tbuckley/cabot-search huggingface dataset:
Serum Adiponectin As a Predictor of Childhood Non-Hodgkin's Lymphoma: A Nationwide Case-Control Study
Authors: Eleni Th. Petridou, Theodoros N. Sergentanis, Nick Dessypris, Iris T. Vlachantoni, Sofia Tseleni-Balafouta, Apostolos Pourtsidis, Maria Moschovi, Sofia Polychronopoulou, Fani Athanasiadou-Piperopoulou, Maria Kalmanti, Christos S. Mantzoros
Journal: Journal of Clinical Oncology (2009)

To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.
Changes in Outcomes for Internal Medicine Inpatients after Work-Hour Regulations
Authors: Leora I. Horwitz, Mikhail Kosiborod, Zhenqiu Lin, Harlan M. Krumholz
Journal: Annals of Internal Medicine (2007)

Background: Limits on resident work hours are intended to reduce fatigue-related errors, but may raise risk by increasing transfers of responsibility for patients. Objective: To examine changes in outcomes for internal medicine patients after the implementation of work-hour regulations. Design: Retrospective cohort study. Setting: Urban, academic medical center. Patients: 14 260 consecutive patients discharged from the teaching (housestaff) service and 6664 consecutive patients discharged from the nonteaching (hospitalist) service between 1 July 2002 and 30 June 2004. Measurements: Outcomes included intensive care unit utilization, length of stay, discharge disposition, 30-day readmission rate to the study institution, pharmacist interventions to prevent error, drug–drug interactions and in-hospital death. Results: The teaching service had net improvements in 3 outcomes. Relative to changes experienced by the nonteaching service, the rate of intensive care unit utilization decreased by 2.1% (95% CI, −3.3% to −0.7%; P = 0.002), the rate of discharge to home or rehabilitation facility versus elsewhere improved by 5.3% (CI, 2.6% to 7.6%; P < 0.001), and pharmacist interventions to prevent error were reduced by 1.92 interventions per 100 patient-days (CI, −2.74 to −1.03 interventions per 100 patient-days; P < 0.001). Teaching and nonteaching services had similar changes over time in length of stay, 30-day readmission rate, and adverse drug–drug interactions. In-hospital death was uncommon in both groups, and change over time was similar in the 2 groups. Limitations: The study was a retrospective, nonrandomized design that assessed a limited number of outcomes. Teaching and nonteaching cohorts may not have been affected similarly by secular trends in patient care. Conclusions: After the implementation of work-hour regulations, 3 of 7 outcomes improved for patients in the teaching service relative to those in the nonteaching service. The authors found no evidence of adverse unintended consequences after the institution of work-hour regulations.
Myocardial alpha 1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism. Species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium.
Authors: M Endoh, T Hiramoto, A Ishihata, M Takanashi, J Inui
Journal: Circulation Research (1991)

Species-dependent variations of myocardial alpha 1-adrenoceptor-mediated positive inotropic effects of epinephrine were assessed in relation to characteristics of alpha 1-receptor bindings and acceleration of phosphatidylinositol metabolism in the isolated rat, rabbit, and dog ventricular myocardium. Epinephrine in the presence of the beta-adrenoceptor antagonist bupranolol (10(-6) M) elicited a positive inotropic effect through activation of alpha 1-adrenoceptors in rat and rabbit, whereas in dog ventricular myocardium, bupranolol abolished the positive inotropic effect of epinephrine. [3H]Prazosin bound to membrane fractions derived from rat, rabbit, and dog ventricular muscle with high affinities in a saturable and reversible manner. In dog, Bmax and Kd values of alpha 1-adrenoceptor binding sites were identical to those in rabbit ventricular muscle. The Bmax value of alpha 1-adrenoceptors in rat ventricle was the highest, amounting to two to four times those in rabbit and dog. Epinephrine displacement curves for the specific binding of [3H]prazosin in the membrane fraction of these species showed high and low affinity sites with slope factors significantly less than unity, which were shifted to single low affinity sites with slope factors close to unity by addition of 5'-guanylylimidodiphosphate. Accumulation of [3H]inositol 1-phosphate [( 3H]IP1) in ventricular slices prelabeled with [3H]myo-inositol was increased by epinephrine in a time- and concentration-dependent manner in rat ventricular slices. [3H]IP1 accumulation likewise was facilitated by alpha 1-adrenoceptor stimulation in rabbit ventricular slices, whereas the extent of [3H]IP1 accumulation was much less than that in rat. In dog ventricular slices, [3H]IP1 was not accumulated by epinephrine. In rabbit papillary muscle, the time course of increase in contractile force induced by alpha-adrenoceptors coincided with the prolongation of the action potential duration with a similar time course, which is in strong contrast to previous findings in rat that the contractile response was dissociated from the electrophysiological response to alpha-adrenoceptor stimulation. The present results indicate that a wide range of variation of alpha 1-adrenoceptor-mediated regulation of myocardial contractility may be ascribed to different contributions of facilitatory as well as inhibitory regulatory processes that lead to intracellular Ca2+ mobilization subsequent to myocardial alpha 1-adrenoceptor activation among mammalian species.
A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas
Authors: Christine M Williamson, Simon T Ball, Wade T Nottingham, Judith A Skinner, Antonius Plagge, Martin D Turner, Nicola Powles, Tertius Hough, David Papworth, William D Fraser, Mark Maconochie, Jo Peters
Journal: Nature Genetics (2004)
Modulation of the pacemaker current If by β-adrenoceptor subtypes in ventricular myocytes isolated from hypertensive and normotensive rats
Authors: E Cerbai
Journal: Cardiovascular Research (1999)

Objective: Both β1- and β2-adrenoceptors (β1-AR and β2-AR) are functionally present in human and rat ventricular myocytes. The two receptor subtypes are differently regulated during the development of myocardial hypertrophy and failure. If is expressed in human and rat ventricular myocytes. In hypertrophied myocytes isolated from old spontaneously hypertensive rats (SHR) the density is much larger than in age-matched normotensive Wistar Kyoto (WKY). Due to the possible relevance of If as an arrhythmogenic mechanism in the rat and human ventricle, we studied and compared the effects of β1-AR and β2-AR stimulation on If in both hypertrophied and normal left ventricular myocytes of 18-month old SHR and WKY. Methods: The whole-cell configuration of the patch-clamp technique was employed. Noradrenaline (NA, 1 μM) was used to stimulate β1-AR and isoprenaline (ISO, 1 μM) in the presence of the β1-AR antagonist CGP 20712A (0.1 μM) to stimulate β2-AR. Results: In SHR, NA increased If by causing a 10.8±0.9 mV (n=10) positive shift in the voltage of maximal activation (V1/2); this effect was completely reversed by CGP 20712A. β2-AR stimulation was effective in seven out of 13 cells tested, where it caused a small positive shift in V1/2 (4.0±1.7 mV). Cyclopentyladenosine (CPA), a selective A1-receptor agonist, reversed the effect of NA; the antiadrenergic action of CPA was abolished in cells pre-incubated with pertussis toxin (PTX) to block inhibitory G proteins (Gi). In PTX-treated cells the shift in V1/2 caused by both β2-AR (9.6±1.7 mV, n=6, p<0.05) and β1-AR (17.6±1.9 mV, n=7, p<0.05) was significantly greater than in control cells. Both β-AR subtypes modulated If activation also in WKY: β1-AR shifted V1/2 by 16.0±1.4 mV (n=15) and β2-AR by 4.2±1.1 mV (n=7). However, in PTX-treated WKY cells only the β2-AR effect was potentiated (shift in V1/2: 11.4±1.4 mV, n=9, p<0.01), while the β1-AR response was unchanged (18.9±4.2 mV, n=5, n.s.). Conclusions:If expressed in SHR hypertrophied ventricular myocytes is modulated by catecholamines mainly through the stimulation of the β1-AR subtype. The β1-AR response is, however, significantly lower than that observed in myocytes from normotensive rats, probably as a consequence of the presence of an increased inhibitory activity of Gi proteins. This post-receptorial control may be seen as a mechanism to limit the arrhythmogenicity of β-AR stimulation in myocardial hypertrophy and failure.
Proliferation-Independent Control of Tumor Glycolysis by PDGFR-Mediated AKT Activation
Authors: Cong Ran, Huan Liu, Yasuyuki Hitoshi, Mark A. Israel
Journal: Cancer Research (2013)

Abstract The differences in glucose metabolism that distinguish most malignant and normal tissues have called attention to the importance of understanding the molecular mechanisms by which tumor energy metabolism is regulated. Receptor tyrosine kinase (RTK) pathways that are implicated in proliferation and transformation have been linked to several aspects of tumor glucose metabolism. However, the regulation of glycolysis has invariably been examined under conditions in which proliferation is concomitantly altered. To determine whether RTKs directly regulate glycolysis without prerequisite growth modulation, we first identified a specific RTK signaling pathway, platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) that regulates glycolysis in glioma-derived tumor stem-like cells from a novel mouse model. We determined that PDGF-regulated glycolysis occurs independent of PDGF-regulated proliferation but requires the activation of AKT, a known metabolic regulator in tumor. Our findings identifying a key characteristic of brain tumors, aerobic glycolysis, mediated by a pathway with multiple therapeutic targets suggests the possibility of inhibiting tumor energy metabolism while also treating with agents that target other pathways of pathologic significance. Cancer Res; 73(6); 1831–43. ©2013 AACR.
Classification of Behavior Problems of Children
Authors: RICHARD L. JENKINS
Journal: American Journal of Psychiatry (1969)

DSM-II subdivides behavior disorders of childhood and adolescence into seven categories: "hyperkinetic reaction," "withdrawing reaction," "overanxious reaction," "runaway reaction," "unsocialized aggressive reaction," and "group delinquent reaction," plus "other reaction." The first six reactions represent clinically recognizable symptomatic clusters supported by research studies. The author outlines the problems of treating children in each of these groups, noting that the treatment can with advantage be individualized from a general pattern appropriate to the general type of problem.
Outcome of second line therapy in rheumatoid arthritis.
Authors: D R Porter, I McInnes, J Hunter, H A Capell
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To study the functional outcome in patients with rheumatoid arthritis (RA) who tolerate second line drug therapy for five years. METHODS--We enrolled into prospective controlled trials, 190 patients with rheumatoid arthritis who tolerated 9disease modifying9 antirheumatic drug therapy for five years. Demographic data were recorded. Disease activity was measured every six months for two years and annually thereafter, using clinical and laboratory variables. Patient function was measured using the modified Health Assessment Questionnaire. The change in each variable was analysed using paired Wilcoxon tests. RESULTS--Patient function improved significantly compared with baseline. The improvement was maximal after one to two years, and thereafter function started to decline slowly. After five years of treatment the patients9 function was still significantly better than before treatment had started. There were highly significant improvements in all variables measured to assess disease activity, which remained well controlled throughout the five year period. CONCLUSION--Good control of disease activity and improved function can be achieved long term in approximately 30% of RA patients treated with injectable gold, sulphasalazine or penicillamine.
Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD
Authors: Samantha A. Natanek, Harry R. Gosker, Ilse G.M. Slot, Gemma S. Marsh, Nicholas S. Hopkinson, John Moxham, Paul R. Kemp, Annemie M.W.J. Schols, Michael I. Polkey
Journal: European Respiratory Journal (2012)

Reduced quadriceps endurance in chronic obstructive pulmonary disease (COPD) is associated with a predominance of type II glycolytic fibres over type I oxidative fibres (fibre shift) and reduced muscle energy stores. The molecular mechanisms responsible for this remain unknown. We hypothesised that expression of known regulators of type I fibres and energy production in quadriceps muscle would differ in COPD patients with and without fibre shift. We measured lung function, physical activity, exercise performance, quadriceps strength and endurance (nonvolitionally) in 38 Global Initiative for Chronic Obstructive Lung Disease stage I–IV COPD patients and 23 healthy age-matched controls. Participants underwent a quadriceps biopsy: type I and II fibre proportions were determined using immunohistochemistry and fibre shift defined using published reference ranges. Calcineurin A, phosphorylated AMP kinase (phospho-AMPK)-α, protein kinase A-α catalytic subunits, modulators of calcineurin activity and calmodulin, 14-3-3 proteins were measured by Western blotting, and myocyte-enriched calcineurin-interacting protein-1 mRNA measured by quantitative PCR. Downstream, nuclear myocyte enhancer factor-2 capable of DNA binding was quantified by transcription factor ELISA. Unexpectedly, calcineurin expression was higher, while phospho-AMPK was lower, in COPD patients with fibre shift compared to COPD patients without fibre shift. Phospho-AMPK levels correlated with quadriceps endurance in patients. Reduced phospho-AMPK may contribute to reduced quadriceps oxidative capacity and endurance in COPD.
SIE-SIES-GITMO Guidelines for the management of adult peripheral T- and NK-cell lymphomas, excluding mature T-cell leukaemias
Authors: P. Corradini, M. Marchetti, G. Barosi, A. Billio, A. Gallamini, S. Pileri, N. Pimpinelli, G. Rossi, P.L. Zinzani, S. Tura
Journal: Annals of Oncology (2014)
Cardiac Failure in the Dog as a Consequence of Exogenous Hyperthyroidism
Authors: DOROTHY PIATNEK-LEUNISSEN, ROBERT E. OLSON
Journal: Circulation Research (1967)

Thirty dogs were made hyperthyroid by feeding them 1 g/kg USP thyroid powder or injecting 1.2 mg/kg of 1-thyroxine/day. Seven of the 30 dogs used had surgically induced mild valvular lesions of the right heart to determine whether preexistent organic disease was a requisite to the induction of failure in hyperthyroidism. At 2 to 27 months the animals were subjected to cardiac catheterization for measurement of cardiac work and metabolism in vivo. The animals were then killed and the levels of the high energy phosphate compounds creatine phosphate (CP) and the adenine nucleotides (ATP+ADP) in the heart were measured as an index of the net efficiency of the processes of oxidative phosphorylation. By hemodynamic or histopathologic criteria, 13 dogs showed signs of failure, only 3 of which had preexistent valvular lesions. The failure was not accompanied by a decreased efficiency of oxidative phosphorylation. Net levels of CP and ATP + ADP in the myocardium were normal. Preliminary studies with sarcosomes isolated from 5 animals also revealed normal P/O ratios in 3 dogs with and in 2 without signs of cardiac failure. Liver mitochondria isolated from these same 5 animals all demonstrated decreased P/O ratios. Decreased myocardial extractions of both glucose and pyruvate occurred with failure, suggesting some degree of myocardial hypoxia with increased intracellular glycolysis. Areas of relative hypoxia may exist in a hypertrophied myocardium of the hyperthyroid animal.
Developing an Evidence-Based Classification of Eating Disorders: Scientific Findings for DSM-5edited by Striegel-MooreRuth H., Ph.D., WonderlichStephen A., Ph.D., WalshB. Timothy, M.D., and MitchellJames E., M.D. Washington, DC, American Psychiatric Publishing, 2011, 429 pp., $65.00.
Authors: Jennifer Hagman
Journal: American Journal of Psychiatry (2012)
Redefining the role of psychiatry in medicine
Authors: J A Lieberman, A J Rush
Journal: American Journal of Psychiatry (1996)

The authors evaluate the forces that are changing psychiatric practice and propose options for redefining the clinical and educational goals of psychiatry within medicine.An overview of current external and internal forces shaping psychiatry is provided. These forces are both social, political, and economic (external) and scientific and technological (internal).The convergence of these forces leads to recommendations for redefining psychiatric practice and education. If psychiatry fails to redefine itself on the basis of its scientific foundations, political and economic forces may lead to an untenable redefinition that could threaten the field.The redefinition process may lead to altered roles and somewhat different knowledge bases for psychiatry. The profession must choose whether to be reactive or proactive given this challenge.
Utility of ergospirometry in the diagnosis of hyperventilation syndrome (HVS)
Authors: Angelica Tiotiu, André Noseda, Sophia Abdelkafi
Journal: European Respiratory Journal (2011)

The hyperventilation syndrome (HVS) is characterized by several somatic and psychological symptoms due to hypocapnia not secondary to any underlying organic disease. The purpose of the present study was to evaluate the place of exercise-induced hyperventilation in the diagnosis of HVS.  Twenty-three patients with normal spirometry, referred for suspicion of HVS on the basis of a Nijmegen9s questionnaire (score ≥23) were eligible. Asthma was documented in 15 patients. The mean score of anxiety by the Spielberberg9s State-Trait Anxiety Inventory for Adults was 53.5 which are suggestive of moderate anxiety. During the hyperventilation provocation test (HVPT), at least two symptoms of Nijmegen9s questionnaire were reproduced in 14 patients. The mean level of PetCO 2 at baseline was 27.6 mm Hg and decreased to 15.2 mm Hg for a maximal ventilation of 57 l/min. No patient recovered the baseline level of PetCO2 at 5 min after the end of the HVPT (mean ratio PetCO2 after/before = 75%). Exercise-induced maximal ventilation (VEmax) was 52 l/min and was accompanied by a PetCO 2 level of 35.8 mm Hg and an EqCO2 of 32 mm Hg. No significant difference in the ventilatory pattern (VEmax, PetCO2, EqCO2) was found between HVS group (n=8) and the asthma and HVS group (n=15).  In conclusion, in our group of patients with HVS, with or without asthma, the hyperventilation during exercise did not induce abnormal reduction in PetCO2 or abnormal increase in EqCO2. Our results suggest that, unexpectedly, the exercise could be a therapeutic tool in the HVS. It could be hypothesized that anxiety plays a role in the genesis of symptoms at rest but not during exercise where the patient has to be concentrated on his effort.
Efficient and specific cardiac IK1 inhibition by a new pentamidine analogue
Authors: H. Takanari, L. Nalos, A. Stary-Weinzinger, K. C. G. de Git, R. Varkevisser, T. Linder, M. J. C. Houtman, M. Peschar, T. P. de Boer, R. R. Tidwell, M. B. Rook, M. A. Vos, M. A. G. van der Heyden
Journal: Cardiovascular Research (2013)

In excitable cells, KIR2.x ion-channel-carried inward rectifier current (IK₁) is thought to set the negative and stable resting membrane potential, and contributes to action potential repolarization. Loss- or gain-of-function mutations correlate with cardiac arrhythmias and pathological remodelling affects normal KIR2.x protein levels. No specific IK1 inhibitor is currently available for in vivo use, which severely hampers studies on the precise role of IK1 in normal cardiac physiology and pathophysiology. The diamine antiprotozoal drug pentamidine (P) acutely inhibits IK₁ by plugging the cytoplasmic pore region of the channel. We aim to develop more efficient and specific IK₁ inhibitors based on the P structure.We analysed seven pentamidine analogues (PA-1 to PA-7) for IK₁ blocking potency at 200 nM using inside-out patches from KIR2.1 expressing HEK-293 cells. PA-6 showed the highest potency and was tested further. PA-6 blocked KIR2.x currents of human and mouse with low IC₅₀ values (12-15 nM). Modelling indicated that PA-6 had less electrostatic but more lipophilic interactions with the cytoplasmic channel pore than P, resulting in a higher channel affinity for PA-6 (ΔG -44.1 kJ/Mol) than for P (ΔG -31.7 kJ/Mol). The involvement of acidic amino acid residues E224 and E299 in drug-channel interaction was confirmed experimentally. PA-6 did not affect INav1.5, ICa-L, IKv4.3, IKv11.1, and IKv7.1/minK currents at 200 nM. PA-6 inhibited the inward (50 nM 40%; 100 nM 59%; 200 nM 77%) and outward (50 nM 40%; 100 nM 76%; 200 nM 100%) components of IK₁ in isolated canine adult-ventricular cardiomyocytes (CMs). PA-6 prolonged action potential duration of CMs by 8 (n = 9), 26 (n = 5), and 34% (n = 11) at 50, 100, and 200 nM, respectively. Unlike P, PA-6 had no effect on KIR2.1 channel expression at concentrations from 0.1 to 3 μM. However, PA-6 at 10 μM increased KIR2.1 expression levels. Also, PA-6 did not affect the maturation of hERG, except when applied at 10 μM.PA-6 has higher efficiency and specificity to KIR2.x-mediated current than P, lengthens action potential duration, and does not affect channel trafficking at concentrations relevant for complete IK₁ block.