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Sample records for acute regulatory protein-dependent

  1. E6-Associated Protein Dependent Estrogen Receptor Regulation of Protein Kinase A Regulatory Subunit R2A Expression in Neuroblastoma.

    Obeid, Jean-Pierre; Zeidan, Youssef H; Zafar, Nawal; El Hokayem, Jimmy

    2017-02-18

    E6ap is a known transcriptional coregulator for estrogen receptor alpha (Er, Erα) in the presence of estrogen. Protein kinase A (PKA) contains two regulatory subunits derived from four genes. Recent evidence demonstrates that PKA regulates E6ap activity. Data generated in our lab indicated estrogen dependent regulation of Pkar2a levels. Our project sets to investigate a possible feedback mechanism constituting of Erα and E6ap transcriptional regulation of Pkar2a expression. Western blot evaluated protein regulation correlations with E2 in mouse neuroblastoma lines. Bioinformatics detected estrogen response element (ERE) sequences. quantitative polymerase chain reaction (qPCR) validated the western blot results. ERE oligonucleotides were synthesized. Reporter gene transcriptional activity was evaluated via Luciferase assay output. Electromobility shift assay (EMSA) assessed direct binding between Erα relevant sequences. Chromatin immunoprecipitation (ChIP) and Re-ChIP were conducted in quantifying protein complex recruitment levels. Pkar2a protein expression directly correlated with E2, and four putative ERE sequences were identified. Pkar2a mRNA expression reverted to baseline with either E2 or E6ap absent. In the presence of E2, ERE-1 and ERE-4 possessed Luciferase reporter gene transcriptional capabilities. ERE-1 portrayed band shifts, representing direct binding to Erα with E2 supplementation. With E2, ERE-1 significantly enhanced Erα and E6ap recruitment levels to the Pkar2a promoter. Pkar2a is directly regulated by Erα and E6ap in the presence of estrogen stimulus. This work indicates a feedback mechanism in the interplay between PKA and E6ap, which may prove crucial for the role of both proteins in cancers and neurogenetic diseases like Angelman syndrome.

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

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

    2016-09-01

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

  3. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  4. Evaluation of Regulatory T Cells in Patients with Acute and Chronic Brucellosis

    Ganji, Ali; Mosayebi, Ghasem; Ghaznavi-Rad, Ehsanollah; khosravi, Khadije; Zarinfar, Nader

    2017-01-01

    Background: Brucellosis is one of the most common chronic diseases, with widespread distribution. In spite of cell-mediated immunity (CMI) modulated mainly via activated T-helper type 1 (Th1) cells, brucellosis can advance to chronic disease in about 10-30% of cases. Regulatory T cells (Treg cells) are involved the immune response to brucellosis; however, their role, particularly in the change from the acute to the chronic phase, have not yet been elucidated. The main hypothesis of this study was that Treg cells play critical roles in the progression of brucellosis from the acute to the chronic phase. Methods: Forty-eight unrelated subjects participated in this case-control study. The percentages of CD4+, CD25+, FoxP3+, and CD25/FoxP3+ T cells in the peripheral blood mononuclear cells (PBMCs) of acute (AB) and chronic brucellosis (CB) patients and healthy controls were determined by flow cytometry. The mean florescence intensities (MFIs) of CD4+, CD25+, and FoxP3+ T cells were also measured. Results: We found a significantly lower percentage of CD25/FoxP3+ Treg cells in CB than in the AB and control groups (p < 0.05). Also, CD4 and CD25 MFIs were significantly less in CB than in AB and controls (p < 0.05). Conclusions: We propose that the reduced number of CD25/FoxP3+ Treg cells in the CB group leads to T cell anergy and this contributes to the development of chronic infection. PMID:28367469

  5. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

    Moine, P; McIntyre, R; Schwartz, M D; Kaneko, D; Shenkar, R; Le Tulzo, Y; Moore, E E; Abraham, E

    2000-02-01

    Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the

  6. Acute HIV Seroconversion Presenting with Active Tuberculosis and Associated with High Levels of T-Regulatory Cells

    Sued, Omar; Quiroga, María Florencia; Socías, María Eugenia; Turk, Gabriela; Salomón, Horacio

    2011-01-01

    Abstract A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients. PMID:21774688

  7. Mitochondrial fusion and ERK activity regulate steroidogenic acute regulatory protein localization in mitochondria.

    Duarte, Alejandra; Castillo, Ana Fernanda; Podestá, Ernesto J; Poderoso, Cecilia

    2014-01-01

    The rate-limiting step in the biosynthesis of steroid hormones, known as the transfer of cholesterol from the outer to the inner mitochondrial membrane, is facilitated by StAR, the Steroidogenic Acute Regulatory protein. We have described that mitochondrial ERK1/2 phosphorylates StAR and that mitochondrial fusion, through the up-regulation of a fusion protein Mitofusin 2, is essential during steroidogenesis. Here, we demonstrate that mitochondrial StAR together with mitochondrial active ERK and PKA are necessary for maximal steroid production. Phosphorylation of StAR by ERK is required for the maintenance of this protein in mitochondria, observed by means of over-expression of a StAR variant lacking the ERK phosphorylation residue. Mitochondrial fusion regulates StAR levels in mitochondria after hormone stimulation. In this study, Mitofusin 2 knockdown and mitochondrial fusion inhibition in MA-10 Leydig cells diminished StAR mRNA levels and concomitantly mitochondrial StAR protein. Together our results unveil the requirement of mitochondrial fusion in the regulation of the localization and mRNA abundance of StAR. We here establish the relevance of mitochondrial phosphorylation events in the correct localization of this key protein to exert its action in specialized cells. These discoveries highlight the importance of mitochondrial fusion and ERK phosphorylation in cholesterol transport by means of directing StAR to the outer mitochondrial membrane to achieve a large number of steroid molecules per unit of StAR.

  8. Regulatory T cells-derived IL-35 promotes the growth of adult acute myeloid leukemia blasts.

    Tao, Qianshan; Pan, Ying; Wang, Yiping; Wang, Huiping; Xiong, Shudao; Li, Qing; Wang, Jia; Tao, Lili; Wang, Zhitao; Wu, Fan; Zhang, Rui; Zhai, Zhimin

    2015-11-15

    Tumor immune escape mechanism mediated by CD4+CD25+regulatory T cells (Tregs) is a key factor in the pathogenesis of acute myeloid leukemia (AML). IL-35, as a novel inhibitory cytokine, is produced by Tregs specially and regulates functions of Tregs in murine. However, IL-35 expression of Tregs in human is still disputed, and its role in AML is yet to be elucidated. In this study, we found that IL-35 was expressed highly in peripheral blood plasma of adult patients with AML and significantly correlated with the clinical stages of malignancy. Tregs-derived from adult AML patients produced IL-35 in a stimulation-dependent manner. IL-35 promoted AML blasts immune escape by expanding Tregs and inhibiting CD4+CD25-effector T cells (Teffs). Furthermore, IL-35 directly promoted the proliferation of AML blasts and reduced the apoptosis of AML blasts. Together, our study demonstrates that IL-35-derived from Tregs promotes the growth of adult AML blasts, suggesting that IL-35 has an important role in the pathogenesis of AML.

  9. Effect of acute resistance exercise and sex on human patellar tendon structural and regulatory mRNA expression

    Sullivan, B.E.; Carroll, C.C.; Jemiolo, B.;

    2009-01-01

    (6 men and 6 women). Collagen type I, collagen type III, and MMP-2 were downregulated (P 0.05) 24 h after RE. All other genes remained unchanged (P > 0.05) after RE. Women had higher resting mRNA expression (P ... = 0.08) toward lower resting expression of MMP-3 than men. All other genes were not influenced (P > 0.05) by sex. Acute RE appears to stimulate a change in collagen type I, collagen type III, and MMP-2 gene regulation in the human patellar tendon. Sex influences the structural and regulatory m...... and mechanical properties, it is uncertain what structural and regulatory components contribute to these responses. We measured the mRNA expression of tendon's main fibrillar collagens (type I and type III) and the main proteoglycans (decorin, biglycan, fibromodulin, and versican) and the regulatory enzymes MMP...

  10. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.

    Robinson, Sally; Delongeas, Jean-Luc; Donald, Elizabeth; Dreher, David; Festag, Matthias; Kervyn, Sophie; Lampo, Ann; Nahas, Kamil; Nogues, Vicente; Ockert, Deborah; Quinn, Kirsty; Old, Sally; Pickersgill, Nigel; Somers, Kev; Stark, Claudia; Stei, Peter; Waterson, Lynne; Chapman, Kathryn

    2008-04-01

    Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.

  11. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter.

    Miller, Walter L

    2007-06-01

    Cholesterol is a vital component of cellular membranes, and is the substrate for biosynthesis of steroids, oxysterols and bile acids. The mechanisms directing the intracellular trafficking of this nearly insoluble molecule have received increased attention through the discovery of the steroidogenic acute regulatory protein (StAR) and similar proteins containing StAR-related lipid transfer (START) domains. StAR can transfer cholesterol between synthetic liposomes in vitro, an activity which appears to correspond to the trans-cytoplasmic transport of cholesterol to mitochondria. However, trans-cytoplasmic cholesterol transport in vivo appears to involve the recently-described protein StarD4, which is expressed in most cells. Steroidogenic cells must also move large amounts of cholesterol from the outer mitochondrial membrane to the first steroidogenic enzyme, which lies on the matrix side of the inner membrane; this action requires StAR. Congenital lipoid adrenal hyperplasia, a rare and severe disorder of human steroidogenesis, results from mutations in StAR, providing a StAR knockout of nature that has provided key insights into its activity. Cell biology experiments show that StAR moves large amounts of cholesterol from the outer to inner mitochondrial membrane, but acts exclusively on the outer membrane. Biophysical data show that only the carboxyl-terminal alpha-helix of StAR interacts with the outer membrane. Spectroscopic data and molecular dynamics simulations show that StAR's interactions with protonated phospholipid head groups on the outer mitochondrial membrane induce a conformational change (molten globule transition) needed for StAR's activity. StAR appears to act in concert with the peripheral benzodiazepine receptor, but the precise itinerary of a cholesterol molecule entering the mitochondrion remains unclear.

  12. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI.

  13. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson; Costa, Fábio Trindade Maranhão; Oliveira, Alexandre Leite Rodrigues; Höfling, Maria Alice da Cruz; Machado, Dagmar Ruth Stach; Thomé, Rodolfo

    2015-01-01

    Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to

  14. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

  15. Expression of steroidogenic acute regulatory protein and its regulation by interferon-gamma in rat corpus luteum

    2000-01-01

    The steroidogenic acute regulatory protein (StAR) is the key regulatory protein of steroidogenesis. De novo synthesis of StAR protein is required for intramitochondrial translocation of cholesterol to the cytochrome P450 side chain cleavage enzyme which is located on the matrix side of the inner mitochondrial membrane. This is the rate-limiting step of steroid biosynthesis. Using in situ hybridization and immunohistochemistry we studied StAR expression in various stages of the corpora luteal and its regulation by interferon-gamma (IFNγ) in the adult pseudopregnant rat. The results indicated that expression of StAR in the corpora luteal was correlated with progesteron production and IFNγ was capable of inhibiting its expression.

  16. Regulatory T cell expression of CLA or α4β7 and skin or gut acute GVHD outcomes

    Engelhardt, BG; Jagasia, M; Savani, BN; Bratcher, NL; Greer, JP; Jiang, A.; Kassim, AA; Lu, P.; Schuening, F; Yoder, SM; Rock, MT; Crowe, JE

    2010-01-01

    Regulatory T cells (Tregs) are a suppressive subset of CD4+ T lymphocytes implicated in the prevention of acute GVHD (aGVHD) after allo-SCT (ASCT). To determine whether increased frequency of Tregs with a skin-homing (cutaneous lymphocyte Ag, CLA+) or a gut-homing (α4β7+) phenotype is associated with reduced risk of skin or gut aGVHD, respectively, we quantified circulating CLA+ or α4β7+ on Tregs at the time of neutrophil engraftment in 43 patients undergoing ASCT. Increased CLA+ Tregs at eng...

  17. Steroidogenic acute regulatory protein in white sturgeon (Acipenser transmontanus): cDNA cloning, sites of expression and transcript abundance in corticosteroidogenic tissue after an acute stressor.

    Kusakabe, Makoto; Zuccarelli, Micah D; Nakamura, Ikumi; Young, Graham

    2009-06-01

    The white sturgeon, Acipenser transmontanus, is a primitive bony fish that is recognized as an important emerging species for aquaculture. However, many aspects of its stress and reproductive physiology remain unclear. These processes are controlled by various steroid hormones. In order to investigate the regulation of steroidogenesis associated with acute stress in sturgeon, a cDNA-encoding steroidogenic acute regulatory protein (StAR) was isolated from white sturgeon. The putative amino acid sequence of sturgeon StAR shares high homology (over 60%) with other vertebrates. Phylogenetic analysis grouped sturgeon StAR within Actinopterygii, but it was clearly segregated from teleost StARs. RT-PCR analysis revealed that transcripts were most abundant in yellow corpuscles found throughout the kidney and weaker signals were detected in gonad and kidney. Very weak signals were also detected in brain and spleen by quantitative real-time PCR. In situ hybridization revealed that StAR is expressed in the cells of yellow corpuscles. No significant changes in StAR gene expression were detected in response to an acute handling stress. These results suggest that StAR is highly conserved throughout vertebrates, but the expression of the functional protein during the stress response may be partially regulated post-transcriptionally.

  18. Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome

    Bueno, Héctor; de Graeff, Pieter; Richard-Lordereau, Isabelle

    2016-01-01

    Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary...... researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients...

  19. Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

    Zheng-Feng Zhu

    Full Text Available OBJECTIVE: CD4(+ latency-associated peptide (LAP(+ regulatory T cells (Tregs are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS has not been explored. We designed to investigate whether circulating frequency and function of CD4(+LAP(+ Tregs are defective in ACS. METHODS: One hundred eleven ACS patients (acute myocardial infarction and unstable angina and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA and chest pain syndrome (CPS. The frequencies of circulating CD4(+LAP(+ Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP on CD4(+ T cells were determined by flow cytometry. The function of CD4(+LAP(+ Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10 and transforming growth factor-β protein (TGF-β levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs was measured by real time-polymerase chain reaction. RESULTS: We found ACS patients had a significantly lower frequency of circulating CD4(+LAP(+ Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+ T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. CONCLUSIONS: A novel regulatory T cell subset, defined as CD4(+LAP(+ T cells is defective in ACS patients.

  20. Effector and regulatory T cells in patients with acute optic neuritis

    Tsakiri, Anna; Kjærsgaard, Erik; Grigoriadis, Nikolaos;

    2012-01-01

    Optic neuritis (ON) is an autoimmune acute demyelinating disease of the optic nerve and may occur in patients with confirmed multiple sclerosis (MS) or as a clinically isolated syndrome. T lymphocytes play a central role in the pathogenesis of MS. The phenotype of different T cell subsets is usua...... is usually characterized by the expression of distinct cell surface receptors such as CD45RA, CD45RO, CCR7, CD27 and CD28. The aim of this study was to characterize the phenotype of distinct subsets of CD4 and CD8 T cells in patients with isolated ON....

  1. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

    Mirlekar, Bhalchandra; Patil, Sachin [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Bopanna, Ramanamurthy [Experimental Animal Facility, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Chattopadhyay, Samit, E-mail: samit@nccs.res.in [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India)

    2015-08-21

    T{sub reg} cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T{sub reg} cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T{sub reg} phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T{sub reg} cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T{sub reg} cells in SMAR1{sup −/−} mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T{sub reg} cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T{sub reg} physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T{sub reg} cells. • SMAR1{sup −/−} T{sub reg} cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1{sup −/−} mice. • Both Foxp3 and SMAR1 maintain T{sub reg} phenotype that controls colitis.

  2. Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia

    Melton, J.E.; Patlak, C.S.; Pettigrew, K.D.; Cserr, H.F.

    1987-04-01

    This study quantitatively evaluates the contribution of tissue Na, Cl, and K loss to brain volume regulation during acute dilutional hyponatremia (DH) and examines the mechanism of Na loss. DH was produced in pentobarbital sodium-anesthetized rats by intraperitoneal infusion of distilled water and brain water and electrolytes analyzed 30 min, 1 h, 3 h, 4 h, or 6 h later. The rate of Na and Cl loss was greatest during the first 30 min of DH. Net loss of Na and Cl was maximal after 3 h of DH. K loss was slower, achieving significance after 3 h. Electrolyte loss was sufficient to account for observed brain volume regulation after three or more hours of DH. Measurements of /sup 22/Na influx and efflux across the blood brain barrier showed that barrier permeability to Na is unchanged during DH. Analysis of results using a two-compartment model of plasma-brain exchange suggests that loss of brain Na during DH does not result solely from a shift of electrolyte across the blood-brain barrier to plasma, and thus provides indirect evidence for an additional pathway for Na loss, presumably via cerebrospinal fluid.

  3. Impairment of Circulating CD4+CD25+GARP+ Regulatory T Cells in Patients with Acute Coronary Syndrome

    Kai Meng

    2014-02-01

    Full Text Available Background: Atherosclerosis (AS is an inflammatory and immune disease. Regulatory T cells (Tregs suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. Methods: To assess whether GARP+ Tregs are downregulated in patients with acute coronary syndrome (ACS, we examined CD4+CD25+GARP+ T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. Results: Patients with ACS demonstrated a significant decrease in circulating CD4+CD25+GARP+ Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA or normal coronary artery (NCA. Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs from patients with ACS exhibited a decrease in CD4+CD25+GARP+ Tregs. Conclusions: These fnding indicate that circulating CD4+CD25+GARP+ Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS.

  4. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.

  5. A protein-dependent side-chain rotamer library.

    Bhuyan, M.S.

    2011-12-14

    Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

  6. The expression of tumor necrosis factor-alpha, its receptors and steroidogenic acute regulatory protein during corpus luteum regression

    Arfuso Frank

    2008-11-01

    Full Text Available Abstract Background Corpus luteum (CL regression is known to occur as two parts; functional regression when steroidogenesis declines and structural regression when apoptosis is induced. Previous studies suggest this process occurs by the production of luteolytic factors, such as tumour necrosis factor-alpha (TNF-alpha. Methods We examined TNF-alpha, TNF-alpha receptors (TNFR1 and 2 and steroidogenic acute regulatory (StAR protein expression during CL regression in albino Wistar rats. CL from Days 16 and 22 of pregnancy and Day 3 post-partum were examined, in addition CL from Day 16 of pregnancy were cultured in vitro to induce apoptosis. mRNA was quantitated by kinetic RT-PCR and protein expression examined by immunohistochemistry and Western blot analyses. Results TNF-alpha mRNA increased on Day 3 post-partum. TNFR were immunolocalized to luteal cells, and an increase in TNFR2 mRNA observed on Day 3 post-partum whilst no change was detected in TNFR1 mRNA relative to Day 16. StAR protein decreased on Day 3 post-partum and following trophic withdrawal but no change was observed following exogenous TNF-alpha treatment. StAR mRNA decreased on Day 3 post-partum; however, it increased following trophic withdrawal and TNF-alpha treatment in vitro. Conclusion These results demonstrate the existence of TNFR1 and TNFR2 in rat CL and suggest the involvement of TNF-alpha in rat CL regression following parturition. Furthermore, decreased StAR expression over the same time points was consistent with the functional regression of the CL.

  7. Stimulatory effects of propylthiouracil on pregnenolone production through upregulation of steroidogenic acute regulatory protein expression in rat granulosa cells.

    Chen, Mei-Chih; Wang, Shyi-Wu; Kan, Shu-Fen; Tsai, Shiow-Chwen; Wu, Yu-Ching; Wang, Paulus S

    2010-12-01

    Propylthiouracil (PTU) is a common and effective clinical medicine for the treatment of hyperthyroidism. Our previous study demonstrated that short-term treatment with PTU inhibits progesterone production in rat granulosa cells. However, our present results indicate that a 16-h treatment with PTU was able to stimulate pregnenolone production in rat granulosa cells, although progesterone production was diminished by PTU through inhibition of 3β-hydroxysteroid dehydrogenase. Notably, we found that PTU treatment enhanced the conversion of cholesterol into pregnenolone, whereas the protein level of the cytochrome P450 side-chain cleavage enzyme (P450scc, which is the enzyme responding to this conversion) was not affected. Interestingly, the levels of steroidogenic acute regulatory protein (StAR) in both total cell lysate and the mitochondrial fraction were significantly increased by PTU treatment. Furthermore, the binding of steroidogenic factor-1 (SF-1) to the StAR promoter region was also enhanced by PTU treatment, which suggests that PTU could upregulate StAR gene expression. In addition to SF-1 regulation, we found that mitogen-activated protein (MAP) kinase kinase activation is an important regulator of PTU-stimulated StAR protein expression, based on the effects of the MEK inhibitor PD98059. In conclusion, these results indicate that PTU plays opposite roles in the production of progesterone and its precursor, pregnenolone. The regulation of negative feedback on speeding the cholesterol transportation and pregnenolone conversion after a 16-h PTU treatment may be the mechanism explaining PTU's inhibition of progesterone production in rat granulosa cells.

  8. Alterations of intestinal immune function and regulatory effects of L-arginine in experimental severe acute pancreatitis rats

    Shi-Feng Qiao; Tian-Jing Lü; Jia-Bang Sun; Fei Li

    2005-01-01

    AIM: To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis(SAP) and the regulatory effect of L-arginine.METHODS: Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3+, CD4+,CD8+ T lymphocytes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A (SIgA) in cecum feces was examined by radioimmunoassay.RESULTS: Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3+ and CD4+ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly,CD4+/CD8+ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3+ and CD4+ T lymphocyte percentage in the end of intestinal mucosal lamina propria,an increased ratio of CD4+/CD8+ and a higher SIgA concentration in cecum feces.CONCLUSION: Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.

  9. No relationship between most polymorphisms of steroidogenic acute regulatory (StAR gene with polycystic ovarian syndrome

    Azadeh-Sadat Nazouri

    2015-12-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is one of the most common endocrine women’s disorders in reproductive age. Hyperandrogenism has a critical role in the etiology of PCOS and it can cause fault in Steroidogenesis process. During steroidogenesis, steroidogenic acute regulatory protein (StAR seems to increase the delivery of cholesterol through mitochondrial membrane. Therefore, polymorphisms of StAR might effect on this protein and play a role in the etiology of PCOS. Objective: The aim of this study was to investigate the association between StAR SNPs with PCOS. Thus, seven polymorphisms in this gene: rs104894086, rs104894089, rs104894090, rs137852689, rs10489487, rs104894085 were detected. Materials and Methods: In this case control study, 45 PCOS women, 40 male factor/unexplained infertile women, and 40 fertile women as two control groups were participated from 2008-2012. Polymorphisms were detected using restriction fragment length polymorphism (PCR-RFLP method. Results: Heterozygote genotyping for rs137852689 SNP (amino acid 218 C > T was only seen in seven PCOS patients, one in normal ovulatory women, and five in male factor/unexplained infertile women (15.5%, 2.5%, 12.5%, respectively (p= 0.12. While, it has shown no association between other SNPS with PCOs. Conclusion: The RFLP results for seven chosen SNPs, which located in exon 5 and 7 showed normal status in three groups, it means no heterozygous or homozygous forms of selected SNPs were observed. So, it seems evaluation of the active amino acid sites should be investigated and also the study population should be increased.

  10. Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

    Christa E Flück

    Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  11. Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

    Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD.

  12. Detection of hCG Responsive Expression of the Steroidogenic Acute Regulatory Protein in Mouse Leydig Cells

    Manna Pulak R.

    2004-01-01

    Full Text Available The steroidogenic acute regulatory (StAR protein, a novel mitochondrial protein, is involved in the regulation of steroid hormone biosynthesis through its mediation of the intramitochondrial transport of the steroid substrate, cholesterol, to the cytochrome P450 cholesterol side chain cleavage (P450scc enzyme. The expression of StAR protein is regulated by cAMP-dependent signaling in steroidogenic cells. During the course of our studies in mouse Leydig cells, we employ several methods for studying the regulation of StAR protein expression by human chorionic gonadotropin (hCG. A sensitive quantitative reverse transcription and polymerase chain reaction (RT-PCR was utilized for determining StAR mRNA expression. Stimulation of mLTC-1 mouse Leydig tumor cells with hCG resulted in the coordinate regulation of StAR mRNA expression and progesterone accumulation in a time-response manner. The validity and accuracy of quantitative RT-PCR results in mLTC-1 cells were verified by a competitive PCR approach and were further confirmed in primary cultures of isolated mouse Leydig cells. Immunoblotting studies demonstrated an increase in the levels of the StAR protein in a concentration dependent manner following hCG stimulation in mLTC-1 cells. Northern hybridization analysis revealed three StAR transcripts, all of which were of sufficient size to encode functional StAR protein, and which were coordinately expressed in response to hCG. Collectively, the experimental approaches utilized in the present investigation allow for the demonstration and characterization of hCG mediated regulation of StAR mRNA and StAR protein expression in mouse Leydig cells.

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

    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.

  14. The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with acute allograft rejection in liver transplantation.

    Wang, Ying; Zhang, Min; Liu, Zhen-Wen; Ren, Wei-Guo; Shi, Yan-Chao; Sun, Yan-Ling; Wang, Hong-Bo; Jin, Lei; Wang, Fu-Sheng; Shi, Ming

    2014-01-01

    CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR) (n = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI) after liver transplantation. In addition, the percentages of CTLA-4(+), HLA-DR(+), Ki67(+), and IL-10(+) Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.

  15. Acute release of tissue-type plasminogen activator (t-PA) from the endothelium ; regulatory mechanisms and therapeutic target

    Schrauwen, Y.; Vries, R.E.M. de; Kooistra, T.; Emeis, J.J.

    1994-01-01

    The acute release of t-PA was studied in vitro in human endothelial cells from different origin. It proved possible to enhance the amounts of t-PA which can be released by increasing t-PA synthesis, both in vitro, and in vivo in rats. These data suggest the feasibility to induce and (or) enhance acu

  16. Loss of regulatory T cell function on anti-inflammation is correlated with increased risk of acute kidney injury development in patients with primary glomerulonephritis.

    Dong, Qin; Cai, Chen; Gao, Feng; Xu, Ziqian; Fang, Yuan; Wang, Lijie; Cui, Jie

    2015-01-01

    Inflammation is believed to play a major role in the pathophysiology of acute kidney injury (AKI). The injury induces the generation of inflammatory mediators like cytokines and chemokines by tubular and endothelial cells which contribute to the recruiting of leukocytes into the kidneys. Early AKI risk evaluation is limited to demographic characteristics and past clinical histories, and no specific treatment is available. To better identify patients at risk of developing AKI, and devise more targeted treatment and prevention regimen, we tracked 158 primary glomerulonephritis patients for their occurrence of AKI, and analyzed the characteristics of their adaptive immune system. We found that in patients that later developed AKI, peripheral blood T cell composition is shifted toward IFN-g-producing Th1-like cells. While the composition of CD4(+)CD25(+) T cells were similar between patients that later developed AKI and patients without AKI development, in patients that later developed AKI, their CD4(+)CD25(+) T cells secreted less regulatory cytokine IL-10, and was unable to suppress proinflammatory cytokine production by CD4(+) T cells, while in patients without AKI development, CD4(+)CD25(+) T cells were able to suppress CD4(+) T cell-mediated IFN-g and IL-17 expression under stimulation, partially through IL-10 secretion. Collectively, we identified a defect in CD4(+)CD25(+) T cell regulatory function in patients at risk of developing AKI.

  17. Homing in on Acute Graft vs. Host Disease: Tissue-Specific T Regulatory and Th17 Cells

    Engelhardt, Brian G.; Crowe, James E.

    2010-01-01

    Acute graft vs. host disease (aGVHD) is a major limitation of hematopoietic stem cell transplantation (HSCT), and it causes significant morbidity and mortality for this patient population. This immune-mediated injury occurs unpredictably and is caused by donor-derived T cells reacting to recipient alloantigens. Although donor Th1 cells play a critical role in aGVHD generation, numerous arms of both the innate and the adaptive immune systems along with determinants of lymphocyte trafficking ar...

  18. Expression of steroidogenic acute regulatory protein (StAR) in male American bullfrog (Rana catesbeiana) and preliminary evaluation of the response to TNT.

    Paden, Norka E; Carr, James A; Kendall, Ronald J; Wages, Mike; Smith, Ernest E

    2010-06-01

    We examined the expression of steroidogenic acute regulatory (StAR) protein mRNA in the American bullfrog (Rana catesbeiana). Primers and probes were designed to obtain a partial sequence of bullfrog StAR cDNA consisting of 349 base pairs. Quantitative PCR analysis of StAR mRNA equivalents was performed in tissues of juvenile and adult bullfrogs. In this study 18S mRNA was used as an internal standard. There were no differences in the expression of 18S RNA among tissues or between age groups. In juvenile males, the rank order for the constitutive levels of StAR was testes>skin>brain>kidneys. In adult males, StAR mRNA equivalent was greatest in testes, followed by kidneys, brain, and skin. In addition, stimulation and induction of testicular StAR by human chorionic gonadotropin significantly increased expression of StAR at 2, 4, and 6h after injection. Preliminary evaluation of 2, 4, 6-trinitrotoluene (TNT) revealed that acute exposure is associated with reduction of StAR mRNA expression. The information provided in this study will be useful for future research on StAR gene expression in amphibian reproductive biology and the development of reproductive biomarkers.

  19. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  20. Comparative analysis of acute and chronic corticosteroid pharmacogenomic effects in rat liver: Transcriptional dynamics and regulatory structures

    DuBois Debra C

    2010-10-01

    Full Text Available Abstract Background Comprehensively understanding corticosteroid pharmacogenomic effects is an essential step towards an insight into the underlying molecular mechanisms for both beneficial and detrimental clinical effects. Nevertheless, even in a single tissue different methods of corticosteroid administration can induce different patterns of expression and regulatory control structures. Therefore, rich in vivo datasets of pharmacological time-series with two dosing regimens sampled from rat liver are examined for temporal patterns of changes in gene expression and their regulatory commonalities. Results The study addresses two issues, including (1 identifying significant transcriptional modules coupled with dynamic expression patterns and (2 predicting relevant common transcriptional controls to better understand the underlying mechanisms of corticosteroid adverse effects. Following the orientation of meta-analysis, an extended computational approach that explores the concept of agreement matrix from consensus clustering has been proposed with the aims of identifying gene clusters that share common expression patterns across multiple dosing regimens as well as handling challenges in the analysis of microarray data from heterogeneous sources, e.g. different platforms and time-grids in this study. Six significant transcriptional modules coupled with typical patterns of expression have been identified. Functional analysis reveals that virtually all enriched functions (gene ontologies, pathways in these modules are shown to be related to metabolic processes, implying the importance of these modules in adverse effects under the administration of corticosteroids. Relevant putative transcriptional regulators (e.g. RXRF, FKHD, SP1F are also predicted to provide another source of information towards better understanding the complexities of expression patterns and the underlying regulatory mechanisms of those modules. Conclusions We have proposed a

  1. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  2. Human chorionic gonadotropin (hCG) regulates the expression of Steroidogenic acute regulatory protein (STAR)via the ERK1/2 pathway

    WANG Xianzhong; SUN Yan; WU Jianyun; PAN Hongmei; ZHANG Jiahua

    2007-01-01

    It has previously been shown that Human Chorionic Gonadotropin (hCG) can stimulate steroidogenesis in Leydig cells.In the present study,the mechanisms of hCGstimulated steroidogenesis in Leydig cells of immaturated pigs were investigated.It was found that both hCG and 8Br-cAMP could enhance the expression level of both the Steroidogenic acute regulatory protein (STAR) and mRNA,and increase the activity of extracellular signal-regulated kinasel/2 (ERK1/2) significantly depending on stimulating time.However,the effect of 8-Br-cAMP was more significant than that of hCG.While appending the inhibitor of Protein Kinase A (PKA) to Leydig cells in culture,the expression level of StAR protein,mRNA and the activity of ERK1/2 began to drop significantly,but the level of StAR mRNA could still be detectable.While appending the inhibitor of MAPK (PD98059),the expression level of StAR protein and mRNA declined significantly.These results infer that at the beginning of hCG stimulation,hCG increases the level of StAR protein by cAMP-PKA.With prolonged stimulating time,hCG increases the level of StAR protein through cAMP-PKA-ERK1/2.

  3. Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells.

    Hashimoto, Akari; Sato, Tsutomu; Iyama, Satoshi; Yoshida, Masahiro; Ibata, Soushi; Tatekoshi, Ayumi; Kamihara, Yusuke; Horiguchi, Hiroto; Murase, Kazuyuki; Kawano, Yutaka; Takada, Kohichi; Miyanishi, Koji; Kobune, Masayoshi; Ichimiya, Shingo; Kato, Junji

    2016-01-01

    Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells.

  4. Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs in patients with acute-on-chronic liver failure (ACLF

    Yang Jiezuan

    2012-09-01

    Full Text Available Abstract Background CD4+CD25+ regulatory T cells (Tregs play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF. The repertoire of TCR beta chain variable (TCRBV regions of peripheral Tregs in ACLF patients is not well understood. Methods Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS. The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak. Results CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs (P P +CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families. Conclusions The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.

  5. Quercetin and vitamin E attenuate Bonny Light crude oil-induced alterations in testicular apoptosis, stress proteins and steroidogenic acute regulatory protein in Wistar rats.

    Ebokaiwe, Azubuike P; Mathur, Premendu P; Farombi, Ebenezer O

    2016-10-01

    Studies have shown the reproductive effects of Bonny Light crude oil (BLCO) via the mechanism of oxidative stress and testicular apoptosis. We investigated the protective role of quercetin and vitamin E on BLCO-induced testicular apoptosis. Experimental rats were divided into four groups of four each. Animals were orally administered 2 ml/kg corn oil (control: group 1), BLCO-800 mg/kg body weight + 10 mg/kg quercetin (group 2), BLCO-800 mg/kg body weight + 50 mg/kg vitamin E (group 3) and BLCO-800 mg/kg body weight only (group 4) for 7 d. Protein levels of caspase 3, FasL, NF-kB, steroidogenic acute regulatory protein and stress response proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunofluorescence staining was used to quantify the expression of caspase 3, FasL and NF-kB. Apoptosis was quantified by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptosis-related proteins by 50% and above after 7 d following BLCO exposure and a concomitant increase in expression of caspase 3, FasL and NF-kB expression by immunofluorescence staining. Apoptosis showed a significant increase in TUNEL positive cells. Co-administration with quercetin or vitamin E reversed BLCO-induced apoptosis and levels of stress protein, relative to control. These findings suggest that quercetin and vitamin E may confer protection against BLCO-induced testicular oxidative stress-related apoptosis.

  6. Mechanisms of action of hormone-sensitive lipase in mouse Leydig cells: its role in the regulation of the steroidogenic acute regulatory protein.

    Manna, Pulak R; Cohen-Tannoudji, Joëlle; Counis, Raymond; Garner, Charles W; Huhtaniemi, Ilpo; Kraemer, Fredric B; Stocco, Douglas M

    2013-03-22

    Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of cholesteryl esters in steroidogenic tissues and, thus, facilitates cholesterol availability for steroidogenesis. The steroidogenic acute regulatory protein (StAR) controls the rate-limiting step in steroid biosynthesis. However, the modes of action of HSL in the regulation of StAR expression remain obscure. We demonstrate in MA-10 mouse Leydig cells that activation of the protein kinase A (PKA) pathway, by a cAMP analog Bt2cAMP, enhanced expression of HSL and its phosphorylation (P) at Ser-660 and Ser-563, but not at Ser-565, concomitant with increased HSL activity. Phosphorylation and activation of HSL coincided with increases in StAR, P-StAR (Ser-194), and progesterone levels. Inhibition of HSL activity by CAY10499 effectively suppressed Bt2cAMP-induced StAR expression and progesterone synthesis. Targeted silencing of endogenous HSL, with siRNAs, resulted in increased cholesteryl ester levels and decreased cholesterol content in MA-10 cells. Depletion of HSL affected lipoprotein-derived cellular cholesterol influx, diminished the supply of cholesterol to the mitochondria, and resulted in the repression of StAR and P-StAR levels. Cells overexpressing HSL increased the efficacy of liver X receptor (LXR) ligands on StAR expression and steroid synthesis, suggesting HSL-mediated steroidogenesis entails enhanced oxysterol production. Conversely, cells deficient in LXRs exhibited decreased HSL responsiveness. Furthermore, an increase in HSL was correlated with the LXR target genes, steroid receptor element-binding protein 1c and ATP binding cassette transporter A1, demonstrating HSL-dependent regulation of steroidogenesis predominantly involves LXR signaling. LXRs interact/cooperate with RXRs and result in the activation of StAR gene transcription. These findings provide novel insight and demonstrate the molecular events by which HSL acts to drive cAMP/PKA-mediated regulation of StAR expression and

  7. High-yield soluble expression, purification and characterization of human steroidogenic acute regulatory protein (StAR) fused to a cleavable Maltose-Binding Protein (MBP).

    Sluchanko, Nikolai N; Tugaeva, Kristina V; Faletrov, Yaroslav V; Levitsky, Dmitrii I

    2016-03-01

    Steroidogenic acute regulatory protein (StAR) is responsible for the rapid delivery of cholesterol to mitochondria where the lipid serves as a source for steroid hormones biosynthesis in adrenals and gonads. Despite many successful investigations, current understanding of the mechanism of StAR action is far from being completely clear. StAR was mostly obtained using denaturation/renaturation or in minor quantities in a soluble form at decreased temperatures that, presumably, limited the possibilities for its consequent detailed exploration. In our hands, existing StAR expression constructs could be bacterially expressed almost exclusively as insoluble forms, even upon decreased expression temperatures and in specific strains of Escherichia coli, and isolated protein tended to aggregate and was difficult to handle. To maximize the yield of soluble protein, optimized StAR sequence encompassing functional domain STARD1 (residues 66-285) was fused to the C-terminus of His-tagged Maltose-Binding Protein (MBP) with the possibility to cleave off the whole tag by 3C protease. The developed protocol of expression and purification comprising of a combination of subtractive immobilized metal affinity chromatography (IMAC) and size-exclusion chromatography allowed us to obtain up to 25 mg/1 L culture of completely soluble StAR protein, which was (i) homogenous according to SDS-PAGE, (ii) gave a single symmetrical peak on a gel-filtration, (iii) showed the characteristic CD spectrum and (iv) pH-dependent ability to bind a fluorescently-labeled cholesterol analogue. We conclude that our strategy provides fully soluble and native StAR protein which in future could be efficiently used for biotechnology and drug discovery aimed at modulation of steroids production.

  8. Acute Exacerbations of Chronic Hepatitis B Are Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments

    Sun-Lung Tsai

    2007-11-01

    Full Text Available Background and Aims: Acute exacerbations (AEs of perinatally-acquired chronic hepatitis B (CHB are accompanied by increased T cell responses to hepatitis B core and e antigens (HBcAg & HBeAg. Naturally-arising forkhead transcription factor Foxp3 (forkhead box p3-expressing CD4+CD25+ regulatory T (Treg cells are thought to be important in the control of infectious diseases. This study aimed to investigate whether HBcAg-specific Treg cells play a role in modulating spontaneous AEs and in influencing the outcome of anti-hepatitis B virus (HBV treatments.Methods: The SYFPEITHI scoring system was employed to predict epitope peptides on HBcAg overlapping with HBeAg for the construction of peptide-HLA class II tetramers to measure HBcAg-specific Treg cell frequencies (Treg f . Results: HBcAg-specific Treg f declined significantly in association with increased HBcAg-specific cytotoxic T lymphocyte frequencies during spontaneous AEs without treatment. Vigorous in vitro expansion of CD4+CD25+ Treg cells from CHB patients responding to HBcAg and/or its peptides plus interleukin-2 (IL-2 was consistently detected. Depletion of Treg cells from peripheral blood mononuclear cells enhanced proliferation to HBcAg. In contrast, patients with AEs who received anti-HBV treatments with oral nucleoside analogues or interferon-alpha injection revealed that more post-treatment increase of HBcAg-specific Treg f correlated with a higher sustained remission rate to the therapy.Conclusions: These data indicate that HBcAg-specific Treg cells from perinatally-acquired CHB patients are proliferative to HBcAg and its peptides and exhibit suppressor activity. They play a crucial role in modulating spontaneous AEs and in successful anti-HBV treatments.

  9. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  10. Regulatory agencies and regulatory risk

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  11. The number of regulatory T cells in transbronchial lung allograft biopsies is related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of acute cellular rejection

    Krustrup, Dorrit; Madsen, Caroline B; Iversen, Martin;

    2013-01-01

    The transcription factor Forkhead Box P3 (FoxP3) is a marker of regulatory T cells (Tregs) - a subset of T cells known to suppress a wide range of immune responses. These cells are considered to be pivotal for the induction of tolerance to donor antigens in human allografts. We aimed to correlate...... the number of lymphocytes expressing FoxP3 in transbronchial biopsies from lung allografts with the FoxP3 expression in bronchoalveolar lavage fluid (BALF). In addition, we aimed to correlate the number of FoxP3+ cells in transbronchial biopsies with the degree of acute cellular rejection in lung allografts....

  12. Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory statesthe examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration.

    Richards, Anna; Kavanagh, David; Atkinson, John P

    2007-01-01

    In this chapter, we examine the role of complement regulatory activity in atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). These diseases are representative of two distinct types of complement-mediated injury, one being acute and self-limited, the other reflecting accumulation of chronic damage. Neither condition was previously thought to have a pathologic relationship to the immune system. However, alterations in complement regulatory protein genes have now been identified as major predisposing factors for the development of both diseases. In aHUS, heterozygous mutations leading to haploinsufficiency and function-altering polymorphisms in complement regulators have been identified, while in AMD, polymorphic haplotypes in complement genes are associated with development of disease. The basic premise is that a loss of function in a plasma or membrane inhibitor of the alternative complement pathway allows for excessive activation of complement on the endothelium of the kidney in aHUS and on retinal debris in AMD. These associations have much to teach us about the host's innate immune response to acute injury and to chronic debris deposition. We all experience cellular injury and, if we live long enough, will deposit debris in blood vessel walls (atherosclerosis leading to heart attacks and strokes), the brain (amyloid proteins leading to Alzheimer's disease), and retina (lipofuscin pigments leading to AMD). These are three common causes of morbidity and mortality in the developed world. The clinical, genetic, and immunopathologic understandings derived from the two examples of aHUS and AMD may illustrate what to anticipate in related conditions. They highlight how a powerful recognition and effector system, the alternative complement pathway, reacts to altered self. A response to acute injury or chronic debris accumulation must be appropriately balanced. In either case, too much activation or too little regulation promotes

  13. Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes

    Krustrup, Dorrit; Iversen, Martin; Martinussen, Torben;

    2014-01-01

    scored for acute rejection according to the ISHLT criteria (A0-A4) and immunohistochemically stained with antibodies against FoxP3. Results: There was a tendency for a decrease in the number of Tregs/mm2 with time. However, the previous levels of Tregs/mm2 did not have any significant effect on future...

  14. HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease

    Li, Jun; Heinrichs, Jessica; Haarberg, Kelley; Semple, Kenrick; Veerapathran, Anandharaman; Liu, Chen; Anasetti, Claudio; Yu, Xue-Zhong

    2015-01-01

    Naturally derived regulatory T cells (nTregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of nTregs has been severely hampered by their scarce availability and non-selectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in pre-clinical models of bone marrow transplantation (BM...

  15. CXCR3 May Help Regulate the Inflammatory Response in Acute Lung Injury via a Pathway Modulated by IL-10 Secreted by CD8 + CD122+ Regulatory T Cells.

    Nie, Li; Wu, Wei; Lu, Zhibing; Zhu, Gangyan; Liu, Juan

    2016-04-01

    The aim of this study is to investigate the role of CXCR3 and IL-10 in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced by LPS injection (10 mg/kg) via the tail vein in C57BL/6 mice. Mice were sacrificed after 2 or 12 h to examine the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and histopathologic assessments. At 12 h after LPS injection, mice exhibited more severe lung infiltration by CD8+ T cell and less infiltration by CD8+CD122+ regulatory T cells than at 2 h after LPS challenge or in the control (mice not exposed to LPS). At 12 h, IFN-γ, CXCR3, and CXCL10 were significantly higher in the lungs. IL-10 in the lungs was significantly lower. CXCR3 may help to recruit CD8+ T cells and promotes IFN-γ and CXCL10 release. Such effects could be inhibited by IL-10 secreted by CD8+CD122+ regulatory T cells.

  16. Influence of trial design, heterogeneity and regulatory environment on the results of clinical trials: An appraisal in the context of recent trials on acute stroke intervention

    P R Srijithesh

    2014-01-01

    Full Text Available The outcome of randomized controlled trials can vary depending on the eligibility criteria of the patients entering into the trial, as well as the heterogeneity of the eligible population and/or the interventions. If the subject population and/or interventions are heterogeneous, the final outcome of the trial depends on the degree of concordance of effects of the subgroups of interventions on the subgroups of the subject population. The considerations that go into the calculation of sample size and determination of the study stopping rules also would affect the nature of the outcome of the study. In this paper we try to examine these phenomena with respect to the recent trials on endovascular therapy in acute ischemic stroke.

  17. Relationship between changes in mRNAs of the genes encoding steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage in head kidney and plasma levels of cortisol in response to different kinds of acute stress in the rainbow trout (Oncorhynchus mykiss).

    Geslin, Malika; Auperin, Benoit

    2004-01-01

    In this study, the expression of several genes involved in cortisol synthesis in head kidneys, the site of cortisol production, and in the rainbow trout (Oncorhynchus mykiss) was examined in response to two different acute stressors and an acute ACTH treatment. mRNAs levels of the "steroidogenic acute regulatory" (StAR) sterol transport protein, which transports cholesterol to the inner mitochondrial membrane as well as cytochrome P450 cholesterol side chain cleavage (P450(SCC)) were determined in head kidney (containing the interrenal tissue). In one experiment, we also quantified 3-beta-hydroxysteroid dehydrogenase (3B-HSD) and cytochrome P450(11beta) (11B-H) mRNAs. The presence of these four transcripts in the head kidney was confirmed by Northern blot analysis. For each stress condition, mRNA levels were quantified by quantitative or real-time RT-PCR. The results of these two methods were highly correlated. An acute stress induced by capture, short confinement (2min), and anesthesia (3min) resulted in significant elevation of plasma cortisol (30-fold higher than controls) and an increase in levels of StAR and P450(SCC) mRNAs 3h post-stress. When fish were submitted to an acute stress caused by 5min of chase with a net in a tank, plasma cortisol reached a peak within 1h, but after 3h, levels were only 5-fold higher in stressed trout than in controls and no variations in the expression of StAR, P450(SCC), 3B-HSD, and 11B-H were observed whatever the time post-stress. One hour after acute ACTH stimulation (5IU/kg), plasma cortisol level was 4-fold higher than in control trout and no changes in StAR and P450(SCC) mRNAs levels were detected. The data suggest that the high levels of cortisol after stress need an activation of genes involved in cortisol synthesis, but lower levels do not. Futhermore, under these three test conditions, we always found a strong positive correlation between mRNA levels of StAR and P450(SCC), in contrast to what has been described in

  18. Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice.

    Morampudi, Vijay; De Craeye, Stephane; Le Moine, Alain; Detienne, Sophie; Braun, M Y; D'Souza, Sushila

    2011-04-01

    CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.

  19. Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

    Song, Haihan; Xi, Jianjun; Li, Guang-Gang; Xu, Shumin; Wang, Chunmei; Cheng, Tingting; Li, Hongqiang; Zhang, Ying; Liu, Xiandong; Bai, Jianwen

    2016-04-01

    Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

  20. A Regulatory miRNA–mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury

    de Almeida, Danilo Candido; Bassi, Ênio Jose; Azevedo, Hatylas; Anderson, Letícia; Origassa, Clarice Silvia Taemi; Cenedeze, Marcos Antônio; de Andrade-Oliveira, Vinicius; Felizardo, Raphael José Ferreira; da Silva, Reinaldo Correia; Hiyane, Meire Ioshie; Semedo, Patricia; dos Reis, Marlene Antônia; Moreira-Filho, Carlos Alberto; Verjovski-Almeida, Sergio; Pacheco-Silva, Álvaro; Câmara, Niels Olsen Saraiva

    2017-01-01

    Mesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidenced in vivo and in vitro by modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-β, fibrosis, and epithelial–mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA–mRNA network. PMID:28096802

  1. Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β.

    Dunoyer-Geindre, Sylvie; Rivier-Cordey, Anne-Sophie; Tsopra, Olga; Lecompte, Thomas; Kruithof, Egbert K O

    2017-03-25

    The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulant activity of cells and microparticles, as measured with calibrated automated thrombography, was delayed and only partial at 24 h. TNF and IL-1β inhibition reduced TF mRNA and activity only partially. Inhibition of the inflammatory signaling intermediate p38 reduced TF mRNA by one third but increased TNF and IL-1β mRNA. NF-κB inhibition reduced, within 1 h, TF and TNF mRNA but did not change IL-1β mRNA, and rapidly and markedly reduced cell survival, with procoagulant properties still being present. In conclusion, although we provide evidence that TNF, IL-1β, and their signaling intermediates have a regulatory function on TF expression by NB4 APL cells, the effect of ATRA and ATO on TF can only partially be accounted for by their impact on these cytokines.

  2. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

    Hyunseong Kim

    Full Text Available The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2 from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg in mice. Acetaminophen (APAP is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/- mice were injected with PLA2 once a day for five days and sacrificed 24 h (h after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST and alanine aminotransferase (ALT. PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  3. Regulatory Anatomy

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  4. Energy coupling to periplasmic binding protein-dependent transport systems: stoichiometry of ATP hydrolysis during transport in vivo.

    Mimmack, M L; Gallagher, M P; Pearce, S R; Hyde, S C; Booth, I R; Higgins, C F

    1989-01-01

    Periplasmic binding protein-dependent transport systems mediate the accumulation of many diverse substrates in prokaryotic cells. Similar transport systems, including the P-glycoprotein responsible for multidrug resistance in human tumors, are also found in eukaryotes. The mechanism by which energy is coupled to the accumulation of substrate by these transport systems has been controversial. In this paper we demonstrate that ATP hydrolysis occurs in vivo concomitantly with transport. These da...

  5. Acute pancreatitis

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  6. Cystitis - acute

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  7. Acute Bronchitis

    ... Smoking also slows down the healing process. Acute bronchitis treatment Most cases of acute bronchitis can be treated at home.Drink fluids, but ... bronchial tree. Your doctor will decide if this treatment is right for you. Living with acute bronchitis Most cases of acute bronchitis go away on ...

  8. CD+4 Foxp3+调节性T淋巴细胞在儿童急性白血病中的表达及其与微小残留病的关系%The level of CD+4 Foxp3+ regulatory T cells in patients with childhood acute leukemia and its relationship with the minimal residual disease of leukemia

    徐翀; 关明; 蒋黎敏; 江华; 孙婴

    2009-01-01

    Objective To study the regulatory T cells (Treg-cell) frequencies in patients with childhood acute leukemia and evaluate its clinical application value by investigating the relationship between the increasing numbers of Treg cells and minimal residual disease of leukemia (MRD), Methods Foxp3-FITC/CD25-PE/CD4-PerCP/CD3-APC four-color staining flow cytometry was established to identify Treg cells. Treg cells frequencies both in 10 healthy controls and in 33 patients with newly diagnosed childhood acute leukemia ( B-ALL 17 cases, T-ALL 9 cases, AML 7 cases) were detected. The possibility of the accumulation of Treg cells being the prognostic marker for acute leukemia was evaluated by comparing the results of Treg cells frequency with that of MRD. Results The percentage of Treg cells in CD+4 CD+3 T cells was M = 8. 09% in normal bone marrows, which was significantly different from the results in the bone marrows of newly diagnosed childhood acute leukemia ( M = 12.77% , U = 3.41, P 0.05).Treg数量与临床病理学参数无显著相关性.此外,Treg数量在MRD阳性组(M=14.74%)与MRD持续阴性组(M=11.3%)中的差异有统计学意义(t=252.5,P<0.05).结论 白血病初发患儿体内的Treg数量显著增高,且患儿中Treg表达水平与MRD有关联.高水平Treg预示白血病患儿预后较差,存在复发的可能.

  9. Acute pancreatitis

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  10. Acute pancreatitis

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  11. Acute cholecystitis

    Halpin, Valerie

    2014-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  12. Regulatory guidance document

    NONE

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  13. Increase of Frequency and Modulation of Phenotype of Regulatory T Cells by Atorvastatin Is Associated with Decreased Lung Inflammatory Cell Infiltration in a Murine Model of Acute Allergic Asthma

    Blanquiceth, Yurany; Rodríguez-Perea, Ana Lucia; Tabares Guevara, Jorge H.; Correa, Luis Alfonso; Sánchez, María Dulfary; Ramírez-Pineda, José Robinson; Velilla, Paula Andrea

    2016-01-01

    Regulatory T cells (Tregs) play an important role by controlling allergic inflammation of airways. Recently, it has been shown that statins have immunomodulatory properties, probably mediated by their effects on Tregs. Therefore, we evaluated the in vivo effect of atorvastatin (ATV) on Tregs and its association with the inflammatory process in a model of allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with intranasal OVA. ATV (40 mg/kg) was delivered by daily intraperitoneal injection for 7 or 15 days before each OVA challenge. ATV treatment for 7 days increased the frequency of Tregs in mediastinal lymph nodes (MLN) and the interleukin (IL)-10 in lungs. After 15 days of treatment, ATV increased the percentage of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+) and programmed cell death protein 1 (PD-1+) Tregs in the lung, without enhancing their suppressive activity, but also increased the percentage of conventional T cells expressing GITR+, PD1+, and OX-40 (tumor necrosis factor receptor superfamily member 4). Although no significant changes were observed in the number of inflammatory cells in the bronchoalveolar lavage (BAL), OVA-specific immunoglobulin E in the serum, and type 2 helper (Th2) cytokines in the lungs, there was a significant decrease of peribronchial inflammation that negatively correlated with the Tregs in MLN and the concentration of IL-10 in the lung. These results suggest that ATV has an immunomodulatory role possibly mediated by their effects on Tregs, which could contribute to the control of inflammation during allergic asthma. Further studies are necessary to elucidate the contribution of Treg to immunomodulatory action of statins in the context of allergic asthma. PMID:28066430

  14. Acute Kidney Failure

    ... out of balance. Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over ... 2015. Palevsky PM. Definition of acute kidney injury (acute renal failure). http://www.uptodate.com/home. Accessed April ...

  15. Acute Pancreatitis and Pregnancy

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  16. Modeling Emergence in Neuroprotective Regulatory Networks

    Sanfilippo, Antonio P.; Haack, Jereme N.; McDermott, Jason E.; Stevens, S.L.; Stenzel-Poore, Mary

    2013-01-05

    The use of predictive modeling in the analysis of gene expression data can greatly accelerate the pace of scientific discovery in biomedical research by enabling in silico experimentation to test disease triggers and potential drug therapies. Techniques that focus on modeling emergence, such as agent-based modeling and multi-agent simulations, are of particular interest as they support the discovery of pathways that may have never been observed in the past. Thus far, these techniques have been primarily applied at the multi-cellular level, or have focused on signaling and metabolic networks. We present an approach where emergence modeling is extended to regulatory networks and demonstrate its application to the discovery of neuroprotective pathways. An initial evaluation of the approach indicates that emergence modeling provides novel insights for the analysis of regulatory networks that can advance the discovery of acute treatments for stroke and other diseases.

  17. NRC regulatory initiatives

    Johnson, T.C. [Nuclear Regulatory Commission (United States)

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

  18. Acute myeloid leukemia cells inhibit the differentiation and maturation of dendritic cells and induce the generation of regulatory T cells%急性髓系白血病细胞对树突状细胞分化、成熟和调节性T细胞生成的影响

    Xingbing Wang; Xin Chen; Jun Liu; Zimin Sun; Shiang Huang

    2008-01-01

    Objective: To investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the phenotypical and functional properties of DCs derived from normal mononuclear cells. Methods: Mononuclear cells were cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), in the presence or absence of 24 h culture supernatants from fresh primary AML cells, to generate immature DCs. The maturation of DCs was induced by cytokines IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin-2 (PGE-2). The phenotypic alterations of DCs and DCs-primed CD4+ T cells were evaluated using flow cytometry. Precursor frequency (PF) was calculated to monitor the allostimulatory effects of DCs on CD4+ and CD8+ T cells. Results:AML cell supernatant-treated DCs showed significantly lower expression of co-stimulatory molecules CD80 and CD86, and reduced response to cytokines IL-1beta, IL-6, TNF-alpha,and PGE-2. The allostimulatory effects of AML cell supernatant-treated DCs on CD4+ and CD8+ T cells were significantly lower than those of normal mature DCs [PF: (1.8±0.5)% vs. (5.2±1.6)% for CD4+ T cells, (2.1±0.6)% vs. (6.5±2.0)%for CD8+ T cells, P<0.01]. These AML supematant-induced DCs could also induce allogeneic CD4+ T cells to differentiate into CD4+CD25high T cells, which had immunophenotyping characteristics of regulatory T cells, i.e. they expressed Foxp3 but not active maker CD69. Conclusion: This study demonstrates that soluble factors secreted by AML cells can inhibit development and functions of DCs. In addition, AML supematant-induced DCs can induce the generation of CD4+CD25high T cells from CD4+T cells, which may be a mechanism of increased prevalence of CD4+CD25high regulatory T cells and immune dysfunction in AML patients.

  19. Rationales for regulatory activity

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  20. The Regulatory Plan

    2010-12-20

    ... reduce obesity. In support of these activities in 2011, the Food and Nutrition Service (FNS) will propose... regulatory choices are based on careful analysis of the evidence, and if opportunities are provided for... billions of dollars while increasing energy security; combating childhood obesity; and creating a ``race...

  1. Prediction of regulatory elements

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet-lab...

  2. mGluR1-mediated excitation of cerebellar GABAergic interneurons requires both G protein-dependent and Src-ERK1/2-dependent signaling pathways.

    Hideo Kubota

    Full Text Available Stimulation of type I metabotropic glutamate receptors (mGluR1/5 in several neuronal types induces slow excitatory responses through activation of transient receptor potential canonical (TRPC channels. GABAergic cerebellar molecular layer interneurons (MLIs modulate firing patterns of Purkinje cells (PCs, which play a key role in cerebellar information processing. MLIs express mGluR1, and activation of mGluR1 induces an inward current, but its precise intracellular signaling pathways are unknown. We found that mGluR1 activation facilitated spontaneous firing of mouse cerebellar MLIs through an inward current mediated by TRPC1 channels. This mGluR1-mediated inward current depends on both G protein-dependent and -independent pathways. The nonselective protein tyrosine kinase inhibitors genistein and AG490 as well as the selective extracellular signal-regulated kinase 1/2 (ERK1/2 inhibitors PD98059 and SL327 suppressed the mGluR1-mediated current responses. Following G protein blockade, the residual mGluR1-mediated inward current was significantly reduced by the selective Src tyrosine kinase inhibitor PP2. In contrast to cerebellar PCs, GABAB receptor activation in MLIs did not alter the mGluR1-mediated inward current, suggesting that there is no cross-talk between mGluR1 and GABAB receptors in MLIs. Thus, activation of mGluR1 facilitates firing of MLIs through the TRPC1-mediated inward current, which depends on not only G protein-dependent but also Src-ERK1/2-dependent signaling pathways, and consequently depresses the excitability of cerebellar PCs.

  3. Small regulatory RNA and Legionella pneumophila

    Sebastien P Faucher

    2011-05-01

    Full Text Available Legionella pneumophila is a gram-negative bacterial species that is ubiquitous in almost any aqueous environment. It is the agent of Legionnaires’ disease, an acute and often under-reported form of pneumonia. In mammals, L. pneumophila replicates inside macrophages within a modified vacuole. Many protein regulators have been identified that control virulence-related properties, including RpoS, LetA/LetS and PmrA/PmrB. In the past few years, the importance of regulation of virulence factors by small regulatory RNA has been increasingly appreciated. This is also the case in L. pneumophila where three sRNAs (RsmY, RsmZ and 6S RNA were recently shown to be important determinants of virulence regulation and 79 actively transcribed sRNAs were identified. In this review we describe current knowledge about sRNAs and their regulatory properties and how this relates to the known regulatory systems of L. pneumophila. We also provide a model for sRNA-mediated control of gene expression that serves as a framework for understanding the regulation of virulence-related properties of L. pneumophila.

  4. Regulatory T cells in viral hepatitis

    Eva Billerbeck; Tobias B(o)ttler; Robert Thimme

    2007-01-01

    The pathogenesis and outcome of viral infections are significantly influenced by the host immune response.The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses,like hepatitis C virus (HCV) and hepatitis B virus (HBV),can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression.Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses.Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.

  5. Nuclear Regulatory Commission information digest

    None,

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  6. Acute abdomen

    Wig J

    1978-01-01

    Full Text Available 550 cases of acute abdomen have been analysed in detail includ-ing their clinical presentation and operative findings. Males are more frequently affected than females in a ratio of 3: 1. More than 45% of patients presented after 48 hours of onset of symptoms. Intestinal obstruction was the commonest cause of acute abdomen (47.6%. External hernia was responsible for 26% of cases of intestinal obstruction. Perforated peptic ulcer was the commonest cause of peritonitis in the present series (31.7% while incidence of biliary peritonitis was only 2.4%.. The clinical accuracy rate was 87%. The mortality in operated cases was high (10% while the over-all mortality rate was 7.5%.

  7. Acute Pancreatitis Concomitant Acute Coronary Syndrome

    Okay Abacı

    2013-03-01

    Full Text Available Acute pancreatitis is an inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction. As in our case rarely, acute pancreatitis can be presented with the coexistance of acute coronary syndrome. To prevent a misdiagnosis of acute situation presented with chest or abdominal pain, physicians must be aware for coexisting pathophysiologies and take into account the differential diagnosis of all life-threatening causes such as cardiac ischemia or acute abdominal situations.

  8. 不同月龄和血脂水平ApoE基因敲除小鼠体内类固醇激素合成急性调节蛋白的表达%Expression of steroidogenic acute regulatory protein following with age and serum lipids levels in apolipoprotein E-deficient mice

    宁艳霞; 江一峰; 徐晨; 赵凤娣; 殷莲华

    2010-01-01

    目的 检测不同月龄和不同血脂水平载脂蛋白E敲除小鼠体内类固醇激素合成急性调节蛋白(steroidogenic acute regulatory protein,StAR)的表达水平.方法 实验分别选取雄性和雌性1天龄新生鼠、1月龄、3月龄及5月龄载脂蛋白E敲除小鼠(apoE-/-)及对照C57BL/6J小鼠,每组6只,共16组.利用试剂盒检测不同年龄小鼠的血脂水平.利用实时定量RT-PCR及Western blot方法检测不同年龄和血脂水平下,小鼠肝脏中StAR基因和蛋白的表达.结果 相比同年龄同性别的正常对照小鼠,载脂蛋白E敲除小鼠血清中含较高水平的低密度脂蛋白(LDL)和较低水平的高密度脂蛋白(HDL).在对照小鼠中,StAR基因和蛋白表达水平随月龄增加逐渐下降;但是在载脂蛋白E敲除小鼠体内,因为血脂水平的提高,StAR基因和蛋白表达水平呈现先增高后降低的趋势.结论 StAR通过调节脂质代谢,可作为一个有效调节动脉粥样硬化以及其他心血管疾病的调节因子.

  9. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  10. Clinical research: regulatory issues.

    Wermeling, D P

    1999-02-01

    The regulatory issues faced by institutions performing clinical research are described. Many institutions do not have on staff an expert who understands the regulatory issues involved in managing investigational new drug research and who knows the institution's obligations under the federal rules. Because pharmacists understand the FDA regulations that apply to the management of drugs in clinical research, institutions are asking pharmacists to expand their role and manage clinical research offices. Many authorities govern various aspects of investigational drug research. FDA has published regulations for good clinical practice (GCP), and the International Conference on Harmonisation is developing an international standard for the proper management of clinical trials. The guidelines published by the Joint Commission on Accreditation of Healthcare Organizations aim to protect patients who are in the institution to receive health care and also participate in clinical trials. The Social Security Administration Acts specifically state that only items and services that are reasonable and necessary for the diagnosis and treatment of injury or disease can be billed to the government; research-related billings are excluded from coverage. Proper management of drug research is crucial to the success of a research program that is integrated with patient care.

  11. Toxicogenomics in regulatory ecotoxicology

    Ankley, Gerald T.; Daston, George P.; Degitz, Sigmund J.; Denslow, Nancy D.; Hoke, Robert A.; Kennedy, Sean W.; Miracle, Ann L.; Perkins, Edward J.; Snape, Jason; Tillitt, Donald E.; Tyler, Charles R.; Versteeg, Donald

    2006-01-01

    Recently, we have witnessed an explosion of different genomic approaches that, through a combination of advanced biological, instrumental, and bioinformatic techniques, can yield a previously unparalleled amount of data concerning the molecular and biochemical status of organisms. Fueled partially by large, well-publicized efforts such as the Human Genome Project, genomic research has become a rapidly growing topical area in multiple biological disciplines. Since 1999, when the term “toxicogenomics” was coined to describe the application of genomics to toxicology (1), a rapid increase in publications on the topic has occurred (Figure 1). The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions and, as with any new technology, has evoked a wide range of opinion (2–6). VIEWPOINT © 2006 american chemical Society july 1, 2006 / EnvironmEntal SciEncE & tEchnology n 4055 The purpose of this feature article is to consider the roles of toxicogenomics in the field of regulatory ecotoxicology, explore current limitations in the science and practice of genomics, and propose possible avenues to approach and resolve some of the major challenges. A significant amount of input to our analysis came from a workshop sponsored by the Society of Environmental Toxicology and Chemistry (SETAC) in Pellston, Mich., in September 2005. A complete list of names and affiliations of the experts participating in that workshop is provided online in Table 1 of the Supporting Information for this paper.

  12. Th17/调节性T淋巴细胞比率在急性乙型肝炎患者外周血的动态变化及其意义%Dynamic change in Th17/regulatory T cell ratio in peripheral blood of patients with acute hepatitis B and its significance

    程雪; 单永业; 罗亚文

    2016-01-01

    Objective To investigate the dynamic changes in the frequencies ofTh17 (CD3+CD8-IL-17+) and regulatory T cells (Treg,CD4+CD25+CD127low) and Th17/Treg ratio in the peripheral blood in patients with acute hepatitis B (AHB),as well as their association with the outcome of AHB.Methods A total of 10 AHB patients were enrolled as observation group,and according to the outcome of AHB,these patients were further divided into acute stage group,early recovery group,and full recovery group.Another 10 healthy subjects who underwent physical examination were enrolled as control group.Flow cytometry was used to measure the frequencies of Th17 and Treg in peripheral blood,and the Th17/Treg ratio was calculated.An automatic biochemical analyzer was used to measure liver function parameters,and RT-PCR was used to measure HBV DNA.An one-way analysis of variance was used for comparison between groups,and the t-test was used for comparison between any two groups.Results Compared with the control group,the acute stage group showed significant increases in the frequencies of Th1 7 and Treg (18.22%±4.13%/6.46%±2.46% vs 0.68%±0.29%/1.62%±0.18%,P < 0.01) and the Th1 7/Treg ratio (3.37±1.73 vs 0.42±0.20,P < 0.01).Compared with the acute stage group,the early recovery group showed a significant reduction in the frequency of Th 17 (3.14%± 1.90%,P < 0.01),a significant increase in the frequency of Treg (11.73 %± 1.76%,P < 0.01),and a significant reduction in the Th17/Treg ratio (0.27±0.19,P < 0.01).Compared with the early recovery group,the full recovery group showed a slight increase in the frequency of Th17 (3.31±0.95,P =0.888),a significant reduction in the frequency of Treg (6.83%±1.85%,P < 0.01),but which was significantly higher than that in the control group (P < 0.01),and a slight increase in the Th17/Treg ratio (0.52±0.21,P < 0.05),which showed no significant difference between this group and the control group (P =0.286).In the

  13. Acute arterial occlusion - kidney

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidney can often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury or trauma to ...

  14. Acute cerebellar ataxia

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  15. 75 FR 54210 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    2010-09-03

    ...-2010-032] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... Transactions August 30, 2010. On June 17, 2010, the Financial Industry Regulatory Authority, Inc....

  16. 硫化氢对急性肺损伤大鼠肺泡上皮细胞内质网应激的调节%Regulatory effects of hydrogen sulfide on alveolar epithelial cell endoplasmic reticulum stress in rats with acute lung injury

    刘志伟; 王海英; 关岚; 赵斌

    2014-01-01

    目的 探索内源性硫化氢对于油酸诱导的急性肺损伤大鼠肺泡上皮细胞内质网应激的调节作用.方法 雄性Sprague Dawley大鼠随机(随机数字法)被分入正常对照组、油酸组、油酸+硫氢化钠组及硫氢化钠对照组.每个组进一步分为2、4和6h3个时间点.对肺组织进行肺组织损伤半定量评分,检测肺组织湿、干质量比和匀浆硫化氢含量.通过免疫组化染色和蛋白印迹法检测内质网应激的标志蛋白(GRP78和elF2α)的表达.结果 肺损伤大鼠肺组织损伤半定量评分及湿、干质量比明显升高,而肺组织硫化氢含量,肺泡上皮细胞GRP78及eIF2α的表达明显降低.在硫氢化钠预处理的大鼠中,肺损伤半定量评分及肺组织湿、干质量比明显降低,而肺组织硫化氢含量,肺泡上皮细胞GRP78及eIF2α的表达明显升高.结论 内源性硫化氢可以通过促进肺泡上皮细胞内质网应激反应进而在肺损伤过程中起到保护作用.%Objective To study the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury (ALI) induced by oleic acid (OA).Methods Seventy-two male Sprague Dawley (SD) rats were equally divided into control group (C group),oleic acid-induced ALI group (OA group),oleic acid-induced ALI with sodium hydrosulfide (NaHS) pretreatment group (OA + NaHS group) and sodium hydrosulfide treatment group (NaHS group).The model of acute lung injury was made by oleic acid intravenous injection in dose of 0.1 mL/kg.NaHS was injected intra-abdominally in dose of 1 ml/kg with concentration of 56 μmol/L 30 min before administration of oleic acid for pretreatment.In control groups,saline was used instead of oleic acid and NaHS in the equivalent volume.Six rats of each group were sacrificed at 2 h,4 h and 6 hours separately after modeling for observing the acute injury of lung tissue.Index of quantitative assessment of

  17. Regulatory mark; Marco regulatorio

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  18. Regulatory considerations for biosimilars

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  19. Acute Appendicitis

    Tind, Sofie; Qvist, Niels

    2017-01-01

    BACKGROUND: The classification of acute appendicitis (AA) into various grades is not consistent, partly because it is not clear whether the perioperative or the histological findings should be the foundation of the classification. When comparing results from the literature on the frequency...... patients were included. In 116 (89 %) of these cases, appendicitis was confirmed histological. There was low concordance between the perioperative and histological diagnoses, varying from 16 to 76 % depending on grade of AA. Only 44 % of the patients receiving antibiotics postoperatively had a positive...... peritoneal fluid cultivation. CONCLUSION: There was a low concordance in clinical and histopathological diagnoses of the different grades of appendicitis. Perioperative cultivation of the peritoneal fluid as a standard should be further examined. The potential could be a reduced postoperative antibiotic use...

  20. Regulatory Foci and Organizational Commitment

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  1. Regulatory focus in groupt contexts

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the g

  2. Disclosure as a regulatory tool

    2006-01-01

    The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law.......The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law....

  3. Acute Myopericarditis Mimicking Acute Myocardial Infarction

    Seval İzdeş

    2011-08-01

    Full Text Available Acute coronary syndromes among young adults are relatively low when compared with older population in the intensive care unit. Electrocardiographic abnormalities mimicking acute coronary syndromes may be caused by non-coronary syndromes and the differential diagnosis requires a detailed evaluation. We are reporting a case of myopericarditis presenting with acute ST elevation and elevated cardiac enzymes simulating acute coronary syndrome. In this case report, the literature is reviewed to discuss the approach to distinguish an acute coronary syndrome from myopericarditis. (Journal of the Turkish Society Intensive Care 2011; 9:68-70

  4. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2010-06-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers... National Association of Securities Dealers, Inc., the Financial Industry Regulatory Authority, Inc., or...

  5. 75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2010-07-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change Relating to the Restated Certificate of Incorporation of Financial Industry Regulatory Authority, Inc. July 2, 2010. On May 21, 2010, Financial Industry Regulatory Authority, Inc....

  6. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    2010-03-10

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and...

  7. Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation

    Halleskog Carina

    2012-05-01

    Thus, WNT-5A-induced and G protein-dependent signaling to ERK1/2 is important for the regulation of proinflammatory responses in mouse primary microglia cells. We show for the first time that WNT-5A/G protein signaling mediates physiologically important processes in primary mammalian cells with natural receptor and G protein stochiometry. Consequently, WNT-5A emerges as an important means of astrocyte-microglia communication and we, therefore, suggest WNT-5A as a new player in neuroinflammatory conditions, such as neurodegenerative disease, hypoxia, stroke, injury and infection.

  8. Regulatory Streamlining and Improvement

    Mark A. Carl

    2006-07-11

    The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FC26-04NT15456 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under future scopes of work submitted annually to DOE's Project Officer for this grant. This report discusses the progress of the projects outlined under the grant scope of work for the 2005-2006 areas of interest, which are as follows: Area of Interest No. 1--Regulatory Streamlining and Improvement: This area of interest continues to support IOGCC's regulatory streamlining efforts that include the identification and elimination of unnecessary duplications of efforts between and among state and federal programs dealing with exploration and production on public lands. Area of Interest No. 2--Technology: This area of interest seeks to improve efficiency in states through the identification of technologies that can reduce costs. Area of Interest No. 3--Training and Education: This area of interest is vital to upgrading the skills of regulators and industry alike. Within the National Energy Policy, there are many appropriate training and education opportunities. Education was strongly endorsed by the President's National Energy Policy Development group. Acting through the governors offices, states are very effective conduits for the dissemination of energy education information. While the IOGCC favors the development of a comprehensive, long-term energy education plan, states are also supportive of immediate action on important concerns, such as energy prices, availability and conservation. Area of Interest No. 4--Resource Assessment and

  9. Bioinformatics analysis of microRNA comprehensive regulatory network in B-cell acute lymphoblastic leukemia%急性B淋巴细胞白血病的差异microRNA综合调控网络的生物信息学分析

    曾妙娜; 马文丽; 郑文岭

    2016-01-01

    目的 通过生物信息分析途径,从系统水平揭示参与急性B淋巴细胞白血病(B-ALL)发病的分子机制,为研究提供新的思路.方法 从公共数据库GEO中下载B-ALL的microRNA(miRNA)芯片数据,利用Qlucore Omics Explorer 3.0软件筛选差异表达miRNA,再分析得到差异miRNA与靶基因、长链非编码RNA和转录因子各自的调控数据,然后构建以差异miRNA为中心的综合调控网络.另外,功能富集分析有功能的靶基因.结果 共筛选出15个差异miRNA,其中7个miRNA表达上调,8个miRNA表达下调.通过差异miRNA为中心的综合调控网络可知,hsa-miR-126和hsa-miR-486-3p调控大量的靶基因,其中hsa-miR-126的靶基因包括MYC基因.hsa-miR-29a、hsa-miR-130a和hsa-miR-181c调控大量的长链非编码RNA,包括XIST.hsa-miR-181a-2、hsa-miR-181b-2和hsa-miR-663调控大量的转录因子,包括CDX2、YY1等.hsa-miR-126靶基因的通路分析显示富集到Wnt通路.结论 通过生物信息学方法分析得出,hsa-miR-29a、hsa-miR-126和hsa-miR-181家族是B-ALL的核心差异miRNA,及其转录因子CDX2、长链非编码RNA XIST和靶基因MYC基因在B-ALL的发生发展中起重要作用,可能为潜在的治疗靶点.%Objective To reveal the involvement of molecules in the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL) by bioinformatics analyses.Methods The microarray data of B-ALL were downloaded from the Gene Expression Omnibus (GEO) database and Qlucore Omics Explorer software was used to screen differentially expressed miRNA.Based on the differentially expressed miRNAs,we predicted the target genes,long non-coding RNAs (lncRNA) and transcription factors (TFs).Then we constructed the miRNAs-centered comprehensive regulatory network.In addition,we performed functional enrichment analysis to analyze the functions of target genes.Results Of all the 15 differentially expressed miRNAs,7 miRNAs were of overexpression,8 miRNAs underexpressed.From the mi

  10. The expression and regulatory mechanism of miR-708 in pediatric common B-cell acute lymphoblastic leukemia%miR-708在儿童普通急性淋巴细胞白血病中的表达及调控机制

    李雪; 李栋; 庄泳; 时庆; 魏伟; 张红; 鞠秀丽

    2013-01-01

    目的 检测普通急性淋巴细胞白血病(common-ALL)患儿中微小RNA(miRNA,miR)的差异性表达,并探讨miR-708的调控机制.方法 研究对象为34例common-ALL患儿及5例行骨关节病手术并排除肿瘤和血液系统疾病患儿的骨髓标本.应用微阵列基因芯片技术筛选common-ALL患儿样本中差异性表达的miRNA,应用茎环状逆转录引物的stem-loop实时荧光定量PCR技术进行验证.应用生物信息学预测、双报告基因检测、RT-PCR和Western blot等方法验证miR-708调控的靶基因及其表达.结果 在common-ALL患儿样本中检测的2006个miRNA中,miR-708、miR-181b和miR-210表达量分别为16.886±16.854、5.710±4.652和9.789±1.178,与正常对照组(1.872±0.339、1.276±0.531和1.005±0.080)相比表达均上调,差异均有统计学意义(P<0.05).miR-27a和miR-345表达量为0.524±0.085和0.675±0.086,与正常对照组(1.123±0.066和1.204±0.140)相比均下调,差异均有统计学意义(P<0.05).miR-708和miR-181b在高危组中表达水平为44.990±6.379和12.980±1.889,高于中危组和标危组(P<0.05).转染miR-708模拟物的人胚胎细胞株中CNTFR、NNAT和GNG12的表达水平均下降,而转染miR-708抑制剂组其表达升高.miR-708与CNTFR的结合区域位于3′-UTR端394~400 bp.结论 miRNA在调控儿童common-ALL发生发展的过程中发挥重要的作用,其中miR-708是高危型common-ALL重要的调控因子.miR-708通过结合靶基因的3′-UTR端,降低其靶基因表达水平.%Objective To evaluate the expression of microRNAs and reveal the regulatory mechanism of miRNA-708 in pediatric common acute lymphoblastic leukemia(ALL) (common-ALL). Methods The expressions of microRNAs in common-ALL patients were detected by microarrays in 3 pediatric common-ALL samples, and then verified by stem-loop quantitative RT-PCR in 34 common-ALL samples. The target genes of miR-708 were found by bioinformatics software, and verified by dual-luciferases reporter assay

  11. Regulating regulatory T cells.

    Le, N T; Chao, N

    2007-01-01

    Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

  12. Internationalization of regulatory requirements.

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  13. 肠源性内毒素与Treg在重症急性胰腺炎肝损伤中的作用%The role of CD4+CD25+ regulatory T cells in peripheral blood and intestinal endotoxin in liver injury of rat severe acute pancreatitis

    李文星; 熊泽翼; 郭建红; 闫浩; 范晓彬; 张慧

    2012-01-01

    目的 探讨肠源性内毒素(ET)及CD4+ CD25+调节性T细胞(Treg)在重症急性胰腺炎(SAP)肝损伤中的作用.方法 雄性Wistar大鼠60只,随机分成假手术组(SO组)和SAP组.逆行性胰胆管注射牛磺胆酸钠造模.分别于术后3、6、12 h留取标本,检测血淀粉酶及丙氨酸转氨酶水平,鲎试剂法测血浆内毒素含量,流式细胞术测外周血Treg百分数,肝脏及胰腺行病理组织学观察,免疫组化法测肝脏组织Foxp3表达,并对以上指标进行相关性分析.结果 病理组织学观察及丙氨酸转氨酶水平证实,SAP组肝脏出现病理性形态改变.与SO组相比,SAP各组Treg百分数显著升高(SAP组3、6、12h分别为:2.26%±0.32%、2.36%±0.48%、2.80%±0.35%),差异有统计学意义(P<0.01).SAP各组ET水平与SO组相比,差异有统计学意义(P<0.01),与12 h(0.85±0.11)相比,3 h(0.74±0.11)和6 h(0.78±0.07)差异无统计学意义(P>0.05).SAP各组肝脏Foxp3蛋白表达明显上调,Treg的表达与ET呈正相关(r=0.89,P<0.01).结论 SAP可致肝损伤,ET与Treg细胞在SAP肝损伤中可能发挥重要作用.%Objective To investigate the role of CD4+ CD25+ regulatory T cells(Treg) in peripheral blood and intestinal endotoxin (ET) in liver injury of rat severe acute pancreatitis (SAP).Methods Sixty male Wistar rats were randomly allocated into sham operation group(SO group) and severe acute pancreatitis group(SAP group).The rats in SAP group recevied the injection of Sodium Taurocholate(NaTc) into their far-end of bile-pancreatic duct and were sacrificed in 3-,6-and 12-hour,serum amylase(AMY) and alanine aminotransferase(ALT) determined by full-automatic biochemistry instrument,limulus reagent method is used to determine ET content in plasma,the proportion of Treg among peripheral lymphocytes was determined by Flow Cytometry(FCM),HE stain is used to observe pathological changes in liver and pancreas,the protein of Foxp3 activity was evaluated by

  14. Acute otitis externa.

    Hui, Charles Ps

    2013-02-01

    Acute otitis externa, also known as 'swimmer's ear', is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.

  15. Acute otitis externa

    2013-01-01

    Acute otitis externa, also known as ‘swimmer’s ear’, is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.

  16. Healthcare regulatory concepts in Brazil.

    Oliveira, Robson Rocha de; Elias, Paulo Eduardo Mangeon

    2012-06-01

    The healthcare regulatory concepts used in Brazilian scientific publications on healthcare management were reviewed. A typo-logical classification for regulatory concepts was developed from the most current ideas in five disciplines: life sciences, law, economics, sociology and political science. Four ideas stood out: control, balance, adaptation and direction, with greatest emphasis on the technical nature of regulation. The political nature of regulation was secondary. It was considered that dis-cussion of healthcare regulatory concepts was connected with comprehension of the role that the state plays in this sector. De-finition of the forms of state intervention is the key convergence point between the different ways of conceptualizing healthcare regulation.

  17. The Danish Regulatory Reform of Telecommunications

    Skouby, Knud Erik

    1998-01-01

    An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

  18. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  19. Current Regulations and Regulatory Actions

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  20. Anti-regulatory T cells

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune......-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles...

  1. Electronic Commerce Removing Regulatory Impediments

    1992-05-01

    AD-A252 691 ELECTRONIC COMMERCE Removing Regulatory Impediments ~DuiG A% ELECTE I JUL1 8 1992 0 C D Daniel J. Drake John A. Ciucci ... - ""N ST AT KE...Management Institute 6400 Goldsboro Road Bethesda, Maryland 20817-5886 92 LMI Executive Summary ELECTRONIC COMMERCE : REMOVING REGULATORY IMPEDIMENTS... Electronic Commerce techniques, such as electronic mail and electronic data interchange (EDI), enable Government agencies to conduct business without the

  2. Regulatory facility guide for Ohio

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  3. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  4. Regulatory criteria: Legal or ecological thresholds?

    Cook, J.M.; Skorupa, J.P.; Schwarzbach, S.E. [Fish and Wildlife Service, Sacramento, CA (United States)

    1994-12-31

    Selenium-laden irrigation drainwater has been identified as a significant threat to breeding waterfowl and shorebirds in terminal sink environments throughout the western United States. Due to historic wetland habitat losses, irrigation drainwater disposal ponds represent virtually all the available breeding habitat for waterbirds in the southern San Joaquin Valley of California. Egg selenium residues from birds breeding at these ponds have been monitored by the US Fish and Wildlife Service since 1987, and physiological risk thresholds for individual and population-level hatchability and teratogenesis have been determined from these studies. For Blacknecked stilt populations, egg selenium below 3 ppm may be considered a safe level, hatchability is significantly depressed at mean egg selenium concentrations above 8 ppm, and induction of teratogenesis is virtually certain at egg selenium levels above 18 ppm (p < 0.05). Egg samples collected in 1993 from these ponds showed concentrations as high as 160 ppm. Despite the high degree of statistical confidence in these effects thresholds, and the incidence of selenium-induced bird death and deformity at these ponds, regulation of evaporation ponds has been problematic. Existing civil statutes regarding water quality are dependent on risk-based criteria, but irrigation drainwater is exempted from these regulations. The only applicable law is the Migratory Bird Treaty Act, a criminal statute with no risk-based guidelines, and consequently no wildlife safety factors. The authors present data from the San Joaquin Valley in the context of these regulatory and legal limitations. Evaluation of acute and chronic models for ambient water quality indicate that this approach may not provide adequate protection for breeding birds. Based on the inadequacy of these models, the authors consider the development of regulatory criteria for egg selenium, a standard which is ecologically relevant.

  5. Histoplasmosis - acute (primary) pulmonary

    ... this page: //medlineplus.gov/ency/article/000098.htm Histoplasmosis - acute (primary) pulmonary To use the sharing features on this page, please enable JavaScript. Acute pulmonary histoplasmosis is a respiratory infection that is caused by ...

  6. Acute respiratory distress syndrome

    ... page: //medlineplus.gov/ency/article/000103.htm Acute respiratory distress syndrome To use the sharing features on this page, please enable JavaScript. Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that ...

  7. Acute kidney failure

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  8. Acute bee paralysis virus [

    Full Text Available Acute bee paralysis virus [gbvrl]: 14 CDS's (15780 codons) fields: [triplet] [frequ...osomal protein / MAP kinase List of codon usage for each CDS (format) Homepage Acute bee paralysis virus ...

  9. Acute Mesenteric Ischemia

    ... Side Effects Additional Content Medical News Acute Mesenteric Ischemia By Parswa Ansari, MD, Department of Surgery, Lenox ... Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ...

  10. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Olfa Kassar; Feten Kallel; Manel Ghorbel; Hatem. Bellaaj; Zeineb Mnif; Moez Elloumi

    2015-01-01

    Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patie...

  11. Nurse leaders' experiences of implementing regulatory changes in sexual health nursing practice in British Columbia, Canada.

    Bungay, Vicky; Stevenson, Janine

    2013-05-01

    Most research about regulatory policy change concerning expanded nursing activities has emphasized advanced practice roles and acute care settings. This study is a contribution to the small pool of research concerned with regulatory policy implementation for nurses undertaking expanded nursing practice activities in a public health context. Using the regulatory changes in certified nursing practice in one Canadian province as our starting point, we investigated the experiences of nurse leaders in implementing this change. Using a qualitative interpretive descriptive approach informed by tenets of complexity theory, we examined the experiences of 16 nurse leaders as situated within the larger public health care system in which nurses practice. Two interrelated themes, (a) preparing for certification and (b) the certification process, were identified to illustrate how competing and contrasting demands between health care and regulatory organizations created substantial barriers to policy change. Implications for health service delivery and future research are discussed.

  12. Regulatory Expectations for Safety Culture

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

  13. Acute mastoiditis in children

    Anthonsen, Kristian; Høstmark, Karianne; Hansen, Søren;

    2013-01-01

    Conservative treatment of acute otitis media may lead to more complications. This study evaluates changes in incidence, the clinical and microbiological findings, the complications and the outcome of acute mastoiditis in children in a country employing conservative guidelines in treating acute...... otitis media....

  14. Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains.

    Grignani, F; Testa, U; Rogaia, D; Ferrucci, P F; Samoggia, P; Pinto, A; Aldinucci, D; Gelmetti, V; Fagioli, M; Alcalay, M; Seeler, J; Grignani, F; Nicoletti, I; Peschle, C; Pelicci, P G

    1996-01-01

    The block of terminal differentiation is a prominent feature of acute promyelocytic leukemia (APL) and its release by retinoic acid correlates with disease remission. Expression of the APL-specific PML/RARalpha fusion protein in hematopoietic precursor cell lines blocks terminal differentiation, suggesting that PML/ RARalpha may have the same activity in APL blasts. We expressed different PML/RARalpha mutants in U937 and TF-1 cells and demonstrated that the integrity of the PML protein dimerization and RARalpha DNA binding domains is crucial for the differentiation block induced by PML/RARalpha, and that these domains exert their functions only within the context of the fusion protein. Analysis of the in vivo dimerization and cell localization properties of the PML/RARalpha mutants revealed that PML/RARalpha--PML and PML/RARalpha--RXR heterodimers are not necessary for PML/RARalpha activity on differentiation. We propose that a crucial mechanism underlying PML/RARalpha oncogenic activity is the deregulation of a transcription factor, RARalpha, through its fusion with the dimerization interface of another nuclear protein, PML. Images PMID:8890168

  15. Imaging of Acute Pancreatitis.

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist.

  16. Subordinate regulatory mode and leader power: Interpersonal regulatory complementarity predicts task performance

    Hamstra, M.R.W.; Orehek, E.; Holleman, M.

    2014-01-01

    This research examines the implications of locomotion regulatory mode (orientation toward making progress on goals) and assessment regulatory mode (orientation toward critically evaluating alternatives) for employees' performance. Regulatory mode theory suggests that, although these are both integra

  17. 75 FR 70757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2010-11-18

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a... 12, 2010. I. Introduction On August 6, 2010, the Financial Industry Regulatory Authority, Inc... Kimmel, Executive Director, Financial Information Forum, to Elizabeth M. Murphy, Secretary,...

  18. 77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    2012-08-08

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal... FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority,...

  19. 76 FR 72736 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2011-11-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... September 22, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities... Killian, Vice President, Securities Industry and Financial Markets Association (``SIFMA''), to Elizabeth...

  20. 77 FR 55517 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2012-09-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a.... Introduction On May 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... General Counsel, Securities Industry and Financial Markets Association, dated June 26, 2012...

  1. 75 FR 62439 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2010-10-08

    ...-2010-043] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., 2010. I. Introduction On August 6, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA..., 2010 (``Wiesenberg Letter''); Letter from Manisha Kimmel, Executive Director, Financial...

  2. 77 FR 12340 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2012-02-29

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Accounting Support Fee February 23, 2012. I. Introduction On December 20, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  3. 76 FR 20757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2011-04-13

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

  4. 75 FR 61793 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2010-10-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... Encrypted September 29, 2010. I. Introduction On June 2, 2010, the Financial Industry Regulatory Authority... Taunt, Chief Executive Officer, Regal Financial Group, to Elizabeth M. Murphy, Secretary,...

  5. Acute loss of consciousness.

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness.

  6. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  7. Acute calcium homeostasis in MHS swine.

    Harrison, G G; Morrell, D F; Brain, V; Jaros, G G

    1987-07-01

    To elucidate a pathogenesis for the reduction in bone calcium content observed in MHS individuals, we studied the acute calcium homeostasis of MHS swine. This was achieved by the serial measurement, with a calcium selective electrode, of calcium transients in Landrace MHS (five) and control Landrace/large white cross MH negative (five) swine following IV bolus injection of calcium gluconate 0.1 mmol X kg-1--a dose which induced an acute 45 per cent increase in plasma ionised calcium. Experimental animals were anaesthetised with ketamine 10 mg X kg-1 IM, thiopentone (intermittent divided doses) 15-25 mg X kg-1 (total) IV and N2O/O2 (FIO2 0.3) by IPPV to maintain a normal blood gas, acid/base state. The plasma ionised calcium decay curve observed in MHS swine did not differ from that of control normal swine. Further it was noted that the induced acute rise in plasma ionised calcium failed to trigger the MH syndrome in any MHS swine. It is concluded that the mechanisms of acute calcium homeostasis in MHS swine are normal. An explanation for the reduction in bone calcium content observed in MHS individuals must be sought, therefore, through study of the slow long-term component of the calcium regulatory process. In addition, the conventional strictures placed on the use, in MHS patients, of calcium gluconate are called in question.

  8. Acute pancreatitis in acute viral hepatitis

    2007-01-01

    AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis.METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain.RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment.The etiology of pancreatitis was hepatitis E virus in 4,hepatitis A virus in 2, and hepatitis B virus in 1 patient.One patient had biliary sludge along with HEV infection.The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule.CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.

  9. Acute otitis media and acute bacterial sinusitis.

    Wald, Ellen R

    2011-05-01

    Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.

  10. Acute chylous peritonitis due to acute pancreatitis.

    Georgiou, Georgios K; Harissis, Haralampos; Mitsis, Michalis; Batsis, Haralampos; Fatouros, Michalis

    2012-04-28

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of "chyle" occurs rapidly, the patient may present with signs of peritonitis. Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation, appendicitis or visceral ischemia. Less than 100 cases of acute chylous peritonitis have been reported. Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis. This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis, and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis. The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer, since, due to hypertriglyceridemia, serum amylase values appeared within the normal range. Moreover, abdominal computed tomography imaging was not diagnostic for pancreatitis. Following abdominal lavage and drainage, the patient was successfully treated with total parenteral nutrition and octreotide.

  11. Acute chylous peritonitis due to acute pancreatitis

    Georgios K Georgiou; Haralampos Harissis; Michalis Mitsis; Haralampos Batsis; Michalis Fatouros

    2012-01-01

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse.The development of chylous ascites is usually a chronic process mostly involving malignancy,trauma or surgery,and symptoms arise as a result of progressive abdominal distention.However,when accumulation of "chyle" occurs rapidly,the patient may present with signs of peritonitis.Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation,appendicitis or visceral ischemia.Less than 100 cases of acute chylous peritonitis have been reported.Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis.This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis,and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis.The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer,since,due to hypertriglyceridemia,serum amylase values appeared within the normal range.Moreover,abdominal computed tomography imaging was not diagnostic for pancreatitis.Following abdominal lavage and drainage,the patient was successfully treated with total parenteral nutrition and octreotide.

  12. Pharm GKB: Leukemia, Nonlymphocytic, Acute [PharmGKB

    Full Text Available Overview Alternate Names: Synonym ANLL; Acute Nonlymphoblastic Leukemia; Acute Nonl...ymphoblastic Leukemias; Acute Nonlymphocytic Leukemia; Acute Nonlymphocytic Leukemias; Leukemia, Acute Nonly...mphoblastic; Leukemia, Acute Nonlymphocytic; Leukemia, Nonlymphoblastic, Acute; Leukemias, Acute Nonlymphoblastic; Leukemias, Acute... Nonlymphocytic; Nonlymphoblastic Leukemia, Acute; Nonlymphoblastic Leukemias, Acut...e; Nonlymphocytic Leukemia, Acute; Nonlymphocytic Leukemias, Acute PharmGKB Accessi

  13. Pharm GKB: Leukemia, Myeloid, Acute [PharmGKB

    Full Text Available Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym AML - Acute... myeloblastic leukaemia; Acute Myeloblastic Leukemia; Acute Myeloblastic Leukemias; Acute... Myelocytic Leukemia; Acute Myelocytic Leukemias; Acute Myelogenous Leukemia; Acute Myelogenous Leukemias; Acute... granulocytic leukaemia; Acute myeloblastic leukemia; Acute myeloid leukaemia; Acute myeloid leukaemia - category; Acute... myeloid leukaemia, disease; Acute myeloid leukemia; Acute myelo

  14. Nuclear Regulatory Commission 1989 Information Digest

    None,

    1989-03-01

    The Nuclear Regulatory Commission 1989 Information Digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the Commission. This is the first of an annual publication for the general use of the NRC staff and is available to the public. The Digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  15. The Political Economy of Regulatory Risk

    Roland Strausz

    2009-01-01

    I investigate the argument that, in a two–party system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an output–expansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatory–risk–averse party ...

  16. The political economy of regulatory risk

    Strausz, Roland

    2009-01-01

    I investigate the argument that, in a twoparty system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an outputexpansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatoryriskaverse party is n...

  17. [Acute rheumatic fever].

    Maier, Alexander; Kommer, Vera

    2016-03-01

    We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.

  18. Acute Idiopathic Scrotal Edema

    Micheál Breen

    2013-01-01

    Full Text Available We report a case of acute idiopathic scrotal edema (AISE in a 4-year-old boy who presented with acute scrotal pain and erythema. The clinical features, ultrasound appearance, and natural history of this rare diagnosis are reviewed. In this report, we highlight the importance of good ultrasound technique in differentiating the etiology of the acute scrotum and demonstrate the color Doppler “Fountain Sign” that is highly suggestive of AISE.

  19. Pharm GKB: Kidney Failure, Acute [PharmGKB

    Full Text Available iew Alternate Names: Synonym ARF - Acute renal failure; Acute Kidney Failure; Acute Kidney Failures; Acute K...idney Insufficiencies; Acute Kidney Insufficiency; Acute Renal Failure; Acute Renal Failures; Acute... Renal Insufficiencies; Acute Renal Insufficiency; Acute renal failure syndrome, NOS; Failure, Acute... Kidney; Failure, Acute Renal; Failures, Acute Kidney; Failures, Acute Renal; Insufficiencies, Acute... Kidney; Insufficiencies, Acute Renal; Insufficiency, Acute Kidney; Insufficiency, Acute

  20. Mixed phenotype acute leukemia

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  1. 40 CFR 94.6 - Regulatory structure.

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this Part 94 are intended to...

  2. 40 CFR 92.6 - Regulatory structure.

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this part 92 are intended...

  3. 21 CFR 500.88 - Regulatory method.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Regulatory method. 500.88 Section 500.88 Food and... § 500.88 Regulatory method. (a) The sponsor shall submit for evaluation and validation a regulatory method developed to monitor compliance with FDA's operational definition of no residue. (b)...

  4. 77 FR 10351 - Regulatory Review Plan

    2012-02-22

    ... XII Regulatory Review Plan AGENCY: Federal Housing Finance Agency. ACTION: Notice of final regulatory review plan. SUMMARY: The Federal Housing Finance Agency (FHFA) is issuing a notice of the final FHFA regulatory review plan for review of existing regulations under Executive Order 13579, ``Regulation...

  5. Genetic flexibility of regulatory networks.

    Hunziker, Alexander; Tuboly, Csaba; Horváth, Péter; Krishna, Sandeep; Semsey, Szabolcs

    2010-07-20

    Gene regulatory networks are based on simple building blocks such as promoters, transcription factors (TFs) and their binding sites on DNA. But how diverse are the functions that can be obtained by different arrangements of promoters and TF binding sites? In this work we constructed synthetic regulatory regions using promoter elements and binding sites of two noninteracting TFs, each sensing a single environmental input signal. We show that simply by combining these three kinds of elements, we can obtain 11 of the 16 Boolean logic gates that integrate two environmental signals in vivo. Further, we demonstrate how combination of logic gates can result in new logic functions. Our results suggest that simple elements of transcription regulation form a highly flexible toolbox that can generate diverse functions under natural selection.

  6. Characterizing disease states from topological properties of transcriptional regulatory networks

    Kluger Harriet M

    2006-05-01

    Full Text Available Abstract Background High throughput gene expression experiments yield large amounts of data that can augment our understanding of disease processes, in addition to classifying samples. Here we present new paradigms of data Separation based on construction of transcriptional regulatory networks for normal and abnormal cells using sequence predictions, literature based data and gene expression studies. We analyzed expression datasets from a number of diseased and normal cells, including different types of acute leukemia, and breast cancer with variable clinical outcome. Results We constructed sample-specific regulatory networks to identify links between transcription factors (TFs and regulated genes that differentiate between healthy and diseased states. This approach carries the advantage of identifying key transcription factor-gene pairs with differential activity between healthy and diseased states rather than merely using gene expression profiles, thus alluding to processes that may be involved in gene deregulation. We then generalized this approach by studying simultaneous changes in functionality of multiple regulatory links pointing to a regulated gene or emanating from one TF (or changes in gene centrality defined by its in-degree or out-degree measures, respectively. We found that samples can often be separated based on these measures of gene centrality more robustly than using individual links. We examined distributions of distances (the number of links needed to traverse the path between each pair of genes in the transcriptional networks for gene subsets whose collective expression profiles could best separate each dataset into predefined groups. We found that genes that optimally classify samples are concentrated in neighborhoods in the gene regulatory networks. This suggests that genes that are deregulated in diseased states exhibit a remarkable degree of connectivity. Conclusion Transcription factor-regulated gene links and

  7. Followers feel valued : When leaders' regulatory focus makes leaders exhibit behavior that fits followers' regulatory focus

    Hamstra, Melvyn; Sassenberg, K.; Van Yperen, Nico W.; Wisse, Barbara

    2014-01-01

    When do followers feel valued by their leader? We propose that leaders' regulatory focus can make followers feel valued when leaders' regulatory focus is the same as followers' regulatory focus, that is, when there is regulatory fit between leaders and followers. We further propose that the reason w

  8. 77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2012-01-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... effective date of the proposed rule change in a Regulatory Notice to be published no later than 60...

  9. 76 FR 20741 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2011-04-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... On February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... implementation of New Rule 13806 (Promissory Note Proceedings) in Regulatory Notice 09-48 (August 2009)....

  10. 78 FR 54359 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2013-09-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 20, 2103, Financial Industry Regulatory.... \\3\\ 15 U.S.C. 78s(b)(3)(A)(i). \\4\\ 17 CFR 240.19b-4(f)(1). ] I. Self-Regulatory...

  11. 78 FR 10655 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2013-02-14

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...) February 8, 2013. I. Introduction On December 20, 2012, Financial Industry Regulatory Authority, Inc... Equity Securities.\\5\\ FINRA may impose a ``Foreign Regulatory Halt'' when a foreign securities...

  12. 75 FR 17810 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-04-07

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 12, 2010, Financial Industry Regulatory...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  13. 77 FR 33527 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-06-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that on May 23, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  14. 77 FR 12092 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-02-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ notice is hereby given that February 9, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  15. 75 FR 28841 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-05-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on May 18, 2010, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  16. 76 FR 2739 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-01-14

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... is hereby given that on January 5, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  17. 76 FR 62128 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-10-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on September 22, 2011, the Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  18. 78 FR 5542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-01-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on January 7, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  19. 77 FR 74249 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-12-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on November 30, 2012, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  20. 76 FR 77283 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-12-12

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that on November 21, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA...\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the...

  1. 76 FR 20065 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-04-11

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 30, 2011, Financial Industry Regulatory... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  2. 75 FR 49542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-08-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on July 27, 2010, Financial Industry Regulatory... from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  3. 76 FR 70195 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-11-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on October 28, 2011, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  4. 78 FR 42581 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2013-07-16

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that on June 27, 2013, Financial Industry Regulatory Authority, Inc.... 78s(b)(3)(A)(i). \\4\\ 17 CFR 240.19b-4(f)(1). I. Self-Regulatory Organization's Statement of the...

  5. 77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-02-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... February 9, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of...

  6. 76 FR 72463 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-11-23

    ...-FINRA-2011-044] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... is hereby given that on November 8, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA...\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the...

  7. 76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-02-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... that on February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  8. 78 FR 78451 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-12-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on December 9, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  9. 78 FR 25331 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    2013-04-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal.... On January 7, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... Regulatory Policy, Wells Fargo Advisors, LLC, dated Feb. 15, 2013; Letter from Tamara K. Salmon,...

  10. 76 FR 67787 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-11-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on October 13, 2011, Financial Industry Regulatory Authority, Inc.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  11. 78 FR 76341 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-12-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that, on December 2, 2013, Financial Industry Regulatory Authority, Inc... considers the subscriber's financial condition and its regulatory history. FINRA believes that the...

  12. 75 FR 2899 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2010-01-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... January 12, 2010. On November 24, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k...- regulatory organizations.\\6\\ \\6\\ See, e.g., Nasdaq Rule 4761 and NYSE-Arca Rule 7.39. It is therefore...

  13. 78 FR 24261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2013-04-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 15, 2013, Financial Industry Regulatory...\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of...

  14. 75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-02-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...,\\2\\ notice is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc... in Regulatory Notice 09-71 that the new financial responsibility rules will be implemented...

  15. 77 FR 58880 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2012-09-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...,\\2\\ notice is hereby given that on September 17, 2012, Financial Industry Regulatory Authority, Inc...\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement...

  16. 75 FR 58004 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-09-23

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on September 7, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA... Securities Exchange, LLC, Financial Industry Regulatory Authority, Inc., The New York Stock Exchange,...

  17. 76 FR 78706 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2011-12-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a... On October 20, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... advised that it would announce the implementation date of the proposed rule change in a Regulatory...

  18. 75 FR 9459 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-03-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association... National Association of Securities Dealers, Inc., the Financial Industry Regulatory Authority, Inc., or...

  19. 75 FR 39069 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-07-07

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 30, 2010, Financial Industry Regulatory.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  20. 77 FR 33537 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-06-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on May 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  1. 78 FR 75954 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-12-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on November 25, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  2. 75 FR 69503 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-11-12

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ notice is hereby given that on October 29, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  3. 76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-02-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... given that on February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  4. 75 FR 15470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-03-29

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that, on March 9, 2010, Financial Industry Regulatory Authority, Inc...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  5. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-09-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 16, 2010, Financial Industry Regulatory.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  6. 77 FR 5611 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    2012-02-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a..., 2012. I. Introduction On October 13, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA... change in a Regulatory Notice to be published no later than 90 days following Commission approval,...

  7. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2011-10-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving.... Introduction On August 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National... Regulatory Notice to be published no later than 90 days following this Commission approval. The...

  8. 75 FR 62901 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-10-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that on September 27, 2010, the Financial Industry Regulatory Authority....19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the...

  9. 76 FR 50515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-08-15

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 5, 2011, Financial Industry Regulatory...-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed...

  10. 76 FR 65758 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-10-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on October 5, 2011, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  11. Infant acute myocarditis mimicking acute myocardial infarction

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  12. Escherichia coli transcriptional regulatory network

    Agustino Martinez-Antonio

    2011-06-01

    Full Text Available Escherichia coli is the most well-know bacterial model about the function of its molecular components. In this review are presented several structural and functional aspects of their transcriptional regulatory network constituted by transcription factors and target genes. The network discussed here represent to 1531 genes and 3421 regulatory interactions. This network shows a power-law distribution with a few global regulators and most of genes poorly connected. 176 of genes in the network correspond to transcription factors, which form a sub-network of seven hierarchical layers where global regulators tend to be set in superior layers while local regulators are located in the lower ones. There is a small set of proteins know as nucleoid-associated proteins, which are in a high cellular concentrations and reshape the nucleoid structure to influence the running of global transcriptional programs, to this mode of regulation is named analog regulation. Specific signal effectors assist the activity of most of transcription factors in E. coli. These effectors switch and tune the activity of transcription factors. To this type of regulation, depending of environmental signals is named the digital-precise-regulation. The integration of regulatory programs have place in the promoter region of transcription units where it is common to observe co-regulation among global and local TFs as well as of TFs sensing exogenous and endogenous conditions. The mechanistic logic to understand the harmonious operation of regulatory programs in the network should consider the globalism of TFs, their signal perceived, coregulation, genome position, and cellular concentration. Finally, duplicated TFs and their horizontal transfer influence the evolvability of members of the network. The most duplicated and transferred TFs are located in the network periphery.

  13. 75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

    2010-05-19

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-3039, ``Standard Format and Content...

  14. 75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

    2010-08-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1228, ``Standard Format and Content...

  15. Acute myopericarditis masquerading as acute myocardial infarction

    Wen Tian; Zixin Zhang; Xiaojuan Bai; Dingyin Zeng; Guoxian Qi

    2008-01-01

    Patients with abrupt onset of chest pain, ischemic ECG abnormalities and elevated levels of cardiac markers could be given a diagnosis of acute myocardial infarction. However, some other diseases should be taken into consideration in this clinical setting when coronary arteries are proven to be normal. Here we report a case of acute myopericarditis with clinical presentation of myocardial infarction and normal coronary anatomy. The Herpes Simplex Virus Ⅱ was considered as the organism causing myopericarditis and the patient was recovered by the treatment with valacicloavir. A precise diagnosis is a prerequisite of successful treatment and favorable prognosis.

  16. [Acute kidney injury

    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  17. Corticosteroids for acute rhinosinusitis

    Venekamp, R.P.

    2012-01-01

    Acute rhinosinusitis is a common reason for consultations in general practice, with typically 50 cases seen by a general practitioner annually. Traditionally, acute rhinosinusitis has been regarded as a bacterial infection of the paranasal sinuses. Therefore, numerous randomised controlled trials ha

  18. Leukocytosis in acute stroke

    Kammersgaard, L P; Jørgensen, H S; Nakayama, H

    1999-01-01

    Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has...

  19. Acute recurrent polyhydramnios

    Rode, Line; Bundgaard, Anne; Skibsted, Lillian

    2007-01-01

    Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated ...

  20. Acute kidney injury during pregnancy.

    Van Hook, James W

    2014-12-01

    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  1. Pharm GKB: Leukemia, Monocytic, Acute [PharmGKB

    Full Text Available Overview Alternate Names: Synonym Acute Monoblastic Leukemia; Acute Monoblastic Leukemias; Acute... Monocytic Leukemia; Acute Monocytic Leukemias; Acute monoblastic leukaemia; Acute monoblastic leukemia; Acute... monocytic leukaemia; Acute monocytic leukemia, morphology; Acute monocytoid leukemia; Leukemia, Acute... Monoblastic; Leukemia, Acute Monocytic; Leukemia, Monoblastic, Acute; Leukemia, Myeloid, Acute... Schilling-Type Myeloid; Leukemias, Acute Monoblastic; Leukemias, Acute Monocytic; M5a - Acute monoblastic leukaemia; M5a - Acute

  2. [Chronic pancreatitis, acute pancreatitis].

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  3. The core regulatory network in human cells.

    Kim, Man-Sun; Kim, Dongsan; Kang, Nam Sook; Kim, Jeong-Rae

    2017-03-04

    In order to discover the common characteristics of various cell types in the human body, many researches have been conducted to find the set of genes commonly expressed in various cell types and tissues. However, the functional characteristics of a cell is determined by the complex regulatory relationships among the genes rather than by expressed genes themselves. Therefore, it is more important to identify and analyze a core regulatory network where all regulatory relationship between genes are active across all cell types to uncover the common features of various cell types. Here, based on hundreds of tissue-specific gene regulatory networks constructed by recent genome-wide experimental data, we constructed the core regulatory network. Interestingly, we found that the core regulatory network is organized by simple cascade and has few complex regulations such as feedback or feed-forward loops. Moreover, we discovered that the regulatory links from genes in the core regulatory network to genes in the peripheral regulatory network are much more abundant than the reverse direction links. These results suggest that the core regulatory network locates at the top of regulatory network and plays a role as a 'hub' in terms of information flow, and the information that is common to all cells can be modified to achieve the tissue-specific characteristics through various types of feedback and feed-forward loops in the peripheral regulatory networks. We also found that the genes in the core regulatory network are evolutionary conserved, essential and non-disease, non-druggable genes compared to the peripheral genes. Overall, our study provides an insight into how all human cells share a common function and generate tissue-specific functional traits by transmitting and processing information through regulatory network.

  4. REGULATORY AGENCIES, CONSUMER AND ENVIROMENT

    Giseli Valezi Raymundo

    2011-03-01

    Full Text Available The aim of this paper is to present the analysis on the insertion of the consumer in the current model of State in Brazil, considering the nowaday legal system. It is wished to be shown, moreover, the already existing reality on the theme, even if modest, so to in a way to question the responsibility of the consumer, according to its consuming habits and its inertia, takes in today’s technological society. To such proposal, the most effective research method, and, for this reason had been used in this paper, is the extensive bibliography research and legislation consultation. Through it, it had been found that the State model has changed over the past decades in order to delegate the execution of various activities of State ownership to private enterprise, in view of the existence of a minimal State and governor. In this sense, there were created the Regulatory Agencies, which are indirect public administration entities, with the ultimate objective of regulating and supervising the execution of those legal activities, performed by the private sector. The consumer, inserted in this reality, is the direct recipient of the action of the mentioned entities, questioning the legislative and sanction legitimacy of the regulatory entities as well as the possibility of judicial review on the merits of administrative actions of these entities and the applicability of the Brazilian Code of Defense of the Consumer (CDC to the execution of public services, a discipline that affects the administrative law rights. Notwithstanding the above analysis in context, all these social workers, consumers and regulatory agencies are immersed in changing habits, due to the optimization of actions, aimed at preserving the environment, the prospect of achieving sustainable development. Based on this perspective, the results brought by the survey showed that the application of the Brazilian Code of Defense of the Consumer in relations between consumers does not preclude

  5. ERCP in acute pancreatitis

    Jijo V Cherian; Joye Varghese Selvaraj; Rajesh Natrayan; Jayanthi Venkataraman

    2007-01-01

    BACKGROUND:The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute pancreatitis has evolved over years since its introduction in 1968. Its importance in diagnosing the etiology of pancreatitis has steadily declined with the advent of less invasive diagnostic tools. The therapeutic implications of ERCP in acute pancreatitis are many fold and are directed towards management of known etiological factors or its related complications. This article highlights the current status of ERCP in acute pancreatitis. DATA SOURCES:An English literature search using PubMed database was conducted on ERCP in acute pancreatitis, the etiologies and complications of pancreatitis amenable to endotherapy and other related subjects, which were reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management of biliary pancreatitis in speciifc situations, pancreatitis due to microlithiasis, speciifc types of sphincter of Oddi dysfunction, pancreas divisum, ascariasis and malignancy. In recurrent acute pancreatitis and smoldering pancreatitis it has a deifnite therapeutic utility. Complications of acute pancreatitis including pancreatic-duct disruptions or leaks, benign pancreatic-lfuid collections and pancreatic necrosis can be beneifcially dealt with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in detecting pancreatic malignancy. CONCLUSIONS:The role of ERCP in acute pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role in the management continues to evolve and advanced invasive procedures should be undertaken only in centers dedicated to pancreatic care.

  6. Childhood poverty and recruitment of adult emotion regulatory neurocircuitry.

    Liberzon, Israel; Ma, Sean T; Okada, Go; Ho, S Shaun; Swain, James E; Evans, Gary W

    2015-11-01

    One in five American children grows up in poverty. Childhood poverty has far-reaching adverse impacts on cognitive, social and emotional development. Altered development of neurocircuits, subserving emotion regulation, is one possible pathway for childhood poverty's ill effects. Children exposed to poverty were followed into young adulthood and then studied using functional brain imaging with an implicit emotion regulation task focused. Implicit emotion regulation involved attention shifting and appraisal components. Early poverty reduced left dorsolateral prefrontal cortex recruitment in the context of emotional regulation. Furthermore, this emotion regulation associated brain activation mediated the effects of poverty on adult task performance. Moreover, childhood poverty also predicted enhanced insula and reduced hippocampal activation, following exposure to acute stress. These results demonstrate that childhood poverty can alter adult emotion regulation neurocircuitry, revealing specific brain mechanisms that may underlie long-term effects of social inequalities on health. The role of poverty-related emotion regulatory neurocircuitry appears to be particularly salient during stressful conditions.

  7. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Olfa Kassar

    2015-01-01

    Full Text Available Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients.

  8. Acute urinary retention in a young man secondary to colonic irrigation: a case report

    Raheem Omer A

    2009-06-01

    Full Text Available Abstract Introduction Autonomic innervation of the bladder is complex and regulated by a hierarchy of mechanisms of the central nervous system. Any dysfunction in these regulatory mechanisms can lead to acute urinary retention. Case presentation A 36-year-old Caucasian man presented with acute urinary retention following extensive bowel irrigation. His urinary bladder was decompressed and his normal voiding mechanism was restored thereafter. Conclusion We postulate that prolonged anorectal and sigmoid dilatation can stimulate the recto-vesicourethral reflex and lead to acute urinary retention via autonomic dysfunction.

  9. Acute oncological emergencies.

    Gabriel, J

    2012-01-01

    The number of people receiving systemic anti-cancer treatment and presenting at emergency departments with treatment-related problems is rising. Nurses will be the first point of contact for most patients and need to be able to recognise oncological emergencies to initiate urgent assessment of patients and referral to the acute oncology team so that the most appropriate care can be delivered promptly. This article discusses the role of acute oncology services, and provides an overview of the most common acute oncological emergencies.

  10. Endocrine cells producing regulatory peptides.

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  11. Regulatory Issues Surrounding Merchant Interconnection

    Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

  12. Global Summit on Regulatory Science 2013.

    Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

    2014-12-01

    Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed.

  13. [Advanced therapy: from European regulatory framework to national regulatory framework].

    Lucas-Samuel, S

    2013-05-01

    The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012.

  14. Environmental Regulatory Update Table, December 1991

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental Regulatory Update Table, April 1989

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  16. Environmental Regulatory Update Table, October 1991

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  17. Environmental Regulatory Update Table, September 1991

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  18. Environmental Regulatory Update Table, August 1991

    Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

    1991-09-01

    This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Regulatory Risk under Optimal Incentive Regulation

    Strausz, Roland

    2009-01-01

    The paper provides a tractable, analytical framework to study regulatory risk under optimal incentive regulation. Regulatory risk is captured by uncertainty about the policy variables in the regulator’s objective function: weights attached to profits and costs of public funds. Results are as follows: 1) The regulator’s reaction to regulatory risk depends on the curvature of the aggregate demand function. 2) It yields a positive information rent effect exactly when demand is convex. 3) Firms b...

  20. Environmental Regulatory Update Table, December 1989

    Houlbert, L.M.; Langston, M.E. (Tennessee Univ., Knoxville, TN (USA)); Nikbakht, A.; Salk, M.S. (Oak Ridge National Lab., TN (USA))

    1990-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental Regulatory Update Table, November 1991

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. Environmental regulatory update table, March 1989

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-04-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. Treatment of acute gout.

    Schlesinger, Naomi

    2014-05-01

    This article presents an overview of the treatment of acute gout. Nonpharmacologic and pharmacologic treatments, monotherapy versus combination therapy, suggested recommendations, guidelines for treatment, and drugs under development are discussed.

  4. Acute genital ulcers.

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora

    2014-01-28

    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers.

  5. Acute Radiation Syndrome

    ... Matters Information on Specific Types of Emergencies Acute Radiation Syndrome (ARS): A Fact Sheet for the Public ... is called the radiation dose. People exposed to radiation will get ARS only if: The radiation dose ...

  6. Acute Intermittent Porphyria (AIP)

    ... attacks, but are usually not chronic. Wearing a Medic Alert bracelet is advisable for patients who have ... Week is ONE Month Away! Mar 17, 2017 Access to Care Toolkit for the Acute Porphyrias is ...

  7. Acute Lymphocytic Leukemia

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/CON-20042915 . Mayo Clinic Footer Legal Conditions and ...

  8. Acute Myelogenous Leukemia (AML)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/basics/definition/CON-20043431 . Mayo Clinic Footer Legal Conditions and ...

  9. Acute mountain sickness

    High altitude cerebral edema; Altitude anoxia; Altitude sickness; Mountain sickness; High altitude pulmonary edema ... Acute mountain sickness is caused by reduced air pressure and lower oxygen levels at high altitudes. The faster you ...

  10. Low back pain - acute

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back ... lower back supports most of your body's weight. Low back pain is the number two reason that ...

  11. Microvascular dysfunction is associated with plasma osteoprotegerin levels in patients with acute myocardial infarction

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2013-01-01

    Osteoprotegerin (OPG) is a glycoprotein that inhibits nuclear factor-κB's regulatory effects on inflammation, skeletal, and vascular systems, and is a potential biomarker of atherosclerosis and seems to be involved in vascular calcifications. The objective of this study was to assess the relation...... the relationship between OPG, left ventricular function, and microvascular function in patients with acute myocardial infarction (AMI)....

  12. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Blous, L.; Peters, J.G.P.; Blaney Davidson, E.N.; Kraan, P.M. van der; Swinkels, D.W.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study wa

  13. Acute local radiation injuries

    Gongora, R. (Institut Curie, 75 - Paris (France)); Jammet, H. (Commissariat a l' Energie Atomique, ISPN, 92 - Fontenay-aux-Roses (France))

    1983-01-01

    Local acute radiation injuries do not occur very often. Their origin is generally accidental. They show specific anatomo-clinical features. The clinical evolution and therapeutic behaviour are dependent on the dose level and topographical distribution. The dosimetric assessment requires physical methods and paraclinical investigations. From a study of 60 cases followed by the International Center of Radiopathology, the clinical symptomatology is described and the problems raised to the radiopathologist physician by local acute radiation injuries are stated.

  14. Acute liver failure

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  15. [Acute Kidney Injury].

    Brix, Silke; Stahl, Rolf

    2017-02-01

    Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.

  16. The split personality of regulatory T cells in HIV infection.

    Chevalier, Mathieu F; Weiss, Laurence

    2013-01-03

    Natural regulatory T cells (Tregs) participate in responses to various chronic infections including HIV. HIV infection is associated with a progressive CD4 lymphopenia and defective HIV-specific CD8 responses known to play a key role in the control of viral replication. Persistent immune activation is a hallmark of HIV infection and is involved in disease progression independent of viral load. The consequences of Treg expansion, observed in HIV infection, could be either beneficial, by suppressing generalized T-cell activation, or detrimental, by weakening HIV-specific responses and thus contributing to viral persistence. The resulting balance between Tregs contrasting outcomes might have critical implications in pathogenesis. Topics covered in this review include HIV-induced alterations of Tregs, Treg cell dynamics in blood and tissues, Treg-suppressive function, and the relationship between Tregs and immune activation. This review also provides a focus on the role of CD39(+) Tregs and other regulatory cell subsets. All these issues will be explored in different situations including acute and chronic infection, antiretroviral treatment-mediated viral control, and spontaneous viral control. Results must be interpreted with regard to both the Treg definition used in context and to the setting of the disease in an attempt to draw clearer conclusions from the apparently conflicting results.

  17. Reduction of regulatory risk: a network economic approach

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

  18. Regulatory T cells as immunotherapy

    Benjamin David Singer

    2014-02-01

    Full Text Available Regulatory T cells (Tregs suppress exuberant immune system activation and promote immunologic tolerance. Because Tregs modulate both innate and adaptive immunity, the biomedical community has developed intense interest in using Tregs for immunotherapy. Conditions that require clinical tolerance to improve outcomes—autoimmune disease, solid organ transplantation, and hematopoietic stem cell transplantation—may benefit from Treg immunotherapy. Investigators have designed ex vivo strategies to isolate, preserve, expand, and infuse Tregs. Protocols to manipulate Treg populations in vivo have also been considered. Barriers to clinically feasible Treg immunotherapy include Treg stability, off-cell effects, and demonstration of cell preparation purity and potency. Clinical trials involving Treg adoptive transfer to treat graft versus host disease preliminarily demonstrated the safety and efficacy of Treg immunotherapy in humans. Future work will need to confirm the safety of Treg immunotherapy and establish the efficacy of specific Treg subsets for the treatment of immune-mediated disease.

  19. Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

    Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

    2016-10-01

    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.

  20. Regulatory fit messages and physical activity motivation.

    Pfeffer, Ines

    2013-04-01

    Targeted communication about health behaviors seems to be more effective than mass communication in which undifferentiated audiences receive identical messages. Regulatory focus is psychological variable that can be used to build two target groups: promotion-focused or prevention-focused people. It is hypothesized that targeting messages to an individual's regulatory focus creates regulatory fit and is more successful to promote a physically active lifestyle than nonfit messages. Two different print messages promoting a physically active lifestyle derived from regulatory focus theory (promotion message vs. prevention message) were randomly assigned to N = 98 participants after measuring their regulatory focus. It was examined whether regulatory fit between the regulatory focus and the assigned print message would lead to more positive evaluations in the dependent variables inclination toward the message (preference for the message), intention to perform the behavior, prospective and retrospective feelings associated with the behavior (positive and negative), and perceived value of the behavior directly after reading the message. Hierarchical linear regression analyses revealed that regulatory fit led to stronger intentions in the prevention-message condition and more prospective positive and retrospective positive feelings associated with the behavior in the promotion-message condition in contrast to the nonfit conditions. Prospective positive feelings associated with the behavior mediated the effect of regulatory fit on intention. The results partly provided support for the regulatory fit concept. Matching print messages to the regulatory focus of individuals seems to be a useful approach to enhance physical activity motivation. Future studies should include an objective measure of physical activity behavior.

  1. 78 FR 70602 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-11-26

    ... financial asset, such as a consumer or student loan, a lease, or a secured or unsecured receivable, but...-2013-046] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... on November 13, 2013, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with...

  2. 77 FR 14052 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-03-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on February 28, 2012, Financial Industry Regulatory..., departmental information barriers, space sharing arrangements, lease and/or sub-lease agreements). Standard...

  3. 77 FR 65436 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2012-10-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Transactions October 23, 2012. I. Introduction On August 29, 2012, the Financial Industry Regulatory Authority... apply to MBS TBA transactions ``not for good delivery'' and standard data elements will be...

  4. 77 FR 8938 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-02-15

    ... regulatory risks and trends, irrespective of firm size. FINRA also explained that many of the line items will... important to identify revenue sources, enable FINRA to segment firms, and identify regulatory risk and... believes that more granular detail for trading revenue is warranted because the regulatory risks...

  5. 78 FR 76973 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    2013-12-20

    ... #0; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER contains regulatory documents #0..., and 225 Regulations H, Q, and Y RIN 7100-AD 87 Regulatory Capital Rules: Regulatory Capital... Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches...

  6. 75 FR 17460 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-04-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 26, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  7. 78 FR 59995 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-09-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on September 16, 2013, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  8. 75 FR 30457 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-06-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change Relating to the Restated Certificate of Incorporation of Financial Industry Regulatory...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on May 21, 2010, Financial...

  9. 77 FR 5610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2012-02-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  10. 78 FR 46652 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-08-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\3\\ notice is hereby given that, on July 18, 2013, Financial Industry Regulatory Authority, Inc... as described in Items I, II and III below, which Items have been prepared by the...

  11. 75 FR 68654 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-11-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  12. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-05-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers,...

  13. 78 FR 37261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-06-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 3, 2013, Financial Industry Regulatory... rule change from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I....

  14. 77 FR 68181 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2012-11-15

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on November 2, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  15. 75 FR 8771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2010-02-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Adopt FINRA Rule 2261 (Disclosure of Financial Condition) in the Consolidated FINRA Rulebook February 18, 2010. On November 18, 2009, the Financial Industry Regulatory Authority,...

  16. 76 FR 65307 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-10-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 6, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  17. 76 FR 11830 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-03-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on February ] 22, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  18. 77 FR 77162 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-12-31

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 20, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  19. 77 FR 4599 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-01-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 10, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  20. 77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2012-02-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  1. 75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-06-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 17, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  2. 75 FR 59300 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-09-27

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on September 17, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  3. 75 FR 39610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-07-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Financial Industry Regulatory Authority, Inc...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 24, 2010, Financial...

  4. 76 FR 29808 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2011-05-23

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Distributions) May 18, 2011. I. Introduction On April 26, 2011, the Financial Industry Regulatory Authority, Inc... 29, 2011. II. Description of the Proposed Rule Change On November 29, 2010, FINRA issued...

  5. 76 FR 11542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2011-03-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... 24, 2011. I. Introduction On November 10, 2010, the Financial Industry Regulatory Authority, Inc... fidelity bond will be a great financial burden for small firms.\\16\\ The third commenter agrees with...

  6. 76 FR 68240 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2011-11-03

    ...-2011-062] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 20, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  7. 77 FR 1119 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2012-01-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  8. 76 FR 77034 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-12-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 2, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  9. 75 FR 56641 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    2010-09-16

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting..., 2010. On June 17, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...''); and letter from Manisha Kimmel, Executive Director, Financial Information Forum, On behalf of the...

  10. 76 FR 61773 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-10-05

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Expansion of the Order Audit Trail System to All NMS Stocks September 29, 2011. Pursuant to Section 19(b)(1... given that on September 27, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed...

  11. 76 FR 81551 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    2011-12-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change Relating to Amendments to the Order Audit Trail System Rules December 21, 2011. I. Introduction On October 28, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with...

  12. 76 FR 25399 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-05-04

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... of the Order Audit Trail System to All NMS Stocks April 29, 2011. Pursuant to Section 19(b)(1) of the... April 26, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  13. 75 FR 69725 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2010-11-15

    ...-2010-058] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... the FINRA Trade Reporting and Order Audit Trail System Rules Approved in SR-FINRA-2010-043 November 8... thereunder,\\2\\ notice is hereby given that on November 5, 2010, Financial Industry Regulatory Authority,...

  14. 76 FR 71404 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-11-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to the Order Audit Trail System Definitions of... November 4, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  15. 76 FR 37384 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-06-27

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Exemptions from the Order Audit Trail System..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  16. 76 FR 74105 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-11-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... November 21, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... significant increase in trading pauses involving rights and warrants since the inclusion of the Phase...

  17. 78 FR 23507 - Notice of Regulatory Review

    2013-04-19

    ... individual comments. Factors that FHFA's regulatory review plan identifies as relevant to the review, and... year, applying factors enumerated in the plan. The regulatory review plan is available at the following... unduly burdensome; (2) Marketplace developments, technological evolution, and related changes that...

  18. The Political Economy of Regulatory Change

    Buch-Hansen, Hubert

    2012-01-01

    This article aims to explain the broader evolution of British merger control. To this end it outlines a novel critical political economy perspective on regulation and regulatory change which differs from established political economy approaches, such as the regulatory capitalism/state perspectives...

  19. 5 CFR 880.102 - Regulatory structure.

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 880.102 Section 880.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... Regulatory structure. (a) This part contains the following subparts: (1) Subpart A contains...

  20. 5 CFR 847.102 - Regulatory structure.

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 847.102 Section 847.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... INSTRUMENTALITIES General Provisions § 847.102 Regulatory structure. (a)(1) Subpart A of this part...

  1. 5 CFR 838.102 - Regulatory structure.

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  2. Meditation and its regulatory role on sleep

    Ravindra P. Nagendra

    2012-04-01

    Full Text Available Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine and immune functions and thus mediate global regulatory changes in various behavioural states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  3. Meditation and its regulatory role on sleep.

    Nagendra, Ravindra P; Maruthai, Nirmala; Kutty, Bindu M

    2012-01-01

    Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine, and immune functions and thus mediate global regulatory changes in various behavioral states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  4. Genomics in the land of regulatory science.

    Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

    2015-06-01

    Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making.

  5. 76 FR 40208 - Regulatory Flexibility Agenda

    2011-07-07

    ... Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility Analysis Required... FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility... 70 FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ............

  6. 77 FR 47328 - Reducing Regulatory Burden

    2012-08-08

    ... health and safety, and other advantages; distributive impacts; and equity). The regulatory process... businesses and the public. Agencies consider low-cost approaches that reduce burdens and maintain flexibility...-regulatory-system . The Department is committed to maintaining a consistent culture of retrospective...

  7. Collective action : a regulatory focus perspective

    Zaal, Maarten Pieter

    2012-01-01

    In this dissertation I investigate how individuals respond to collective disadvantage from the perspective of regulatory focus theory. Regulatory focus theory distinguishes between two motivational systems: promotion focus, the system in charge of the approach of positive end-states, and prevention

  8. Meditation and Its Regulatory Role on Sleep

    Nagendra, Ravindra P.; Maruthai, Nirmala; Kutty, Bindu M.

    2012-01-01

    Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine, and immune functions and thus mediate global regulatory changes in various behavioral states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  9. 21 CFR 26.18 - Regulatory collaboration.

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory collaboration. 26.18 Section 26.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL... Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.18 Regulatory...

  10. Regulatory Reform: Low Risk, High Promise.

    Tanenbaum, Morris

    The press of telecommunication technologies and their progeny have undermined the natural monopoly basis for long distance telecommunications and customer premise products, forced open regulatory doors, toppled barriers to market entry, and led to the reshaping of regulatory philosophy as regulators have seen new, wider horizons for the industry.…

  11. Department of Agriculture Semiannual Regulatory Agenda

    2010-04-26

    ... Part III Department of Agriculture Semiannual Regulatory Agenda ] DEPARTMENT OF AGRICULTURE (USDA) DEPARTMENT OF AGRICULTURE Office of the Secretary 7 CFR Subtitle A, Chs. I-VII, IX-XII, XIV-XVIII, XXI, XXIV.... Department of Agriculture (USDA) in conformance with Executive Order 12866 ``Regulatory Planning and...

  12. 49 CFR 355.21 - Regulatory review.

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Regulatory review. 355.21 Section 355.21... AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Requirements § 355.21 Regulatory review... review are provided in the appendix to this part. (b) Responsibility. The State agency designated as...

  13. Precision Medicine for Acute Myeloid Leukemia

    Lai, Catherine; Karp, Judith E.; Hourigan, Christopher S.

    2016-01-01

    The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints. PMID:26514194

  14. Management of acute hepatitis B.

    Shiffman, Mitchell L

    2010-02-01

    Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV. These patients will frequently remain undiagnosed for years or decades. Approximately 1% of persons with acute HBV develop acute liver failure. Preventing acute HBV with vaccination is the best treatment. Although universal vaccination is now administered to newborns in many countries, the majority of adults have not been vaccinated and remain at risk. Because the majority of patients with acute HBV resolve this infection spontaneously, treatment with an oral anti-HBV agent is not necessary. However, the use of an oral anti-HBV agent is not unreasonable to use in a patient who is developing acute liver failure from severe acute HBV.

  15. Adaptive Dynamics of Regulatory Networks: Size Matters

    Martinetz Thomas

    2009-01-01

    Full Text Available To accomplish adaptability, all living organisms are constructed of regulatory networks on different levels which are capable to differentially respond to a variety of environmental inputs. Structure of regulatory networks determines their phenotypical plasticity, that is, the degree of detail and appropriateness of regulatory replies to environmental or developmental challenges. This regulatory network structure is encoded within the genotype. Our conceptual simulation study investigates how network structure constrains the evolution of networks and their adaptive abilities. The focus is on the structural parameter network size. We show that small regulatory networks adapt fast, but not as good as larger networks in the longer perspective. Selection leads to an optimal network size dependent on heterogeneity of the environment and time pressure of adaptation. Optimal mutation rates are higher for smaller networks. We put special emphasis on discussing our simulation results on the background of functional observations from experimental and evolutionary biology.

  16. Adaptive Dynamics of Regulatory Networks: Size Matters

    2009-03-01

    Full Text Available To accomplish adaptability, all living organisms are constructed of regulatory networks on different levels which are capable to differentially respond to a variety of environmental inputs. Structure of regulatory networks determines their phenotypical plasticity, that is, the degree of detail and appropriateness of regulatory replies to environmental or developmental challenges. This regulatory network structure is encoded within the genotype. Our conceptual simulation study investigates how network structure constrains the evolution of networks and their adaptive abilities. The focus is on the structural parameter network size. We show that small regulatory networks adapt fast, but not as good as larger networks in the longer perspective. Selection leads to an optimal network size dependent on heterogeneity of the environment and time pressure of adaptation. Optimal mutation rates are higher for smaller networks. We put special emphasis on discussing our simulation results on the background of functional observations from experimental and evolutionary biology.

  17. 75 FR 79449 - Introduction to The Regulatory Plan and the Unified Agenda of Federal Regulatory and Deregulatory...

    2010-12-20

    ... proposed or final form during the upcoming fiscal year. The Regulatory Plan (Plan) and the Unified Agenda... Information Service Center Introduction to The Regulatory Plan and the Unified Agenda of Federal Regulatory... Unified Agenda of Federal Regulatory and Deregulatory Actions AGENCY: Regulatory Information...

  18. Acute pancreatitis in children

    Jokić Radoica

    2012-01-01

    Full Text Available Introduction. Acute pancreatitis in children is mostly due to abdominal trauma, diseases or congenital anomalies of the biliary-pancreatic tree. Both exogenous and endogenous functions of the gland could be disturbed by various levels of damage. Clinical Finding and Diagnostics. Acute abdominal pain, gastrointestinal signs and general deterioration are the main clinical findings. The examination can be completed by blood and urine tests of amylase, electrolytes level, and the C-reactive protein. In addition to these tests, ultrasound, computed tomography and endoscopy are required as well. Therapeutic Methods. The therapy of choice is non-operative treatment using medicaments to control the pain, decrease the pancreatic activity and prevent further complications. If the conservative treatment fails, the surgical approach is necessary: drainage, resections, by-pass procedures, etc. Conclusion. Acute pancreatitis is a very serious disease in childhood. Clinical experience and rational approach are very important in the diagnostic and therapeutic methods.

  19. Treatment of acute pancreatitis

    Al-Mofleh Ibrahim

    1998-01-01

    Full Text Available There is no specific treatment for acute pancreatitis. Majority of patients with acute pancreatitis respond to medical therapy. Supportive measures and close observations represent the cornerstone of the medical therapy. Failure to respond to medical treatment may indicate choledocholithiasis or infected necrosis. Endoscopic papillotomy with stone retrieval is beneficial in patients with severe biliary pancreatitis. Image-guided fine needle aspiration and bacteriological examination of aspirate is reliable in detecting infection and deliniating causative pathogen. Surgical debridement is the method of choice for treatment of infected necrosis. In contrast, in pancreatic abscess, surgery is preserved for those, who do not respond to percutaneous drainage combined with antibiotics. The benefit of antisecretory and antiproteolytic agents is debatable. A combination of antioxidants, calcium channel antagonists and antibiotics may play a major role in the treatment of acute pancreatitis in the future.

  20. [Acute hypertrygliceridemic pancreatitis].

    Senosiain Lalastra, Carla; Tavío Hernández, Eduardo; Moreira Vicente, Victor; Maroto Castellanos, Maite; García Sánchez, Maria Concepción; Aicart Ramos, Marta; Téllez Vivajos, Luis; Cuño Roldán, José Luis

    2013-04-01

    Acute hypertriglyceridemic pancreatitis is the third cause of acute pancreatitis in the Western population. There is usually an underlying alteration in lipid metabolism and a secondary factor. Clinical presentation is similar to that of pancreatitis of other etiologies, but the course of acute hypertriglyceridemic pancreatitis seems to be worse and more recurrent. Some laboratory data can be artefacts, leading to diagnostic errors. This is the case of amylase, which can show false low levels. Treatment is based on intense fluidotherapy and analgesia. When there is no response to conservative management, other methods to lower triglyceride levels should be used. Several options are available, such as plasmapheresis, insulin, and heparin. The present article provides a review of the current literature on this entity.

  1. Acute management of stones

    Jung, Helene; Osther, Palle J S

    2015-01-01

    INTRODUCTION: Stone management is often conservative due to a high spontaneous stone passage rate or non-symptomatic calyceal stones that do not necessarily require active treatment. However, stone disease may cause symptoms and complications requiring urgent intervention. MATERIAL AND METHODS......: In this review, we update latest research and current recommendations regarding acute management of stones, with particular focus on imaging, pain management, active stone interventions, medical expulsive therapy, and urolithiasis in pregnancy and childhood. RESULTS: Acute stone management should be planned...... with careful consideration of stone size and location, symptoms, patient comorbidity and radiation dose. CONCLUSION: In case of infective hydronephrosis, compromised renal function or persistent pain despite adequate analgesic treatment acute intervention is indicated....

  2. Review of Quantitative Structure - Activity Relationships for Acute Mammalian Toxicity

    Iglika Lessigiarska

    2006-12-01

    Full Text Available This paper reviews Quantitative Structure-Activity Relationship (QSAR models for acute mammalian toxicity published in the last decade. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate system for predicting acute toxicity to mammals. On the basis of the review, the following conclusions can be made: i a relatively small number of models for in vivo toxicity are published in the literature. This is due to the nature of the endpoint - acute systemic toxicity is usually related to whole body phenomena and therefore is very complex. The complexity of the mechanisms involved leads to difficulties in the QSAR modelling; ii most QSAR models identify hydrophobicity as a parameter of high importance for the modelled toxicity. In addition, many models indicate the role of the electronic and steric effects; iii most of the literature-based models are restricted to single chemical classes. Models based on more heterogeneous data sets are those incorporated in expert systems. In general, the QSAR models for mammalian toxicity identified in this review are considered useful for investigating the mechanisms of toxicity of defined chemical classes. However, for predictive purposes in the regulatory assessment of chemicals most of the models require additional information to satisfy internationally agreed validation principles. In addition, the development of new models covering larger chemical domains would be useful for the regulatory assessment of chemicals.

  3. Pharm GKB: Leukemia, Promyelocytic, Acute [PharmGKB

    Full Text Available Overview Alternate Names: Synonym APL - Acute promyelocytic leukaemia; APL - Acute ...promyelocytic leukemia; APML - Acute promyelocytic leukaemia; APML - Acute promyelocytic leukemia; Acute Promyelocytic Leukemia; Acut...e Promyelocytic Leukemias; Acute myeloid leukaemia, PML/RAR-alpha; Acute myeloid le...ukemia, PML/RAR-alpha; Acute myeloid leukemia, t(15;17)(q22;q11-12); Acute promye...locytic leukaemia (clinical); Acute promyelocytic leukaemia, FAB M3; Acute promyelocytic leukaemia, PML/RAR-alpha; Acute

  4. Pharm GKB: Leukemia, Erythroblastic, Acute [PharmGKB

    Full Text Available Overview Alternate Names: Synonym AML M6; Acute Erythroblastic Leukemia; Acute Erythroblastic Leukemias; Acu...te erythraemic myelosis [obs]; Acute erythremia [obs]; Acute erythremic myelosis [obs]; Acute... erythroid leukaemia; Acute erythroid leukemia; Acute myeloid leukaemia, M6 type; Acute myeloid le...Erythroblastic Leukemia, Acute; Erythroblastic Leukemias, Acute; Erythroleukaemia...; Erythroleukemia; Erythroleukemias; FAB M6; Leukemia, Acute Erythroblastic; Leukemia, Myeloid, Acute, M6; Leukemias, Acute

  5. Orphan drugs: the regulatory environment.

    Franco, Pedro

    2013-02-01

    The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases.

  6. Congenital acute megakaryocytic leukemia

    N B Mathur

    2011-01-01

    Full Text Available Congenital leukemia (CL is an extremely rare disorder in the newborn, significant proportion of which is of myeloid origin, primarily of M4 or M5 morphology. As compared to pediatric leukemia, CL is a more aggressive disease. Acute myeloid leukemia (AML-M7 or acute megakaryocytic leukemia is a rare type of AML with an incidence of 0.5 per million per year. Median age of presentation is 6 years, and children may present with a broad variety of symptoms including low-grade fever, diarrhea, easy bruising, failure to gain weight and life-threatening conditions.

  7. 77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

    2012-09-28

    ... Promoting U.S. EC Regulatory Compatibility AGENCY: Office of the United States Trade Representative. ACTION... greater transatlantic regulatory compatibility generally. Concrete ideas on how greater compatibility... and EC invite your views on how to promote greater transatlantic regulatory compatibility...

  8. Regulatory focus and the assignment of punishment

    Chloe Carmichael

    2007-06-01

    Full Text Available Regulatory Focus has been demonstrated to influence human behavior in a number of domains, such as object valuation and readiness to commit time or money to social projects. It has also been demonstrated to influence an individual’s approach to mistakes; and a person’s preference for global or local processing of information. The present work seeks to consider how regulatory focus might interact with punitive behaviors, specifically, the assignment of legal punishment. In this study, 240 undergraduates completed a series of written instruments that assessed their regulatory focus. They read a vignette that described a target that commits a crime, is detected by the police, and is arrested due to a careless mistake. Participants were asked what level of legal punishment they deemed appropriate. Participants’ punitive evaluations show that there are significant interactions a between the regulatory focus of the participant and the regulatory focus of the target and b between the regulatory focus of the participant and the level of detail used to describe the target and her behavior. In each case, when the regulatory foci matched, causing ‘fit,’ the participant was more lenient than in the non-fit condition.

  9. Regulatory analysis technical evaluation handbook. Final report

    NONE

    1997-01-01

    The purpose of this Handbook is to provide guidance to the regulatory analyst to promote preparation of quality regulatory analysis documents and to implement the policies of the Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission (NUREG/BR-0058 Rev. 2). This Handbook expands upon policy concepts included in the NRC Guidelines and translates the six steps in preparing regulatory analyses into implementable methodologies for the analyst. It provides standardized methods of preparation and presentation of regulatory analyses, with the inclusion of input that will satisfy all backfit requirements and requirements of NRC`s Committee to Review Generic Requirements. Information on the objectives of the safety goal evaluation process and potential data sources for preparing a safety goal evaluation is also included. Consistent application of the methods provided here will result in more directly comparable analyses, thus aiding decision-makers in evaluating and comparing various regulatory actions. The handbook is being issued in loose-leaf format to facilitate revisions. NRC intends to periodically revise the handbook as new and improved guidance, data, and methods become available.

  10. Modeling of hysteresis in gene regulatory networks.

    Hu, J; Qin, K R; Xiang, C; Lee, T H

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function.

  11. Regulatory bioinformatics for food and drug safety.

    Healy, Marion J; Tong, Weida; Ostroff, Stephen; Eichler, Hans-Georg; Patak, Alex; Neuspiel, Margaret; Deluyker, Hubert; Slikker, William

    2016-10-01

    "Regulatory Bioinformatics" strives to develop and implement a standardized and transparent bioinformatic framework to support the implementation of existing and emerging technologies in regulatory decision-making. It has great potential to improve public health through the development and use of clinically important medical products and tools to manage the safety of the food supply. However, the application of regulatory bioinformatics also poses new challenges and requires new knowledge and skill sets. In the latest Global Coalition on Regulatory Science Research (GCRSR) governed conference, Global Summit on Regulatory Science (GSRS2015), regulatory bioinformatics principles were presented with respect to global trends, initiatives and case studies. The discussion revealed that datasets, analytical tools, skills and expertise are rapidly developing, in many cases via large international collaborative consortia. It also revealed that significant research is still required to realize the potential applications of regulatory bioinformatics. While there is significant excitement in the possibilities offered by precision medicine to enhance treatments of serious and/or complex diseases, there is a clear need for further development of mechanisms to securely store, curate and share data, integrate databases, and standardized quality control and data analysis procedures. A greater understanding of the biological significance of the data is also required to fully exploit vast datasets that are becoming available. The application of bioinformatics in the microbiological risk analysis paradigm is delivering clear benefits both for the investigation of food borne pathogens and for decision making on clinically important treatments. It is recognized that regulatory bioinformatics will have many beneficial applications by ensuring high quality data, validated tools and standardized processes, which will help inform the regulatory science community of the requirements

  12. Acute myeloid leukemia (AML) - children

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  13. Loperamide-Induced Acute Pancreatitis

    Halla Vidarsdottir

    2013-01-01

    Full Text Available Acute pancreatitis is a common disease leading to hospitalizations, most often caused by gallstones or alcohol. We present a case of a patient diagnosed with acute pancreatitis considered to be due to loperamide treatment for diarrhea.

  14. Delegation to Independent Regulatory Authorities in the Media Sector: A Paradigm Shift through the Lens of Regulatory Theory

    K. Irion; R. Radu

    2014-01-01

    Today, it seems that independent regulatory authorities have almost become a natural institutional form for regulatory governance. This trend has economic and political roots, and numerous normative arguments for creating independent regulatory authorities have been put forward in the international

  15. Childhood Acute Lymphoblastic Leukemia

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P;

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was re...

  16. Acute cough in adults

    Jochen W L Cals; Nick A Francis

    2010-01-01

    @@ A healthy, non-smoking 54 year old woman consults with a severe acute cough. It started two weeks ago with symptoms of a common cold, but she is worried about its duration and would like something to "clear it up. "

  17. Acute hemiplegia in childhood

    Okuno, Takehiko; Takao, Tatsuo; Itoh, Masatoshi; Konishi, Yukuo; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

    1983-04-01

    The results of CT in 100 patients with acute hemiplegia in childhood are reported here. The etiology was various: 2 patients had infratentorial brain tumors, 56 had cerebral vascular diseases, 3 had head injuries, 16 had intracranial infectious diseases, one had postinfectious encephalomyelitis, one had multiple sclerosis, 2 had epilepsy, and the diagnosis of 19 were unknown. Eleven patients had a normal CT and a good prognosis. As for the type of onset, there were patients of type 1 with fever and 42 with convulsions and unconsciousness; those of type 2 with convulsions and unconsciousness were 12, and those of type 3 without fever and convulsions were 46. This classification is assumed to be useful, as the type of onset is characteristic of the etiology. Six patients were diagnosed correctly by repeated examinations, although the first CT did not reveal any remarkable findings. Capsular infarction, occlusion of the posterior cerebral artery in acute hemiplegia in childhood, abnormal findings of the internal capsule, thalamus, and midbrain in a patient with postinfectious encephalomyelitis, and a diffuse low density in the CT of the unilateral hemisphere in the patients with acute encephalopathy and acute hemiplegia of an obscure origin have been found after the introduction of computerized tomography.

  18. [Acute pancreatitis and pregnancy].

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery.

  19. Acute liver failure

    Bernal, William; Lee, William M; Wendon, Julia;

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  20. [Acute arsenic poisoning].

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment.

  1. [Acute plasma cell leukemia].

    Monsalbe, V; Domíngues, C; Roa, I; Busel, D; González, S

    1989-01-01

    Plasma Cell Leukemia is a very rare form of plasmocytic dyscrasia, whose clinical and pathological characteristics warrant its recognition as a distinct subentity. We report the case of a 60 years old man who presented a rapidly fatal acute plasma cell leukemia, with multiple osteolytic lesions, hipercalcemia, renal and cardiac failure.

  2. Drug-induced acute pancreatitis

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are consid

  3. Acute periodontal lesions.

    Herrera, David; Alonso, Bettina; de Arriba, Lorenzo; Santa Cruz, Isabel; Serrano, Cristina; Sanz, Mariano

    2014-06-01

    This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute

  4. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model

    Pilat, Nina; Farkas, Andreas M.; Mahr, Benedikt; Schwarz, Christoph; Unger, Lukas; Hock, Karin; Oberhuber, Rupert; Aumayr, Klaus; Wrba, Fritz; Wekerle, Thomas

    2014-01-01

    Background The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection. Metho...

  5. Vpu Mediates Depletion of Interferon Regulatory Factor 3 during HIV Infection by a Lysosome-Dependent Mechanism

    Doehle, Brian P.; Chang, Kristina; Rustagi, Arjun; McNevin, John; McElrath, M. Juliana; Gale, Michael

    2012-01-01

    HIV has evolved sophisticated mechanisms to avoid restriction by intracellular innate immune defenses that otherwise serve to control acute viral infection and virus dissemination. Innate defenses are triggered when pattern recognition receptor (PRR) proteins of the host cell engage pathogen-associated molecule patterns (PAMPs) present in viral products. Interferon regulatory factor 3 (IRF3) plays a central role in PRR signaling of innate immunity to drive the expression of type I interferon ...

  6. Acute pyelonephritis in ER

    Giovanni Volpicelli

    2007-10-01

    Full Text Available Symptoms and signs of acute pyelonephritis sometimes are subtle and emergency physicians attending overcrowded and busy institutions could easily miss the right diagnosis. The presence of a renal damage is decisive in the therapeutic choice. Aims of our study are: 1 to assess prevalence of renal damage in patients presenting to our ED with symptoms and signs of primary urinary tract infection (UTI; 2 to evaluate the reliability of such symptoms and signs in predicting a renal damage; 3 to assess accuracy of the contrast enhanced ultrasound (CEUS in the ED diagnosis of renal damage due to acute uncomplicated pyelonephritis. We studied 54 patients with suspected UTI. Each patient underwent clinical examination, routine blood and urine sampling and conventional renal ultrasound (US. 23 patients had confirmation of acute primary UTI, and performed renal magnetic resonance (MR to rule out renal parenchymal involvement. In 16 patients (69,6% one or more parenchymal lesions were visualized at MR, and diagnosis of acute uncomplicated pyelonephritis was confirmed (group A. The other 7 patients had a diagnosis of UTI without renal involvement (group B. Some of 23 patients presented with few atypical symptoms. Lumbar pain was the most frequent symptom (n = 21, without a statistically significant difference between group A and B (P 0,958; p = 0,328. No other symptom or sign has demonstrated statistically valid in predicting the renal involvement. Renal US was positive in only 3 patients of group A (18,7%. During this first part of our study, CEUS was performed in a limited number of patients (n = 8, and in 7 examinations data were concordant with MR. In conclusion, analysis of our preliminary data confirms that a distinction between patients with different extension of the UTI is not possible through the simple clinical examination and routine tests. CEUS is very promising and its routine employment in the ED could simplify the diagnostic practice in

  7. Modernizing the Regulatory System for Biotechnology Products

    This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

  8. Electricity distribution networks: Changing regulatory approaches

    Cambini, Carlo

    2016-09-01

    Increasing the penetration of distributed generation and smart grid technologies requires substantial investments. A study proposes an innovative approach that combines four regulatory tools to provide economic incentives for distribution system operators to facilitate these innovative practices.

  9. A study of bacterial gene regulatory mechanisms

    Hansen, Sabine

    the different regulatory mechanisms affect system dynamics. We have designed a synthetic gene regulatory network (GRN) in bacterial cells that enables us to study the dynamics of GRNs. The results presented in this PhD thesis show that model equations based on the established mechanisms of action of each...... of a particular type of regulatory mechanism. The synthetic system presented in this thesis is, to our knowledge, the first of its kind to allow a direct comparison of the dynamic behaviors of gene regulatory networks that employ different mechanisms of regulation. In addition to studying the dynamic behavior...... of GRNs this thesis also provided the first evidence of the sensor histidine kinase VC1831 being an additional player in the Vibrio cholerae quorum sensing (QS) GRN. Bacteria use a process of cell-cell communication called QS which enable the bacterial cells to collectively control their gene expression...

  10. Safety & Regulatory Strategy : Food Safety and Innovation

    Kalk, C.

    2013-01-01

    Food and feed safety is strictly regulated within the EU. Our team of toxicologists, risk assessors and consultants offers strategic advice and valuable expertise in regulatory affairs and health risk assessment.

  11. 78 FR 44331 - Semiannual Regulatory Agenda

    2013-07-23

    ... programs as vital tools for creating and preserving American jobs. SBA proposes to strip away regulatory... 500-employee based size standard for NAICS 113310, Logging, but will review it in the near future...

  12. Systemic Risk and Optimal Regulatory Architecture

    Espinosa-Vega, M.A.; Kahn, C.; Matta, R.; Sole, J.

    2011-01-01

    Until the recent financial crisis, the safety and soundness of financial institutions was assessed from the perspective of the individual institution. The financial crisis highlighted the need to take systemic externalities seriously when rethinking prudential oversight and the regulatory architectu

  13. Mobile Source Emissions Regulatory Compliance Data Inventory

    U.S. Environmental Protection Agency — The Mobile Source Emissions Regulatory Compliance Data Inventory data asset contains measured summary compliance information on light-duty, heavy-duty, and non-road...

  14. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    Galli, Maria Cristina

    2016-01-01

    This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described.

  15. Measuring Regulatory Restrictions in Logistics Services

    Claire HOLLWEG; Marn-Heong WONG

    2009-01-01

    This study measures the extent of restrictions on trade in logistics services in the ASEAN+6 economies by constructing a logistics regulatory restrictiveness index for each economy that quantifies the extent of government regulations faced by logistics service providers. This is the first study of its kind to construct a regulatory index of the entire logistics sector, which includes the main modes of international transport and customs restrictions. The indices show that large differences ex...

  16. Mission Risk Reduction Regulatory Change Management

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  17. IPTV Market Development and Regulatory Aspects

    Tadayoni, Reza; Sigurdsson, Halldór Matthias

    2006-01-01

    The aim of this paper is to analyse the development of IPTV technology / market and to discuss major regulatory parameters. A general overview of architectures and the technologies deployed for establishing IPTV services is given and the main stake holder identified, along with, the current service...... architecture, the available content in IPTV platforms, and the current business models. Furthermore the regulatory framework of the TV broadcast and IPTV in Europe is analysed....

  18. Cis-regulatory mutations in human disease.

    Epstein, Douglas J

    2009-07-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few.

  19. Severe Acute Pancreatitis in Pregnancy

    Bahiyah Abdullah

    2015-01-01

    Full Text Available This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes.

  20. KWOC (Key-Word-Out-of-Context) Index of US Nuclear Regulatory Commission Regulatory Guide Series

    Jennings, S.D.

    1990-04-01

    To meet the objectives of the program funded by the Department of Energy (DOE)-Nuclear Energy (NE) Technology Support Programs, the Performance Assurance Project Office (PAPO) administers a Performance Assurance Information Program that collects, compiles, and distributes program-related information, reports, and publications for the benefit of the DOE-NE program participants. THE KWOC Index of US Nuclear Regulatory Commission Regulatory Guide Series'' is prepared as an aid in searching for specific topics in the US Nuclear Regulatory Commission, Regulatory Guide Series.

  1. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  2. Acute chylous ascites mimicking acute appendicitis in a patient with pancreatitis

    Emily K Smith; Edmund Ek; Daniel Croagh; Lavinia A Spain; Stephen Farrell

    2009-01-01

    We report a case of acute chylous peritonitis mimicking acute appendicitis in a man with acute on chronic pancreatitis. Pancreatitis, both acute and chronic, causing the development of acute chylous ascites and peritonitis has rarely been reported in the English literature. This is the fourth published case of acute chylous ascites mimicking acute appendicitis in the literature.

  3. Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes

    Ventre, I.; Goodman, A.L.; Vallet-Gely, I.

    2006-01-01

    S, a hybrid sensor kinase that controls the reciprocal expression of genes for type III secretion and biofilm-promoting polysaccharicles. Domain organization of LadS and the range of LadS-controlled genes suggest that it counteracts the activities of another sensor kinase, RetS. These two pathways converge...... by controlling the transcription of a small regulatory RNA, RsmZ. This work identifies a previously undescribed signal transduction network in which the activities of signal-receiving sensor kinases LadS, RetS, and GacS regulate expression of virulence genes associated with acute or chronic infection...

  4. Prevention of acute malnutrition

    de Pee, Saskia; Grais, Rebecca; Fenn, Bridget;

    2015-01-01

    Acute malnutrition is associated with increased morbidity and mortality risk. When episodes are prolonged or frequent, acute malnutrition is also associated with poor growth and development, which contributes to stunting Nutrition-specific and nutrition-sensitive strategies to prevent...... undernutrition during the first 1,000 days from conception to 24 months of age can reduce the risks of wasting, stunting, and micronutrient deficiencies. Under circumstances that exacerbate the underlying causes of undernutrition and increase the incidence of wasting, such as food insecurity related to lean...... seasons or emergencies, or increased incidence of illness, such as diarrhea or measles, additional efforts are required to prevent and treat wasting. Special nutritious foods directly meet the increased nutrient requirements of children at risk for wasting; assistance to vulnerable households, in the form...

  5. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    Wosten-van Asperen, Roelie M.; Bos, Albert; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, Rene

    2013-01-01

    Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts a

  6. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function

    Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways ...

  7. 75 FR 20868 - Notice of Issuance of Regulatory Guide

    2010-04-21

    ... Issuance and Availability of Regulatory Guide 1.68.2, Revision 2, ``Initial Startup Test Program to... review of applications for permits and licenses. Revision 2 of Regulatory Guide 1.68.2, ``Initial Startup... Regulatory Guide 1.68.2, Revision 2 are available through the NRC's public Web site under ``Regulatory...

  8. 12 CFR 914.1 - Regulatory Report defined.

    2010-01-01

    ... Bank. (b) Examples. Regulatory Report includes: (1) Call reports and reports of instrument-level risk... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Regulatory Report defined. 914.1 Section 914.1... DATA AVAILABILITY AND REPORTING § 914.1 Regulatory Report defined. (a) Definition. Regulatory...

  9. Streptococcal acute pharyngitis

    Lais Martins Moreira Anjos

    2014-07-01

    Full Text Available Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

  10. Acute appendicitis in pregnancy

    Ortiz-Gualdrón César Augusto

    2012-01-01

    Acute appendicitis is the most common non-obstetric surgery pathology in pregnancy, itsincidence can be varied and occurs at a higher rate during the first and second trimesterof gestation. Its diagnosis is difficult and can be confused by the anatomical andphysiological changes during pregnancy, which alter their clinical presentation. Commonsymptoms are abdominal located pain, vomiting and nausea. The diagnosis is mainlyclinical, but laboratory tests and additional imaging help confirm or r...

  11. Acute ischemic cerebral attack

    Franco-Garcia Samir; Barreiro-Pinto Belis

    2010-01-01

    The decrease of the cerebral blood flow below the threshold of autoregulation led to changes of cerebral ischemia and necrosis that traduce in signs and symtoms of focal neurologic dysfunction called acute cerebrovascular symdrome (ACS) or stroke. Two big groups according to its etiology are included in this category the hemorragic that constitue a 20% and the ischemic a 80% of cases. Great interest has wom the ischemic ACS because of its high social burden, being the third cause of no violen...

  12. Perioperative acute renal failure.

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  13. Diagnosis of acute rhinosinusitis.

    Esposito, Susanna; Marchisio, Paola; Tenconi, Rossana; Tagliaferri, Laura; Albertario, Giada; Patria, Maria Francesca; Principi, Nicola

    2012-08-01

    Rhinosinusitis is almost always a complication of a viral infection involving the upper respiratory tract. A common cold is the first symptom of rhinosinusitis, but infectious processes involving the nose inevitably affect the paranasal sinuses because of their anatomical contiguity. The symptoms remain those of a common cold as long as nasal phlogosis is moderate and the ostia between the nose and sinuses are patent. If the inflammation is intense, edema may obliterate the ostia and isolate the sinuses, thus stopping the removal of the exudates. The duration of symptoms makes it possible to distinguish acute (10-30 days) from subacute (30-90 days) and chronic rhinosinusitis (>90 days). The diagnosis of rhinosinusitis should only be based on anamnestic and clinical criteria in children with serious or persistent symptoms of upper respiratory tract infection, or which appear within a short time of an apparent recovery. Computed tomography and magnetic resonance images of the paranasal sinuses should be reserved for children reasonably considered to be candidates for surgery. Antibiotics are recommended in cases of mild acute bacterial rhinosinusitis as a means of accelerating the resolution of symptoms. The use of antibiotics is mandatory in severe acute bacterial rhinosinusitis to cure the disease and avoid the possible onset of severe complications.

  14. 77 FR 8034 - Semiannual Regulatory Agenda and Fiscal Year 2011 Regulatory Plan

    2012-02-13

    ... February 13, 2012 Part XXI Bureau of Consumer Financial Protection Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 77 , No. 29 / Monday, February 13, 2012 / Unified Agenda#0;#0; ] BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Ch. X Semiannual Regulatory Agenda and Fiscal Year 2011...

  15. 76 FR 64419 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    2011-10-18

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Revise the Series 7 Examination Program September...

  16. 78 FR 40776 - Issuance of Regulatory Guide 1.124 and Regulatory Guide 1.130

    2013-07-08

    ...) Boiler and Pressure Vessel Code (B&PVC). Regulatory Guides 1.124 and 1.130 delineates levels of service... 2008 Addenda of the Boiler and Pressure Vessel Code (ASME B&PV Code), Section III, Division 1 (limited... Improvement of Regulatory Guides The NRC typically seeks public comment on a draft version of a...

  17. 78 FR 62417 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    2013-10-22

    ... Part 324 RIN 3064-AD95 Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy, Transition Provisions, Prompt Corrective Action, Standardized Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches Risk-Based Capital Rule,...

  18. 75 FR 52380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-08-25

    ...-2010-044] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change Relating to the Expansion of the Order Audit Trail System to All NMS...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 6, 2010, the Financial...

  19. 75 FR 53362 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2010-08-31

    ..., director, partner or employee of another business organization or owning any stock or having any direct or... controlling, controlled by or under common control with a member or member organization shall have associated... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

  20. 78 FR 37267 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    2013-06-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 1934 (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 3, 2013, Financial... the mandatory inclusion of a non- public arbitrator in a three-arbitrator case raised a...

  1. Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

    Lee, Yang Deok; Lee, Soo Teik

    2002-06-01

    Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.

  2. 77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

    2012-06-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear...

  3. Regulator of G protein signaling 2 (RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1 in live cells.

    Sungho Ghil

    Full Text Available Protease-activated receptor 1 (PAR1 is a G-protein coupled receptor (GPCR that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins interact directly with certain GPCRs to modulate their signals, though cellular mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here, using bioluminescence resonance energy transfer (BRET, we tested whether RGS2 and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Gα-mediated signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in a G protein-dependent manner. Very little BRET activity is observed between PAR1-Venus (PAR1-Ven and either RGS2-Luciferase (RGS2-Luc or RGS4-Luc in the absence of Gα. However, in the presence of specific Gα subunits, BRET activity was markedly enhanced between PAR1-RGS2 by Gαq/11, and PAR1-RGS4 by Gαo, but not by other Gα subunits. Gαq/11-YFP/RGS2-Luc BRET activity is promoted by PAR1 and is markedly enhanced by agonist (TFLLR stimulation. However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A that eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1 binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4 inhibited PAR1/Gα-mediated calcium and MAPK/ERK signaling, respectively, but not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly with PAR1 in Gα-dependent manner to modulate PAR1/Gα-mediated signaling, and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

  4. Pharm GKB: Leukemia, Biphenotypic, Acute [PharmGKB

    Full Text Available Overview Alternate Names: Synonym Acute bilineal leukaemia; Acute bilineal leukemia; Acute... biphenotypic leukaemia; Acute biphenotypic leukemia; Acute mixed lineage leukaemia; Acute mixed line...age leukemia; B and T Cell Acute Lymphoblastic Leukemia; B and T Cell Leukemia, Acute; B- and T-Cell Acute L...ymphoblastic Leukemia; B- and T-Cell Leukemia, Acute; Leukemia, Lymphocytic, Acute..., Mixed Cell; Leukemia, Lymphocytic, Acute, Mixed-Cell; Leukemia, Mixed Cell; Leukemia, Mixed, B and T Cell

  5. Regulatory focus affects physician risk tolerance.

    Veazie, Peter J; McIntosh, Scott; Chapman, Benjamin P; Dolan, James G

    2014-01-01

    Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention-regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (p = 0.01). The Cohen's d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (p = 0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor.

  6. Functional characterization of variations on regulatory motifs.

    Michal Lapidot

    2008-03-01

    Full Text Available Transcription factors (TFs regulate gene expression through specific interactions with short promoter elements. The same regulatory protein may recognize a variety of related sequences. Moreover, once they are detected it is hard to predict whether highly similar sequence motifs will be recognized by the same TF and regulate similar gene expression patterns, or serve as binding sites for distinct regulatory factors. We developed computational measures to assess the functional implications of variations on regulatory motifs and to compare the functions of related sites. We have developed computational means for estimating the functional outcome of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. We predict the effects of nucleotide variations within motifs on gene expression patterns. In cases where such predictions could be compared to suitable published experimental evidence, we found very good agreement. We further accumulated statistics from multiple substitutions across various binding sites in an attempt to deduce general properties that characterize nucleotide substitutions that are more likely to alter expression. We found that substitutions involving Adenine are more likely to retain the expression pattern and that substitutions involving Guanine are more likely to alter expression compared to the rest of the substitutions. Our results should facilitate the prediction of the expression outcomes of binding site variations. One typical important implication is expected to be the ability to predict the phenotypic effect of variation in regulatory motifs in promoters.

  7. Phylogeny based discovery of regulatory elements

    Cohen Barak A

    2006-05-01

    Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

  8. [Acute pulmonary edema secondary to acute upper airway obstruction].

    Sánchez-Ortega, J L; Carpintero-Moreno, F; Olivares-López, A; Borrás-Rubio, E; Alvarez-López, M J; García-Izquierdo, A

    1992-01-01

    We report a 72 years old woman with mild arterial hypertension and no other pathological history who presented an acute pulmonary edema due to acute obstruction of the upper airway secondary to vocal chord paralysis developing during the immediate postoperative phase of thyroidectomy. The acute pulmonary edema resolved after application of tracheal reintubation, mechanical ventilation controlled with end expiratory positive pressure, diuretics, morphine, and liquid restriction. We discuss the possible etiopathogenic possibilities of this infrequent clinical picture and we suggest that all patients who suffered and acute obstruction of the upper airways require a careful clinical surveillance in order to prevent the development of the pulmonary syndrome.

  9. A focus on acute cholecystitis and acute cholangitis

    Massimo Sartelli; Cristian Tranà

    2012-01-01

    Biliary infections are very common intra-abdominal infections. Laparoscopic cholecystectomy for acute cholecystitis and endoscopic retrograde management of acute cholangitis play important roles in the treatment of biliary infections. Also antimicrobial therapy is nevertheless important in the overall management of biliary infections. A multidisciplinary team of physicians, including surgeons trained in laparoscopic techniques, interventional gastroenterologists, and interventional radiologists may improve outcomes of patients with biliary infections. This review focuses the clinical presentation, diagnosis, and state of the art management of acute cholecystitis and acute cholangitis.

  10. A focus on acute cholecystitis and acute cholangitis

    Massimo Sartelli

    2012-01-01

    Full Text Available Biliary infections are very common intra-abdominal infections. Laparoscopic cholecystectomy for acute cholecystitis and endoscopic retrograde management of acute cholangitis play important roles in the treatment of biliary infections. Also antimicrobial therapy is nevertheless important in the overall management of biliary infections. A multidisciplinary team of physicians, including surgeons trained in laparoscopic techniques, interventional gastroenterologists, and interventional radiologists may improve outcomes of patients with biliary infections. This review focuses the clinical presentation, diagnosis, and state of the art management of acute cholecystitis and acute cholangitis.

  11. ICAM-1 and Acute Pancreatitis Complicated by Acute Lung Injury

    XiPing Zhang

    2009-01-01

    Full Text Available One of the most common complications of acute pancreatitis is acute lung injury, during which intercellular adhesion molecule-1 (ICAM-1 plays an important role by participating in leukocyte adhesion and activation as well as by inducing the “cascade effect” of inflammatory mediators, pulmonary microcirculation dysfunction and even acute respiratory distress syndrome, multiple organ failure or death. Although it is generally believed that the modulatory mechanism of ICAM-1 during this process is associated with the activation of nuclear transcription factor kappa B which is mediated by IL-1, IL-6, IL-18 and oxygen free radical, etc., further studies are still required to clarify it. Since the upregulation of ICAM-1 expression in the lung during acute lung injury is one of main pathogeneses, the early detection of the ICAM-1 expression level may contribute to the prevention and treatment of acute lung injury. Moreover, reducing pulmonary ICAM-1 expression levels through treatment with anti-ICAM-1 monoclonal antibody (aICAM-1 and antagonists of the neurokinin 1 receptor, etc., should have a positive effect on protecting the lungs during acute pancreatitis. This review aims to further clarify the relationship between ICAM-1 and acute pancreatitis complicated by acute lung injury, and therefore provides a theoretical basis for the formulation of corresponding therapeutic measures in clinical practice for acute pancreatitis.

  12. Acute leukemic appendicitis in a patient with acute promyelocytic leukemia

    Hatim Karachiwala

    2012-01-01

    Full Text Available Leukemic and lymphomatous infiltration of the appendix is a rare complication. We present the case of a 31-year-old male with acute promyelocytic leukemia who developed acute abdomen on day 11 of induction chemotherapy with idarubicin and cytarabine. After appropriate work-up, a clinical diagnosis of acute appendicitis was made. Despite severe pancytopenia, he successfully underwent laparoscopic appendectomy. The final pathology revealed leukemic infiltration of the appendix. It is hypothesized that the leukemic infiltration may play a role in the development of acute appendicitis. Further, this case demonstrates the need to maintain a high index of suspicion and prompt surgical intervention for surgical pathologies in neutropenic patients.

  13. 电磁辐射后大鼠睾丸类固醇激素合成急性调节蛋白和细胞色素P450胆固醇侧链裂解酶mRNA的变化%Change of steroidogenic acute regulatory protein and cytochrome P450 cholesterol side-chain cleavage mRNA in testis of rats after electromagnetic irradiation

    周文; 杨进清; 王虚步; 刘勇; 张广斌

    2005-01-01

    electromagnetic irradiation.But under the condition of electromagnetic exposure,the change of testosterone and its mechanism remain unknown. OBJECTIVE:To study the effect of electromagnetic irradiation on steroidogenic acute regulatory protein(StAR) and cytochrome P450 cholesterol side-chain cleavage(P450scc) in the tissues of the testis of the adult rats,and to preliminarily reveal the molecular mechanism of electromagnetic radiation that affects the synthesis of testosterone. DESIGN:A randomized controlled study. SETTING:Department of Nuclear Medicine and Staff Room of Labour Hygiene, Institute of Field Surgery,Daping Hospital of the Third Military Medical University of Chinese PLA. PARTICIPANTS:The study was completed in the Department of Nuclear Medicine and Staff Room of Labour Hygiene, Institute of Field Surgery,Daping Hospital of the Third Military Medical University of Chinese PLA from June 2003 to May 2004.A total of 75 male Wistar rats of clean degree II,weighing 180 to 220 g,were randomly divided into 5 groups:control group,and groups of 3,6,24,72 hours after electromagnetic irradiation with 15 rats in each group. INTERVENTIONS:The rats were exposed to microwave with the peak power of 90 W/cm2 for 15 minutes successively,and all the rats survived the irradiation.The serum contents of testosterone of rats in the groups of 3,6,24,72 hours after electromagnetic irradiation and control group were measured by using radioimmunoassay(RIA) respectively;meanwhile the levels of the StAR and P450scc mRNA in testis tissue were also determined with RT-PCR. MAIN OUTCOME MEASURES:Serum contents of testosterone in the groups of 3,6,24,72 hours after electromagnetic irradiation and control group;the expression levels of the StAR and P450scc mRNA in testis tissues. RESULTS:The serum contents of testosterone,the StAR and P450scc mRNA levels at the point of 3 hours after electromagnetic irradiation were significantly lower than those in the control group,and they were decreased by 83

  14. Circulating FGF23 levels in response to acute changes in plasma Ca(2+).

    Gravesen, Eva; Mace, Maria L; Hofman-Bang, Jacob; Olgaard, Klaus; Lewin, Ewa

    2014-07-01

    The regulation of fibroblast growth factor 23 (FGF23) synthesis and secretion is still incompletely understood. FGF23 is an important regulator of renal phosphate excretion and has regulatory effects on the calciotropic hormones calcitriol and parathyroid hormone (PTH). Calcium (Ca) and phosphate homeostasis are closely interrelated, and it is therefore likely that Ca is involved in FGF23 regulation. It has recently been reported that dietary Ca influenced FGF23 levels, with high Ca increasing FGF23. The mechanism remains to be clarified. It remains unknown whether acute changes in plasma Ca influence FGF23 levels and whether a close relationship, similar that known for Ca and PTH, exists between Ca and FGF23. Thus, the aim of the present study was to examine whether acute hypercalcemia and hypocalcemia regulate FGF23 levels in the rat. Acute hypercalcemia was induced by an intravenous Ca infusion and hypocalcemia by infusion of ethylene glycol tetraacetic acid (EGTA) in normal and acutely parathyroidectomized rats. Intact plasma FGF23 and intact plasma PTH and plasma Ca(2+) and phosphate were measured. Acute hypercalcemia and hypocalcemia resulted as expected in adequate PTH secretory responses. Plasma FGF23 levels remained stable at all plasma Ca(2+) levels; acute parathyroidectomy did not affect FGF23 secretion. In conclusion, Ca is not a regulator of acute changes in FGF23 secretion.

  15. CD4-regulatory cells in COPD patients

    Smyth, Lucy J C; Starkey, Cerys; Vestbo, Jørgen

    2007-01-01

    BACKGROUND: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD. OBJECTIVE: To compare T-regulatory cell numbers in the BAL from COPD patients......, smokers with normal lung function, and healthy nonsmokers (HNS). METHODS: BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers. RESULTS: COPD patients had increased BAL CD8...... numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells...

  16. Transcription regulatory networks analysis using CAGE

    Tegnér, Jesper N.

    2009-10-01

    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  17. Current status of developmental neurotoxicity: regulatory view

    Hass, Ulla

    2003-01-01

    . Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...... in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US...

  18. Targeting regulatory T cells in cancer.

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  19. Current approaches to gene regulatory network modelling

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  20. Acute otitis media in children

    Cherpillod J

    2011-06-01

    Full Text Available Jacques CherpillodEar, Nose and Throat Department, Childrens’ University Hospital, Lausanne, SwitzerlandDate of preparation: 6th March 2011Conflict of interest: None declaredClinical question: What is the best treatment for acute otitis media in children?Results: Watchful waiting, followed by amoxicillin treatment, if necessary, is the best first-line treatment for acute otitis media in children aged six months or older.Keywords: acute otitis media, antibiotics, watchful waitin

  1. KEGG PATHWAY / Acute myeloid leukemia [KEGG

    Full Text Available PATHWAY: map05221 Entry map05221Pathway Name Acute myeloid leukemia Description Acute...Class Human Diseases; Cancers Pathwaymap map05221Acute myeloid leukemia Disease H00003Acute myeloid leukemia...inkDB DBGET integrated database retrieval system KEGG PATHWAY / Acute myeloid leukemia ...

  2. Pharm GKB: Acute abdomen [PharmGKB

    Full Text Available Overview Alternate Names: PharmGKB Accession Id: PA165109055 External Vocabularies MeSH: Abdomen, Acute... (D000006) SnoMedCT: Acute abdomen (9209005) UMLS: C0000727 (C0000727) MedDRA: Abdominal... syndrome acute (10000096) NDFRT: Abdomen, Acute [Disease/Finding] (N0000000260) Common Searches Search Medline Plus Search CTD Pharm GKB: Acute abdomen ...

  3. Acute Pancreatitis Associated with Brucellosis

    Demetrios Papaioannides

    2006-01-01

    Full Text Available Context :Acute pancreatitis can be caused by a variety of infectious agents but it is regarded as an extremely rare complication of brucellosis. Case report: We briefly describe a 56-yearold man who presented with acute pancreatitis, fever, myalgia, and other clinical symptoms. Brucella melitensis was cultured from his blood. All clinical manifestations gradually resolved with the institution of intramuscular streptomycin and oral doxycycline therapy. Conclusion :Acute pancreatitis may rarely be a complication of infection with B. melitensis. In areas where brucellosis is endemic, it should be kept in mind that acute pancreatitis may result from infection with brucella organisms..

  4. Acute Paraplegia After General Anesthesia

    Gholam Hossein Ghaedi

    2011-08-01

    Full Text Available Acute paraplegia is a rare but catastrophic complication of surgeries performed on aorta and corrective operations of vertebral column. Trauma to spinal cord after spinal anesthesia and ischemia of spinal cord also may lead to acute paraplegia. Acute paraplegia as a complication of general anesthesia in surgeries performed on sites other than aorta and vertebral column is very rare. Here we present a 56 year old woman with acute paraplegia due to spinal cord infarction after laparoscopic cholecystectomy under general anesthesia probably caused by atherosclerosis of feeding spinal arteries and ischemia of spinal cord after reduction of blood flow possibly due to hypotension during general anesthesia.

  5. Regulatory affairs for biomaterials and medical devices

    Amato, Stephen F; Amato, B

    2015-01-01

    All biomaterials and medical devices are subject to a long list of regulatory practises and policies which must be adhered to in order to receive clearance. This book provides readers with information on the systems in place in the USA and the rest of the world. Chapters focus on a series of procedures and policies including topics such as commercialization, clinical development, general good practise manufacturing and post market surveillance.Addresses global regulations and regulatory issues surrounding biomaterials and medical devicesEspecially useful for smaller co

  6. Regulatory Competition in Global Financial Markets

    Ringe, Georg

    2015-01-01

    The decades-long discussion on the merits of regulatory competition appears in a new light on the global financial market. There are a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities...... competition are a reality in today’s global financial market, and the financial sector is different from their traditional fields of application: the ease of arbitrage, the fragility of banking and the risks involved are exceptional. Most importantly, regulatory arbitrage does not or only rarely occurs...

  7. Theory of Regulatory Compliance for Requirements Engineering

    Jureta, Ivan; Mylopoulos, John; Perini, Anna; Susi, Angelo

    2010-01-01

    Regulatory compliance is increasingly being addressed in the practice of requirements engineering as a main stream concern. This paper points out a gap in the theoretical foundations of regulatory compliance, and presents a theory that states (i) what it means for requirements to be compliant, (ii) the compliance problem, i.e., the problem that the engineer should resolve in order to verify whether requirements are compliant, and (iii) testable hypotheses (predictions) about how compliance of requirements is verified. The theory is instantiated by presenting a requirements engineering framework that implements its principles, and is exemplified on a real-world case study.

  8. Regulatory issues in accreditation of toxicology laboratories.

    Bissell, Michael G

    2012-09-01

    Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

  9. Modular arrangement of regulatory RNA elements

    Roßmanith, Johanna; Narberhaus, Franz

    2017-01-01

    ABSTRACT Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed. PMID:28010165

  10. Excessive crying in infants with regulatory disorders.

    Maldonado-Duran, M; Sauceda-Garcia, J M

    1996-01-01

    The authors point out a correlation between regulatory disorders in infants and the problem of excessive crying. The literature describes other behavioral problems involving excessive crying in very young children, but with little emphasis on this association. The recognition and diagnosis of regulatory disorders in infants who cry excessively can help practitioners design appropriate treatment interventions. Understanding these conditions can also help parents tailor their caretaking style, so that they provide appropriate soothing and stimulation to their child. In so doing, they will be better able to develop and preserve a satisfactory parent-child relationship, as well as to maintain their own sense of competence and self-esteem as parents.

  11. Acute exacerbation of COPD.

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

  12. Acute otitis media.

    Dickson, Gretchen

    2014-03-01

    One in 4 children will have at least 1 episode of acute otitis media (AOM) by age 10 years. AOM results from infection of fluid that has become trapped in the middle ear. The bacteria that most often cause AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Differentiating AOM from otitis media with effusion (OME) is a critical skill for physicians, as accurate diagnosis will guide appropriate treatment of these conditions. Although fluid is present in the middle ear in both conditions, the fluid is not infected in OME as is seen in AOM patients.

  13. [Treatment of acute leukemias].

    Gross, R; Gerecke, D

    1982-11-12

    The effective treatment of acute (myeloblastic and lymphoblastic) leukaemias depends on the induction of remissions as well as on the maintenance of these remissions. Whereas the use of anthracyclines and of cytosine arabinoside in different combinations notably increased the rate of induction of remissions, their maintenance was less successful until now. We present a scheme using, beside MTX and 6-MP, modified COAP regimes periodically every 3 months. The follow-up of 26 patients treated in this way is encouraging since nearly one third remained in full haematological remission after 3 years of observation.

  14. Acute calculous cholecystitis

    Angarita, Fernando A.; University Health Network; Acuña, Sergio A.; Mount Sinai Hospital; Jimenez, Carolina; University of Toronto; Garay, Javier; Pontificia Universidad Javeriana; Gömez, David; University of Toronto; Domínguez, Luis Carlos; Pontificia Universidad Javeriana

    2010-01-01

    Acute calculous cholecystitis is the most important cause of cholecystectomies worldwide. We review the physiopathology of the inflammatory process in this organ secondary to biliary tract obstruction, as well as its clinical manifestations, workup, and the treatment it requires. La colecistitis calculosa aguda es la causa más importante de colecistectomías en el mundo. En esta revisión de tema se resume la fisiopatología del proceso inflamatorio de la vesículabiliar secundaria a la obstru...

  15. Diagnosis of acute neuropathies

    Crone, Clarissa; Krarup, Christian

    2007-01-01

    Acute and subacute polyneuropathies present diagnostic challenges since many require prompt initiation of treatment in order to limit axonal degeneration and since an exact and detailed diagnosis is a prerequisite for making the correct choice of treatment. It is for instance of utmost importance...... to recognize whether the underlying pathological changes are due to demyelination or to axonal degeneration and electrodiagnostic tests can thus in most cases contribute considerably to the securing of an exact diagnosis. The specific and characteristic electrophysiological findings in the different types...

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

    2003-01-01

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

  17. Testosterone physiology in resistance exercise and training: the up-stream regulatory elements.

    Vingren, Jakob L; Kraemer, William J; Ratamess, Nicholas A; Anderson, Jeffrey M; Volek, Jeff S; Maresh, Carl M

    2010-12-01

    Testosterone is one of the most potent naturally secreted androgenic-anabolic hormones, and its biological effects include promotion of muscle growth. In muscle, testosterone stimulates protein synthesis (anabolic effect) and inhibits protein degradation (anti-catabolic effect); combined, these effects account for the promotion of muscle hypertrophy by testosterone. These physiological signals from testosterone are modulated through the interaction of testosterone with the intracellular androgen receptor (AR). Testosterone is important for the desired adaptations to resistance exercise and training; in fact, testosterone is considered the major promoter of muscle growth and subsequent increase in muscle strength in response to resistance training in men. The acute endocrine response to a bout of heavy resistance exercise generally includes increased secretion of various catabolic (breakdown-related) and anabolic (growth-related) hormones including testosterone. The response of testosterone and AR to resistance exercise is largely determined by upper regulatory elements including the acute exercise programme variable domains, sex and age. In general, testosterone concentration is elevated directly following heavy resistance exercise in men. Findings on the testosterone response in women are equivocal with both increases and no changes observed in response to a bout of heavy resistance exercise. Age also significantly affects circulating testosterone concentrations. Until puberty, children do not experience an acute increase in testosterone from a bout of resistance exercise; after puberty some acute increases in testosterone from resistance exercise can be found in boys but not in girls. Aging beyond 35-40 years is associated with a 1-3% decline per year in circulating testosterone concentration in men; this decline eventually results in the condition known as andropause. Similarly, aging results in a reduced acute testosterone response to resistance exercise in men

  18. Steps forward in regulatory pathways for acute and chronic heart failure.

    Pani, Luca; Pecorelli, Sergio; Rosano, Giuseppe; Anker, Stefan D; Peracino, Andrea; Fregonese, Laura; Prasad, Krishna; Rasi, Guido

    2015-01-01

    A workshop was organized by the Agenzia Italiana del Farmaco (AIFA) to discuss unmet needs and ways forward in the development of medicines in heart failure, their rationale, and cost-effective use. An integrated, multidisciplinary approach, including patients' needs and perspectives, was advocated by all the participants as the way to the most effective treatment regimens. More work is needed for reaching consensus on clinical and functional endpoints, for validating patient reported outcomes and measurements of well-being. Similarly, the integration into the clinical programmes of the health technology assessment/payers perspective, in particular, the evaluation of 'real-life' treatment effectiveness and of health as a value, would help in shifting the development and authorization of medicines from the molecule paradigm to their evaluation in the context of the whole health care regimen. Through this kind of workshop, AIFA is trying to build a template for meetings devoted to debate unmet needs with all stakeholders towards tentative road maps for the future.

  19. Acute retinal necrosis

    Hugo Hernán Ocampo

    2009-12-01

    Full Text Available Purpose: Clinical features in a case of acute retinal necrosis are described as well as its diagnostic approach and response to early treatment. Methods: This is a descriptive and retrospective study case report of a 26 year old male patient who arrived to the emergency room with a three day history of sudden visual loss in the right eye (RE. At initial evaluation a visual acuity of hand movements in the RE, 20/15 in the left eye (LE and a right relative afferent pupillary defect were found. Fundoscopy revealed profuse soft exudates and hemorrhages involving posterior pole, inferior hemiretina and superotemporal periphery. Infectious workup and fluoresceinic angiography were made and positive serologies for herpes virus types 1 and 2, without HIV, were found. A diagnosis of acute retinal necrosis was made and treatment with intravenous valgancyclovir for two weeks and intra-vitreous triamcinolone for severe vasculitis, was given. Then a 3 months treatment with oral antiviral agents was prescribed. Results: Patient’s evolution showed improvement with treatment and at two and a half months of follow up, visual acuity was 20/50 in the right eye, normal slit lamp examination, tonometry of 12 mm Hg and fundoscopy improved when compared to initial pictures.Conclusions: A high index of suspicion is needed for diagnosing ARN taking into account clinical findings. Prompt intravenous and intra-vitreous treatments are needed to achieve good clinical and functional outcomes and to avoid central nervous system complications.

  20. Escroto agudo Acute scrotum

    Lisieux Eyer de Jesus

    2000-08-01

    Full Text Available Este artigo pretende fazer uma revisão geral do tema, com ênfase em conceitos atuais e/ou controversos no manejo das situações clínicas em questão, em especial conceitos ainda polêmicos quanto à fisiopatologia e ao manejo diagnóstico. Também é feita uma revisão extensa quanto aos aspectos clínicos e terapêuticos da torção de testículo neonatal e quanto aos aspectos de diagnóstico diferencial na síndrome do escroto agudo. São citadas informações estatísticas derivadas dos principais estudos clínicos publicados nos últimos 20 anos em literatura médica ocidental.This article intends to review "Acute Scrotum" emphasizing modern and controversial aspects on clinical situations, specially concepts on physiopathology and diagnosis. We also review clinical and therapeutic aspects of neonatal testicular torsion and the differential diagnosis in the acute scrotum syndrome. Statistical information are derived from main studies published in the last 20 years.

  1. Acute Recurrent Pancreatitis

    Glen A Lehman

    2003-01-01

    Full Text Available History, physical examination, simple laboratory and radiological tests, and endoscopic retrograde cholangiopancreatography (ERCP are able to establish the cause of recurrent acute pancreatitis in 70% to 90% of patients. Dysfunction of the biliary and/or pancreatic sphincter, as identified by sphincter of Oddi manometry, accounts for the majority of the remaining cases. The diagnosis may be missed if the pancreatic sphincter is not evaluated. Pancreas divisum is a prevalent congenital abnormality that is usually innocuous but can lead to recurrent attacks of acute pancreatitis or abdominal pain. In select cases, endoscopic sphincterotomy of the minor papilla can provide relief of symptoms and prevent further attacks. A small proportion of patients with idiopathic pancreatitis have tiny stones in the common bile duct (microlithiasis. Crystals can be visualized during microscopic analysis of bile that is aspirated at the time of ERCP. Neoplasia is a rare cause of pancreatitis, and the diagnosis can usually be established by computerized tomography or ERCP. A wide variety of medications can also cause recurrent pancreatitis. ERCP, sphincter of Oddi manometry, and microscopy of aspirated bile should be undertaken in patients with recurrent pancreatitis in whom the diagnosis is not obvious.

  2. [Acute coronary syndrome -- 2012].

    Becker, Dávid; Merkely, Béla

    2012-12-23

    The acute coronary syndrome is the most severe form of coronary artery disease. It is an immediate threat of life and the mortality rate can be high without proper therapy and patient management. Based on the first ECG, two different forms can be distinguished: acute coronary syndrome with and without ST elevation. Besides adequate medication, management of these patients is an essential part of treatment. In case of ST elevation, coronarography and percutaneous coronary intervention is needed in general, within 24 hours from the onset of symptoms. When ST elevation is not detected on the ECG, individual ischemic risk factors and predictable mortality of the patient may define the necessity and the date of the invasive examination. The Hungarian hemodynamic laboratory network covers almost the whole country and, therefore, practically each patient may receive a state-of-the-art therapy. Although indicators of cardiovascular diseases are still prominent, the mortality rate of myocardial Infarction is decreasing in Hungary due to the well-organized invasive care.

  3. 76 FR 18467 - Pennsylvania Regulatory Program

    2011-04-04

    ... a partial disapproval of a 1998 submission that included regulations about remining financial... effective regulatory program) relating to incidental extraction of coal under noncoal mining permits.... Section 86.5, Extraction of Coal Incidental to Noncoal Surface Mining Section 86.5(m) is amended to...

  4. Department of Commerce Semiannual Regulatory Agenda

    2010-04-26

    ... Part IV Department of Commerce Semiannual Regulatory Agenda ] DEPARTMENT OF COMMERCE (DOC) DEPARTMENT OF COMMERCE Office of the Secretary 13 CFR Ch. III 15 CFR Subtitle A; Subtitle B, Chs. I, II, III..., and VI Spring 2010 Semiannual Agenda of Regulations AGENCY: Office of the Secretary, Commerce....

  5. Inferring latent gene regulatory network kinetics

    González, Javier; Vujačić, Ivan; Wit, Ernst

    2013-01-01

    Regulatory networks consist of genes encoding transcription factors (TFs) and the genes they activate or repress. Various types of systems of ordinary differential equations (ODE) have been proposed to model these networks, ranging from linear to Michaelis-Menten approaches. In practice, a serious d

  6. 78 FR 42893 - Statement on Regulatory Burden

    2013-07-18

    ... serve the credit needs of its customers, i.e., America's farmers, ranchers, aquatic producers and... CREDIT ADMINISTRATION 12 CFR Chapter VI RIN 3052-AC88 Statement on Regulatory Burden AGENCY: Farm Credit Administration. ACTION: Notice of intent; request for comment. SUMMARY: The Farm Credit Administration (FCA,...

  7. Regulatory capital requirements and bail in mechanisms

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks, withou

  8. Regulatory Challenges for Cartilage Repair Technologies.

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  9. 78 FR 1646 - Semiannual Regulatory Agenda

    2013-01-08

    ... provides flexibility for agencies to conduct the privacy training or require the contractor to conduct the...; Organizational Conflicts of Interest. 416 FAR Case 2010-013, Privacy 9000-AM02 Training. 417 Federal Acquisition...: Action Date FR Cite NPRM 12/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact:...

  10. Regulatory Promotion of Emergent CCS Technology

    Davies, Lincoln; Uchitel, Kirsten; Johnson, David

    2014-01-01

    Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensive regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.

  11. 77 FR 28518 - Reducing Regulatory Burden

    2012-05-15

    ..., and other advantages; distributive impacts; and equity). The regulatory process encourages public..., simplify, and harmonize regulations to reduce costs and promote certainty for businesses and the public... culture of retrospective review and analysis. DOE will continually engage in review of its rules...

  12. Mutational robustness of gene regulatory networks.

    Aalt D J van Dijk

    Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

  13. Deferred Tax Assests and Bank Regulatory Capital

    Gallemore, J.

    2012-01-01

    Abstract: In this study, I examine three issues: (1) whether the probability of bank failure is increasing in the proportion of regulatory capital composed of deferred tax assets (DTA), (2) whether market participants incorporate the increased failure risk associated with the DTA component of capita

  14. Regulatory Proteolysis in Arabidopsis-Pathogen Interactions

    Miklós Pogány; Tamás Dankó; Evelin Kámán-Tóth; Ildikó Schwarczinger; Zoltán Bozsó

    2015-01-01

    Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is s...

  15. Department of Agriculture Semiannual Regulatory Agenda

    2010-12-20

    ...: September 21, 2010. Michael Poe, Chief, Legislative and Regulatory Staff. Agricultural Marketing Service.... Agricultural Marketing Service--Final Rule Stage Regulation Sequence Title Identifier Number Number 178...; Importation of Bovines and Bovine Products 0579-AC68 188 Viral Hemorrhagic Septicemia; Interstate Movement...

  16. Shaping Formal Networks throug the Regulatory Process

    Hall, Thad E.; O'Toole, Laurence J.

    2004-01-01

    Recent research has shown that, at the federal level, new or amended programs typically create networks consisting of multiactor structures spanning governments, sectors, and/or agencies. This study examines the implementation structures created through the regulatory process. We find that in a majo

  17. HIDEN: Hierarchical decomposition of regulatory networks

    Gülsoy Günhan

    2012-09-01

    Full Text Available Abstract Background Transcription factors regulate numerous cellular processes by controlling the rate of production of each gene. The regulatory relations are modeled using transcriptional regulatory networks. Recent studies have shown that such networks have an underlying hierarchical organization. We consider the problem of discovering the underlying hierarchy in transcriptional regulatory networks. Results We first transform this problem to a mixed integer programming problem. We then use existing tools to solve the resulting problem. For larger networks this strategy does not work due to rapid increase in running time and space usage. We use divide and conquer strategy for such networks. We use our method to analyze the transcriptional regulatory networks of E. coli, H. sapiens and S. cerevisiae. Conclusions Our experiments demonstrate that: (i Our method gives statistically better results than three existing state of the art methods; (ii Our method is robust against errors in the data and (iii Our method’s performance is not affected by the different topologies in the data.

  18. Regulatory T-cells and autoimmunity.

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  19. Independent regulatory authorities in European electricity market

    Olsen, Ole Jess; Larsen, Anders; Sørensen, Eva Moll

    2006-01-01

    Liberalisation of the electricity market has taken place in most European countries within the last decade. It is considered a precondition of successful liberalisation to establish so-called independent regulatory authorities. In this article, we compare the status and practice of them in 16...

  20. 75 FR 79929 - Semiannual Regulatory Agenda

    2010-12-20

    ... be a ``significant regulatory action'' under the definition in Executive Order 12866. Beginning with the fall 2007 edition, the Internet became the basic means for disseminating the Unified Agenda. The... requirements. Additional information on these entries is available in the Unified Agenda published on...

  1. 76 FR 37996 - West Virginia Regulatory Program

    2011-06-29

    ... surface coal mining and reclamation operations on non- Federal and non-Indian lands within its borders by... of approval of the West Virginia program in the January 21, 1981, Federal Register (46 FR 5915). You... actual language of State regulatory programs and program amendments because each program is drafted...

  2. Pre-commercial procurement : regulatory effectiveness?

    Apostol, Anca Ramona

    2014-01-01

    Is public procurement of research and development (‘R&D’) services the key to European Union (‘EU’)’s sustainable welfare? Is it being regulated in accordance with economic prescripts for effectiveness? Is the regulatory and policy setting clear and comprehensive in order to stimulate a widespread u

  3. 76 FR 76111 - Montana Regulatory Program

    2011-12-06

    ...--Regulatory Planning and Review This rule is exempted from review by the Office of Management and Budget (OMB... to and additions of statutory definitions for ``approximate original contour,'' ``in situ coal..., Federal Register (45 FR 21560). You can also find later actions concerning Montana's program and...

  4. RSAT 2015: Regulatory Sequence Analysis Tools.

    Medina-Rivera, Alejandra; Defrance, Matthieu; Sand, Olivier; Herrmann, Carl; Castro-Mondragon, Jaime A; Delerce, Jeremy; Jaeger, Sébastien; Blanchet, Christophe; Vincens, Pierre; Caron, Christophe; Staines, Daniel M; Contreras-Moreira, Bruno; Artufel, Marie; Charbonnier-Khamvongsa, Lucie; Hernandez, Céline; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

    2015-07-01

    RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative genomics and (iv) analysis of regulatory variations. Nine new programs have been added to the 43 described in the 2011 NAR Web Software Issue, including a tool to extract sequences from a list of coordinates (fetch-sequences from UCSC), novel programs dedicated to the analysis of regulatory variants from GWAS or population genomics (retrieve-variation-seq and variation-scan), a program to cluster motifs and visualize the similarities as trees (matrix-clustering). To deal with the drastic increase of sequenced genomes, RSAT public sites have been reorganized into taxon-specific servers. The suite is well-documented with tutorials and published protocols. The software suite is available through Web sites, SOAP/WSDL Web services, virtual machines and stand-alone programs at http://www.rsat.eu/.

  5. Regulatory pathways in the European Union.

    Kohler, Manuela

    2011-01-01

    In principle, there are three defined procedures to obtain approval for a medicinal product in the European Union. As discussed in this overview of the procedures, the decision on which regulatory pathway to use will depend on the nature of the active substance, the target indication(s), the history of product and/or the marketing strategy.

  6. Regulatory guidelines for biosimilars in Malaysia.

    Abas, Arpah

    2011-09-01

    The biosimilars sector continues to attract huge interest and controversy. Biosimilars are new biopharmaceuticals that are "similar" but not identical to the innovator product. Characteristics of biopharmaceuticals are closely related to the manufacturing process, which implies that the products cannot be exactly duplicated. Minuscule differences in the product's structure and manufacturing process can result in different clinical outcome. This raises concerns over the safety, efficacy and even pharmacovigilance of biosimilars. Thus, biosimilars are unique - they are not a true chemical generic and are regulated via a distinct regulatory framework. This report discusses the features of Malaysian regulatory oversight of biosimilars and experience acquired in the evaluation of some products from various countries. Ensuring regulatory position adequately reflects scientific advancement, expertise/resources is key. The regulatory situation is an evolving process. Various guidance documents are being prepared with the aim of developing a uniform global framework towards assuring the dual goal of lower costs and patient safety while expediting the availability of important biosimilar products.

  7. Acute brain hemorrhage in dengue

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2014-01-01

    Dengue is a tropical arboviral infection that can have severe hemorrhagic complication.Acute brain hemorrhage in dengue is rare and is a big challenge in neurosurgery.To perform surgery for management of acute brain hemorrhage in dengue is a controversial issue.Here, the authors try to summarize the previous reports on this topic and compare neurosurgery versus conservative management.

  8. Acute arsenic poisoning diagnosed late.

    Shumy, Farzana; Anam, Ahmad Mursel; Kamruzzaman, A K M; Amin, Md Robed; Chowdhury, M A Jalil

    2016-04-01

    Acute arsenicosis, although having a 'historical' background, is not common in our times. This report describes a case of acute arsenic poisoning, missed initially due to its gastroenteritis-like presentation, but suspected and confirmed much later, when the patient sought medical help for delayed complications after about 2 months.

  9. Canagliflozin-Associated Acute Pancreatitis.

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.

  10. A strategy to reduce the numbers of fish used in acute ecotoxicity testing of pharmaceuticals.

    Hutchinson, Thomas H; Barrett, Sarah; Buzby, Mary; Constable, David; Hartmann, Andreas; Hayes, Eileen; Huggett, Duane; Laenge, Reinhard; Lillicrap, Adam D; Straub, Jürg Oliver; Thompson, Roy S

    2003-12-01

    The pharmaceutical industry gives high priority to animal welfare in the process of drug discovery and safety assessment. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data used to derive the predicted no-effect concentration [PNECwater] from the most sensitive of three species). Subject to regulatory approval, it is proposed that testing can be moved from fish median lethal concentration (LC50) testing (typically using > or = 42 fish/API) to acute threshold tests using fewer fish (typically 10 fish/API). To support this strategy, we have collated base-set ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for approximately 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence of fish LC50 data to derive PNECwater values. For the other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is predicted to give comparable PNECwater outcomes. Based on this preliminary scenario of 91 APIs, this approach is predicted to reduce the total number of fish used from 3,822 to 1,025 (approximately 73%). The present study, although preliminary, suggests that the current regulatory requirement for fish LC50 data regarding APIs should be succeeded by fish acute threshold (step-down) test data, thereby achieving significant animal welfare benefits with no loss of data for PNECwater estimates.

  11. CLINICAL STUDY OF ACUTE POISONING

    Panduranga

    2014-09-01

    Full Text Available BACKGROUND AND OBJECTIVE: Acute poisoning is an important medical emergency. Studies of this nature will be useful tool in planning, early diagnosis and management of acute poisoning cases. The objective of the study are to study the clinical features, diagnosis and management, morbidity and mortality of various acute poisoning. METHODOLOGY: This study comprises of 350 patients of acute poisoning admitted to Chigateri General Hospital and Bapuji Hospital attached to J. J. M. Medical College, Davangere, between 1st March 2011 to 31st October 2011. REUSLTS: Out of 350 cases of acute poisoning studied, there were 268 males and 82 females. Males comprised 76.57%and females 23.42% of the total, in this series, Organophosphorous compounds were the commonest (30%, majority of the patients hailed from rural area 70%. Mortality is 10.57%.

  12. [Acute rhinosinusitis: diagnostics and treatment].

    Lazarevich, I A; Kozlov, V S

    2013-01-01

    Acute rhinosinusitis is a challenging clinical problem due to its high prevalence. The overwhelming majority of the cases of acute rhinosinusitis (ARS) have viral etiology. Clinical manifestations of viral and bacterial rhinosinusitis can be very similar. Similar expert communities have proposed their recommendations on diagnostics and treatment of acute rhinosinusitis in the recent decade. These recommendations are underlain by the principles of evidence-based medicine, take into consideration the result of reliable investigations, and reflect the opinions of leading specialists in otorhinolaryngology, allergology and immunology. The present review contains the analysis of consensus documents and recommendations. The results of ongoing research provide convincing evidence of the effectiveness of intranasal application of corticosteroids in the patients presenting with acute rhinosinusitis. Antibacterial therapy of acute rhinosinusitis is indicated only in the case of severe or complicated clinical course of the disease.

  13. Nutrition Support in Acute Pancreatitis

    Orestis Ioannidis

    2008-07-01

    Full Text Available The management of acute pancreatitis differs according to its severity. Approximately 75% of patients with acute pancreatitis have mild disease with a mortality rate below 1%. Mortality increases up to 20% if the disease progresses to its severe necrotizing form and, in the most severe cases, mortality can increase to 30-40%. Severe acute pancreatitis is usually accompanied by systemic inflammatory response syndrome (SIRS which results in hypermetabolism with prominent protein catabolism. Acute malnutrition, commonly observed in patients with acute pancreatitis, is associated with immunological disturbances, septic complications and delayed healing of surgical wounds, and may lead to multiorgan dysfunction or failure syndrome (MODS or MOFS and increased morbidity and mortality [1].

  14. Regulatory network operations in the Pathway Tools software

    Paley Suzanne M

    2012-09-01

    Full Text Available Abstract Background Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data. Results The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene. Conclusions Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism’s genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

  15. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    2016-07-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  16. Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs.

    Moine, P; Shenkar, R; Kaneko, D; Le Tulzo, Y; Abraham, E

    1997-07-01

    The nuclear regulatory factor (NF)-kappa B is activated in the lungs of patients with acute respiratory distress syndrome (ARDS). In experimental models of acute lung injury, activation of NF-kappa B contributes to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in the lungs. Because of the important role that NF-kappa B activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kappa B counterregulatory mechanisms in lung mononuclear cells, using a murine model in which inflammatory lung injury develops after blood loss. Sustained activation of NF-kappa B was present in lung mononuclear cells over the 4-h period after blood loss. The activation of NF-kappa B after hemorrhage was accompanied by alterations in levels of the NF-kappa B regulatory proteins I kappa B alpha and Bcl-3. Cytoplasmic and nuclear I kappa B alpha were increased and nuclear Bcl-3 was decreased during the first hour after blood loss, but, by 4 h posthemorrhage, cytoplasmic and nuclear I kappa B alpha levels were decreased and nuclear levels of Bcl-3 were increased. Inhibition of xanthine oxidase activity in otherwise unmanipulated unhemorrhaged mice resulted in increased levels of I kappa B alpha and decreased amounts of Bcl-3 in nuclear extracts from lung mononuclear cells. No changes in the levels of nuclear I kappa B alpha or Bcl-3 occurred after hemorrhage when xanthine oxidase activity was inhibited. These results demonstrate that blood loss, at least partly through xanthine oxidase-dependent mechanisms, produces alterations in the levels of both I kappa B alpha and Bcl-3 in lung mononuclear cell populations. The effects of hemorrhage on proteins that regulate activation of NF-kappa B may contribute to the frequent development of inflammatory lung injury in this setting.

  17. Recommendations on legislative and regulatory framework and regulatory body of nuclear security in China

    PU Jilong; LI Xiaoyan

    2007-01-01

    This paper describes the definition of nuclear security that has been changing from the cold war age to the post-911 period, and clarifies the close relationship and yet a clear distinction between nuclear security, nuclear safety and nuclear safeguard. Based on analyses of the current state of nuclear security activities in China as well as the requirements and the law infrastructure, a legislative and regulatory framework of nuclear security and the mandate of a regulatory body in China are recommended.

  18. Isolation of active regulatory elements from eukaryotic chromatin using FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements)

    Giresi, Paul G.; Lieb, Jason D.

    2009-01-01

    The binding of sequence-specific regulatory factors and the recruitment of chromatin remodeling activities cause nucleosomes to be evicted from chromatin in eukaryotic cells. Traditionally, these active sites have been identified experimentally through their sensitivity to nucleases. Here we describe the details of a simple procedure for the genome-wide isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements). We also pro...

  19. Acute upper gastrointestinal bleeding.

    Kurien, Matthew; Lobo, Alan J

    2015-10-01

    Acute upper gastrointestinal bleeding (AUGIB) is a frequently encountered medical emergency with an incidence of 84-160/100000 and associated with mortality of approximately 10%. Guidelines from the National Institute for Care and Care Excellence outline key features in the management of AUGIB. Patients require prompt resuscitation and risk assessment using validated tools. Upper gastrointestinal endoscopy provides accurate diagnosis, aids in estimating prognosis and allows therapeutic intervention. Endoscopy should be undertaken immediately after resuscitation in unstable patients and within 24 hours in all other patients. Interventional radiology may be required for bleeding unresponsive to endoscopic intervention. Drug therapy depends on the cause of bleeding. Intravenous proton pump inhibitors should be used in patients with high-risk ulcers. Terlipressin and broad-spectrum antibiotics should be used following variceal haemorrhage. Hospitals admitting patients with AUGIB need to provide well organised services and ensure access to relevant services for all patients, and particularly to out of hours endoscopy.

  20. Acute human schistosomiasis mansoni

    Ana Rabello

    1995-04-01

    Full Text Available The acute schistosomiasis is the toxemic disease that follow the Schistosoma cercariae active penetration trough screen in the immunologicaly naive vertebrate host. The clinical picture starts two to eight weeks after the first contact with the contaminated water. Susceptible patients present a syndrome comprising fever, diarrhea, toxemia and hepatosplenomegaly. Diagnosis is based on epidemiological and clinical features, presence of Schistosoma eggs in the feces, enlargement of abdominal lymph nodes by ultrasonography and by detection of high antibodies levels against the antigen keyhole limpet haemocyanin. Different rates of cure have been observed with specific medication and for the most severe clinical presentations the use of steroids reduces the systemic and allergic manifestations.

  1. [Acute postpartum psychoses].

    Tabbane, K; Charfi, F; Dellagi, L; Guizani, L; Boukadida, L

    1999-11-01

    The post-partum is a high risk period for the development of acute psychotic disorders. The frequence of post-partum psychoses is evaluated at 1 to 2 per 1,000 births. Post-partum psychosis include major affective disorders which is the most frequent diagnosis. The clinical pictures have specific characteristics: rapid change of symptomatology, liability of mood, and frequent confusional signs. The short-term prognosis is generally good but the risk of recurrence of the mental disorder, in or outside puerperal context, is high. At clinical, evolutive and genetic levels, the studies do not provide arguments for nosological autonomy of post-partum psychosis. At therapeutic level, the ECT is particularly efficient in this indication.

  2. Acute intermittent porphyria.

    Herrick, Ariane L; McColl, Kenneth E L

    2005-04-01

    Acute intermittent porphyria (AIP) is characterised by neurovisceral crises the most common clinical presentation of which is abdominal pain. It is an autosomal dominant condition with incomplete penetrance and is potentially life-threatening. The key point in management is to suspect and confirm the diagnosis as early as possible in order to treat the attack and to avoid inappropriate treatments which may exacerbate the crisis. In this chapter we briefly outline the haem biosynthetic pathway and how deficiencies in individual enzymes give rise to the different porphyrias. We then describe the clinical features and diagnosis of AIP, followed by a discussion of pathogenesis, highlighting advances in the molecular biology of AIP and introducing the debate as to whether neurovisceral crises might result from porphyrin precursor neurotoxicity or from haem deficiency. Finally we discuss management, including family screening, avoidance of triggering factors, analgesia, maintenance of a high calorie intake, and administration of haem derivatives.

  3. Acute capsular infarction

    Kashihara, M.; Matsumoto, K.

    1985-05-01

    Sixty-three patients with lacunar-type of acute capsular infarction were treated in our service during the last 2 years. Their lesions were identified by computed tomography (CT) and classified into six types according to their locations: anterior, lateral, posterior, superior, inferior and multiple. The lesions were thought to be in the watershed areas of the regional arterial supplies, and the areas were considered to be prone to ischemia. The clinical course of each type showed characteristic features of ischemic strokes. In the majority of the patients with the lateral type, reversible ischemic neurological deficit (RIND) was seen as the predominant symptom, transient ischemic attack (TIA) was noted in the patients with the superior type, and major completed stroke was observed in those with posterior type.

  4. Acute coagulopathy of trauma

    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......, is an 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...

  5. National Strategy for Modernizing the Regulatory System for Biotechnology Products

    This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

  6. Legal principles of regulatory administration and nuclear safety regulation

    Lee, Kyeong Hui; Cheong, Sang Kee [Hannam Univ., Taejon (Korea, Republic of)

    2000-12-15

    This research presents a critical analysis and evaluation of principles of administrative laws in order to provide framework of structural reform on the nuclear safety regulation system. The focus of this analysis and evaluation is centered around the area of origin of regulatory administrative laws; authorities of regulation; procedures of regulatory actions; regulatory enforcement; and administrative relief system. In chapter 2 the concept of regulatory administration is analysed. Chapter 3 identifies the origin of regulatory administration and the principles of administration laws. It also examines legal nature of the nuclear safety standard. In relation to regulatory authorities. Chapter 4 identifies role and responsibility of administration authorities and institutions. It also examines fundamental principles of delegation of power. Then the chapter discusses the nuclear safety regulation authorities and their roles and responsibilities. Chapter 5 classifies and examines regulatory administration actions. Chapter 6 evaluates enforcement measure for effectiveness of regulation. Finally, chapter 7 discusses the administrative relief system for reviewing unreasonable regulatory acts.

  7. Environmental regulatory and policy framework in China: an overview

    2001-01-01

    China has developed one of the most comprehensive environmental regulatory and policy framework in the world. This paper provides a description of the main institutions for environmental management in China, and overviews the regulatory and policy framework in place.

  8. Logical knowledge representation of regulatory relations in biomedical pathways

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...

  9. Anosognosia in patients with acute hemispheric ischemic stroke

    V. N. Grigoryeva

    2016-01-01

    Full Text Available Objective: to investigate the frequency of anosognosia (a deficit of self-awareness, its anatomic correlates associated with other neuropsychological and neurological disorders in acute hemispheric ischemic stroke (IS.Patients and methods 150 patients (83 men and 67 women; mean age, 63.0±9.3 years with acute hemispheric IS were examined. All the patients underwent neurological, neuroimaging, and neuropsychological (by the procedure described by A.R. Luria examinations. neuropsychological investigations. Anosognosia was diagnosed using the Dysexecutive Questionnaire (DEX and the authors' procedure involving a scale to measure impaired self-rating of motor abilities and a scale to measure impaired self-rating of cognitive abilities in everyday life.Results and discussion. In the acute period of hemispheric IS, reduced self-awareness of motor and cognitive abilities was noted in 14% of the patients and unawareness of only cognitive abilities was recorded in 15%. Patients with anosognosia and cognitive dysfunction (ACD and those with anosognosia and motor dysfunction (AMD had right-sided hemispheric IS more frequently (76% while this was not found in patients with isolated ACD. The development of anosognosia for paralysis and paresis was favored by the large sizes of an ischemic focus that involved a few lobes in the posterior regions of the brain although no lesions were found in the anosognosia-specific anatomical regions. ACD and AMD proved to be associated with unilateral spatial and tactile neglect and obvious regulatory dysfunction. 

  10. Acute oral toxicities of wildland fire control chemicals to birds

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  11. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie

    2014-09-26

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  12. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  13. Acute pancreatitis and acute renal failure following multiple hornet stings

    N. Sharma

    2006-04-01

    Full Text Available Hymenoptera is a class of insects that sting in order to subdue their prey. Humans coming into accidental contact with these insects results in stings that may cause from mild local reaction like weal formation around the sting site to severe systemic reactions such as intravascular hemolysis, acute renal failure, pulmonary edema, cerebral edema, and rarely pancreatitis. We report here the clinical course of a patient who developed concurrent acute pancreatitis and pigment-induced acute renal failure after multiple hornet stings.

  14. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction

    Andreas; Kumar; Rodrigo; Bagur; Patrick; Béliveau; Jean-Michel; Potvin; Pierre; Levesque; Nancy; Fillion; Benoit; Tremblay; éric; Larose; Valérie; Gaudreault

    2014-01-01

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  15. Acute myelogenous leukemia and acute leukemic appendicitis: A case report

    Po-Jen Hsiao; Shih-Ming Kuo; Jia-Hong Chen; Hsuen-Fu Lin; Pau-Ling Chu; Shih-Hua Lin; Ching-Liang Ho

    2009-01-01

    Acute myelogenous leukemia (AML) can involve the gastrointestinal tract but rarely involves the appendix.We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leukemia relapse. Pathological findings of the appendix revealed transmural infiltrates of myeloblasts, whichindicated a diagnosis of leukemia. Unfortunately, the patient died from progression of the disease on the 19th d after admission. Although leukemic cell infiltration of the appendix is uncommon, patients with leukemia relapse can present with symptoms mimicking acute appendicitis.

  16. Acute pericarditis and renal failure complicating acute hepatitis A infection.

    Beyazit, Yavuz; Guven, Gulay Sain; Kekilli, Murat; Koklu, Seyfettin; Yolcu, Omer Faruk; Shorbagi, Ali

    2006-01-01

    Hepatitis A infection may result in acute hepatitis, and rarely, fulminant hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The authors present the case of a 77-year-old male who had development of acute renal failure and pericarditis during the clinical course of acute hepatitis A infection. He died as a result of septic shock on the fifth day of hospitalization. To the best of our knowledge, this is the first report of both these rare and serious complications appearing in the same patient.

  17. Regulatory reform of Finnish environmental policy

    Sairinen, R.

    2000-07-01

    The main question of this study concerns the regulatory reform i.e. formation and design of new policy instruments in the Finnish environmental policy. The research question is divided into two parts: (1) How have the new policy instruments evolved and been designed (2) What are the political, administrative, historical and ideological factors underlying the processes of policy instrument formation and design? Three main approaches for analysis are introduced: the model of policy instrument choice by Linder and Peters, the model of policy explanation by Jaenicke, and the concept of governmentality developed by Foucault. Within the developed theoretical framework, the general societal background of regulatory reform is composed of the various features of 'environmental governmentality'. The research questions are divided into two empirical research tasks. (1) Analysis of the historical development of Finnish environmental governing and policy style provides background information about the national institutional settings and policy cultures in order to understand the role of the new policy instruments in the Finnish environmental policy during last two decades. Here, Finnish environmental policy divides into consensual pollution policies and adversial nature conservation. Four main periods of environmental governmentality in Finland is presented: the early nature conservation initiatives (1800-1939), the neglect of environmental issues (1945-1969), the environmental institutionalisation (1970-1986), and the regulatory reform (1987-). (2) The contextual case studies concerns: the drafting of the EIA Act in 1982-1994; the formation of the carbon tax policy in 1989-1996; and the implementation of voluntary environmental agreements in 1987-99. The study shows that regulatory reform has not been an easy policy process in Finland. There has been no common environmental governmentality behind the on-going regulatory reform. The new policy instruments have been

  18. The Longitudinal Evolution of Cerebral Blood Flow Regulation after Acute Ischaemic Stroke

    Angela S.M. Salinet

    2014-08-01

    Full Text Available Background: Acute stroke is known to impair cerebral blood flow (CBF regulation, but the longitudinal changes of these effects have been poorly reported. The main CBF regulatory mechanisms [cerebral autoregulation (CA and neurovascular coupling (NVC] were assessed over 3 months after acute ischaemic stroke. Methods: Recordings of CBF velocity (CBFv, blood pressure (BP, and end-tidal CO2 were performed during 5 min baseline and 1 min passive movement of the elbow. Stroke patients were assessed Results: Fifteen acute stroke subjects underwent all 4 sessions and were compared to 22 control subjects. Baseline recordings revealed a significantly lower CBFv in the affected hemisphere within 72 h after stroke compared to controls (p = 0.02 and a reduction in CA index most marked at 2 weeks (p = 0.009. CBFv rise in response to passive arm movement was decreased bilaterally after stroke, particularly in the affected hemisphere (p Conclusion: The major novel finding of this study was that both CA and NVC regulatory mechanisms deteriorated initially following stroke onset, but returned to control levels during the recovery period. These findings are relevant to guide the timing of interventions to manipulate BP and potentially for the impact of intensive rehabilitation strategies that may precipitate acute physiological perturbations but require further exploration in a larger population that better reflects the heterogeneity of stroke. Further, they will also enable the potential influence of stroke subtype to be investigated.

  19. Circulating FGF23 levels in response to acute changes in plasma Ca(2+)

    Gravesen, E; Mace, M.L.; Hofman-Bang, J.

    2014-01-01

    The regulation of fibroblast growth factor 23 (FGF23) synthesis and secretion is still incompletely understood. FGF23 is an important regulator of renal phosphate excretion and has regulatory effects on the calciotropic hormones calcitriol and parathyroid hormone (PTH). Calcium (Ca) and phosphate...... homeostasis are closely interrelated, and it is therefore likely that Ca is involved in FGF23 regulation. It has recently been reported that dietary Ca influenced FGF23 levels, with high Ca increasing FGF23. The mechanism remains to be clarified. It remains unknown whether acute changes in plasma Ca influence...... FGF23 levels and whether a close relationship, similar that known for Ca and PTH, exists between Ca and FGF23. Thus, the aim of the present study was to examine whether acute hypercalcemia and hypocalcemia regulate FGF23 levels in the rat. Acute hypercalcemia was induced by an intravenous Ca infusion...

  20. 76 FR 59066 - Notice of Regulatory Review Plan

    2011-09-23

    ...; ] FEDERAL HOUSING FINANCE AGENCY 12 CFR Chapter XII Notice of Regulatory Review Plan AGENCY: Federal Housing...) is issuing a notice of and requesting comments on the FHFA interim regulatory review plan for review.... Comments FHFA invites comments on all aspects of the interim regulatory review plan, including legal...

  1. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl... B, Vecchi A. Publication Autoimmun Rev. 2007 Nov;7(1):8-11. Epub 2007 Mar 26. Pathway - PNG File (.png) SVG

  2. Regulatory RNAs in prokaryotes: here, there and everywhere.

    Narberhaus, Franz; Vogel, Jörg

    2009-10-01

    A recent meeting on 'Regulatory RNAs in prokaryotes' reflected the growing interest in this research topic. Almost 200 scientists met to discuss the identification, structure, function and mechanistic details of regulatory RNAs in bacteria and archaea. The topics included small regulatory RNAs, riboswitches, RNA thermosensors and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) elements.

  3. Roadmapping as a Tool for Renewing Regulatory Practices

    Borch, Kristian; Norus, Jesper

    2004-01-01

    in this emerging and discontinuedtechnology can provide critical policy information. This type of policy intelligence canbe used to rethink the regulatory practices away from today's framework basedregulation of the emerging technologies towards a regulatory policy based on how todevelop regulatory practices based...

  4. 40 CFR 73.86 - State regulatory autonomy.

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State regulatory autonomy. 73.86 Section 73.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulatory autonomy. Nothing in this subpart shall preclude a State or State regulatory authority...

  5. Security issues of new innovative payments and their regulatory challenges

    Kasiyanto, Safari; Gabriella, Gimigliano

    2016-01-01

    Kasiyanto discusses how the security issues of M-payments and Bitcoin as new forms of innovative payments challenge the existing EU regulatory frameworks, and whether the proposed regulatory frameworks suffice to address such challenges. The regulatory frameworks Kasiyanto discusses mainly focus on

  6. 18 CFR 367.2540 - Account 254, Other regulatory liabilities.

    2010-04-01

    ... GAS ACT Balance Sheet Chart of Accounts Deferred Credits § 367.2540 Account 254, Other regulatory... regulatory liabilities. 367.2540 Section 367.2540 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY HOLDING COMPANY ACT OF...

  7. Attribute Exploration of Gene Regulatory Processes

    Wollbold, Johannes

    2012-01-01

    This thesis aims at the logical analysis of discrete processes, in particular of such generated by gene regulatory networks. States, transitions and operators from temporal logics are expressed in the language of Formal Concept Analysis. By the attribute exploration algorithm, an expert or a computer program is enabled to validate a minimal and complete set of implications, e.g. by comparison of predictions derived from literature with observed data. Here, these rules represent temporal dependencies within gene regulatory networks including coexpression of genes, reachability of states, invariants or possible causal relationships. This new approach is embedded into the theory of universal coalgebras, particularly automata, Kripke structures and Labelled Transition Systems. A comparison with the temporal expressivity of Description Logics is made. The main theoretical results concern the integration of background knowledge into the successive exploration of the defined data structures (formal contexts). Applyi...

  8. Regulatory Competition in Global Financial Markets

    Ringe, Georg

    2016-01-01

    Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of moving trading abroad or relocating activities or operations of financial institutions to other jurisdictions. Where this happens...... their standards solely to attract business and thereby impose externalities on the worldwide financial market by undermining financial stability as a global public good. Policymakers worldwide are experimenting with remedies to respond to the phenomenon. I introduce the importance of an effective special...... institutions' excessive risk-taking. If such risk-taking would be judged by market discipline instead of posing a risk to global financial stability, the main downside of regulatory competition could be restrained. Within the boundaries of such a system, competition could then operate and contribute...

  9. Regulatory research / Pesquisa regulatória

    Altair Souza de Assis

    2013-05-01

    Full Text Available We present in this paper the concept, importance, and scope of research into the regulatory framework of regulation and legislation, with a particular focus on legislation related to legal metrology. This study also describes a comparative analysis of the various forms of regulation and the associated regulatory research, with the ultimate goal of better defi ning the concept and to validate the need to have research groups within a country’s regulatory bodies. Based on this work, we conclude that regulatory research is a key factor in the success of any regulatory body’s activities. Such research helps to avoid the creation of absurd or impractical regulatory barriers to a country’s technological development, or worse, to permit “orphans,” that is, technologies that are outside regulatory control, as is currently the case. Indeed, for a country to have a robust technological infrastructure, especially if it is still a developing country, strong and competent regulatory control is essential. However, this must be balanced by an atmosphere that fosters continuous and consistent technological innovation, and such development must also be self-sustainable from economic, social, and environmental viewpoints. ------------------------------------------------ Apresenta-se neste trabalho o conceito, a importância e a abrangência da pesquisa regulatória no âmbito da regulação e da regulamentação, com foco particular na regulamentação relacionada à metrologia legal. Faz-se também uma análise comparativa entre as várias formas de regular e regulamentar, e as suas pesquisas regulatórias afi ns, tendo como meta principal situar melhor o conceito e validar a necessidade de se fazer pesquisa nos órgãos e agências regulatórias do país. Com base neste trabalho, concluímos que a pesquisa regulatória é um fator chave para o sucesso de qualquer plano de ação de regulação para os agentes regulatórios do país. Ela ajuda a

  10. Regulatory mechanisms link phenotypic plasticity to evolvability.

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  11. Papers on the nuclear regulatory dilemma

    Barkenbus, J.N.; Freeman, S.D.; Weinberg, A.M.

    1985-10-01

    The four papers contained in this report are titled: (1) From Prescriptive to Performance-Based Regulation of Nuclear Power; (2) Nuclear Regulatory Reform: A Technology-Forcing Approach; (3) Improving the Regulation of Nuclear Power; and (4) Science and Its Limits: The Regulators' Dilemma. These four papers investigate issues relating to the long-term regulation of nuclear energy. They were prepared as part of the Institute for Energy Analysis' project on Nuclear Regulation funded by a grant from the Mellon Foundation and a smaller grant by the MacArthur Foundation. Originally this work was to be supplemented by contributions from the Nuclear Regulatory Commission and from the Department of Energy. These contributions were not forthcoming, and as a result the scope of our investigations was more restricted than we had originally planned.

  12. The regulatory niche of intestinal stem cells.

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders.

  13. Regulatory norm”: myth or reality?

    Hugo Alberto Marín Hernández

    2010-06-01

    Full Text Available A controversy has arisen from identifying the nature and position, in the system of sources, of the decisions taken by the regulation commissions of home public service utilities (Spanish acronym crspd. In order to explain our position towards this matter, this document makes reference to (1 the explanatory criteria of the relations between the law and the regulations in the Colombian legal code and (2 the identification of the types of regulations determined by the existence of said criteria; (3 the proposal of distinction between regulation power –regulation- and regulatory faculty –“regulatory norm”- in the national jurisprudence and doctrine, in order to finally (4 outline which are the legal nature of the regulation function and the position, in the administrative law system of sources, of the regulating products derived from the CRSPD.

  14. Genomic regulatory landscapes and chromosomal rearrangements

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

  15. Medical research misconduct need regulatory reforms.

    Bedi, Neeraj

    2014-10-01

    The medical research misconduct has become a global problem. Except from countries like the USA, China, and Germany the exact figures of misconduct are not available. The research misconduct include fabricating the data, falsifying data, and plagiarism. The irresponsible research practices are publishing research data more than once, conflicts of interest is not declared, selective reporting of data and including an author who has not contributed at all and many more. About 2% of scientists have been found to admit the fabricating the data and 33% researchers were involved in irresponsible research practices. There is no formal regulatory programs available to monitor the research projects. Few developed countries like the USA, Germany, and China tried to develop programs which can monitor the medical research misconduct. There is a need to develop a regulatory system at national and institutional level to regulate the research activity to ensure that good ethical and scientific standards are practiced by medical researchers.

  16. Medical research misconduct need regulatory reforms

    Neeraj Bedi

    2014-01-01

    Full Text Available The medical research misconduct has become a global problem. Except from countries like the USA, China, and Germany the exact figures of misconduct are not available. The research misconduct include fabricating the data, falsifying data, and plagiarism. The irresponsible research practices are publishing research data more than once, conflicts of interest is not declared, selective reporting of data and including an author who has not contributed at all and many more. About 2% of scientists have been found to admit the fabricating the data and 33% researchers were involved in irresponsible research practices. There is no formal regulatory programs available to monitor the research projects. Few developed countries like the USA, Germany, and China tried to develop programs which can monitor the medical research misconduct. There is a need to develop a regulatory system at national and institutional level to regulate the research activity to ensure that good ethical and scientific standards are practiced by medical researchers.

  17. Antibiotic prescribing for acute bronchitis

    Llor, Carl; Bjerrum, Lars

    2016-01-01

    INTRODUCTION: Acute bronchitis is a self-limiting infectious disease characterized by acute cough with or without sputum but without signs of pneumonia. About 90% of cases are caused by viruses. AREAS COVERED: Antibiotics for acute bronchitis have been associated with an approximately half...... discusses the reason for this antibiotic overprescription. Other therapies targeted to control symptoms have also demonstrated a marginal or no effect. EXPERT COMMENTARY: Clinicians should be aware of the marginal effectiveness of antibiotic therapy. Some strategies like the use of rapid tests, delayed...

  18. Bacteriotherapy of acute radiation sickness

    Mal' tsev, V.N.; Korshunov, V.M.; Strel' nikov, V.A.; Ikonnikova, T.B.; Kissina, E.V.; Lyannaya, A.M.; Goncharova, G.I.; Pinegin, B.V.

    1979-04-01

    Acute sickness is associated with intestinal dysbacteriosis; there is a radical decrease in number of microorganisms of lactic fermentation (bifidobacterium, lactobacillus) and an increase in E. coli proteus, enterococcus, and clostridium. Extensive use is made of live microorganisms in the treatment of various diseases associated with intestinal dysbacteriosis; in the case of acute radiation sickness, yeast, colibacterin, and E. coli have been used. In a number of cases, such therapy increased survival and life expectancy of irradiated animals. In this study, microorganisms of lactic fermentation (lactobacillus, bifidobacterium) and colibacterin were used for treatment of acute radiation sickness.

  19. Early management of acute pancreatitis.

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  20. Cerebrogenic tachyarrhythmia in acute stroke

    A S Praveen Kumar

    2012-01-01

    Full Text Available The electrocardiac abnormalities following acute stroke are frequent and seen in both ischemic and hemorrhagic stroke. The changes seen in electrocardiogram (ECG consist of repolarization abnormalities such as ST elevation, ST depression, negative T waves, and QT prolongation. Among tachyarrhythmias, atrial fibrillation is the most common and occurrence of focal atrial tachycardia is very rare though any cardiac arrhythmias can follow acute stroke. We report a case of focal atrial tachycardia following acute ischemic stroke in 50-year-old female without structural heart disease, and their mechanisms and clinical implications.