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Sample records for acute minimally differentiated

  1. Minimally differentiated acute myelogenous leukemia (AML-M0) granulocytic sarcoma presenting in the oral cavity.

    PubMed

    Amin, Kay S; Ehsan, Aamir; McGuff, H Stan; Albright, Steven C

    2002-07-01

    Acute myelogenous leukemia with minimal differentiation (AML-M0) is a rare subtype of acute leukemia in which blasts fail to show morphologic differentiation and conventional cytochemical stains and myeloid markers are negative. Acute myelogenous leukemia (AML) presents primarily with peripheral blood and/or bone marrow involvement. Presentation in extramedullary sites, including the head and neck region, is not uncommon. Acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) have had the highest incidence of associated oral infiltrates. We report a case of a 58-year-old gentleman, with no prior history of acute leukemia, presenting with a solitary palatal swelling. Initial morphologic examination favored high-grade non-Hodgkin's lymphoma (NHL). Conventional cytochemical and immunohistochemical stains were negative for lymphoid and myeloid markers. Subsequent immunophenotyping via flow cytometry performed on peripheral blood and bone marrow aspirate demonstrated myeloid lineage without lymphoid differentiation, confirming the diagnosis of AML-M0.To our knowledge, this subtype of AML-M0 has not been previously reported involving the oral cavity. With absence of morphologic differentiation, and negative findings on conventional cytochemical and immunohistochemical stains, this subtype of leukemia may be misdiagnosed as non-Hodgkin's lymphoma (NHL). Flow cytometry is useful in detecting the myeloid lineage of this leukemia. PMID:12110349

  2. Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.

    PubMed

    de Rooij, Jasmijn D E; van den Heuvel-Eibrink, Marry M; Kollen, Wouter J W; Sonneveld, Edwin; Kaspers, Gertjan J L; Beverloo, H Berna; Fornerod, Maarten; Pieters, Rob; Zwaan, C Michel

    2016-03-01

    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease, characterized by different collaborating karyotypic and molecular abnormalities, which are used in risk group stratification. In ∼20% of the pediatric AML cases a specific genetic aberration is still unknown. Minimally differentiated myeloid leukemia or FAB-type M0 is a rare morphological subtype of AML. The translocation t(10;17)(p15;q21) is described to be recurrent in minimally differentiated AML, but the involved genes and location of the breakpoints have so far not been identified. In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids, while the reciprocal fusion product is predicted to lack a productive start codon. Gene expression profiling of the leukemic cells showed high HOXA expression. ZMYND11, also known as BS69, is a tumor suppressor that specifically recognizes H3K36me3, which is linked to aberrant HOXA expression in leukemogenesis. Aberrant expression of the genes involved in this fusion may thus contribute to the HOXA-phenotype observed with gene expression profiling. PMID:26608508

  3. Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.

    PubMed

    de Rooij, Jasmijn D E; van den Heuvel-Eibrink, Marry M; Kollen, Wouter J W; Sonneveld, Edwin; Kaspers, Gertjan J L; Beverloo, H Berna; Fornerod, Maarten; Pieters, Rob; Zwaan, C Michel

    2016-03-01

    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease, characterized by different collaborating karyotypic and molecular abnormalities, which are used in risk group stratification. In ∼20% of the pediatric AML cases a specific genetic aberration is still unknown. Minimally differentiated myeloid leukemia or FAB-type M0 is a rare morphological subtype of AML. The translocation t(10;17)(p15;q21) is described to be recurrent in minimally differentiated AML, but the involved genes and location of the breakpoints have so far not been identified. In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids, while the reciprocal fusion product is predicted to lack a productive start codon. Gene expression profiling of the leukemic cells showed high HOXA expression. ZMYND11, also known as BS69, is a tumor suppressor that specifically recognizes H3K36me3, which is linked to aberrant HOXA expression in leukemogenesis. Aberrant expression of the genes involved in this fusion may thus contribute to the HOXA-phenotype observed with gene expression profiling.

  4. Differentially Private Empirical Risk Minimization

    PubMed Central

    Chaudhuri, Kamalika; Monteleoni, Claire; Sarwate, Anand D.

    2011-01-01

    Privacy-preserving machine learning algorithms are crucial for the increasingly common setting in which personal data, such as medical or financial records, are analyzed. We provide general techniques to produce privacy-preserving approximations of classifiers learned via (regularized) empirical risk minimization (ERM). These algorithms are private under the ε-differential privacy definition due to Dwork et al. (2006). First we apply the output perturbation ideas of Dwork et al. (2006), to ERM classification. Then we propose a new method, objective perturbation, for privacy-preserving machine learning algorithm design. This method entails perturbing the objective function before optimizing over classifiers. If the loss and regularizer satisfy certain convexity and differentiability criteria, we prove theoretical results showing that our algorithms preserve privacy, and provide generalization bounds for linear and nonlinear kernels. We further present a privacy-preserving technique for tuning the parameters in general machine learning algorithms, thereby providing end-to-end privacy guarantees for the training process. We apply these results to produce privacy-preserving analogues of regularized logistic regression and support vector machines. We obtain encouraging results from evaluating their performance on real demographic and benchmark data sets. Our results show that both theoretically and empirically, objective perturbation is superior to the previous state-of-the-art, output perturbation, in managing the inherent tradeoff between privacy and learning performance. PMID:21892342

  5. Minimizing physical restraints in acute care.

    PubMed

    Struck, Bryan D

    2005-08-01

    The use of restraints to protect patients and insure continuation of care is an accepted fact in today's medical practice. However over the last 20 years a growing body of evidence supports the idea that restraints are harmful and should be used as the last resort. Since 1987, federal law requires long term care facilities to be restraint free. This article describes the use of restraints in the acute care setting, complications of using restraints and efforts to minimize restraint use in order to compliant with national policies.

  6. Minimal residual disease in acute promyelocytic leukemia.

    PubMed

    Weil, S C

    2000-03-01

    In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from "indolent disease" remains among the future challenges in APL. PMID:10702899

  7. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD, the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help clarifying the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  8. [Differential diagnosis of acute arthritis].

    PubMed

    Eviltis, Egidijus

    2003-01-01

    Acute arthritis can first present as a symptom of dangerous and rapidly progressing disease. It is quite easy to differentiate between arthritis and periarthritis. More problematical is correct early differential diagnosis of the acute arthritis. Determining whether one, several or many joints are affected can narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing provide much information and should be done at initial evaluation if possible. The presence or absence of fever, rash, family history of joint disease and exposure to infective organisms can further direct diagnostic studies and treatment. In general, to avoid masking clues, drug therapy should be delayed for mild symptoms until diagnosis is complete. This article is designed mostly for primary care physicians, residents and includes author's original data and review of recommended reading. PMID:12794379

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

    PubMed

    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. PMID:27613655

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

    PubMed

    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.

  11. Minimal model for stem-cell differentiation

    NASA Astrophysics Data System (ADS)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.

  12. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

    2015-01-01

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

  13. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  14. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  15. Identifying and designing chemicals with minimal acute aquatic toxicity.

    PubMed

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

    2015-05-19

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

  16. MINIMAL RESIDUAL DISEASE QUANTITATION IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Shook, David; Coustan-Smith, Elaine; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Campana, Dario

    2009-01-01

    The prognosis for patients with acute myeloid leukemia (AML) is heterogeneous. A minority of patients has clinical and biologic features that are associated with a very high risk of relapse. For the remaining patients no clear prognostic factors can be identified at diagnosis. The degree of treatment response is likely to be an informative predictor of outcome for these patients. Modern assays to detect AML cells that are undetectable by conventional morphologic techniques, i.e. minimal residual disease (MRD), can potentially improve measurements of treatment response. It is plausible that modifications to treatment based on the results of these assays will improve clinical management and ultimately increase cure rates. Established MRD assays for AML are based on either polymerase chain reaction (PCR) amplification of genetic abnormalities or flow cytometric detection of abnormal immunophenotypes. Residual disease and treatment response can be measured by these assays in a manner that is much more sensitive and objective than that afforded by conventional morphologic examination. The expanding use of MRD testing is beginning to change the definition of treatment response and of remission. Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents. PMID:19778853

  17. [Differentiated treatment of acute diffuse brain injuries].

    PubMed

    Pedachenko, E G; Dziak, L A; Sirko, A G

    2012-01-01

    Diagnosis and treatment results of 57 patients with acute diffuse brain injury have been analyzed. Patients were divided into two groups: first study period 2000-2005; second study period 2006-2010. The main differences between the first and the second study periods were in health condition and brain functions monitoring parameters, therapy approaches and goals. Increasing of axial and lateral dislocation symptoms during progression from the first type of diffuse injury to the fourth one is related to intracranial hypertension (ICH) occurrence rate and significance it's significance. During the second study period, ICH was found in 25% patients with the second type of injury, 57% patients with the third type of injury, and 80%, with the fourth type of injury. Mean ICP in the group of patients with the second type of diffuse injury comprised 14.4 +/- 6.6 mmHg; with the third type of injury, 30 +/- 20.6 mmHg; with the fourth type of injuty, 37.6 +/- 14.1 mmHg. Introduction of differentiated approach to conservative or surgical treatment method application to acute diffuse brain injuries patients based on ICP monitoring data led to 13.8% reduction in mortality in the second study period compared with the first study period.

  18. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  19. Comparison of the Asynchronous Differential Evolution and JADE Minimization Algorithms

    NASA Astrophysics Data System (ADS)

    Zhabitsky, Mikhail

    2016-02-01

    Differential Evolution (DE) is an efficient evolutionary algorithm to solve global optimization problems. In this work we compare performance of the recently proposed Asynchronous Differential Evolution with Adaptive Correlation Matrix (ADEACM) to the widely used JADE algorithm, a DE variant with adaptive control parameters.

  20. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-07-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348.

  1. Differential Effect of Amphetamine Optical Isomers on Bender Gestalt Performance of the Minimally Brain Dysfunctioned

    ERIC Educational Resources Information Center

    Arnold, L. Eugene; And Others

    1978-01-01

    The differential effect of amphetamine optical isomers on Bender Gestalt performance was examined in 31 hyperkinetic minimally brain dysfunctioned children between the ages of 4 and 12 years, using a double-blind Latin-square crossover comparison. (Author)

  2. Minimal parameter solution of the orthogonal matrix differential equation

    NASA Technical Reports Server (NTRS)

    Baritzhack, Itzhack Y.; Markley, F. Landis

    1988-01-01

    As demonstrated in this work, all orthogonal matrices solve a first order differential equation. The straightforward solution of this equation requires n sup 2 integrations to obtain the element of the nth order matrix. There are, however, only n(n-1)/2 independent parameters which determine an orthogonal matrix. The questions of choosing them, finding their differential equation and expressing the orthogonal matrix in terms of these parameters are considered. Several possibilities which are based on attitude determination in three dimensions are examined. It is shown that not all 3-D methods have useful extensions to higher dimensions. It is also shown why the rate of change of the matrix elements, which are the elements of the angular rate vector in 3-D, are the elements of a tensor of the second rank (dyadic) in spaces other than three dimensional. It is proven that the 3-D Gibbs vector (or Cayley Parameters) are extendable to other dimensions. An algorithm is developed employing the resulting parameters, which are termed Extended Rodrigues Parameters, and numerical results are presented of the application of the algorithm to a fourth order matrix.

  3. Minimal parameter solution of the orthogonal matrix differential equation

    NASA Technical Reports Server (NTRS)

    Bar-Itzhack, Itzhack Y.; Markley, F. Landis

    1990-01-01

    As demonstrated in this work, all orthogonal matrices solve a first order differential equation. The straightforward solution of this equation requires n sup 2 integrations to obtain the element of the nth order matrix. There are, however, only n(n-1)/2 independent parameters which determine an orthogonal matrix. The questions of choosing them, finding their differential equation and expressing the orthogonal matrix in terms of these parameters are considered. Several possibilities which are based on attitude determination in three dimensions are examined. It is shown that not all 3-D methods have useful extensions to higher dimensions. It is also shown why the rate of change of the matrix elements, which are the elements of the angular rate vector in 3-D, are the elements of a tensor of the second rank (dyadic) in spaces other than three dimensional. It is proven that the 3-D Gibbs vector (or Cayley Parameters) are extendable to other dimensions. An algorithm is developed emplying the resulting parameters, which are termed Extended Rodrigues Parameters, and numerical results are presented of the application of the algorithm to a fourth order matrix.

  4. Minimally Invasive Treatment of Acute Intrahepatic Fluid Collections With Acute Biliary Pancreatitis

    PubMed Central

    Ambrosi, Antonio; Fersini, Alberto; Tartaglia, Nicola; Valentino, Tiziano Pio

    2009-01-01

    Background: Peripancreatic fluid collection suggests the anatomical-clinical scenario of necrotizing acute pancreatitis. However, intrahepatic fluid collection is a rare occurrence with fewer than 30 cases being reported in the medical literature. We describe 2 cases of intrahepatic fluid collection in 2 patients with acute biliary pancreatitis and discuss the therapeutic possibilities. Case Reports: The first case report is that of a 68-year-old female with a diagnosis of acute biliary pancreatitis with several necrotizing fluid collections and a large infected intrahepatic collection in the left lobe. The patient was successfully treated by percutaneous US/CT guided drainage. The second case report is that of a 72-year-old female with a diagnosis of acute biliary pancreatitis with several peripancreatic fluid collections and a voluminous intrahepatic fluid collection in the left lobe that caused epigastric pain. This patient was also successfully treated with percutaneous US/CT guided drainage. Conclusion: Intrahepatic fluid collection in the course of acute biliary pancreatitis is a rare occurrence. The therapeutic approach is the same as that for pancreatic and peripancreatic fluid collections. In case of infection, the patient undergoes percutaneous US/CT guided drainage. This therapeutic procedure can be added to the therapeutic program for necrotizing acute biliary pancreatitis together with ERCP/ES and videolaparocholecystectomy (VLC). PMID:19660231

  5. The acute pediatric scrotum: presentation, differential diagnosis and management.

    PubMed

    Vasdev, Nikhil; Chadwick, David; Thomas, David

    2012-09-01

    Both pediatric and adult urologists frequently evaluate pediatric patients with an acute scrotum. We present a detailed review on the acute pediatric scrotum highlighting the clinical presentation, differential diagnosis and management of this common clinical condition. It is important to highlight that a testicular torsion is the most important differential diagnosis and the main priority in each case is to diagnosis and treat a potential testicular torsion is of the essence. The aim of our extensive review is to update/review the appropriate evaluation and management of the acute scrotum and to guide the clinician in distinguishing testicular torsion from the other conditions that commonly mimic this surgical emergency. This review is useful for trainees in UK and Europe who plan to take the FRCS (Urol) examination. PMID:24917714

  6. [The mode of differential diagnostic of and acute alcoholic gastroenteritis].

    PubMed

    Makarov, V K; Makarov, P V

    2014-12-01

    The study was carried out to develop mode of differential diagnostic of salmonella and acute alcoholic gastroenteritis on the basis of phospholipid specter of blood serum. The indicators of phospholipid fractions of blood serum were analyzed in 50 healthy persons, 50 patients with acute alcoholic gastroenteritis and 50 patients with salmonella gastroenteritis were analyzed. The relative content of following fractions of whole phospholipids were analyzed--total lysophospholipids, sphyngomiyelin, phosphatidcholine, phosphatidyletanolamin. The phospholipid spectrum of blood serum can be applied in differential diagnostic of salmonella gastroenteritis and acute alcoholic gastroenteritis. The disorders of metabolism of lipids under given pathological conditions have a multidirectional character. The salmonella gastroenteritis is characterized by decreasing of relative content of total lysophospholipids and increasing of phosphatidcholine as compared with standard conditions. The acute alcoholic gastroenteritis is characterized by increasing of relative content of total lysophospholipids and phosphatidcholine and decreasing of level of phosphatidcholine. The content of total Iysophospholipids in blood serum is lower on 35% or 30.0 mg% permits diagnosing acute alcoholic gastroenteritis. The content of phosphaltidcholine in blood serum higher than 40% or 50 mg% permits diagnosing salmonella gastroenteritis.

  7. Approximate polynomial solutions for Riccati differential equations using the squared remains minimization method

    NASA Astrophysics Data System (ADS)

    Bota, C.; Cǎruntu, B.; Bundǎu, O.

    2013-10-01

    In this paper we applied the Squared Remainder Minimization Method (SRMM) to find analytic approximate polynomial solutions for Riccati differential equations. Two examples are included to demonstrated the validity and applicability of the method. The results are compared to those obtained by other methods.

  8. The role of multiparametric flow cytometry in the detection of minimal residual disease in acute leukaemia.

    PubMed

    Lee, Denise; Grigoriadis, George; Westerman, David

    2015-12-01

    Flow cytometry is the most accessible method for minimal residual disease (MRD) detection due to its availability in most haematological centres. Using a precise combination of different antibodies, immunophenotypic detection of MRD in acute leukaemia can be performed by identifying abnormal combinations or expressions of antigens on malignant cells at diagnosis, during and post treatment. These abnormal phenotypes, referred to as leukaemia-associated immunophenotypes (LAIPs) are either absent or expressed at low frequency in normal bone marrow (BM) cells and are used to monitor the behaviour and quantitate the amount of residual disease following treatment. In paediatric acute lymphoblastic leukaemia (ALL), the level of MRD by multiparametric flow cytometry (MPFC) during therapy is recognised as an important predictor of outcome. Although less extensively studied, adult ALL and adult and paediatric acute myeloid leukaemia (AML) have also demonstrated similar findings. The challenge now is incorporating this information for risk-stratification so that therapy can be tailored individually and ultimately improve outcome while also limiting treatment-related toxicity. In this review we will elaborate on the current and future role of MPFC in MRD in acute leukaemia while also addressing its limitations.

  9. Oncogenic NRAS Primes Primary Acute Myeloid Leukemia Cells for Differentiation.

    PubMed

    Brendel, Cornelia; Teichler, Sabine; Millahn, Axel; Stiewe, Thorsten; Krause, Michael; Stabla, Kathleen; Ross, Petra; Huynh, Minh; Illmer, Thomas; Mernberger, Marco; Barckhausen, Christina; Neubauer, Andreas

    2015-01-01

    RAS mutations are frequently found among acute myeloid leukemia patients (AML), generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We have previously shown that treatment of AML patients with high-dose cytarabine is preferentially beneficial for those harboring oncogenic RAS. On the basis of a murine AML cell culture model, we ascribed this effect to a RAS-driven, p53-dependent induction of differentiation. Hence, in this study we sought to confirm the correlation between RAS status and differentiation of primary blasts obtained from AML patients. The gene expression signature of AML blasts with oncogenic NRAS indeed corresponded to a more mature profile compared to blasts with wildtype RAS, as demonstrated by gene set enrichment analysis (GSEA) and real-time PCR analysis of myeloid ecotropic viral integration site 1 homolog (MEIS1) in a unique cohort of AML patients. In addition, in vitro cell culture experiments with established cell lines and a second set of primary AML cells showed that oncogenic NRAS mutations predisposed cells to cytarabine (AraC) driven differentiation. Taken together, our findings show that AML with inv(16) and NRAS mutation have a differentiation gene signature, supporting the notion that NRAS mutation may predispose leukemic cells to AraC induced differentiation. We therefore suggest that promotion of differentiation pathways by specific genetic alterations could explain the superior treatment outcome after therapy in some AML patient subgroups. Whether a differentiation gene expression status may generally predict for a superior treatment outcome in AML needs to be addressed in future studies. PMID:25901794

  10. Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies.

    PubMed

    Ommen, Hans Beier

    2016-02-01

    Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon.

  11. ROLE OF MINIMAL RESIDUAL DISEASE MONITORING IN ADULT AND PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    SYNOPSIS Assays that measure minimal residual disease (MRD) can determine the response to treatment in patients with acute lymphoblastic leukemia (ALL) much more precisely than morphological screening of bone marrow smears. The clinical significance of MRD detected by flow cytometry or polymerase chain reaction-based methods in childhood ALL has been conclusively established. Hence, MRD is being used in several clinical trials to adjust treatment intensity. Similar findings have been gathered in adult patients with ALL, making MRD one of the most powerful and informative parameters to guide clinical management. This article discusses practical issues related to MRD methodologies and the evidence supporting the use of MRD for risk assignment in clinical trials. PMID:19825454

  12. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    ClinicalTrials.gov

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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); Recurrent Adult Acute Myeloid Leukemia

  13. Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by next-generation sequencing.

    PubMed

    Salipante, Stephen J; Fromm, Jonathan R; Shendure, Jay; Wood, Brent L; Wu, David

    2014-11-01

    Detection of minimal residual disease predicts adverse outcome in patients with acute myeloid leukemia. Currently, minimal residual disease may be detected by RQ-PCR or flow cytometry, both of which have practical and diagnostic limitations. Here, we describe a next-generation sequencing assay for minimal residual disease detection in NPM1-mutated acute myeloid leukemia, which encompasses ∼60% of patients with normal karyotype acute myeloid leukemia. Exon 12 of NPM1 was PCR amplified using sequencing adaptor-linked primers and deep sequenced to enable detection of low-prevalence, acute myeloid leukemia-specific activating mutations. We benchmarked our results against flow cytometry, the standard of care for acute myeloid leukemia minimal residual disease diagnosis at our institution. The performance of both approaches was evaluated using defined dilutions of an NPM1 mutation-positive cell line and longitudinal clinical samples from acute myeloid leukemia patients. Using defined control material, we found this assay sensitive to approximately 0.001% mutant cells, outperforming flow cytometry by an order of magnitude. Next-generation sequencing was precise and semiquantitative over four orders of magnitude. In 22 longitudinal samples from six acute myeloid leukemia patients, next-generation sequencing detected minimal residual disease in all samples deemed negative by flow cytometry. Further, in one-third of patients, sequencing detected alternate NPM1 mutations in addition to the patient's index mutation, consistent with tumor heterogeneity. Next-generation sequencing provides information without prior knowledge of NPM1 mutation subtype or validation of allele-specific probes as required for RQ-PCR assays, and without generation and interpretation of complex multidimensional flow cytometry data. This approach may complement current technologies to enhance patient-specific clinical decision-making.

  14. Reweighted ℓ{sub 1} minimization method for stochastic elliptic differential equations

    SciTech Connect

    Yang, Xiu; Karniadakis, George Em

    2013-09-01

    We consider elliptic stochastic partial differential equations (SPDEs) with random coefficients and solve them by expanding the solution using generalized polynomial chaos (gPC). Under some mild conditions on the coefficients, the solution is “sparse” in the random space, i.e., only a small number of gPC basis makes considerable contribution to the solution. To exploit this sparsity, we employ reweighted l{sub 1} minimization to recover the coefficients of the gPC expansion. We also combine this method with random sampling points based on the Chebyshev probability measure to further increase the accuracy of the recovery of the gPC coefficients. We first present a one-dimensional test to demonstrate the main idea, and then we consider 14 and 40 dimensional elliptic SPDEs to demonstrate the significant improvement of this method over the standard l{sub 1} minimization method. For moderately high dimensional (∼10) problems, the combination of Chebyshev measure with reweighted l{sub 1} minimization performs well while for higher dimensional problems, reweighted l{sub 1} only is sufficient. The proposed approach is especially suitable for problems for which the deterministic solver is very expensive since it reuses the sampling results and exploits all the information available from limited sources.

  15. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil.

  16. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil. PMID:26670404

  17. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  18. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10(-3) a 10(-5)), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  19. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia.

    PubMed

    Wu, David; Sherwood, Anna; Fromm, Jonathan R; Winter, Stuart S; Dunsmore, Kimberly P; Loh, Mignon L; Greisman, Harvey A; Sabath, Daniel E; Wood, Brent L; Robins, Harlan

    2012-05-16

    High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging technology that can comprehensively assess the diversity of the immune system. Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal residual disease (MRD) at day 29 after treatment. The variable regions of TCRB and TCRG were sequenced using an Illumina HiSeq platform after performance of multiplexed polymerase chain reaction, which targeted all potential V-J rearrangement combinations. Pretreatment samples were used to define clonal T cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, and paired posttreatment samples were evaluated for MRD. Abnormal T lymphoblast identification by multiparametric flow cytometry was concurrently performed for comparison. We found that TCRB and TCRG HTS not only identified clonality at diagnosis in most cases (31 of 43 for TCRB and 27 of 43 for TCRG) but also detected subsequent MRD. As expected, HTS of TCRB and TCRG identified MRD that was not detected by flow cytometry in a subset of cases (25 of 35 HTS compared with 13 of 35, respectively), which highlights the potential of this technology to define lower detection thresholds for MRD that could affect clinical treatment decisions. Thus, next-generation sequencing of lymphoid receptor gene repertoire may improve clinical diagnosis and subsequent MRD monitoring of lymphoproliferative disorders.

  20. Minimal residual disease detection using flow cytometry: Applications in acute leukemia.

    PubMed

    Chatterjee, T; Mallhi, R S; Venkatesan, S

    2016-04-01

    Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia.

  1. Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia.

    PubMed

    Will, Britta; Vogler, Thomas O; Narayanagari, Swathi; Bartholdy, Boris; Todorova, Tihomira I; da Silva Ferreira, Mariana; Chen, Jiahao; Yu, Yiting; Mayer, Jillian; Barreyro, Laura; Carvajal, Luis; Neriah, Daniela Ben; Roth, Michael; van Oers, Johanna; Schaetzlein, Sonja; McMahon, Christine; Edelmann, Winfried; Verma, Amit; Steidl, Ulrich

    2015-10-01

    Modest transcriptional changes caused by genetic or epigenetic mechanisms are frequent in human cancer. Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice, a similar degree of PU.1 impairment is exceedingly rare in human AML; yet, moderate PU.1 inhibition is common in AML patients. We assessed functional consequences of modest reductions in PU.1 expression on leukemia development in mice harboring DNA lesions resembling those acquired during human stem cell aging. Heterozygous deletion of an enhancer of PU.1, which resulted in a 35% reduction of PU.1 expression, was sufficient to induce myeloid-biased preleukemic stem cells and their subsequent transformation to AML in a DNA mismatch repair-deficient background. AML progression was mediated by inhibition of expression of a PU.1-cooperating transcription factor, Irf8. Notably, we found marked molecular similarities between the disease in these mice and human myelodysplastic syndrome and AML. This study demonstrates that minimal reduction of a key lineage-specific transcription factor, which commonly occurs in human disease, is sufficient to initiate cancer development, and it provides mechanistic insight into the formation and progression of preleukemic stem cells in AML.

  2. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies

    PubMed Central

    van der Velden, Vincent H. J.; Brüggemann, Monika; Orfao, Alberto

    2015-01-01

    Monitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions. This is also why the efficacy of innovative drugs, such as antibodies and small molecules, are currently being evaluated with MRD diagnostics within clinical trials. In fact, MRD measurements might well be used as a surrogate end point, thereby significantly shortening the follow-up. The MRD techniques need to be sensitive (≤10−4), broadly applicable, accurate, reliable, fast, and affordable. Thus far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]-PCR) are claimed to meet these criteria, but classical flow cytometry does not reach a solid 10−4, whereas classical ASO-PCR is time-consuming and labor intensive. Therefore, 2 high-throughput technologies are being explored, ie, high-throughput sequencing and next-generation (multidimensional) flow cytometry, both evaluating millions of sequences or cells, respectively. Each of them has specific advantages and disadvantages. PMID:25999452

  3. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. A method of minimizing the frequency stabilization sensitivity for four frequency differential laser gyro

    NASA Astrophysics Data System (ADS)

    Yang, Jianqiang; Zhu, Yong; Luo, Yun; Jiang, Tian

    2010-10-01

    The frequency stabilization error is an important error source to limit the precision of four frequency differential ring laser gyro (DILAG) in navigation application. Different from the traditional technology mainly related to frequency stabilization circuits design, this paper introduces a new method to solve the problem. The method can essentially minimize the frequency stabilization sensitivity of DILAG, by applying an outer longitudinal magnetic field to the gain region of DILAG. Through adjusting the value of magnetic field to make the frequency splitting equal to the Faraday splitting, the minimum frequency stabilization sensitivity of DILAG will be available. The physics mechanism and mathematic model of this method are analyzed and set up. Concrete steps to realize the method are given in detail. Experimental results have verified its validity and it can decrease the startup drift. Hence, this new method can improve the performance of DILAG, which will be helpful to navigation application.

  5. A branch-and-bound algorithm for makespan minimization in differentiation flow shops

    NASA Astrophysics Data System (ADS)

    Liu, Yen-Cheng; Fang, Kuei-Tang; Lin, Bertrand

    2013-12-01

    This article considers a differentiation flow-shop model, where the jobs are divided into various categories, each of which consists of two stages of operations. All products should be processed first on the single common machine at stage 1. At the second stage, each individual product proceeds to a dedicated machine according to its type. The problem of makespan minimization under the setting with two product types is known to be strongly NP hard. This article considers an arbitrary number of job types by developing a lower bound and two dominance rules, based upon which branch-and-bound algorithms are designed. Computational experiments are carried out to examine the performance of the proposed properties. The statistics show that the proposed properties can substantially reduce the computing efforts required for finding optimal solutions.

  6. Evaluation of Minimal Residual Disease in Acute Myeloid Leukemia with NPM1 Marker

    PubMed Central

    Alizad Ghandforoush, Nasrin; Chahardouli, Bahram; Rostami, Shahrbano; Ghadimi, Habibeh; Ghasemi, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Nadali, Fatemeh

    2016-01-01

    Background: Minimal residual disease (MRD) tests provide early identification of hematologic relapse and timely management of acute myeloid leukemia (AML) patients. Approximately, 50% of AML patients do not have clonal chromosomal aberrations and categorize as a cytogenetically normal acute myeloid leukemia (CN-AML). About 60% of adult CN-AML has a mutation in exon 12 of NPM1 gene. This mutation is specific for malignant clone and potentially is a good marker of MRD. In this retrospective study, we set up a quantitative test for quantifying NPM1 type A mutation and AML patients carrying this mutation at the time of diagnosis, were followed-up. Materials and Methods : We prepared plasmids containing a cDNA fragment of NPM1 and ABL genes by PCR cloning. The plasmids were used to construct standard curves. Eleven patients were analyzed using established method. Serial PB and/or BM samples (n=71) were taken in 1-3 months intervals (mean 1.5-month intervals) and median follow-up duration after chemotherapy was 11 months (5-28.5 months). Results: In this study, we developed RNA-based RQ-PCR to quantitation of NPM1 mutation A with sensitivities of 10(-5). The percent of NPMmut/ABL level showed a range between 132 and 757 with median of 383.5 in samples at diagnosis. The median NPMmut transcript level log reduction was 3 logs. Relapse occurred in 54.5% of patients (n=6), all cases at diagnosis demonstrated the same mutation at relapse. In patients who experienced relapse, log reduction levels of NPM1 mRNA transcript after therapy were 4 (n=2), 3 (n=2) and 1 log (n=2). Totally, NPMmut level showed less than 5 log reduction in all of them, whereas this reduction was 5-6 logs in other patients. Conclusion: Despite the limitations of this study in terms of sample size and duration of follow-up, it showed the accuracy of set up for detection of mutation and this marker has worth for following-up at different stages of disease. Because of high frequency, stability, specificity

  7. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: A Clinical Evidence Review

    PubMed Central

    2016-01-01

    Background Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD). Poor event-free survival (EFS) as well as overall survival for those who are classified as MRD-positive have been substantiated in seminal studies demonstrating the prognostic value of MRD for EFS in the past few decades. This review sought to further elucidate the relationship between MRD and EFS by looking at relapse, the primary determinant of EFS and the biological mechanism through which MRD is thought to act. This evidence review aimed to ascertain whether MRD is an independent prognostic factor for relapse and to assess the effect of MRD-directed treatment on patient-important outcomes in childhood ALL. Methods Large prospective cohort studies with a priori multivariable analysis that includes potential confounders are required to draw confirmatory conclusions about the independence of a prognostic factor. Data on the prognostic value of MRD for relapse measured by molecular methods (polymerase chain reaction [PCR] of immunoglobulin or T-cell receptor rearrangements) or flow cytometry for leukemia-associated immunophenotypes or difference-from-normal approach were abstracted from included studies. Relevant data on relapse, EFS, and overall survival were abstracted from randomized controlled trials (RCTs) evaluating the effect of MRD-directed treatment. Results A total of 2,832 citations were reviewed, of which 12 studies were included in this

  8. Epigenetic mechanisms regulate stage differentiation in the minimized protozoan Giardia lamblia.

    PubMed

    Sonda, Sabrina; Morf, Laura; Bottova, Iveta; Baetschmann, Hansruedi; Rehrauer, Hubert; Caflisch, Amedeo; Hakimi, Mohamed-Ali; Hehl, Adrian B

    2010-04-01

    Histone modification is an important mechanism regulating both gene expression and the establishment and maintenance of cellular phenotypes during development. Regulation of histone acetylation via histone acetylases and deacetylases (HDACs) appears to be particularly crucial in determining gene expression patterns. In this study we explored the effect of HDAC inhibition on the life cycle of the human pathogen Giardia lamblia, a highly reduced parasitic protozoan characterized by minimized cellular processes. We found that the HDAC inhibitor FR235222 increased the level of histone acetylation and induced transcriptional regulation of approximately 2% of genes in proliferating and encysting parasites. In addition, our analyses showed that the levels of histone acetylation decreased during differentiation into cysts, the infective stage of the parasite. Importantly, FR235222 treatment during encystation reversed this histone hypo-acetylation and potently blocked the formation of cysts. These results provide the first direct evidence for epigenetic regulation of gene expression in this simple eukaryote. This suggests that regulation of histone acetylation is involved in the control of Giardia stage differentiation, and identifies epigenetic mechanisms as a promising target to prevent Giardia transmission. PMID:20132448

  9. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. PMID:24740809

  10. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.

  11. Quantitative evaluation of monocyte differentiation by electron microscopy: impairment of differentiation ability in monocytes from children with acute lymphoblastic leukaemia.

    PubMed

    Tsukada, M; Hara, Y; Sugiyama, H; Yoda, S; Hara, T; Komiyama, A; Akabane, T

    1985-05-01

    The differentiation of monocytes was evaluated quantitatively by electron microscopy and was analyzed in relation to the clinical features of childhood acute lymphoblastic leukaemia (ALL). The monocyte cellular size increased and cell organellae became mature after a 72-h culture. Phagolysosome formation developed markedly- and the nucleus became circular--accompanied by chromatin deconcentration. The differentiation degree of the cell organellae was indexed and classified as mature by electron microscopy. The indexes of nuclear shape, chromatin deconcentration, cytoplasmonuclear ratio and vacuole formation increased with time. The total index increased linearly with time dependence. These results indicate that the ultrastructural parameters and indexes allowed a quantitative assessment of cell organellae and cellular differentiation of the monocyte. At the acute phase of ALL, the degrees of cell organnellae and cellular differentiation were significantly lower than the control. The above findings suggest that monocytes from children with ALL have impaired differentiation ability, which results in defective function of macrophages.

  12. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation.

  13. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    PubMed Central

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  14. [Differential magnetic resonance diagnosis of central lung cancer and acute pneumonia].

    PubMed

    Gamova, E V; Nudnov, N V

    2006-01-01

    The paper analyzes the authors' own data of chest magnetic resonance imaging (MRI) in 86 patients with verified central lung cancer and acute pneumonia. The MRI signs of lung cancer are systematized in exo-, endo-, and peribronchial forms of growth. The additional capacities of contrast enhancement are analyzed. The MRI semiotics of acute pneumonia has been developed. The differential diagnostic criteria for recognizing central lung cancer and acute pneumonia have been also elaborated.

  15. Novel tools for the diagnosis and differentiation of acute and chronic bovine besnoitiosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diagnosis of acute bovine besnoitiosis is a major diagnostic problem. We developed diagnostic tests to serologically diagnose and differentiate acute and chronic cases of bovine besnoitiosis using affinity purified antigens of Besnoitia besnoiti tachyzoites in immunoblots and in both, a conventional...

  16. Using Taguchi method to optimize differential evolution algorithm parameters to minimize workload smoothness index in SALBP

    NASA Astrophysics Data System (ADS)

    Mozdgir, A.; Mahdavi, Iraj; Seyyedi, I.; Shiraqei, M. E.

    2011-06-01

    An assembly line is a flow-oriented production system where the productive units performing the operations, referred to as stations, are aligned in a serial manner. The assembly line balancing problem arises and has to be solved when an assembly line has to be configured or redesigned. The so-called simple assembly line balancing problem (SALBP), a basic version of the general problem, has attracted attention of researchers and practitioners of operations research for almost half a century. There are four types of objective functions which are considered to this kind of problem. The versions of SALBP may be complemented by a secondary objective which consists of smoothing station loads. Many heuristics have been proposed for the assembly line balancing problem due to its computational complexity and difficulty in identifying an optimal solution and so many heuristic solutions are supposed to solve this problem. In this paper a differential evolution algorithm is developed to minimize workload smoothness index in SALBP-2 and the algorithm parameters are optimized using Taguchi method.

  17. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  18. A Brain Signature to Differentiate Acute and Chronic Pain in Rats

    PubMed Central

    Guo, Yifei; Wang, Yuzheng; Sun, Yabin; Wang, Jin-Yan

    2016-01-01

    The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID:27199727

  19. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.

    PubMed

    Alten, Julia; Klapper, Wolfram; Leuschner, Ivo; Eckert, Cornelia; Beier, Rita; Vallo, Elisabeth; Krause, Martin; Claviez, Alexander; Vieth, Simon; Bleckmann, Kirsten; Möricke, Anja; Schrappe, Martin; Cario, Gunnar

    2015-09-01

    Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow. Thus, HS should be considered in ALL when MRD appears to persist or reappear.

  1. Cooperative antiproliferative and differentiation-enhancing activity of medicinal plant extracts in acute myeloid leukemia cells.

    PubMed

    Zhamanbayeva, Gulzhan T; Aralbayeva, Araylim N; Murzakhmetova, Maira K; Tuleukhanov, Sultan T; Danilenko, Michael

    2016-08-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and limited treatment options. Sea buckthorn (Hippophae rhamnoides) berries, dog rose (Rosa canina) rosehips, and garden sage (Salvia officinalis) and oregano (Origanum vulgare) aerial parts are widely used in traditional medicine and exhibit antitumor effects in preclinical models. However, these plants remain scarcely tested for antileukemic activity. Here, we show that their water-ethanol leaf extracts reduced the growth and viability of AML cells and, at non-cytotoxic doses, potentiated cell differentiation induced by a low concentration of 1α,25-dihydroxyvitamin D3, the hormonal form of vitamin D, in a cell type-dependent manner. The latter effect was accompanied by upregulation of the vitamin D receptor protein components and its transcriptional activity. Furthermore, at minimally effective doses the extracts cooperated with one another to produce marked cytostatic effects associated with a partial S-phase arrest and a modest induction of apoptosis. In contrast, these combinations only slightly affected the growth and viability of proliferating normal human peripheral blood mononuclear cells. In addition, the extracts strongly inhibited microsomal lipid peroxidation and protected normal erythrocytes against hypoosmotic shock. Our results suggest that further exploration of the enhanced antileukemic effects of the combinations tested here may lead to the development of alternative therapeutic and preventive approaches against AML. PMID:27470342

  2. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    PubMed

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.

  3. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  4. Induction of differentiation and apoptosis- a possible strategy in the treatment of adult acute myelogenous leukemia.

    PubMed

    Bruserud, O; Gjertsen, B T; Huang, Ts

    2000-01-01

    A differentiation block with accumulation of immature myeloid cells characterizes acute myelogenous leukemia (AML). However, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment for the acute promyelocytic leukemia variant of AML. Several agents can induce leukemic cell differentiation for other AML subtypes, although these effects differ between patients. Differentiation may then be associated with induction of apoptosis, and differentiation-inducing therapy may therefore become useful in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. However, it should be emphasized that differentiation and apoptosis can occur as separate events with different regulation in AML cells, and future studies in AML should therefore focus on: A) the identification of new agents with more predictable effects on differentiation and apoptosis; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation/apoptosis induction has a predictable and beneficial effect, and C) further characterization of how AML blast sensitivity to drug-induced apoptosis is modulated by differentiation induction.

  5. [THE COMPARISON OF RESULTS OF DETECTION OF MINIMAL RESIDUAL DISEASE IN PERIPHERAL BLOOD AND MARROW IN CHILDREN OF THE FIRST YEAR OF LIFE WITH ACUTE LYMPHOBLASTIC LEUCOSIS].

    PubMed

    Tsaur, G A; Riger, T O; Popov, A M; Nasedkina, T V; Kustanovich, A M; Solodovnikov, A G; Streneva, O V; Shorikov, E V; Tsvirenko, S V; Saveliev, L I; Fechina, L G

    2015-04-01

    The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic

  6. Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.

    PubMed

    Sykes, David B; Kfoury, Youmna S; Mercier, François E; Wawer, Mathias J; Law, Jason M; Haynes, Mark K; Lewis, Timothy A; Schajnovitz, Amir; Jain, Esha; Lee, Dongjun; Meyer, Hanna; Pierce, Kerry A; Tolliday, Nicola J; Waller, Anna; Ferrara, Steven J; Eheim, Ashley L; Stoeckigt, Detlef; Maxcy, Katrina L; Cobert, Julien M; Bachand, Jacqueline; Szekely, Brian A; Mukherjee, Siddhartha; Sklar, Larry A; Kotz, Joanne D; Clish, Clary B; Sadreyev, Ruslan I; Clemons, Paul A; Janzer, Andreas; Schreiber, Stuart L; Scadden, David T

    2016-09-22

    While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the observation that the majority of AML, despite their genetically heterogeneity, share in the expression of HoxA9, a gene normally downregulated during myeloid differentiation. Using a conditional HoxA9 model system, we performed a high-throughput phenotypic screen and defined compounds that overcame differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) enables myeloid differentiation in human and mouse AML models. In vivo, DHODH inhibitors reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival. These data demonstrate the role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in AML.

  7. Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.

    PubMed

    Bal, Naresh C; Maurya, Santosh K; Singh, Sushant; Wehrens, Xander H T; Periasamy, Muthu

    2016-08-12

    Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized.

  8. Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.

    PubMed

    Bal, Naresh C; Maurya, Santosh K; Singh, Sushant; Wehrens, Xander H T; Periasamy, Muthu

    2016-08-12

    Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized. PMID:27298322

  9. Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia

    PubMed Central

    Paula, Francisco Danilo Ferreira; Elói-Santos, Silvana Maria; Xavier, Sandra Guerra; Ganazza, Mônica Aparecida; Jotta, Patricia Yoshioka; Yunes, José Andrés; Viana, Marcos Borato; Assumpção, Juliana Godoy

    2015-01-01

    Introduction Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. Objective The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. Methods Seventy-four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan–Meier and multivariate Cox methods and the log-rank test were used for statistical analysis. Results Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1 × 10−3 for precursor B-cell acute lymphoblastic leukemia and 1 × 10−2 for T-cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1% ± 5.6% versus 41.7% ± 17.3%, respectively; p-value = 0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. Conclusion Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. PMID:26670399

  10. Quantitative detection of the human cervical cancer oncogene for monitoring the minimal residual disease in acute leukemia

    PubMed Central

    Guo, Xiao-Nan; Ren, Jin-Hai; Zhang, Jing-Nan; Wang, Ying

    2015-01-01

    The human cervical cancer oncogene (HCCR) has been shown to be over-expressed in some solid tumors, and its function is involved in negative regulation of p53 tumor suppressor gene. However, the roles of HCCR in leukemia remain unclear. The present study is to investigate whether the expression levels of HCCR mRNA are associated with clinical prognosis in patients with acute leukemia (AL) and to explore the potential use as a biomarker for monitoring minimal residual disease (MRD) in AL. The mRNA levels of HCCR1 and HCCR2 were quantified by real-time reverse transcription polymerase chain reaction in bone marrow samples from 80 adult de novo AL patients and 20 normal healthy donors. The expressions of HCCR1 and HCCR2 were significantly higher in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) than those in healthy donors (P < 0.01), but there was no significant difference between AML and ALL (P > 0.05). Besides white blood cell count, we did not find any significant correlation between HCCR expression and clinical characteristics, such as age, sex, CD34 antigen expression, and response to chemotherapy. HCCR was monitored in 12 cases during remission and/or relapse. Significant reductions of both HCCR1 and HCCR2 mRNA levels were observed in patients who had achieved complete remission after chemotherapy but not in patients with non-responsive. However, an increased HCCR expression was detected in these patients who relapsed. Our findings suggest that HCCR gene is over-expressed in AL patients and may be as a useful biomarker for monitoring MRD in AL. PMID:25034723

  11. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-07-26

    Adult Acute Myeloid Leukemia in Remission; 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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Late differentiation syndrome in acute promyelocytic leukemia: a challenging diagnosis.

    PubMed

    Cabral, Renata; Caballero, Juan Carlos; Alonso, Sara; Dávila, Julio; Cabrero, Monica; Caballero, Dolores; Vázquez, Lourdes; Sánchez-Guijo, Fermin; López, Lucia; Cañizo, Maria C; Mateos, Maria V; González, Marcos

    2014-11-19

    Detailed knowledge about differentiation syndrome (DS) has remained limited. There are 2 large studies conducted by the Spanish workgroup PETHEMA (Programa Español de Tratamientos en Hematología; Spanish Program on Hematology Treatments) and the European group trial (LPA 96-99 and APL 93) in which the incidence, characteristics, prognostic factors and outcome of patients developing DS are evaluated. Both have described the median time of DS development between 10 and 12 days. The severity of the DS has been evaluated in the study conducted by PETHEMA, and severe DS usually occurs at the beginning of the treatment (median of 6 days), as compared with moderate DS (median of 15 days). We report here in two cases of late severe DS, with late diagnosis due to both time and form of presentation. We discuss the physiopathology, clinical presentation, prophylaxis and treatment of DS.

  13. Differential item functioning on the Five Facet Mindfulness Questionnaire is minimal in demographically matched meditators and nonmeditators.

    PubMed

    Baer, Ruth A; Samuel, Douglas B; Lykins, Emily L B

    2011-03-01

    A recent study of the Five Facet Mindfulness Questionnaire reported high levels of differential item functioning (DIF) for 18 of its 39 items in meditating and nonmeditating samples that were not demographically matched. In particular, meditators were more likely to endorse positively worded items whereas nonmeditators were more likely to deny negatively worded (reverse-scored) items. The present study replicated these analyses in demographically matched samples of meditators and nonmeditators (n = 115 each) and found that evidence for DIF was minimal. There was little or no evidence for differential relationships between positively and negatively worded items for meditators and nonmeditators. Findings suggest that DIF based on items' scoring direction is not problematic when the Five Facet Mindfulness Questionnaire is used to compare demographically similar meditators and nonmeditators.

  14. Small and cheap: accurate differential blood count with minimal sample volume by laser scanning cytometry (LSC)

    NASA Astrophysics Data System (ADS)

    Mittag, Anja; Lenz, Dominik; Smith, Paul J.; Pach, Susanne; Tarnok, Attila

    2005-04-01

    Aim: In patients, e.g. with congenital heart diseases, a differential blood count is needed for diagnosis. To this end by standard automatic analyzers 500 μl of blood is required from the patients. In case of newborns and infants this is a substantial volume, especially after operations associated with blood loss. Therefore, aim of this study was to develop a method to determine a differential blood picture with a substantially reduced specimen volume. Methods: To generate a differential blood picture 10 μl EDTA blood were mixed with 10 μl of a DRAQ5 solution (500μM, Biostatus) and 10 μl of an antibody mixture (CD45-FITC, CD14-PE, diluted with PBS). 20 μl of this cell suspension was filled into a Neubauer counting chamber. Due to the defined volume of the chamber it is possible to determine the cell count per volume. The trigger for leukocyte counting was set on DRAQ5 signal in order to be able to distinguish nucleated white blood cells from erythrocytes. Different leukocyte subsets could be distinguished due to the used fluorescence labeled antibodies. For erythrocyte counting cell suspension was diluted another 150 times. 20 μl of this dilution was analyzed in a microchamber by LSC with trigger set on forward scatter signal. Results: This method allows a substantial decrease of blood sample volume for generation of a differential blood picture (10 μl instead of 500μl). There was a high correlation between our method and the results of routine laboratory (r2=0.96, p<0.0001 n=40). For all parameters intra-assay variance was less than 7 %. Conclusions: In patients with low blood volume such as neonates and in critically ill infants every effort has to be taken to reduce the blood volume needed for diagnostics. With this method only 2% of standard sample volume is needed to generate a differential blood picture. Costs are below that of routine laboratory. We suggest this method to be established in paediatric cardiology for routine diagnostics and for

  15. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  16. Minimal Residual Disease Detection and Evolved IGH Clones Analysis in Acute B Lymphoblastic Leukemia Using IGH Deep Sequencing

    PubMed Central

    Wu, Jinghua; Jia, Shan; Wang, Changxi; Zhang, Wei; Liu, Sixi; Zeng, Xiaojing; Mai, Huirong; Yuan, Xiuli; Du, Yuanping; Wang, Xiaodong; Hong, Xueyu; Li, Xuemei; Wen, Feiqiu; Xu, Xun; Pan, Jianhua; Li, Changgang; Liu, Xiao

    2016-01-01

    Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment. PMID:27757113

  17. The application of CD73 in minimal residual disease monitoring using flow cytometry in B-cell acute lymphoblastic leukemia.

    PubMed

    Wang, Wei; Gao, Li; Li, Yan; Li, Zhen-Ling; Gong, Ming; Huang, Fan-Zhou; Chen, Yan-Rong; Zhang, Chun-Xia; Gao, Ya-Yue; Ma, Yi-Gai

    2016-05-01

    The expression of CD73 by flow cytometry (FC) in bone marrow (BM) specimens of B-cell acute lymphoblastic leukemia (B-ALL) with or without minimal residual disease (MRD) was studied, and its advantages were evaluated using the MRD assay. This study also detected the expression profile of CD73 in hematogones and mature B cells in BM specimens of 18 healthy donors. Results showed that the mean value of CD73 expression in MRD-positive B cells was 6-fold greater than that in the MRD negative ones. Also, 41.82% MRD-positive B-ALL cases expressed high CD73 and the sensitivity of CD73-based MRD detection reached 10(-4). Since the expression of CD73 increases with the maturation of normal B cells, it is better to mix it with CD34, CD10 and CD20 in one tube to prevent the disturbance of mature B cells. CD73 is recommended as an optional MRD marker for B-ALL patients by using FC.

  18. Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia.

    PubMed

    Sun, Hui; Li, Yi; Zhang, Zhi-fen; Ju, Ying; Li, Li; Zhang, Bing-chang; Liu, Bin

    2015-11-01

    Myeloid-derived suppressor cells (MDSCs) are thought to help provide a cellular microenvironments in many solid tumors, in which transformed cells proliferate, acquire new mutations, and evade host immunosurveillance. In the present study, we found that MDSCs (CD33 + CD11b + HLA-DR(low/neg)) in bone marrow were significantly increased in adult acute myeloid leukemia (AML) patients. MDSCs levels in newly diagnosed AML patients correlated well with extramedullary infiltration and plasma D-dimer levels. Remission rates in the MDSCs > 1500 group and MDSCs < 1500 group were 72.73 and 81.25 %, respectively. No significant differences were found between the two groups. MDSC levels in the complete remission group were significantly decreased after chemotherapy, while in the partial remission and non-remission groups, there were no significant differences. The level of MDSCs in the high minimal residual disease (MRD) group was significantly higher than that in the middle and low MRD groups. High levels of Wilms' Tumor-1 (WT-1) protein were strongly correlated with higher bone marrow MDSC levels. In conclusion, we report here a population of immunosuppressive monocytes in the bone marrow of patients with AML characterized by the CD33(high)CD11b + HLA-DR(low/neg) phenotype. These cells appear to impact the clinical course and prognosis of AML. This data may provide potentially important targets for novel therapies.

  19. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    PubMed

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. PMID:26598032

  20. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    PubMed

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.

  1. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2016-03-16

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  2. Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-03-22

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Cellular Diagnosis, Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines

    PubMed Central

    Ge, Dong-zheng; Sheng, Yan; Cai, Xun

    2014-01-01

    All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In ATRA resistant APL cell lines NB4-R1 and NB4-R2, the combination of staurosporine and ATRA synergized to trigger differentiation accompanied by significantly enhanced protein level of CCAAT/enhancer binding protein ε (C/EBPε) and C/EBPβ as well as the phosphorylation of mitogen-activated protein (MEK) and extracellular signal-regulated kinase (ERK). Furthermore, attenuation of the MEK activation blocked not only the differentiation but also the increased protein level of C/EBPε and C/EBPβ. Taken together, we concluded that the combination of ATRA and staurosporine could overcome differentiation block via MEK/ERK signaling pathway in ATRA-resistant APL cell lines. PMID:24769642

  4. Minimal deviation mucinous adenocarcinoma of the uterine cervix that proved difficult to differentiate from endometrial cancer: A case report

    PubMed Central

    NISHII, YUKO; FUKUDA, TAKESHI; IMAI, KENJI; YAMAUCHI, MAKOTO; HASHIGUCHI, YASUNORI; ICHIMURA, TOMOYUKI; YASUI, TOMOYO; SUMI, TOSHIYUKI

    2014-01-01

    Minimal deviation adenocarcinoma (MDA), also known as adenoma malignum of the uterine cervix, accounts for only ~1% of uterine cervical adenocarcinomas. Adenoma malignum of the uterine cervix was initially described by Gusserow in 1870. Using magnetic resonance imaging (MRI), MDA appears as multilocular lesions with solid components that extend from the endocervical glands to the deep cervical stroma. Cytological evaluation and biopsies have low detection rates, therefore, it is difficult to diagnose MDA accurately prior to treatment. The current study describes a rare case of MDA that was difficult to differentiate from endometrial adenocarcinoma of the corpus uteri preoperatively, as the endometrial biopsy results suggested a well-differentiated endometrioid adenocarcinoma and MRI did not show typical images for MDA. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the diagnosis of endometrial cancer, and the mass was subsequently diagnosed as MDA of the uterine cervix by pathological examination of the hysterectomy specimen. Postoperatively, although two types of adjuvant chemotherapy were performed, the remaining tumor continued to grow, causing obstruction of the bilateral ureters and leading to bilateral hydronephrosis. The patient is currently alive with the disease 10 months following the surgery. PMID:25364411

  5. C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia.

    PubMed

    Alberich-Jordà, Meritxell; Wouters, Bas; Balastik, Martin; Shapiro-Koss, Clara; Zhang, Hong; Di Ruscio, Annalisa; DiRuscio, Annalisa; Radomska, Hanna S; Ebralidze, Alexander K; Amabile, Giovanni; Ye, Min; Zhang, Junyan; Lowers, Irene; Avellino, Roberto; Melnick, Ari; Figueroa, Maria E; Valk, Peter J M; Delwel, Ruud; Tenen, Daniel G

    2012-12-01

    C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.

  6. Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.

    PubMed

    Sykes, David B; Kfoury, Youmna S; Mercier, François E; Wawer, Mathias J; Law, Jason M; Haynes, Mark K; Lewis, Timothy A; Schajnovitz, Amir; Jain, Esha; Lee, Dongjun; Meyer, Hanna; Pierce, Kerry A; Tolliday, Nicola J; Waller, Anna; Ferrara, Steven J; Eheim, Ashley L; Stoeckigt, Detlef; Maxcy, Katrina L; Cobert, Julien M; Bachand, Jacqueline; Szekely, Brian A; Mukherjee, Siddhartha; Sklar, Larry A; Kotz, Joanne D; Clish, Clary B; Sadreyev, Ruslan I; Clemons, Paul A; Janzer, Andreas; Schreiber, Stuart L; Scadden, David T

    2016-09-22

    While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the observation that the majority of AML, despite their genetically heterogeneity, share in the expression of HoxA9, a gene normally downregulated during myeloid differentiation. Using a conditional HoxA9 model system, we performed a high-throughput phenotypic screen and defined compounds that overcame differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) enables myeloid differentiation in human and mouse AML models. In vivo, DHODH inhibitors reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival. These data demonstrate the role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in AML. PMID:27641501

  7. Novel Management of Acute or Secondary Biliary Liver Conditions Using Hepatically Differentiated Human Dental Pulp Cells

    PubMed Central

    Ishkitiev, Nikolay; Imai, Toshio; Tanaka, Tomoko; Fushimi, Naho; Mitev, Vanyo; Okada, Mio; Tominaga, Noriko; Ono, Sachie; Ishikawa, Hiroshi

    2015-01-01

    The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis remains. We have recently developed a protocol for hepatic differentiation of CD117+ stem cells from human exfoliated deciduous teeth (SHED). In the present study, we examine whether SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117+ cell fraction was magnetically separated from SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem cell source for regenerative medicine. PMID:25234861

  8. The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

    PubMed

    Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas

    2014-07-01

    The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

  9. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol.

    PubMed

    Van der Velden, V H J; Corral, L; Valsecchi, M G; Jansen, M W J C; De Lorenzo, P; Cazzaniga, G; Panzer-Grümayer, E R; Schrappe, M; Schrauder, A; Meyer, C; Marschalek, R; Nigro, L L; Metzler, M; Basso, G; Mann, G; Den Boer, M L; Biondi, A; Pieters, R; Van Dongen, J J M

    2009-06-01

    Acute lymphoblastic leukemia (ALL) in infants younger than 1 year is a rare but relatively homogeneous disease ( approximately 80% MLL gene rearranged, approximately 70% CD10-negative) when compared with childhood and adult ALL. Several studies in children and adults with ALL have shown that minimal residual disease (MRD) status is a strong and independent prognostic factor. We therefore evaluated the prognostic significance of MRD in infant ALL. Ninety-nine infant patients treated according to the Interfant-99 protocol were included in this study. MRD was analyzed by real-time quantitative PCR analysis of rearranged immunoglobulin genes, T-cell receptor genes and MLL genes at various time points (TP) during therapy. Higher MRD levels at the end of induction (TP2) and consolidation (TP3) were significantly associated with lower disease-free survival. Combined MRD information at TP2 and TP3 allowed recognition of three patients groups that significantly differed in outcome. All MRD-high-risk patients (MRD levels > or =10(-4) at TP3; 26% of patients) relapsed. MRD-low-risk patients (MRD level <10(-4) at both TP2 and TP3) constituted 44% of patients and showed a relapse-rate of only 13%, whereas remaining patients (MRD-medium-risk patients; 30% of patients) had a relapse rate of 31%. Comparison between the current Interfant-06 stratification at diagnosis and the here presented MRD-based stratification showed that both stratifications recognized different subgroups of patients. These data indicate that MRD diagnostics has added value for recognition of risk groups in infant ALL and that MRD diagnostics can be used for treatment intervention in infant ALL as well.

  10. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    PubMed

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

  11. Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia.

    PubMed

    Pettersson, Louise; Levéen, Per; Axler, Olof; Dvorakova, Dana; Juliusson, Gunnar; Ehinger, Mats

    2016-10-01

    Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. © 2016 Wiley Periodicals, Inc.

  12. Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia.

    PubMed

    Pettersson, Louise; Levéen, Per; Axler, Olof; Dvorakova, Dana; Juliusson, Gunnar; Ehinger, Mats

    2016-10-01

    Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. © 2016 Wiley Periodicals, Inc. PMID:27191933

  13. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis.

    PubMed

    Tan, Melanie; Mol, Gerben C; van Rooden, Cornelis J; Klok, Frederikus A; Westerbeek, Robin E; Iglesias Del Sol, Antonio; van de Ree, Marcel A; de Roos, Albert; Huisman, Menno V

    2014-07-24

    Accurate diagnostic assessment of suspected ipsilateral recurrent deep vein thrombosis (DVT) is a major clinical challenge because differentiating between acute recurrent thrombosis and residual thrombosis is difficult with compression ultrasonography (CUS). We evaluated noninvasive magnetic resonance direct thrombus imaging (MRDTI) in a prospective study of 39 patients with symptomatic recurrent ipsilateral DVT (incompressibility of a different proximal venous segment than at the prior DVT) and 42 asymptomatic patients with at least 6-month-old chronic residual thrombi and normal D-dimer levels. All patients were subjected to MRDTI. MRDTI images were judged by 2 independent radiologists blinded for the presence of acute DVT and a third in case of disagreement. The sensitivity, specificity, and interobserver reliability of MRDTI were determined. MRDTI demonstrated acute recurrent ipsilateral DVT in 37 of 39 patients and was normal in all 42 patients without symptomatic recurrent disease for a sensitivity of 95% (95% CI, 83% to 99%) and a specificity of 100% (95% CI, 92% to 100%). Interobserver agreement was excellent (κ = 0.98). MRDTI images were adequate for interpretation in 95% of the cases. MRDTI is a sensitive and reproducible method for distinguishing acute ipsilateral recurrent DVT from 6-month-old chronic residual thrombi in the leg veins.

  14. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    SciTech Connect

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min; Wang, Jianxiang

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  15. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

    PubMed Central

    YAMAMOTO, NOBUYUKI; KOZAKI, AIKO; HARTOMO, TRI BUDI; YANAI, TOMOKO; HASEGAWA, DAIICHIRO; KAWASAKI, KEIICHIRO; KOSAKA, YOSHIYUKI; MATSUO, MASAFUMI; HIRASE, SATOSHI; MORI, TAKESHI; HAYAKAWA, AKIRA; IIJIMA, KAZUMOTO; NISHIO, HISAHIDE; NISHIMURA, NORIYUKI

    2015-01-01

    Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients. PMID:26722317

  17. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review.

    PubMed

    Christou, Andri; Papastavrou, Evridiki; Merkouris, Anastasios; Frangos, Savvas; Tamana, Panayiota; Charalambous, Andreas

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000-10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  18. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

    PubMed Central

    Papastavrou, Evridiki; Frangos, Savvas; Tamana, Panayiota

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  19. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  20. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia

    PubMed Central

    Weisberg, Stuart P.; Smith-Raska, Matthew R.; Esquilin, Jose M.; Zhang, Ji; Arenzana, Teresita L.; Lau, Colleen M.; Churchill, Michael; Pan, Haiyan; Klinakis, Apostolos; Dixon, Jack E.; Mirny, Leonid A.; Mukherjee, Siddhartha; Reizis, Boris

    2014-01-01

    Summary Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem cell-related genetic regulator. PMID:24485662

  2. Differential changes in platelet reactivity induced by acute physical compared to persistent mental stress.

    PubMed

    Hüfner, Katharina; Koudouovoh-Tripp, Pia; Kandler, Christina; Hochstrasser, Tanja; Malik, Peter; Giesinger, Johannes; Semenitz, Barbara; Humpel, Christian; Sperner-Unterweger, Barbara

    2015-11-01

    Platelets are important in hemostasis, but also contain adhesion molecules, pro-inflammatory and immune-modulatory compounds, as well as most of the serotonin outside the central nervous system. Dysbalance in the serotonin pathways is involved in the pathogenesis of depressive symptoms. Thus, changes in platelet aggregation and content of bioactive compounds are of interest when investigating physiological stress-related mental processes as well as stress-related psychiatric diseases such as depression. In the present study, a characterization of platelet reactivity in acute physical and persistent mental stress was performed (aggregation, serotonin and serotonin 2A-receptor, P-selectin, CD40 ligand, matrix metalloproteinase-2 and -9 (MMP-2 and -9), platelet/endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), β-thromboglobulin (β-TG) and platelet factor 4 (PF-4). Acute physical stress increased platelet aggregability while leaving platelet content of bioactive compounds unchanged. Persistent mental stress led to changes in platelet content of bioactive compounds and serotonin 2A-receptor only. The values of most bioactive compounds correlated with each other. Acute physical and persistent mental stress influences platelets through distinct pathways, leading to differential changes in aggregability and content of bioactive compounds. PMID:26192713

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

    PubMed

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

    2015-07-01

    B-lymphocyte development in the bone marrow is controlled by the coordinated action of transcription factors creating regulatory networks ensuring activation of the B-lymphoid program and silencing of alternative cell fates. This process is tightly connected to malignant transformation because B-lineage acute lymphoblastic leukemia cells display a pronounced block in differentiation resulting in the expansion of immature progenitor cells. Over the last few years, high-resolution analysis of genetic changes in leukemia has revealed that several key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and PAX5, are genetically altered in a large portion of the human B-lineage acute leukemias. This opens the possibility of directly linking the disrupted development as well as aberrant gene expression patterns in leukemic cells to molecular functions of defined transcription factors in normal cell differentiation. This review article focuses on the roles of transcription factors in early B-cell development and their involvement in the formation of human leukemia.

  4. Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias?

    PubMed

    Minucci, S; Nervi, C; Lo Coco, F; Pelicci, P G

    2001-05-28

    Recent discoveries have identified key molecular events in the pathogenesis of acute promyelocytic leukemia (APL), caused by chromosomal rearrangements of the transcription factor RAR (resulting in a fusion protein with the product of other cellular genes, such as PML). Oligomerization of RAR, through a self-association domain present in PML, imposes an altered interaction with transcriptional co-regulators (NCoR/SMRT). NCoR/SMRT are responsible for recruitment of histone deacetylases (HDACs), which is required for transcriptional repression of PML-RAR target genes, and for the transforming potential of the fusion protein. Oligomerization and altered recruitment of HDACs are also responsible for transformation by the fusion protein AML1-ETO, extending these mechanisms to other forms of acute myeloid leukemias (AMLs) and suggesting that HDAC is a common target for myeloid leukemias. Strikingly, AML1-ETO expression blocks retinoic acid (RA) signaling in hematopoietic cells, suggesting that interference with the RA pathway (genetically altered in APL) by HDAC recruitment may be a common theme in AMLs. Treatment of APLs with RA, and of other AMLs with RA plus HDAC inhibitors (HDACi), results in myeloid differentiation. Thus, activation of the RA signaling pathway and inhibition of HDAC activity might represent a general strategy for the differentiation treatment of myeloid leukemias.

  5. Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  6. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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 Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  7. Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.

    PubMed

    Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R; Zombeck, Jonathan A; Nosek, Michael R; Sweedler, Jonathan V; Rhodes, Justin S

    2015-12-01

    Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.

  8. Proteins Involved in Platelet Signaling Are Differentially Regulated in Acute Coronary Syndrome: A Proteomic Study

    PubMed Central

    Fernández Parguiña, Andrés; Grigorian-Shamajian, Lilian; Agra, Rosa M.; Teijeira-Fernández, Elvis; Rosa, Isaac; Alonso, Jana; Viñuela-Roldán, Juan E.; Seoane, Ana; González-Juanatey, José Ramón; García, Ángel

    2010-01-01

    Background Platelets play a fundamental role in pathological events underlying acute coronary syndrome (ACS). Because platelets do not have a nucleus, proteomics constitutes an optimal approach to follow platelet molecular events associated with the onset of the acute episode. Methodology/Principal Findings We performed the first high-resolution two-dimensional gel electrophoresis-based proteome analysis of circulating platelets from patients with non-ST segment elevation ACS (NSTE-ACS). Proteins were identified by mass spectrometry and validations were by western blotting. Forty protein features (corresponding to 22 unique genes) were found to be differentially regulated between NSTE-ACS patients and matched controls with chronic ischemic cardiopathy. The number of differences decreased at day 5 (28) and 6 months after the acute event (5). Interestingly, a systems biology approach demonstrated that 16 of the 22 differentially regulated proteins identified are interconnected as part of a common network related to cell assembly and organization and cell morphology, processes very related to platelet activation. Indeed, 14 of those proteins are either signaling or cytoskeletal, and nine of them are known to participate in platelet activation by αIIbβ3 and/or GPVI receptors. Several of the proteins identified participate in platelet activation through post-translational modifications, as shown here for ILK, Src and Talin. Interestingly, the platelet-secreted glycoprotein SPARC was down-regulated in NSTE-ACS patients compared to stable controls, which is consistent with a secretion process from activated platelets. Conclusions/Significance The present study provides novel information on platelet proteome changes associated with platelet activation in NSTE-ACS, highlighting the presence of proteins involved in platelet signaling. This investigation paves the way for future studies in the search for novel platelet-related biomarkers and drug targets in ACS. PMID

  9. Acute Thermal Stressor Increases Glucocorticoid Response but Minimizes Testosterone and Locomotor Performance in the Cane Toad (Rhinella marina)

    PubMed Central

    Narayan, Edward J.; Hero, Jean-Marc

    2014-01-01

    Climatic warming is a global problem and acute thermal stressor in particular could be considered as a major stressor for wildlife. Cane toads (Rhinella marina) have expanded their range into warmer regions of Australia and they provide a suitable model species to study the sub-lethal impacts of thermal stressor on the endocrine physiology of amphibians. Presently, there is no information to show that exposure to an acute thermal stressor could initiate a physiological stress (glucocorticoid) response and secondly, the possible effects on reproductive hormones and performance. Answering these questions is important for understanding the impacts of extreme temperature on amphibians. In this study, we experimented on cane toads from Queensland, Australia by acclimating them to mildly warm temperature (25°C) and then exposing to acute temperature treatments of 30°, 35° or 40°C (hypothetical acute thermal stressors). We measured acute changes in the stress hormone corticosterone and the reproductive hormone testosterone using standard capture and handling protocol and quantified the metabolites of both hormones non-invasively using urinary enzyme-immunoassays. Furthermore, we measured performance trait (i.e. righting response score) in the control acclimated and the three treatment groups. Corticosterone stress responses increased in all toads during exposure to an acute thermal stressor. Furthermore, exposure to a thermal stressor also decreased testosterone levels in all toads. The duration of the righting response (seconds) was longer for toads that were exposed to 40°C than to 30°, 35° or 25°C. The increased corticosterone stress response with increased intensity of the acute thermal stressor suggests that the toads perceived this treatment as a stressor. Furthermore, the results also highlight a potential trade-off with performance and reproductive hormones. Ultimately, exposure acute thermal stressors due to climatic variability could impact amphibians at

  10. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  11. p53 independent epigenetic-differentiation treatment in xenotransplant models of acute myeloid leukemia

    PubMed Central

    Ng, Kwok Peng; Ebrahem, Quteba; Negrotto, Soledad; Mahfouz, Reda Z.; Link, Kevin A.; Hu, Zhenbo; Gu, Xiaorong; Advani, Anjali; Kalaycio, Matt; Sobecks, Ronald; Sekeres, Mikkael; Copelan, Edward; Radivoyevitch, Tomas; Maciejewski, Jaroslaw; Mulloy, James C.; Saunthararajah, Yogen

    2013-01-01

    Suppression of apoptosis by TP53 mutation contributes to resistance of acute myeloid leukemia (AML) to conventional cytotoxic treatment. Using differentiation to induce irreversible cell cycle exit in AML cells could be a p53-independent treatment alternative, however, this possibility requires evaluation. In vitro and in vivo regimens of the deoxycytidine analogue decitabine that deplete the chromatin modifying enzyme DNA methyl-transferase 1 (DNMT1) without phosphorylating p53 or inducing early apoptosis were determined. These decitabine regimens but not equimolar DNA-damaging cytarabine up regulated the key late differentiation factors CEBPε and p27/CDKN1B, induced cellular differentiation, and terminated AML cell-cycle, even in cytarabine-resistant p53- and p16/CDKN2A-null AML cells. Leukemia initiation by xeno-transplanted AML cells was abrogated but normal hematopoietic stem cell (HSC) engraftment was preserved. In vivo, the low toxicity allowed frequent drug administration to increase exposure, an important consideration for S-phase specific decitabine therapy. In xeno-transplant models of p53-null and relapsed/refractory AML, the non-cytotoxic regimen significantly extended survival compared to conventional cytotoxic cytarabine. Modifying in vivo dose and schedule to emphasize this pathway of decitabine action can bypass a mechanism of resistance to standard therapy. PMID:21701495

  12. [Role of biomarkers in the differential diagnosis of acute respiratory failure in the immediate postoperative period of lung transplantation].

    PubMed

    Ruano, L; Sacanell, J; Roman, A; Rello, J

    2013-01-01

    Lung transplant recipients are at high risk of suffering many complications during the immediate postoperative period, such as primary graft dysfunction, acute graft rejection or infection. The most common symptom is the presence of acute respiratory failure, and the use of biomarkers could be useful for establishing an early diagnosis of these conditions. Different biomarkers have been studied, but none have proven to be the gold standard in the differential diagnosis of acute respiratory failure. This paper offers a review of the different biomarkers that have been studied in this field.

  13. [Role of biomarkers in the differential diagnosis of acute respiratory failure in the immediate postoperative period of lung transplantation].

    PubMed

    Ruano, L; Sacanell, J; Roman, A; Rello, J

    2013-01-01

    Lung transplant recipients are at high risk of suffering many complications during the immediate postoperative period, such as primary graft dysfunction, acute graft rejection or infection. The most common symptom is the presence of acute respiratory failure, and the use of biomarkers could be useful for establishing an early diagnosis of these conditions. Different biomarkers have been studied, but none have proven to be the gold standard in the differential diagnosis of acute respiratory failure. This paper offers a review of the different biomarkers that have been studied in this field. PMID:23462428

  14. Performance of CMR Methods for Differentiating Acute From Chronic Myocardial Infarction

    PubMed Central

    Smulders, Martijn W.; Bekkers, Sebastiaan C.A.M.; Kim, Han W.; Van Assche, Lowie M.R.; Parker, Michele A.; Kim, Raymond J.

    2015-01-01

    Objectives To assess the performance of cardiovascular magnetic resonance (CMR) methods for discriminating acute from chronic myocardial infarction (MI). Background Although T2-weighted-CMR is thought to be accurate in differentiating acute from chronic MI, few studies have reported on diagnostic accuracy, and these generally compared extremes in infarct age (e.g. <1-week-old versus >6-months-old) and did not evaluate other CMR methods that could be informative. Methods 221 CMR studies were performed at various time-points after STEMI in 117 consecutive patients without prior history of MI or revascularization enrolled prospectively at 2 centers. Imaging markers of acute MI (<1-month) were T2-hyperintensity on double inversion-recovery turbo-spin-echo (DIR-TSE) images, microvascular obstruction (MO) on delayed-enhancement-CMR, and focally increased end-diastolic wall thickness (EDWT) on cine-CMR. Results The prevalence of T2-DIR-TSE hyperintensity decreased with infarct age but remained substantial up to 6-months post-MI. In contrast, the prevalence of both MO and increased-EDWT dropped sharply after 1-month. T2-DIR-TSE sensitivity, specificity, and accuracy for identifying acute MI were 88%, 66%, and 77% compared with 73%, 97%, and 85% for the combination of MO-or-increased-EDWT. On multivariable analysis, persistence of T2-hyperintensity in intermediate-aged infarcts (1–6 months-old) was predicted by larger infarct size, diabetes, and better T2-DIR-TSE image quality score. For infarct size ≥10% LV, a simple algorithm incorporating all CMR components allowed classification of infarct age into 3 categories (<1-month-old, 1–6 months-old, and ≥6-months-old) with 80% [95% CI: 73–87%] accuracy. Conclusions T2-DIR-TSE hyperintensity is specific for infarcts less than 6-months-old, whereas microvascular obstruction and increased end-diastolic wall-thickness are specific for infarcts less than 1-month-old. Incorporating multiple CMR markers of acute MI and their

  15. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-02-17

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  18. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2014-10-30

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  19. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    PubMed Central

    Vilchis-Ordoñez, Armando; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Reyes-López, Alfonso; Quintela-Nuñez del Prado, Henry Martin; Venegas-Vázquez, Jorge; Mayani, Hector; Ortiz-Navarrete, Vianney; López-Martínez, Briceida; Pelayo, Rosana

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow. PMID:26090405

  20. Differential Effects of Acute Alcohol on EEG and Sedative Responses in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Walker, Brendan M.; Ehlers, Cindy L.

    2008-01-01

    Age-related developmental differences in sensitivity to the acute effects of alcohol may play an important role in the development of alcoholism. The present study was designed to evaluate the acute effects of alcohol on cortical electroencephalogram (EEG) in adolescent (P36) and adult (P78) Wistar rats. Five minutes of EEG was recorded after administration of 0, 0.75 or 1.5 g/kg alcohol. The righting reflex was performed to measure the sedative effects of alcohol (3.5 g/kg) and total sleeping time for each rat. Our results showed that alcohol (1.5 g/kg) increased power in the 1–2 Hz band and decreased the power in the 32–50 Hz band in the parietal cortical region of adolescent rats. Alcohol (1.5 g/kg) also increased stability of the EEG power in the slow-wave frequency bands (2–4 Hz, 4–6 Hz, and 6–8 Hz) of adolescent rats. In the frontal cortex of adult rats, but not in adolescent rats, alcohol (1.5 or 0.75 g/kg) decreased the power in the 16–32 Hz frequency band. Alcohol (1.5 g/kg) differentially increased power in a multiple of slow-wave frequency bands (2–4 Hz and 4–6 Hz) in the parietal cortex of adult rats as compared to adolescent rats. Adolescent rats were shown significantly shorter sleeping time and higher blood alcohol levels after regaining reflex than adult rats. Our results provide additional evidence of age-related differences in the effects of acute alcohol on cortical EEG, sedation and tolerance. PMID:18191821

  1. The role of gasless laparoscopy in differential diagnosis of acute abdomen

    PubMed Central

    Moga, MA; Arvatescu, CA; Pratilas, GC; Bigiu, NF; Dinas, K; Burtea, V

    2015-01-01

    Background: The diagnosis of acute abdomen in the emergency setting, still remains a challenging problem. In these cases timely diagnosis and management is of great importance, while the anesthetic risk is high. The combination of the risk of an open laparotomy and the relative high likelihood of negative findings when performed, creates the need for a better approach. The alternative actually exists since 1911 when Eruheim made the first gasless laparoscopy. The aim of this study is to put back into the spotlight, gasless laparoscopy in the differential diagnosis of acute abdomen and to underline the advantages of this simple, cheap and very useful technique, especially in patients that require prompt diagnosis and have relative or absolute contraindications to general anesthesia or pneumoperitoneum. Methods: This study included 49 patients that were managed with gasless laparoscopy for the diagnosis of acute abdomen, from 2011 to 2013. Two techniques were used: the mechanical lift of the anterior abdominal wall and the LapVision device. Results: From the 49 patients included in the study, 41 were diagnosed with gasless laparoscopy while in eight the results were uncertain or there wasn’t any pathology involved. With both techniques used, sample of the intraperitoneal fluid or biopsy could be obtained. Conclusion: The gasless technique for laparoscopy is an extremely useful mean of diagnosis in emergency conditions, or for patients with contraindications to undergo laparoscopy by pneumoperitoneum. Requiring only local or regional anesthesia, this technique could easily find application in diagnosis and treatment, while avoiding unnecessary laparotomies. Hippokratia 2015, 19 (1): 69-72. PMID:26435651

  2. End of induction minimal residual disease alone is not a useful determinant for risk stratified therapy in pediatric T-cell acute lymphoblastic leukemia.

    PubMed

    Parekh, Chintan; Gaynon, Paul S; Abdel-Azim, Hisham

    2015-11-01

    The role of end of induction minimal residual disease (MRD) as determined by flow cytometry for treatment assignment in pediatric T-cell acute lymphoblastic leukemia (T-ALL) is not well defined. We studied 33 children with newly diagnosed T-ALL. Thirty-two of 33 patients remain in continuous complete remission at a median of 4 years. Nineteen patients were MRD positive at the end of induction and all remain in remission with augmented Berlin Frankfurt Münster-based therapy. One patient underwent hematopoietic stem cell transplant for rising MRD. Persistent end of induction MRD alone is not an indication to alter therapy in pediatric T-ALL.

  3. A patient with minimal change disease and acute focal tubulointerstitial nephritis due to traditional medicine: a case report and small literature review.

    PubMed

    Lee, Keun-Hyeun; Jeong, Han-Sol; Rhee, Harin

    2014-01-01

    Gongjin-dan (GJD) is a traditional formula that is widely used in Korea and China, and it has been used from 1345 AD in China to improve the circulation between the kidneys and the heart and to prevent all diseases. However, its adverse effects have not yet been reported. We present a patient with minimal change disease and focal tubulointerstitial nephritis associated with GJD. A 72-year-old man visited the clinic for generalized edema 20 days after starting GJD. His serum albumin level was low and nephrotic-range proteinuria was detected. A kidney biopsy showed minimal change disease and acute tubulointerstitial nephritis. After stopping GJD, a spontaneous complete remission was achieved. We discuss the possible pathogenesis of GJD-induced minimal change disease and review the adverse effects of GJD's ingredients and traditional Chinese medicines that can induce proteinuria. We report a new adverse effect of GJD, which might induce increased IL-13 production and an allergic response, leading to minimal change disease and focal tubulointerstitial nephritis.

  4. [Differential diagnostics of acute inflammatory diseases and tumors of the neck].

    PubMed

    Vuĭtsik, N B; Butkevich, A Ts; Kuntsevich, G I; Zemlianoĭ, A B

    2008-01-01

    The purpose of the investigation was to assess the clinical significance of ultrasonography for differential diagnostics between acute inflammatory and tumorous lesions of the neck. One hundred and eighty-six patients with soft-tissue lesions of the neck aged 18 to 74 (mean age 31.45 +/- 8.39 years), 95 (51%) males and 91 (49%) females were examined. Basing on clinical and ultrasonographic examination, the patients were divided into two groups: 149 or 80% patients with acute inflammatory lesions (Group 1), and 37 or 20% patients with tumorous lesions (Group 2). Thirty-four of the 149 Group 1 patients (22.82%) had lymphadenitis, 30 (20.13%) had soft tissue infiltrates, 13 (8.72%) had abscesses, 19 (12.72%) had phlegmons, 32 (21.48%) had acute inflammatory changes in the major salivary glands, 3 (2.01%) had teratomas with signs of inflammation, and 17 (11.41%) patients had inflammatory changes in the tumors. Of 37 patients with tumorous lesions, 16 (43.2%) had salivary gland tumors, 12 (32.4%) had metastases in the lymphatic nodes, and 9 (24.3%) had neurofibromatosis. Soft tissue ultrasonography was performed using Sonos-5500 and Image-Point ultrasound scanners with 7.5 MHz sensors (Hewlett-Packard, USA), Logio-pro, Uoluson-730 Expert (General Electric, USA), and Premium Edition (ACUSON Antares, Siemens, Germany) with 5 to 13 MHz wide-frequency sensors. Visualization was performed in B-modes using tissue harmonics, color duplex scanning, Sie Scape panoramic visualization, contrast visualization and Sight 4D and 3D-Scape modes. The results of ultrasonography were analyzed taking into account additional methods such as computed and magnetic resonance tomography, intraoperative findings, the results of puncture biopsy, histological, morphological, and bacteriological studies. The study demonstrates that ultrasonography is the method of choice, which is in some cases enough to establish a diagnosis of an acute inflammatory disease or a tumorous formation of various

  5. Differential Effects of Differing Intensities of Acute Exercise on Speed and Accuracy of Cognition: A Meta-Analytical Investigation

    ERIC Educational Resources Information Center

    McMorris, Terry; Hale, Beverley J.

    2012-01-01

    The primary purpose of this study was to examine, using meta-analytical techniques, the differential effects of differing intensities of acute exercise on speed and accuracy of cognition. Overall, exercise demonstrated a small, significant mean effect size (g = 0.14, p less than 0.01) on cognition. Examination of the comparison between speed and…

  6. CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia

    PubMed Central

    Bertoli, Sarah; Boutzen, Helena; David, Laure; Larrue, Clément; Vergez, François; Fernandez-Vidal, Anne; Yuan, Lingli; Hospital, Marie-Anne; Tamburini, Jérôme; Demur, Cécile; Delabesse, Eric; Saland, Estelle; Sarry, Jean-Emmanuel; Galcera, Marie-Odile; Mas, Véronique Mansat-De; Didier, Christine; Dozier, Christine; Récher, Christian; Manenti, Stéphane

    2015-01-01

    We investigated cell cycle regulation in acute myeloid leukemia cells expressing the FLT3-ITD mutated tyrosine kinase receptor, an underexplored field in this disease. Upon FLT3 inhibition, CDC25A mRNA and protein were rapidly down-regulated, while levels of other cell cycle proteins remained unchanged. This regulation was dependent on STAT5, arguing for FLT3-ITD-dependent transcriptional regulation of CDC25A. CDC25 inhibitors triggered proliferation arrest and cell death of FLT3-ITD as well as FLT3-ITD/TKD AC-220 resistant cells, but not of FLT3-wt cells. Consistently, RNA interference-mediated knock-down of CDC25A reduced the proliferation of FLT3-ITD cell lines. Finally, the clonogenic capacity of primary FLT3-ITD AML cells was reduced by the CDC25 inhibitor IRC-083864, while FLT3-wt AML and normal CD34+ myeloid cells were unaffected. In good agreement, in a cohort of 100 samples from AML patients with intermediate-risk cytogenetics, high levels of CDC25A mRNA were predictive of higher clonogenic potential in FLT3-ITD+ samples, not in FLT3-wt ones. Importantly, pharmacological inhibition as well as RNA interference-mediated knock-down of CDC25A also induced monocytic differentiation of FLT3-ITD positive cells, as judged by cell surface markers expression, morphological modifications, and C/EBPα phosphorylation. CDC25 inhibition also re-induced monocytic differentiation in primary AML blasts carrying the FLT3-ITD mutation, but not in blasts expressing wild type FLT3. Altogether, these data identify CDC25A as an early cell cycle transducer of FLT3-ITD oncogenic signaling, and as a promising target to inhibit proliferation and re-induce differentiation of FLT3-ITD AML cells. PMID:26515730

  7. Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready?

    PubMed

    Boyiadzis, Michael; Whiteside, Theresa L

    2016-06-01

    The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients' plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML. The rationale for developing exosome-based methodology for minimal residual disease detection is based on promising early observations. However, standards need to be established for evaluating exosome identity, isolation from body fluids, and assessment methods. The rapidly expanding knowledge of the exosome biology suggests that the exosome status as potential biomarkers may become clarified in the near future.

  8. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    PubMed Central

    Chen, Yu-Jen; Fang, Li-Wen; Su, Wen-Chi; Hsu, Wen-Yi; Yang, Kai-Chien; Huang, Huey-Lan

    2016-01-01

    Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA) partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of macrophagic differentiation in AML U937 cells by lapatinib. We also noted the synergistic effects of the use of lapatinib and cytotoxic drugs in U937 leukemia cells. These results indicate that lapatinib may have potential for development as a novel antileukemia agent. PMID:27499639

  9. 9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia.

    PubMed

    Chowdhury, Suchandra; Chandra, Sarmila; Mandal, Chitra

    2014-10-01

    Childhood acute lymphoblastic leukaemia (ALL) originates from mutations in haematopoietic progenitor cells (HPCs). For high-risk patients, treated with intensified post-remission chemotherapy, haematopoietic stem cell (HSC) transplantation is considered. Autologous HSC transplantation needs improvisation till date. Previous studies established enhanced disease-associated expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on lymphoblasts of these patients at diagnosis, followed by its decrease with clinical remission and reappearance with relapse. Based on this differential expression of Neu5,9Ac2-GPs, identification of a normal HPC population was targeted from patients at diagnosis. This study identifies two distinct haematopoietic progenitor populations from bone marrow of diagnostic ALL patients, exploring the differential expression of Neu5,9Ac2-GPs with stem cell (CD34, CD90, CD117, CD133), haematopoietic (CD45), lineage-commitment (CD38) antigens and cytosolic aldehyde dehydrogenase (ALDH). Normal haematopoietic progenitor cells (ALDH(+)SSC(lo)CD45(hi)Neu5,9Ac2 -GPs(lo)CD34(+)CD38(-)CD90(+)CD117(+)CD133(+)) differentiated into morphologically different, lineage-specific colonies, being crucial for autologous HSC transplantation while leukemic stem cells (ALDH(+)SSC(lo)CD45(lo)Neu5,9Ac2 -GPs(hi)CD34(+)CD38(+)CD90(-)CD117(-)CD133(-)) lacking this ability can be potential targets for minimal residual disease detection and drug-targeted immunotherapy.

  10. Creating a Nurse-Led Culture to Minimize Horizontal Violence in the Acute Care Setting: A Multi-Interventional Approach.

    PubMed

    Parker, Karen M; Harrington, Ann; Smith, Charlene M; Sellers, Kathleen F; Millenbach, Linda

    2016-01-01

    Horizontal violence (HV) is prevalent in nursing. However, few strategies are identified to address this phenomenon that undermines communication and patient safety. Nurses at an acute care hospital implemented multiple interventions to address HV resulting in increased knowledge of hospital policies regarding HV, and significantly (p < .05) less HV prevalence than was reported by nurses in other organizations throughout New York State. With the aid and oversight of nursing professional development specialists, evidence-based interventions to address HV were developed including policies, behavioral performance reviews, and staff/manager educational programs. PMID:26985749

  11. Cell Adhesion Minimization by a Novel Mesh Culture Method Mechanically Directs Trophoblast Differentiation and Self-Assembly Organization of Human Pluripotent Stem Cells

    PubMed Central

    Kurosawa, Osamu; Yamazaki, Satoshi; Oana, Hidehiro; Kotera, Hidetoshi; Nakauchi, Hiromitsu; Washizu, Masao

    2015-01-01

    Mechanical methods for inducing differentiation and directing lineage specification will be instrumental in the application of pluripotent stem cells. Here, we demonstrate that minimization of cell-substrate adhesion can initiate and direct the differentiation of human pluripotent stem cells (hiPSCs) into cyst-forming trophoblast lineage cells (TLCs) without stimulation with cytokines or small molecules. To precisely control cell-substrate adhesion area, we developed a novel culture method where cells are cultured on microstructured mesh sheets suspended in a culture medium such that cells on mesh are completely out of contact with the culture dish. We used microfabricated mesh sheets that consisted of open meshes (100∼200 μm in pitch) with narrow mesh strands (3–5 μm in width) to provide support for initial cell attachment and growth. We demonstrate that minimization of cell adhesion area achieved by this culture method can trigger a sequence of morphogenetic transformations that begin with individual hiPSCs attached on the mesh strands proliferating to form cell sheets by self-assembly organization and ultimately differentiating after 10–15 days of mesh culture to generate spherical cysts that secreted human chorionic gonadotropin (hCG) hormone and expressed caudal-related homeobox 2 factor (CDX2), a specific marker of trophoblast lineage. Thus, this study demonstrates a simple and direct mechanical approach to induce trophoblast differentiation and generate cysts for application in the study of early human embryogenesis and drug development and screening. PMID:25914965

  12. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  13. Proteomic Profiles in Acute Respiratory Distress Syndrome Differentiates Survivors from Non-Survivors

    PubMed Central

    Bhargava, Maneesh; Becker, Trisha L.; Viken, Kevin J.; Jagtap, Pratik D.; Dey, Sanjoy; Steinbach, Michael S.; Wu, Baolin; Kumar, Vipin; Bitterman, Peter B.; Ingbar, David H.; Wendt, Christine H.

    2014-01-01

    Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS. PMID:25290099

  14. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  15. Impact of d-Dimers on the Differential Diagnosis of Acute Chest Pain: Current Aspects Besides the Widely Known.

    PubMed

    Hahne, Kathrin; Lebiedz, Pia; Breuckmann, Frank

    2014-01-01

    d-dimers are cleavage products of fibrin that occur during plasmin-mediated fibrinolysis of blood clots. In the emergency department, d-dimer measurement represents a valuable and cost-effective tool in the differential diagnosis of acute chest pain including the main life-threatening entities: acute coronary syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic and prognostic values of d-dimer testing in acute coronary syndrome is of less priority, increases of d-dimers are frequently found in venous thromboembolism and acute aortic syndromes, especially acute aortic dissection. As to the high negative predictive value of d-dimer in those disorders, patients with low to intermediate pretest probability may profit in terms of less necessity of further non-invasive or even invasive imaging, simultaneously reducing potential complications and healthcare-related costs. However, because of the low specificity of the different d-dimer tests in contrast to its frequent usage, adequate interpretation is required. Age-related adjustment of d-dimer levels may be used to increase its diagnostic power. PMID:25392700

  16. Differential microRNA expression in childhood B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Ju, Xiuli; Li, Dong; Shi, Qing; Hou, Huaishui; Sun, Nianzheng; Shen, Baijun

    2009-01-01

    MiRNAs play important roles in the development of both hematopoiesis and leukemogenesis. The analysis of differential microRNA expression profiles may be a powerful tool to allow us insight on the mechanisms of childhood B-cell precursor acute lymphoblastic leukemia (pre-B-ALL). The present study provides an informative profile of the expression of miRNAs in pre-B-ALL using two independent and quantitative methods: miRNA chip and qRT-PCR of mature miRNA from 40 newly diagnosed pre-B-ALL children. Additionally, putative hematopoiesis-specific target genes were analyzed with informatics technique. Both approaches showed that miR-222, miR-339, and miR-142-3p were dramatically overexpressed in pre-B-ALL patients, and downregulation of hsa-miR-451 and hsa-miR-373* was confirmed. The results of this study offer a comprehensive and quantitative profile of miRNA expression in pre-B-ALL and their healthy counterpart, suggesting that miRNAs could play a primary role in the disease itself.

  17. Untargeted LC-MS Metabolomics of Bronchoalveolar Lavage Fluid Differentiates Acute Respiratory Distress Syndrome from Health

    PubMed Central

    Evans, Charles R.; Karnovsky, Alla; Kovach, Melissa A.; Standiford, Theodore J.; Burant, Charles F.; Stringer, Kathleen A.

    2014-01-01

    Acute respiratory distress syndrome (ARDS) remains a significant hazard to human health and is clinically challenging because there are no prognostic biomarkers and no effective pharmacotherapy. The lung compartment metabolome may detail the status of the local environment that could be useful in ARDS biomarker discovery and the identification of drug target opportunities. However, neither the utility of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the optimal analytical platform for metabolite identification are established. To address this, we undertook a study to compare metabolites in BALF samples from patients with ARDS and healthy controls using a newly developed liquid chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics. Following initial testing of three different high performance liquid chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and hydrophilic interaction chromatography (HILIC), were the most informative chromatographic methods because they yielded the most and highest quality data. Following confirmation of metabolite identification, statistical analysis resulted in 37 differentiating metabolites in the BALF of ARDS compared with health across both analytical platforms. Pathway analysis revealed networks associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid biosynthesis, phospholipids and purine metabolism in the ARDS BALF. The complementary analytical platforms of RPLC and HILIC-LC generated informative, insightful metabolomics data of the ARDS lung environment. PMID:24289193

  18. Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

    PubMed

    Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

    2016-08-01

    A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

  19. Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

    PubMed

    Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

    2016-08-01

    A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis. PMID:27599414

  20. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  1. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-09

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  6. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  8. Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection

    PubMed Central

    Song, Jung-Soo

    2016-01-01

    Purpose Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. Materials and Methods Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. Results Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798–0.917, p<0.001], 0.808 (95% CI, 0.738–0.878, p<0.001), and 0.638 (95% CI, 0.544–0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). Conclusion Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections. PMID:27401644

  9. The impact of pre-transplant minimal residual disease on outcome of intensified myeloablative cord blood transplant for acute myeloid leukemia in first or second complete remission.

    PubMed

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Zhang, Lei; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2016-01-01

    The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%; p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group, p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group, p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning. PMID:26690538

  10. Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR.

    PubMed

    Cassinat, B; Zassadowski, F; Balitrand, N; Barbey, C; Rain, J D; Fenaux, P; Degos, L; Vidaud, M; Chomienne, C

    2000-02-01

    We took advantage of a recently developed system allowing performance of real-time quantitation of polymerase chain reaction to develop a quantitative method of measurement of PML-RARalpha transcripts which are hallmarks of acute promyelocytic leukemia (APL) with t(15;17) translocation. Indeed, although quantitation of minimal residual disease has proved to be useful in predicting clinical outcome in other leukemias such as chronic myeloid leukemia or acute lymphoblastic leukemia, no quantitative data have been provided in the case of APL. We present here a method for quantitation of the most frequent subtypes of t(15;17) transcripts (namely bcr1 and bcr3). One specific forward primer is used for each subtype in order to keep amplicon length under 200 bp. The expression of PML-RARalpha transcripts is normalized using the housekeeping porphobilinogen deaminase (PBGD) gene. This technique allows detection of 10 copies of PML-RARalpha or PBGD plasmids, and quantitation was efficient up to 100 copies. One t(15;17)-positive NB4 cell could be detected among 106 HL60 cells, although quantitation was efficient up to one cell among 105. Repeatability and reproducibility of the method were satisfying as intra- and inter-assay variation coefficients were not higher than 15%. The efficiency of the method was finally tested in patient samples, showing a decrease of the PML-RARalpha copy number during therapy, and an increase at the time of relapse.

  11. The impact of pre-transplant minimal residual disease on outcome of intensified myeloablative cord blood transplant for acute myeloid leukemia in first or second complete remission.

    PubMed

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Zhang, Lei; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2016-01-01

    The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%; p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group, p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group, p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning.

  12. Quantification of TEL-AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia.

    PubMed

    Drunat, S; Olivi, M; Brunie, G; Grandchamp, B; Vilmer, E; Bièche, I; Cavé, H

    2001-08-01

    Strategies currently used for residual disease detection in acute lymphoblastic leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of immunoglobulin and T-cell receptor rearrangements. The TEL-AML1 fusion transcript, which is associated with t(12;21) (p13;q22), is found in 25% of childhood B-cell precursor ALL, and represents an interesting alternative target. We compared two methods for quantitating TEL-AML1 fusion transcripts: competitive PCR and real-time PCR. These techniques showed similar sensitivity (5 x 10(-5)) and reproducibility. Giving highly correlated results, both techniques can be conveniently used for TEL-AML1 transcript quantification. The constancy of TEL-AML1 expression was evaluated by measuring TEL-AML1 transcripts at different steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation in TEL-AML1 expression was observed during the cell cycle or in 20/21 of the ALL patients. Residual disease was then determined after completion of induction therapy in 20 patients with a TEL-AML1-positive ALL. Seven patients out of 20 (35%) were still positive, including two patients with high level of residual blasts (close to or beyond 10(-2)). When comparison was possible, results obtained using TEL-AML1 quantification were in accordance with those obtained using T-cell receptor rearrangements analysis.

  13. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment.

  14. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment. PMID:26238033

  15. [Differential diagnosis of reduced uptake images revealed by bone scan: about a case of acute lymphoblastic leukemia].

    PubMed

    Bahadi, Nisrine; Biyi, Abdelhamid; Oueriagli, Salah Nabih; Doudouh, Abderrahim

    2016-01-01

    If increased uptake during bone scan usually bring to light many bone pathologies, reduced uptakes are a rare occurrence and they require careful analysis to avoid erroneous interpretations. We report the case of a 17-year old admitted with diffuse bone pain, hypercalcemia and thrombopenia. Bone scan showed areas of low uptakes. Bone marrow tests allowed the diagnosis of acute lymphoblastic leukemia. This case report aims to discuss the main differential diagnoses based on such bone scan abnormalities. PMID:27642484

  16. The differentiation syndrome in patients with acute promyelocytic leukemia: experience of the pethema group and review of the literature.

    PubMed

    Montesinos, Pau; Sanz, Miguel A

    2011-01-01

    Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO]) in patients with acute promyelocytic leukemia (APL). The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Español de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005), in which more than one thousand patients were treated with ATRA plus idarubicin for induction.

  17. Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions

    PubMed Central

    Connolly, Niamh M. C.; D’Orsi, Beatrice; Monsefi, Naser; Huber, Heinrich J.; Prehn, Jochen H. M.

    2016-01-01

    Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK), re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult. PMID:26840769

  18. Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia.

    PubMed

    Bibault, Jean-Emmanuel; Figeac, Martin; Hélevaut, Nathalie; Rodriguez, Céline; Quief, Sabine; Sebda, Shéhérazade; Renneville, Aline; Nibourel, Olivier; Rousselot, Philippe; Gruson, Bérengère; Dombret, Hervé; Castaigne, Sylvie; Preudhomme, Claude

    2015-09-01

    Minimal Residual Disease (MRD) detection can be used for early intervention in relapse, risk stratification, and treatment guidance. FLT3 ITD is the most common mutation found in AML patients with normal karyotype. We evaluated the feasibility of NGS with high coverage (up to 2.4.10(6) PE fragments) for MRD monitoring on FLT3 ITD. We sequenced 37 adult patients at diagnosis and various times of their disease (64 samples) and compared the results with FLT3 ITD ratios measured by fragment analysis. We found that NGS could detect variable insertion sites and lengths in a single test for several patients. We also showed mutational shifts between diagnosis and relapse, with the outgrowth of a clone at relapse different from that dominant at diagnosis. Since NGS is scalable, we were able to adapt sensitivity by increasing the number of reads obtained for follow-up samples, compared to diagnosis samples. This technique could be applied to detect biological relapse before its clinical consequences and to better tailor treatments through the use of FLT3 inhibitors. Larger cohorts should be assessed in order to validate this approach.

  19. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

  20. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

  1. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision

    PubMed Central

    Bansal, Aditya; Bhama, Jay K.; Patel, Rajan; Desai, Sapna; Mandras, Stacy A.; Patel, Hamang; Collins, Tyrone; Reilly, John P.; Ventura, Hector O.; Parrino, P. Eugene

    2016-01-01

    Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Conclusion

  2. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision

    PubMed Central

    Bansal, Aditya; Bhama, Jay K.; Patel, Rajan; Desai, Sapna; Mandras, Stacy A.; Patel, Hamang; Collins, Tyrone; Reilly, John P.; Ventura, Hector O.; Parrino, P. Eugene

    2016-01-01

    Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Conclusion

  3. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-01

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  4. Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice

    SciTech Connect

    Yin Huquan; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2007-09-15

    Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayed {>=} 2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1.

  5. [The acute visual hallucinosis in infancy. Clinical, neurophysiological and psychodevelopmental aspects and differential typology (author's transl)].

    PubMed

    Eggers, C

    1975-09-01

    By introducing the definition "hallucinosis" (Wernicke) it has become possible to confine the psychoses of organic origin more closely. Therefore, this term should also be used in pediatry and pedopsychiatry in order to designate cases with corresponding clinical aspects. Thus, accordance to the phenomenological characteristics of such syndromes as described in this paper, it is justified to emphasize that the acute hallucinosis in children is a special type of disease as compared to other psychoses caused by exogenic influences in this age group. The 10 case reports deal with visual hallucinoses which turned out to be characteristically different compared to those in adults. Hallucinating children at the age of 3 to 9 years predominantly visualized animals and legendary beings. Contrary to findings in adults, scenic and systematized visions were scarcely noticed, which psychodevelopmentally may be attributed to the fact that creative power in children is still little pronounced. Etiologically intoxications and infectious diseases were the cause for the visual hallucinations of the 10 children described. In the development of visual hallucinations somatic and psychic factors are significant. They have been discussed on the basis of today's knowledge. As today, however, there exists no satisfactory theory concerning the conditions favoring the development of hallucinations. To explain the somatogenesis of visual hallucinations three theories have been outlined, based on the present neurophysiological findings. It has been worked out that especially in children emotion plays an essential role in the origin of hallucinations. In infancy and early school age, while rational control of reality is still suppressed to a great extent, domination of emotional life goes along with lack of differentiation. At the same time the difference between imagination and perception is still little precise; therefore, phenomena, impressing as hallucinations in the adult, occur with

  6. [The acute visual hallucinosis in infancy. Clinical, neurophysiological and psychodevelopmental aspects and differential typology (author's transl)].

    PubMed

    Eggers, C

    1975-09-01

    By introducing the definition "hallucinosis" (Wernicke) it has become possible to confine the psychoses of organic origin more closely. Therefore, this term should also be used in pediatry and pedopsychiatry in order to designate cases with corresponding clinical aspects. Thus, accordance to the phenomenological characteristics of such syndromes as described in this paper, it is justified to emphasize that the acute hallucinosis in children is a special type of disease as compared to other psychoses caused by exogenic influences in this age group. The 10 case reports deal with visual hallucinoses which turned out to be characteristically different compared to those in adults. Hallucinating children at the age of 3 to 9 years predominantly visualized animals and legendary beings. Contrary to findings in adults, scenic and systematized visions were scarcely noticed, which psychodevelopmentally may be attributed to the fact that creative power in children is still little pronounced. Etiologically intoxications and infectious diseases were the cause for the visual hallucinations of the 10 children described. In the development of visual hallucinations somatic and psychic factors are significant. They have been discussed on the basis of today's knowledge. As today, however, there exists no satisfactory theory concerning the conditions favoring the development of hallucinations. To explain the somatogenesis of visual hallucinations three theories have been outlined, based on the present neurophysiological findings. It has been worked out that especially in children emotion plays an essential role in the origin of hallucinations. In infancy and early school age, while rational control of reality is still suppressed to a great extent, domination of emotional life goes along with lack of differentiation. At the same time the difference between imagination and perception is still little precise; therefore, phenomena, impressing as hallucinations in the adult, occur with

  7. Effects of acute hypoxia/acidosis on intracellular pH in differentiating neural progenitor cells.

    PubMed

    Nordström, Tommy; Jansson, Linda C; Louhivuori, Lauri M; Akerman, Karl E O

    2012-06-21

    The response of differentiating mouse neural progenitor cells, migrating out from neurospheres, to conditions simulating ischemia (hypoxia and extracellular or intracellular acidosis) was studied. We show here, by using BCECF and single cell imaging to monitor intracellular pH (pH(i)), that two main populations can be distinguished by exposing migrating neural progenitor cells to low extracellular pH or by performing an acidifying ammonium prepulse. The cells dominating at the periphery of the neurosphere culture, which were positive for neuron specific markers MAP-2, calbindin and NeuN had lower initial resting pH(i) and could also easily be further acidified by lowering the extracellular pH. Moreover, in this population, a more profound acidification was seen when the cells were acidified using the ammonium prepulse technique. However, when the cell population was exposed to depolarizing potassium concentrations no alterations in pH(i) took place in this population. In contrast, depolarization caused an increase in pH(i) (by 0.5 pH units) in the cell population closer to the neurosphere body, which region was positive for the radial cell marker (GLAST). This cell population, having higher resting pH(i) (pH 6.9-7.1) also responded to acute hypoxia. During hypoxic treatment the resting pH(i) decreased by 0.1 pH units and recovered rapidly after reoxygenation. Our results show that migrating neural progenitor cells are highly sensitive to extracellular acidosis and that irreversible damage becomes evident at pH 6.2. Moreover, our results show that a response to acidosis clearly distinguishes two individual cell populations probably representing neuronal and radial cells.

  8. Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis.

    PubMed

    Lee, Kwang-Hoon; Choi, Sang-Tae; Lee, Soo-Kyung; Lee, Joo-Hyun; Yoon, Bo-Young

    2015-06-01

    Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.

  9. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-25

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

    PubMed Central

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  11. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  12. A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

    PubMed Central

    Martinez-Sanchez, Mariana Esther; Mendoza, Luis; Villarreal, Carlos; Alvarez-Buylla, Elena R.

    2015-01-01

    CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core

  13. Differential Effects of Acute Alcohol on Prepulse Inhibition and Event-Related Potentials in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Ehlers, Cindy L.

    2009-01-01

    Background Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram (EEG). However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). Methods Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. Results Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse+pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. Conclusions These data suggest that alcohol’s effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol influenced response to PPI. PMID:18828807

  14. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

    PubMed Central

    Riise, Øystein Rolandsen; Kirkhus, Eva; Handeland, Kai Samson; Flatø, Berit; Reiseter, Tor; Cvancarova, Milada; Nakstad, Britt; Wathne, Karl-Olaf

    2008-01-01

    Background Osteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute (< 14 days disease duration) and subacute osteomyelitis (≥ 14 days disease duration), and differentiate osteomyelitis patients from those with other acute onset musculoskeletal features. Methods In a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed. Results The total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000). The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7). The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002). Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7). ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43%) patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctor's delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients. Conclusion The annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients

  15. Minimally-Myelosuppressive Asparaginase-Containing Induction Regimen for Treatment of a Jehovah’s Witness with mutant IDH1/NPM1/NRAS Acute Myeloid Leukemia

    PubMed Central

    Emadi, Ashkan; Bade, Najeebah A.; Stevenson, Brandi; Singh, Zeba

    2016-01-01

    Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah’s Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions of blood products, without which such treatment will be life-threatening. Finding a well tolerable, minimally myelosuppressive induction regimen for such patients with AML is a clear example of area of unmet medical need. Here, we report a successful treatment of a 52-year-old Jehovah’s Witness with newly diagnosed AML with peg-asparaginase, vincristine and methylprednisolone. The AML was characterized with normal karyotype, and mutations in isocitrate dehydrogenase 1 (IDH1-Arg132Ser), nucleophosmin 1 (NPM1-Trp289Cysfs*12) and neuroblastoma RAS viral oncogene homolog (NRAS-G1y12Va1). After one 28-day cycle of treatment, the patient achieved complete remission with incomplete count recovery (CRi) and after the second cycle, he achieved CR with full blood count recovery. The patient has never received any blood products. Notwithstanding that myeloperoxidase-induced oxidative degradation of vincristine results in its lack of activity as monotherapy in AML, its combination with corticosteroid and asparaginase has resulted in a robust remission in this patient. Diminished steroid clearance by asparaginase activity as well as reduction in serum glutamine level induced by glutaminase enzymatic activity of asparaginase may have contributed to effective killing of the myeloblasts that carry IDH1/NPM1/NRAS mutations. In conclusion, asparaginase-containing regimens, which are approved for treatment of acute lymphoblastic leukemia (ALL) but not AML, can be used to treat patients with AML who do not accept blood transfusion. PMID:27064021

  16. Minimally-Myelosuppressive Asparaginase-Containing Induction Regimen for Treatment of a Jehovah's Witness with mutant IDH1/NPM1/NRAS Acute Myeloid Leukemia.

    PubMed

    Emadi, Ashkan; Bade, Najeebah A; Stevenson, Brandi; Singh, Zeba

    2016-01-01

    Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah's Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions of blood products, without which such treatment will be life-threatening. Finding a well tolerable, minimally myelosuppressive induction regimen for such patients with AML is a clear example of area of unmet medical need. Here, we report a successful treatment of a 52-year-old Jehovah's Witness with newly diagnosed AML with peg-asparaginase, vincristine and methylprednisolone. The AML was characterized with normal karyotype, and mutations in isocitrate dehydrogenase 1 (IDH1-Arg132Ser), nucleophosmin 1 (NPM1-Trp289Cysfs*12) and neuroblastoma RAS viral oncogene homolog (NRAS-G1y12Va1). After one 28-day cycle of treatment, the patient achieved complete remission with incomplete count recovery (CRi) and after the second cycle, he achieved CR with full blood count recovery. The patient has never received any blood products. Notwithstanding that myeloperoxidase-induced oxidative degradation of vincristine results in its lack of activity as monotherapy in AML, its combination with corticosteroid and asparaginase has resulted in a robust remission in this patient. Diminished steroid clearance by asparaginase activity as well as reduction in serum glutamine level induced by glutaminase enzymatic activity of asparaginase may have contributed to effective killing of the myeloblasts that carry IDH1/NPM1/NRAS mutations. In conclusion, asparaginase-containing regimens, which are approved for treatment of acute lymphoblastic leukemia (ALL) but not AML, can be used to treat patients with AML who do not accept blood transfusion. PMID:27064021

  17. Ureteritis Cystica: Important Consideration in the Differential Diagnosis of Acute Renal Colic

    PubMed Central

    Padilla-Fernández, B.; Díaz-Alférez, FJ.; Herrero-Polo, M.; Martín-Izquierdo, M.; Silva-Abuín, JM.; Lorenzo-Gómez, MF.

    2012-01-01

    Ureteritis cystica is an uncommon cause of acute renal pain. The aetiology remains unclear and the diagnosis may be difficult to establish. We report the case of a 29 year old woman with a history of repeated urinary tract infections presenting with acute renal colic in the absence of lithiasis. We review the diagnostic tools available to make the diagnosis and the recent pertinent literature. PMID:22474406

  18. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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 Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Ixazomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  20. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  1. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  2. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  3. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Malignant Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  4. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-03-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

  6. Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-04

    Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  7. Acute stress differentially affects aromatase activity in specific brain nuclei of adult male and female quail.

    PubMed

    Dickens, Molly J; Cornil, Charlotte A; Balthazart, Jacques

    2011-11-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

  8. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia

    PubMed Central

    Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A.; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K.; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian

    2016-01-01

    Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD–Scid–IL2rγnull mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies. PMID:26951332

  9. Predictive role of minimal residual disease and log clearance in acute myeloid leukemia: a comparison between multiparameter flow cytometry and Wilm's tumor 1 levels.

    PubMed

    Rossi, Giovanni; Minervini, Maria Marta; Melillo, Lorella; di Nardo, Francesco; de Waure, Chiara; Scalzulli, Potito Rosario; Perla, Gianni; Valente, Daniela; Sinisi, Nicola; Cascavilla, Nicola

    2014-07-01

    In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) as well as the degree of log clearance similarly identifies patients with poor prognosis. No comparison was provided between the two approaches in order to identify the best one to monitor follow-up patients. In this study, MRD and clearance were assessed by both multiparameter flow cytometry (MFC) and WT1 expression at different time points on 45 AML patients achieving complete remission. Our results by WT1 expression showed that log clearance lower than 1.96 after induction predicted the recurrence better than MRD higher than 77.0 copies WT1/10(4) ABL. Conversely, on MFC, MRD higher than 0.2 % after consolidation was more predictive than log clearance below 2.64. At univariate and multivariate analysis, positive MRD values and log clearance below the optimal cutoffs were associated with a shorter disease-free survival (DFS). At the univariate analysis, positive MRD values were also associated with overall survival (OS). Therefore, post-induction log clearance by WT1 and post-consolidation MRD by MFC represented the most informative approaches to identify the relapse. At the optimal timing of assessment, positive MRD and log-clearance values lower than calculated thresholds similarly predicted an adverse prognosis in AML.

  10. Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia.

    PubMed

    Cassaday, Ryan D; Alan Potts, D; Stevenson, Philip A; Bar, Merav; Georges, George E; Shustov, Andrei R; Sorror, Mohamed L; Wood, Brent L; Delaney, Colleen; Doney, Kristine C; Storb, Rainer F; Sandmaier, Brenda M

    2016-09-01

    Comparisons without hematopoietic cell transplantation (HCT) to myeloablative (MAC) or reduced-intensity HCT (RIC) for adults with acute lymphoblastic leukemia (ALL) in first minimal-residual-disease negative remission (MRD(Neg) CR1) are limited. Further, the importance of MRD(Neg) following salvage therapy (MRD(Neg) CR2+) is unknown. We evaluated 89 patients in MRD(Neg) CR1 after adult-inspired treatment: 33 received MAC (12 Philadelphia chromosome [Ph]+), 17 received RIC (13 Ph+), and 39 Deferred HCT (3 Ph+). Three-year overall survival (OS) estimates for MAC, RIC, and Deferred HCT were 71%, 69%, and 68%, while 3-year event-free survival (EFS) estimates were 65%, 54%, and 28%, respectively. Further, HCT in MRD(Neg) CR1 performed similarly to MRD(Neg) CR2+: 3-year OS estimates were 70% and 69%, and 3-year EFS estimates were 62% and 62%, respectively. In conclusion, adults with ALL in MRD(Neg) CR1 following adult-inspired therapy had similar OS with or without HCT, and HCT in MRD(Neg) CR2 + can yield long-term survival. PMID:27002921

  11. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    PubMed

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs. PMID:25748682

  12. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available. PMID:23210797

  13. Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia.

    PubMed

    Terwey, Theis Helge; Hemmati, Philipp Georg; Nagy, Marion; Pfeifer, Heike; Gökbuget, Nicola; Brüggemann, Monika; Le Duc, Tanja Melinh; le Coutre, Philipp; Dörken, Bernd; Arnold, Renate

    2014-10-01

    Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.

  14. Reduction of Minimal Residual Disease in Pediatric B-lineage Acute Lymphoblastic Leukemia by an Fc-optimized CD19 Antibody.

    PubMed

    Seidel, Ursula Jördis Eva; Schlegel, Patrick; Grosse-Hovest, Ludger; Hofmann, Martin; Aulwurm, Steffen; Pyz, Elwira; Schuster, Friedhelm R; Meisel, Roland; Ebinger, Martin; Feuchtinger, Tobias; Teltschik, Heiko-Manuel; Witte, Kai-Erik; Schwarze, Carl-Philipp; Rammensee, Hans-Georg; Handgretinger, Rupert; Jung, Gundram; Lang, Peter

    2016-09-01

    Prognosis of primary refractory and relapsed pediatric B-lineage acute lymphoblastic leukemia (ALL) is very poor. Relapse rates significantly correlate with persistent minimal residual disease (MRD). In MRD, favorable effector-target ratios prevail and thus this situation might be optimally suited for immunotherapy with antibodies recruiting immunological effector cells. We here report on the generation, preclinical characterization and first clinical application in B-lineage ALL of an Fc-optimized CD19 antibody. This third-generation antibody (4G7SDIE) mediated enhanced antibody-dependent cellular cytotoxicity (ADCC) against leukemic blasts with effector cells from healthy volunteers and B-lineage ALL patients. The antibody was produced in a university-owned production unit and was applied on a compassionate use basis to 14 pediatric patients with refractory and relapsed B-lineage ALL at the stage of MRD. In 10/14 patients, MRD was reduced by ≥ 1 log or below the patient-individual detection limit, and 5/14 patients have achieved ongoing complete molecular remission with a median leukemia-free survival of 428 days. Two additional patients died in complete molecular remission due to complications not related to antibody therapy. Besides profound in vivo B-cell depletion, side effects were negligible. A clinical phase 1/2 study to further assess the therapeutic activity of 4G7SDIE is in preparation.

  15. Acute heat stress induces differential gene expressions in the testes of a broiler-type strain of Taiwan country chickens.

    PubMed

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

    2015-01-01

    The expression of testicular genes following acute heat stress has been reported in layer-type roosters, but few similar studies have been conducted on broilers. This study investigated the effect of acute heat stress on the gene expression in the testes of a broiler-type strain of Taiwan country chickens. Roosters were subjected to acute heat stress (38°C) for 4 h, and then exposed to 25°C, with testes collected 0, 2, and 6 h after the cessation of heat stress, using non-heat-stressed roosters as controls (n = 3 roosters per group). The body temperature and respiratory rate increased significantly (p<0.05) during the heat stress. The numbers of apoptotic cells increased 2 h after the acute heat stress (79 ± 7 vs. 322 ± 192, control vs. heat stress; p<0.05), which was earlier than the time of increase in layer-type roosters. Based on a chicken 44 K oligo microarray, 163 genes were found to be expressed significantly different in the testes of the heat-stressed chickens from those of the controls, including genes involved in the response to stimulus, protein metabolism, signal transduction, cell adhesion, transcription, and apoptosis. The mRNA expressions of upregulated genes, including HSP25, HSP90AA1, HSPA2, and LPAR2, and of downregulated genes, including CDH5, CTNNA3, EHF, CIRBP, SLA, and NTF3, were confirmed through quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, numerous transcripts in the testes exhibited distinct expressions between the heat-stressed broiler-type and layer-type chickens. We concluded that the transcriptional responses of testes to acute heat stress may differ between the broiler-type and layer-type roosters. Whether the differential expression patterns associate with the heat-tolerance in the strains require a further exploration.

  16. Urinary messenger RNA of the receptor activator of NF-kappaB could be used to differentiate between minimal change disease and membranous nephropathy.

    PubMed

    Liu, Shuangxin; Mei, Ping; Shi, Wei; Zhang, Bin; Li, Sijia; Liang, Xinling; Ye, Zhiming; Xu, Lixia; Ma, Jianchao; Li, Zhilian; Zhang, Li; Wang, Wenjian; Wang, Liping; Li, Rizhao; Feng, Zhonglin; Dong, Wei; Tao, Yiming

    2014-11-01

    Podocyte damage and loss together have an important role in the pathogenesis and progression of glomerulonephritis. Glomerulonephritis patients and healthy controls were enrolled in this study. Biochemical, clinical and experimental procedures included measurement of total urinary protein, renal biopsy and gene expression analysis of the receptor activator of NF-kappaB (RANK). The urinary mRNA levels of RANK were significantly higher in the glomerulonephritis group compared to the controls. The urinary RANK level of glomerular subtypes was correlated significantly with proteinuria. The calculated area of RANK mRNA levels under the curve was 0.61 for minimal change disease (MCD), 0.97 for membranous nephropathy (MN), 0.65 for IgA nephropathy (IgAN), 0.70 for lupus nephritis (LN) and 0.70 for focal segmental glomerulosclerosis (FSGS). The urinary mRNA of RANK might be used to differentiate histologic subtypes of glomerulonephritis, particularly between MCD and MN.

  17. The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia.

    PubMed

    Shen, Chao; Chen, Ming-Tai; Zhang, Xin-Hua; Yin, Xiao-Lin; Ning, Hong-Mei; Su, Rui; Lin, Hai-Shuang; Song, Li; Wang, Fang; Ma, Yan-Ni; Zhao, Hua-Lu; Yu, Jia; Zhang, Jun-Wu

    2016-09-01

    MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy. PMID:27617961

  18. The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia

    PubMed Central

    Shen, Chao; Chen, Ming-Tai; Zhang, Xin-Hua; Yin, Xiao-Lin; Ning, Hong-Mei; Su, Rui; Lin, Hai-Shuang; Song, Li; Wang, Fang; Ma, Yan-Ni; Zhao, Hua-Lu; Yu, Jia; Zhang, Jun-Wu

    2016-01-01

    MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy. PMID:27617961

  19. ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias.

    PubMed

    D'Amato, Loredana; Dell'Aversana, Carmela; Conte, Mariarosaria; Ciotta, Alfonso; Scisciola, Lucia; Carissimo, Annamaria; Nebbioso, Angela; Altucci, Lucia

    2015-01-01

    Altered expression and activity of histone deacetylases (HDACs) have been correlated with tumorigenesis. Inhibitors of HDACs (HDACi) induce acetylation of histone and non-histone proteins affecting gene expression, cell cycle progression, cell migration, terminal differentiation and cell death. Here, we analyzed the regulation of ARHGEF3, a RhoA-specific guanine nucleotide exchange factor, by the HDACi MS275 (entinostat). MS275 is a well-known benzamide-based HDACi, which induces differentiation of the monoblastic-like human histiocytic lymphoma cell line U937 to monocytes/macrophages. Incubation of U937 cells with MS275 resulted in an up regulation of ARHGEF3, followed by a significant enhancement of the marker of macrophage differentiation CD68. ARHGEF3 protein is primarily nuclear, but MS275 treatment rapidly induced its translocation into the cytoplasm. ARHGEF3 cytoplasmic localization is associated with activation of the RhoA/Rho-associated Kinase (ROCK) pathway. In addition to cytoskeletal rearrangements orchestrated by RhoA, we showed that ARHGEF3/RhoA-dependent signals involve activation of SAPK/JNK and then Elk1 transcription factor. Importantly, MS275-induced CD68 expression was blocked by exposure of U937 cells to exoenzyme C3 transferase and Y27632, inhibitors of Rho and ROCK respectively. Moreover, ARHGEF3 silencing prevented RhoA activation leading to a reduction in SAPK/JNK phosphorylation, Elk1 activation and CD68 expression, suggesting a crucial role for ARHGEF3 in myeloid differentiation. Taken together, our results demonstrate that ARHGEF3 modulates acute myeloid leukemia differentiation through activation of RhoA and pathways directly controlled by small GTPase family proteins. The finding that GEF protein modulation by HDAC inhibition impacts on cell differentiation may be important for understanding the antitumor mechanism(s) by which HDACi treatment stimulates differentiation in cancer.

  20. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  2. Acute stimulation of mesenchymal stem cells with cigarette smoke extract affects their migration, differentiation, and paracrine potential

    PubMed Central

    Wahl, Elizabeth A.; Schenck, Thilo L.; Machens, Hans-Günther; Egaña, J. Tomás

    2016-01-01

    Mesenchymal stem cells (MSCs) are known to play a key role in tissue regeneration, while smoking cigarettes is described to impair it. This work focuses on the effect cigarette smoke extract (CSE) has on the migration, differentiation, and paracrine potential of human adipose derived MSCs (AdMSCs). To mimic native conditions in vitro, AdMSCs were cultured in either monolayer or three-dimensional pellet cultures. While constant exposure to high concentrations of CSE had lethal effects on AdMSCs, lower concentrations of CSE impaired cell migration when compared to control conditions. The secretion of key interleukins was downregulated when CSE was exposed to the cells at low concentrations. Moreover, in this work AdMSCs were exposed to CSE while simultaneously being induced to differentiate into adipocytes, osteoblasts, and chondrocytes to determine the effect of CSE on the cells potential to differentiate. While adipogenic differentiation showed no significant variation, AdMSCs exposed to osteogenic and chondrogenic supplements showed both early and late genetic level variation when acutely exposed to low concentrations of CSE. Our results indicate that even a small amount of cigarette smoke can have detrimental effects on the regenerative potential of MSCs. PMID:26976359

  3. Differential presynaptic control of the synaptic effectiveness of cutaneous afferents evidenced by effects produced by acute nerve section

    PubMed Central

    Rudomin, P; Jiménez, I; Chávez, D

    2013-01-01

    In the anaesthetized cat, the acute section of the saphenous (Saph) and/or the superficial peroneal (SP) nerves was found to produce a long-lasting increase of the field potentials generated in the dorsal horn by stimulation of the medial branch of the sural (mSU) nerve. This facilitation was associated with changes in the level of the tonic primary afferent depolarization (PAD) of the mSU intraspinal terminals. The mSU afferent fibres projecting into Rexed's laminae III–IV were subjected to a tonic PAD that was reduced by the acute section of the SP and/or the Saph nerves. The mSU afferents projecting deeper into the dorsal horn (Rexed's laminae V–VI) were instead subjected to a tonic PAD that was increased after Saph and SP acute nerve section. A differential control of the synaptic effectiveness of the low-threshold cutaneous afferents according to their sites of termination within the dorsal horn is envisaged as a mechanism that allows selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks. PMID:23478136

  4. Hyperhomocysteinemia, a Biochemical Tool for Differentiating Ischemic and Nonischemic Central Retinal Vein Occlusion during the Early Acute Phase

    PubMed Central

    Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-01-01

    Purpose The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Methods Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Results Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p < 0.001). Analysis also showed that hyperhomocysteinemia was associated with increased incidence of ischemic CRVO (odds ratio, 18) than that for nonischemic CRVO (odds ratio, 4.5). Serum vitamin B12 and folate levels were significantly lower (p < 0.001) in CRVO patients compared to the control but were not significantly different between nonischemic and ischemic CRVO patients (p > 0.1). Conclusions Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population. PMID:25829824

  5. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2016-01-19

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  6. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2016-09-16

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia

  7. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine.

    PubMed

    Jacobson, Laura H; Sweeney, Fabian F; Kaupmann, Klemens; O'Leary, Olivia F; Gassmann, Martin; Bettler, Bernhard; Cryan, John F

    2016-02-01

    GABAB receptors are crucial modulators of the behavioural effects of drug abuse, and agonists and positive allosteric modulators show promise as pharmacological strategies for anti-addiction therapeutics. GABAB receptors are functional heterodimers of GABAB1 and GABAB2 subunits. The predominant neuronal GABAB1 subunit isoforms are GABAB1a and GABAB1b. Selective ablation of these isoforms in mice revealed differential behavioural responses in fear, cognition and stress sensitivity. However, the influence of the two GABAB1 isoforms on responses to drugs of abuse is unclear. Therefore we examined the responses of GABAB1 subunit isoform null mice to cocaine in acute locomotor activity and conditioned place preference (CPP) paradigms. During habituation for the acute locomotor activity assay, GABAB1b(-/-) mice showed higher levels of locomotor activity relative to wild-type (WT) and GABAB1a(-/-) mice, in accordance with previous studies. Acute cocaine (10 mg/kg) increased locomotor activity in habituated mice of all three genotypes, with GABAB1a(-/-) mice showing sustained hyperlocomotor responses 30 min after cocaine relative to WT and GABAB1b(-/-) mice. No genotypes demonstrated a cocaine-induced place preference, however, GABAB1a(-/-) mice demonstrated enhanced locomotor sensitisation to chronic cocaine in the CPP paradigm in comparison to WT mice, whereas GABAB1b(-/-) mice failed to develop locomotor sensitisation, despite higher levels of basal locomotor activity. These findings indicate that GABAB1a and GABAB1b isoforms differentially regulate behavioural responses to cocaine, with deletion of GABAB1a enhancing cocaine-induced locomotor activity and deletion of GABAB1b protecting from cocaine-induced sensitisation.

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

    PubMed

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

    2015-11-01

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

  10. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers

    PubMed Central

    Sheets, Erin S.; Bujarski, Spencer; Leventhal, Adam M.; Ray, Lara A.

    2015-01-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers’ subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d = 0.55), along with more intense negative emotion (d = 0.97) and greater negative emotion variability (d = 0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not. PMID:25885662

  11. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers.

    PubMed

    Sheets, Erin S; Bujarski, Spencer; Leventhal, Adam M; Ray, Lara A

    2015-08-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers' subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d=0.55), along with more intense negative emotion (d=0.97) and greater negative emotion variability (d=0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not. PMID:25885662

  12. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers.

    PubMed

    Sheets, Erin S; Bujarski, Spencer; Leventhal, Adam M; Ray, Lara A

    2015-08-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers' subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d=0.55), along with more intense negative emotion (d=0.97) and greater negative emotion variability (d=0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not.

  13. Acute stress differentially affects spatial configuration learning in high and low cortisol-responding healthy adults

    PubMed Central

    Meyer, Thomas; Smeets, Tom; Giesbrecht, Timo; Quaedflieg, Conny W. E. M.; Merckelbach, Harald

    2013-01-01

    Background Stress and stress hormones modulate memory formation in various ways that are relevant to our understanding of stress-related psychopathology, such as posttraumatic stress disorder (PTSD). Particular relevance is attributed to efficient memory formation sustained by the hippocampus and parahippocampus. This process is thought to reduce the occurrence of intrusions and flashbacks following trauma, but may be negatively affected by acute stress. Moreover, recent evidence suggests that the efficiency of visuo-spatial processing and learning based on the hippocampal area is related to PTSD symptoms. Objective The current study investigated the effect of acute stress on spatial configuration learning using a spatial contextual cueing task (SCCT) known to heavily rely on structures in the parahippocampus. Method Acute stress was induced by subjecting participants (N = 34) to the Maastricht Acute Stress Test (MAST). Following a counterbalanced within-subject approach, the effects of stress and the ensuing hormonal (i.e., cortisol) activity on subsequent SCCT performance were compared to SCCT performance following a no-stress control condition. Results Acute stress did not impact SCCT learning overall, but opposing effects emerged for high versus low cortisol responders to the MAST. Learning scores following stress were reduced in low cortisol responders, while high cortisol-responding participants showed improved learning. Conclusions The effects of stress on spatial configuration learning were moderated by the magnitude of endogenous cortisol secretion. These findings suggest a possible mechanism by which cortisol responses serve an adaptive function during stress and trauma, and this may prove to be a promising route for future research in this area. PMID:23671762

  14. Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  15. Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

    PubMed Central

    Lai, Xiaoyu; Tan, Yamin; Zheng, Weiyan; Shi, Jimin; Zhao, Yanmin; Lin, Maofang; He, Jingsong; Cai, Zhen; Luo, Yi; Huang, He

    2016-01-01

    We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off points of MRD at CR1 for risk stratification using receiver operating characteristic analysis. The 3-year overall survival (OS) and leukemia free survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a significantly negative correlation with survival in both arms. Three-year OS rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low, intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate, and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that higher level of MRD at CR1 was a significant adverse factor for OS and LFS. Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1, but not patients with low level of MRD at CR1 (P = 0.851). These results suggested that MRD at CR1 could strongly predict the outcome of adult ALL. Patients with intermediate and high levels of MRD at CR1 would benefit from allo-HSCT. PMID:27695097

  16. Oral infection with enteropathogenic Escherichia coli triggers immune response and intestinal histological alterations in mice selected for their minimal acute inflammatory responses.

    PubMed

    Vulcano, Amanda Bardella; Tino-De-Franco, Milene; Amaral, José Araujo; Ribeiro, Orlando Garcia; Cabrera, Wafa Hanna Koury; Bordenalli, Marcela Aparecida; Carbonare, Cristiane Barros; Álvares, Eliana Parisi; Carbonare, Solange Barros

    2014-06-01

    Enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea, is an important public health problem in Brazil and other developing countries. In vitro assays of bacterial adhesion to cultured cells are important tools for studying bacterial pathogenicity but do not reproduce all the events that occur in natural infections. In this study, the effects of oral infection with EPEC on mice selected for their minimal acute inflammatory response (AIR min) were evaluated. Mice were orally infected with EPEC and variations in body weight, bacterial shedding and antibody production observed. The infected animals developed seric and secretory anti-EPEC antibodies; however, neither mortality nor diarrhea was observed. Light microscopy of their intestines demonstrated histological modifications that were not present in controls. However, electron microscopy did not show bacteria attached to the intestinal epithelia to form attaching and effacing lesions, characteristic of EPEC in humans. The bacteria were detected in Peyer's patches and intestinal contents up to 5 hr post-infection. When human anti-EPEC secretory immunoglobulin A or avian immunoglobulin Y antibodies were administered to infected animals, they developed minor histological alterations compared with non-treated animals. In summary, it was found that EPEC triggers immune responses and intestinal histological alterations but does not produce evidence of diarrheal disease in mice infected by the oral route. This study of EPEC experimental infection provides a better understanding of the effects of antibodies on bacterial infections and may provide a suitable model for the design and testing of immunobiological products for active or passive immunization. PMID:24750489

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

    PubMed

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

    2014-10-01

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

  18. Interferon-α: A Potentially Effective Treatment for Minimal Residual Disease in Acute Leukemia/Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2015-11-01

    In this prospective clinical study, the safety and efficacy of preemptive interferon-α (IFN-α) treatment were investigated and compared with preemptive donor lymphocyte infusion (DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). Patients undergoing allogeneic HSCT were eligible if they had acute leukemia or myelodysplastic syndrome and were MRD-positive after HSCT. Patients who were able to receive DLI were assigned to a preemptive DLI group (n = 45); patients who could not or did not agree to receive DLI after HSCT received preemptive IFN-α. A total of 22 patients received preemptive IFN-α; the median treatment duration was 35 days (range, 4 to 180 days). Seven patients relapsed, and 1 patient died from severe pneumonia. The 1-year cumulative incidence of chronic graft-versus-host disease (cGVHD) after intervention was 90.9% for the IFN-α group and 62.9% for the DLI group (P < .001). MRD status after preemptive intervention was comparable in the 2 groups, and the 1-year cumulative incidence of relapse after intervention was 27.3% for the IFN-α group and 35.6% for the DLI group (P = .514). The 1-year cumulative incidence of nonrelapse mortality after intervention was 4.5% for the IFN-α group and 4.4% for the DLI group (P = .985). The 1-year probability of disease-free survival after intervention was 68.2% for the IFN-α group and 60.0% for the DLI group (P = .517). In multivariate analysis, early-onset MRD, persistent MRD after intervention, and absence of cGVHD after intervention were significantly associated with poorer clinical outcomes. Thus, preemptive IFN-α may be a potential alternative for MRD-positive patients who cannot receive preemptive DLI after HSCT.

  19. Differential Effects of Opioid-Related Ligands and NSAIDs in Nonhuman Primate Models of Acute and Inflammatory Pain

    PubMed Central

    Sukhtankar, Devki D.; Lee, Heeseung; Rice, Kenner C.; Ko, Mei-Chuan

    2013-01-01

    Rationale Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates. Objective The aims of this study were to develop carrageenan-induced hyperalgesia in rhesus monkeys and determine the efficacy and potency of agonists selective for the four opioid receptor subtypes in this model versus acute pain, as compared to NSAIDs. Results Tail-injection of carrageenan produced long-lasting thermal hyperalgesia in monkeys. Systemically administered agonists selective for opioid receptor subtypes i.e. fentanyl (mu/MOP), U-50488H (kappa/KOP), SNC80 (delta/DOP) and Ro 64-6198 (nociceptin/orphanin FQ/NOP) dose-dependently attenuated carrageenan-induced thermal hyperalgesia with different potencies. In absence of carrageenan, these agonists, except SNC80, blocked acute thermal nociception. Opioid-related ligands, especially Ro 64-6198, were much more potent for their antihyperalgesic than antinociceptive effects. Both effects were mediated by the corresponding receptor mechanisms. Only fentanyl produced scratching at antihyperalgesic and antinociceptive doses consistent with its pruritic effects in humans, illustrating a translational profile of MOP agonists in nonhuman primates. Similar to SNC80, systemically administered NSAIDs ketorolac and naproxen dose-dependently attenuated carrageenan-induced hyperalgesia but not acute nociception. Conclusion Using two different pain modalities in nonhuman primates, effectiveness of clinically available analgesics like fentanyl, ketorolac and naproxen was distinguished and their efficacies and potencies were compared with the selective KOP, DOP, and NOP agonists. The opioid-related ligands displayed differential pharmacological properties in regulating hyperalgesia and acute nociception in the same subjects. Such preclinical primate models can be used to investigate novel

  20. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

    PubMed Central

    Roumier, Christophe; Cheok, Meyling; Marceau-Renaut, Alice; Nibourel, Olivier; Geffroy, Sandrine; Helevaut, Nathalie; Rousselot, Philippe; Gruson, Bérengère; Gardin, Claude; Chretien, Marie-Lorraine; Sebda, Shéhérazade; Figeac, Martin; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Castaigne, Sylvie; Dombret, Hervé; Renneville, Aline; Preudhomme, Claude

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis. PMID:26486081

  1. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association.

    PubMed

    Debarri, Houria; Lebon, Delphine; Roumier, Christophe; Cheok, Meyling; Marceau-Renaut, Alice; Nibourel, Olivier; Geffroy, Sandrine; Helevaut, Nathalie; Rousselot, Philippe; Gruson, Bérengère; Gardin, Claude; Chretien, Marie-Lorraine; Sebda, Shéhérazade; Figeac, Martin; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Castaigne, Sylvie; Dombret, Hervé; Renneville, Aline; Preudhomme, Claude

    2015-12-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.

  2. [THE ROLE OF BIOLOGICAL MEMBRANES IN DIFFERENTIAL DIAGNOSTICS OF SALMONELLA AND ACUTE ALCOHOL GASTROENTERITIS].

    PubMed

    Makarov, V K; Makarov, P V

    2015-01-01

    We evaluated the influence of Salmonella infection and alcohol on biological membranes from the content of serum phospholipid fraction known to be a component ofenterocyte membranes. Any change of membrane phospholipid content leads to a change of their blood level. The study included 50 patients with acute alcohol gastroenteritis, 50 ones with salmonella gastroenteritis, and 50 healthy subjects. Both salmonellosis and alcohol caused differently directed changes in biological membranes. The mechanism of diarrhea in patients with salmonella and acute alcohol gastroenteritis is different. Diarrhea associated with alcohol gastroenteritis is due to enhanced viscosity of biomembranes that decreases in salmonella gastroenteritis. It suggests different approaches to the treatment of these conditions. The membrane destruction coefficient below 2 is an additional proof of alcoholic etiology of gastroenteritis whereas its value above 3 confirms the involvement of salmonellosis in pathogenesis of gastroenteritis.

  3. Scintigraphy for the diagnosis of testicular torsion and differential diagnosis of acute intrascrotal processes.

    PubMed

    Romics, I; Wesseler, T; Bach, D

    1988-01-01

    Twenty-five patients suffering from acute painful testicular processes were subjected to scintigraphy. Testicular torsion in the early and delayed phases were diagnosed with 100% accuracy, but one out of 7 cases of epididymitis was wrongly recognized as negative. Interoperative diagnosis in two cases of hydatid torsion proved the foregoing scintigraphic finding to have been wrong. Nevertheless, scintigraphy was found to be reliable in testicular torsion diagnosis.

  4. [Differential diagnosis of chest pain: a case of acute aortic syndrome].

    PubMed

    Córdoba-Soriano, J G; Hidalgo-Olivares, V; Cambronero-Cortinas, E; Fernández-Anguita, M

    2014-03-01

    Chest pain is one of the most frequent reasons for consulting in any healthcare setting, however its diagnosis remains a challenge for both Primary Care and Emergency Department physicians. We report a case of an Acute Aortic Syndrome which was diagnosed late after an insidious course of chest pain, repetitive syncope, and in which the delay in diagnosis and treatment could be fatal. We also describe the definition, diagnosis, treatment, and outcome of this condition. PMID:24655911

  5. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  6. Amylase clearance in differentiating acute pancreatitis from peptic ulcer with hyperamylasemia.

    PubMed

    Warshaw, A L; Lesser, P B

    1975-03-01

    Thirty-four patients with abdominal pain, tenderness, and hyperamylasemia suggesting acute pancreatitis were studied prospectively to elucidate the relationship between peptic ulcer disease and pancreatitis. Confirming evidence of pancreatitis and/or ulcer was obtained either at laparotomy of by upper gastrointestinal roentgenograms. The presence or absence of pancreatitis was substantiated by measurement of the amylase/creatinine clearance ratio, which is significantly higher (p less than 0.001) in patients with acute pancreatitis (9.3 plus or minus 0.9), than in patients without pancreatitis (3.1 plus or minus 0.2). Nine of the 34 patients were found to have gastric or duodenal ulcers. However, seven of the nine, despite an elevated serum amylase, had no sign of pancreatitis at surgery, on radiological examination, or by elevation of the amylase/creatinine clearance ratio (3.1 plus or minus 0.4). It is suggested that hyperamylasemia associated with peptic ulcer disease is most often not indicative of acute pancreatitis and that treatment is most appropriately directed at the ulcer.

  7. Differential effects of acute and chronic fructose administration on pyruvate dehydrogenase activity and lipogenesis

    SciTech Connect

    Wilson, L.

    1988-01-01

    These studies were undertaken to distinguish between the acute and chronic effects of fructose administration. In vivo, liver lipogenesis, as measured by {sup 3}H{sub 2}O incorporation, was greater in rats fed 60% fructose than in their glucose fed controls. Both fructose feeding, and fructose feeding plus intraperitoneal fructose injection increased the activities of 6-phosphogluconate dehydrogenase and malic enzyme. Liver PDH activity was increased by fructose feeding, and was increased even more by fructose feeding and injection of fructose, but this was not associated with any changes in hepatic ATP concentrations.

  8. Gambogic acid induces growth inhibition and differentiation via upregulation of p21waf1/cip1 expression in acute myeloid leukemia cells.

    PubMed

    Chen, Yan; Hui, Hui; Li, Zheng; Wang, Hong-Mei; You, Qi-Dong; Lu, Na

    2014-10-01

    Gambogic acid (GA) is the major active ingredient of gamboges, a brownish to orange resin product from Garcinia hanburyi tree in Southeast Asia. This compound exhibits anti-cancer effect on solid tumors. In this study, we investigated the effects of GA on the growth and differentiation of acute myeloid leukemia cells by growth-inhibition detection, morphological changes observation, nitroblue tetrazolium reduction, and the expression of the relative cell-surface differentiation markers. The results showed that GA could inhibit cell growth and promote differentiation in U937 and HL-60 cells. In addition, GA upregulated the expression of p21waf1/cip1 in the two cell lines. Finally, downregulating the p21waf1/cip1 expression with small interfering RNA partially blocked GA-induced cell growth inhibition and differentiation. These results of this study revealed that GA may be used as one of the investigational drugs for acute myeloid leukemia.

  9. Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia

    PubMed Central

    dos Santos, Guilherme Augusto; Kats, Lev

    2013-01-01

    Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nuclear bodies that regulate numerous signaling pathways. The empirical discoveries that PML-RARa–associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Critically, the mechanistic insights gleaned from these studies have resulted not only in a better understanding of APL itself, but also carry valuable lessons for other malignancies. PMID:24344243

  10. The functional role of microRNA in acute lymphoblastic leukemia: relevance for diagnosis, differential diagnosis, prognosis, and therapy

    PubMed Central

    Luan, Chengxin; Yang, Zixue; Chen, Baoan

    2015-01-01

    MicroRNAs (miRNAs), a new class of noncoding RNAs, which can hybridize to target messenger RNAs and regulate their expression posttranscriptionally, express differentially in distinct stages of lymphopoiesis and influence the direction of lymphoid precursor maturation. Hence, there is aberrant expression of miRNAs involved in malignant lymphopoiesis, and these aberrations can be used as signatures of acute lymphoblastic leukemia (ALL) with different subtypes. In addition, changes in the expression of several miRNAs may have functional relevance with leukemogenesis or drug resistance. As a result, the reversal of the expression of these miRNAs may alleviate the disease to some extent and improve clinical outcomes. However, among the studies of miRNAs, there are still some problems that need to be solved to understand the function of miRNAs in ALL more thoroughly. PMID:26508875

  11. Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction

    PubMed Central

    Cheng, Suk Hang; Lau, Kin Mang; Li, Chi Kong; Chan, Natalie P. H.; Ip, Rosalina K. L.; Cheng, Chi Keung; Lee, Vincent; Shing, Matthew M. K.; Leung, Alex W. K.; Ha, Shau Yin; Cheuk, Daniel K. L.; Lee, Anselm C. W.; Li, Chak Ho; Luk, Chung Wing; Ling, Siu Cheung; Hrusak, Ondrej; Mejstrikova, Ester; Leung, Yonna; Ng, Margaret H. L.

    2013-01-01

    Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1–10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15≥10% or day-33≥0.01% but not both, II-C: day-15≥10% and day-33≥0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD≥10−4 were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients’ prognosis, with 20–35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥10−4. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring. PMID:23936021

  12. Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

    PubMed Central

    Roberts, Kathryn G.; Pei, Deqing; Campana, Dario; Payne-Turner, Debbie; Li, Yongjin; Cheng, Cheng; Sandlund, John T.; Jeha, Sima; Easton, John; Becksfort, Jared; Zhang, Jinghui; Coustan-Smith, Elaine; Raimondi, Susana C.; Leung, Wing H.; Relling, Mary V.; Evans, William E.; Downing, James R.; Mullighan, Charles G.; Pui, Ching-Hon

    2014-01-01

    Purpose BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Patients and Methods Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Results Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Conclusion Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies. PMID:25049327

  13. Differential acute effects of selenomethionine and sodium selenite on the severity of colitis.

    PubMed

    Hiller, Franziska; Oldorff, Lisa; Besselt, Karolin; Kipp, Anna Patricia

    2015-04-01

    The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. PMID:25867950

  14. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo.

    PubMed

    Pavlin-Premrl, Davor; Waterston, John; McGuigan, Sean; Infeld, Bernard; Sultana, Ron; O'Sullivan, Richard; Gerraty, Richard P

    2015-03-01

    Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators' physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo.

  15. Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels

    PubMed Central

    García-Cáceres, Cristina; Fuente-Martín, Esther; Burgos-Ramos, Emma; Granado, Miriam; Frago, Laura M.; Barrios, Vicente; Horvath, Tamas

    2011-01-01

    Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus. Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes. Leptin modulates synaptic inputs in the hypothalamus, but whether astrocytes participate in this action is unknown. Here we report that astrocyte structural proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are induced and astrocyte morphology modified by chronic leptin administration (intracerebroventricular, 2 wk), with these changes being inversely related to modifications in synaptic protein densities. Similar changes in glial structural proteins were observed in adult male rats that had increased body weight and circulating leptin levels due to neonatal overnutrition (overnutrition: four pups/litter vs. control: 12 pups/litter). However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin. In primary hypothalamic astrocyte cultures leptin also reduced GFAP levels at 1 h, with an induction at 24 h, indicating a possible direct effect of leptin. Hence, one mechanism by which leptin may affect metabolism is by modifying hypothalamic astrocyte morphology, which in turn could alter synaptic inputs to hypothalamic neurons. Furthermore, the responses to acute and chronic leptin exposure are inverse, raising the possibility that increased glial activation in response to chronic leptin exposure could be involved in central leptin resistance. PMID:21343257

  16. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-09-26

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  17. A New Differential Diagnosis: Synthetic Cannabinoids-Associated Acute Renal Failure.

    PubMed

    Gudsoorkar, Vineet S; Perez, Jose A

    2015-01-01

    Synthetic cannabinoids (SCs) are herbal blends that use plant material with varying concentrations of synthetic analogues of cannabinoids. These products are sold as incense or potpourri and are labeled "Not for human use." Even so, rates of abuse are rapidly increasing worldwide, especially in the young adult population. An extensive network of users exists, and the products can easily be ordered on the Internet under various brand names, including the most popular ones, "K2" and "Spice." Not much is known about their spectrum of toxicity and no specific antidote is available at present. Renal failure is a rare complication associated with SC abuse. We describe a case of acute kidney injury associated with use of SCs and present a review of the current literature, including the history and some key pharmacologic and epidemiologic findings related to synthetic cannabinoid compounds. PMID:26634029

  18. A New Differential Diagnosis: Synthetic Cannabinoids-Associated Acute Renal Failure

    PubMed Central

    Gudsoorkar, Vineet S.; Perez, Jose A.

    2015-01-01

    Synthetic cannabinoids (SCs) are herbal blends that use plant material with varying concentrations of synthetic analogues of cannabinoids. These products are sold as incense or potpourri and are labeled “Not for human use.” Even so, rates of abuse are rapidly increasing worldwide, especially in the young adult population. An extensive network of users exists, and the products can easily be ordered on the Internet under various brand names, including the most popular ones, “K2” and “Spice.” Not much is known about their spectrum of toxicity and no specific antidote is available at present. Renal failure is a rare complication associated with SC abuse. We describe a case of acute kidney injury associated with use of SCs and present a review of the current literature, including the history and some key pharmacologic and epidemiologic findings related to synthetic cannabinoid compounds. PMID:26634029

  19. The acute glucocorticoid stress response does not differentiate between rewarding and aversive social stimuli in rats.

    PubMed

    Buwalda, Bauke; Scholte, Jan; de Boer, Sietse F; Coppens, Caroline M; Koolhaas, Jaap M

    2012-02-01

    The mere presence of elevated plasma levels of corticosterone is generally regarded as evidence of compromised well-being. However, environmental stimuli do not necessarily need to be of a noxious or adverse nature to elicit activation of the stress response systems. In the present study, the physiological and neuroendocrine responses to repeated social stimuli that can be regarded as emotional opposites, i.e. social defeat and sexual behavior, were compared. Similar corticosterone responses were observed in animals confronted for the first time with either a highly aggressive male intruder or a receptive female, but a decrease was noticed in defeated rats tested during a third interaction. Only if animals are being physically attacked does the corticosterone response remain similar to the one observed during sexual behavior. In addition, the number of activated cells in the parvocellular hypothalamic paraventricular nucleus, as visualized by c-Fos immunocytochemistry, shows no difference between rats 1h after the third exposure to defeat or sex. Finally, biotelemetric recordings of heart rate, body temperature and locomotor activity show a robust response to both social stimuli that is generally, however, higher in animals being confronted with a receptive female. The data clearly indicate that acute plasma corticosterone levels are not reflecting the emotional valence of a salient stimulus. The magnitude of the response seems to be a direct reflection of the behavioral activity and hence of the metabolic requirements of activated tissues. Next to its direct metabolic role, acute increases in plasma corticosterone will have neurobiological and behavioral effects that largely depend on the neural circuitry that is activated by the stimulus that triggered its release. PMID:22210197

  20. Acute and chronic mu opioids differentially regulate thrombospondins 1 and 2 isoforms in astrocytes.

    PubMed

    Phamduong, Ellen; Rathore, Maanjot K; Crews, Nicholas R; D'Angelo, Alexander S; Leinweber, Andrew L; Kappera, Pranay; Krenning, Thomas M; Rendell, Victoria R; Belcheva, Mariana M; Coscia, Carmine J

    2014-02-19

    Chronic opioids induce synaptic plasticity, a major neuronal adaptation. Astrocyte activation in synaptogenesis may play a critical role in opioid tolerance, withdrawal, and dependence. Thrombospondins 1 and 2 (TSP1/2) are astrocyte-secreted matricellular glycoproteins that promote neurite outgrowth as well as dendritic spine and synapse formation, all of which are inhibited by chronic μ opioids. In prior studies, we discovered that the mechanism of TSP1 regulation by μ opioids in astrocytes involves crosstalk between three different classes of receptors, μ opioid receptor, EGFR and TGFβR. Moreover, TGFβ1 stimulated TSP1 expression via EGFR and ERK/MAPK activation, indicating that EGFR is a signaling hub for opioid and TGFβ1 actions. Using various selective antagonists, and inhibitors, here we compared the mechanisms of chronic opioid regulation of TSP1/2 isoform expression in vivo and in immortalized rat cortical astrocytes. TSP1/2 release from astrocytes was also monitored. Acute and chronic μ opioids, morphine, and the prototypic μ ligand, DAMGO, modulated TSP2 protein levels. TSP2 but not TSP1 protein content was up-regulated by acute (3 h) morphine or DAMGO by an ERK/MAPK dependent mechanism. Paradoxically, TSP2 protein levels were altered neither by TGFβ1 nor by astrocytic neurotrophic factors, EGF, CNTF, and BMP4. TSP1/2 immunofluorescence was increased in astrocytes subjected to scratch-wounding, suggesting TSPs may be useful markers for the "reactive" state of these cells and potentially for different types of injury. Previously, we determined that chronic morphine attenuated both neurite outgrowth and synapse formation in cocultures of primary astrocytes and neurons under similar temporal conditions that μ opioids reduced TSP1 protein levels in astrocytes. Here we found that, after the same 8 day treatment, morphine or DAMGO diminished TSP2 protein levels in astrocytes. Therefore, μ opioids may deter synaptogenesis via both TSP1/2 isoforms, but

  1. Differentiation of acute renal failure and chronic renal failure by 2-dimensional analysis of urinary dipeptidase versus serum creatinine.

    PubMed

    Lee, S H; Kang, B Y; We, J S; Park, S K; Park, H S

    1999-03-01

    The differential diagnosis of acute renal failure (ARF) and chronic renal failure (CRF) may be possible by measuring urinary dipeptidase (Udpase) activity and serum creatinine (Scr) concentration. When the mass test of 246 individuals was examined on a 2-dimensional plot of Udpase (y-axis) versus Scr (x-axis) with the data obtained from healthy volunteers (n = 189), ARF (n = 19) and CRF (n = 38) patients, the characteristic distribution of each group was obvious. It is summarized by the mean values of healthy volunteers (1.44 +/- 0.39 mg/dL, 1.19 (0.59 mU/mL), ARF (6.04 +/- 5.04 mg/dL, 0.12 +/- 0.08 mU/mL), and CRF patients (8.72 +/- 2.93 mg/dL, 0.81 +/- 0.44 mU/mL). The healthy volunteers are distributed along the y-axis and the ARF patients the x-axis, thus separating the two groups 90 degrees apart. The CRF patients are scattered away from both x-, and y-axis. This 2-dimensional approach is thought to be very useful for the differential diagnosis of ARF suggesting Udpase as a new member of the marker enzymes of renal disease.

  2. Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

    PubMed Central

    Merhi, Faten; Auger, Jacques; Rendu, Francine; Bauvois, Brigitte

    2008-01-01

    Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All2TS), dipropyl TS (Pr2TS) and dimethyl TS (Me2TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML. PMID:19707466

  3. 3,5,3'-Triiodothyroacetic acid minimizes the pituitary thyrotrophin secretion in patients on levo-thyroxine therapy after ablative therapy for differentiated thyroid carcinoma.

    PubMed

    Mueller-Gaertner, H W; Schneider, C

    1988-04-01

    The aim of this study was to examine the influence of 3,5,3'-triiodothyroacetic acid (TRIAC) on serum thyrotrophin (TSH) concentration in 25 patients on levo-thyroxine (L-T4) therapy after ablative therapy for differentiated thyroid carcinoma. The daily L-T4 intake amounted to 2.6 +/- 0.7 micrograms/kg body weight (+/- SD). Serum TSH concentration was determined by means of a sensitive radioimmunometric method (lower detection limit 0.03 mU/l). The median (means) basal TSH concentration under L-T4 amounted to 0.11 mU/l (range less than 0.03 mU/l-7.39 mU/l). During supplementary intake of 500 micrograms TRIAC daily the median basal TSH decreased to 0.04 mU/l range less than 0.03 mU/l-0.24 mU/l; P less than 0.0003). The TRIAC-induced decrease in 17 out of 20 basal TSH-concentrations exceeding 0.03 mU/l ranged from 38% to as much as 98%. TRIAC reduced the median TRH-stimulated TSH concentration from 0.25 mU/l (range less than 0.03 mU/l-47.3 mU/l) to 0.04 mU/l (range less than 0.03 mU/l-1.43 mU/l; P less than 0.0001). A blunted TSH-response to TRH occurred in 8.7% prior to and in 52% of the patients during TRIAC medication. Side effects such as nervousness, cardiac arrhythmia or tachycardia under supplementary TRIAC (500 micrograms daily) were observed in four patients. The conclusion is that the supplementary medication of 500 micrograms TRIAC daily in euthyroid patients on L-T4 medication after thyroid gland ablation for differentiated thyroid cancer is an effective means to minimize serum-TSH concentration.

  4. Retinoid-induced differentiation of acute promyelocytic leukemia involves PML-RARalpha-mediated increase of type II transglutaminase.

    PubMed

    Benedetti, L; Grignani, F; Scicchitano, B M; Jetten, A M; Diverio, D; Lo Coco, F; Avvisati, G; Gambacorti-Passerini, C; Adamo, S; Levin, A A; Pelicci, P G; Nervi, C

    1996-03-01

    All-trans retinoic acid (t-RA) administration leads to complete remission in acute promyelocytic leukemia (APL) patients by inducing growth arrest and differentiation of the leukemic clone. In the present study, we show that t-RA treatment dramatically induced type II transglutaminase (type II TGase) expression in cells carrying the t(15;17) translocation and expressing the PML-RARalpha product such as the APL-derived NB4 cell line and fresh leukemic cells from APL patients. This induction correlated with t-RA-induced growth arrest, granulocytic differentiation, and upregulation of the leukocyte adherence receptor beta subunit (CD18) gene expression. The increase in type II TGase was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate was not required for the induction. t-RA did not significantly alter the rate of growth arrest and did not stimulate differentiation and type II TGase activity in NB4.306 cells, a t-RA-resistant subclone of the NB4 cell line, or in leukemic cells derived from two patients morphologically defined as APL but lacking the t(15;17). However, in NB4.306 cells, t-RA treatment was able to increase CD18 mRNA expression in a manner similar to NB4 cells. The molecular mechanisms involved in the induction of these genes were investigated. In NB4 cells, using novel receptor-selective ligands such as 9-cis-RA, TTNPB, AM580, and SR11217, we found that RAR- and RARalpha-selective retinoids were able to induce growth arrest, granulocytic differentiation, and type II TGase, whereas the RXR-selective retinoid SR11217 was inactive. Moreover, an RAR alpha-antagonist completely inhibited the expression of type II TGase and CD18 induced by these selective retinoids in NB4 cells. In NB4.306 cells, an RARalpha-dependent signaling pathway was found involved in the modulation of CD18 expression. In addition, expression of the PML-RARalpha gene in myeloid U937 precursor cells resulted in the ability of these cells to

  5. Mutation of Lon protease differentially affects the expression of Pseudomonas syringae type III secretion system genes in rich and minimal media and reduces pathogenicity.

    PubMed

    Lan, Lefu; Deng, Xin; Xiao, Yanmei; Zhou, Jian-Min; Tang, Xiaoyan

    2007-06-01

    The bacterial Lon protease participates in a variety of biological processes. In Pseudomonas syringae, mutation of lon is known to activate hrpL and a few hrpL-regulated genes in rich medium. The elevated expression of hrpL and hrpL-regulated genes results from increased stability of HrpR, the transcriptional activator of hrpL, in the lon mutant. Here, we conducted a microarray analysis to identify genes that are differentially expressed in a lon- mutant of P. syringae pv. tomato DC3000 grown in the rich medium King's B (KB). Most genes induced in the lon- mutant belong to the HrpL regulon or are related to transcription, protein synthesis, and energy metabolism. A major group of genes reduced in the lon- mutant are related to cell wall biogenesis. The HrpL-regulated genes exhibit different induction patterns in the lon- mutant, suggesting that additional regulators other than HrpL are likely to be involved in regulation of these genes. Compared with the wild-type bacteria, lon- mutants of P. syringae pv. tomato DC3000 and P. syringae pv. phaseolicola NPS3121 strains exhibit elevated hrpL expression in KB medium, but reduced hrpL expression in minimal medium (MM). The reduced hrpL RNA is correlated with reduced hrpR and hrpS RNAs, suggesting that the Lon-mediated regulation of hrpL involves different mechanisms in KB and MM. The lon- mutation also reduced bacterial pathogenicity.

  6. Mcl-1 regulates effector and memory CD8 T-cell differentiation during acute viral infection.

    PubMed

    Kim, Eui Ho; Neldner, Brandon; Gui, Jingang; Craig, Ruth W; Suresh, M

    2016-03-01

    Mcl-1, an anti-apoptotic member of Bcl-2 family maintains cell viability during clonal expansion of CD8 T cells, but the cell intrinsic role of Mcl-1 in contraction of effectors or the number of memory CD8 T cells is unknown. Mcl-1 levels decline during the contraction phase but rebound to high levels in memory CD8 T cells. Therefore, by overexpressing Mcl-1 in CD8 T cells we asked whether limiting levels of Mcl-1 promote contraction of effectors and constrain CD8 T-cell memory. Mcl-1 overexpression failed to affect CD8 T-cell expansion, contraction or the magnitude of CD8 T-cell memory. Strikingly, high Mcl-1 levels enhanced mTOR phosphorylation and augmented the differentiation of terminal effector cells and effector memory CD8 T cells to the detriment of poly-cytokine-producing central memory CD8 T cells. Taken together, these findings provided unexpected insights into the role of Mcl-1 in the differentiation of effector and memory CD8 T cells.

  7. Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains.

    PubMed

    Di Francesco, P; Tavazzi, B; Gaziano, R; Lazzarino, G; Casalinuovo, I A; Di Pierro, D; Garaci, E

    1998-01-01

    This paper shows that an acute morphine treatment dose-dependently alters the energetic and oxidative metabolism of polymorphonuclear leukocytes obtained from BALB/c and DBA/2 mice, while phagocytic cells from C57BL/6 were not affected. In sensitive mouse strains, i.e. BALB/c and DBA/2, morphine decreased both ATP concentration and energy charge potential. At the same time, ATP catabolic products, i.e. nucleosides (inosine+adenosine) and oxypurines (hypoxanthine+xanthine+uric acid), significantly increased, indicating an imbalance between energy production and consumption. Morphine treatment also induced malondialdehyde and superoxide anions production in leukocyte cells from sensitive mice. The opiate antagonist naloxone blocked morphine-induced modifications by the lower morphine dose. The same parameters in cells from C57BL/6 mice were not affected. These findings confirm that: i) the phagocytic cells are an important target for the in vivo effects of morphine, and ii) the genotype-dependent variation influences the immunological responsiveness to opiates.

  8. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  9. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    PubMed Central

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  10. Differential Dynamics of CD4+ and CD8+ T-Lymphocyte Proliferation and Activation in Acute Simian Immunodeficiency Virus Infection

    PubMed Central

    Kaur, Amitinder; Hale, Corrina L.; Ramanujan, Saroja; Jain, Rakesh K.; Johnson, R. Paul

    2000-01-01

    Although lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been extensively studied, there is little information on turnover in acute infection. We carried out a prospective kinetic analysis of lymphocyte proliferation in 13 rhesus macaques inoculated with pathogenic SIV. A short-lived dramatic increase in circulating Ki-67+ lymphocytes observed at 1 to 4 weeks was temporally related to the onset of SIV replication. A 5- to 10-fold increase in Ki-67+ CD8+ T lymphocytes and a 2- to 3-fold increase in Ki-67+ CD3− CD8+ natural killer cells accounted for >85% of proliferating lymphocytes at peak proliferation. In contrast, there was little change in the percentage of Ki-67+ CD4+ T lymphocytes during acute infection, although transient increases in Ki-67− and Ki-67+ CD4+ T lymphocytes expressing CD69, Fas, and HLA-DR were observed. A two- to fourfold decline in CD4+ T lymphocytes expressing CD25 and CD69 was seen later in SIV infection. The majority of Ki-67+ CD8+ T lymphocytes were phenotypically CD45RA− CD49dhi Fashi CD25− CD69− CD28− HLA-DR− and persisted at levels twofold above baseline 6 months after SIV infection. Increased CD8+ T-lymphocyte proliferation was associated with cell expansion, paralleled the onset of SIV-specific cytotoxic T-lymphocyte activity, and had an oligoclonal component. Thus, divergent patterns of proliferation and activation are exhibited by CD4+ and CD8+ T lymphocytes in early SIV infection and may determine how these cells are differentially affected in AIDS. PMID:10954541

  11. Differential Effects of Acute Stress on Anticipatory and Consummatory Phases of Reward Processing

    PubMed Central

    Kumar, Poornima; Berghorst, Lisa H.; Nickerson, Lisa D.; Dutra, Sunny J.; Goer, Franziska; Greve, Douglas; Pizzagalli, Diego A.

    2014-01-01

    Anhedonia is one of the core symptoms of depression and has been linked to blunted responses to rewarding stimuli in striatal regions. Stress, a key vulnerability factor for depression, has been shown to induce anhedonic behavior, including reduced reward responsiveness in both animals and humans, but the brain processes associated with these effects remain largely unknown in humans. Emerging evidence suggests that stress has dissociable effects on distinct components of reward processing, as it has been found to potentiate motivation/‘wanting’ during the anticipatory phase but reduce reward responsiveness/‘liking’ during the consummatory phase. To examine the impact of stress on reward processing, we used a monetary incentive delay (MID) task and an acute stress manipulation (negative performance feedback) in conjunction with functional magnetic resonance imaging (fMRI). Fifteen healthy participants performed the MID task under no-stress and stress conditions. We hypothesized that stress would have dissociable effects on the anticipatory and consummatory phases in reward-related brain regions. Specifically, we expected reduced striatal responsiveness during reward consumption (mirroring patterns previously observed in clinical depression) and increased striatal activation during reward anticipation consistent with non-human findings. Supporting our hypotheses, significant Phase (Anticipation/Consumption) x Stress (Stress/No-stress) interactions emerged in the putamen, nucleus accumbens, caudate and amygdala. Post-hoc tests revealed that stress increased striatal and amygdalar activation during anticipation but decreased striatal activation during consumption. Importantly, stress-induced striatal blunting was similar to the profile observed in clinical depression under baseline (no-stress) conditions in prior studies. Given that stress is a pivotal vulnerability factor for depression, these results offer insight to better understand the etiology of this

  12. Differentiation of viable and nonviable myocardium after acute reperfusion using serial thallium-201 imaging

    SciTech Connect

    Okada, R.D.; Boucher, C.A.

    1987-02-01

    This study was performed to determine if differences in regional myocardial thallium clearance rates could differentiate salvaged from nonsalvaged myocardium after reperfusion. Twenty-one dogs underwent 2 hours of left anterior descending coronary artery ligation followed by reperfusion. Thallium was administered 5 minutes later and serial images were acquired over 3 hours. Of the 21 dogs, 15 had infarctions of which nine had initially reduced anterior wall thallium activity (group 1) and six had normal or increased activity (group 2). Six dogs did not have an infarction (group 3). All group 1 dogs demonstrated reduced clearance rates in the anterior wall (T1/2 = 15.0 +/- 4.7 hours, SD) compared to the posterior wall (T1/2 = 9.0 +/- 4.4 hours; p less than 0.001). Group 2 dogs demonstrated increased clearance rates in the anterior wall (T1/2 = 5.7 +/- 2.0 hours) compared to the posterior wall (T1/2 = 10.5 +/- 4.6 hours; p less than 0.001). Group 3 dogs demonstrated no difference in clearance rates. In conclusion, although thallium uptake is frequently reduced in nonsalvaged myocardium, tracer uptake can be normal or increased if perfusion has been completely restored. However, an increased clearance rate from the reperfused zone compared to the normal zone is a reliable indicator of nonsalvaged myocardium, despite normal initial thallium uptake.

  13. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial.

    PubMed

    Willekens, Christophe; Blanchet, Odile; Renneville, Aline; Cornillet-Lefebvre, Pascale; Pautas, Cécile; Guieze, Romain; Ifrah, Norbert; Dombret, Hervé; Jourdan, Eric; Preudhomme, Claude; Boissel, Nicolas

    2016-03-01

    In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558).

  14. Retinoid-dependent growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia cells. Expression and activation of caspases.

    PubMed

    Gianni, M; Ponzanelli, I; Mologni, L; Reichert, U; Rambaldi, A; Terao, M; Garattini, E

    2000-05-01

    In the NB4 model of acute promyelocytic leukemia (APL), ATRA, 9-cis retinoic acid (9-cis RA), the pan-RAR and RARalpha-selective agonists, TTNPB and AM580, induce growth inhibition, granulocytic differentiation and apoptosis. By contrast, two RXR agonists, a RARbeta agonist and an anti-AP1 retinoid have very limited activity, ATRA- and AM580-dependent effects are completely inhibited by RAR antagonistic blockade, while 9-cis RA-induced cell-growth-inhibition and apoptosis are equally inhibited by RAR and RXR antagonists. ATRA, 9-cis RA and AM580 cause upregulation of the mRNAs coding for pro-caspase-1, -7, -8, and -9, which, however, results in increased synthesis of only pro-caspase-1 and -7 proteins. These phenomena are associated with activation of pro-caspase-6, -7 and -8, cytochrome c release from the mitochondria, inversion of Bcl-2/Bax ratio and degradation of PML-RARalpha. Caspase activation is fundamental for retinoid-induced apoptosis, which is suppressed by the caspase-inhibitor z-VAD.

  15. Differential diagnosis of acute rejection and chronic cyclosporine nephropathy after rat renal transplantation by detection of endothelial microparticles (EMP).

    PubMed

    Cui, Jiewei; Yang, Jing; Cao, Weike; Sun, Yi

    2010-12-01

    Endothelial microparticles (EMP) are small vesicles smaller than 1.0μm, released from endothelial cells (EC) during their activation and (or) apoptosis. The assay of the level of elevated EMP is a new approach to evaluate the dysfunction of endothelial cell. EMP can be classified into several types according to their membrane molecular, and the levels of various types of EMP may be different. As the most cost-effective immunodepressant, cyclosporine A (CsA) has been used widely in organ transplantation. But its dose is hard to control, under-medication may cause the acute rejection (AR) and overdose may cause chronic cyclosporine nephropathy (CCN). The cyclosporine A (CsA) caused CCN and the AR caused renal injury after renal transplantation are both vascular diseases related with endothelial dysfunction, and up to now, there is still no effective method to distinguish the two kinds of diseases. Owing to distinct pathogenesis of the two kinds of vascular diseases, the level of each type of EMP originated from vascular endothelial cells may be different. We hypothesize that maybe we can distinguish them by detecting the different levels of some types of EMP which is also related with vascular disease, and we propose to prove our hypothesis through animal experiment. If our hypothesis is proved, it will be more helpful for clinicians to adjust the dose of CsA promptly according to the differential diagnosis of the two kinds of diseases.

  16. The extracts of Japanese willow tree species are effective forapoptotic desperation or differentiation of acute myeloid leukemia cells

    PubMed Central

    Fujita, Kounosuke; Nomura, Yuji; Sawajiri, Masahiko; Mohapatra, Pravat K.; El-Shemy, Hany A.; Nguyen, Nguyen T.; Hosokawa, Masashi; Miyashita, Kazuo; Maeda, Teruo; Saneoka, Hirofumi; Fujita, Shohei; Fujita, Takayuki

    2014-01-01

    Background: The antileukemic activity of hot water extract of plant parts of some Japanese willow tree species grown at different levels of nitrogen were examined. Materials and Methods: Water extracts of willow leaves were prepared for this studies in different level of nitrogen nutrition. Results: The extracts obtained from the leaves and stem exhibited anti-leukemic activities prominently. The crude hot water extracts of the young growing parts including apex, matured leaves and stem, killed the blasts of acute myeloid leukemia (AML) cells, (HL60 and NB4) after 48h incubation, however, such desperation was far less in the root extract. Similar to the plant parts, response of extracts obtained from different willow species was not identical; the proportion of dead cells relative to whole cells of the culture medium ranged from 21% to 93% among the species. Leaf extracts obtained from the responsive willow species decreased the live cell percentage and increased the dead cell percentage at higher level of nitrogen nutrition. The mode of desperation of leaf extract treated AML cells in such species appeared to be cell apoptosis as shown by binding with fluorescein isothiocyanate (FITC) -labeled Annexin V. Conclusion: Differentiation of alive AML cells continued unabated and apoptosis was poor when extract of an unresponsive species added to the culture medium. PMID:24914277

  17. Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting

    PubMed Central

    2011-01-01

    Introduction We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet-tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP) and clinical assessment (according to the modified Boston criteria) in differentiating heart failure (HF)-related acute dyspnea from pulmonary (chronic obstructive pulmonary disease (COPD)/asthma)-related acute dyspnea in the prehospital setting. Methods Our prospective study was performed at the Center for Emergency Medicine, Maribor, Slovenia, between July 2007 and April 2010. Two groups of patients were compared: a HF-related acute dyspnea group (n = 129) and a pulmonary (asthma/COPD)-related acute dyspnea group (n = 89). All patients underwent lung ultrasound examinations, along with basic laboratory testing, rapid NT-proBNP testing and chest X-rays. Results The ultrasound comet-tail sign has 100% sensitivity, 95% specificity, 100% negative predictive value (NPV) and 96% positive predictive value (PPV) for the diagnosis of HF. NT-proBNP (cutoff point 1,000 pg/mL) has 92% sensitivity, 89% specificity, 86% NPV and 90% PPV. The Boston modified criteria have 85% sensitivity, 86% specificity, 80% NPV and 90% PPV. In comparing the three methods, we found significant differences between ultrasound sign and (1) NT-proBNP (P < 0.05) and (2) Boston modified criteria (P < 0.05). The combination of ultrasound sign and NT-proBNP has 100% sensitivity, 100% specificity, 100% NPV and 100% PPV. With the use of ultrasound, we can exclude HF in patients with pulmonary-related dyspnea who have positive NT-proBNP (> 1,000 pg/mL) and a history of HF. Conclusions An ultrasound comet-tail sign alone or in combination with NT-proBNP has high diagnostic accuracy in differentiating acute HF-related from COPD/asthma-related causes of acute dyspnea in the prehospital emergency setting. Trial registration ClinicalTrials.gov NCT01235182. PMID:21492424

  18. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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 Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  19. NPM-RAR, not the RAR-NPM reciprocal t(5;17)(q35;q21) acute promyelocytic leukemia fusion protein, inhibits myeloid differentiation.

    PubMed

    Pollock, Sheri L; Rush, Elizabeth A; Redner, Robert L

    2014-06-01

    The t(5;17) variant of acute promyelocytic leukemia (APL) fuses the nucleophosmin (NPM) gene at 5q35 with the retinoic acid receptor alpha (RARA) at 17q12-22. We have previously shown that leukemic cells express both NPM-RAR and RAR- NPM reciprocal translocation products. In this study we investigated the potential role of both proteins in modulating myeloid differentiation. Expression of NPM-RAR inhibited vitamin D3/transforming growth factor β (TGFβ)-mediated differentiation of U937 cells by more than 50%. In contrast, RAR-NPM expression did not alter vitamin D3/TGFβ-induced differentiation of U937 clones. These results indicate that NPM-RAR, not RAR-NPM, is the prime mediator of myeloid differentiation arrest in t(5;17) APL.

  20. Minimal Reduplication

    ERIC Educational Resources Information Center

    Kirchner, Jesse Saba

    2010-01-01

    This dissertation introduces Minimal Reduplication, a new theory and framework within generative grammar for analyzing reduplication in human language. I argue that reduplication is an emergent property in multiple components of the grammar. In particular, reduplication occurs independently in the phonology and syntax components, and in both cases…

  1. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  2. Differential aspects of the disease and treatment of Thoracic Acute Aortic Dissection (TAAD)-the European experience.

    PubMed

    Pepper, John

    2016-07-01

    The management of patients with acute aortic dissection continues to be a challenge. It is an uncommon but lethal condition which continues to be under-diagnosed and under-treated. In this review, the term acute aortic syndrome is preferred in order to embrace the closely related pathologies of intramural hematoma (IMH) and penetrating aortic ulcer (PAU). PMID:27563549

  3. Differential aspects of the disease and treatment of Thoracic Acute Aortic Dissection (TAAD)—the European experience

    PubMed Central

    2016-01-01

    The management of patients with acute aortic dissection continues to be a challenge. It is an uncommon but lethal condition which continues to be under-diagnosed and under-treated. In this review, the term acute aortic syndrome is preferred in order to embrace the closely related pathologies of intramural hematoma (IMH) and penetrating aortic ulcer (PAU). PMID:27563549

  4. Minimal biofilm eradication concentration of antimicrobial agents against nontypeable Haemophilus influenzae isolated from middle ear fluids of intractable acute otitis media.

    PubMed

    Takei, Shin; Hotomi, Muneki; Yamanaka, Noboru

    2013-06-01

    Nontypeable Haemophilus influenzae (NTHi) makes the clinical course of acute otitis media (AOM) intractable by forming a biofilm that may hamper the clearance of the bacteria from middle ear cavity. In this study, we evaluated the minimum biofilm eradication concentration (MBEC) of antimicrobial agents against biofilm-forming NTHi strains. Twelve NTHi strains isolated from middle ear fluids of Japanese children with intractable AOM before antimicrobial treatment were evaluated for MBEC of fluoroquinolones in comparison with those of β-lactams and macrolides. AMPC and CDTR required much higher concentration, i.e., high MBECs, to suppress the biofilm formation of NTHi. In contrast, fluoroquinolones followed by macrolides showed lower MBECs. MBEC would be a good parameter to infer the efficacies of antimicrobials against NTHi in biofilm.

  5. Minimal biofilm eradication concentration of antimicrobial agents against nontypeable Haemophilus influenzae isolated from middle ear fluids of intractable acute otitis media.

    PubMed

    Takei, Shin; Hotomi, Muneki; Yamanaka, Noboru

    2013-06-01

    Nontypeable Haemophilus influenzae (NTHi) makes the clinical course of acute otitis media (AOM) intractable by forming a biofilm that may hamper the clearance of the bacteria from middle ear cavity. In this study, we evaluated the minimum biofilm eradication concentration (MBEC) of antimicrobial agents against biofilm-forming NTHi strains. Twelve NTHi strains isolated from middle ear fluids of Japanese children with intractable AOM before antimicrobial treatment were evaluated for MBEC of fluoroquinolones in comparison with those of β-lactams and macrolides. AMPC and CDTR required much higher concentration, i.e., high MBECs, to suppress the biofilm formation of NTHi. In contrast, fluoroquinolones followed by macrolides showed lower MBECs. MBEC would be a good parameter to infer the efficacies of antimicrobials against NTHi in biofilm. PMID:23549738

  6. Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database.

    PubMed

    Manzotti, Gloria; Parenti, Sandra; Ferrari-Amorotti, Giovanna; Soliera, Angela Rachele; Cattelani, Sara; Montanari, Monica; Cavalli, Daniel; Ertel, Adam; Grande, Alexis; Calabretta, Bruno

    2015-01-01

    The transcription factor C/EBPα is required for granulocytic differentiation of normal myeloid progenitors and is frequently inactivated in acute myeloid leukemia (AML) cells. Ectopic expression of C/EBPα in AML cells suppresses proliferation and induces differentiation suggesting that restoring C/EBPα expression/activity in AML cells could be therapeutically useful. Unfortunately, current approaches of gene or protein delivery in leukemic cells are unsatisfactory. However, "drug repurposing" is becoming a very attractive strategy to identify potential new uses for existing drugs. In this study, we assessed the biological effects of candidate C/EBPα-mimetics identified by interrogation of the Connectivity Map database. We found that amantadine, an antiviral and anti-Parkinson agent, induced a monocyte-macrophage-like differentiation of HL60, U937, Kasumi-1 myeloid leukemia cell lines, as indicated by morphology and differentiation antigen expression, when used in combination with suboptimal concentration of all trans retinoic acid (ATRA) or Vit D3. The effect of amantadine depends, in part, on increased activity of the vitamin D receptor (VDR), since it induced VDR expression and amantadine-dependent monocyte-macrophage differentiation of HL60 cells was blocked by expression of dominant-negative VDR. These results reveal a new function for amantadine and support the concept that screening of the Connectivity Map database can identify small molecules that mimic the effect of transcription factors required for myelo-monocytic differentiation.

  7. A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells

    PubMed Central

    Song, Guanhua; Shi, Lulu; Guo, Yuqi; Yu, Linchang; Wang, Lin; Zhang, Xiaoyu; Li, Lianlian; Han, Yang; Ren, Xia; Guo, Qiang; Bi, Kehong; Jiang, Guosheng

    2016-01-01

    All-trans retinoic acid (ATRA) treatment yields cure rates > 80% through proteasomal degradation of the PML-RARα fusion protein that typically promotes acute promyelocytic leukemia (APL). However, recent evidence indicates that ATRA can also promote differentiation of leukemia cells that are PML-RARα negative, such as HL-60 cells. Here, gene expression profiling of HL-60 cells was used to investigate the alternative mechanism of impaired differentiation in APL. The expression of peptidylarginine deiminase 4 (PADI4), encoding PAD4, a protein that post-translationally converts arginine into citrulline, was restored during ATRA-induced differentiation. We further identified that hypermethylation in the PADI4 promoter was associated with its transcriptional repression in HL-60 and NB4 (PML-RARα positive) cells. Functionally, PAD4 translocated into the nucleus upon ATRA exposure and promoted ATRA-mediated differentiation. Mechanistic studies using RNAi knockdown or electroporation-mediated delivery of PADI4, along with chromatin immunoprecipitation, helped identify PU.1 as an indirect target and SOX4 as a direct target of PAD4 regulation. Indeed, PAD4 regulates SOX4-mediated PU.1 expression, and thereby the differentiation process, in a SOX4-dependent manner. Taken together, our results highlight an association between PAD4 and DNA hypermethylation in APL and demonstrate that targeting PAD4 or regulating its downstream effectors may be a promising strategy to control differentiation in the clinic. PMID:26673819

  8. The microRNA-26a target E2F7 sustains cell proliferation and inhibits monocytic differentiation of acute myeloid leukemia cells.

    PubMed

    Salvatori, B; Iosue, I; Mangiavacchi, A; Loddo, G; Padula, F; Chiaretti, S; Peragine, N; Bozzoni, I; Fazi, F; Fatica, A

    2012-01-01

    Blocks in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia (AML) cells. 1,25-Dihydroxy-vitamin D3 (VitD3) arrests proliferation of AML cells and induces their differentiation into mature monocytes. In a previous study, we showed that miR-26a was induced upon VitD3-mediated monocytic differentiation. Here, we identify E2F7 as a novel target of miR-26a. We show that E2F7 significantly promotes cell cycle progression and inhibits monocytic differentiation of AML cells. We also demonstrate that E2F7 binds the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (cyclin-dependent kinase inhibitor 1A) promoter repressing its expression. Moreover, interfering with E2F7 expression results in inhibition of c-Myc (v-myc myelocytomatosis viral oncogene homolog) transcriptional activity. This leads to the downregulation of c-Myc transcriptional target miR-17-92 cluster, whose expression has a well-defined role in contributing to block monocytic differentiation and sustain AML cell proliferation. Finally, we show that the expression of E2F7 is upregulated in primary blasts from AML patients. Thus, these findings indicate that the newly identified miR-26a target E2F7 might have an important role in monocytic differentiation and leukemogenesis.

  9. Differential expression of heat shock transcription factors and heat shock proteins after acute and chronic heat stress in laying chickens (Gallus gallus).

    PubMed

    Xie, Jingjing; Tang, Li; Lu, Lin; Zhang, Liyang; Xi, Lin; Liu, Hsiao-Ching; Odle, Jack; Luo, Xugang

    2014-01-01

    Heat stress due to high environmental temperature negatively influences animal performances. To better understand the biological impact of heat stress, laying broiler breeder chickens were subjected either to acute (step-wisely increasing temperature from 21 to 35°C within 24 hours) or chronic (32°C for 8 weeks) high temperature exposure. High temperature challenges significantly elevated body temperature of experimental birds (P<0.05). However, oxidation status of lipid and protein and expression of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) 70 and 90 were differently affected by acute and chronic treatment. Tissue-specific responses to thermal challenge were also found among heart, liver and muscle. In the heart, acute heat challenge affected lipid oxidation (P = 0.05) and gene expression of all 4 HSF gene expression was upregulated (P<0.05). During chronic heat treatment, the HSP 70 mRNA level was increased (P<0.05) and HSP 90 mRNA (P<0.05) was decreased. In the liver, oxidation of protein was alleviated during acute heat challenge (P<0.05), however, gene expression HSF2, 3 and 4 and HSP 70 were highly induced (P<0.05). HSP90 expression was increased by chronic thermal treatment (P<0.05). In the muscle, both types of heat stress increased protein oxidation, but HSFs and HSPs gene expression remained unaltered. Only tendencies to increase were observed in HSP 70 (P = 0.052) and 90 (P = 0.054) gene expression after acute heat stress. The differential expressions of HSF and HSP genes in different tissues of laying broiler breeder chickens suggested that anti-heat stress mechanisms might be provoked more profoundly in the heart, by which the muscle was least protected during heat stress. In addition to HSP, HSFs gene expression could be used as a marker during acute heat stress.

  10. Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

    PubMed Central

    Wernly, Bernhard; Lichtenauer, Michael; Franz, Marcus; Kabisch, Bjoern; Muessig, Johanna; Masyuk, Maryna; Kelm, Malte; Hoppe, Uta C.; Jung, Christian

    2016-01-01

    Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient

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

    ClinicalTrials.gov

    2015-04-27

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

  12. Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy

    PubMed Central

    Linhares-Lacerda, Leandra; Palu, Cintia Cristina; Ribeiro-Alves, Marcelo; Paredes, Bruno Diaz; Morrot, Alexandre; Garcia-Silva, Maria Rosa; Cayota, Alfonso; Savino, Wilson

    2015-01-01

    A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease. PMID:26347748

  13. Acute radiation risk models

    NASA Astrophysics Data System (ADS)

    Smirnova, Olga

    Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

  14. Different profiles of acute stress disorder differentially predict posttraumatic stress disorder in a large sample of female victims of sexual trauma.

    PubMed

    Shevlin, Mark; Hyland, Philip; Elklit, Ask

    2014-12-01

    This study aimed to test the dimensional structure of acute stress disorder (ASD). Latent profile analysis was conducted on scores from the Acute Stress Disorder Scale (Bryant, Moulds, & Guthrie, 2000) using a large sample of female victims of sexual trauma. Four distinct classes were found. Two of the classes represented high and low levels of ASD, and the high ASD class was associated with a high probability of subsequent posttraumatic stress disorder (PTSD). There were 2 intermediate classes that were differentiated by the number of arousal symptoms, and the class with high levels of arousal symptoms had a higher risk of PTSD. The results suggested that ASD is best described by qualitatively and quantitatively differing subgroups in this sample, whereas previous research has assumed ASD to be dimensional. This may explain the limited success of using ASD to predict subsequent PTSD. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  15. Minimal residual disease after allogeneic stem cell transplant: a comparison among multiparametric flow cytometry, Wilms tumor 1 expression and chimerism status (Complete chimerism versus Low Level Mixed Chimerism) in acute leukemia.

    PubMed

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; Savino, Lucia; Fontana, Andrea; Pellegrini, Fabio; Greco, Michele Mario; Merla, Emanuela; Quarta, Gianni; Loseto, Giacomo; Capalbo, Silvana; Palumbo, Gaetano; Cascavilla, Nicola

    2013-12-01

    Relapse represents the main cause of treatment failure after allogeneic stem cell transplant (allo-SCT). The detection of minimal residual disease (MRD) by multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular analysis may be critical to prevent relapse. Therefore, we assessed the overall agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated the impact of MRD obtained from the three methods on patient outcome. Sixty-seven fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML], seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo-SCT were investigated at different time points. A moderate agreement was found among the three techniques investigated. A higher concordance between positive results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p = 0.090) was detected among LL-MC rather than CC samples. Relapse-free survival (RFS) and overall survival (OS) were found to be higher in MRD negative patients than in MRD positive patients analyzed with MFC and WT1. Our results discourage the use of low autologous signals as the only marker of MRD, and suggest the usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ-PCR) in stratifying patients with respect to risk of relapse.

  16. Perspectives of Differentiation Therapies of Acute Myeloid Leukemia: The Search for the Molecular Basis of Patients’ Variable Responses to 1,25-Dihydroxyvitamin D and Vitamin D Analogs

    PubMed Central

    Marchwicka, Aleksandra; Cebrat, Małgorzata; Sampath, Preetha; Śnieżewski, Łukasz; Marcinkowska, Ewa

    2014-01-01

    The concept of differentiation therapy of cancer is ~40 years old. Despite many encouraging results obtained in laboratories, both in vitro and in vivo studies, the only really successful clinical application of differentiation therapy was all-trans-retinoic acid (ATRA)-based therapy of acute promyelocytic leukemia (APL). ATRA, which induces granulocytic differentiation of APL leukemic blasts, has revolutionized the therapy of this disease by converting it from a fatal to a curable one. However, ATRA does not work for other acute myeloid leukemias (AMLs). Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing monocytic differentiation of leukemic cells, the idea of treating other AMLs with vitamin D analogs (VDAs) was widely accepted. Also, some types of solid cancers responded to in vitro applied VDAs, and hence it was postulated that VDAs can be used in many clinical applications. However, early clinical trials in which cancer patients were treated either with 1,25D or with VDAs, did not lead to conclusive results. In order to search for a molecular basis of such unpredictable responses of AML patients toward VDAs, we performed ex vivo experiments using patient’s blast cells. Experiments were also performed using 1,25D-responsive and 1,25D-non-responsive cell lines, to study their mechanisms of resistance toward 1,25D-induced differentiation. We found that one of the possible reasons might be due to a very low expression level of vitamin D receptor (VDR) mRNA in resistant cells, which can be increased by exposing the cells to ATRA. Our considerations concerning the molecular mechanism behind the low VDR expression and its regulation by ATRA are reported in this paper. PMID:24904835

  17. Role of M2 Muscarinic Receptor in the Airway Response to Methacholine of Mice Selected for Minimal or Maximal Acute Inflammatory Response

    PubMed Central

    Castro, Juciane Maria de Andrade; Resende, Rodrigo R.; Florsheim, Esther; Albuquerque, Layra Lucy; Lino-dos-Santos-Franco, Adriana; Gomes, Eliane; Tavares de Lima, Wothan; de Franco, Marcelo; Ribeiro, Orlando Garcia

    2013-01-01

    Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh), which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic) and allergen-induced (extrinsic) airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax) or minimally (AIRmin) to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation. PMID:23691511

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

    PubMed

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

    2016-02-01

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

  19. Differential effects of acute and repeated stress on hippocampus and amygdala inputs to the nucleus accumbens shell

    PubMed Central

    Gill, Kathryn M.; Grace, Anthony A.

    2013-01-01

    The basolateral amygdala (BLA) and ventral subiculum (vSub) of the hippocampus convey emotion and context information, respectively, to the nucleus accumbens (NAc). Using in vivo extracellular recordings from NAc neurons, we examined how acute and repeated restraint stress alters the plasticity of the vSub and BLA afferent pathways. High frequency (HFS) and low frequency (LFS) stimulation was applied to the vSub to assess the impact on NAc responses to vSub and BLA inputs. In addition, iontophoretic application of the D2-antagonist sulpiride was used to explore the role of dopamine in the NAc in mediating the effects of stress on plasticity. Acute and repeated restraint caused disparate effects on BLA- and vSub-evoked responses in the NAc. Following repeated restraint, but not after acute restraint, HFS of the vSub failed to potentiate the vSub-NAc pathway while instead promoting a long lasting reduction of the BLA-NAc pathway, and these effects were independent of D2-receptor activity. In contrast, LFS to the vSub pathway after acute restraint resulted in potentiation in the vSub-NAc pathway while BLA-evoked responses were unchanged. When sulpiride was applied prior to LFS of the vSub after acute stress, there was a pronounced decrease in vSub-evoked responses similar to control animals. This work provides new insight into the impact of acute and repeated stress on the integration of context and emotion inputs in the nucleus accumbens. These data support a model of stress whereby the hippocampus is inappropriately activated and dominates the information processing within this circuit via a dopaminergic mechanism after acute bouts of stress. PMID:23745764

  20. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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 Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Minimal cosmography

    NASA Astrophysics Data System (ADS)

    Piazza, Federico; Schücker, Thomas

    2016-04-01

    The minimal requirement for cosmography—a non-dynamical description of the universe—is a prescription for calculating null geodesics, and time-like geodesics as a function of their proper time. In this paper, we consider the most general linear connection compatible with homogeneity and isotropy, but not necessarily with a metric. A light-cone structure is assigned by choosing a set of geodesics representing light rays. This defines a "scale factor" and a local notion of distance, as that travelled by light in a given proper time interval. We find that the velocities and relativistic energies of free-falling bodies decrease in time as a consequence of cosmic expansion, but at a rate that can be different than that dictated by the usual metric framework. By extrapolating this behavior to photons' redshift, we find that the latter is in principle independent of the "scale factor". Interestingly, redshift-distance relations and other standard geometric observables are modified in this extended framework, in a way that could be experimentally tested. An extremely tight constraint on the model, however, is represented by the blackbody-ness of the cosmic microwave background. Finally, as a check, we also consider the effects of a non-metric connection in a different set-up, namely, that of a static, spherically symmetric spacetime.

  2. Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

    PubMed Central

    Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

    2014-01-01

    Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

  3. Usefulness of MRI to differentiate between temporary and long-term coronary artery occlusion in a minimally invasive model of experimental myocardial infarction.

    PubMed

    Abegunewardene, Nico; Vosseler, Markus; Gori, Tommaso; Hoffmann, Nico; Schmidt, Kai-Helge; Becker, Dietmar; Kreitner, Karl-Friedrich; Petersen, Steffen E; Schreiber, Laura M; Horstick, Georg; Münzel, Thomas

    2009-09-01

    The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 +/- 4.4%; p = 0.008) and group 2 (9.4 +/- 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 +/- 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 +/- 0.3, 5.9 +/- 0.7, and 6.1 +/- 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 +/- 2.1%) compared to group 1 (5.3 +/- 5.4%; p = 0.003) and group 2 (9.7 +/- 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development. PMID:19472001

  4. Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction

    SciTech Connect

    Abegunewardene, Nico Vosseler, Markus; Gori, Tommaso; Hoffmann, Nico; Schmidt, Kai-Helge; Becker, Dietmar; Kreitner, Karl-Friedrich; Petersen, Steffen E.; Schreiber, Laura M.; Horstick, Georg; Muenzel, Thomas

    2009-09-15

    The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 {+-} 4.4%; p = 0.008) and group 2 (9.4 {+-} 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 {+-} 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 {+-} 0.3, 5.9 {+-} 0.7, and 6.1 {+-} 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 {+-} 2.1%) compared to group 1 (5.3 {+-} 5.4%; p = 0.003) and group 2 (9.7 {+-} 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.

  5. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    PubMed

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol.

  6. Annotation of Differential Gene Expression in Small Yellow Follicles of a Broiler-Type Strain of Taiwan Country Chickens in Response to Acute Heat Stress

    PubMed Central

    Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan

    2015-01-01

    This study investigated global gene expression in the small yellow follicles (6–8 mm diameter) of broiler-type B strain Taiwan country chickens (TCCs) in response to acute heat stress. Twelve 30-wk-old TCC hens were divided into four groups: control hens maintained at 25°C and hens subjected to 38°C acute heat stress for 2 h without recovery (H2R0), with 2-h recovery (H2R2), and with 6-h recovery (H2R6). Small yellow follicles were collected for RNA isolation and microarray analysis at the end of each time point. Results showed that 69, 51, and 76 genes were upregulated and 58, 15, 56 genes were downregulated after heat treatment of H2R0, H2R2, and H2R6, respectively, using a cutoff value of two-fold or higher. Gene ontology analysis revealed that these differentially expressed genes are associated with the biological processes of cell communication, developmental process, protein metabolic process, immune system process, and response to stimuli. Upregulation of heat shock protein 25, interleukin 6, metallopeptidase 1, and metalloproteinase 13, and downregulation of type II alpha 1 collagen, discoidin domain receptor tyrosine kinase 2, and Kruppel-like factor 2 suggested that acute heat stress induces proteolytic disintegration of the structural matrix and inflamed damage and adaptive responses of gene expression in the follicle cells. These suggestions were validated through gene expression, using quantitative real-time polymerase chain reaction. Functional annotation clarified that interleukin 6-related pathways play a critical role in regulating acute heat stress responses in the small yellow follicles of TCC hens. PMID:26587838

  7. Annotation of Differential Gene Expression in Small Yellow Follicles of a Broiler-Type Strain of Taiwan Country Chickens in Response to Acute Heat Stress.

    PubMed

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

    2015-01-01

    This study investigated global gene expression in the small yellow follicles (6-8 mm diameter) of broiler-type B strain Taiwan country chickens (TCCs) in response to acute heat stress. Twelve 30-wk-old TCC hens were divided into four groups: control hens maintained at 25°C and hens subjected to 38°C acute heat stress for 2 h without recovery (H2R0), with 2-h recovery (H2R2), and with 6-h recovery (H2R6). Small yellow follicles were collected for RNA isolation and microarray analysis at the end of each time point. Results showed that 69, 51, and 76 genes were upregulated and 58, 15, 56 genes were downregulated after heat treatment of H2R0, H2R2, and H2R6, respectively, using a cutoff value of two-fold or higher. Gene ontology analysis revealed that these differentially expressed genes are associated with the biological processes of cell communication, developmental process, protein metabolic process, immune system process, and response to stimuli. Upregulation of heat shock protein 25, interleukin 6, metallopeptidase 1, and metalloproteinase 13, and downregulation of type II alpha 1 collagen, discoidin domain receptor tyrosine kinase 2, and Kruppel-like factor 2 suggested that acute heat stress induces proteolytic disintegration of the structural matrix and inflamed damage and adaptive responses of gene expression in the follicle cells. These suggestions were validated through gene expression, using quantitative real-time polymerase chain reaction. Functional annotation clarified that interleukin 6-related pathways play a critical role in regulating acute heat stress responses in the small yellow follicles of TCC hens. PMID:26587838

  8. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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 Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  9. Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus

    PubMed Central

    Pusalkar, Madhavi; Ghosh, Shreya; Jaggar, Minal; Husain, Basma Fatima Anwar; Galande, Sanjeev

    2016-01-01

    Background: Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. Methods: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure. Results: Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure. Conclusions: Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure. PMID

  10. Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia.

    PubMed

    Sokalski, Kristen M; Li, Stephen K H; Welch, Ian; Cadieux-Pitre, Heather-Anne T; Gruca, Marek R; DeKoter, Rodney P

    2011-09-01

    The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors. We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage.

  11. Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols.

    PubMed

    Breccia, Massimo; Mazzarella, Luca; Bagnardi, Vincenzo; Disalvatore, Davide; Loglisci, Giuseppina; Cimino, Giuseppe; Testi, Anna Maria; Avvisati, Giuseppe; Petti, Maria Concetta; Minotti, Clara; Latagliata, Roberto; Foà, Robin; Pelicci, Pier Giuseppe; Lo-Coco, Francesco

    2012-01-01

    We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI ≥ 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio = 7.24; 95% CI, 1.50-34; P = .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P = .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio = 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P = .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols.

  12. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients.

  13. Pre-transplant achievement of negativity in minimal residual disease and French-American-British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome.

  14. Minimal residual disease in early phase of chemotherapy reflects poor outcome in children with acute lymphoblastic leukemia--a retrospective study by the Children's Cancer and Leukemia Study Group in Japan.

    PubMed

    Okamoto, Tomomi; Yokota, Shouhei; Katano, Naoyuki; Seriu, Taku; Nakao, Makoto; Taniwaki, Masafumi; Watanabe, Arata; Asami, Keiko; Kikuta, Atsushi; Koizumi, Shoichi; Kawakami, Tetsuo; Ohta, Shigeru; Miyake, Munenori; Watanabe, Tsutomu; Iwai, Asayuki; Kamitamari, Akira; Ijichi, Osamu; Hyakuna, Nobuyuki; Mimaya, Junichi; Fujimoto, Takeo; Tsurusawa, Masahito

    2002-05-01

    We analyzed the minimal residual disease (MRD) in 50 children with acute lymphoblastic leukemia (ALL) by amplifying the clonally rearranged T-cell receptor (TCR) gamma/delta chain and/or immunoglobulin (Ig) kappa chain gene using the allele-specific-PCR method. All children were treated according to the protocols of the Children's Cancer and Leukemia Study Group of Japan (CCLSG). The patients were stratified into four risk-groups according to the leukocyte count and age at diagnosis. We prospectively sampled the patients' bone marrow at 1 month (point 1) and 3 months (point 2) after the initiation of chemotherapy and quantitated the MRD retrospectively. The results of MRD were closely related with the clinical outcome. The relapse rate of the patients MRD-positive at points 1 and 2 was 46% (6/13) and 86% (6/7), respectively, whereas those MRD-negative results at point 1 and 2 were 13% (3/13) and 3% (3/30), respectively. We found significant differences in the event-free survival between MRD-positive children and MRD-negative children like the reports, which have been made by BFM and EORTC groups. We conclude that MRD in an early phase of chemotherapy can be a good predictor of the prognosis of childhood ALL regardless of the protocol of chemotherapy or race.

  15. Differential modulation of antipredator defensive behavior in Swiss-Webster mice following acute or chronic administration of imipramine and fluoxetine.

    PubMed

    Griebel, G; Blanchard, D C; Agnes, R S; Blanchard, R J

    1995-07-01

    The Mouse Defense Test Battery (MDTB) has been designed to assess defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat. Primary measures taken before, during and after predator confrontation comprise escape attempts, predator assessment, defensive attack and flight. Previous reports from this laboratory have shown that the panic-promoting drug yohimbine potentiated flight behavior, while long-term treatment with the panicolytic agent alprazolam reduced this response. In order to evaluate further the possibility that the MDTB may represent an effective animal model of panic attacks, the present study investigated the behavioral effect of imipramine and fluoxetine, two serotonin reuptake inhibitors (SRIs) known to alleviate panic symptoms when given on a repeated basis. Both drugs were administered acutely and chronically (one daily IP injection for 21 days) at 5, 10 and 15 mg/kg. Our results showed that a single dose of imipramine or fluoxetine strongly potentiated flight reactions in response to an approaching predator and increased defensive attack toward the rat. This was in contrast to chronic treatment with each drug which dramatically decreased flight responses and defensive attack behaviors. In addition, long-term administration with both SRIs produced a reliable attenuation of predator assessment activities. Taken together, these findings suggest an acute anxiogenic-like effect of imipramine and fluoxetine followed by a fear/anxiety reducing effect after repeated administrations. These results support clinical observations revealing an acute anxiogenic effect of SRIs followed by an anxiolytic and/or panicolytic effect after chronic use, and support previous results suggesting that the MDTB may be useful for the investigation of panic-modulating agents.

  16. Eating disorders should be considered in the differential diagnosis of patients presenting with acute kidney injury and electrolyte derangement

    PubMed Central

    Talbot, Ben Edward Michael; Lawman, Sarah H A

    2014-01-01

    We present a case of a 40-year-old woman with a history of ongoing anorexia nervosa and bulimia nervosa who has required multiple admissions to hospital for management of acute kidney injury (AKI) and electrolyte derangement. This case is of interest as recent studies have highlighted the significant prevalence of disordered eating and the major public health implications this may have. We discuss the unusual finding of hypercalcaemia in this case and address the investigation and management of AKI and electrolyte disturbance in a patient with anorexia and bulimia. PMID:24654247

  17. Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

    PubMed

    Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

    2011-11-01

    The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

  18. Adhesion- and Degranulation-Promoting Adapter Protein Promotes CD8 T Cell Differentiation and Resident Memory Formation and Function during an Acute Infection.

    PubMed

    Fiege, Jessica K; Beura, Lalit K; Burbach, Brandon J; Shimizu, Yoji

    2016-09-15

    During acute infections, naive Ag-specific CD8 T cells are activated and differentiate into effector T cells, most of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion- and degranulation-promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naive Ag-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after Listeria monocytogenes or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response. However, reduced numbers of ADAP-deficient CD8 T cells were present in the spleen after the peak of the response. ADAP deficiency resulted in a greater frequency of CD127(+) CD8 memory precursors in secondary lymphoid organs during the contraction phase. Reduced numbers of ADAP-deficient killer cell lectin-like receptor G1(-) CD8 resident memory T (TRM) cell precursors were present in a variety of nonlymphoid tissues at the peak of the immune response, and consequently the total numbers of ADAP-deficient TRM cells were reduced at memory time points. TRM cells that did form in the absence of ADAP were defective in effector molecule expression. ADAP-deficient TRM cells exhibited impaired effector function after Ag rechallenge, correlating with defects in their ability to form T cell-APC conjugates. However, ADAP-deficient TRM cells responded to TGF-β signals and recruited circulating memory CD8 T cells. Thus, ADAP regulates CD8 T cell differentiation events following acute pathogen challenge that are critical for the formation and selected functions of TRM cells in nonlymphoid tissues. PMID:27521337

  19. Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression.

    PubMed

    Garssen, J; van Steeg, H; de Gruijl, F; de Boer, J; van der Horst, G T; van Kranen, H; van Loveren, H; van Dijk, M; Fluitman, A; Weeda, G; Hoeijmakers, J H

    2000-06-15

    Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression. PMID:10843671

  20. The evaluation of acute pain in individuals with cognitive impairment: a differential effect of the level of impairment.

    PubMed

    Defrin, Ruth; Lotan, Meir; Pick, Chaim G

    2006-10-01

    The present study investigated whether the level of cognitive impairment (CI) affects acute pain behavior and how it is manifested. Participants were 159 individuals (mean age 42+/-12), 121 with CI (divided into four groups according to the level of CI: mild, moderate, severe, profound) and 38 with normal cognition (controls). The behavior of the participants before and during acute pain (influenza vaccination) was coded by two raters with the Facial Action Coding System (FACS - scores facial reactions to pain) and the Non-Communicating Children's Pain Checklist (NCCPC-R - scores both facial and general body reactions). Individuals with severe-profound CI exhibited elevated FACS and NCCPC-R values at baseline compared with all other groups (p<0.01). Both FACS and NCCPC-R scores of individuals with mild-moderate CI and controls increased significantly during vaccination (p<0.001). In contrast, individuals with severe-profound CI exhibited high rates of "freezing reaction" (stillness) during vaccination, manifested mainly in the face and therefore resulting in elevation of only NCCPC-R scores but not of FACS's. The results suggest that the level of CI affects baseline as well as pain behavior and it is therefore necessary to choose an appropriate behavioral tool to measure pain in these individuals accordingly. For example, tools based on facial reactions alone might provide the false impression that individuals with severe-profound CI are insensitive to pain (due to freezing).

  1. Acute kidney injury with hypoxic respiratory failure

    PubMed Central

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diagnosis. He was extubated after 2 days of mechanical ventilation and after pulse dose steroids. His lung biopsy showed pulmonary capillaritis. Our case describes a patient with clinically appearing renopulmonary syndrome, but found to have pulmonary capillaritis, a rare form of lung disease that may also cause acute kidney injury. PMID:25246473

  2. Acute Flaccid Paralysis and Its Differential Diagnosis in in Kurdistan Province, Western Iran; an 11-Year Surveillance

    PubMed Central

    Soltani, Jafar; Esmailnasab, Nader; Roshani, Daem; Karimi, Mohamad; Amjadi, Mohamad-Jamil

    2014-01-01

    Abstract Objective The surveillance of acute flaccid paralysis (AFP) is a key strategy for monitoring the progress of poliomyelitis eradication and is a sensitive measure for detecting potential cases of poliomyelitis and poliovirus infection. This study was conducted to describe the characteristics of patients reported with AFP, and to evaluate the performance of the surveillance system in Kurdistan province, western Iran, using indicators recommended by the World Health Organization (WHO). Methods This observational study was conducted from January 2000 to December 2010 at the Kurdistan Center for Disease Control and the Department of Pediatrics. All children who fulfilled the WHO definition for AFP were included in our study. The stool samples of all the children were sent for poliovirus isolation. All the patients were evaluated for 60 days after the onset of symptoms to identify the signs of residual weakness. Findings One-hundred thirty nine children aged <15 years were reported to the Center for Diseases Control with AFP. In 138 (99%) stool samples no poliovirus was isolated. None of the patients was diagnosed as having acute poliomyelitis or polio-compatible paralysis. Guillain-Barré syndrome was the most frequent final diagnosis (79 cases) followed by Transverse Myelitis (7 cases) and Encephalitis (6 cases). By detecting 1.3 to 3.6 (mean 3.2) AFP cases per 100 000 population in Kurdistan during the study period, we achieved the WHO target for AFP surveillance. All performance indicators but one consistently met the WHO requirements and therefore demonstrated the effectiveness of the AFP surveillance program in Kurdistan. Conclusion The effective surveillance system in Kurdistan and its evaluation may serve as a model for the surveillance of other infectious diseases. PMID:25535530

  3. Treadmill exercise training and estradiol differentially modulate hypothalamic-pituitary-adrenal cortical responses to acute running and immobilization.

    PubMed

    White-Welkley, J E; Bunnell, B N; Mougey, E H; Meyerhoff, J L; Dishman, R K

    1995-03-01

    It is generally believed that physical fitness promotes health by attenuating responsiveness to other stressors. The experimental evidence for this belief is limited and does not extend to interactions between the hypothalamic-pituitary-adrenal cortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We tested the hypothesis that treadmill exercise training would lead to an estrogen-dependent hyporesponsiveness of the HPA axis that would generalize to immobilization stress. Ovariectomized female Sprague-Dawley rats (N = 74) that had been treadmill trained (TT) or sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of acute treadmill running or immobilization. Plasma (adrenocorticotrophin) (ACTH), (corticosterone) (B) and (prolactin) (PRL) were determined from trunk blood by radioimmunoassay and compared in a 2 group (TT vs. sedentary)-by-2 treatment (Eb vs. oil)-by-2 acute stressor (running vs. immobilization) design. Home-cage (HC) animals (N = 24) provided baseline hormone levels. ACTH and B levels were elevated after stressors in animals treated with either Eb or oil compared to HC, but increases in PRL after stressors were dependent on Eb. Treadmill exercise training led to an attenuation of ACTH and prolactin to running, but the attenuation did not generalize to immobilization. In contrast, treadmill exercise training led to a hyperresponsiveness of ACTH. Treadmill training did not modulate prolactin responses to immobilization. The modulating effects of the estradiol treatment are consistent with an interaction of the HPA and HPG axes in response to stress.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. A Double Negative Loop Comprising ETV6/RUNX1 and MIR181A1 Contributes to Differentiation Block in t(12;21)-Positive Acute Lymphoblastic Leukemia

    PubMed Central

    Pai, Chen-Hsueh; Chen, Hsuan-Yu; Yu, Sung-Liang; Lin, Chien-Yu; Hu, Chung-Yi; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Lin, Shu-Rung; Lin, Shu-Wha

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) with t(12;21), which results in expression of the ETV6/RUNX1 fusion gene, is the most common chromosomal lesion in precursor-B (pre-B) ALL. We identified 17 microRNAs that were downregulated in ETV6/RUNX1+ compared with ETV6/RUNX1− clinical samples. Among these microRNAs, miR-181a-1 was the most significantly reduced (by ~75%; P < 0.001). Using chromatin immunoprecipitation, we demonstrated that ETV6/RUNX1 directly binds the regulatory region of MIR181A1, and knockdown of ETV6/RUNX1 increased miR-181a-1 level. We further showed that miR-181a (functional counterpart of miR-181a-1) could target ETV6/RUNX1 and cause a reduction in the level of the oncoprotein ETV6/RUNX1, cell growth arrest, an increase in apoptosis, and induction of cell differentiation in ETV6/RUNX1+ cell line. Moreover, ectopic expression of miR-181a also resulted in decreased CD10 hyperexpression in ETV6/RUNX1+ primary patient samples. Taken together, our results demonstrate that MIR181A1 and ETV6/RUNX1 regulate each other, and we propose that a double negative loop involving MIR181A1 and ETV6/RUNX1 may contribute to ETV6/RUNX1-driven arrest of differentiation in pre-B ALL. PMID:26580398

  5. Design and stereoselective synthesis of retinoids with ferrocene or N-butylcarbazole pharmacophores that induce post-differentiation apoptosis in acute promyelocytic leukemia cells.

    PubMed

    Ivanova, Diana; Gronemeyer, Hinrich; de Lera, Angel R

    2011-08-01

    New ferrocene and N-alkylcarbazole retinoids were designed and synthesized stereoselectively in good yields. A number of these synthesized ligands, in particular 2, 3, and 11, were found to exhibit a high RARα activation potential and to effectively induce post-differentiation apoptosis in NB4 acute promyelocytic leukemia (APL) cells. Increasing the length of the side chain attached to the heterocycle of the carbazole arotinoids creates new opportunities for altered compound catabolism and for fine-tuning of the apoptosis-inducing potential of the ligand. In the carbazole series of new retinoids, maximal activity was established for N-butylcarbazole analogue 11 in all assays (i.e., RARα activation, differentiation induction, and apoptosis induction). Study of the mechanism of apoptosis revealed an activation of initiator caspases-8 and -9, followed by efficient cleavage of effector caspase-3 on day 6 of treatment. Subsequent induction of a caspase cascade in NB4 cells triggered ultimate leukemic cell death. The selected ligands 2, 3, and 11 may provide alternate options for the treatment of APL in cases of life-threatening ATRA syndrome, resistance, and high toxicity to conventionally used retinoids.

  6. Survival, Differentiation, and Migration of High-Purity Mouse Embryonic Stem Cell-derived Progenitor Motor Neurons in Fibrin Scaffolds after Sub-Acute Spinal Cord Injury.

    PubMed

    McCreedy, D A; Wilems, T S; Xu, H; Butts, J C; Brown, C R; Smith, A W; Sakiyama-Elbert, S E

    2014-11-01

    Embryonic stem (ES) cells can be differentiated into many neural cell types that hold great potential as cell replacement therapies following spinal cord injury (SCI). Coupling stem cell transplantation with biomaterial scaffolds can produce a unified combination therapy with several potential advantages including enhanced cell survival, greater transplant retention, reduced scarring, and improved integration at the transplant/host interface. Undesired cell types, however, are commonly present in ES-cell derived cultures due to the limited efficiency of most ES cell induction protocols. Heterogeneous cell populations can confound the interaction between the biomaterial and specific neural populations leading to undesired outcomes. In particular, biomaterials scaffolds may enhance tumor formation by promoting survival and proliferation of undifferentiated ES cells that can persist after induction. Methods for purification of specific ES cell-derived neural populations are necessary to recognize the full potential of combination therapies involving biomaterials and ES cell-derived neural populations. We previously developed a method for enriching ES cell-derived progenitor motor neurons (pMNs) induced from mouse ES cells via antibiotic selection and showed that the enriched cell populations are depleted of pluripotent stem cells. In this study, we demonstrate the survival and differentiation of enriched pMNs within three dimensional (3D) fibrin scaffolds in vitro and when transplanted into a sub-acute dorsal hemisection model of SCI into neurons, oligodendrocytes and astrocytes. PMID:25346848

  7. The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013.

    PubMed

    Olsson, Linda; Ivanov Öfverholm, Ingegerd; Norén-Nyström, Ulrika; Zachariadis, Vasilios; Nordlund, Jessica; Sjögren, Helene; Golovleva, Irina; Nordgren, Ann; Paulsson, Kajsa; Heyman, Mats; Barbany, Gisela; Johansson, Bertil

    2015-09-01

    Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (∆IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether ∆IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N = 218) or multiplex ligation-dependent probe amplification (N = 116) analyses. ∆IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P < 0·001) and overall survival (pOS; 73% vs. 89%; P = 0·001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, ∆IKZF1 was the strongest independent factor for relapse and death. ∆IKZF1 was present in 27% of cases with non-informative cytogenetics ('BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P < 0·001). Importantly, neither MRD nor WBC count predicted events in the ∆IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and ∆IKZF1 increased the risk of relapse (75% vs. 30% for cases with only ∆IKZF1; P = 0·045), indicating that BCP-other ALL with both P2RY8-CRLF2 and ∆IKZF1 constitutes a particularly high-risk group.

  8. Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.

    PubMed

    Malagola, Michele; Skert, Cristina; Borlenghi, Erika; Chiarini, Marco; Cattaneo, Chiara; Morello, Enrico; Cancelli, Valeria; Cattina, Federica; Cerqui, Elisa; Pagani, Chiara; Passi, Angela; Ribolla, Rossella; Bernardi, Simona; Giustini, Viviana; Lamorgese, Cinzia; Ruggeri, Giuseppina; Imberti, Luisa; Caimi, Luigi; Russo, Domenico; Rossi, Giuseppe

    2016-02-01

    Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML.

  9. Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease

    PubMed Central

    Pérez-Calvo, Juan I; Sánchez-Marteles, Marta; Ruiz-Ruiz, Francisco-José; Morales-Rull, José-Luis; Nieto-Rodríguez, José-Antonio

    2010-01-01

    Objectives To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. Design Prospective, observational, non-interventional study. Setting CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. Participants Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. Main outcome measures NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. Results During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44–4628.55) vs 502.70 pg/mL (95% CI 395.44–645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21–1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09–1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57–1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80–632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). Conclusions In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can

  10. Muscle lengthening surgery causes differential acute mechanical effects in both targeted and non-targeted synergistic muscles.

    PubMed

    Ateş, Filiz; Özdeşlik, Rana N; Huijing, Peter A; Yucesoy, Can A

    2013-10-01

    Epimuscular myofascial force transmission (EMFT) is a major determinant of muscle force exerted, as well as length range of force exertion. Therefore, EMFT is of importance in remedial surgery performed, e.g., in spastic paresis. We aimed to test the following hypotheses: (1) muscle lengthening surgery (involving preparatory dissection (PD) and subsequent proximal aponeurotomy (AT)) affects the target muscle force exerted at its distal and proximal tendons differentially, (2) forces of non-operated synergistic muscles are affected as well, (3) PD causes some of these effects. In three conditions (control, post-PD, and post-AT exclusively on m. extensor digitorum longus (EDL)), forces exerted by rat anterior crural muscles were measured simultaneously. Our results confirm hypotheses (1-2), and hypothesis (3) in part: Reduction of EDL maximal force differed by location (i.e. 26.3% when tested distally and 44.5% when tested proximally). EDL length range of active force exertion increased only distally. Force reductions were shown also for non-operated tibialis anterior (by 11.9%), as well as for extensor hallucis longus (by 8.4%) muscles. In tibialis anterior only, part of the force reduction (4.9%) is attributable to PD. Due to EMFT, remedial surgery should be considered to have differential effects for targeted and non-targeted synergistic muscles.

  11. Differential effect of plasma and red blood cell transfusion on acute lung injury and infection risk following liver transplantation

    PubMed Central

    Benson, Alexander B.; Burton, James R.; Austin, Gregory L.; Biggins, Scott W.; Zimmerman, Michael A.; Kam, Igal; Mandell, Susan; Silliman, Christopher C.; Rosen, Hugo; Moss, Marc

    2010-01-01

    Rationale Patients with chronic liver disease are at an increased risk of developing transfusion-associated acute lung injury (TRALI) from plasma containing blood products. Similarly, red blood cell transfusions have been associated with post-operative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive a large amount of cellular and plasma containing blood products, but it is presently unclear which blood components are associated with these post-operative complications. Results A retrospective cohort study of 525 consecutive liver transplant patients revealed a peri-operative TRALI incidence of 1.3% (7/525), 95%CI [0.6%–2.7%], associated with an increased hospital mortality (28.6% (2/7) vs. 2.9% (15/518), p=0.02) and intensive care unit (ICU) length of stay (2 days, [1–11] vs. 0 days [0–2], 0.03). Only high plasma containing blood products (plasma and platelets) were associated with the development of TRALI. A total of 14.3% (74/525) of patients developed a post-operative infection which was also associated with an increased in-hospital mortality (10.8% (8/74) vs. 2.0% (9/451), p < 0.01) and prolonged length of stay. Multivariate logistic regression identified the number of red blood cell units transfused (adj OR 1.08 95%CI [1.02–1.14], p<0.01), the presence of peri-operative renal dysfunction and re-operation to be significantly associated with post-operative infection. Conclusions Patients undergoing liver transplantation are at high risk of developing post-operative complications from blood transfusion. Plasma containing blood products were associated with the development of TRALI while red blood cells were associated with the development of post-operative infection in a dose dependent manner. PMID:21280188

  12. Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

    PubMed

    Heden, Timothy D; Liu, Ying; Park, Youngmin; Dellsperger, Kevin C; Kanaley, Jill A

    2013-09-01

    Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

  13. Acute Dietary Tryptophan Manipulation Differentially Alters Social Behavior, Brain Serotonin and Plasma Corticosterone in Three Inbred Mouse Strains

    PubMed Central

    Zhang, Wynne Q.; Smolik, Corey M.; Barba-Escobedo, Priscilla A.; Gamez, Monica; Sanchez, Jesus J.; Javors, Martin A.; Daws, Lynette C.; Gould, Georgianna G.

    2014-01-01

    Clinical evidence indicates brain serotonin (5-HT) stores and neurotransmission may be inadequate in subpopulations of individuals with autism, and this may contribute to characteristically impaired social behaviors. Findings that depletion of the 5-HT precursor tryptophan (TRP) worsens autism symptoms support this hypothesis. Yet dietetic studies show and parents report that many children with autism consume less TRP than peers. To measure the impact of dietary TRP content on social behavior, we administered either diets devoid of TRP, with standard TRP (0.2 gm%), or with 1% added TRP (1.2 gm%) overnight to three mouse strains. Of these, BTBRT+Itpr3tf/J and 129S1/SvImJ consistently exhibit low preference for social interaction relative to C57BL/6. We found that TRP depletion reduced C57BL/6 and 129S social interaction preference, while TRP enhancement improved BTBR sociability (p < 0.05; N= 8–10). Subsequent marble burying was similar regardless of grouping. After behavior tests, brain TRP levels and plasma corticosterone were higher in TRP enhanced C57BL/6 and BTBR, while 5-HT levels were reduced in all strains by TRP depletion (p <0.05; N= 4 −10). Relative hyperactivity of BTBR and hypoactivity of 129S, evident in self-grooming and chamber entries during sociability tests, were uninfluenced by dietary TRP. Our findings demonstrate mouse sociability and brain 5-HT turnover are reduced by acute TRP depletion, and can be enhanced by TRP supplementation. This outcome warrants further basic and/or clinical studies employing biomarker combinations such as TRP metabolism and 5-HT regulated hormones to characterize the conditions wherein TRP supplementation can best ameliorate sociability deficits. PMID:25445490

  14. AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells.

    PubMed

    Gianní, M; Li Calzi, M; Terao, M; Guiso, G; Caccia, S; Barbui, T; Rambaldi, A; Garattini, E

    1996-02-15

    All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating

  15. Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

    PubMed Central

    Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

    2015-01-01

    Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

  16. A Randomised Placebo-Controlled Trial to Differentiate the Acute Cognitive and Mood Effects of Chlorogenic Acid from Decaffeinated Coffee

    PubMed Central

    Camfield, David A.; Silber, Beata Y.; Scholey, Andrew B.; Nolidin, Karen; Goh, Antionette; Stough, Con

    2013-01-01

    In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB) or 540mg pure chlorogenic acids (CGA) or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP). Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT), Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS). No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05), as well as decision time on a 2-choice reaction time task (Jensen box) in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05). Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02) and the caffeine Research VAS relative to CGA (t=3.09, p=0.009) and placebo (t=2.75,p=0.02) at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively), whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively). These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be

  17. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    PubMed

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

  18. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  19. Differential Benefit of Statin in Secondary Prevention of Acute Myocardial Infarction according to the Level of Triglyceride and High Density Lipoprotein Cholesterol

    PubMed Central

    Kim, Kyung Hwan; Kim, Cheol Hwan; Ahn, Youngkeun; Kim, Young Jo; Cho, Myeong Chan; Kim, Wan; Kim, Jong Jin

    2016-01-01

    Background and Objectives The differential benefit of statin according to the state of dyslipidemia has been sparsely investigated. We sought to address the efficacy of statin in secondary prevention of myocardial infarction (MI) according to the level of triglyceride and high density lipoprotein cholesterol (HDL-C) on admission. Subjects and Methods Acute MI patients (24653) were enrolled and the total patients were divided according to level of triglyceride and HDL-C on admission: group A (HDL-C≥40 mg/dL and triglyceride<150 mg/dL; n=11819), group B (HDL-C≥40 mg/dL and triglyceride≥150 mg/dL; n=3329), group C (HDL-C<40 mg/dL and triglyceride<150 mg/dL; n=6062), and group D (HDL-C<40 mg/dL & triglyceride≥150 mg/dL; n=3443). We evaluated the differential efficacy of statin according to the presence or absence of component of dyslipidemia. The primary end points were major adverse cardiac events (MACE) for 2 years. Results Statin therapy significantly reduced the risk of MACE in group A (hazard ratio=0.676; 95% confidence interval: 0.582-0.785; p<0.001). However, the efficacy of statin was not prominent in groups B, C, or D. In a propensity-matched population, the result was similar. In particular, the benefit of statin in group A was different compared with group D (interaction p=0.042) Conclusion The benefit of statin in patients with MI was different according to the presence or absence of dyslipidemia. In particular, because of the insufficient benefit of statin in patients with MI and dyslipidemia, a different lipid-lowering strategy is necessary in these patients. PMID:27275169

  20. Identification of Follistatin-Like 1 by Expression Cloning as an Activator of the Growth Differentiation Factor 15 Gene and a Prognostic Biomarker in Acute Coronary Syndrome

    PubMed Central

    Widera, Christian; Giannitsis, Evangelos; Kempf, Tibor; Korf-Klingebiel, Mortimer; Fiedler, Beate; Sharma, Sarita; Katus, Hugo A.; Asaumi, Yasuhide; Shimano, Masayuki; Walsh, Kenneth; Wollert, Kai C.

    2012-01-01

    BACKGROUND Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers. METHODS We expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin-like 1 (FSTL1) and GDF15 in 1369 patients with ACS. RESULTS One cDNA clone that activated the GDF15 promoter–luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R2 = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables. CONCLUSIONS Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS. PMID:22675198

  1. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry.

    PubMed

    Hassan, Sevda; Westwood, John-Paul; Ellis, Debra; Laing, Chris; Mc Guckin, Siobhan; Benjamin, Sylvia; Scully, Marie

    2015-12-01

    Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24·57%) and haemolytic uraemic syndrome (HUS) (27·17% aHUS, 2·83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 × 10(9) /l; range 0-96) than aHUS (57 × 10(9) /l; range 13-145, P < 0·0001) or STEC-HUS (35 × 10(9) /l; range 14-106, P < 0·0001); they also had lower creatinine levels (92 μmol/l; range 43-374) than aHUS (255 μmol/l; range 23-941, P < 0·0001) and STEC-HUS (324 μmol/l; range 117-639, P < 0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count <30 × 10(9) /l and 26/150 (17·3%) of TTP patients had a platelet count >30 × 10(9) /l; 23/150 (15·3%) of TTP patients had a creatinine level >150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis. PMID:26359646

  2. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.

    PubMed

    Montesinos, Pau; Bergua, Juan M; Vellenga, Edo; Rayón, Chelo; Parody, Ricardo; de la Serna, Javier; León, Angel; Esteve, Jordi; Milone, Gustavo; Debén, Guillermo; Rivas, Concha; González, Marcos; Tormo, Mar; Díaz-Mediavilla, Joaquín; González, Jose D; Negri, Silvia; Amutio, Elena; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A

    2009-01-22

    Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).

  3. Unilateral Acute Closed-Angle Glaucoma After Elective Lumbar Surgery Reveals Multiple Intracranial Aneurysms. A Case Report and Discussion on Workup of Differential Diagnoses.

    PubMed

    Storey, Christopher; Menger, Richard; Hefner, Matthew; Keating, Patrick; Ahmed, Osama; Guthikonda, Bharat

    2015-11-01

    The purpose of our paper is to present a case of a rare complication of posterior lumbar surgery. Our patient presented for elective lumbar decompression, which was complicated by durotomy. She then developed sudden headache and right eye pain once upright on postoperative day 2. Then on postoperative day 3, she developed a dilated nonreactive pupil with extraocular movements intact. A computed tomography scan of the head was negative for subarachnoid hemorrhage. Magnetic resonance angiography showed a possible right posterior communicating artery aneurysm. She was transferred to a tertiary center with a severe headache and a nonreactive pupil, raising concern for evolving third nerve palsy due to aneurysm. A cerebral angiogram was performed and showed multiple aneurysms. Aneurysm location did not explain the patient's symptoms, and ophthalmology was consulted. Elevated intraocular pressure was noted, and the patient was diagnosed with acute angle-closure glaucoma (AACG). Our patient was medically treated and subsequently underwent laser peripheral iridotomy. She has had improved vision and pupillary function at 1 month follow-up. The diagnosis is complicated by a durotomy, which led to cascade in the differential diagnosis to rule out intracranial pathology. Her age and home medications, which had sympathomimetic effects, placed her at increased risk, but lying prone in the dark under the drapes was likely the lead causative factor. In conclusion, a postoperative posterior spine patient with eye pain and changes in vision and pupils should be evaluated with AACG in mind due to the devastating consequences if left untreated or treatment is delayed.

  4. Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen.

    PubMed

    Lynch, James T; McEwen, Robert; Crafter, Claire; McDermott, Ultan; Garnett, Mathew J; Barry, Simon T; Davies, Barry R

    2016-04-19

    Selective phosphoinositide 3-kinase (PI3K)/AKT/mTOR inhibitors are currently under evaluation in clinical studies. To identify tumor types that are sensitive to PI3K pathway inhibitors we screened compounds targeting PI3Kα/δ (AZD8835), PI3Kβ/δ (AZD8186), AKT (AZD5363) and mTORC1/2 (AZD2014) against a cancer cell line panel (971 cell lines). There was an enrichment of hematological malignancies that were sensitive to AKT and mTOR inhibition, with the greatest degree of sensitivity observed in T-cell acute lymphoblastic leukemia (T-ALL). We found that all NOTCH mutant T-ALL cell lines were sensitive to AKT and mTORC1/2 inhibitors, with only partial sensitivity to agents that target the PI3K α, β or δ isoforms. Induction of apoptosis only occurred following AKTi treatment in cell lines with PTEN protein loss and high levels of active AKT. In summary, we have demonstrated that T-ALL cell lines show differential sensitivity to inhibition at different nodes in the PI3K/AKT/mTOR pathway and inhibiting AKT or mTOR may have a therapeutic benefit in this disease setting. PMID:26989080

  5. Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen

    PubMed Central

    Lynch, James T.; McEwen, Robert; Crafter, Claire; McDermott, Ultan; Garnett, Mathew J.; Barry, Simon T.; Davies, Barry R.

    2016-01-01

    Selective phosphoinositide 3-kinase (PI3K)/AKT/mTOR inhibitors are currently under evaluation in clinical studies. To identify tumor types that are sensitive to PI3K pathway inhibitors we screened compounds targeting PI3Kα/δ (AZD8835), PI3Kβ/δ (AZD8186), AKT (AZD5363) and mTORC1/2 (AZD2014) against a cancer cell line panel (971 cell lines). There was an enrichment of hematological malignancies that were sensitive to AKT and mTOR inhibition, with the greatest degree of sensitivity observed in T-cell acute lymphoblastic leukemia (T-ALL). We found that all NOTCH mutant T-ALL cell lines were sensitive to AKT and mTORC1/2 inhibitors, with only partial sensitivity to agents that target the PI3K α, β or δ isoforms. Induction of apoptosis only occurred following AKTi treatment in cell lines with PTEN protein loss and high levels of active AKT. In summary, we have demonstrated that T-ALL cell lines show differential sensitivity to inhibition at different nodes in the PI3K/AKT/mTOR pathway and inhibiting AKT or mTOR may have a therapeutic benefit in this disease setting. PMID:26989080

  6. Differential Roles of Ventral and Dorsal Streams for Conceptual and Production-Related Components of Tool Use in Acute Stroke Patients.

    PubMed

    Martin, Markus; Beume, Lena; Kümmerer, Dorothee; Schmidt, Charlotte S M; Bormann, Tobias; Dressing, Andrea; Ludwig, Vera M; Umarova, Roza M; Mader, Irina; Rijntjes, Michel; Kaller, Christoph P; Weiller, Cornelius

    2016-09-01

    Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams. PMID:26271112

  7. Growth and differentiation in culture of leukemic leukocytes from a patient with acute myelogenous leukemia and re-identification of type-C virus.

    PubMed Central

    Gallagher, R E; Salahuddin, S Z; Hall, W T; McCredie, K B; Gallo, R C

    1975-01-01

    Conditioned medium from a culture of whole human embryo cells stimulated prolonged exponential growth in suspension culture of leukocytes from a patient with acute myelogenous leukemia. Ten to 20% of the cultured cells consistently differentiated into mature granulocytes including neutrophils, eosinophils, and basophils. The proportion of lymphocytes declined after culturing, and tests for Epstein-Barr virus antigens were negative. An abnormality of a G group chromosome was observed in some metaphases from the patient's fresh bone marrow and from the cultured leukocytes, indicating growth in vitro of leukemic cells. After 4-10 weeks in culture, a budding type-C virus was continuously released by the cultured leukocytes, predominantly by undifferentiated blast cells. This virus was originally identified in three different cultures of a peripheral blood specimen obtained at the time of diagnosis. Subsequently, this virus was identified by reverse transcriptase (RNA-dependent DNA polymerase) assays and by electron microscopy in cultured leukocytes from a bone marrow specimen obtained 14 months later from the same patient. Virus produced by cultures of both specimens was closely related, if not identical, to the woolly monkey type-C virus. Images PMID:172897

  8. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  9. The combination of urinary IL - 6 and renal biometry as useful diagnostic tools to differentiate acute pyelonephritis from lower urinary tract infection

    PubMed Central

    Azab, Sherif; Zakaria, Mostafa; Raafat, Mona; Seief, Hadeel

    2016-01-01

    ABSTRACT Objective: To evaluate the role of renal ultrasound (RUS) and urinary IL-6 in the differentiation between acute pyelonephritis (APN) and lower urinary tract infection (LUTI). Patients and methods: This prospective study was carried out at the Pediatric and urology outpatient and inpatient departments of Cairo University Children's Hospital as well as October 6 University Hospital and it included 155 children between one month and fourteen years old with positive culture UTI. Patients were categorized into APN and LUTI based on their clinical features and laboratory parameters. Thirty healthy children, age and sex matched constituted the control group. Children with positive urine cultures were treated with appropriate antibiotics. Before treatment, urinary IL-6 was measured by enzyme immunoassay technique (ELISA), and renal ultrasound (RUS) was done. CRP (C-reactive protein), IL-6 and RUS were repeated on the 14th day of antibiotic treatment to evaluate the changes in their levels in response to treatment. Results: UIL-6 levels were more significantly higher in patients with APN than in patients with LUTI (24.3±19.3pg/mL for APN vs. 7.3±2.7pg/mL in LUTI (95% CI: 2.6-27.4; p<0.01). Similarly, serum CRP was more significantly higher in patients with APN than in children with LUTI (19.7±9.1μg/mL vs. 5.5±2.3μg/mL (p<0.01). IL-6 levels >20pg/mL and serum CRP >20μg/mL were highly reliable markers of APN. Mean renal volume and mean volume difference between the two kidneys in the APN group were more than that of the LUTI and control groups (P<0.001). Renal volume between 120-130% of normal was the best for differentiating APN from LUTI. Conclusions: RUS and urinary IL-6 levels have a highly dependable role in the differentiation between APN and LUTI especially in places where other investigations are not available and/ or affordable. PMID:27564295

  10. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    PubMed Central

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

  11. Effect of Serum Growth Differentiation Factor-15 and the Syntax Score on 2-Year Outcomes in Patients With Acute Coronary Syndrome.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Avanzas, Pablo; Consuegra-Sanchez, Luciano

    2016-05-15

    Growth differentiation factor-15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions, but little is known about its relation with severity and complexity of coronary lesions. The aim of this study was to investigate the association between GDF-15 and the syntax score for risk prediction of major adverse cardiovascular events (MACE) at 2-year follow-up in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). This is a prospective cohort study of 502 patients with NSTEACS. The syntax score was calculated from baseline coronary angiography. Blood samples were obtained at study entry for the assessment of GDF-15 and high-sensitivity C reactive protein. One hundred and three patients (20.5%) showed MACE at 2-year follow-up. Patients who developed MACE had greater GDF-15 concentrations and syntax score (p <0.001) compared to patients who did not. There was a positive, but moderate, correlation between GDF-15 and syntax score (ρ = 0.45, p <0.0001). On Cox regression analysis, only GDF-15 levels (p <0.001), body mass index (p = 0.04), and syntax score (p <0.001) remained independent predictors of the MACE. The area under the curve of GDF-15 (0.912, 95% confidence interval 0.894 to 0.944) was significantly greater compared to high-sensitivity C reactive protein and syntax score. In conclusion, in patients with NSTEACS, levels of GDF-15 at admission were correlated with the syntax score and independently associated with an increased risk of MACE during 2-year follow-up. PMID:27013387

  12. Bone Marrow Mesenchymal Stromal Cells from Patients with Acute and Chronic Graft-versus-Host Disease Deploy Normal Phenotype, Differentiation Plasticity, and Immune-Suppressive Activity.

    PubMed

    Copland, Ian B; Qayed, Muna; Garcia, Marco A; Galipeau, Jacques; Waller, Edmund K

    2015-05-01

    The success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often limited by the development of acute and/or chronic graft-versus-host disease (GVHD). The lack of effective therapies to treat steroid-refractory GVHD patients has bolstered clinical evaluation of mesenchymal stromal cell (MSC) therapy for GVHD. Currently, testing of MSCs for the treatment of GVHD has exclusively used allogeneic MSCs despite emerging evidence that MSCs lose their immunoprivileged status in vivo. We hypothesized that autologous MSCs could be a viable alternative MSC source for treating active GVHD. MSCs were isolated and successfully expanded from the bone marrow of 12 volunteers (ages 2 to 55 years) who had allo-HSCT transplants and subsequently developed GVHD. MSCs from subjects with GVHD demonstrated an initial lag in growth compared with healthy control subjects; however, this lag disappeared with continued ex vivo expansion. Immunophenotype and mesodermal differentiation capacity of MSCs from GVHD patients were indistinguishable from that of healthy control MSCs. In vitro immunomodulatory functional analyses also demonstrated that GVHD MSCs were equivalent to healthy control MSCs with regards to dose dependently suppressing T cell proliferation and up-regulating indoleamine 2,3-dioxygenase expression when primed with IFN-γ. Single tandem repeat chimerism analyses further demonstrated that MSCs expanded from GVHD patients were exclusively recipient derived. Based on these data, we conclude that recipient-derived MSCs from patients with GVHD are analogous to MSCs from healthy volunteers and represent a viable option for clinical testing as an immunomodulatory option for symptomatic GVHD.

  13. Effect of Serum Growth Differentiation Factor-15 and the Syntax Score on 2-Year Outcomes in Patients With Acute Coronary Syndrome.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Avanzas, Pablo; Consuegra-Sanchez, Luciano

    2016-05-15

    Growth differentiation factor-15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions, but little is known about its relation with severity and complexity of coronary lesions. The aim of this study was to investigate the association between GDF-15 and the syntax score for risk prediction of major adverse cardiovascular events (MACE) at 2-year follow-up in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). This is a prospective cohort study of 502 patients with NSTEACS. The syntax score was calculated from baseline coronary angiography. Blood samples were obtained at study entry for the assessment of GDF-15 and high-sensitivity C reactive protein. One hundred and three patients (20.5%) showed MACE at 2-year follow-up. Patients who developed MACE had greater GDF-15 concentrations and syntax score (p <0.001) compared to patients who did not. There was a positive, but moderate, correlation between GDF-15 and syntax score (ρ = 0.45, p <0.0001). On Cox regression analysis, only GDF-15 levels (p <0.001), body mass index (p = 0.04), and syntax score (p <0.001) remained independent predictors of the MACE. The area under the curve of GDF-15 (0.912, 95% confidence interval 0.894 to 0.944) was significantly greater compared to high-sensitivity C reactive protein and syntax score. In conclusion, in patients with NSTEACS, levels of GDF-15 at admission were correlated with the syntax score and independently associated with an increased risk of MACE during 2-year follow-up.

  14. Pleomorphic adenoma causing acute airway obstruction.

    PubMed

    Moraitis, D; Papakostas, K; Karkanevatos, A; Coast, G J; Jackson, S R

    2000-08-01

    A case is reported of a pleomorphic adenoma of the minor salivary glands of the oral cavity presenting with acute airway obstruction. This is the first reported case to our knowledge of a mixed salivary tumour of the upper respiratory tract causing upper airway obstruction and acute respiratory failure. The patient had to be intubated and transferred to the intensive care unit. After an elective tracheostomy was performed, the adenoma was excised from its fibrous capsule. It was found to originate from the soft palate and occupied the parapharyngeal space. A high index of suspicion should be kept in order to diagnose tumours of the parapharyngeal space with unusual presentation. These tumours which are usually benign should be considered in the differential diagnosis from more common infectious or traumatic conditions and surgical morbidity should be minimal.

  15. Minimal change disease

    MedlinePlus

    ... seen under a very powerful microscope called an electron microscope. Minimal change disease is the most common ... biopsy and examination of the tissue with an electron microscope can show signs of minimal change disease.

  16. [Acute optic neuropathy: differential diagnoses].

    PubMed

    Buompadre, María Celeste

    2013-09-01

    Introduccion. La alteracion funcional del nervio optico se caracteriza por un deficit en la agudeza visual, en la vision cromatica y en el campo visual, defecto pupilar aferente y, en algunos casos, edema del nervio o atrofia y palidez. Objetivo. Describir el espectro de neuropatias opticas agudas, su clinica, diagnostico y tratamiento, con mayor interes en aquellas de presentacion en la edad pediatrica. Desarrollo. La neuritis optica puede ser monofasica, recurrente o el componente de un cuadro desmielinizante polisintomatico. El objetivo del tratamiento es reducir el numero y la gravedad de los ataques y prevenir discapacidad. La infecciosa es secundaria a diferentes microorganismos (bacterias, virus, hongos y protozoos). El tratamiento depende de la etiologia. La isquemica anterior no arteritica o idiopatica es la forma mas frecuente y es secundaria a enfermedad de pequeños vasos (ciliares posteriores). La neuropatia optica hereditaria o de Leber representa una causa importante de afectacion visual cronica y se caracteriza por la afectacion selectiva de las celulas ganglionares de la retina. Hasta el momento, la terapia solo es de apoyo. En el papiledema asociado a hipertension endocraneal, la agudeza visual generalmente se conserva pero existe aumento de la mancha ciega. El tratamiento se basa en disminuir la hipertension y el factor etiologico si existe. Conclusiones. Las neuropatias opticas agudas constituyen un amplio grupo de entidades, de etiologia diversa y con un pronostico visual variable. La presencia de signos del examen neurologico, fondo de ojo y neuroimagenes pueden orientar hacia el diagnostico y tratamiento oportuno.

  17. Acute Vestibulopathy

    PubMed Central

    Cha, Yoon-Hee

    2011-01-01

    The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835

  18. Matrine cooperates with all-trans retinoic acid on differentiation induction of all-trans retinoic acid-resistant acute promyelocytic leukemia cells (NB4-LR1): possible mechanisms.

    PubMed

    Wu, Dijiong; Shao, Keding; Sun, Jie; Zhu, Fuyun; Ye, Baodong; Liu, Tingting; Shen, Yiping; Huang, He; Zhou, Yuhong

    2014-03-01

    Retinoic acid resistance results in refractory disease, and recovery in acute promyelocytic leukemia remains a challenge in clinical practice, with no ideal chemotherapeutic drug currently available. Here we report on the effect of an active compound of Sophora flavescens called matrine (0.1 mmol/L) combined with all-trans retinoic acid (1 µmol/L) in alleviating retinoic acid resistance in acute promyelocytic leukemia-derived NB4-LR1 cells by differentiation induction, as can be seen by an induced morphology change, increased CD11b expression, and nitro blue tetrazolium reduction activity, and a decreased expression of the promyelocytic leukemia-retinoic acid receptor α fusion gene and protein product. We further explored the probable mechanism of how matrine promotes the recovery of differentiation ability in NB4-LR1 cells when exposed to all-trans retinoic acid. We observed that the combination of all-trans retinoic acid and matrine can increase the level of cyclic adenosine monophosphate and protein kinase A activity, reduce telomerase activity, and downregulate the protein expression of topoisomerase II beta in NB4-LR1 cells. The results of this study suggest the possible clinical utility of matrine in the treatment of retinoic acid-resistant acute promyelocytic leukemia.

  19. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  20. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    PubMed

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

  1. Lifting the Differentiation Embargo.

    PubMed

    Latif, Anne-Louise; Holyoake, Tessa L

    2016-09-22

    Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. PMID:27662083

  2. Minimally Invasive Valve Surgery

    PubMed Central

    Pope, Nicolas H.; Ailawadi, Gorav

    2014-01-01

    Cardiac valve surgery is life saving for many patients. The advent of minimally invasive surgical techniques has historically allowed for improvement in both post-operative convalescence and important clinical outcomes. The development of minimally invasive cardiac valve repair and replacement surgery over the past decade is poised to revolutionize the care of cardiac valve patients. Here, we present a review of the history and current trends in minimally invasive aortic and mitral valve repair and replacement, including the development of sutureless bioprosthetic valves. PMID:24797148

  3. [Management of acute tendinitis].

    PubMed

    Rapp, H J; Heisse, K; Becker, M; Stechele, M

    1992-12-01

    Ultrasonography must be used in combination with physical examination for the appropriate diagnosis of acute tendon injuries. Therapy should be designed to return the tendon to its normal function and appearance. Local and systemic anti-inflammatory agents, cold hydrotherapy and massage minimize excessive scar formation and progressively increasing tensile forces directs scar tissue to replace the tendon function.

  4. New flow cytometric method for detection of minimally expressed multidrug resistance P-glycoprotein on normal and acute leukemia cells using biotinylated MRK16 and streptavidin-RED670 conjugate.

    PubMed

    Takeshita, A; Shinjo, K; Ohnishi, K; Ohno, R

    1995-06-01

    To evaluate the expression of multidrug resistance (MDR) on normal and leukemia cells, we examined P-glycoprotein (P-gp) by a newly devised flow cytometric method, utilizing a biotinylated monoclonal antibody (mAb) against P-gp (MRK16), a streptavidin-RED670 conjugate (SA-RED670) and appropriate emission filters. The combination of biotinylated MRK16 (b-MRK16) and SA-RED670 resulted in higher sensitivity as compared with standard methods such as the use of streptavidin-phycoerythrin (SA-PE) conjugate. The sensitivity was examined in K562, K562/ADR, NOMO-1, NOMO-1/ADR and HL60 cells, and compared with the data obtained from reverse transcription polymerase chain reaction (RT-PCR) of mdr-1 gene. P-gp positivity on flow cytometry was 10.4%, 99.9%, 1.4%, 90.4% and 0%, respectively. Mdr-1 mRNA was well expressed in K562/ADR and NOMO-1/ADR cells, but not in NOMO-1 and HL60 cells. In K562 cells, mdr-1 was found after 40 cycles of PCR, but not 25 cycles. These data are well correlated with those from the flow cytometry. We then studied the P-gp expression on normal peripheral blood cells and acute leukemia cells. P-gp was little expressed on peripheral lymphocytes, monocytes and granulocytes. It was also little expressed on blast cells from 5 patients with acute promyelocytic leukemia (AML) and 5 acute lymphocytic leukemia (ALL) expressed P-gp at diagnosis, ranging from 8.5% to 34.5% (16.9 +/- 11.8%) and from 2.3% to 45.6% (24.0 +/- 17.8%), respectively. All 9 relapsed or refractory cases expressed P-gp, ranging from 21.1% to 99.8% (52.2 +/- 29.9%). Significant differences were found in APL, CD34-positive and relapse and refractory cases (P = 0.0006, 0.0007 and 0.0088, respectively). These results indicate that this flow cytometric analysis is useful for the evaluation of clinical MDR status and can identify a group of patients with resistant leukemia. PMID:7622426

  5. [Minimal Change Esophagitis].

    PubMed

    Ryu, Han Seung; Choi, Suck Chei

    2016-01-25

    Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms and long-term complications. GERD can be divided into erosive reflux disease and non-erosive reflux disease based on endoscopic findings defined by the presence of mucosal break. The Los Angeles classification excludes minimal changes as an evidence of reflux esophagitis because of poor interobserver agreement. In the Asian literature, minimal changes are considered as one of the endoscopic findings of reflux esophagitis, but the clinical significance is still controversial. Minimal change esophagitis is recognized quite frequently among patients with GERD and many endoscopists recognize such findings in their clinical practice. This review is intended to clarify the definition of minimal change esophagitis and their histology, interobserver agreement, and symptom association with GERD.

  6. Minimizing Shortness of Breath

    MedlinePlus

    ... Top Doctors in the Nation Departments & Divisions Home Health Insights Stress & Relaxation Breathing and Relaxation Minimizing Shortness of Breath ... Management Assess Your Stress Coping Strategies Identifying ... & Programs Health Insights Doctors & Departments Research & Science Education & Training Make ...

  7. [Correlation between hyperamylasemia and acute pancreatitis].

    PubMed

    Monaco, R; Durante, E; Pampolini, M; Tioli, P

    1981-05-31

    It is often difficult to differentiate acute pancreatitis (A.P.) from some other acute abdominal diseases, when there is an elevated serum amylase. In contrast, the renal clearance of amylase, expressed as a percentage of creatinine clearance, can separate patients with A.P. from patients with acute colecistitis, common duct stone without pancreatitis, hyperamylasemia after biliary surgery, acute peptic ulcer and acute salivary diseases.

  8. The management of acute pericarditis.

    PubMed

    Wells, T A; Curzen, N P

    2005-01-01

    Acute pericarditis is usually a benign self-limiting condition, often of unexplained or viral aetiology, involving inflammation of the pericardial layers. It is often part of the differential diagnosis in patients admitted with acute chest pain and can be confused with acute myocardial infarction, acute pulmonary embolism and pleurisy. Occasionally it can result in cardiac tamponade and, if associated with myocarditis, in heart failure. This article sets out how to diagnose acute pericarditis, the common underlying causes, the possible treatment options and outcomes. PMID:21655516

  9. Minimally invasive procedures

    PubMed Central

    Baltayiannis, Nikolaos; Michail, Chandrinos; Lazaridis, George; Anagnostopoulos, Dimitrios; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Kioumis, Ioannis; Pitsiou, Georgia; Katsikogiannis, Nikolaos; Tsakiridis, Kosmas; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

    2015-01-01

    Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small “ports” from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry—meaning only one small incision, like the “uniport” video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional “open” surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. PMID:25861610

  10. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  11. Restoration of CCAAT enhancer binding protein α P42 induces myeloid differentiation and overcomes all-trans retinoic acid resistance in human acute promyelocytic leukemia NB4-R1 cells

    PubMed Central

    WANG, LIMENGMENG; XIAO, HAOWEN; ZHANG, XING; LIAO, WEICHAO; FU, SHAN; HUANG, HE

    2015-01-01

    All-trans retinoic acid (ATRA) is one of the first line agents in differentiation therapy for acute promyelocytic leukemia (APL). However, drug resistance is a major problem influencing the efficacy of ATRA. Identification of mechanisms of ATRA resistance are urgenly needed. In the present study, we found that expression of C/EBPα, an important transcription factor for myeloid differentiation, was significantly suppressed in ATRA resistant APL cell line NB4-R1 compared with ATRA sensitive NB4 cells. Moreover, two forms of C/EBPα were unequally suppressed in NB4-R1 cells. Suppression of the full-length form P42 was more pronounced than the truncated form P30. Inhibition of PI3K/Akt/mTOR pathway was also observed in NB4-R1 cells. Moreover, C/EBPα expression was reduced by PI3K inhibitor LY294002 and mTOR inhibitor RAD001 in NB4 cells, suggesting that inactivation of the PI3K/Akt/mTOR pathway was responsible for C/EBPα suppression in APL cells. We restored C/EBPα P42 and P30 by lentivirus vectors in NB4-R1 cells, respectively, and found C/EBPα P42, but not P30, could increase CD11b, CD14, G-CSFR and GM-CSFR expression, which indicated the occurrence of myeloid differentiation. Further upregulating of CD11b expression and differential morphological changes were found in NB4-R1 cells with restored C/EBPα P42 after ATRA treatment. However, CD11b expression and differential morphological changes could not be induced by ATRA in NB4-R1 cells infected with P30 expressing or control vector. Thus, we inferred that ATRA sensitivity of NB4-R1 cells was enhanced by restoration of C/EBPα P42. In addition, we used histone deacetylase inhibitor trichostatin (TSA) to restore C/EBPα expression in NB4-R1 cells. Similar enhancement of myeloid differentiation and cell growth arrest were detected. Together, the present study demonstrated that suppression of C/EBPα P42 induced by PI3K/Akt/mTOR inhibition impaired the differentiation and ATRA sensitivity of APL cells. Restoring C

  12. Optimal time-points for minimal residual disease monitoring change on the basis of the method used in patients with acute myeloid leukemia who underwent allogeneic stem cell transplantation: a comparison between multiparameter flow cytometry and Wilms' tumor 1 expression.

    PubMed

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; di Nardo, Francesco; Waure, Chiara de; Greco, Michele Mario; Merla, Emanuela; Cillis, Giovanni Pio de; Di Renzo, Nicola; Melpignano, Angela; Capalbo, Silvana; Palumbo, Gaetano; Pisapia, Giovanni; Cascavilla, Nicola

    2015-02-01

    Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p=0.006 and p=0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p=0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used.

  13. Inhibition of all-trans-retinoic acid-induced proteasome activation potentiates the differentiating effect of retinoid in acute myeloid leukemia cells.

    PubMed

    Fang, Yanfen; Zhou, Xinglu; Lin, Meihua; Ying, Meidan; Luo, Peihua; Zhu, Difeng; Lou, Jianshu; Yang, Bo; He, Qiaojun

    2011-01-01

    All-trans retinoic acid (ATRA) is nowadays considered to be the sole efficient agent for differentiation-based therapy in leukemia; however, the mechanisms of ATRA's biological effects remain largely unknown. Here we first reported that ATRA-induced myeloid leukemia differentiation was accompanied with the increased level of ubiquitin-protein conjugates and the upregulation of proteasome activity. To explore the functional role of the activated proteasome in retinoic acid (RA) signaling, the effects of proteasome inhibitors on RA-induced cell differentiation were determined. Our results demonstrated that inhibition of ATRA-elevated proteasome activity obviously promoted the myeloid maturation program triggered by ATRA, suggesting that the overactivated proteasome is not beneficial for ATRA's effects. Further studies demonstrated that the synergistic differentiating effects of ATRA and proteasome inhibitors might be associated with the protection of retinoic acid receptor alpha (RARα) from degradation by the ubiquitin-proteasome pathway (UPP). Moreover, the accumulated RARα was able to enhance the transcription of its target gene, which might also contribute to the enhanced differentiation of leukemia cells. Together, by linking the UPP to ATRA-dependent signaling, our data provide a novel insight into studying the mechanisms of ATRA-elicited cellular effects and imply the possibility of combination of ATRA and proteasome inhibitors in leukemia therapy.

  14. Ways To Minimize Bullying.

    ERIC Educational Resources Information Center

    Mueller, Mary Ellen; Parisi, Mary Joy

    This report delineates a series of interventions aimed at minimizing incidences of bullying in a suburban elementary school. The social services staff was scheduled to initiate an anti-bullying incentive in fall 2001 due to the increased occurrences of bullying during the prior year. The target population consisted of third- and fourth-grade…

  15. Minimally invasive periodontal therapy.

    PubMed

    Dannan, Aous

    2011-10-01

    Minimally invasive dentistry is a concept that preserves dentition and supporting structures. However, minimally invasive procedures in periodontal treatment are supposed to be limited within periodontal surgery, the aim of which is to represent alternative approaches developed to allow less extensive manipulation of surrounding tissues than conventional procedures, while accomplishing the same objectives. In this review, the concept of minimally invasive periodontal surgery (MIPS) is firstly explained. An electronic search for all studies regarding efficacy and effectiveness of MIPS between 2001 and 2009 was conducted. For this purpose, suitable key words from Medical Subject Headings on PubMed were used to extract the required studies. All studies are demonstrated and important results are concluded. Preliminary data from case cohorts and from many studies reveal that the microsurgical access flap, in terms of MIPS, has a high potential to seal the healing wound from the contaminated oral environment by achieving and maintaining primary closure. Soft tissues are mostly preserved and minimal gingival recession is observed, an important feature to meet the demands of the patient and the clinician in the esthetic zone. However, although the potential efficacy of MIPS in the treatment of deep intrabony defects has been proved, larger studies are required to confirm and extend the reported positive preliminary outcomes.

  16. Minimizing Promotion Trauma.

    ERIC Educational Resources Information Center

    Darling, LuAnn W.; McGrath, Loraine

    1983-01-01

    Nursing administrators can minimize promotion trauma and its unnecessary cost by building awareness of the transition process, clarifying roles and expectations, and attending to the promoted employee's needs. This article will help nursing administrators develop a concept of manager care combined with programs for orientation of new managers,…

  17. Periodic minimal surfaces

    NASA Astrophysics Data System (ADS)

    Mackay, Alan L.

    1985-04-01

    A minimal surface is one for which, like a soap film with the same pressure on each side, the mean curvature is zero and, thus, is one where the two principal curvatures are equal and opposite at every point. For every closed circuit in the surface, the area is a minimum. Schwarz1 and Neovius2 showed that elements of such surfaces could be put together to give surfaces periodic in three dimensions. These periodic minimal surfaces are geometrical invariants, as are the regular polyhedra, but the former are curved. Minimal surfaces are appropriate for the description of various structures where internal surfaces are prominent and seek to adopt a minimum area or a zero mean curvature subject to their topology; thus they merit more complete numerical characterization. There seem to be at least 18 such surfaces3, with various symmetries and topologies, related to the crystallographic space groups. Recently, glyceryl mono-oleate (GMO) was shown by Longley and McIntosh4 to take the shape of the F-surface. The structure postulated is shown here to be in good agreement with an analysis of the fundamental geometry of periodic minimal surfaces.

  18. Minimally invasive pancreatic surgery.

    PubMed

    Yiannakopoulou, E

    2015-12-01

    Minimally invasive pancreatic surgery is feasible and safe. Laparoscopic distal pancreatectomy should be widely adopted for benign lesions of the pancreas. Laparoscopic pancreaticoduodenectomy, although technically demanding, in the setting of pancreatic ductal adenocarcinoma has a number of advantages including shorter hospital stay, faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. Furthermore, it seems that progression-free survival is longer in patients undergoing laparoscopic pancreaticoduodenectomy in comparison with those undergoing open pancreaticoduodenectomy. Minimally invasive middle pancreatectomy seems appropriate for benign or borderline tumors of the neck of the pancreas. Technological advances including intraoperative ultrasound and intraoperative fluorescence imaging systems are expected to facilitate the wide adoption of minimally invasive pancreatic surgery. Although, the oncological outcome seems similar with that of open surgery, there are still concerns, as the majority of relevant evidence comes from retrospective studies. Large multicenter randomized studies comparing laparoscopic with open pancreatectomy as well as robotic assisted with both open and laparoscopic approaches are needed. Robotic approach could be possibly shown to be less invasive than conventional laparoscopic approach through the less traumatic intra-abdominal handling of tissues. In addition, robotic approach could enable the wide adoption of the technique by surgeon who is not that trained in advanced laparoscopic surgery. A putative clinical benefit of minimally invasive pancreatic surgery could be the attenuated surgical stress response leading to reduced morbidity and mortality as well as lack of the detrimental immunosuppressive effect especially for the oncological patients. PMID:26530291

  19. Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults.

    PubMed

    Bartholdy, Savani; Cheng, Jiumu; Schmidt, Ulrike; Campbell, Iain C; O'Daly, Owen G

    2016-01-01

    Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a "need" state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide some

  20. Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults

    PubMed Central

    Bartholdy, Savani; Cheng, Jiumu; Schmidt, Ulrike; Campbell, Iain C.; O'Daly, Owen G.

    2016-01-01

    Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a “need” state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide

  1. Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults

    PubMed Central

    Bartholdy, Savani; Cheng, Jiumu; Schmidt, Ulrike; Campbell, Iain C.; O'Daly, Owen G.

    2016-01-01

    Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a “need” state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide

  2. Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults.

    PubMed

    Bartholdy, Savani; Cheng, Jiumu; Schmidt, Ulrike; Campbell, Iain C; O'Daly, Owen G

    2016-01-01

    Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a "need" state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide some

  3. Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice.

    PubMed Central

    Murphy, W J; Welniak, L A; Taub, D D; Wiltrout, R H; Taylor, P A; Vallera, D A; Kopf, M; Young, H; Longo, D L; Blazar, B R

    1998-01-01

    Graft-versus-host disease (GVHD), in which immunocompetent donor cells attack the host, remains a major cause of morbidity after allogeneic bone marrow transplantation (BMT). To understand the role of cytokines in the pathobiology of GVHD, we used cytokine knockout (KO) mice as a source of donor T cells. Two different MHC-disparate strain combinations were examined: BALB/c (H2(d)) donors into lethally irradiated C57BL/6 (H2(b)) recipients or C57BL/6 (H2(b)) donors into B10.BR (H2(k)) recipients. Donor cells were from mice in which either the interferon-gamma (IFN-gamma) or the IL-4 gene was selectively disrupted to understand the role of these cytokines in acute GVHD. In both strain combinations the same pattern was noted with regard to GVHD onset and morbidity. All mice exhibited the classic signs of acute GVHD: weight loss with skin, gut, and liver pathology resulting in morbidity and mortality. Surprisingly, donor cells obtained from mice lacking IFN-gamma gave rise to accelerated morbidity from GVHD when compared with cells from wild-type control donors. Similar results were obtained using normal donors when neutralizing antibodies to IFN-gamma were administered immediately after the BMT. These results suggest that IFN-gamma plays a role in protection from acute GVHD. In marked contrast, cells obtained from IL-4 KO mice resulted in protection from GVHD compared with control donors. Splenocytes from IFN KO mice stimulated with a mitogen proliferated to a significantly greater extent and produced more IL-2 compared with splenocytes obtained from IL-4 KO or control mice. Additionally, there was increased IL-2 production in the spleens of mice undergoing GVHD using IFN-gamma KO donors. These results therefore indicate, with regard to the TH1/ TH2 cytokine paradigm, the absence of a TH1-type cytokine can be deleterious in acute GVHD, whereas absence of a TH2 cytokine can be protective. PMID:9802888

  4. SUB-ACUTE TREATMENT WITH METHYLMERCURY DURING DIFFERENTIATION OF PHEOCHROMOCYTOMA (PC12) CELLS DOES NOT ALTER BINDING OF ION CHANNEL LIGANDS OR CELL MORPHOLOGY.

    EPA Science Inventory

    We demonstrated recently that 6 days of exposure to nanomolar concentrations (3-10 nM) of methylmercury (MeHg) during nerve growth factor (NGF) induced PC12 cell differentiation reduced the amplitude and density of voltage-gated sodium and calcium currents. In the present study,...

  5. Constrained minimization of smooth functions using a genetic algorithm

    NASA Technical Reports Server (NTRS)

    Moerder, Daniel D.; Pamadi, Bandu N.

    1994-01-01

    The use of genetic algorithms for minimization of differentiable functions that are subject to differentiable constraints is considered. A technique is demonstrated for converting the solution of the necessary conditions for a constrained minimum into an unconstrained function minimization. This technique is extended as a global constrained optimization algorithm. The theory is applied to calculating minimum-fuel ascent control settings for an energy state model of an aerospace plane.

  6. The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.

    PubMed

    Kai, Shinichi; Tanaka, Tomoharu; Matsuyama, Tomonori; Suzuki, Kengo; Hirota, Kiichi

    2014-06-01

    Erythropoietin (EPO) is a glycoprotein hormone essential for the regulation of erythroid homeostasis. Although EPO production is prominent in the kidney and liver, its production in the central nervous system has also been detected. Tissue hypoxia due to systemic or local hypoxemia and acute anemia due to blood loss occurs frequently during various clinical settings, leading to a high possibility of elevated plasma EPO levels. However, it is largely unknown whether volatile anesthetic agents affect EPO production elicited by acute hypoxia in vivo. Male C57BL/6N CrSlc mice were exposed to a hypoxic insult as a result of bleeding-related anemia or hypoxemia while they were under anesthetized using various concentrations of isoflurane. EPO protein concentrations were assessed by enzyme-linked immunosorbent assay and mRNA levels were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. Plasma EPO concentration was induced as early as 3h following acute anemic and hypoxemic hypoxia and suppressed by clinically relevant doses of isoflurane in a dose-dependent manner. Anemic hypoxia induced EPO mRNA and protein synthesis in the kidney. In the kidney, isoflurane inhibited EPO induction caused by anemia but not that caused by hypoxemia. On the other hand, in the brain hypoxemia-induced EPO production was suppressed by isoflurane. Finally, qRT-PCR studies demonstrate that isoflurane differentially inhibit HIF-1α and HIF-2α mRNA expression in brain and kidney, indicating the involvement of HIF-2 in the hypoxia-induced EPO expression and inhibition of the induction by isoflurane. PMID:24680923

  7. Integrative Metabolome and Transcriptome Profiling Reveals Discordant Energetic Stress between Mouse Strains with Differential Sensitivity to Acrolein-Induced Acute Lung Injury

    PubMed Central

    Fabisiak, James P.; Medvedovic, Mario; Alexander, Danny C.; McDunn, Jonathan E.; Concel, Vincent J.; Bein, Kiflai; Jang, An Soo; Brendt, Annerose; Vuga, Louis J.; Brant, Kelly A.; Pope-Varsalona, Hannah; Dopico, Richard A.; Ganguly, Koustav; Upadhyay, Swapna; Li, Qian; Hu, Zhen; Kaminski, Naftali; Leikauf, George D.

    2012-01-01

    A respiratory irritant, acrolein is generated by overheating cooking oils or by domestic cooking using biomass fuels, and is in tobacco smoke, an occupational health hazard in the restaurant workplace. To better understand the metabolic role of the lung and to generate insights into the pathogenesis of acrolein-induced acute lung injury, SM/J (sensitive) and 129×1/SvJ (resistant) inbred mouse strains were exposed and the lung metabolome was integrated with the transcriptome profile. A total of 280 small molecules were identified and mean values (log 2 >0.58 or <−0.58, .p<0.05) were considered different for between-strain comparisons or within-strain responses to acrolein treatment. At baseline, 24 small molecules increased and 33 small molecules decreased in the SM/J mouse lung as compared to 129×1/SvJ mouse lung. Notable among the increased compounds was malonyl carnitine. Following acrolein exposure, several compounds indicative of glycolysis and branched chain amino acid metabolism increased similarly in both strains, whereas SM/J mice were less effective in generating metabolites related to fatty acid β-oxidation. These findings suggest management of energetic stress varies between these strains, and that the ability to evoke auxiliary energy generating pathways rapidly and effectively may be critical in enhancing survival during acute lung injury in mice. PMID:21823223

  8. Discrete Minimal Surface Algebras

    NASA Astrophysics Data System (ADS)

    Arnlind, Joakim; Hoppe, Jens

    2010-05-01

    We consider discrete minimal surface algebras (DMSA) as generalized noncommutative analogues of minimal surfaces in higher dimensional spheres. These algebras appear naturally in membrane theory, where sequences of their representations are used as a regularization. After showing that the defining relations of the algebra are consistent, and that one can compute a basis of the enveloping algebra, we give several explicit examples of DMSAs in terms of subsets of sln (any semi-simple Lie algebra providing a trivial example by itself). A special class of DMSAs are Yang-Mills algebras. The representation graph is introduced to study representations of DMSAs of dimension d ≤ 4, and properties of representations are related to properties of graphs. The representation graph of a tensor product is (generically) the Cartesian product of the corresponding graphs. We provide explicit examples of irreducible representations and, for coinciding eigenvalues, classify all the unitary representations of the corresponding algebras.

  9. The method of minimal normal forms

    SciTech Connect

    Mane, S.R.; Weng, W.T.

    1992-01-01

    Normal form methods for solving nonlinear differential equations are reviewed and the comparative merits of three methods are evaluated. The concept of the minimal normal form is explained and is shown to be superior to other choices. The method is then extended to apply to the evaluation of discrete maps of an accelerator or storage ring. Such an extension, as suggested in this paper, is more suited for accelerator-based applications than a formulation utilizing continuous differential equations. A computer code has been generated to systematically implement various normal form formulations for maps in two-dimensional phase space. Specific examples of quadratic and cubic nonlinear fields were used and solved by the method developed. The minimal normal form method shown here gives good results using relatively low order expansions.

  10. The method of minimal normal forms

    SciTech Connect

    Mane, S.R.; Weng, W.T.

    1992-12-31

    Normal form methods for solving nonlinear differential equations are reviewed and the comparative merits of three methods are evaluated. The concept of the minimal normal form is explained and is shown to be superior to other choices. The method is then extended to apply to the evaluation of discrete maps of an accelerator or storage ring. Such an extension, as suggested in this paper, is more suited for accelerator-based applications than a formulation utilizing continuous differential equations. A computer code has been generated to systematically implement various normal form formulations for maps in two-dimensional phase space. Specific examples of quadratic and cubic nonlinear fields were used and solved by the method developed. The minimal normal form method shown here gives good results using relatively low order expansions.

  11. Acute and chronic cocaine behavioral effects in novel versus familiar environments: open-field familiarity differentiates cocaine locomotor stimulant effects from cocaine emotional behavioral effects.

    PubMed

    Carey, Robert J; DePalma, Gail; Damianopoulos, Ernest

    2005-03-30

    Cocaine is a potent stimulant drug, but its stimulant effects can be substantially modulated by environmental novelty versus familiarity. In this report, we varied exposures to a novel environment as a way to assess the impact of environmental familiarity versus novelty upon the locomotor activation induced by acute and chronic cocaine treatments. In experiment 1, the effects of 1 (PE1) versus 0 (PE0) pre-exposures to the test environment were compared for their impact upon the locomotor stimulant, central zone entry and grooming effects induced by an acute cocaine (10 mg/kg) treatment. In experiment 2, the effects of 10 (PE10) versus 0 (PE0) pre-exposures upon the cocaine effects were compared. Experiment 3 assessed the effects of nine cocaine treatments (10.0 mg/kg) initiated in a novel environment (PE0) versus familiar environment (PE10). In all experiments, cocaine had a potent locomotor stimulant effect in a novel environment, which was attenuated by environmental familiarity such that in PE10 groups, cocaine did not reliably induce an acute locomotor stimulant effect. Environmental novelty/familiarity, however, did not reliably alter cocaine effects upon central zone penetration, grooming behavior, or the neurochemical effects induced by cocaine. In the chronic treatment regimen, the PE0 group exhibited a tolerance-like decrease in locomotor activation, but the PE10 group exhibited a sensitization-like increase in locomotor activation. Despite the marked directional changes in the locomotor stimulant effects of cocaine treatments, initiated in a novel (PE0) versus familiar (PE10) environment, the same asymptotic levels of locomotor activation were achieved. In contrast, the behavioral measures of central zone activity progressively increased with repeated treatments regardless of whether the environment was initially novel (PE0) or familiar (PE10). Thus, habituation factors can profoundly alter the locomotor stimulant effects of cocaine and can induce pseudo

  12. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    SciTech Connect

    Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  13. [Clinical case--voluminous diaphragmatic hernia--surgically acute abdomen: diagnostic and therapeutical challenges].

    PubMed

    Dumitrescu, D; Savlovschi, C; Borcan, R; Pantu, H; Serban, D; Gradinaru, S; Smarandache, G; Trotea, T; Branescu, C; Musat, L; Comandasu, M; Priboi, M; Baldir, M; Sandolache, B; Oprescu, S

    2011-01-01

    We present the case of a 58-year old male patient admitted in the surgery section of the University Emergency Hospital of Bucharest and diagnosed with acute abdomen. The minimal clinical-paraclinical investigation (i.e., thorax-pulmonary Xray, biological probes) raises questions as to the differentiated diagnosis and other associated diseases, also suggesting the existence of voluminous diaphragmatic hernia. The CT thorax-abdomen examination confirms the diaphragmatic hernia suspicion, with intra-thorax ascent of the colon up to the anterior C4 level, but does not explain the abdominal suffering; thus we suspected a biliary ileus or acute appendicitis. Medial laparotomy was imperative. Intrasurgically peritonitis was noticed located by gangrenous acute apendicitis, perforated, with coprolite, for which apendictomy and lavage-drainage pf the peritoneal cavity was performed. Post-surgical status: favourable to recovery.

  14. New Role for Granulocyte Colony-Stimulating Factor-Induced Extracellular Signal-Regulated Kinase 1/2 in Histone Modification and Retinoic Acid Receptor α Recruitment to Gene Promoters: Relevance to Acute Promyelocytic Leukemia Cell Differentiation

    PubMed Central

    Cassinat, B.; Zassadowski, F.; Ferry, C.; Llopis, L.; Bruck, N.; Lainey, E.; Duong, V.; Cras, A.; Despouy, G.; Chourbagi, O.; Beinse, G.; Fenaux, P.; Rochette Egly, C.; Chomienne, C.

    2011-01-01

    The induction of the granulocytic differentiation of leukemic cells by all-trans retinoic acid (RA) has been a major breakthrough in terms of survival for acute promyelocytic leukemia (APL) patients. Here we highlight the synergism and the underlying novel mechanism between RA and the granulocyte colony-stimulating factor (G-CSF) to restore differentiation of RA-refractory APL blasts. First, we show that in RA-refractory APL cells (UF-1 cell line), PML-RA receptor alpha (RARα) is not released from target promoters in response to RA, resulting in the maintenance of chromatin repression. Consequently, RARα cannot be recruited, and the RA target genes are not activated. We then deciphered how the combination of G-CSF and RA successfully restored the activation of RA target genes to levels achieved in RA-sensitive APL cells. We demonstrate that G-CSF restores RARα recruitment to target gene promoters through the activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and the subsequent derepression of chromatin. Thus, combinatorial activation of cytokines and RARs potentiates transcriptional activity through epigenetic modifications induced by specific signaling pathways. PMID:21262770

  15. Minimally invasive mediastinal surgery

    PubMed Central

    Melfi, Franca M. A.; Mussi, Alfredo

    2016-01-01

    In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a “no-touch” technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally

  16. The ZOOM minimization package

    SciTech Connect

    Fischler, Mark S.; Sachs, D.; /Fermilab

    2004-11-01

    A new object-oriented Minimization package is available for distribution in the same manner as CLHEP. This package, designed for use in HEP applications, has all the capabilities of Minuit, but is a re-write from scratch, adhering to modern C++ design principles. A primary goal of this package is extensibility in several directions, so that its capabilities can be kept fresh with as little maintenance effort as possible. This package is distinguished by the priority that was assigned to C++ design issues, and the focus on producing an extensible system that will resist becoming obsolete.

  17. Minimally refined biomass fuel

    DOEpatents

    Pearson, Richard K.; Hirschfeld, Tomas B.

    1984-01-01

    A minimally refined fluid composition, suitable as a fuel mixture and derived from biomass material, is comprised of one or more water-soluble carbohydrates such as sucrose, one or more alcohols having less than four carbons, and water. The carbohydrate provides the fuel source; water solubilizes the carbohydrates; and the alcohol aids in the combustion of the carbohydrate and reduces the vicosity of the carbohydrate/water solution. Because less energy is required to obtain the carbohydrate from the raw biomass than alcohol, an overall energy savings is realized compared to fuels employing alcohol as the primary fuel.

  18. Minimal E6 unification

    NASA Astrophysics Data System (ADS)

    Susič, Vasja

    2016-06-01

    A realistic model in the class of renormalizable supersymmetric E6 Grand Unified Theories is constructed. Its matter sector consists of 3 × 27 representations, while the Higgs sector is 27 +27 ¯+35 1'+35 1' ¯+78 . An analytic solution for a Standard Model vacuum is found and the Yukawa sector analyzed. It is argued that if one considers the increased predictability due to only two symmetric Yukawa matrices in this model, it can be considered a minimal SUSY E6 model with this type of matter sector. This contribution is based on Ref. [1].

  19. [Pathogenesis of acute encephalitis and acute encephalopathy].

    PubMed

    Shiomi, Masashi

    2011-03-01

    Many aspects of the pathogenesis of acute encephalitis and acute encephalopathy have been clarified in this decade, although many unknown mechanisms remain to be elucidated. According to progress of MRI and neuroimmunological analysis and the observation of clinical findings, many new syndromes were found, which enhanced our understanding of acute encephalitis and acute encephalopathy. The pathogenesis of encephalitis is divided into infection and immune mediated mechanisms. The antibodies to neuronal surface antigens(NSA) such as NMDA receptors, leucin-rich glioma inactivated 1 (LGI1) and aquaporin 4 were demonstrated in specific encephalitis, limbic encephalitis and neuromyelitis optica. Anti-NSA antibody encephalitis should be treated by immunotherapy such as corticosteroid and plasmapheresis. Acute encephalitis with refractory repetitive partial seizures (AERRPS) is a devastating postinfectious disease in children and adults, although the pathogenesis of AERRPS is poorly understood. Influenza associated encephalopathy(IAE) is characterized by it's high incidence in Japanese children between 1 year and 5 years of age, its onset in the first or the second day of illness and its high mortality (15-30%) and morbidity (25-40%). We proposed the classification of IAE with poor prognosis from the neuroradiological findings. Four types of encephalopathy seem to be differentiated from each other, acute necrotizing encephalopathy (ANE) type, hemorrhagic shock and encephalopathy syndrome (HSES) type, acute brain swelling (ABS) type, febrile convulsive status epilepticus (FCSE) type. The notable radiological features are thalamic lesions in ANE, diffuse cerebral cortical cytotoxic edema in HSES, reversible cerebral swelling in ABS which sometimes reaches lethal brain herniation, and in FCSE type, dendritic high signal in subcortical white matter by DWI ("bright tree appearance") appears simultaneously with the later onset of repetitive focal seizure. These four types are

  20. Acute injury directs the migration, proliferation, and differentiation of solid organ stem cells: evidence from the effect of hypoxia-ischemia in the CNS on clonal "reporter" neural stem cells.

    PubMed

    Park, Kook In; Hack, Michael A; Ourednik, Jitka; Yandava, Booma; Flax, Jonathan D; Stieg, Philip E; Gullans, Stephen; Jensen, Francis E; Sidman, Richard L; Ourednik, Vaclav; Snyder, Evan Y

    2006-05-01

    Clonal neural cells with stem-like features integrate appropriately into the developing and degenerating central and peripheral nervous system throughout the neuraxis. In response to hypoxic-ischemic (HI) injury, previously engrafted, integrated, and quiescent clonal neural stem cells (NSCs) transiently re-enter the cell cycle, migrate preferentially to the site of ischemia, and differentiate into neurons and oligodendrocytes, the neural cell types typically lost following HI brain injury. They also replenish the supply of immature uncommitted resident stem/progenitor cells. Although they yield astrocytes, scarring is inhibited. These responses appear to occur most robustly within a 3-7 day "window" following HI during which signals are elaborated that upregulate genetic programs within the NSC that mediate proliferation, migration, survival, and differentiation, most of which appear to be terminated once the "window closes" and the chronic phase ensues, sending the NSCs into a quiescent state. These insights derived from using the stem cell in a novel role--as a "reporter" cell--to both track and probe the activity of endogenous stem cells as well as to "interrogate" and "report" the genes differentially induced by the acutely vs. chronically injured milieu. NSCs may be capable of the replacement of cells, genes, and non-diffusible factors in both a widespread or more circumscribed manner (depending on the therapeutic demands of the clinical situation). They may be uniquely responsive to some types of neurodegenerative conditions. We submit that these various capabilities are simply the normal expression of the basic homeostasis-preserving biologic properties and attributes of a stem cell which, if used rationally and in concert with this biology, may be exploited for therapeutic ends.

  1. Synergistic decrease of clonal proliferation, induction of differentiation, and apoptosis of acute promyelocytic leukemia cells after combined treatment with novel 20-epi vitamin D3 analogs and 9-cis retinoic acid.

    PubMed Central

    Elstner, E; Linker-Israeli, M; Le, J; Umiel, T; Michl, P; Said, J W; Binderup, L; Reed, J C; Koeffler, H P

    1997-01-01

    Patients with acute promyelocytic leukemia (APL) usually relapse after all-trans retinoic acid (RA) treatment because this therapy fails to eradicate the malignant clone. Our data showed that KH 1060 and other 20-epi vitamin D3 analogs alone were potent inhibitors of clonal growth of NB4 cells, an APL cell line (ED50, approximately 5 x 10(-11) M). The combination of KH 1060 and 9-cis-RA synergistically and irreversibly enhanced this effect. Neither KH 1060 nor 9-cis-RA (10(-6) M, 3 d) were strong inducers of differentiation of NB4 cells. However, 98% of the cells underwent differentiation to a mature phenotype with features of both granulocytes and monocytes after exposure to a combination of both compounds. Apoptosis only increased after incubation of NB4 cells with 9-cis-RA alone (28%) or with a combination of 9-cis-RA plus KH1060 (32%). Immunohistochemistry showed that the bcl-2 protein decreased from nearly 100% of the wild-type NB4 cells to 2% after incubation with a combination of KH 1060 and 9-cis-RA, and the bax protein increased from 50% of wild-type NB4 cells to 92% after culture with both analogs (5 x 10(-7) M, 3 d). Western blot analysis paralleled these results. Studies of APL cells from one untreated individual paralleled our results with NB4 cells. Taken together, the data demonstrated that nearly all of the NB4 cells can be irreversibly induced to differentiate terminally when exposed to the combination of KH 1060 and 9-cis-RA. PMID:9006004

  2. Acute Decompensated Heart Failure

    PubMed Central

    Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.

    2009-01-01

    Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075

  3. Logarithmic superconformal minimal models

    NASA Astrophysics Data System (ADS)

    Pearce, Paul A.; Rasmussen, Jørgen; Tartaglia, Elena

    2014-05-01

    The higher fusion level logarithmic minimal models {\\cal LM}(P,P';n) have recently been constructed as the diagonal GKO cosets {(A_1^{(1)})_k\\oplus (A_1^ {(1)})_n}/ {(A_1^{(1)})_{k+n}} where n ≥ 1 is an integer fusion level and k = nP/(P‧- P) - 2 is a fractional level. For n = 1, these are the well-studied logarithmic minimal models {\\cal LM}(P,P')\\equiv {\\cal LM}(P,P';1). For n ≥ 2, we argue that these critical theories are realized on the lattice by n × n fusion of the n = 1 models. We study the critical fused lattice models {\\cal LM}(p,p')_{n\\times n} within a lattice approach and focus our study on the n = 2 models. We call these logarithmic superconformal minimal models {\\cal LSM}(p,p')\\equiv {\\cal LM}(P,P';2) where P = |2p - p‧|, P‧ = p‧ and p, p‧ are coprime. These models share the central charges c=c^{P,P';2}=\\frac {3}{2}\\big (1-{2(P'-P)^2}/{P P'}\\big ) of the rational superconformal minimal models {\\cal SM}(P,P'). Lattice realizations of these theories are constructed by fusing 2 × 2 blocks of the elementary face operators of the n = 1 logarithmic minimal models {\\cal LM}(p,p'). Algebraically, this entails the fused planar Temperley-Lieb algebra which is a spin-1 Birman-Murakami-Wenzl tangle algebra with loop fugacity β2 = [x]3 = x2 + 1 + x-2 and twist ω = x4 where x = eiλ and λ = (p‧- p)π/p‧. The first two members of this n = 2 series are superconformal dense polymers {\\cal LSM}(2,3) with c=-\\frac {5}{2}, β2 = 0 and superconformal percolation {\\cal LSM}(3,4) with c = 0, β2 = 1. We calculate the bulk and boundary free energies analytically. By numerically studying finite-size conformal spectra on the strip with appropriate boundary conditions, we argue that, in the continuum scaling limit, these lattice models are associated with the logarithmic superconformal models {\\cal LM}(P,P';2). For system size N, we propose finitized Kac character formulae of the form q^{-{c^{P,P';2}}/{24}+\\Delta ^{P,P';2} _{r

  4. Differential and irreversible CNS ontogenic reduction in maximal MK-801 binding site number in the NMDA receptor after acute hypoxic hypoxia.

    PubMed

    Vacotto, M; Rodríguez Gil, D J; Mitridate de Novara, A; Fiszer de Plazas, S

    2003-06-27

    CNS exposure to hypoxia impairs excitatory and inhibitory neurotransmission. Our aim was to determine variations induced by normobaric acute hypoxic hypoxia (8% O(2) for 60 min) on the NMDA receptor complex, as well as their potential reversibility after normoxic recovery. To this end, [3H]MK-801 binding assays to a synaptic membrane fraction isolated from chick optic lobes were performed. Previous studies throughout development had disclosed a characteristic age-dependent pattern. Results at embryonic day (ED) 12 and 18 indicated two distinct MK-801 binding sites. Hypoxic treatment failed to alter either the high affinity site dissociation constant (K(d)) or its maximal binding capacity (B(max)), whereas the low affinity site B(max) was significantly decreased (50% and 30% at ED12 and 18, respectively), without alteration in its K(d) values. Hypoxic embryos restored for 48 h at ED12 to normoxic conditions displayed unchanged MK-801 binding reduction, unlike those treated likewise at ED18 whose values fully recovered control levels. To conclude, hypoxic treatment reduces low affinity MK-801 B(max) in the NMDA receptor which proves irreversible up to ED12. Such early neuronal vulnerability may be due to post-transcriptional changes, to endocytosis followed by receptor degradation, or alternatively to cell death.

  5. Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    Tao, Yan-Fang; Pang, Li; Du, Xiao-Juan; Sun, Li-Chao; Hu, Shao-Yan; Lu, Jun; Cao, Lan; Zhao, Wen-Li; Feng, Xing; Wang, Jian; Wu, Dong; Wang, Na; Ni, Jian; Pan, Jian

    2013-01-01

    Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300. Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL. PMID:23389039

  6. Minimizing fan energy costs

    SciTech Connect

    Monroe, R.C.

    1985-05-27

    Minimizing fan energy costs and maximizing fan efficiency is the subject of this paper. Blade design itself can cause poor flow distribution and inefficiency. A basic design criterion is that a blade should produce uniform flow over the entire plane of the fan. Also an inherent problem with the axial fan is swirl -- the tangential deflection of exit-flow caused by the effect of torque. Swirl can be prevented with an inexpensive hub component. Basic efficiency can be checked by means of the fan's performance curve. Generally, fewer blades translate into higher axial-fan efficiency. A crowded inboard area creates hub turbulence which lessens efficiency. Whether the pitch of fan blades is fixed or variable also affects energy consumption. Power savings of 50% per year or more can be realized by replacing fixed-pitch, continuously operating fans with fans whose blade pitch or speed is automatically varied.

  7. Transanal Minimally Invasive Surgery

    PubMed Central

    deBeche-Adams, Teresa; Nassif, George

    2015-01-01

    Transanal minimally invasive surgery (TAMIS) was first described in 2010 as a crossover between single-incision laparoscopic surgery and transanal endoscopic microsurgery (TEM) to allow access to the proximal and mid-rectum for resection of benign and early-stage malignant rectal lesions. The TAMIS technique can also be used for noncurative intent surgery of more advanced lesions in patients who are not candidates for radical surgery. Proper workup and staging should be done before surgical decision-making. In addition to the TAMIS port, instrumentation and set up include readily available equipment found in most operating suites. TAMIS has proven its usefulness in a wide range of applications outside of local excision, including repair of rectourethral fistula, removal of rectal foreign body, control of rectal hemorrhage, and as an adjunct in total mesorectal excision for rectal cancer. TAMIS is an easily accessible, technically feasible, and cost-effective alternative to TEM. PMID:26491410

  8. [Minimal invasive implantology].

    PubMed

    Bruck, N; Zagury, A; Nahlieli, O

    2015-07-01

    Endoscopic surgery has changed the philosophy and practice of modern surgery in all aspects of medicine. It gave rise to minimally invasive surgery procedures based on the ability to visualize and to operate via small channels. In maxillofacial surgery, our ability to see clearly the surgical field opened an entirely new world of exploration, as conditions that were once almost impossible to control and whose outcome was uncertain can be now predictably managed. in this article we will descripe the advantage of using the oral endoscope during the dental implantology procedure, and we will describe a unique implant which enable us in combination with the oral endoscope to create a maxillary sinus lift with out the need of the major surgery with all of its risks and complication.

  9. [Minimally invasive breast surgery].

    PubMed

    Mátrai, Zoltán; Gulyás, Gusztáv; Kunos, Csaba; Sávolt, Akos; Farkas, Emil; Szollár, András; Kásler, Miklós

    2014-02-01

    Due to the development in medical science and industrial technology, minimally invasive procedures have appeared in the surgery of benign and malignant breast diseases. In general , such interventions result in significantly reduced breast and chest wall scars, shorter hospitalization and less pain, but they require specific, expensive devices, longer surgical time compared to open surgery. Furthermore, indications or oncological safety have not been established yet. It is quite likely, that minimally invasive surgical procedures with high-tech devices - similar to other surgical subspecialties -, will gradually become popular and it may form part of routine breast surgery even. Vacuum-assisted core biopsy with a therapeutic indication is suitable for the removal of benign fibroadenomas leaving behind an almost invisible scar, while endoscopically assisted skin-sparing and nipple-sparing mastectomy, axillary staging and reconstruction with latissimus dorsi muscle flap are all feasible through the same short axillary incision. Endoscopic techniques are also suitable for the diagnostics and treatment of intracapsular complications of implant-based breast reconstructions (intracapsular fluid, implant rupture, capsular contracture) and for the biopsy of intracapsular lesions with uncertain pathology. Perception of the role of radiofrequency ablation of breast tumors requires further hands-on experience, but it is likely that it can serve as a replacement of surgical removal in a portion of primary tumors in the future due to the development in functional imaging and anticancer drugs. With the reduction of the price of ductoscopes routine examination of the ductal branch system, guided microdochectomy and targeted surgical removal of terminal ducto-lobular units or a "sick lobe" as an anatomical unit may become feasible. The paper presents the experience of the authors and provides a literature review, for the first time in Hungarian language on the subject. Orv. Hetil

  10. Minimally invasive parathyroid surgery

    PubMed Central

    Noureldine, Salem I.; Gooi, Zhen

    2015-01-01

    Traditionally, bilateral cervical exploration for localization of all four parathyroid glands and removal of any that are grossly enlarged has been the standard surgical treatment for primary hyperparathyroidism (PHPT). With the advances in preoperative localization studies and greater public demand for less invasive procedures, novel targeted, minimally invasive techniques to the parathyroid glands have been described and practiced over the past 2 decades. Minimally invasive parathyroidectomy (MIP) can be done either through the standard Kocher incision, a smaller midline incision, with video assistance (purely endoscopic and video-assisted techniques), or through an ectopically placed, extracervical, incision. In current practice, once PHPT is diagnosed, preoperative evaluation using high-resolution radiographic imaging to localize the offending parathyroid gland is essential if MIP is to be considered. The imaging study results suggest where the surgeon should begin the focused procedure and serve as a road map to allow tailoring of an efficient, imaging-guided dissection while eliminating the unnecessary dissection of multiple glands or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may be measured during the procedure, or a gamma probe used during radioguided parathyroidectomy, to ascertain that the correct gland has been excised and that no other hyperfunctional tissue is present. MIP has many advantages over the traditional bilateral, four-gland exploration. MIP can be performed using local anesthesia, requires less operative time, results in fewer complications, and offers an improved cosmetic result and greater patient satisfaction. Additional advantages of MIP are earlier hospital discharge and decreased overall associated costs. This article aims to address the considerations for accomplishing MIP, including the role of preoperative imaging studies, intraoperative adjuncts, and surgical techniques. PMID:26425454

  11. Differential effects of pirfenidone on acute pulmonary injury and ensuing fibrosis in the hamster model of amiodarone-induced pulmonary toxicity.

    PubMed

    Card, Jeffrey W; Racz, William J; Brien, James F; Margolin, Solomon B; Massey, Thomas E

    2003-09-01

    Pulmonary toxicity, including fibrosis, is a serious adverse effect associated with the antidysrhythmic drug amiodarone (AM). We tested the potential usefulness of pirfenidone against AM-induced pulmonary toxicity in the hamster model. Intratracheal AM administration resulted in pulmonary fibrosis 21 days posttreatment, as evidenced by an increased hydroxyproline content and histological damage. Dietary pirfenidone administration (0.5% w/w in chow), for 3 days prior to and continuously after AM, prevented fibrosis and suppressed elevation of pulmonary transforming growth factor (TGF)-beta1 mRNA content at 7 and 21 days post-AM. Protection against AM-induced lung damage was not observed when supplementation with pirfenidone was delayed until 7 days following AM administration, suggesting that alteration of early events in AM lung toxicity is necessary for the protective effect of pirfenidone. Both AM and bleomycin, another pulmonary fibrogen, caused inflammation 24 h after intratracheal dosing, measured as increased lactate dehydrogenase activity, protein content, and cellular alterations in bronchoalveolar lavage fluid, with the response to AM markedly greater than that to bleomycin. Administration of AM, but not bleomycin, also caused whole lung mitochondrial dysfunction, alveolar macrophage death, and an influx of eosinophils into the lung, of which pirfenidone was able to decrease only the latter. We conclude that: (1) AM induces alveolar macrophage death and severe, acute pulmonary inflammation with associated eosinophilia following intratracheal administration; (2) mitochondrial dysfunction may play an early role in AM pulmonary injury; and (3) pirfenidone decreases AM-induced pulmonary fibrosis in the hamster, probably through suppression of TGF-beta1 gene expression.

  12. Microarray and real-time RT-PCR analyses of differential human gene expression patterns induced by severe acute respiratory syndrome (SARS) coronavirus infection of Vero cells.

    PubMed

    Leong, W F; Tan, H C; Ooi, E E; Koh, D R; Chow, Vincent T K

    2005-02-01

    Vero E6 African green monkey kidney cells are highly susceptible to infection with the newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV), and they are permissive for rapid viral replication, with resultant cytopathic effects. We employed cDNA microarray analysis to characterize the cellular transcriptional responses of homologous human genes at 12 h post-infection. Seventy mRNA transcripts belonging to various functional classes exhibited significant alterations in gene expression. There was considerable induction of heat shock proteins that are crucial to the immune response mechanism. Modified levels of several transcripts involved in pro-inflammatory and anti-inflammatory processes exemplified the balance between opposing forces during SARS pathogenesis. Other genes displaying altered transcription included those associated with host translation, cellular metabolism, cell cycle, signal transduction, transcriptional regulation, protein trafficking, protein modulators, and cytoskeletal proteins. Alterations in the levels of several novel transcripts encoding hypothetical proteins and expressed sequence tags were also identified. In addition, transcription of apoptosis-related genes DENN and hIAP1 was upregulated in contrast to FAIM. Elevated Mx1 expression signified a strong host response to mediate antiviral resistance. Also expressed in infected cells was the C-terminal alternative splice variant of the p53 tumor suppressor gene encoding a modified truncated protein that can influence the activity of wild-type p53. We observed the interplay between various mechanisms to favor virus multiplication before full-blown apoptosis and the triggering of several pathways in host cells in an attempt to eliminate the pathogen. Microarray analysis identifies the critical host-pathogen interactions during SARS-CoV infection and provides new insights into the pathophysiology of SARS.

  13. Differential expression of miR-17~92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia.

    PubMed

    Scherr, M; Elder, A; Battmer, K; Barzan, D; Bomken, S; Ricke-Hoch, M; Schröder, A; Venturini, L; Blair, H J; Vormoor, J; Ottmann, O; Ganser, A; Pich, A; Hilfiker-Kleiner, D; Heidenreich, O; Eder, M

    2014-03-01

    Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL. PMID:24280866

  14. Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room.

    PubMed

    Gregory, Christopher J; Lorenzi, Olga D; Colón, Lisandra; García, Arleene Sepúlveda; Santiago, Luis M; Rivera, Ramón Cruz; Bermúdez, Liv Jossette Cuyar; Báez, Fernando Ortiz; Aponte, Delanor Vázquez; Tomashek, Kay M; Gutierrez, Jorge; Alvarado, Luisa

    2011-12-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm(3)) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2-7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue.

  15. Utility of the Tourniquet Test and the White Blood Cell Count to Differentiate Dengue among Acute Febrile Illnesses in the Emergency Room

    PubMed Central

    Gregory, Christopher J.; Lorenzi, Olga D.; Colón, Lisandra; Sepúlveda García, Arleene; Santiago, Luis M.; Cruz Rivera, Ramón; Cuyar Bermúdez, Liv Jossette; Ortiz Báez, Fernando; Vázquez Aponte, Delanor; Tomashek, Kay M.; Gutierrez, Jorge; Alvarado, Luisa

    2011-01-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm3) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2–7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue. PMID:22163057

  16. The acute toxicity of coal liquefaction-derived materials.

    PubMed

    McKee, R H; Biles, R W; Kapp, R W; Hinz, J P

    1984-08-01

    The acute toxicity of a series of potential streams from the EDS coal liquefaction process have been assessed in animal bioassays. In general, the materials present minimal acute toxic hazards. However, there was some evidence of ocular and dermal irritation. These results indicate that eye and dermal contact should be minimized, particularly when the process streams contain high concentrations of phenolic materials.

  17. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  18. A minimal lentivirus Tat.

    PubMed Central

    Derse, D; Carvalho, M; Carroll, R; Peterlin, B M

    1991-01-01

    Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop. Images PMID:1658392

  19. Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise.

    PubMed

    Morton, James P; MacLaren, Don P M; Cable, Nigel T; Bongers, Thomas; Griffiths, Richard D; Campbell, Iain T; Evans, Louise; Kayani, Anna; McArdle, Anne; Drust, Barry

    2006-07-01

    The exercise-induced expression of heat shock proteins (HSPs) in rodent models is relatively well defined. In contrast, comparable data from human studies are limited and the exercise-induced stress response of human skeletal muscle is far from understood. This study has characterized the time course and magnitude of the HSP response in the skeletal muscles of a healthy active, but untrained, young male population following a running exercise protocol. Eight subjects performed 45 min of treadmill running at a speed corresponding to their lactate threshold (11.7 +/- 0.5 km/h; 69.8 +/- 4.8% maximum O2 uptake). Muscle biopsies were obtained from the vastus lateralis muscle immediately before and at 24 h, 48 h, 72 h, and 7 days postexercise. Exercise induced a significant (P < 0.05) but variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression with peak increases (typically occurring at 48 h postexercise) to 210, 170, and 139% of preexercise levels, respectively. In contrast, exercise did not induce a significant increase in either HSP27, alphaB-crystallin, SOD 2 (MnSOD) protein content, or the activity of SOD and catalase. When examining baseline protein levels, HSC70, HSP27, and alphaB-crystallin appeared consistently expressed between subjects, whereas HSP70 and MnSOD displayed marked individual variation of up to 3- and 1.5-fold, respectively. These data are the first to define the time course and extent of HSP production in human skeletal muscle following a moderately demanding and nondamaging running exercise protocol. Data demonstrate a differential effect of aerobic exercise on specific HSPs.

  20. Ester Hydrolysis Differentially Reduces Aconitine-Induced Anti-hypersensitivity and Acute Neurotoxicity: Involvement of Spinal Microglial Dynorphin Expression and Implications for Aconitum Processing

    PubMed Central

    Li, Teng-Fei; Gong, Nian; Wang, Yong-Xiang

    2016-01-01

    Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression. This study aimed to elucidate whether the acetylester and benzoylester groups are involved in aconitine-induced dynorphin A expression, anti-hypersensitivity, neurotoxicity in neuropathic rats. Intrathecal administration of aconitine and benzoylaconine (but not aconine) attenuated mechanical allodynia and heat hyperalgesia, with normalized ED50 values of 35 pmol and 3.6 nmol, respectively. Aconitine and benzoylaconine anti-allodynia was completely blocked by the microglial inhibitor, dynorphin A antiserum, and κ-opioid receptor antagonist. Aconitine and benzoylaconine, but not aconine, stimulated dynorphin A expression in cultured primary spinal microglia, with EC50 values of 32 nM and 3 μM, respectively. Intrathecal aconitine, benzoylaconine and aconine induced flaccid paralysis and death, with normalized TD50 values of 0.5 nmol, 0.2 μmol, and 1.6 μmol, respectively. The TD50/ED50 ratios of aconitine and benzolyaconine were 14:1 and 56:1. Our results suggest that both the C8-acetyl and C14-benzoyl groups are essential for aconitine to stimulate spinal microglial dynorphin A expression and subsequent anti-hypersensitivity, which can be separated from neurotoxicity, because both benzoylaconine and aconine differentially produced anti-hypersensitivity and neurotoxicity due to their different stimulatory ability on dynorphin A expression. Our results support the scientific rationale for Aconitum processing, but caution should be taken to

  1. Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection▿

    PubMed Central

    Meythaler, Mareike; Martinot, Amanda; Wang, Zichun; Pryputniewicz, Sarah; Kasheta, Melissa; Ling, Binhua; Marx, Preston A.; O'Neil, Shawn; Kaur, Amitinder

    2009-01-01

    In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8+ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8+ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4+ and CD4−CD8− T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection. PMID:18987149

  2. CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia

    PubMed Central

    Haferlach, Claudia; Bacher, Ulrike; Kohlmann, Alexander; Schindela, Sonja; Alpermann, Tamara; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Torsten

    2011-01-01

    Background Alterations of the short arm of chromosome 12 (12p) occur in various hematologic malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest. Design and Methods We selected seven patients with myeloid malignancies and small 12p deletions detected by fluorescence in situ hybridization encompassing only the region centromeric of ETV6 and further evaluated them by single nucleotide polymorphism microarrays. Results The minimally deleted region contained only nine genes. These genes were subsequently analyzed by microarray expression profiling in an independent cohort of 781 patients, most, but not all, of whom had different hematologic malignancies CREBL2, MANSC1, and CDKN1B were expressed in more than 25% of cases, while the other six genes were expressed in only a minority of cases. As CDKN1B is a cell cycle regulator and functions as a tumor suppressor gene, this gene was selected for further expression studies in 286 patients with acute myeloid leukemia. When comparing patients with low CDKN1B expression (expression level <1,160; 1st quartile) with those with intermediate or high expression (2nd–4th quartiles), certain mutations were observed more frequently in the former: RUNX1-RUNX1T1 (11/83, 13.3% versus 5/203; 2.5%; P=0.001), PML-RARA rearrangements (11/83, 13.3% versus 4/203, 2.0%; P<0.001), 11q23/MLL rearrangements (6/83, 7.2% versus 4/203, 2.0%; P=0.038), and FLT3-TKD mutations (7/63, 11.1% versus 6/167, 3.6%; P=0.047). The median overall survival of patients with low CDKN1B expression was longer than that of patients with intermediate/high expression (not reached versus 14.9 months; P=0.005). Likewise, patients with low CDKN1B expression had a longer event-free survival than those with intermediate/high expression (31.0 versus 9.7 months; P=0.013). Conclusions CDKN1B is an interesting candidate gene as a potential biomarker for prognostication in acute myeloid leukemia. PMID:21422114

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

    PubMed

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

    2015-06-01

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

  4. Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up

    PubMed Central

    Cho, Young-Eun; Latour, Lawrence L.; Kim, Hyungsuk; Turtzo, L. Christine; Olivera, Anlys; Livingston, Whitney S.; Wang, Dan; Martin, Christiana; Lai, Chen; Cashion, Ann; Gill, Jessica

    2016-01-01

    Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging. PMID

  5. Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up.

    PubMed

    Cho, Young-Eun; Latour, Lawrence L; Kim, Hyungsuk; Turtzo, L Christine; Olivera, Anlys; Livingston, Whitney S; Wang, Dan; Martin, Christiana; Lai, Chen; Cashion, Ann; Gill, Jessica

    2016-01-01

    Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging. PMID

  6. Salvage chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion with graft-vs.-host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes.

    PubMed

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-03-01

    This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion (Chemo-DLI) according to minimal residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndromes who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft-vs.-host disease (GVHD) after Chemo-DLI. The 3-yr cumulative incidences of relapse, non-relapse mortality, and disease-free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early-onset MRD. Forty-four patients turned MRD negative 1 month after Chemo-DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo-DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early-onset MRD, persistent MRD after Chemo-DLI, and non-cGVHD after Chemo-DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo-DLI.

  7. Reflections concerning triply-periodic minimal surfaces.

    PubMed

    Schoen, Alan H

    2012-10-01

    In recent decades, there has been an explosion in the number and variety of embedded triply-periodic minimal surfaces (TPMS) identified by mathematicians and materials scientists. Only the rare examples of low genus, however, are commonly invoked as shape templates in scientific applications. Exact analytic solutions are now known for many of the low genus examples. The more complex surfaces are readily defined with numerical tools such as Surface Evolver software or the Landau-Ginzburg model. Even though table-top versions of several TPMS have been placed within easy reach by rapid prototyping methods, the inherent complexity of many of these surfaces makes it challenging to grasp their structure. The problem of distinguishing TPMS, which is now acute because of the proliferation of examples, has been addressed by Lord & Mackay (Lord & Mackay 2003 Curr. Sci. 85, 346-362).

  8. Reflections concerning triply-periodic minimal surfaces

    PubMed Central

    Schoen, Alan H.

    2012-01-01

    In recent decades, there has been an explosion in the number and variety of embedded triply-periodic minimal surfaces (TPMS) identified by mathematicians and materials scientists. Only the rare examples of low genus, however, are commonly invoked as shape templates in scientific applications. Exact analytic solutions are now known for many of the low genus examples. The more complex surfaces are readily defined with numerical tools such as Surface Evolver software or the Landau–Ginzburg model. Even though table-top versions of several TPMS have been placed within easy reach by rapid prototyping methods, the inherent complexity of many of these surfaces makes it challenging to grasp their structure. The problem of distinguishing TPMS, which is now acute because of the proliferation of examples, has been addressed by Lord & Mackay (Lord & Mackay 2003 Curr. Sci. 85, 346–362). PMID:24098851

  9. Guidelines for mixed waste minimization

    SciTech Connect

    Owens, C.

    1992-02-01

    Currently, there is no commercial mixed waste disposal available in the United States. Storage and treatment for commercial mixed waste is limited. Host States and compacts region officials are encouraging their mixed waste generators to minimize their mixed wastes because of management limitations. This document provides a guide to mixed waste minimization.

  10. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A.

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  11. Waste minimization handbook, Volume 1

    SciTech Connect

    Boing, L.E.; Coffey, M.J.

    1995-12-01

    This technical guide presents various methods used by industry to minimize low-level radioactive waste (LLW) generated during decommissioning and decontamination (D and D) activities. Such activities generate significant amounts of LLW during their operations. Waste minimization refers to any measure, procedure, or technique that reduces the amount of waste generated during a specific operation or project. Preventive waste minimization techniques implemented when a project is initiated can significantly reduce waste. Techniques implemented during decontamination activities reduce the cost of decommissioning. The application of waste minimization techniques is not limited to D and D activities; it is also useful during any phase of a facility`s life cycle. This compendium will be supplemented with a second volume of abstracts of hundreds of papers related to minimizing low-level nuclear waste. This second volume is expected to be released in late 1996.

  12. Acute gastroenteritis.

    PubMed

    Graves, Nancy S

    2013-09-01

    Acute gastroenteritis is a common infectious disease syndrome, causing a combination of nausea, vomiting, diarrhea, and abdominal pain. There are more than 350 million cases of acute gastroenteritis in the United States annually and 48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea affects more than half of people traveling from developed countries to developing countries. In adult and pediatric patients, the prevalence of Clostridium difficile is increasing. Contact precautions, public health education, and prudent use of antibiotics are necessary goals in decreasing the prevalence of Clostridium difficle. Preventing dehydration or providing appropriate rehydration is the primary supportive treatment of acute gastroenteritis.

  13. [Acute pancreatitis and pregnancy].

    PubMed

    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.

  14. Minimizing the Fluid Used to Induce Fracturing

    NASA Astrophysics Data System (ADS)

    Boyle, E. J.

    2015-12-01

    The less fluid injected to induce fracturing means less fluid needing to be produced before gas is produced. One method is to inject as fast as possible until the desired fracture length is obtained. Presented is an alternative injection strategy derived by applying optimal system control theory to the macroscopic mass balance. The picture is that the fracture is constant in aperture, fluid is injected at a controlled rate at the near end, and the fracture unzips at the far end until the desired length is obtained. The velocity of the fluid is governed by Darcy's law with larger permeability for flow along the fracture length. Fracture growth is monitored through micro-seismicity. Since the fluid is assumed to be incompressible, the rate at which fluid is injected is balanced by rate of fracture growth and rate of loss to bounding rock. Minimizing injected fluid loss to the bounding rock is the same as minimizing total injected fluid How to change the injection rate so as to minimize the total injected fluid is a problem in optimal control. For a given total length, the variation of the injected rate is determined by variations in overall time needed to obtain the desired fracture length, the length at any time, and the rate at which the fracture is growing at that time. Optimal control theory leads to a boundary condition and an ordinary differential equation in time whose solution is an injection protocol that minimizes the fluid used under the stated assumptions. That method is to monitor the rate at which the square of the fracture length is growing and adjust the injection rate proportionately.

  15. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  16. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  17. Basic aspects of musculoskeletal pain: from acute to chronic pain

    PubMed Central

    Arendt-Nielsen, Lars; Fernández-de-las-Peñas, César; Graven-Nielsen, Thomas

    2011-01-01

    The transition from acute to chronic musculoskeletal pain is not well understood. To understand this transition, it is important to know how peripheral and central sensitization are manifested and how they can be assessed. A variety of human pain biomarkers have been developed to quantify localized and widespread musculoskeletal pain. In addition, human surrogate models may be used to induce sensitization in otherwise healthy volunteers. Pain can arise from different musculoskeletal structures (e.g. muscles, joints, ligaments, or tendons), and differentiating the origin of pain from those different structures is a challenge. Tissue specific pain biomarkers can be used to tease these different aspects. Chronic musculoskeletal pain patients in general show signs of local/central sensitization and spread of pain to degrees which correlate to pain intensity and duration. From a management perspective, it is therefore highly important to reduce pain intensity and try to minimize the duration of pain. PMID:23115471

  18. ACUTE PELVIC PAIN IN THE ADOLESCENT: A CASE REPORT

    PubMed Central

    Samuels-Kalow, M.; Mollen, C.

    2015-01-01

    Diagnosis and treatment of acute pelvic pain in the adolescent female requires differentiating among a broad differential diagnosis that includes potentially serious illness across several organ systems. The case presented provides an illustration of the assessment and management of acute pelvic pain, and key teaching points about important potential causes. PMID:26273230

  19. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A.

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement. PMID:27630988

  20. Influenza SIRS with Minimal Pneumonitis.

    PubMed

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement. PMID:27630988

  1. Acute intestinal anisakiasis: CT findings.

    PubMed

    Ozcan, H N; Avcu, S; Pauwels, W; Mortelé, K J; De Backer, A I

    2012-09-01

    Small bowel anisakiasis is a relatively uncommon disease that results from consumption of raw or insufficiently pickled, salted, smoked, or cooked wild marine fish infected with Anisakis larvae. We report a case of intestinal anisakiasis in a 63-year-old woman presenting with acute onset of abdominal complaints one day after ingestion of raw wild-caught herring from the Northsea. Computed tomography (CT) scanning demonstrated thickening of the distal small bowel wall, mucosa with hyperenhancement, mural stratification, fluid accumulation within dilated small-bowel loops and hyperemia of mesenteric vessels. In patients with a recent history of eating raw marine fish presenting with acute onset of abdominal complaints and CT features of acute small bowel inflammation the possibility of anisakiasis should be considered in the differential diagnosis of acute abdominal syndromes.

  2. Acute incarcerated external abdominal hernia

    PubMed Central

    Yang, Xue-Fei

    2014-01-01

    External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surgery in some cases to achieve minimally invasive treatment. However, strict adherence to the indications and contraindications is still required. PMID:25489584

  3. Biomarkers in acute heart failure.

    PubMed

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure.

  4. Lipase turbidimetric assay and acute pancreatitis.

    PubMed

    Orda, R; Orda, S; Baron, J; Wiznitzer, T

    1984-04-01

    The simplified turbidimetric assay for lipase activity was used for the differential diagnosis of acute pancreatitis. Serum lipase levels were found to be increased in a group of 17 patients in whom acute pancreatitis was clinically suspected and confirmed by a high ACCR and decreased uptake of the radionuclide in the pancreas scan. The lipase levels were within normal limits in a control group of 14 patients suffering from diseases other than acute pancreatitis. The turbidimetric test was helpful for rapid quantitative determination of serum lipase and thus for the early and accurate diagnosis of acute pancreatitis. PMID:6200277

  5. Accuracy of the new radiographic sign of fecal loading in the cecum for differential diagnosis of acute appendicitis in comparison with other inflammatory diseases of right abdomen: a prospective study

    PubMed Central

    Petroianu, A; Alberti, LR

    2012-01-01

    Rationale: To assess the importance of the new radiographic sign of faecal loading in the cecum for the diagnosis of acute appendicitis, in comparison with other inflammatory diseases, and to verify the maintenance of this radiographic sign after surgical treatment of appendicitis. Methods: 470 consecutive patients admitted to the hospital due to acute abdomen were prospectively studied: Group 1 [n=170] – diagnosed with acute appendicitis, subdivided into: Subgroup 1A – [n=100] – submitted to an abdominal radiographic study before surgical treatment, Subgroup 1B – [n=70] – patients who had plain abdominal X-rays done before the surgical procedure and also the following day; Group 2 [n=100] – right nephrolithiasis; Group 3 [n=100] – right acute inflammatory pelvic disease; Group 4 [n=100] – acute cholecystitis. The patients of Groups 2,3 and 4 were submitted to abdominal radiography during the pain episode. Results: The sign of faecal loading in the cecum, characterized by hypo transparency interspersed with multiple small foci of hyper transparent images, was present in 97 patients of Subgroup 1A, in 68 patients of Subgroup 1B, in 19 patients of Group 2, in 12 patients of Group 3 and in 13 patients of Group 4. During the postoperative period the radiographic sign disappeared in 66 of the 68 cases that had presented with the sign. The sensitivity of the radiographic sign for acute appendicitis was 97.05% and its specificity was 85.33%. The positive predictive value for acute appendicitis was 78.94% and its negative predictive value was 98. 08%. Discussion: The radiographic image of faecal loading in the cecum is associated with acute appendicitis and disappears after appendectomy. This sign is uncommon in other acute inflammatory diseases of the right side of the abdomen. PMID:22574093

  6. Acute otitis media.

    PubMed

    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. PMID:24439877

  7. Acute otitis media.

    PubMed

    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.

  8. Minimal but non-minimal inflation and electroweak symmetry breaking

    NASA Astrophysics Data System (ADS)

    Marzola, Luca; Racioppi, Antonio

    2016-10-01

    We consider the most minimal scale invariant extension of the standard model that allows for successful radiative electroweak symmetry breaking and inflation. The framework involves an extra scalar singlet, that plays the rôle of the inflaton, and is compatibile with current experimental bounds owing to the non-minimal coupling of the latter to gravity. This inflationary scenario predicts a very low tensor-to-scalar ratio r ≈ 10‑3, typical of Higgs-inflation models, but in contrast yields a scalar spectral index ns simeq 0.97 which departs from the Starobinsky limit. We briefly discuss the collider phenomenology of the framework.

  9. Laparoscopic rectosigmoid resection for acute sigmoid diverticulitis.

    PubMed

    Zdichavsky, Marty; Königsrainer, Alfred; Granderath, Frank A

    2009-04-01

    Laparoscopic sigmoid colectomy has been widely accepted as elective approach but is, however, still discussed controversially for acute cases. Patients receiving a laparoscopic early single-stage procedure benefit from an early postoperative convalescence with a minimum of disability. As more surgeons gain expertise in minimally invasive surgery of the rectosigmoid, this video highlights the main steps of a rectosigmoid resection for acute complicated diverticulitis. PMID:18795376

  10. Microbial life detection with minimal assumptions

    NASA Astrophysics Data System (ADS)

    Kounaves, Samuel P.; Noll, Rebecca A.; Buehler, Martin G.; Hecht, Michael H.; Lankford, Kurt; West, Steven J.

    2002-02-01

    To produce definitive and unambiguous results, any life detection experiment must make minimal assumptions about the nature of extraterrestrial life. The only criteria that fits this definition is the ability to reproduce and in the process create a disequilibrium in the chemical and redox environment. The Life Detection Array (LIDA), an instrument proposed for the 2007 NASA Mars Scout Mission, and in the future for the Jovian moons, enables such an experiment. LIDA responds to minute biogenic chemical and physical changes in two identical 'growth' chambers. The sensitivity is provided by two differentially monitored electrochemical sensor arrays. Growth in one of the chambers alters the chemistry and ionic properties and results in a signal. This life detection system makes minimal assumptions; that after addition of water the microorganism replicates and in the process will produce small changes in its immediate surroundings by consuming, metabolizing, and excreting a number of molecules and/or ionic species. The experiment begins by placing an homogenized split-sample of soil or water into each chamber, adding water if soil, sterilizing via high temperature, and equilibrating. In the absence of any microorganism in either chamber, no signal will be detected. The inoculation of one chamber with even a few microorganisms which reproduce, will create a sufficient disequilibrium in the system (compared to the control) to be detectable. Replication of the experiment and positive results would lead to a definitive conclusion of biologically induced changes. The split sample and the nanogram inoculation eliminates chemistry as a causal agent.

  11. LLNL Waste Minimization Program Plan

    SciTech Connect

    Not Available

    1990-02-14

    This document is the February 14, 1990 version of the LLNL Waste Minimization Program Plan (WMPP). The Waste Minimization Policy field has undergone continuous changes since its formal inception in the 1984 HSWA legislation. The first LLNL WMPP, Revision A, is dated March 1985. A series of informal revision were made on approximately a semi-annual basis. This Revision 2 is the third formal issuance of the WMPP document. EPA has issued a proposed new policy statement on source reduction and recycling. This policy reflects a preventative strategy to reduce or eliminate the generation of environmentally-harmful pollutants which may be released to the air, land surface, water, or ground water. In accordance with this new policy new guidance to hazardous waste generators on the elements of a Waste Minimization Program was issued. In response to these policies, DOE has revised and issued implementation guidance for DOE Order 5400.1, Waste Minimization Plan and Waste Reduction reporting of DOE Hazardous, Radioactive, and Radioactive Mixed Wastes, final draft January 1990. This WMPP is formatted to meet the current DOE guidance outlines. The current WMPP will be revised to reflect all of these proposed changes when guidelines are established. Updates, changes and revisions to the overall LLNL WMPP will be made as appropriate to reflect ever-changing regulatory requirements. 3 figs., 4 tabs.

  12. Minimally invasive aortic valve surgery

    PubMed Central

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-01-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  13. Minimally invasive aortic valve surgery.

    PubMed

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-09-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  14. What is minimally invasive dentistry?

    PubMed

    Ericson, Dan

    2004-01-01

    Minimally Invasive Dentistry is the application of "a systematic respect for the original tissue." This implies that the dental profession recognizes that an artifact is of less biological value than the original healthy tissue. Minimally invasive dentistry is a concept that can embrace all aspects of the profession. The common delineator is tissue preservation, preferably by preventing disease from occurring and intercepting its progress, but also removing and replacing with as little tissue loss as possible. It does not suggest that we make small fillings to restore incipient lesions or surgically remove impacted third molars without symptoms as routine procedures. The introduction of predictable adhesive technologies has led to a giant leap in interest in minimally invasive dentistry. The concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The evidence-base for survival of restorations clearly indicates that restoring teeth is a temporary palliative measure that is doomed to fail if the disease that caused the condition is not addressed properly. Today, the means, motives and opportunities for minimally invasive dentistry are at hand, but incentives are definitely lacking. Patients and third parties seem to be convinced that the only things that count are replacements. Namely, they are prepared to pay for a filling but not for a procedure that can help avoid having one.

  15. A Defense of Semantic Minimalism

    ERIC Educational Resources Information Center

    Kim, Su

    2012-01-01

    Semantic Minimalism is a position about the semantic content of declarative sentences, i.e., the content that is determined entirely by syntax. It is defined by the following two points: "Point 1": The semantic content is a complete/truth-conditional proposition. "Point 2": The semantic content is useful to a theory of…

  16. Assembly of a minimal protocell

    NASA Astrophysics Data System (ADS)

    Rasmussen, Steen

    2007-03-01

    What is minimal life, how can we make it, and how can it be useful? We present experimental and computational results towards bridging nonliving and living matter, which results in life that is different and much simpler than contemporary life. A simple yet tightly coupled catalytic cooperation between genes, metabolism, and container forms the design underpinnings of our protocell, which is a minimal self-replicating molecular machine. Experimentally, we have recently demonstrated this coupling by having an informational molecule (8-oxoguanine) catalytically control the light driven metabolic (Ru-bpy based) production of container materials (fatty acids). This is a significant milestone towards assembling a minimal self-replicating molecular machine. Recent theoretical investigations indicate that coordinated exponential component growth should naturally emerge as a result from such a catalytic coupling between the main protocellular components. A 3-D dissipative particle simulation (DPD) study of the full protocell life-cycle exposes a number of anticipated systemic issues associated with the remaining experimental challenges for the implementation of the minimal protocell. Finally we outline how more general self-replicating materials could be useful.

  17. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  18. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.

  19. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child

    PubMed Central

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  20. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  1. Anaesthesia for minimally invasive surgery

    PubMed Central

    Dec, Marta

    2015-01-01

    Minimally invasive surgery (MIS) is rising in popularity. It offers well-known benefits to the patient. However, restricted access to the surgical site and gas insufflation into the body cavities may result in severe complications. From the anaesthetic point of view MIS poses unique challenges associated with creation of pneumoperitoneum, carbon dioxide absorption, specific positioning and monitoring a patient to whom the anaesthetist has often restricted access, in a poorly lit environment. Moreover, with refinement of surgical procedures and growing experience the anaesthetist is presented with patients from high-risk groups (obese, elderly, with advanced cardiac and respiratory disease) who once were deemed unsuitable for the laparoscopic technique. Anaesthetic management is aimed at getting the patient safely through the procedure, minimizing the specific risks arising from laparoscopy and the patient's coexisting medical problems, ensuring quick recovery and a relatively pain-free postoperative course with early return to normal function. PMID:26865885

  2. Minimal universal quantum heat machine.

    PubMed

    Gelbwaser-Klimovsky, D; Alicki, R; Kurizki, G

    2013-01-01

    In traditional thermodynamics the Carnot cycle yields the ideal performance bound of heat engines and refrigerators. We propose and analyze a minimal model of a heat machine that can play a similar role in quantum regimes. The minimal model consists of a single two-level system with periodically modulated energy splitting that is permanently, weakly, coupled to two spectrally separated heat baths at different temperatures. The equation of motion allows us to compute the stationary power and heat currents in the machine consistent with the second law of thermodynamics. This dual-purpose machine can act as either an engine or a refrigerator (heat pump) depending on the modulation rate. In both modes of operation, the maximal Carnot efficiency is reached at zero power. We study the conditions for finite-time optimal performance for several variants of the model. Possible realizations of the model are discussed.

  3. Principle of minimal work fluctuations

    NASA Astrophysics Data System (ADS)

    Xiao, Gaoyang; Gong, Jiangbin

    2015-08-01

    Understanding and manipulating work fluctuations in microscale and nanoscale systems are of both fundamental and practical interest. For example, in considering the Jarzynski equality =e-β Δ F , a change in the fluctuations of e-β W may impact how rapidly the statistical average of e-β W converges towards the theoretical value e-β Δ F, where W is the work, β is the inverse temperature, and Δ F is the free energy difference between two equilibrium states. Motivated by our previous study aiming at the suppression of work fluctuations, here we obtain a principle of minimal work fluctuations. In brief, adiabatic processes as treated in quantum and classical adiabatic theorems yield the minimal fluctuations in e-β W. In the quantum domain, if a system initially prepared at thermal equilibrium is subjected to a work protocol but isolated from a bath during the time evolution, then a quantum adiabatic process without energy level crossing (or an assisted adiabatic process reaching the same final states as in a conventional adiabatic process) yields the minimal fluctuations in e-β W, where W is the quantum work defined by two energy measurements at the beginning and at the end of the process. In the classical domain where the classical work protocol is realizable by an adiabatic process, then the classical adiabatic process also yields the minimal fluctuations in e-β W. Numerical experiments based on a Landau-Zener process confirm our theory in the quantum domain, and our theory in the classical domain explains our previous numerical findings regarding the suppression of classical work fluctuations [G. Y. Xiao and J. B. Gong, Phys. Rev. E 90, 052132 (2014), 10.1103/PhysRevE.90.052132].

  4. Principle of minimal work fluctuations.

    PubMed

    Xiao, Gaoyang; Gong, Jiangbin

    2015-08-01

    Understanding and manipulating work fluctuations in microscale and nanoscale systems are of both fundamental and practical interest. For example, in considering the Jarzynski equality 〈e-βW〉=e-βΔF, a change in the fluctuations of e-βW may impact how rapidly the statistical average of e-βW converges towards the theoretical value e-βΔF, where W is the work, β is the inverse temperature, and ΔF is the free energy difference between two equilibrium states. Motivated by our previous study aiming at the suppression of work fluctuations, here we obtain a principle of minimal work fluctuations. In brief, adiabatic processes as treated in quantum and classical adiabatic theorems yield the minimal fluctuations in e-βW. In the quantum domain, if a system initially prepared at thermal equilibrium is subjected to a work protocol but isolated from a bath during the time evolution, then a quantum adiabatic process without energy level crossing (or an assisted adiabatic process reaching the same final states as in a conventional adiabatic process) yields the minimal fluctuations in e-βW, where W is the quantum work defined by two energy measurements at the beginning and at the end of the process. In the classical domain where the classical work protocol is realizable by an adiabatic process, then the classical adiabatic process also yields the minimal fluctuations in e-βW. Numerical experiments based on a Landau-Zener process confirm our theory in the quantum domain, and our theory in the classical domain explains our previous numerical findings regarding the suppression of classical work fluctuations [G. Y. Xiao and J. B. Gong, Phys. Rev. E 90, 052132 (2014)].

  5. Minimally invasive surgery. Future developments.

    PubMed

    Wickham, J E

    1994-01-15

    The rapid development of minimally invasive surgery means that there will be fundamental changes in interventional treatment. Technological advances will allow new minimally invasive procedures to be developed. Application of robotics will allow some procedures to be done automatically, and coupling of slave robotic instruments with virtual reality images will allow surgeons to perform operations by remote control. Miniature motors and instruments designed by microengineering could be introduced into body cavities to perform operations that are currently impossible. New materials will allow changes in instrument construction, such as use of memory metals to make heat activated scissors or forceps. With the reduced trauma associated with minimally invasive surgery, fewer operations will require long hospital stays. Traditional surgical wards will become largely redundant, and hospitals will need to cope with increased through-put of patients. Operating theatres will have to be equipped with complex high technology equipment, and hospital staff will need to be trained to manage it. Conventional nursing care will be carried out more in the community. Many traditional specialties will be merged, and surgical training will need fundamental revision to ensure that surgeons are competent to carry out the new procedures. PMID:8312776

  6. [Acute diarrhea].

    PubMed

    Burgmann, Konstantin; Schoepfer, Alain

    2014-09-01

    Diarrhea, defined as three or more loose or watery stools per day, represents a frequent problem in outpatients as well as inpatients. As most of the patients with acute diarrhea show a self-limiting disease course, the main challenge for the physician is to discriminate patients for whom symptomatic therapy is sufficient from those with severe disease course and threatening complications. This review aims to provide a practical guidance for such decisions.

  7. Posterior interosseous and ulnar nerve motor palsies after a minimally displaced radial neck fracture.

    PubMed

    Stepanovich, Matthew T; Hogan, Christopher J

    2012-08-01

    Peripheral nerve injury is a serious potential complication following an upper extremity fracture. A rare case of acute posterior interosseous nerve and ulnar nerve palsy following a minimally displaced radial neck fracture is reported. With nonsurgical management, both nerves demonstrated excellent functional recovery. Although rare, nerve palsies can occur during a variety of upper extremity clinical situations, including minimally displaced fractures, and the importance of a detailed neurologic examination cannot be overstated.

  8. [Radionuclide diagnosis of acute pyelonephritis].

    PubMed

    Mil'ko, V I; Moskalenko, N I; Tikhonenko, E P

    1986-01-01

    Nephroscintigraphy using a 67Ga-citrate complex and 99mTc-pyrophosphate was performed in 88 patients with acute pyelonephritis. Nuclide hyperfixation was revealed in 97.8% of the cases. Three groups of patients were singled out on the basis of the intensity of incorporation and nature of the distribution of the radiopharmaceuticals (RP) in the kidneys. In the 1st group the RP incorporation was insignificant but higher than normal values; the RP distribution in the affected kidney was diffuse-inhomogenous. These changes were considered to be typical of acute serous pyelonephritis. In the 2nd and 3rd groups a sharp rise of the RP accumulation was noted, being typical of acute purulent pyelonephritis. One could distinguish between diffuse and focal lesions by the picture of the RP distribution in the renal parenchyma. Diuresis stimulation made it possible to differentiate an actual nuclide fixation during inflammation from nuclide mechanical retention as a result of urine outflow disorder. According to the authors, both radiopharmaceuticals could be applied for the diagnosis of acute pyelonephritis as well as for differential diagnosis of various forms of the disease. PMID:3001474

  9. Strain energy minimization in SSC (Superconducting Super Collider) magnet winding

    SciTech Connect

    Cook, J.M.

    1990-09-24

    Differential geometry provides a natural family of coordinate systems, the Frenet frame, in which to specify the geometric properties of magnet winding. By a modification of the Euler-Bernoulli thin rod model, the strain energy is defined with respect to this frame. Then it is minimized by a direct method from the calculus of variations. The mathematics, its implementation in a computer program, and some analysis of an SSC dipole by the program will be described. 16 refs.

  10. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia. PMID:27123874

  11. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.

  12. Minimal model for Brownian vortexes.

    PubMed

    Sun, Bo; Grier, David G; Grosberg, Alexander Y

    2010-08-01

    A Brownian vortex is a noise-driven machine that uses thermal fluctuations to extract a steady-state flow of work from a static force field. Its operation is characterized by loops in a probability current whose topology and direction can change with changes in temperature. We present discrete three- and four-state minimal models for Brownian vortexes that can be solved exactly with a master-equation formalism. These models elucidate conditions required for flux reversal in Brownian vortexes and provide insights into their thermodynamic efficiency through the rate of entropy production. PMID:20866791

  13. [Minimally invasive iridocorneal angle surgery].

    PubMed

    Jordan, J F

    2012-07-01

    The classical filtration surgery with trabeculectomy or drainage of chamber fluid with episcleral implants is the most effective method for permanent reduction of intraocular pressure to lower and normal levels. Even though both operative procedures are well-established the high efficiency of the method causes potentially dangerous intraoperative as well as interoperative complications with a frequency which cannot be ignored. In the past this led to a search for low complication alternatives with non-penetrating glaucoma surgery (NPGS) and the search is still continuing. Trabecular meshwork surgery in particular with continuous development of new operation techniques steered the focus to a complication-poor and minimally invasive, gonioscopic glaucoma surgery.

  14. The minimal scenario of leptogenesis

    NASA Astrophysics Data System (ADS)

    Blanchet, Steve; Di Bari, Pasquale

    2012-12-01

    We review the main features and results of thermal leptogenesis within the type I seesaw mechanism, the minimal extension of the Standard Model explaining neutrino masses and mixing. After presenting the simplest approach, the vanilla scenario, we discuss various important developments of recent years, such as the inclusion of lepton and heavy neutrino flavour effects, a description beyond a hierarchical heavy neutrino mass spectrum and an improved kinetic description within the density matrix and the closed-time-path formalisms. We also discuss how leptogenesis can ultimately represent an important phenomenological tool to test the seesaw mechanism and the underlying model of new physics.

  15. Radiometric calibration by rank minimization.

    PubMed

    Lee, Joon-Young; Matsushita, Yasuyuki; Shi, Boxin; Kweon, In So; Ikeuchi, Katsushi

    2013-01-01

    We present a robust radiometric calibration framework that capitalizes on the transform invariant low-rank structure in the various types of observations, such as sensor irradiances recorded from a static scene with different exposure times, or linear structure of irradiance color mixtures around edges. We show that various radiometric calibration problems can be treated in a principled framework that uses a rank minimization approach. This framework provides a principled way of solving radiometric calibration problems in various settings. The proposed approach is evaluated using both simulation and real-world datasets and shows superior performance to previous approaches.

  16. Minimizing medical litigation, part 2.

    PubMed

    Harold, Tan Keng Boon

    2006-01-01

    Provider-patient disputes are inevitable in the healthcare sector. Healthcare providers and regulators should recognize this and plan opportunities to enforce alternative dispute resolution (ADR) a early as possible in the care delivery process. Negotiation is often the main dispute resolution method used by local healthcare providers, failing which litigation would usually follow. The role of mediation in resolving malpractice disputes has been minimal. Healthcare providers, administrators, and regulators should therefore look toward a post-event communication-cum-mediation framework as the key national strategy to resolving malpractice disputes. PMID:16711089

  17. BIFURCATIONS OF RANDOM DIFFERENTIAL EQUATIONS WITH BOUNDED NOISE ON SURFACES.

    PubMed

    Homburg, Ale Jan; Young, Todd R

    2010-03-01

    In random differential equations with bounded noise minimal forward invariant (MFI) sets play a central role since they support stationary measures. We study the stability and possible bifurcations of MFI sets. In dimensions 1 and 2 we classify all minimal forward invariant sets and their codimension one bifurcations in bounded noise random differential equations. PMID:22211081

  18. Minimizing travel claims cost with minimal-spanning tree model

    NASA Astrophysics Data System (ADS)

    Jamalluddin, Mohd Helmi; Jaafar, Mohd Azrul; Amran, Mohd Iskandar; Ainul, Mohd Sharizal; Hamid, Aqmar; Mansor, Zafirah Mohd; Nopiah, Zulkifli Mohd

    2014-06-01

    Travel demand necessitates a big expenditure in spending, as has been proven by the National Audit Department (NAD). Every year the auditing process is carried out throughout the country involving official travel claims. This study focuses on the use of the Spanning Tree model to determine the shortest path to minimize the cost of the NAD's official travel claims. The objective is to study the possibility of running a network based in the Kluang District Health Office to eight Rural Clinics in Johor state using the Spanning Tree model applications for optimizing travelling distances and make recommendations to the senior management of the Audit Department to analyze travelling details before an audit is conducted. Result of this study reveals that there were claims of savings of up to 47.4% of the original claims, over the course of the travel distance.

  19. Annual Waste Minimization Summary Report

    SciTech Connect

    Alfred J. Karns

    2007-01-01

    This report summarizes the waste minimization efforts undertaken by National Security Technologies, LLC (NSTec), for the U. S. Department of Energy (DOE) National Nuclear Security Administration Nevada Site Office (NNSA/NSO), during CY06. This report was developed in accordance with the requirements of the Nevada Test Site (NTS) Resource Conservation and Recovery Act (RCRA) Permit (No. NEV HW0021) and as clarified in a letter dated April 21, 1995, from Paul Liebendorfer of the Nevada Division of Environmental Protection to Donald Elle of the DOE, Nevada Operations Office. The NNSA/NSO Pollution Prevention (P2) Program establishes a process to reduce the volume and toxicity of waste generated by the NNSA/NSO and ensures that proposed methods of treatment, storage, and/or disposal of waste minimize potential threats to human health and the environment. The following information provides an overview of the P2 Program, major P2 accomplishments during the reporting year, a comparison of the current year waste generation to prior years, and a description of efforts undertaken during the year to reduce the volume and toxicity of waste generated by the NNSA/NSO.

  20. Less minimal supersymmetric standard model

    SciTech Connect

    de Gouvea, Andre; Friedland, Alexander; Murayama, Hitoshi

    1998-03-28

    Most of the phenomenological studies of supersymmetry have been carried out using the so-called minimal supergravity scenario, where one assumes a universal scalar mass, gaugino mass, and trilinear coupling at M{sub GUT}. Even though this is a useful simplifying assumption for phenomenological analyses, it is rather too restrictive to accommodate a large variety of phenomenological possibilities. It predicts, among other things, that the lightest supersymmetric particle (LSP) is an almost pure B-ino, and that the {mu}-parameter is larger than the masses of the SU(2){sub L} and U(1){sub Y} gauginos. We extend the minimal supergravity framework by introducing one extra parameter: the Fayet'Iliopoulos D-term for the hypercharge U(1), D{sub Y}. Allowing for this extra parameter, we find a much more diverse phenomenology, where the LSP is {tilde {nu}}{sub {tau}}, {tilde {tau}} or a neutralino with a large higgsino content. We discuss the relevance of the different possibilities to collider signatures. The same type of extension can be done to models with the gauge mediation of supersymmetry breaking. We argue that it is not wise to impose cosmological constraints on the parameter space.

  1. Next-to-minimal SOFTSUSY

    NASA Astrophysics Data System (ADS)

    Allanach, B. C.; Athron, P.; Tunstall, Lewis C.; Voigt, A.; Williams, A. G.

    2014-09-01

    We describe an extension to the SOFTSUSY program that provides for the calculation of the sparticle spectrum in the Next-to-Minimal Supersymmetric Standard Model (NMSSM), where a chiral superfield that is a singlet of the Standard Model gauge group is added to the Minimal Supersymmetric Standard Model (MSSM) fields. Often, a Z3 symmetry is imposed upon the model. SOFTSUSY can calculate the spectrum in this case as well as the case where general Z3 violating (denoted as =) terms are added to the soft supersymmetry breaking terms and the superpotential. The user provides a theoretical boundary condition for the couplings and mass terms of the singlet. Radiative electroweak symmetry breaking data along with electroweak and CKM matrix data are used as weak-scale boundary conditions. The renormalisation group equations are solved numerically between the weak scale and a high energy scale using a nested iterative algorithm. This paper serves as a manual to the NMSSM mode of the program, detailing the approximations and conventions used. Catalogue identifier: ADPM_v4_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADPM_v4_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 154886 No. of bytes in distributed program, including test data, etc.: 1870890 Distribution format: tar.gz Programming language: C++, fortran. Computer: Personal computer. Operating system: Tested on Linux 3.x. Word size: 64 bits Classification: 11.1, 11.6. Does the new version supersede the previous version?: Yes Catalogue identifier of previous version: ADPM_v3_0 Journal reference of previous version: Comput. Phys. Comm. 183 (2012) 785 Nature of problem: Calculating supersymmetric particle spectrum and mixing parameters in the next-to-minimal supersymmetric standard model. The solution to the

  2. Acute interstitial pneumonia and acute exacerbations of idiopathic pulmonary fibrosis.

    PubMed

    Swigris, Jeffrey J; Brown, Kevin K

    2006-12-01

    Acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (AEIPF) are similar respiratory disorders characterized by the rapid development of progressive dyspnea and cough. Both frequently lead to respiratory failure and death. Pathologically, each is characterized by the presence of a diffuse alveolar damage (DAD) pattern; in AIP, DAD is the sole pattern, whereas in AEIPF DAD is superimposed upon a background usual interstitial pneumonia. They differ in that patients with AEIPF have preexisting idiopathic pulmonary fibrosis, whereas patients with AIP have no predisposing disorders to account for their disease. Because both presentations overlap with multiple other causes of acute lung injury, a comprehensive evaluation is necessary to rule out disorders such as overwhelming infection or congestive heart failure. Although a confident diagnosis can be achieved without it, a surgical lung biopsy is necessary to provide a definitive diagnosis. Despite minimal evidence, glucocorticoids are frequently begun once microbiological evaluation confirms the absence of infection. Despite therapy, the case fatality rate ranges up to 70% for both, with most patients dying in the first 2 weeks. Survivors of the acute event can recover to their previous baseline; however, most AIP survivors will stabilize with some functional impairment, whereas in those with AEIPF, progressive fibrosis with functional deterioration is the rule.

  3. Minimal change disease in association with fire coral (Millepora species) exposure.

    PubMed

    Prasad, G V Ramesh; Vincent, Lloyd; Hamilton, Robert; Lim, Ki

    2006-01-01

    Numerous agents have been associated with minimal change disease. We describe a previously unreported association in a 45-year-old white woman of scuba diving exposure to fire coral (Millepora species) that was followed by the development of nephrotic syndrome, acute renal failure, pulmonary edema, and intubation. The renal biopsy specimen was consistent with minimal change disease. Institution of corticosteroid therapy resulted in symptomatic improvement and resolution of proteinuria. Physicians, particularly those in scuba-diving areas, should consider minimal change disease in exposed patients with proteinuria because a prompt diagnostic and therapeutic approach may potentially limit complications.

  4. Differentiated Staffing.

    ERIC Educational Resources Information Center

    Geisinger, Robert W.; And Others

    This report describes school operation changes in scheduling, curriculum, decisionmaking powers, and individualization of instruction that are concurrent with the adoption of differentiated staffing. The author defines differentiated staffing, explains where and at what levels it has been utilized, provides descriptions of results achieved, gives…

  5. Differential games.

    NASA Technical Reports Server (NTRS)

    Varaiya, P. P.

    1972-01-01

    General discussion of the theory of differential games with two players and zero sum. Games starting at a fixed initial state and ending at a fixed final time are analyzed. Strategies for the games are defined. The existence of saddle values and saddle points is considered. A stochastic version of a differential game is used to examine the synthesis problem.

  6. 77 FR 14813 - Public Workshop on Minimal Residual Disease; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... HUMAN SERVICES Food and Drug Administration Public Workshop on Minimal Residual Disease; Public Workshop... residual disease (MRD) as a biomarker for evaluating new drugs for the treatment of acute lymphoblastic...., a measurable characteristic that is predictive of disease outcome) that can be used to...

  7. Acute treatment of migraine headaches.

    PubMed

    Taylor, Frederick R

    2010-04-01

    Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. PMID:20352584

  8. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    PubMed

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  9. Minimal unitary (covariant) scattering theory

    SciTech Connect

    Lindesay, J.V.; Markevich, A.

    1983-06-01

    In the minimal three particle equations developed by Lindesay the two body input amplitude was an on shell relativistic generalization of the non-relativistic scattering model characterized by a single mass parameter ..mu.. which in the two body (m + m) system looks like an s-channel bound state (..mu.. < 2m) or virtual state (..mu.. > 2m). Using this driving term in covariant Faddeev equations generates a rich covariant and unitary three particle dynamics. However, the simplest way of writing the relativisitic generalization of the Faddeev equations can take the on shell Mandelstam parameter s = 4(q/sup 2/ + m/sup 2/), in terms of which the two particle input is expressed, to negative values in the range of integration required by the dynamics. This problem was met in the original treatment by multiplying the two particle input amplitude by THETA(s). This paper provides what we hope to be a more direct way of meeting the problem.

  10. A minimally invasive smile enhancement.

    PubMed

    Peck, Fred H

    2014-01-01

    Minimally invasive dentistry refers to a wide variety of dental treatments. On the restorative aspect of dental procedures, direct resin bonding can be a very conservative treatment option for the patient. When tooth structure does not need to be removed, the patient benefits. Proper treatment planning is essential to determine how conservative the restorative treatment will be. This article describes the diagnosis, treatment options, and procedural techniques in the restoration of 4 maxillary anterior teeth with direct composite resin. The procedural steps are reviewed with regard to placing the composite and the variety of colors needed to ensure a natural result. Finishing and polishing of the composite are critical to ending with a natural looking dentition that the patient will be pleased with for many years.

  11. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  12. Minimally packed phases in holography

    NASA Astrophysics Data System (ADS)

    Donos, Aristomenis; Gauntlett, Jerome P.

    2016-03-01

    We numerically construct asymptotically AdS black brane solutions of D = 4 Einstein-Maxwell theory coupled to a pseudoscalar. The solutions are holographically dual to d = 3 CFTs at finite chemical potential and in a constant magnetic field, which spontaneously break translation invariance leading to the spontaneous formation of abelian and momentum magnetisation currents flowing around the plaquettes of a periodic Bravais lattice. We analyse the three-dimensional moduli space of lattice solutions, which are generically oblique, and show, for a specific value of the magnetic field, that the free energy is minimised by the triangular lattice, associated with minimal packing of circles in the plane. We show that the average stress tensor for the thermodynamically preferred phase is that of a perfect fluid and that this result applies more generally to spontaneously generated periodic phases. The triangular structure persists at low temperatures indicating the existence of novel crystalline ground states.

  13. Waste minimization in chrome plating

    SciTech Connect

    Scheuer, J.; Walter, K.; Nastasi, M.

    1996-09-01

    This is the final report of a one year laboratory directed research and development project at the Los Alamos National Laboratory (LANL). Traditional wet chemical electroplating techniques utilize toxic materials and pose environmental hazards in the disposal of primary baths and waste waters. Pollutants include metals and nonmetals, such as oil, grease, phosphates, and toxic and organic compounds. This project is focused on development of plasma source ion implantation (PSII), a novel and cost-effective surface modification technique, to minimize and ultimately eliminate waste generated in chrome plating. We are collaborating with and industrial partner to design material systems, utilize the PSII processes in existing Los Alamos experimental facilities, and analyze both material and performance characteristics.

  14. Non-minimal Inflationary Attractors

    SciTech Connect

    Kallosh, Renata; Linde, Andrei E-mail: alinde@stanford.edu

    2013-10-01

    Recently we identified a new class of (super)conformally invariant theories which allow inflation even if the scalar potential is very steep in terms of the original conformal variables. Observational predictions of a broad class of such theories are nearly model-independent. In this paper we consider generalized versions of these models where the inflaton has a non-minimal coupling to gravity with a negative parameter ξ different from its conformal value -1/6. We show that these models exhibit attractor behavior. With even a slight increase of |ξ| from |ξ| = 0, predictions of these models for n{sub s} and r rapidly converge to their universal model-independent values corresponding to conformal coupling ξ = −1/6. These values of n{sub s} and r practically coincide with the corresponding values in the limit ξ → −∞.

  15. Waste minimization in analytical methods

    SciTech Connect

    Green, D.W.; Smith, L.L.; Crain, J.S.; Boparai, A.S.; Kiely, J.T.; Yaeger, J.S. Schilling, J.B.

    1995-05-01

    The US Department of Energy (DOE) will require a large number of waste characterizations over a multi-year period to accomplish the Department`s goals in environmental restoration and waste management. Estimates vary, but two million analyses annually are expected. The waste generated by the analytical procedures used for characterizations is a significant source of new DOE waste. Success in reducing the volume of secondary waste and the costs of handling this waste would significantly decrease the overall cost of this DOE program. Selection of appropriate analytical methods depends on the intended use of the resultant data. It is not always necessary to use a high-powered analytical method, typically at higher cost, to obtain data needed to make decisions about waste management. Indeed, for samples taken from some heterogeneous systems, the meaning of high accuracy becomes clouded if the data generated are intended to measure a property of this system. Among the factors to be considered in selecting the analytical method are the lower limit of detection, accuracy, turnaround time, cost, reproducibility (precision), interferences, and simplicity. Occasionally, there must be tradeoffs among these factors to achieve the multiple goals of a characterization program. The purpose of the work described here is to add waste minimization to the list of characteristics to be considered. In this paper the authors present results of modifying analytical methods for waste characterization to reduce both the cost of analysis and volume of secondary wastes. Although tradeoffs may be required to minimize waste while still generating data of acceptable quality for the decision-making process, they have data demonstrating that wastes can be reduced in some cases without sacrificing accuracy or precision.

  16. Acute sinusitis.

    PubMed

    Feldt, Brent; Dion, Gregory R; Weitzel, Erik K; McMains, Kevin C

    2013-10-01

    Sinusitis is a common patient complaint that carries with it a large economic burden. It is one of the most common reasons patients visit their primary care physician. Acute bacterial rhinosinusitis (ABRS) can be distinguished from other forms of rhinosinusitis based on symptom duration of <4 weeks in a patient with purulent rhinorrhea associated with facial pain or pressure. Native upper aerodigestive tract bacteria are the most common etiologic agents. Treatment of ABRS is targeted primarily at symptom improvement. Amoxicillin can be used based on the clinical scenario and patient comorbidities. Computed tomographic scans are reserved for complicated presentations or when there is concern for intracranial extension or other complications. A systematic approach to ABRS will allow for improved patient quality of life and a decreased overall economic burden of this common entity.

  17. Acute pancreatitis in children and adolescents

    PubMed Central

    Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

    2014-01-01

    In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985

  18. Should minimal residual disease guide therapy in AML?

    PubMed

    Paietta, Elisabeth

    2015-01-01

    The prognostic power of minimal residual disease after therapy for acute leukemias is not in question. It is only logical that the finding of leukemic blast cells after therapy predicts for impending relapse or at least the need for additional treatment. Which level of what is called minimal residual disease (MRD) is clinically relevant, however, depends on the efficacy of the initial treatment as well as the treatment strategies available to target MRD. There are a multitude of additional factors that can alter the clinical significance of MRD, including the genotype of the patient's leukemic cells. The fact that methodologies of MRD detection are not standardized and thresholds for defining MRD positivity vary depending upon MRD detection method and the operator's skills or convictions only add to the complexity of MRD interpretation. While enormous efforts are devoted to enhancing the sensitivity of MRD detection, eg, by next-generation sequencing, improvements of methods for detecting MRD per se will not automatically lead to a more reliable estimation of total tumor burden. Most importantly, even the best assay will yield accurate MRD results only if the tissue source for MRD determination is of good quality. Another aspect of potentially crucial importance is the heterogenous distribution of leukemic cells throughout the skeleton after treatment, recently demonstrated for acute myeloid leukemia (AML) by bone marrow imaging. Once technical difficulties of MRD measurement are resolved and better MRD-targeting drugs are developed, we still need to learn about alternate proposed mechanisms to explain MRD-independent prognostication, well described in acute lymphoid leukemia, before MRD can be included routinely in the guidance of therapy in AML.

  19. Postoperative Acute Pulmonary Embolism Following Pulmonary Resections

    PubMed Central

    Shonyela, Felix Samuel; Liu, Bo; Jiao, Jia

    2015-01-01

    Postoperative acute pulmonary embolism after pulmonary resections is highly fatal complication. Many literatures have documented cancer to be the highest risk factor for acute pulmonary embolism after pulmonary resections. Early diagnosis of acute pulmonary embolism is highly recommended and computed tomographic pulmonary angiography is the gold standard in diagnosis of acute pulmonary embolism. Anticoagulants and thrombolytic therapy have shown a great success in treatment of acute pulmonary embolism. Surgical therapies (embolectomy and inferior vena cava filter replacement) proved to be lifesaving but many literatures favored medical therapy as the first choice. Prophylaxis pre and post operation is highly recommended, because there were statistical significant results in different studies which supported the use of prophylaxis in prevention of acute pulmonary embolism. Having reviewed satisfactory number of literatures, it is suggested that thoroughly preoperative assessment of patient conditions, determining their risk factors complicating to pulmonary embolism and the use of appropriate prophylaxis measures are the key options to the successful minimization or eradication of acute pulmonary embolism after lung resections. PMID:26354232

  20. Mini-Med School Planning Guide

    ERIC Educational Resources Information Center

    National Institutes of Health, Office of Science Education, 2008

    2008-01-01

    Mini-Med Schools are public education programs now offered by more than 70 medical schools, universities, research institutions, and hospitals across the nation. There are even Mini-Med Schools in Ireland, Malta, and Canada! The program is typically a lecture series that meets once a week and provides "mini-med students" information on some of the…

  1. Closed locally minimal nets on tetrahedra

    SciTech Connect

    Strelkova, Nataliya P

    2011-01-31

    Closed locally minimal networks are in a sense a generalization of closed geodesics. A complete classification is known of closed locally minimal networks on regular (and generally any equihedral) tetrahedra. In the present paper certain necessary and certain sufficient conditions are given for at least one closed locally minimal network to exist on a given non-equihedral tetrahedron. Bibliography: 6 titles.

  2. Minimally Invasive Mitral Valve Surgery II

    PubMed Central

    Wolfe, J. Alan; Malaisrie, S. Chris; Farivar, R. Saeid; Khan, Junaid H.; Hargrove, W. Clark; Moront, Michael G.; Ryan, William H.; Ailawadi, Gorav; Agnihotri, Arvind K.; Hummel, Brian W.; Fayers, Trevor M.; Grossi, Eugene A.; Guy, T. Sloane; Lehr, Eric J.; Mehall, John R.; Murphy, Douglas A.; Rodriguez, Evelio; Salemi, Arash; Segurola, Romualdo J.; Shemin, Richard J.; Smith, J. Michael; Smith, Robert L.; Weldner, Paul W.; Lewis, Clifton T. P.; Barnhart, Glenn R.; Goldman, Scott M.

    2016-01-01

    Abstract Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery. PMID:27654406

  3. DIFFERENTIAL ANALYZER

    DOEpatents

    Sorensen, E.G.; Gordon, C.M.

    1959-02-10

    Improvements in analog eomputing machines of the class capable of evaluating differential equations, commonly termed differential analyzers, are described. In general form, the analyzer embodies a plurality of basic computer mechanisms for performing integration, multiplication, and addition, and means for directing the result of any one operation to another computer mechanism performing a further operation. In the device, numerical quantities are represented by the rotation of shafts, or the electrical equivalent of shafts.

  4. Sexual differentiation.

    PubMed

    Sinisi, A A; Pasquali, D; Notaro, A; Bellastella, A

    2003-01-01

    In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for differentiation of the internal and external genitalia during fetal life, and for the development of secondary sex characteristics at puberty. Antimullerian hormone (AMH) secreted by Sertoli cells inhibits the development of female internal genitalia (tube, uterus, upper part of vagina); testosterone secreted by Leydig cells induces stabilization of wolffian ducts and development of internal male genitalia. Differentiation of external male genitalia requires the transformation of testosterone to dihydrotestosterone by 5alpha reductase type 2 expressed in genital skin and urogenital sinus. The effects of androgens occur in presence of functional androgen receptor (AR) protein. Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity. PMID:12834017

  5. Recursively minimally-deformed oscillators

    NASA Astrophysics Data System (ADS)

    Katriel, J.; Quesne, C.

    1996-04-01

    A recursive deformation of the boson commutation relation is introduced. Each step consists of a minimal deformation of a commutator [a,a°]=fk(... ;n̂) into [a,a°]qk+1=fk(... ;n̂), where ... stands for the set of deformation parameters that fk depends on, followed by a transformation into the commutator [a,a°]=fk+1(...,qk+1;n̂) to which the deformed commutator is equivalent within the Fock space. Starting from the harmonic oscillator commutation relation [a,a°]=1 we obtain the Arik-Coon and Macfarlane-Biedenharn oscillators at the first and second steps, respectively, followed by a sequence of multiparameter generalizations. Several other types of deformed commutation relations related to the treatment of integrable models and to parastatistics are also obtained. The ``generic'' form consists of a linear combination of exponentials of the number operator, and the various recursive families can be classified according to the number of free linear parameters involved, that depends on the form of the initial commutator.

  6. Against Explanatory Minimalism in Psychiatry.

    PubMed

    Thornton, Tim

    2015-01-01

    The idea that psychiatry contains, in principle, a series of levels of explanation has been criticized not only as empirically false but also, by Campbell, as unintelligible because it presupposes a discredited pre-Humean view of causation. Campbell's criticism is based on an interventionist-inspired denial that mechanisms and rational connections underpin physical and mental causation, respectively, and hence underpin levels of explanation. These claims echo some superficially similar remarks in Wittgenstein's Zettel. But attention to the context of Wittgenstein's remarks suggests a reason to reject explanatory minimalism in psychiatry and reinstate a Wittgensteinian notion of levels of explanation. Only in a context broader than the one provided by interventionism is that the ascription of propositional attitudes, even in the puzzling case of delusions, justified. Such a view, informed by Wittgenstein, can reconcile the idea that the ascription mental phenomena presupposes a particular level of explanation with the rejection of an a priori claim about its connection to a neurological level of explanation.

  7. Against Explanatory Minimalism in Psychiatry

    PubMed Central

    Thornton, Tim

    2015-01-01

    The idea that psychiatry contains, in principle, a series of levels of explanation has been criticized not only as empirically false but also, by Campbell, as unintelligible because it presupposes a discredited pre-Humean view of causation. Campbell’s criticism is based on an interventionist-inspired denial that mechanisms and rational connections underpin physical and mental causation, respectively, and hence underpin levels of explanation. These claims echo some superficially similar remarks in Wittgenstein’s Zettel. But attention to the context of Wittgenstein’s remarks suggests a reason to reject explanatory minimalism in psychiatry and reinstate a Wittgensteinian notion of levels of explanation. Only in a context broader than the one provided by interventionism is that the ascription of propositional attitudes, even in the puzzling case of delusions, justified. Such a view, informed by Wittgenstein, can reconcile the idea that the ascription mental phenomena presupposes a particular level of explanation with the rejection of an a priori claim about its connection to a neurological level of explanation. PMID:26696908

  8. LESSons in minimally invasive urology.

    PubMed

    Dev, Harveer; Sooriakumaran, Prasanna; Tewari, Ashutosh; Rane, Abhay

    2011-05-01

    Since the introduction of laparoscopic surgery, the promise of lower postoperative morbidity and improved cosmesis has been achieved. LaparoEndoscopic Single Site (LESS) surgery potentially takes this further. Following the first human urological LESS report in 2007, numerous case series have emerged, as well as comparative studies comparing LESS with standard laparoscopy. Technological developments in instrumentation, access and optics devices are overcoming some of the challenges that are raised when operating through a single site. Further advances in the technique have included the incorporation of robotics (R-LESS), which exploit the ergonomic benefits of ex vivo robotic platforms in an attempt to further improve the implementation of LESS procedures. In the future, urologists may be able to benefit from in vivo micro-robots that will allow the manipulation of tissue from internal repositionable platforms. The use of magnetic anchoring and guidance systems (MAGS) might allow the external manoeuvring of intra-corporeal instruments to reduce clashing and facilitate triangulation. However, the final promise in minimally invasive surgery is natural orifice transluminal endoscopic surgery (NOTES), with its scarless technique. It remains to be seen whether NOTES, LESS, or any of these future developments will prove their clinical utility over standard laparoscopic methods.

  9. Medical waste: a minimal hazard.

    PubMed

    Keene, J H

    1991-11-01

    Medical waste is a subset of municipal waste, and regulated medical waste comprises less than 1% of the total municipal waste volume in the United States. As part of the overall waste stream, medical waste does contribute in a relative way to the aesthetic damage of the environment. Likewise, some small portion of the total release of hazardous chemicals and radioactive materials is derived from medical wastes. These comments can be made about any generated waste, regulated or unregulated. Healthcare professionals, including infection control personnel, microbiologists, public health officials, and others, have unsuccessfully argued that there is no evidence that past methods of treatment and disposal of regulated medical waste constitute any public health hazard. Historically, discovery of environmental contamination by toxic chemical disposal has followed assurances that the material was being disposed of in a safe manner. Therefore, a cynical public and its elected officials have demanded proof that the treatment and disposal of medical waste (i.e., infectious waste) do not constitute a public health hazard. Existent studies on municipal waste provide that proof. In order to argue that the results of these municipal waste studies are demonstrative of the minimal potential infectious environmental impact and lack of public health hazard associated with medical waste, we must accept the following: that the pathogens are the same whether they come from the hospital or the community, and that the municipal waste studied contained waste materials we now define as regulated medical waste.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Acute hematogenous osteomyelitis of the rib

    SciTech Connect

    Levinsohn, E.M.; Sternick, A.; Echeverria, T.S.; Yuan, H.A.

    1982-08-01

    Two cases of acute hematogenous osteomyelitis of the rib are presented. In one case the etiologic agent was Staphylococcus aureus coagulase-positive and in the other it was Bacteroides corrodens. Although an uncommon disease, hematogenous osteomyelitis should be considered in the differential diagnosis of destructive lesions of the rib. Anaerobic and aerobic cultures should be obtained for bacteriologic analysis.

  11. [Peripheral artery disease and acute coronary syndrome].

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Peripheral arterial disease is a common manifestation of systemic atherosclerosis that is associated with increased cardiovascular risk. When presented in the context of an acute coronary syndrome a differential diagnosis with aorta dissection should be made, because peripheral arterial disease may be asymptomatic despite the absence or asymmetry of femoral pulses.

  12. Minimizers with discontinuous velocities for the electromagnetic variational method

    SciTech Connect

    De Luca, Jayme

    2010-08-15

    The electromagnetic two-body problem has neutral differential delay equations of motion that, for generic boundary data, can have solutions with discontinuous derivatives. If one wants to use these neutral differential delay equations with arbitrary boundary data, solutions with discontinuous derivatives must be expected and allowed. Surprisingly, Wheeler-Feynman electrodynamics has a boundary value variational method for which minimizer trajectories with discontinuous derivatives are also expected, as we show here. The variational method defines continuous trajectories with piecewise defined velocities and accelerations, and electromagnetic fields defined by the Euler-Lagrange equations on trajectory points. Here we use the piecewise defined minimizers with the Lienard-Wierchert formulas to define generalized electromagnetic fields almost everywhere (but on sets of points of zero measure where the advanced/retarded velocities and/or accelerations are discontinuous). Along with this generalization we formulate the generalized absorber hypothesis that the far fields vanish asymptotically almost everywhere and show that localized orbits with far fields vanishing almost everywhere must have discontinuous velocities on sewing chains of breaking points. We give the general solution for localized orbits with vanishing far fields by solving a (linear) neut