematopoietic cells a

  8. The molacular mechanism of ACE gene in acute cerebro-vascullar discasc

    Institute of Scientific and Technical Information of China (English)

    Dr.QiuXiuLan; Jiaxing

    2000-01-01

    [Objective] Our research is aimed to study a possible involvement of angiotension converting enzyine (ACE) gene types and hypertension upon the molecular mechanism of clinic ACVD [Method] Using a polymerize chain reaction (PCR), a DNA fragment of intone 16 of ACE gene was studied in 203 patients with ACVD (including 87 cases of CH and 116 cases of Al) and 51 control samples [Rrsult] (l) The frequency of the ACE allele polymorphism jsn't similcantly different between ACVD, CO and Al patients. (2)There is no significant difference in the ACE gene types and ACE gene allele frequency among CH、 Al and the controls. (3) There are no significant difference between history of hypertension and the incidence of CH and Al. However, patients with hypertension and ACE DD allele shoed more significant Al incidence than those with hypertension and ACE Ⅱ allele. [Conclusion] We didn' t find any correlation between the polymorphism of the ACE gene and ACVD. Neither the history of hypertension nor polymorphism of ACE gene was a risk factor of ACVD. We didn't find a correlation between Al and hypertension with ACE gene polymorphism. Our study suggests that ACE gene polymorphism combined with hypcnension is a possible molecular mechanism underlying Al.

  9. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  10. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    Science.gov (United States)

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  11. Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure

    Institute of Scientific and Technical Information of China (English)

    Qin Jun; Huang Lan; Tian Kaixin; Yu Shiyong; Yu Yang; Long Min

    2008-01-01

    Objective: To investigate the changes of autonomic nervous system (ANS) function during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level male residents were studied in Chengdu plain and then Tibet plateau. Heart rate variability (HRV), cold pressor test (CPT), resting heart rate (HR) and blood pressure (BP) were measured at baseline (560 m altitude) and in 2 to 4 d after arriving at Tibet plateau (3 675 m altitude) to assess the ANS function. Results: Compared with baseline, on day 2 in Tibet the standard deviation of normal to normal intervals (SDNN), high-frequency (HF) power, total power (TP), root mean square of delta RR (rMSSD), percentage of delta RR>50 ms (PNN50), normalized high-frequency (Hfnu) and fractal dimension (FD) decreased significantly (SDNN, HF,TP P<0.01, rMSSD, PNNs0, Hfnu, FD P<0.05), while the normalized low-frequency (Lfnu) and LF/HF increased significantly (P<0.01). During day 3-4 in Tibet, SDNN, rMSSD, HF, TP and Hfnu tended to rebound while Lfnu and LF/HF decreased towards baseline day by day. In addition, in Tibet the increase in systolic pressure (SP) and diastolic pressure (DP) during CPT decreased significantly (P<0.01, 0.05), but resting HR increased compared with baseline (P<0.01). Conclusion: ANS modulation is generally blunted, and the relatively predominant sympathetic control is enhanced originally, then it reverts to the sea level states gradually during the initial days of acute high-altitude exposure.

  12. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    Science.gov (United States)

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  13. Comparison of acute proton, photon, and low-dose priming effects on genes associated with extracellular matrix and adhesion molecules in the lungs

    Directory of Open Access Journals (Sweden)

    Tian Jian

    2013-02-01

    Full Text Available Abstract Background Crew members on space missions inevitably are exposed to low background radiation and can receive much higher doses during solar particle events (SPE that consist primarily of protons. Ionizing radiation could cause lung pathologies. Cell adhesion molecules (CAM are believed to participate in fibrogenesis. Interactions between CAM and extracellular matrix (ECM affect epithelial repair mechanisms in the lung. However, there are very limited data on biological effects of protons on normal lung tissue. Numerous reports have shown that exposure to low-dose/low-dose-rate (LDR radiation can result in radioadaptation that renders cells more resistant to subsequent acute radiation. The goal of this study was to compare expression of genes associated with ECM and CAM, as well as critical profibrotic mediators, in mouse lungs after acute irradiation with photons and protons, and also determine whether pre-exposure to LDR γ-rays induces an adaptive effect. Results Overall, a marked difference was present in the proton vs. photon groups in gene expression. When compared to 0 Gy, more genes were affected by protons than by photons at both time points (11 vs. 6 on day 21 and 14 vs. 8 on day 56, and all genes affected by protons were upregulated. Many genes were modulated by LDR γ-rays when combined with photons or protons. Col1a1, mmp14, and mmp15 were significantly upregulated by all radiation regimens on day 21. Similarly, the change in expression of profibrotic proteins was also detected after acute and combination irradiation. Conclusion These data show that marked differences were present between acutely delivered protons and photons in modulating genes, and the effect of protons was more profound than that of photons. Pre-exposure to LDR γ-rays ‘normalized’ some genes that were modified by acute irradiation.

  14. Cells and mediators of inflammation (C-reactive protein, nitric oxide, platelets and neutrophils) in the acute and convalescent phases of uncomplicated Plasmodium vivax and Plasmodium falciparum infection.

    Science.gov (United States)

    Lima-Junior, Josué da Costa; Rodrigues-da-Silva, Rodrigo Nunes; Pereira, Virgínia Araújo; Storer, Fábio Luiz; Perce-da-Silva, Daiana de Souza; Fabrino, Daniela Leite; Santos, Fátima; Banic, Dalma Maria; Oliveira-Ferreira, Joseli de

    2012-12-01

    The haematological changes and release of soluble mediators, particularly C-reactive protein (CRP) and nitric oxide (NO), during uncomplicated malaria have not been well studied, especially in Brazilian areas in which the disease is endemic. Therefore, the present study examined these factors in acute (day 0) and convalescent phase (day 15) patients infected with Plasmodium falciparum and Plasmodium vivax malaria in the Brazilian Amazon. Haematologic parameters were measured using automated cell counting, CRP levels were measured with ELISA and NO plasma levels were measured by the Griess reaction. Our data indicate that individuals with uncomplicated P. vivax and P. falciparum infection presented similar inflammatory profiles with respect to white blood cells, with high band cell production and a considerable degree of thrombocytopaenia during the acute phase of infection. Higher CRP levels were detected in acute P. vivax infection than in acute P. falciparum infection, while higher NO was detected in patients with acute and convalescent P. falciparum infections. Although changes in these mediators cannot predict malaria infection, the haematological aspects associated with malaria infection, especially the roles of platelets and band cells, need to be investigated further.

  15. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

    Institute of Scientific and Technical Information of China (English)

    Yi Gao; Ning Mu; Xiao-Ping Xu; Yan Wang

    2005-01-01

    AIM: To establish a highly reproducible animal model of acute liver failure (ALF), for assessing theeffect of bioartificial liver support system (BALSS).METHODS: A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrieradhering hepatocytes, and a double pump, heparinized,thermostabilized, micro-capsulized activated carbonadsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals.RESULTS: Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase Ⅱ surgery, ammonia (Amm) increased to (269±37) μmol/L.After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5±0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6±1.8) nka/L, (40±5) nka/L, (55±8) μmol/L and (17.5±1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27±4) g/L and (87±9) μmol/L. After 13 h of surgery, BUN was (3.5±0.9) μmol/L. All the above values were different from those determined before surgery.Survival time of pigs averaged 13.5±1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes

  16. Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Regina Ebert

    2015-07-01

    Full Text Available The role of serum amyloid A (SAA proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs and their osteogenic offspring with a focus on senescence, differentiation and mineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP, resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1β, CXCL1, CXCL2 expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1 induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.

  17. Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells.

    Science.gov (United States)

    Ebert, Regina; Benisch, Peggy; Krug, Melanie; Zeck, Sabine; Meißner-Weigl, Jutta; Steinert, Andre; Rauner, Martina; Hofbauer, Lorenz; Jakob, Franz

    2015-07-01

    The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation and mineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1β, CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.

  18. Comparison between gene expression of conidia and germinating phase in Trichophyton rubrum

    Institute of Scientific and Technical Information of China (English)

    YANG Li; ZHANG Qian; QI YiPeng; JIN Qi; WANG LingLing; PENG JunPing; YU Lu; LIU Tao; LENG WenChuan; YANG Jian; CHEN LiHong; ZHANG WenLiang

    2007-01-01

    Trichophyton rubrum is a dominating superficial dermatophyte, whose conidial germination is correlated to pathopoiesis and a highly important developmental process. To investigate the changes of physiology, biochemistry and cytology during the germination, we selected 3364 function identified ESTs from T. rubrum cDNA library to construct cDNA microarrays, and compared the gene expression levels of conidia and germinating phase. Data analysis indicated that 335 genes were up-regulated during the germination, which mainly encoded translated, modified proteins and structural proteins.The constituents of cell wall and cell membrane were synthetized abundantly, suggesting that they are the foundation of cell morphogenesis. The ingredients of the two-component signal transduction system were up-regulated, presuming that they were important for the conidial germination. Genes of various metabolic pathways were expressed prosperously, especially the genes that participated in glycolysis and oxidative phosphorylation were up-regulated on the whole, demonstrating that in the environment with sufficient oxygen and glucose, conidia obtained energy through aerobic respiration.This paper provides important clues which are helpful to understanding the changes in gene expression, signal conduction and metabolism characteristics during T. rubrum conidial germination, and possess significant meaning to the study of other superficial dermatophytes.

  19. Comparison between gene expression of conidia and germinating phase in Trichophyton rubrum

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Trichophyton rubrum is a dominating superficial dermatophyte, whose conidial germination is corre- lated to pathopoiesis and a highly important developmental process. To investigate the changes of physiology, biochemistry and cytology during the germination, we selected 3364 function identified ESTs from T. rubrum cDNA library to construct cDNA microarrays, and compared the gene expression levels of conidia and germinating phase. Data analysis indicated that 335 genes were up-regulated during the germination, which mainly encoded translated, modified proteins and structural proteins. The constituents of cell wall and cell membrane were synthetized abundantly, suggesting that they are the foundation of cell morphogenesis. The ingredients of the two-component signal transduction sys- tem were up-regulated, presuming that they were important for the conidial germination. Genes of various metabolic pathways were expressed prosperously, especially the genes that participated in glycolysis and oxidative phosphorylation were up-regulated on the whole, demonstrating that in the environment with sufficient oxygen and glucose, conidia obtained energy through aerobic respiration. This paper provides important clues which are helpful to understanding the changes in gene expres- sion, signal conduction and metabolism characteristics during T. rubrum conidial germination, and possess significant meaning to the study of other superficial dermatophytes.

  20. Genomics-based Approach and Prognostic Stratification Significance of Gene Mutations in Intermediate-risk Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    Bian-Hong Wang; Yong-Hui Li; Li Yu

    2015-01-01

    Objective:Intermediate-risk acute myeloid leukemia (IR-AML),which accounts for a substantial number of AML cases,is highly heterogeneous.We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML.Data Sources:We conducted a systemic search from the PubMed database up to October,2014 using various search terms and their combinations including IR-AML,gene mutations,mutational analysis,prognosis,risk stratification,next generation sequencing (NGS).Study Selection:Clinical or basic research articles on NGS and the prognosis of gene mutations in IR-AML were included.Results:The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis,and some of them have been used for prognostic risk stratification.Several studies have consistently identified that some gene mutations have prognostic relevance,however,there are still many controversies for some genes because of lacking sufficient evidence.In addition,tumor cells harbor hundreds of mutated genes and multiple mutations often coexist,therefore,single mutational analysis is not sufficient to make accurate prognostic predictions.The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years.Conclusions:NGS represents a pioneering and helpful approach to prognostic risk stratification of IR-AML patients.Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.

  1. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs.

    OpenAIRE

    Nakamura, T.(International Center for Elementary Particle Physics and Department of Physics, The University of Tokyo, Tokyo, Japan); Alder, H; Y. Gu; R. Prasad; Canaani, O; Kamada, N; Gale, R P; Lange, B; Crist, W M; Nowell, P C

    1993-01-01

    Chromosome translocations involving band 11q23 are associated with human acute leukemias. These translocations fuse the ALL-1 gene, homolog of Drosophila trithorax and located at chromosome band 11q23, to genes from a variety of chromosomes. We cloned and sequenced cDNAs derived from transcripts of the AF-4 and AF-9 genes involved in the most common chromosome abnormalities, t(4:11)(q21:q23) and t(9:11)(p22:q23), respectively. Sequence analysis indicates high homology between the AF-9 gene pr...

  2. R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Pan Xin-Min

    2008-07-01

    Full Text Available Abstract Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CAn repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006. However, no significant relationship between the number of (CAn repeats of EGFR intron 1 (both alleles P = 0.911. Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.

  3. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  4. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  5. Lunar Phase Modulates Circadian Gene Expression Cycles in the Broadcast Spawning Coral Acropora millepora.

    Science.gov (United States)

    Brady, Aisling K; Willis, Bette L; Harder, Lawrence D; Vize, Peter D

    2016-04-01

    Many broadcast spawning corals in multiple reef regions release their gametes with incredible temporal precision just once per year, using the lunar cycle to set the night of spawning. Moonlight, rather than tides or other lunar-regulated processes, is thought to be the proximate factor responsible for linking the night of spawning to the phase of the Moon. We compared patterns of gene expression among colonies of the broadcast spawning coral Acropora millepora at different phases of the lunar cycle, and when they were maintained under one of three experimentally simulated lunar lighting treatments: i) lunar lighting conditions matching those on the reef, or lunar patterns mimicking either ii) constant full Moon conditions, or iii) constant new Moon conditions. Normal lunar illumination was found to shift both the level and timing of clock gene transcription cycles between new and full moons, with the peak hour of expression for a number of genes occurring earlier in the evening under a new Moon when compared to a full Moon. When the normal lunar cycle is replaced with nighttime patterns equivalent to either a full Moon or a new Moon every evening, the normal monthlong changes in the level of expression are destroyed for most genes. In combination, these results indicate that daily changes in moonlight that occur over the lunar cycle are essential for maintaining normal lunar periodicity of clock gene transcription, and this may play a role in regulating spawn timing. These data also show that low levels of light pollution may have an impact on coral biological clocks. PMID:27132135

  6. CHP2 gene expression and quantitation in Egyptian patients with acute leukemia

    OpenAIRE

    Amira Ahmed Hammam; Hisham Hasan Eissa; Mohamed Roshdy El Masry; Sarah Mahmoud

    2014-01-01

    Aim: CHP2 (calcineurin B homologous protein 2) is identified as a tumor-associated antigen highly expressed in different malignancies. It plays a critical role in cancer cell development, proliferation, motility and survival. It is suggested that the human tumor related gene CHP2 expression in leukemia primary cells and leukemia cell lines significantly increase, which may play an important role in growth process of leukemia cells. Methods: In this study, the expression of CHP2 gene was an...

  7. Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events.

    Directory of Open Access Journals (Sweden)

    Pertti Happonen

    Full Text Available BACKGROUND: The role of coffee intake as a risk factor for coronary heart disease (CHD has been debated for decades. We examined whether the relationship between coffee intake and incidence of CHD events is dependent on the metabolism of circulating catecholamines, as determined by functional polymorphism of the catechol-O-methyltransferase (COMT gene. METHODOLOGY/PRINCIPAL FINDINGS: In a cohort of 773 men who were 42 to 60 years old and free of symptomatic CHD at baseline in 1984-89, 78 participants experienced an acute coronary event during an average follow-up of 13 years. In logistic regression adjusting for age, smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma cholesterol concentration, and diabetes, the odds ratio (90% confidence interval comparing heavy coffee drinkers with the low activity COMT genotype with those with the high activity or heterozygotic genotypes was 3.2 (1.2-8.4. Urinary adrenaline excretion increased with increasing coffee intake, being over two-fold in heavy drinkers compared with nondrinkers (p = 0.008 for trend. CONCLUSIONS/SIGNIFICANCE: Heavy coffee consumption increases the incidence of acute coronary events in men with low but not high COMT activity. Further studies are required to determine to which extent circulating catecholamines mediate the relationship between coffee intake and CHD.

  8. The acute impact of polyphenols from Hibiscus sabdariffa in metabolic homeostasis: an approach combining metabolomics and gene-expression analyses.

    Science.gov (United States)

    Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Fernández-Arroyo, Salvador; Senan-Campos, Oriol; Massucci, Francesco A; Hernández-Aguilera, Anna; Sales-Pardo, Marta; Guimerà, Roger; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-09-01

    We explored the acute multifunctional effects of polyphenols from Hibiscus sabdariffa in humans to assess possible consequences on the host's health. The expected dynamic response was studied using a combination of transcriptomics and metabolomics to integrate specific functional pathways through network-based methods and to generate hypotheses established by acute metabolic effects and/or modifications in the expression of relevant genes. Data were obtained from healthy male volunteers after 3 hours of ingestion of an aqueous Hibiscus sabdariffa extract. The data were compared with data obtained prior to the ingestion, and the overall findings suggest that these particular polyphenols had a simultaneous role in mitochondrial function, energy homeostasis and protection of the cardiovascular system. These findings suggest beneficial actions in inflammation, endothelial dysfunction, and oxidation, which are interrelated mechanisms. Among other effects, the activation of the heme oxygenase-biliverdin reductase axis, the systemic inhibition of the renin-angiotensin system, the inhibition of the angiotensin-converting enzyme, and several actions mirroring those of the peroxisome proliferator-activated receptor agonists further support this notion. We also found concordant findings in the serum of the participants, which include a decrease in cortisol levels and a significant increase in the active vasodilator metabolite of bradykinin (des-Arg(9)-bradykinin). Therefore, our data support the view that polyphenols from Hibiscus sabdariffa play a regulatory role in metabolic health and in the maintenance of blood pressure, thus implying a multi-faceted impact in metabolic and cardiovascular diseases. PMID:26234931

  9. Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis.

    Directory of Open Access Journals (Sweden)

    W Conan Mustain

    Full Text Available BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT has been implicated in the pathogenesis of inflammatory bowel disease (IBD. Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF, and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.

  10. Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene

    Science.gov (United States)

    van Ingen, Gijs; Li, Jin; Goedegebure, André; Pandey, Rahul; Li, Yun Rose; March, Michael E.; Jaddoe, Vincent W. V.; Bakay, Marina; Mentch, Frank D.; Thomas, Kelly; Wei, Zhi; Chang, Xiao; Hain, Heather S.; Uitterlinden, André G.; Moll, Henriette A.; van Duijn, Cornelia M.; Rivadeneira, Fernando; Raat, Hein; Baatenburg de Jong, Robert J.; Sleiman, Patrick M.; van der Schroeff, Marc P.; Hakonarson, Hakon

    2016-01-01

    Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 × 10−09), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10−06), and further show it is an eQTL for FNDC1 (P=9.3 × 10−05). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM. PMID:27677580

  11. 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...... were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty......-two leukocyte genes were significantly regulated at at least one time point during the experimental period. By close inspection of the temporal responses the dynamic changes in mRNA abundance revealed a very rapid onset of both pro-and anti-inflammatory mediators and a substantial variation in both expression...

  12. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    International Nuclear Information System (INIS)

    Highlights: ► Development of a quantitative high throughput in situ expression profiling method. ► Application to a tissue microarray of 242 AML bone marrow samples. ► Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  13. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  14. The effect of acute dose charge particle radiation on expression of DNA repair genes in mice.

    Science.gov (United States)

    Tariq, Muhammad Akram; Soedipe, Ayodotun; Ramesh, Govindarajan; Wu, Honglu; Zhang, Ye; Shishodia, Shishir; Gridley, Daila S; Pourmand, Nader; Jejelowo, Olufisayo

    2011-03-01

    The space radiation environment consists of trapped particle radiation, solar particle radiation, and galactic cosmic radiation (GCR), in which protons are the most abundant particle type. During missions to the moon or to Mars, the constant exposure to GCR and occasional exposure to particles emitted from solar particle events (SPE) are major health concerns for astronauts. Therefore, in order to determine health risks during space missions, an understanding of cellular responses to proton exposure is of primary importance. The expression of DNA repair genes in response to ionizing radiation (X-rays and gamma rays) has been studied, but data on DNA repair in response to protons is lacking. Using qPCR analysis, we investigated changes in gene expression induced by positively charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine different DNA repair genes isolated from the testes of irradiated mice. DNA repair genes were selected on the basis of their known functions. These genes include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit, DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM (activates checkpoint signaling upon double strand breaks), MLH1 (post-replicative DNA mismatch repair), and PARP1 (base excision repair). Our results demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold, respectively), and a remarkable increase in gene expression at 2.0 Gy radiation (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes, including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up-regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were unable to detect gene expression for the

  15. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1) GeneExpression in Egyptian Patients with AcuteMyeloid Leukemia

    OpenAIRE

    Nadia El Menshawy; Doaa Shahin; Hayam Fathi Ghazi

    2014-01-01

    Objective: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1) gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic sig...

  16. Acute physiological stress down-regulates mRNA expressions of growth-related genes in coho salmon.

    Directory of Open Access Journals (Sweden)

    Toshiki Nakano

    Full Text Available Growth and development in fish are regulated to a major extent by growth-related factors, such as liver-derived insulin-like growth factor (IGF -1 in response to pituitary-secreted growth hormone (GH binding to the GH receptor (GHR. Here, we report on the changes in the expressions of gh, ghr, and igf1 genes and the circulating levels of GH and IGF-1 proteins in juvenile coho salmon (Oncorhynchus kisutch in response to handling as an acute physiological stressor. Plasma GH levels were not significantly different between stressed fish and prestressed control. Plasma IGF-1 concentrations in stressed fish 1.5 h post-stress were the same as in control fish, but levels in stressed fish decreased significantly 16 h post-stress. Real-time quantitative PCR (qPCR analysis showed that ghr mRNA levels in pituitary, liver, and muscle decreased gradually in response to the stressor. After exposure to stress, hepatic igf1 expression transiently increased, whereas levels decreased 16 h post-stress. On the other hand, the pituitary gh mRNA level did not change in response to the stressor. These observations indicate that expression of gh, ghr, and igf1 responded differently to stress. Our results show that acute physiological stress can mainly down-regulate the expressions of growth-related genes in coho salmon in vivo. This study also suggests that a relationship between the neuroendocrine stress response and growth-related factors exists in fish.

  17. A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer

    International Nuclear Information System (INIS)

    Background: Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients’ quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods: We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440 μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results: Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly (P = 0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline (P = 0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion: This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment

  18. Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes

    Directory of Open Access Journals (Sweden)

    Cannon Christopher P

    2004-06-01

    Full Text Available Abstract Background Elevated white blood cell counts (WBC in acute coronary syndromes (ACS increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP in an ACS population. Methods WBC and genotype of interleukin 6 (IL-6 G-174C and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event. Results An increased white blood cell count (WBC was associated with an increased C-reactive protein (r = 0.23, p 3 (95% CI = -0.41, 0.77, and -0.03/mm3 (95% CI = -0.55, 0.86 for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61 or IL6 (p = 0.48 genotype. Conclusions Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.

  19. The radioprotective efficacy of the rat acute-phase protein alpha2-macroglobulin on bone marrow cells

    Directory of Open Access Journals (Sweden)

    Mihailović Mirjana

    2009-01-01

    Full Text Available The rat acute phase protein α2-macroglobulin (α2M plays an important role in the restoration of disrupted homeostasis by inhibiting different types of non-specific proteases and facilitating the transport of cytokines, growth factors and hormones. Previously, we observed that administration of α2M to experimental animals prior to the infliction of life- threatening trauma in the form of scalding or total-body irradiation, significantly improved their survival rates. The aim of the present work was to evaluate the radioprotective effect on blood cells of α2M that, when administered 30 min before irradiation with 6.7 Gy (LD50/30, provides 100% survival of experimental animals where in unprotected irradiated rats the said dose results in 50% lethality. We observed that rats pretreated with α2M, after an initial decline, exhibited complete recovery of the leukocyte count due to the preservation of bone marrow cells, observed as a stable mitotic index. In untreated irradiated rats the decrease of the mitotic index reflected the significant destruction of bone marrow cells that resulted in a protracted decline in the leukocyte count. We conclude that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow.

  20. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  1. Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania

    DEFF Research Database (Denmark)

    Stavrum, Ruth; PrayGod, George; Range, Nyagosya;

    2014-01-01

    isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the 'modern' (TbD1-) Euro......-American lineage induced higher levels of α1-acid glycoprotein (β = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (β = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (β = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (β = 24.4, P = 0...... and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by 'modern' lineage isolates compared to 'ancient' lineages may suggest increased virulence among 'modern' lineage isolates....

  2. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.

    Science.gov (United States)

    Koh, Katsuyoshi; Ogawa, Chitose; Okamoto, Yasuhiro; Kudo, Kazuko; Inagaki, Jiro; Morimoto, Tsuyoshi; Mizukami, Hideya; Ecstein-Fraisse, Evelyne; Kikuta, Atsushi

    2016-08-01

    A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance. PMID:27086352

  3. The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Dulger Ahmet

    2010-09-01

    Full Text Available Abstract Backgraund Acute-phase response proteins (APRP, cytokines and hormones have been claimed to be an independent prognostic factor of malignancies, however the basis for their association with prognosis remains unexplained. We suggest that in colon malignancies, as similar to pancreatic and lung cancers, changes in APRP are associated with angiogenesis. Methods C-reactive protein (CRP, albumin, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, midkine, VEGF-A, VEGF-C, leptin, adiponectin, and ghrelin serum levels are studied in 126 colon cancer patients and 36 healthy subjects. Results We found statistically significant difference and correlations between two groups. We found significantly higher serum CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF-A, VEGF-C and leptin concentrations in patients relative to controls (p Conclusions Cachexia in patients with colon cancers is associated with changes in APRP, cytokines and hormone concentrations. These biomarkers and cachexia together have a direct relationship with accelerated angiogenesis. This may lead to a connection between the outcomes in malignancies and the biomarkers.

  4. Exacerbated Skeletal Muscle Inflammation and Calcification in the Acute Phase of Infection by Mexican Trypanosoma cruzi DTUI Strain

    Directory of Open Access Journals (Sweden)

    Andrea Vizcaíno-Castillo

    2014-01-01

    Full Text Available A murine model was used to study the histopathological aspects and cytokine expression levels in skeletal muscle provoked by the infection with Mexican TcI strains. BALB/c mice were inoculated with the virulent Querétaro strain and the nonvirulent Ninoa strain. Parasite numbers were counted in blood and skeletal muscle at different times post-infection, and real time-PCR expression levels of the cytokines IL-12, IL-4, IL-10, IFN-γ, and TNF-α were evaluated. In the acute phase of infection, a high parasitic load, both in blood and skeletal muscle, was detected. The histopathological analyses showed an exacerbated inflammation and granulomatous-like infiltrate with the Querétaro strain. Interestingly, extensive calcification areas were observed in the skeletal muscle surrounded by inflammatory infiltrates. TNF-α and IL-10 expression exhibited a significant increase at the peak of infection. In summary, Querétaro strain, a Mexican TcI strain, is virulent enough to induce high inflammation and calcification in skeletal muscle of the hind limbs, which could be related to high expression levels of TNF-α.

  5. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    Science.gov (United States)

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  6. Phase variation leads to the misidentification of a Neisseria gonorrhoeae virulence gene.

    Directory of Open Access Journals (Sweden)

    Mark T Anderson

    Full Text Available Neisseria gonorrhoeae is the causative agent of gonorrhea and an obligate pathogen of humans. The Opa proteins of these bacteria are known to mediate attachment and internalization by host cells, including neutrophils. The Opa protein repertoire of a typical N. gonorrhoeae isolate is encoded on ~11 genes distributed throughout the chromosome and is subject to stochastic changes in expression through phase variation. Together, these characteristics make Opa proteins a critical yet unpredictable aspect of any experimental investigation into the interaction of N. gonorrhoeae with host cells. The goal of this study was to identify novel virulence factors of N. gonorrhoeae by assessing the contribution of a set of uncharacterized hydrogen peroxide-induced genes to bacterial survival against neutrophil-mediated killing. To this end, a strain harboring an engineered mutation in the NGO0322 gene was identified that exhibited increased sensitivity to neutrophil-mediated killing, enhanced internalization by neutrophils, and the ability to induce high levels of neutrophil-generated reactive oxygen species. Each of these phenotypes reverted to near wild-type levels following genetic complementation of the NGO0322 mutation. However, after immunoblot analysis of Opa proteins expressed by the isogenic parent, mutant, and genetically complemented strains, it was determined that phase variation had resulted in a disparity between the Opa profiles of these strains. To determine whether Opa phase variation, rather than NGO0322 mutation, was the cause of the observed neutrophil-related phenotypes, NGO0322 function was investigated in N. gonorrhoeae strains lacking all Opa proteins or constitutively expressing the OpaD variant. In both cases, mutation of NGO0322 did not alter survival of gonococci in the presence of neutrophils. These results demonstrate the importance of controlling for the frequent and random variation in Opa protein production by N. gonorrhoeae

  7. Meta-Analysis of Cytochrome P2D6 Gene Polymorphisms and Susceptibility to Acute Leukemia

    Institute of Scientific and Technical Information of China (English)

    Ma Limin; Ruan Linhai

    2013-01-01

    Objective:To provide a more robust assessment to the effect of cytochrome P2D6 (CYP2D6) polymorphisms on the risk of acute leukemia (AL), and to evaluate the association between the two most commonly studied CYP2D6 polymorphisms (CYP2D6*3 and CYP2D6*4) and AL risk by meta-analysis. Methods:All case-control studies investigating an association between the CYP2D6*3 or CYP2D6*4 polymorphisms and AL risk were included. Either fixed-effects or random-effects models were applied to combine odds ratios (ORs) and 95%conifdence intervals (CIs) by RevMan 5.1. Q-statistic was used to evaluate the heterogeneity, and both Egger’s test and funnel plots were used to assess publication bias. Results:Six studies were included in the meta-analysis. The results we acquired were that the OR value and 95%CI of CYP2D6*4 wild type, heterozygous mutant and homozygous mutant were 0.94 (0.66-1.35), 1.04(0.74-1.45) and 1.63 (0.95-2.81), respectively with Z=0.33, 0.23 and 1.76 (P>0.05), indicating that there was no signiifcant association between CYP2D6*4 polymorphism and the risk of AL. We also performed subgroup analysis by the AL immunophenotype for those groups with heterogeneity. The results of the combined analysis of CYP2D6*4 wild type, heterozygous mutant and acute lymphoblastic leukemia (ALL) were Z=0.08, 0.08 (P>0.05), for acute myeloblastic leukemia (AML) were Z=0.17, 0.26 (P>0.05), indicating that there was no signiifcant association between CYP2D6*4 polymorphism and the development of both ALL and AML. Conclusion:CYP2D6 polymorphisms are not associated with AL risk.

  8. Gene Polymorphisms of the Macrophage Migration Inhibitory Factor and Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Rohit Makhija

    2007-05-01

    Full Text Available Acute pancreatitis is a commonly encountered intra-abdominal catastrophe. The disease course is variable and usually results in a benign outcome; however in about 20-25% patients the disease follows a more severe course with pancreatic necrosis, organ dysfunction and septicaemia [1]. The initial clinical response to pancreatitis is a systemic inflammatory response syndrome (SIRS which, if abnormally persistent develops into a worsening scenario of tissue damage and sepsis resulting in multiple organ dysfunction syndrome (MODS [2]. The primary humoral mediators of this process are the cytokines. The proinflammatory cytokines, such as interleukin-1 (IL-1, tumour necrosis factor (TNF, and interleukin-8 (IL-8, are responsible for the tissue damage as well as organ dysfunction, while the antiinflammatory factors such as interleukin-1 receptor antagonist (IL-1ra are the protective arm of the immune system [3].

  9. Adenovirus-mediated interteukin-13 gene therapy attenuates acute kidney allograft injury

    NARCIS (Netherlands)

    Sandovici, Maria; Deelmani, Leo E.; van Goor, Harry; Helfrich, Wijnand; de Zeeuw, Dick; Henning, Robert H.

    2007-01-01

    Background Kidney transplantation is possible by virtue of systemic immunosuppression, which is in turn accompanied by serious side effects. The search for novel therapeutic agents and strategies is ongoing. Here we investigate the effects of adenovirus-mediated gene therapy with interleukin (IL)-13

  10. Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.

    Science.gov (United States)

    van Miert, A S; van Duin, C T; Wensing, T

    1992-12-01

    Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r

  11. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    International Nuclear Information System (INIS)

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2–4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2–4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2–4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  12. Gender affects acute organ toxicity during radiochemotherapy for rectal cancer: Long-term results of the German CAO/ARO/AIO-94 phase III trial

    International Nuclear Information System (INIS)

    Introduction: The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome. Patients and methods: According to actual treatment analyses, 654 of 799 patients had received pre- (n = 406) or postoperative CRT (n = 248); in 145 patients postoperative CRT was not applied. Gender, age and clinicopathological parameters were correlated with CRT-associated acute toxicity and survival. Results: The 10-year survival was higher in women than in men, with 72.4% versus 65.6% for time to recurrence (p = 0.088) and 62.7% versus 58.4% for overall-survival (OS) (p = 0.066), as expected. For patients receiving CRT, women showed higher hematologic (p < 0.001) and acute organ toxicity (p < 0.001) in the entire cohort as well as in subgroup analyses according to pre- (p = 0.016) and postoperative CRT (p < 0.001). Lowest OS was seen in patients without acute toxicity (p = 0.0271). Multivariate analyses for OS showed that acute organ toxicity (p = 0.034) was beneficial while age (p < 0.001) was associated with worse OS. Discussion: Female gender is significantly associated with CRT-induced acute toxicity in rectal cancer. Acute toxicity during CRT may be associated with improved long-term outcome

  13. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  14. Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian hamsters.

    Science.gov (United States)

    Ikeno, Tomoko; Nelson, Randy J

    2015-02-01

    In the hippocampus of Siberian hamsters, dendritic length and dendritic complexity increase in the CA1 region whereas dendritic spine density decreases in the dentate gyrus region at night. However, the underlying mechanism of the diurnal rhythmicity in hippocampal neuronal remodeling is unknown. In mammals, most daily rhythms in physiology and behaviors are regulated by a network of circadian clocks. The central clock, located in the hypothalamus, controls melatonin secretion at night and melatonin modifies peripheral clocks by altering expression of circadian clock genes. In this study, we examined the effects of acute melatonin treatment on the circadian clock system as well as on morphological changes of hippocampal neurons. Male Siberian hamsters were injected with melatonin in the afternoon; 4 h later, mRNA levels of hypothalamic and hippocampal circadian clock genes and hippocampal neuron dendritic morphology were assessed. In the hypothalamus, melatonin treatment did not alter Period1 and Bmal1 expression. However, melatonin treatment increased both Period1 and Bmal1 expression in the hippocampus, suggesting that melatonin affected molecular oscillations in the hippocampus. Melatonin treatment also induced rapid remodeling of hippocampal neurons; melatonin increased apical dendritic length and dendritic complexity in the CA1 region and reduced the dendritic spine density in the dentate gyrus region. These data suggest that structural changes in hippocampal neurons are regulated by a circadian clock and that melatonin functions as a nighttime signal to coordinate the diurnal rhythm in neuronal remodeling.

  15. Detection of MYC gene rearrangements by conventional cytogenetics and fluorescent in situ hybridization in patients with acute lymphoblastic leukemia cases

    Directory of Open Access Journals (Sweden)

    Seda Eren

    2015-03-01

    Full Text Available Objective: The aim of this study is to investigate rearrangements at the region of MYC gene by conventional cytogenetics and interphase FISH methods in patients with acute lymphoblastic leukemia (ALL. Methods: The study was carried out on bone marrow specimens of 25 ALL patients who were referred to our laboratory. Fourteen children and 11 adult ALL cases were examined. Conventional cytogenetic analysis was performed using G banding technique and fluorescence in situ hybridization technique was applied using MYC breakapart probe (Cytocell. Results: Totally, in 2 of 25 cases available metaphases were not obtained. While in 9 of 23 cases were found to have normal karyotype (39.1%, numerical chromosomal abnormalities were detected in 6 cases, structural abnormalities in 4 and both numerical and structural abnormalities were found in 4 cases. In one case (4% t(8;14(q24;q32 was found as a cytogenetic aberration in which MYC gene locus involved.FISH analysis was performed successfully in all cases and MYC rearrangements were found in 3 cases (12% by FISH method. Conclusion: By comparing two techniques, it was observed that FISH method showed more sensitivity, however conventional cytogenetic techniques were also effective to reveal all changes of the chromosomes. Therefore, we concluded that it would be more efficient to useof these two techniques together.J Clin Exp Invest 2015;6 (1: 21-26

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

    OpenAIRE

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline

    2015-01-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance ...

  17. Profiling of differential gene expression in the hypothalamus of broiler-type Taiwan country chickens in response to acute heat stress.

    Science.gov (United States)

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

    2016-02-01

    Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens. PMID:26462659

  18. CSP and takeout genes modulate the switch between attraction and repulsion during behavioral phase change in the migratory locust.

    Directory of Open Access Journals (Sweden)

    Wei Guo

    Full Text Available Behavioral plasticity is the most striking trait in locust phase transition. However, the genetic basis for behavioral plasticity in locusts is largely unknown. To unravel the molecular mechanisms underlying the behavioral phase change in the migratory locust Locusta migratoria, the gene expression patterns over the time courses of solitarization and gregarization were compared by oligonucleotide microarray analysis. Data analysis revealed that several gene categories relevant to peripheral olfactory perception are strongly regulated in a total of 1,444 differentially expressed genes during both time courses. Among these candidate genes, several CSP (chemosensory protein genes and one takeout gene, LmigTO1, showed higher expression in gregarious and solitarious locusts, respectively, and displayed opposite expression trends during solitarization and gregarization. qRT-PCR experiments revealed that most CSP members and LmigTO1 exhibited antenna-rich expressions. RNA interference combined with olfactory behavioral experiments confirmed that the CSP gene family and one takeout gene, LmigTO1, are involved in the shift from repulsion to attraction between individuals during gregarization and in the reverse transition during solitarization. These findings suggest that the response to locust-emitted olfactory cues regulated by CSP and takeout genes is involved in the behavioral phase change in the migratory locust and provide a previously undescribed molecular mechanism linked to the formation of locust aggregations.

  19. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  20. Acute-phase proteins in stroke: influences of its cause (cerebral hemorrhage or infarction), of the cerebral site of infarction, and of the sex of patients.

    Science.gov (United States)

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Scu, M G

    1991-01-01

    In most of the 129 patients with a recent stroke by cerebral hemorrhage or infarction a note-worthy acute-phase response was found, as demonstrated by important quantitative alterations of blood levels of several acute-phase proteins (APP). These alterations were different in patients with cerebral hemorrhage as compared to those with cerebral infarction. The alterations due to cerebral infarction were not different according to the site of the infarction in brain, i.e. in the brain territories irrigated by the carotid artery system or by the basilar artery system. The APP alterations do not depend on the sex of patients or on the time elapsed from stroke-onset to blood collection.

  1. Correlation between neurologic defect and blood pressure regulation in acute phase of ischemic stroke caused by hypertension%高血压缺血性脑卒中神经功能缺损与急性期 血压调控的相关分析

    Institute of Scientific and Technical Information of China (English)

    刘江; 翟明; 丁里; 朱之庄

    2001-01-01

    @@Background:Various managements were employed for acute phase of ischemic stroke caused by hypertension.Regulation of hypertension in acute phase was closely associated with prognosis of ischemic stroke . Objective:To study relationship between neurologic function defect and blood pressure regulation in acute phase of ischemic stroke caused by hypertension.

  2. Chronic myelogenous leukemia in chronic phase transforming into acute leukemia under treatment with dasatinib 4 months after diagnosis.

    Science.gov (United States)

    Nakamura, Yukitsugu; Tokita, Katsuya; Nagasawa, Fusako; Takahashi, Wataru; Nakamura, Yuko; Sasaki, Ko; Ichikawa, Motoshi; Mitani, Kinuko

    2016-03-01

    We report a 64-year-old woman morphologically diagnosed with chronic myelogenous leukemia in the chronic phase. Despite having achieved a complete hematological response following treatment with dasatinib, she developed lymphoblastic crisis 4 months later. Blastic cells were in a CD45-negative and SSC-low fraction, and positive for CD10, CD19, CD34, and HLA-DR expression and rearrangement in the immunoglobulin heavy chain gene. Chemotherapy using the HyperCVAD/MA regimen led to a complete cytogenetic response, and after cord blood transplantation, she obtained a complete molecular remission. However, the crisis recurred 6 months later. Another salvage therapy using L-AdVP regimen followed by nilotinib led to a complete molecular remission. Retrospective analyses using flow cytometry and polymerase chain reaction revealed a minimal blastic crisis clone present in the initial marrow in chronic phase. This case is informative as it suggests that sudden blastic crisis may occur from an undetectable blastic clone present at initial diagnosis and that leukemic stem cells may survive cytotoxic chemotherapy that eliminates most of the blastic cells. PMID:26662559

  3. What Triggers transient AIDS in the Acute Phase of HIV Infection and chronic AIDS at the End of the Incubation Period?

    OpenAIRE

    Ivan Kramer

    2007-01-01

    Novel dynamical models are introduced demonstrating that the T helper cell (THC) density drops in the acute infection phase of HIV infection, sometimes causing transient AIDS, and at the end of the incubation period causing chronic AIDS have a common dynamical cause. The immune system's inability to produce enough uninfected THCs to replace the infected ones it is destroying causes a drop in the THC density at any stage of HIV infection. Increases in viral infectivity, probably caused by rand...

  4. Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age

    OpenAIRE

    Vigil, Carlos E; Tan, Wei; Deeb, George; Sait, Sheila; Block, AnneMarie W; Starostik, Petr; Griffiths, Elizabeth A.; Thompson, James E.; Greene, Jessica D.; Ford, Laurie A.; Wang, Eunice S.; Wetzler, Meir

    2013-01-01

    We designed a phase II study evaluating the upfront combination of clofarabine and daunorubicin in acute myeloid leukemia (AML) patients ≥60 years old. The median age of the 21 patients was 69 (range 60–85) years. Fourteen patients (67%) had unfavorable risk features. The principal toxicities were grade ≥3 infections and prolonged myelosuppression. Three (14%) deaths occurred from infectious complications. Six (28.6%) patients achieved complete remission including three (21.4%) of 14 patients...

  5. Effects of combined liver and udder biopsying on the acute phase response of dairy cows with experimentally induced E. coli mastitis

    DEFF Research Database (Denmark)

    Khatun, Momena; Sørensen, Peter; Ingvartsen, Klaus Lønne;

    2013-01-01

    A minimally invasive biopsy technique was evaluated for udder tissue collection in dairy cows with Escherichia coli mastitis. Meanwhile, the effect of taking repeated liver and udder biopsies on the systemic and local acute phase response (APR) of the dairy cows was investigated during the disease...... the systemic and local APR in dairy cows during E. coli mastitis, if the timing of biopsying and other types of sampling is planned accordingly...

  6. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    OpenAIRE

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja; Szarek, Jozef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Nicklas R. Jacobsen; Yauk, Carole L.; Wallin, Hakan; Halappanavar, Sabina; Vogel, Ulla Birgitte

    2015-01-01

    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 pla...

  7. Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis

    OpenAIRE

    Truninger, Kaspar; Köck, Josef; Wirth, Hans-Peter; Muellhaupt, Beat; Arnold, Christian; von Weizsäcker, Fritz; Seifert, Burkhardt; Ammann, Rudolf W.; Blum, Hubert E.

    2001-01-01

    Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently k...

  8. Morphological analysis and muscle-associated gene expression during different muscle growth phases of Megalobrama amblycephala.

    Science.gov (United States)

    Zhu, K C; Yu, D H; Zhao, J K; Wang, W M; Wang, H L

    2015-01-01

    Skeletal muscle growth is regulated by both positive and negative factors, such as myogenic regulatory factors (MRFs) and myostatin (MSTN), and involves both hyperplasia and hypertrophy. In the present study, morphological changes during muscle development in Megalobrama amblycephala were characterized and gene expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in juvenile [60, 90, 120, and 180 days post-hatching (dph)] and adult fish. Our results show that during muscle development, the frequency of muscle fibers with a diameter muscles, with a concomitant increase in the frequency of >30 μm fibers in red muscle and >50 μm fibers in white muscle. At 90-120 dph, the ratio of hyperplastic to hypertrophic areas in red and white muscles increased, but later decreased at 120-180 dph. The effect of hypertrophy was significantly larger than hyperplasia during these phases. qRT-PCR indicated MRF and MSTN (MSTNa and MSTNb) genes had similar expression patterns that peaked at 120 dph, with the exception of MSTNa. This new information on the molecular regulation of muscle growth and rapid growth phases will be of value to the cultivation of M. amblycephala.

  9. Mutation of NPM1 and FLT3 Genes in Acute Myeloid Leukemia and Their Association with Clinical and Immunophenotypic Features

    Directory of Open Access Journals (Sweden)

    Pradeep Singh Chauhan

    2013-01-01

    Full Text Available Background. Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML. Objective. We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children. Results. NPM1 mutation was found in 21% and FLT3 mutation in 25% of the AML patients. Thirteen (8% samples were positive for both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (25.8% versus 8.8%; P=0.02. Further, NPM1 mutation was found to be more frequent in patients above 45 years of age (P=0.02. NPM1 mutation was significantly associated with higher platelet count (P=0.05 and absence of hepatosplenomegaly (P=0.01, while FLT3/ITD mutation was associated with higher white blood count (P=0.01. Immunophenotypically, NPM1 mutation was associated with the lack of CD34 (P<0.001 and HLD-DR expression (P<0.001, while FLT3/ITD mutation was positively associated with the expression of CD7 (P=0.04. No correlation was found between NPM1 mutation and fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely associated with AML/ETO fusion gene (P=0.04. Conclusions. The results suggest that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD mutations present further insight into the molecular mechanism of leukemogenesis.

  10. Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans.

    Science.gov (United States)

    Sheldon, Ryan D; Roseguini, Bruno T; Thyfault, John P; Crist, Brett D; Laughlin, M H; Newcomer, Sean C

    2012-06-01

    The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.

  11. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria.

    Science.gov (United States)

    Ohnishi, K

    1999-02-01

    Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.

  12. Clinical Observation on Acupuncture Combined with Hyperbaric Oxygenation in Treating Patients with Cervical Spondylosis of Nerve Root Type in Acute Phase

    Institute of Scientific and Technical Information of China (English)

    Wang Jian-xiong; Zhang Jun-feng

    2014-01-01

    Objective: To observe the therapeutic efficacy of acupuncture combined with hyperbaric oxygenation for cervical spondylosis of nerve root type in acute phase. Methods: One hundred cases with cervical spondylosis of nerve root type in acute phase were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group were treated by acupuncture combined with hyperbaric oxygenation, and those in the control group only received the same acupuncture therapy as the treatment group. The therapeutic efficacy was evaluated after 2 courses of treatment. Results: In the treatment group, 27cases were cured, 9 cases showed markedly effective, and 4 cases were invalid, and the recovery rate was 67.5%, the total effective rate was 90.0%; in the control group, 18 cases were cured, 17 cases showed markedly effective, 15 cases were invalid, and the recovery rate was 36.0%, the total effective rate was 70.0%. There were statistically significant differences between two groupsin the recovery rate and the total effective rate (bothP Conclusion: Acupuncture combined with hyperbaric oxygenationhas rapid and reliable effects for cervical spondylosis of nerve root type in acute phase.

  13. Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

    Directory of Open Access Journals (Sweden)

    Localio A Russell

    2011-05-01

    Full Text Available Abstract Background Peroxiredoxin 6 (PRDX6 is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI. In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma. Methods To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma, which uncovered 80 SNPs. In silico modeling was performed using Patrocles and Transcriptional Element Search System (TESS. Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma. Results Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using in silico modeling. Chi2 analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses. Conclusions This study revealed novel SNPs within the PRDX6 gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of

  14. A retinoblastoma orthologue is a major regulator of S-phase, mitotic, and developmental gene expression in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Kimchi Strasser

    Full Text Available BACKGROUND: The retinoblastoma tumour suppressor, Rb, has two major functions. First, it represses genes whose products are required for S-phase entry and progression thus stabilizing cells in G1. Second, Rb interacts with factors that induce cell-cycle exit and terminal differentiation. Dictyostelium lacks a G1 phase in its cell cycle but it has a retinoblastoma orthologue, rblA. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis and mRNA-Seq transcriptional profiling, we show that RblA strongly represses genes whose products are involved in S phase and mitosis. Both S-phase and mitotic genes are upregulated at a single point in late G2 and again in mid-development, near the time when cell cycling is reactivated. RblA also activates a set of genes unique to slime moulds that function in terminal differentiation. CONCLUSIONS: Like its mammalian counterpart Dictyostelium, RblA plays a dual role, regulating cell-cycle progression and transcriptional events leading to terminal differentiation. In the absence of a G1 phase, however, RblA functions in late G2 controlling the expression of both S-phase and mitotic genes.

  15. Reduction of liver function delays resumption of postpartum ovarian activity and alters the synthesis of acute phase proteins in dairy cows.

    Science.gov (United States)

    Montagner, Paula; Krause, Ana Rita Tavares; Schwegler, Elizabeth; Weschenfelder, Marina Menoncin; Rabassa, Viviane Rohrig; Schneider, Augusto; Pereira, Rubens Alves; Brauner, Cássio Cassal; Del Pino, Francisco Augusto Burkert; Gonçalves, Fernanda Medeiros; Corrêa, Marcio Nunes

    2016-06-01

    The aim of this study was to evaluate the concentration of acute phase proteins, milk production, and resumption of postpartum ovarian activity of clinically healthy dairy cows in a semi-extensive system with different Liver Functionality Index (LFI) values. The animals were divided into two groups: Low LFI (LLFI: -7 to -12; n: 10) and High LFI (HLFI: -7 to -4; n: 10). Animals with LLFI had lower paraoxonase activity and lower albumin concentration in the pre- and postpartum periods (Pacute phase proteins and the first ovulation interval, and it can be used to improve the production and reproductive performance. PMID:27234541

  16. Evaluation of Sialic Acid and Acute Phase Proteins (Haptoglobin and Serum Amyloid A in Clinical and Subclinical Bovine Mastitis

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    S. Nazifi*, M. Haghkhah1, Z. Asadi, M. Ansari-Lari2, M. R. Tabandeh3, Z. Esmailnezhad and M. Aghamiri

    2011-01-01

    Full Text Available The present study was conducted to evaluate the concentrations of sialic acids (total, lipid bound and protein bound and their correlation with acute phase proteins (haptoglobin and serum amyloid A in clinical and subclinical mastitis of cattle. Thirty subclinical mastitic cows with positive California mastitis test (CMT test and no clinical signs of mastitis, 10 clinical mastitic cows and 10 healthy cows with negative CMT test and normal somatic cell count were selected. Milk and blood samples were collected after confirmation of clinical and subclinical mastitis by somatic cell count and bacterial identification. Serum haptoglobin (Hp, serum amyloid A (SAA, total sialic acid (TSA, lipid bound sialic acid (LBSA and protein bound sialic acid (PBSA were measured by validated standard methods. Haptoglobin and SAA increased significantly in both types of mastitis compared with control group (P<0.001. However, the ratio of HP/SAA was significantly different from the control group only in clinical mastitis. The results showed that TSA and LBSA were significantly different in control group compared with clinical and subclinical mastitis (P<0.001. Protein bound sialic acid did not change in subclinical mastitis in comparison with control group (P=0.86. There was positive correlation between LBSA and PBSA in clinical mastitis (r=0.72, P=0.02 whereas significant negative correlation was observed between LBSA and PBSA in subclinical mastitis (r=-0.62, P<0.001. Results also showed no correlation between Hp and SAA with each other or with any other parameters in study groups.

  17. Immune and acute phase response in pigs experimentally infected with H1N2 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof

    2012-12-01

    Acute phase proteins (APPs) and immune responses in pigs after experimental infection with H1N2 swine influenza virus (SwH1N2) were studied. Eight piglets were infected intranasally with SwH1N2. Four served as controls. Antibodies against swine influenza virus (SIV)s were measured by hemagglutination inhibition assay. The proliferation assay was used to measure influenza-specific cell-mediated response. Hematological parameters were measured on a hematology analyzer. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major APP (Pig-MAP) concentrations in serum were measured using commercial ELISAs. Antibodies against SwH1N2 in the serum of infected pigs were detected from 7 dpi. SwH1N2-specific T-cell response was observed from 5 dpi. A significant drop in lymphocyte numbers and an increase in medium-sized cell (MID) counts with no accompanying leukopenia was observed in all infected pigs from 3 to 7 dpi. In infected pigs, concentrations of CRP, Hp and SAA increased significantly when the greatest amounts of virus were shed (from 1 to 3 dpi). The level of Pig-MAP remained unchanged during study. The significant positive correlation found between maximum concentrations of SAA in serum and lung scores, makes SAA a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, but to confirm this hypothesis more studies are needed.

  18. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

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    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes

  19. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.

    Science.gov (United States)

    Kane, John M; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh

    2015-08-01

    This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P < 0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia. PMID:26075487

  20. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

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    Dragun, Anthony E., E-mail: aedrag01@louisville.edu [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Quillo, Amy R. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Riley, Elizabeth C. [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Roberts, Teresa L.; Hunter, Allison M. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Rai, Shesh N. [Department of Biostatistics and Epidemiology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Callender, Glenda G. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Jain, Dharamvir [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); McMasters, Kelly M. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Spanos, William J. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States)

    2013-03-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes.