tbuckley/cabot-search huggingface dataset:
Diminished LDL Receptor and High Heparin Binding of Apolipoprotein E2 Sendai Associated with Lipoprotein Glomerulopathy
Authors: MICHAEL M. HOFFMANN, HUBERT SCHARNAGL, ELEFTHERIA PANAGIOTOU, WERNER T. BANGHARD, HEINRICH WIELAND, WINFRIED MA[Combining Diaeresis]RZ
Journal: Journal of the American Society of Nephrology (2001)

Variants of apolipoprotein E (apoE) have been linked to lipoprotein glomerulopathy, a new glomerular disease characterized by the deposition of lipoproteins in mesangial capillaries. One third of affected patients are heterozygous for apoE2 Sendai (Arg(145) Pro). Variants of apoE can also produce type III hyperlipoproteinemia (HLP). Recessive type III HLP is caused by apoE2 (Arg(158) Cys), a mutant with diminished low-density lipoprotein (LDL) receptor binding but halfnormal heparin binding. Dominant type III HLP is caused by mutations that markedly alter heparin binding but modestly reduce receptor binding. This study examined whether apoE2 Sendai (Arg(145) Pro) was functionally different from type III HLP-producing apoE variants by expressing apoE3, apoE2 (Arg(158) Cys), apoE1 (Arg(146) Glu), a dominant apoE variant, and apoE2 Sendai (Arg(145) Pro) in the baculovirus system. LDL receptor binding was studied using recombinant apoE complexed to phospholipid vesicles and to very lowdensity lipoprotein from a patient with familiar apoE deficiency. Compared with apoE3, receptor-binding activities of apoE2 (Arg(158) Cys), apoE1 (Arg(146) Glu), and apoE2 Sendai (Arg(145) Pro) all were less than 5%. Heparin-binding activities were 53%, 23%, and 66%, respectively, of apoE3. The distribution of apoE2 Sendai among the major plasma lipoprotein fractions was similar to that of apoE3 and apoE2 (Arg(158) Cys). ApoE2 Sendai (Arg(145) Pro) represents the only known mutation within the heparin-binding domain of apoE (residues 142 through 147), revealing diminished receptor binding and almost normal heparin binding. These unique characteristics of apoE2 Sendai (Arg(145) Pro) may relate to the development of lipoprotein glomerulopathy.
Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension
Authors: M. C. Tamby, M. Humbert, P. Guilpain, A. Servettaz, N. Dupin, J. J. Christner, G. Simonneau, J. Fermanian, B. Weill, L. Guillevin, L. Mouthon
Journal: European Respiratory Journal (2006)

The aim of the present study was to investigate the presence of anti-fibroblast antibodies in patients with idiopathic or scleroderma-associated pulmonary arterial hypertension (PAH) and healthy controls. PAH was documented by right-heart catheterisation (mean pulmonary artery pressure at rest &gt;25 mmHg). Serum immunoglobulin (Ig)G and IgM reactivities of patients with idiopathic PAH (n = 35), scleroderma-associated PAH (n = 10), diffuse (n = 10) or limited cutaneous (n = 10) scleroderma without PAH and age- and sex-matched healthy individuals (n = 65) were analysed by cell-based ELISA and immunoblotting on normal human fibroblasts. As assessed by ELISA, 14 out of 35 (40%) patients with idiopathic PAH and three out of 10 (30%) patients with scleroderma-associated PAH expressed anti-fibroblast IgG antibodies. IgG from all individuals bound to one major 40-kDa protein band. IgG from patients with idiopathic PAH bound to two 25- and 60-kDa bands with a higher intensity than IgG from other individuals. In conclusion, immunoglobulin G anti-fibroblast antibodies are present in the serum of patients with pulmonary arterial hypertension. Immunoglobulin G from patients with idiopathic pulmonary arterial hypertension or scleroderma-associated pulmonary arterial hypertension express distinct reactivity profiles with fibroblasts antigens, suggesting distinct target antigens.
Repeatability and Reproducibility of Retinal Thickness Measurements by Optical Coherence Tomography in Age-Related Macular Degeneration
Authors: Ilse Krebs, Stefan Hagen, Werner Brannath, Paulina Haas, Irene Womastek, Gabriella de Salvo, Siamak Ansari-Shahrezaei, Susanne Binder
Journal: Ophthalmology (2010)
The effect of mindfulness meditation on cough reflex sensitivity
Authors: E C Young, C Brammer, E Owen, N Brown, J Lowe, C Johnson, R Calam, S Jones, A Woodcock, J A Smith
Journal: Thorax (2009)

<h3>Background:</h3> Chronic cough is common, and medical treatment can be ineffective. Mindfulness is a psychological intervention that aims to teach moment-to-moment non-judgemental awareness of thoughts, feelings and sensations. <h3>Method:</h3> 30 healthy subjects and 30 patients with chronic cough were studied in two sequential trials. For both studies, cough reflex sensitivity to citric acid (C5) was measured on two occasions, with urge to cough rated following each inhalation; between challenges subjects were randomised to (1) no intervention, (2) mindfulness or (3) no intervention but modified cough challenge (subjects suppress coughing). For the healthy volunteers, measures were 1 h apart and mindfulness was practised for 15 min. For the patients with chronic cough measures were 1 week apart and mindfulness was practised daily for 30 min. <h3>Results:</h3> In healthy volunteers, median change (interquartile range (IQR)) in cough reflex sensitivity (logC5) for no intervention, mindfulness and suppression was +1.0 (0.0 to +1.3), +2.0 (+1.0 to +3.0) and +3.0 (+2.8 to +3.0) doubling concentrations (p = 0.003); there were significant reductions for both mindfulness (p = 0.043) and suppression (p = 0.002) over no intervention. In patients with cough, median change (IQR) in logC5 for no intervention, mindfulness training and voluntary suppression was 0.0 (−1.0 to +1.0), +1.0 (−0.3 to +1.0) and +1.0 (+1.0 to +2.0) doubling concentrations (p = 0.046); there was a significant reduction for suppression (p = 0.02) but not mindfulness (p = 0.35). Urge to cough did not change after mindfulness compared with control in either healthy subjects (p = 0.33) or those with chronic cough (p = 0.47). <h3>Conclusion:</h3> Compared with control, mindfulness decreased cough reflex sensitivity in healthy volunteers, but did not alter cough threshold in patients with chronic cough. Both groups were able to suppress cough responses to citric acid inhalation.
High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients
Authors: T.G.P. Grunewald, A. Ranft, I. Esposito, P. da Silva-Buttkus, M. Aichler, D. Baumhoer, K.L. Schaefer, L. Ottaviano, C. Poremba, G. Jundt, H. Jürgens, U. Dirksen, G.H.S. Richter, S. Burdach
Journal: Annals of Oncology (2012)
Achieving Effective Treatment of Patients With Chronic Psychotic Illness and Comorbid Substance Dependence
Authors: Andrew P. Ho, John W. Tsuang, Robert P. Liberman, Richard Wang, Jeffrey N. Wilkins, Thad A. Eckman, Andrew L. Shaner
Journal: American Journal of Psychiatry (1999)

The changing effectiveness of a treatment program for dual-diagnosis patients was evaluated over a 2-year period with the use of a sequential study group design.The treatment outcome of 179 consecutively enrolled patients with chronic psychotic illness and comorbid substance dependence who entered a specialized day hospital dual-diagnosis treatment program from Sept. 1, 1994, to Aug. 31, 1996, was evaluated. The 24 months were divided into four successive 6-month periods for comparing the evolving effectiveness of the program for groups of patients entering the day hospital during these four periods. Treatment attendance, hospital utilization, and twice weekly urine toxicology analyses were used as outcome measures.The initial treatment engagement rate, defined as at least 2 days of attendance in the first month, increased significantly from group 1 to group 4, more than doubling. Thirty-day and 90-day treatment retention rates also substantially increased from group 1 to group 4. More patients had no hospitalization in the 6 months after entering the day hospital program than in the 6 months before entering the day hospital program. Urine toxicology monitoring indicated that the patients in group 4 were more likely than those in group 1 to remain abstinent at follow-up.The evolving clinical effectiveness of a developing program can be quantified by using a sequential group comparison design. The sequential outcome improvements may be related to the incremental contributions of assertive case management and skills training for relapse prevention.
CPAP for OSA is cost effective
Authors: G Hands
Journal: Thorax (2006)

▴ Ayas NT, FitzGerald JM, Fleetham JA, et al . Cost-effectiveness of continuous positive airway pressure therapy for moderate to severe obstructive sleep apnea/hypopnea. Arch Intern Med2006;166:977–84 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Untreated obstructive sleep apnoea/hypopnoea (OSAH) is known to be associated with daytime sleepiness, deteriorating health related quality of life (HRQL), hypertension to an individual sufferer, and reduction in daytime performance and an increased incidence of road traffic accidents (RTAs) which has a significant impact on society. Continuous positive airway pressure (CPAP) is known to be an effective treatment of OSAH, which improves symptoms and HRQL. Hitherto, a few studies have found CPAP also to be cost … [1]: {openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DAyas%26rft.auinit1%253DN.%2BT.%26rft.volume%253D166%26rft.issue%253D9%26rft.spage%253D977%26rft.epage%253D984%26rft.atitle%253DCost-effectiveness%2Bof%2BContinuous%2BPositive%2BAirway%2BPressure%2BTherapy%2Bfor%2BModerate%2Bto%2BSevere%2BObstructive%2BSleep%2BApnea%252FHypopnea.%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.166.9.977%26rft_id%253Dinfo%253Apmid%252F16682570%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/archinte.166.9.977&link_type=DOI [3]: /lookup/external-ref?access_num=16682570&link_type=MED&atom=%2Fthoraxjnl%2F61%2F11%2F999.atom [4]: /lookup/external-ref?access_num=000237334900005&link_type=ISI
Magnetic resonance colonography for the detection of inflammatory diseases of the large bowel: quantifying the inflammatory activity
Authors: W M Ajaj
Journal: Gut (2005)

The purpose of this study was to assess the diagnostic accuracy of magnetic resonance colonography (MRC) for its ability to detect and quantify inflammatory bowel disease (IBD) affecting the colon. Endoscopically obtained histopathology specimens were used as the standard of reference.Fifteen normal subjects and 23 patients with suspected IBD of the large bowel underwent MRC. Three dimensional T1 weighted data sets were collected following rectal administration of water prior to and 75 seconds after intravenous administration of paramagnetic contrast (gadolinium-BOPTA). The presence of inflammatory changes in patients was documented based on bowel wall contrast enhancement, bowel wall thickness, presence of perifocal lymph nodes, and loss of haustral folds. All four criteria were quantified relative to data obtained from normal subjects and summarised in a single score. This MRC based score was compared with histopathological data based on conventional endoscopic findings.MRC correctly identified 68 of 73 segments found to reveal IBD changes by histopathology. All severely inflamed segments were correctly identified as such and there were no false positive findings. Based on the proposed composite score, MRC detected and characterised clinically relevant IBD of the large bowel with sensitivity and specificity values of 87% and 100%, respectively, for all investigated colonic segments.MRC may be considered a promising alternative to endoscopic biopsy in monitoring IBD activity or assessing therapeutic effectiveness.
Risk Stratification of Patients With Acute Anterior Myocardial Infarction and Right Bundle-Branch Block
Authors: Cheuk-Kit Wong, Wanzhen Gao, Ralph A.H. Stewart, Niels van Pelt, John K. French, Philip E.G. Aylward, Harvey D. White
Journal: Circulation (2006)

Patients with an acute anterior ST-segment elevation myocardial infarction and right bundle-branch block (RBBB) have a high mortality risk, which may be stratified by early ECG changes.In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial infarction (AMI) within 6 hours of symptom onset were treated with streptokinase and randomized to receive bivalirudin or heparin. There was no difference in the primary end point of 30-day mortality. ECGs were recorded at randomization and 60 minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6% in the 415 patients with RBBB and anterior AMI at randomization and 33% in the 100 patients who developed new RBBB at 60 minutes from normal baseline conduction accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was associated with increasing 30-day mortality rate in both RBBB groups on multivariable analyses with covariates of age, Killip class, systolic blood pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2% versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups, respectively). For the patients with RBBB and anterior MI at randomization, RBBB resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged. For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006).In patients with anterior AMI and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST-segment resolution after fibrinolytic therapy despite persisting RBBB is associated with lower mortality rate.
Utility of Circulating <i>B-RAF</i> DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy
Authors: Masaru Shinozaki, Steven J. O'Day, Minoru Kitago, Farin Amersi, Christine Kuo, Joseph Kim, He-Jing Wang, Dave S.B. Hoon
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Somatic B-RAF gene mutation has been identified in many malignancies and detected at a high frequency in cutaneous malignant melanoma. However, the significance of the B-RAF mutation (B-RAFmt) in terms of its prognostic and predictive capabilities for treatment response or disease outcome is not known. We hypothesized that circulating serum B-RAFmt (B-RAFsmt) at V600E, detected in serum, predicts response in melanoma patients receiving concurrent biochemotherapy. Experimental Design: A real-time clamp quantitative reverse transcription-PCR assay was designed to assess B-RAFsmt by peptide nucleic acid clamping and a locked nucleic acid hybrid probe. Normal (n = 18) and American Joint Committee on Cancer stage I to IV melanoma patients (n = 103) were evaluated. These included stage IV patients (n = 48) with blood drawn before and after biochemotherapy. Patients were classified as biochemotherapy responders or nonresponders. Responders (n = 24) had a complete or partial response following biochemotherapy; nonresponders (n = 24) developed progressive disease. Results: Of the 103 melanoma patients, 38 (37%) had B-RAFsmt DNA, of which 11 of 34 (32%) were stage I or II, and 27 of 69 (39%) were stage III or IV. Of the 48 biochemotherapy patients, 10 of 24 (42%) patients were positive for the B-RAFsmt in the respective responder and nonresponder groups before treatment. After biochemotherapy, B-RAFsmt was detected in only 1 of 10 patients (10%) in the responder group and 7 of 10 patients (70%) in the nonresponder group. B-RAFsmt is associated with significantly worse (P = 0.039) overall survival in patients receiving biochemotherapy. Conclusion: These studies show the presence and utility of circulating B-RAFsmt DNA in melanoma patients.
Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients
Authors: Giovanni Targher, Lorenzo Bertolini, Roberto Padovani, Stefano Rodella, Roberto Tessari, Luciano Zenari, Christopher Day, Guido Arcaro
Journal: Diabetes Care (2007)

OBJECTIVE—To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic population and to compare the prevalence of cardiovascular disease (CVD) and its risk factors between people with and without NAFLD. RESEARCH DESIGN AND METHODS—The entire sample of type 2 diabetic outpatients (n = 2,839) who regularly attended our clinic was screened. Main outcome measures were NAFLD (by patient history and liver ultrasound) and manifest CVD (by patient history, review of patient records, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries). RESULTS—The unadjusted prevalence of NAFLD was 69.5% among participants, and NAFLD was the most common cause (81.5%) of hepatic steatosis on ultrasound examination. The prevalence of NAFLD increased with age (65.4% among participants aged 40–59 years and 74.6% among those aged ≥60 years; P &amp;lt; 0.001) and the age-adjusted prevalence of NAFLD was 71.1% in men and 68% in women. NAFLD patients had remarkably (P &amp;lt; 0.001) higher age and sex-adjusted prevalences of coronary (26.6 vs. 18.3%), cerebrovascular (20.0 vs. 13.3%), and peripheral (15.4 vs. 10.0%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD independent of classical risk factors, glycemic control, medications, and metabolic syndrome features. CONCLUSIONS—NAFLD is extremely common in people with type 2 diabetes and is associated with a higher prevalence of CVD. Follow-up studies are needed to determine whether NAFLD predicts the development and progression of CVD.
Reduction in leukotriene B4 generation by bronchoalveolar lavage cells in asthma.
Authors: L J Restrick, A P Sampson, P J Piper, J F Costello
Journal: Thorax (1995)

BACKGROUND--Leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypothesis was tested using bronchoalveolar lavage (BAL) to sample cells within the airways from atopic asthmatic and normal subjects, and by measuring their capacity to generate leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in response to A23187, a potent stimulus of leukotriene generation. METHODS--Bronchoalveolar lavage was performed in 12 mild asymptomatic atopic asthmatic patients and 12 normal subjects. Mixed BAL cell aliquots (approximately 80% alveolar macrophages) were incubated with 0-20 microM A23187 for 10 minutes and with 4 microM A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography. RESULTS--Mixed BAL cells from asthmatic subjects generated less LTB4 than cells from normal subjects in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng.min.10(-6) cells in asthmatic subjects and 197.9 (13.9-935.6) ng.min.10(-6) cells in normal subjects. There were no differences in LTC4 generation between BAL cells from asthmatic and normal subjects. CONCLUSIONS--Generation of LTB4 by BAL cells from atopic asthmatic subjects in response to A23187 was reduced. As the alveolar macrophage is the major source of LTB4 in BAL cells, these results probably reflect reduced generation of LTB4 by alveolar macrophages from asthmatic patients. This may be a consequence of monocyte migration into the lung, or altered alveolar macrophage function in asthma, or both.
Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
Authors: Mario Sznol, Mayer Fishman, Bernard Escudier, David F McDermott, Harriet Kluger, Walter M Stadler, Jose Perez-Gracia, Douglas G McNeel, Brendan D Curti, Michael R Harrison, Elizabeth R Plimack, Leonard Appleman, Lawrence Fong, Charles G Drake, Tina C Young, Scott D Chasalow, Petra Ross-MacDonald, Jason S Simon, Dana Walker, Toni K Choueiri
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In previously treated patients with metastatic renal cell carcinoma (mRCC), the programmed death-1 (PD-1) inhibitor antibody nivolumab demonstrated objective response rates of 20%–22% and median overall survival (OS) of 18.2– 25.5 months[[1][1]]. An exploratory biomarker
Comparative study between swedish and sudanese RA patients
Authors: A I Elshafie, E Ahlin, S A Norein, K E Khalafalla, M Al-Edreese, E M Elagib, M A M Nur, J Ronnelid
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is a systemic infl ammatory autoimmune disease, characterised by chronic, erosive polyarthritis and by the presence of various autoantibodies.These autoantibodies play an important role in the pathogenesis, especially rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP).According to our knowledge there are no data published concerning serologic RA phenotypes in Sudan.Our aim was to evaluate the presence of RF and Anti-CCP in well-characterised cross-sectional hospital-based consecutive cohort of Sudanese RA patients and to compare with an earlier described Swedish early RA cohort.Serum samples were collected from 96 Sudanese patients with established RA with mean age 49.5 years, mean disease duration 5.6 years (range 2 months to 30 years) and 50 healthy Sudanese blood donor controls.Detailed clinical and laboratory investigations for the diagnosis had been done between December 2008 and August 2009 by senior rheumatologists following the 1987 ACR criteria.All patients were on regular follow-up.77/91 (84.6%) were treated with DMARDs: 65/91 (71.4%) with methotrexate, 18/91 (19.8%) on July 30,
Exchange protein directly activated by cAMP 1 promotes autophagy during cardiomyocyte hypertrophy
Authors: Anne-Coline Laurent, Malik Bisserier, Alexandre Lucas, Florence Tortosa, Marie Roumieux, Annélie De Régibus, Audrey Swiader, Yannis Sainte-Marie, Christophe Heymes, Cécile Vindis, Frank Lezoualc'h
Journal: Cardiovascular Research (2014)

Stimulation of β-adrenergic receptors (β-AR) increases cAMP production and contributes to the pathogenesis of cardiac hypertrophy and failure through poorly understood mechanisms. We previously demonstrated that Exchange protein directly activated by cAMP 1 (Epac1)-induced hypertrophy in primary cardiomyocytes. Among the mechanisms triggered by cardiac stress, autophagy has been highlighted as a protective or harmful response. Here, we investigate whether Epac1 promotes cardiac autophagy and how altered autophagy has an impact on Epac1-induced cardiomyocyte hypertrophy. We reported that direct stimulation of Epac1 with the agonist, Sp-8-(4-chlorophenylthio)-2′-O-methyl-cAMP (Sp-8-pCPT) promoted autophagy activation in neonatal cardiomyocytes. Stimulation of β-AR with isoprenaline (ISO) mimicked the effect of Epac1 on autophagy markers. Conversely, the induction of autophagy flux following ISO treatment was prevented in cardiomyocytes pre-treated with a selective inhibitor of Epac1, CE3F4. Importantly, we found that Epac1 deletion in mice protected against β-AR-induced cardiac remodelling and prevented the induction of autophagy. The signalling mechanisms underlying Epac1-induced autophagy involved a Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ)/AMP-dependent protein kinase (AMPK) pathway. Finally, we provided evidence that pharmacological inhibition of autophagy using 3-methyladenine (3-MA) or down-regulation of autophagy-related protein 5 (Atg5) significantly potentiated Epac1-promoted cardiomyocyte hypertrophy. Altogether, these findings demonstrate that autophagy is an adaptive response to antagonize Epac1-promoted cardiomyocyte hypertrophy.