tbuckley/cabot-search huggingface dataset:
Broad Suppression of NADPH Oxidase Activity Exacerbates Ischemia/Reperfusion Injury Through Inadvertent Downregulation of Hypoxia-inducible Factor-1α and Upregulation of Peroxisome Proliferator–activated Receptor-α
Authors: Shouji Matsushima, Junya Kuroda, Tetsuro Ago, Peiyong Zhai, Yoshiyuki Ikeda, Shinichi Oka, Guo-Hua Fong, Rong Tian, Junichi Sadoshima
Journal: Circulation Research (2013)

Rationale: NADPH oxidase (Nox) 2 and Nox4 are major components of the Nox family which purposefully produce reactive oxidative species, namely O 2 − and H 2 O 2 , in the heart. The isoform-specific contribution of Nox2 and Nox4 to ischemia/reperfusion (I/R) injury is poorly understood. Objective: We investigated the role of Nox2 and Nox4 in mediating oxidative stress and myocardial injury during I/R using loss-of-function mouse models. Methods and Results: Systemic (s) Nox2 knockout (KO), sNox4 KO, and cardiac-specific (c) Nox4 KO mice were subjected to I/R (30 minutes/24 hours, respectively). Both myocardial infarct size/area at risk and O 2 − production were lower in sNox2 KO, sNox4 KO, and cNox4 KO than in wild-type mice. Unexpectedly, however, the myocardial infarct size/area at risk was greater, despite less O 2 − production, in sNox2 KO+cNox4 KO (double-KO) mice and transgenic mice (Tg) with cardiac-specific expression of dominant-negative Nox, which suppresses both Nox2 and Nox4, than in wild-type or single KO mice. Hypoxia-inducible factor-1α was downregulated whereas peroxisome proliferator–activated receptor-α was upregulated in Tg-dominant-negative Nox mice. A cross with mice deficient in prolyl hydroxylase 2, which hydroxylates hypoxia-inducible factor-1α, rescued the I/R injury and prevented upregulation of peroxisome proliferator–activated receptor-α in Tg-dominant–negative Nox mice. A cross with peroxisome proliferator–activated receptor-α KO mice also attenuated the injury in Tg- dominant–negative Nox mice. Conclusions: Both Nox2 and Nox4 contribute to the increase in reactive oxidative species and injury by I/R. However, low levels of reactive oxidative species produced by either Nox2 or Nox4 regulate hypoxia-inducible factor-1α and peroxisome proliferator–activated receptor-α, thereby protecting the heart against I/R, suggesting that Noxs also act as a physiological sensor for myocardial adaptation.
Overweight in Children and Adolescents
Authors: Stephen R. Daniels, Donna K. Arnett, Robert H. Eckel, Samuel S. Gidding, Laura L. Hayman, Shiriki Kumanyika, Thomas N. Robinson, Barbara J. Scott, Sachiko St. Jeor, Christine L. Williams
Journal: Circulation (2005)

The prevalence of overweight among children and adolescents has dramatically increased. There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight. Overweight in children and adolescents can result in a variety of adverse health outcomes, including type 2 diabetes, obstructive sleep apnea, hypertension, dyslipidemia, and the metabolic syndrome. The best approach to this problem is prevention of abnormal weight gain. Several strategies for prevention are presented. In addition, treatment approaches are presented, including behavioral, pharmacological, and surgical treatment. Childhood and adolescent overweight is one of the most important current public health concerns.
Phenotypic correction of a mouse model of hemophilia A using AAV2 vectors encoding the heavy and light chains of FVIII
Authors: Ciaran D. Scallan, Tongyao Liu, Amy E. Parker, Susannah L. Patarroyo-White, Haifeng Chen, Haiyan Jiang, Joseph Vargas, Dea Nagy, Sharon K. Powell, J. Fraser Wright, Rita Sarkar, Haig H. Kazazian, Alan McClelland, Linda B. Couto
Journal: Blood (2003)
Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases
Authors: J-E Gottenberg
Journal: Annals of the Rheumatic Diseases (2004)

To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice.866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated.In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease.Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.
Forebrain mechanisms of dreaming are activated from a variety of sources
Authors: Mark Solms
Journal: Behavioral and Brain Sciences (2000)

The central question facing sleep and dream science today seems to be: What is the physiological basis of the subset of NREM dreams that are qualitatively indistinguishable from REM dreams (“apex dreams”)? Two competing answers have emerged: (1) all apex dreams are generated by REM sleep control mechanisms, albeit sometimes covertly; and (2) all such dreams are generated by forebrain mechanisms, independently of classical pontine sleep-cycle control mechanisms. The principal objection to the first answer is that it lacks evidential support. The principal objection to the second answer (which is articulated in my target article) is that it takes inadequate account of interactions that surely exist between the putative forebrain mechanisms and the well established brainstem mechanisms of conscious state control. My main response to this objection (elaborated below) is that it conflates nonspecific brainstem modulation – which supports consciousness in general – with a specific pontine mechanism that is supposed to generate apex dreaming in particular. The latter mechanism is in fact neither necessary nor sufficient for apex dreaming. The putative forebrain mechanisms, by contrast, are necessary for apex dreaming (although they are nor sufficient, in the limited sense that all conscious states of the forebrain are modulated by the brainstem).
Acute myelogenous leukemia in elderly patients not eligible for intensive chemotherapy: the dark side of the moon
Authors: R. Latagliata, V. Bongarzoni, I. Carmosino, A. Mengarelli, M. Breccia, P.A. Borza, M. D'Andrea, G.M. D'Elia, S. Mecarocci, S.G. Morano, M.C. Petti, F. Mandelli, G. Alimena
Journal: Annals of Oncology (2005)
Risk-Taking Behaviors Among Israeli Adolescents Exposed to Recurrent Terrorism: Provoking Danger Under Continuous Threat?
Authors: Ruth Pat-Horenczyk, Osnat Peled, Tomer Miron, Daniel Brom, Yael Villa, Claude M Chemtob
Journal: American Journal of Psychiatry (2007)

Objective: This study aimed to assess 1) the relationship between risk-taking behaviors and exposure to terrorism, 2) the relationship between posttraumatic symptoms and risk-taking behaviors, and 3) gender differences in the type and frequency of risk-taking behaviors and their differential associations with posttraumatic symptoms. Method: The participants were 409 Israeli adolescents 15 to 18 years of age. Exposure to terrorism was assessed with a questionnaire developed specifically for the Israeli security situation. Posttraumatic symptoms were measured with the University of California at Los Angeles Reaction Index. Functional impairment was measured with the Diagnostic Interview Schedule for Children. Risk-taking behavior—and the adolescents’ perceptions of such behavior—was assessed with a self-report questionnaire. Results: Israeli adolescents exposed to continuous threats of terrorist attacks reported high levels of risk-taking behaviors. The severity of risk-taking was associated with greater terrorism exposure. Adolescents suffering from posttraumatic symptoms reported more risk-taking behaviors than nonsymptomatic adolescents. Although there was no gender difference in the degree of exposure to terrorism, boys reported taking more risks than girls. The association between posttraumatic symptoms and risk-taking behaviors was stronger in boys than girls. Functional impairment, gender, avoidance symptoms, level of exposure, and degree of fear predicted the severity of risk-taking behaviors. Conclusions: Clinicians and educators should be aware of the strong link between posttraumatic distress and risk-taking behaviors. Risk-taking behaviors may be a manifestation of functional impairment and posttraumatic distress, especially for boys exposed to terrorism.
Phase II Trial of Continuous Dose-Intense Temozolomide in Recurrent Malignant Glioma: RESCUE Study
Authors: James R. Perry, Karl Bélanger, Warren P. Mason, Dorcas Fulton, Petr Kavan, Jacob Easaw, Claude Shields, Sarah Kirby, David R. Macdonald, David D. Eisenstat, Brian Thiessen, Peter Forsyth, Jean-François Pouliot
Journal: Journal of Clinical Oncology (2010)

Purpose Concomitant temozolomide (TMZ)/radiotherapy followed by adjuvant TMZ has increased survival in patients with glioblastoma multiforme (GBM). However, few options are effective for patients who experience treatment failure. We conducted a multicenter, phase II study to assess the efficacy and safety of continuous dose-intense TMZ for recurrent GBM. Patients and Methods Patients with malignant glioma at progression after standard TMZ 150 to 200 mg/m 2 × 5 days in a 28-day cycle for three or more cycles were stratified by tumor type (anaplastic glioma group A, GBM, group B). Ninety-one patients with GBM were prospectively divided into three groups (early [B1], extended [B2], and rechallenge [B3]) according to the timing of progression during adjuvant therapy. All patients received continuous dose-intense TMZ 50 mg/m 2 /d for up to 1 year or until progression occurred. Response was assessed by using RECIST (Response Evaluation Criteria in Solid Tumors). Results A total of 116 of 120 patients were evaluable for efficacy. For patients with GBM, 6-month progression-free survival (PFS) was 23.9% (B1, 27.3%; B2, 7.4%; B3, 35.7%). One-year survival from time of study entry was 27.3%, 14.8%, and 28.6% for the B1, B2 and B3 groups, respectively. For patients with anaplastic glioma, 6-month PFS was 35.7%; 1-year survival was 60.7%. The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). Grades 3 and 4 hematologic toxicities were uncommon. Conclusion Rechallenge with continuous dose-intense TMZ 50 mg/m 2 /d is a valuable therapeutic option for patients with recurrent GBM. Patients who experience progression during the first six cycles of conventional adjuvant TMZ therapy or after a treatment-free interval get the most benefit from therapy.
Prevalence of the Metabolic Syndrome Among U.S. Adolescents Using the Definition From the International Diabetes Federation
Authors: Earl S. Ford, Chaoyang Li, Guixiang Zhao, William S. Pearson, Ali H. Mokdad
Journal: Diabetes Care (2008)

Our objective was to estimate the prevalence of the metabolic syndrome using the 2007 pediatric International Diabetes Federation (IDF) definition among adolescents in the U.S.We used data from 2,014 participants aged 12-17 years of the National Health and Nutrition Examination Survey 1999-2004.The prevalence of the metabolic syndrome for the period 1999-2004 was approximately 4.5% ( approximately 1.1 million adolescents aged 12-17 years in 2006). It increased with age, was higher among males (6.7%) than females (2.1%) (P = 0.006), and was highest among Mexican-American adolescents (7.1%). The prevalence of the metabolic syndrome was relatively stable across the 6-year period: 4.5% for 1999-2000, 4.4-4.5% for 2001-2002, and 3.7-3.9% for 2003-2004 (P for linear trend >0.050).Our results provide the first estimates of the prevalence of the metabolic syndrome using the pediatric IDF definition among adolescents in the U.S.
Morphological, ultrastructural, and genetic characterization of an unusual T‐cell lymphoma in a patient with sinus histiocytosis with massive lymphadenopathy
Authors: P. R. K. Koduru, M. Susin, J. E. Kolitz, M. Sonl, S. Teichberg, M. J. Siques, T. Sun, E. Amorosi, D. R. Budman
Journal: American Journal of Hematology (1995)

Abstract Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare benign disease of unknown etiology. It is rarely associated with malignant lymphoma. This report documents the first case of a T‐cell lymphoma, which developed in a patient with a 10‐year history of SHML. The disease was complicated by hypereosinophilia and massive retroperitoneal lymphadenopathy. Histological examination of a cervical lymph node biopsy during the terminal phase identified a lymphoma composed of cells with morphological plasmacytoid features. Ultrastructurally, the tumor cells showed poorly developed cytoplasm, nuclei with peripheral chromatin clumping, and inconspicuous nucleoli. Cytogenetic studies showed two related clones. On immunohistochemical staining tumor cells were positive with monoclonal antibodies (mAb) CD3 and CD45RO. Southern blotting analysis identified clonal rearrangements in the T‐cell receptor (TCR) alpha, beta and gamma genes. Thus, T‐cell lineage of the tumor cells was established. In situ hybridization of interleukin‐2 (IL‐2) and interleukin‐5 (IL‐5) cDNA probes on tissue sections identified the synthesis of IL‐5 by the eosinophils, suggesting an autocrine pathway of eosinophilopoiesis leading to hypereosinophilia in this patient. ©1995 Wiley‐Liss, Inc.
Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers
Authors: M.E.A.C. Broeders, J. Molema, N.A. Vermue, H.Th.M. Folgering
Journal: European Respiratory Journal (2001)

Aerosol delivery depends on device design and inhalation technique. <i>In vitro</i> device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus® and Turbuhaler® inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus® and Turbuhaler® were significantly correlated. The r-;values were 0.865 and 0.882, respectively (p&lt;0.01). Percentage explained variance was 74.8% for Diskus® and 77.8% for Turbuhaler®. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups.
Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties
Authors: Chantal Kopecky, Michael Haidinger, Ruth Birner-Grünberger, Barbara Darnhofer, Christopher C. Kaltenecker, Gunther Marsche, Michael Holzer, Thomas Weichhart, Marlies Antlanger, Johannes J. Kovarik, Johannes Werzowa, Manfred Hecking, Marcus D. Säemann
Journal: Journal of the American Society of Nephrology (2014)

Cardiovascular disease remains the leading cause of death in renal transplant recipients, but the underlying causative mechanisms for this important problem remain elusive. Recent work has indicated that qualitative alterations of HDL affect its functional and compositional properties in ESRD. Here, we systematically analyzed HDL from stable renal transplant recipients, according to graft function, and from patients with ESRD to determine whether structural and functional properties of HDL remain dysfunctional after renal transplantation. Cholesterol acceptor capacity and antioxidative activity, representing two key cardioprotective mechanisms of HDL, were profoundly suppressed in kidney transplant recipients independent of graft function and were comparable with levels in patients with ESRD. Using a mass spectroscopy approach, we identified specific remodeling of transplant HDL with highly enriched proteins, including α-1 microglobulin/bikunin precursor, pigment epithelium-derived factor, surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates that HDL from kidney recipients is uniquely altered at the molecular and functional levels, indicating a direct pathologic role of HDL that could contribute to the substantial cardiovascular risk in the transplant population.
N-WASP Is Required for Stabilization of Podocyte Foot Processes
Authors: Christoph Schell, Lisa Baumhakl, Sarah Salou, Ann-Christin Conzelmann, Charlotte Meyer, Martin Helmstädter, Christoph Wrede, Florian Grahammer, Stefan Eimer, Dontscho Kerjaschki, Gerd Walz, Scott Snapper, Tobias B. Huber
Journal: Journal of the American Society of Nephrology (2013)

Alteration of cortical actin structures is the common final pathway leading to podocyte foot process effacement and proteinuria. The molecular mechanisms that safeguard podocyte foot process architecture and maintain the three-dimensional actin network remain elusive. Here, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP), which promotes actin nucleation, is required to stabilize podocyte foot processes. Mice lacking N-WASP specifically in podocytes were born with normal kidney function but developed significant proteinuria 3 weeks after birth, suggesting an important role for N-WASP in maintaining foot processes. In addition, inducing deletion of N-WASP in adult mice resulted in severe proteinuria and kidney failure. Electron microscopy showed an accumulation of electron-dense patches of actin and strikingly altered morphology of podocyte foot processes. Although basic actin-based processes such as cell migration were not affected, primary cultures of N-WASP–deficient podocytes revealed significant impairment of dynamic actin reorganization events, including the formation of circular dorsal ruffles. Taken together, our findings suggest that N-WASP–mediated actin nucleation of branched microfilament networks is specifically required for the maintenance of foot processes, presumably sustaining the mechanical resistance of the filtration barrier.
Effect of ethanol on splanchnic hemodynamics in awake and unrestrained rats with portal hypertension
Authors: Bikram Verma-Ansil, Frederick J. Carmichael, Victor Saldivia, George Varghese, Hector Orrego
Journal: Hepatology (1989)

Alcoholic liver disease is frequently accompanied by portal hypertension. We have previously shown that alcohol intake in awake, unrestrained rats is followed by an increase in portal tributary blood flow. In this study, the effect of ethanol on splanchnic hemodynamics in rats with portal hypertension was analyzed. Portal hypertension was induced by partial ligation of the portal vein. This procedure resulted in an increase in portal tributary and hepatic arterial blood flows compared to sham-operated animals. Ethanol (2 gm per kg, oral) increased portal tributary blood flow in both sham-operated and portal vein-ligated rats (sham + water = 37.6 +/- 1.4; sham + ethanol = 63.1 +/- 1.9; p less than 0.01; partial portal vein stenosis + water = 53.2 +/- 3.3; partial portal vein stenosis + ethanol = 69.5 +/- 2.2 ml.kg-1.min-1; p less than 0.01). In sham-operated rats, hepatic artery blood flow was unchanged following ethanol (sham + water = 6.6 +/- 0.7; sham + ethanol = 7.1 +/- 1.0 ml.kg-1.min-1), whereas in portal vein-ligated rats, flow was increased (partial portal vein stenosis + water = 13.7 +/- 1.4; partial portal vein stenosis + ethanol = 19.8 +/- 1.1 ml.kg-1.min-1; p less than 0.025). The adenosine receptor blocker 8-phenyltheophylline suppressed only the ethanol-induced increase in both portal tributary and hepatic artery blood flows in portal vein-ligated rats. The increases in hepatic artery and portal tributary blood flows observed in portal vein-ligated rats without ethanol were not influenced by 8-phenyltheophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Pathways: Targeting the TGF-β Pathway for Cancer Therapy
Authors: Anna L. Smith, Tyler P. Robin, Heide L. Ford
Journal: Clinical Cancer Research (2012)

Abstract TGF-β is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-β, as well as the ability to respond to TGF-β via the presence of TGF-β receptors on the cell surface. Consequently, gain or loss of function of the TGF-β pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial cells, TGF-β functions as a tumor suppressor, where it inhibits proliferation, induces apoptosis, and mediates differentiation. Conversely, in other contexts, TGF-β promotes tumor progression through increasing tumor cell invasion and metastasis. Thus, TGF-β can have opposing roles, likely dependent, in part, on whether the cancer is early or late stage. The effects of TGF-β on tumor suppression and promotion are not limited to the tumor cell itself; rather, these effects can also be mediated through the stroma and the immune system. The dichotomous role of TGF-β in cancer highlights our need to understand the contextual effects of this cytokine to better guide patient selection for the use of anti–TGF-β therapies currently in clinical trials. Clin Cancer Res; 18(17); 4514–21. ©2012 AACR.
IMMUNOLOGIC PROPERTIES OF MOUSE THYMUS CELLS
Authors: Susumu Konda, Yoshinobu Nakao, Richard T. Smith
Journal: The Journal of Experimental Medicine (1972)

The functional attributes of minor subpopulations of mouse thymus cells derived by bovine serum albumin density gradient centrifugation, cortisone treatment, or selective depletion by anti-TL or anti-θ treatment have been examined. A subpopulation derived in each fashion contains the cells required to evoke graft-versus-host reactions in neonatal F1 hybrid recipients and to be stimulated by alloantigens in vitro in one-way mixed lymphocyte cultures and by phytohemagglutinin. The functions of this subpopulation are abrogated by treatment with anti-H-2 plus complement and by high concentrations of anti-θ. A tentative ordering of the various thymus cell subpopulations, on the basis of these and other data, is described.
Surface Molecule Loss and Bleb Formation by Human Germinal Center B Cells Undergoing Apoptosis: Role of Apoptotic Blebs in Monocyte Chemotaxis
Authors: Carmen Segundo, Francisco Medina, Carmen Rodrı́guez, Rosalı́a Martı́nez-Palencia, Francisco Leyva-Cobián, José A. Brieva
Journal: Blood (1999)