tbuckley/cabot-search huggingface dataset:
Contribution of Glycogen and Exogenous Glucose to Glucose Metabolism During Ischemia in the Hypertrophied Rat Heart
Authors: Brett O. Schönekess, Michael F. Allard, Sarah L. Henning, Richard B. Wambolt, Gary D. Lopaschuk
Journal: Circulation Research (1997)

Abstract Although hypertrophied hearts have increased rates of glycolysis under aerobic conditions, it is controversial as to whether glucose metabolism during ischemia is altered in the hypertrophied heart. Because endogenous glycogen stores are a key source of glucose during ischemia, we developed a protocol to label the glycogen pool in hearts with either [ 3 H]glucose or [ 14 C]glucose, allowing for direct measurement of both glycogen and exogenous glucose metabolism during ischemia. Cardiac hypertrophy was produced in rats by banding the abdominal aorta for an 8-week period. Isolated hearts from aortic-banded and sham-operated rats were initially perfused under substrate-free conditions to decrease glycogen content to 40% of the initial pool size. Resynthesis and radiolabeling of the glycogen pool with [ 3 H]glucose or [ 14 C]glucose were accomplished in working hearts by perfusion for a 60-minute period with 11 mmol/L [ 3 H]glucose or [ 14 C]glucose, 0.5 mmol/L lactate, 1.2 mmol/L palmitate, and 100 μmol/mL insulin. Although glycolytic rates during the aerobic perfusion were significantly greater in hypertrophied hearts compared with control hearts, glycolytic rates from exogenous glucose were not different during low-flow ischemia. The contribution of glucose from glycogen was also not different in hypertrophied hearts compared with control hearts during ischemia (1314±665 versus 776±310 nmol · min −1 · g dry wt −1 , respectively). Glucose oxidation rates decreased during ischemia but were not different between the two groups. However, in both hypertrophied and control hearts, the ratio of glucose oxidation to glycolysis was greater for glucose originating from glycogen than from exogenous glucose. Our data demonstrate that glycogen is a significant source of glucose during low-flow ischemia, but the data do not differ between hypertrophied and control hearts.
Antitumor Activity of BIBF 1120, a Triple Angiokinase Inhibitor, and Use of VEGFR2+pTyr+ Peripheral Blood Leukocytes as a Pharmacodynamic Biomarker <i>In Vivo</i>
Authors: Kanae Kudo, Tokuzo Arao, Kaoru Tanaka, Tomoyuki Nagai, Kazuyuki Furuta, Kazuko Sakai, Hiroyasu Kaneda, Kazuko Matsumoto, Daisuke Tamura, Keiichi Aomatsu, Marco A. De Velasco, Yoshihiko Fujita, Nagahiro Saijo, Masatoshi Kudo, Kazuto Nishio
Journal: Clinical Cancer Research (2010)

Abstract Purpose: BIBF 1120 is a potent, orally available triple angiokinase inhibitor that inhibits VEGF receptors (VEGFR) 1, 2, and 3, fibroblast growth factor receptors, and platelet-derived growth factor receptors. This study examined the antitumor effects of BIBF 1120 on hepatocellular carcinoma (HCC) and attempted to identify a pharmacodynamic biomarker for use in early clinical trials. Experimental Design: We evaluated the antitumor and antiangiogenic effects of BIBF 1120 against HCC cell line both in vitro and in vivo. For the pharmacodynamic study, the phosphorylation levels of VEGFR2 in VEGF-stimulated peripheral blood leukocytes (PBL) were evaluated in mice inoculated with HCC cells and treated with BIBF 1120. Results: BIBF 1120 (0.01 μmol/L) clearly inhibited the VEGFR2 signaling in vitro. The direct growth inhibitory effects of BIBF 1120 on four HCC cell lines were relatively mild in vitro (IC50 values: 2–5 μmol/L); however, the oral administration of BIBF 1120 (50 or 100 mg/kg/d) significantly inhibited the tumor growth and angiogenesis in a HepG2 xenograft model. A flow cytometric analysis revealed that BIBF 1120 significantly decreased the phosphotyrosine (pTyr) levels of VEGFR2+CD45dim PBLs and the percentage of VEGFR2+pTyr+ PBLs in vivo; the latter parameter seemed to be a more feasible pharmacodynamic biomarker. Conclusions: We found that BIBF 1120 exhibited potent antitumor and antiangiogenic activity against HCC and identified VEGFR2+pTyr+ PBLs as a feasible and noninvasive pharmacodynamic biomarker in vivo. Clin Cancer Res; 17(6); 1373–81. ©2010 AACR.
Living with rheumatoid arthritis: expenditures, health status, and social impact on patients
Authors: H M Lapsley
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To determine costs related to living with rheumatoid arthritis (RA), and to identify the association between health status—as measured by the Health Status Questionnaire short form-36 (SF-36) and the disease specific index Health Assessment Questionnaire (HAQ)—and the social impact of RA. <b>Methods:</b> A prospective cohort study was carried out on 81 patients with RA who completed four consecutive three month cost diaries. The SF-36, HAQ, and social impact at baseline and one year follow up were also assessed. <b>Results:</b> Women reported worse SF-36 physical function and HAQ scores than men and received more assistance from family and friends. Women spent more on non-prescription medication and devices to assist them than men. Older patients had higher expenditure on visits to health professionals, whereas younger patients spent more on prescription medication and tests. Pension status and membership of private health insurance schemes were important determinants in these differences in expenditure. <b>Conclusion:</b> Costs increased with duration of disease, those with private health insurance had greater out of pocket costs (excluding membership fees), and those with pension support had fewer costs. Women were more affected by RA than men in health status, social impact, and out of pocket costs.
Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome
Authors: Dani Bercovich, Ithamar Ganmore, Linda M Scott, Gilad Wainreb, Yehudit Birger, Arava Elimelech, Chen Shochat, Giovanni Cazzaniga, Andrea Biondi, Giuseppe Basso, Gunnar Cario, Martin Schrappe, Martin Stanulla, Sabine Strehl, Oskar A Haas, Georg Mann, Vera Binder, Arndt Borkhardt, Helena Kempski, Jan Trka, Bella Bielorei, Smadar Avigad, Batia Stark, Owen Smith, Nicole Dastugue, Jean-Pierre Bourquin, Nir Ben Tal, Anthony R Green, Shai Izraeli
Journal: The Lancet (2008)
Cardiovascular Mortality in Obstructive Sleep Apnea in the Elderly: Role of Long-Term Continuous Positive Airway Pressure Treatment
Authors: Miguel-Angel Martínez-García, Francisco Campos-Rodríguez, Pablo Catalán-Serra, Juan-José Soler-Cataluña, Carmen Almeida-Gonzalez, Ines De la Cruz Morón, Joaquin Durán-Cantolla, Josep-Maria Montserrat
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in middle-aged subjects, but it is not known whether it is also a risk factor in the elderly.To investigate whether OSA is a risk factor for cardiovascular death and to assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk in the elderly.Prospective, observational study of a consecutive cohort of elderly patients (≥65 yr) studied for suspicion of OSA between 1998 and 2007. Patients with an apnea-hypopnea index (AHI) less than 15 were the control group. OSA was defined as mild to moderate (AHI, 15-29) or severe (AHI, ≥30). Patients with OSA were classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). Participants were monitored until December 2009. The end point was cardiovascular death. A multivariate Cox survival analysis was used to determine the independent impact of OSA and CPAP treatment on cardiovascular mortality.A total of 939 elderly were studied (median follow-up, 69 mo). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 2.25 (confidence interval [CI], 1.41 to 3.61) for the untreated severe OSA group, 0.93 (CI, 0.46 to 1.89) for the CPAP-treated group, and 1.38 (CI, 0.73 to 2.64) for the untreated mild to moderate OSA group.Severe OSA not treated with CPAP is associated with cardiovascular death in the elderly, and adequate CPAP treatment may reduce this risk.
Multimodality Imaging of Tumor Response to Doxil
Authors: Fan Zhang, Lei Zhu, Gang Liu, Naoki Hida, Guangming Lu, Henry S. Eden, Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2011)

Purpose: Early assessment of tumor responses to chemotherapy could enhance treatment outcomes by ensuring that, from the beginning, treatments meet the individualized needs of patients.In this study, we applied multiple modality molecular imaging techniques to pre-clinical monitoring of early tumor responses to Doxil, focusing on imaging of apoptosis.Methods: Mice bearing UM-SCC-22B human head and neck squamous cancer tumors received either PBS or 1 to 2 doses of Doxil® (doxorubicin HCl liposome injection) (10 mg/kg/dose).Bioluminescence signals from an apoptosis-responsive reporter gene were captured for apoptosis evaluation.Tumor metabolism and proliferation were assessed by 18 F-FDG and 3'-18 F-fluoro-3'-deoxythymidine ( 18 F-FLT) positron emission tomography.Diffusion-weighted magnetic resonance imaging (DW-MRI) was performed to calculate averaged apparent diffusion coefficients (ADCs) for the whole tumor volume.After imaging, tumor samples were collected for histological evaluation, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), anti-CD31, and Ki-67 immunostaining.Results: Two doses of Doxil significantly inhibited tumor growth.Bioluminescence imaging (BLI) indicated apoptosis of tumor cells after just 1 dose of Doxil treatment, before apparent tumor shrinkage. 18F-FDG and 18 F-FLT PET imaging identified decreased tumor metabolism and proliferation at later time points than those at which BLI indicated apoptosis.MRI measurements of ADC altered in response to Doxil, but only after tumors were treated with 2 doses.Decreased tumor proliferation and increased apoptotic cells were confirmed by changes of Ki-67 index and apoptotic ratio. Conclusion:Our study of tumor responses to different doses of Doxil demonstrated that it is essential to combine apoptosis imaging strategies with imaging of other critical biological or pathological pathways, such as metabolism and proliferation, to improve clinical decision making in apoptosis-related diseases and interventions.
Editing Anti-DNA B Cells by Vλx
Authors: Yijin Li, Yoram Louzoun, Martin Weigert
Journal: The Journal of Experimental Medicine (2004)

Receptor editing is performed by replacement of Vκ genes that contribute to autoreactivity. In addition, the Cκ locus can be deleted by Vκ rearrangement to intronic or 3′ of Cκ RS sequences (also referred to as κ deletion elements). B cells that delete the Cκ can then express λ light chains. However, the λ locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive λ B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of λ1 in association with an anti-DNA heavy chain often coexpress a κ chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vλ family, Vλx. The λx B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.
Refining Personality Disorder Diagnosis: Integrating Science and Practice
Authors: Jonathan Shedler, Drew Westen
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Personality disorder researchers are currently evaluating a range of potential solutions to problems with the DSM-IV diagnostic categories. This article proposes changes to the diagnostic categories and criteria based on empirical findings from a national sample of patients with personality disorder diagnoses. METHOD: The Shedler-Westen Assessment Procedure (SWAP-200) is a personality assessment tool designed to capture the richness and complexity of clinical personality descriptions while providing reliable and quantifiable data. A national sample of experienced psychiatrists and psychologists used the SWAP-200 to describe either their conceptions (prototypes) of personality disorders (N=267) or current patients with personality disorder diagnoses (N=530). RESULTS: Clinicians" conceptions of personality disorders and their descriptions of actual patients overlapped with the DSM descriptions but also differed in systematic ways. Their descriptions were clinically richer than the DSM descriptions and placed greater emphasis on patients" mental life or inner experience. The study identifies potential diagnostic criteria that may be more defining of personality syndromes than some of the current DSM criteria. CONCLUSIONS: Diagnostic criterion sets should be expanded to better address the multiple domains of functioning inherent in the concept of personality and should more explicitly address patients’ mental life or inner experience. The authors offer recommendations for revision of the diagnostic categories and criteria and also propose a prototype matching approach to personality disorder diagnosis that may overcome limitations inherent in the current diagnostic system.
Efficacy and safety of 300IR 5-grass pollen sublingual tablet in allergic patients with and without asthma
Authors: Robert K. Zeldin, Armelle Montagut, Josiane Cognet-Sicé, Kathy Abiteboul
Journal: European Respiratory Journal (2012)

Background   Efficacy and safety of 300IR tablet has been demonstrated. Here we report the impact of asthma status on efficacy and safety.   Methods   Grass pollen allergic adults were randomised to placebo or 300IR pre- and co-seasonally for 3 seasons, starting 4 months (4M) or 2 months (2M) prior to each season and continuing for its duration. Asthmatic patients requiring no more than GINA Step 1 therapy could be included. The primary efficacy endpoint, Average Adjusted Symptom Score (AAdSS, adjusting rhinoconjunctivitis symptoms for rescue medication use, scale 0-18) during the pollen period in Year 3, was analysed by ANCOVA. Asthma presence at baseline was a pre-specified covariate. Treatment by asthma status interaction was tested.   Results   Among 581 patients included in the Year 1 full analysis set, 14.1% were asthmatic, with balance between groups.  In Year 3, differences in AAdSS Least-Squares means vs. placebo during the pollen period were significant in the two active groups (p  During the 3 treatment years, 3 patients had an asthma exacerbation (moderate): 2 in Year 1 (placebo) and one in Year 3 (4M). None was drug-related.   Conclusion    Efficacy and tolerability of 300IR 5-grass pollen sublingual tablet in patients with grass pollen allergic rhinoconjunctivitis were similar in those with and without asthma.
Magnetic Resonance Imaging Determination of Cardiac Prognosis
Authors: W. Gregory Hundley, Timothy M. Morgan, Christina M. Neagle, Craig A. Hamilton, Pairoj Rerkpattanapipat, Kerry M. Link
Journal: Circulation (2002)

Regional assessments of left ventricular (LV) wall motion obtained during MRI cardiac stress tests can be used to identify myocardial injury and ischemia, but the utility of MRI stress test results for the assessment of cardiac prognosis is not known.Two hundred seventy-nine patients referred (because of poor LV endocardial visualization with echocardiography) for dobutamine/atropine MRI for the detection of inducible ischemia were followed for an average of 20 months. After MRI stress testing, the occurrence of myocardial infarction, cardiac death, death attributable to any cause, coronary arterial revascularization, and unstable angina or congestive heart failure requiring hospitalization was determined. In a multivariate analysis, the presence of inducible ischemia (hazard ratio 3.3, CI 1.1 to 9.7) or an LV ejection fraction <40% (hazard ratio 4.2, CI 1.3 to 13.9) was associated with future MI or cardiac death independent of the presence of risk factors for coronary arteriosclerosis.In patients with poor echocardiograms, the results of cardiac MRI stress tests can be used to forecast myocardial infarction or cardiac death.
Presentation and Management of Post-treatment Relapse in Autoimmune Pancreatitis/Immunoglobulin G4-Associated Cholangitis
Authors: Neomal S. Sandanayake, Nicholas I. Church, Michael H. Chapman, Gavin J. Johnson, Dipok K. Dhar, Zahir Amin, Maesha G. Deheragoda, Marco Novelli, Alison Winstanley, Manuel Rodriguez–Justo, Adrian R.W. Hatfield, Stephen P. Pereira, George J.M. Webster
Journal: Clinical Gastroenterology and Hepatology (2009)
The Presence of Nipah Virus in Respiratory Secretions and Urine of Patients during an Outbreak of Nipah Virus Encephalitis in Malaysia
Authors: K.B. Chua, S.K. Lam, K.J. Goh, P.S. Hooi, T.G. Ksiazek, A. Kamarulzaman, J. Olson, C.T. Tan
Journal: Journal of Infection (2001)
Short-term comparative study of high frequency chest wall oscillation and European airway clearance techniques in patients with cystic fibrosis
Authors: L. P Osman, M. Roughton, M. E Hodson, J. A Pryor
Journal: Thorax (2009)

High frequency chest wall oscillation (HFCWO) is standard treatment for airway clearance in the USA and has recently been introduced in the UK and Europe. There is little published research comparing HFCWO with airway clearance techniques (ACTs) frequently used in the UK and Europe. The aim of this study was to compare the short-term effects of HFCWO with usual ACTs in patients with cystic fibrosis hospitalised with an infective pulmonary exacerbation.A 4-day randomised crossover design was used. Patients received either HFCWO on days 1 and 3 and usual ACTs on days 2 and 4 or vice versa. Wet weight of sputum, spirometry and oxygen saturation were measured. Perceived efficacy, comfort, incidence of urinary leakage and preference were assessed. Data were analysed by mixed model analysis.29 patients (72% male) of mean (SD) age 29.4 (8.4) years and mean (SD) forced expiratory volume in 1 s (FEV(1)) percentage predicted (FEV(1)%) 38 (16.7) completed the study. Significantly more sputum was expectorated during a single treatment session and over a 24 h period (mean difference 4.4 g and 6.9 g, respectively) with usual ACTs than with HFCWO (p<0.001). No statistically significant change in FEV(1)% or oxygen saturation was observed after either HFCWO or usual ACTs compared with baseline. 17 patients (55%) expressed a preference for their usual ACT.During both a finite treatment period and over 24 h, less sputum was cleared using HFCWO than usual ACT. HFCWO does not appear to cause any adverse physiological effects and may influence adherence.
New Strategies in Colorectal Cancer: Biomarkers of Response to Epidermal Growth Factor Receptor Monoclonal Antibodies and Potential Therapeutic Targets in Phosphoinositide 3-Kinase and Mitogen-Activated Protein Kinase Pathways
Authors: Arvind Dasari, Wells A. Messersmith
Journal: Clinical Cancer Research (2010)

Initial experience with the epidermal growth factor receptor monoclonal antibodies (EGFR MoAb) in unselected patients with metastatic colorectal cancer (mCRC) showed that most of the treated patients did not derive therapeutic benefit. This outcome has driven the search for biomarkers for this population. Recent advances have further shown the heterogeneous nature of this disease with multiple interlinked pathways being implicated. Two such pathways downstream to the EGFR, mitogen-activated protein kinase (MAPK) and (phosphoinositide 3-kinase) PI3K, have gained increasing attention and become targets for development of novel biomarkers and therapeutic agents. Here, we highlight recent progress.
Evidence That an Acute Increase in Glomerular Filtration Has Little Effect on Sodium Excretion in the Dog unless Extracellular Volume is Expanded*
Authors: Marshall D. Lindheimer, Richard C. Lalone, Norman G. Levinsky
Journal: Journal of Clinical Investigation (1967)

The concept that acute increases in glomerular filtration rate (GFR) will cause large concomitant increases in sodium excretion has been re-examined. In previous work, GFR was elevated by volume expansion, usually with saline infusions. Recent evidence shows that tubular reabsorption is depressed during saline loading; hence, the independent effect of increased GFR on sodium excretion cannot be assessed.TO DETERMINE THE EFFECT OF ACUTE INCREASES IN GFR PER SE ON SODIUM EXCRETION, WE RAISED GFR BY FOUR TECHNIQUES NOT INVOLVING VOLUME EXPANSION: protein feeding, dopamine infusion, intravenous dexamethasone, and cross-circulation. GFR increased acutely by 5 to 85% in these experiments. In 12 of 24 experiments, GFR increased by more than 30%. In all but one experiment, sodium excretion increased by less than 75 muEq per minute. Data from experiments using each of the four techniques were comparable. The results were the same whether mineralocorticoid activity was high or low. In contrast, during saline loading, sodium excretion increased more than 800 muEq per minute with equal or lesser changes in GFR. These results demonstrate that acute increases in GFR per se have little effect on sodium excretion. We suggest that, due to constant fractional sodium reabsorption in the proximal tubule (glomerulotubular balance) and increased distal reabsorption, virtually all of the increase in filtered sodium is reabsorbed when GFR increases. Depression of tubular reabsorption is required for natriuresis.
Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings
Authors: C M Chu
Journal: Thorax (2004)

<b>Background:</b> The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. <b>Methods:</b> The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. <b>Results:</b> In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% <i>v</i> 28.8%, p&lt;0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p&lt;0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. <b>Conclusions:</b> The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.