tbuckley/cabot-search huggingface dataset:
Embryonic Expression Suggests an Important Role for CRP2/SmLIM in the Developing Cardiovascular System
Authors: Mukesh K. Jain, Saori Kashiki, Chung-Ming Hsieh, Matthew D. Layne, Shaw-Fang Yet, Nicholas E. S. Sibinga, Michael T. Chin, Mark W. Feinberg, Ian Woo, Richard L. Maas, Edgar Haber, Mu-En Lee
Journal: Circulation Research (1998)

Abstract —Proteins of the LIM family are critical regulators of development and differentiation in various cell types. We have described the cloning of cysteine-rich protein 2/smooth muscle LIM protein (CRP2/SmLIM), a LIM-only protein expressed in differentiated vascular smooth muscle cells. As a first step toward understanding the potential functions of CRP2/SmLIM, we analyzed its expression after gastrulation in developing mice and compared the expression of CRP2/SmLIM with that of the other 2 members of the CRP subclass, CRP1 and CRP3/MLP. In situ hybridization in whole-mount and sectioned embryos showed that CRP2/SmLIM was expressed in the sinus venosus and the 2 cardiac chambers at embryonic day 9. Vascular expression of CRP2/SmLIM was first seen at embryonic day 10. At subsequent time points, CRP2/SmLIM expression decreased in the heart but remained high in the vasculature. CRP1 was expressed both in vascular and nonvascular tissues containing smooth muscle cells, whereas CRP3/MLP was expressed only in tissues containing striated muscle. These patterns of expression were maintained in the adult animal and suggest an important role for this gene family in the development of smooth and striated muscle.
Negative Effect of DNA Hypermethylation on the Outcome of Intensive Chemotherapy in Older Patients with High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia following Myelodysplastic Syndrome
Authors: Michael Grövdal, Rasheed Khan, Anni Aggerholm, Petar Antunovic, Jan Astermark, Per Bernell, Lena-Maria Engström, Lars Kjeldsen, Olle Linder, Lars Nilsson, Anna Olsson, Jonas Wallvik, Jon Magnus Tangen, Gunnar Öberg, Sten Eirik Jacobsen, Peter Hokland, Anna Porwit, Eva Hellström-Lindberg
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. Experimental Design: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-β-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15ink4b (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. Results: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. Conclusions: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.
Metaphoric threat is more real than real threat
Authors: Jordan B. Peterson, Colin G. DeYoung
Journal: Behavioral and Brain Sciences (2000)

Dreams represent threat, but appear to do so metaphorically more often than realistically. The metaphoric representation of threat allows it to be conceptualized in a manner that is constant across situations (as what is common to all threats begins to be understood and portrayed). This also means that response to threat can come to be represented in some way that works across situations. Conscious access to dream imagery, and subsequent social communication of that imagery, can facilitate this generalized adaptive process, by allowing the communicative dreamer access to the problem solving resources of the community. [Revonsuo; Solms]
Smoking, allergy, and the differential white blood cell count.
Authors: R G Taylor, E Gross, H Joyce, F Holland, N B Pride
Journal: Thorax (1985)

Dutch workers have proposed that people with asthma and those smokers who develop chronic airflow obstruction share a common allergic constitution. To study whether smoking itself is associated with indicators of allergy, we have examined 237 men aged 51-61 years (120 smokers, 73 ex-smokers, and 44 non-smokers) who were recruited to a long term study of lung function in 1974, at which time men with a clinical diagnosis of asthma were excluded. Smokers, ex-smokers, and non-smokers did not differ in personal or family history of allergic disease, but the prevalence of positive responses to skinprick tests was greater in ex-smokers (59%) than in the other two groups (33% and 34%). In men with negative responses to skinprick tests total serum IgE was greater in smokers (log10 mean 1.41 IU/ml) and in ex-smokers (log10 mean 1.53 IU/ml) than in non-smokers (log10 mean 1.12 IU/ml). In men with positive skin test responses serum IgE was similar in the three groups (log10 mean ranging from 1.68 to 1.78 IU/ml). Geometric mean total white cell counts in the peripheral blood were higher in smokers (7.34 X 10(9)/l) than in non-smokers (5.82 X 10(9)/l); the value in ex-smokers (6.16 X 10(9)/l) was intermediate. Absolute blood eosinophil counts were increased in smokers disproportionately to the increase in total white cell count. Thus smoking is associated with small increases in some markers of allergy. These changes are probably acquired after the onset of smoking but sequential studies are required to amplify these cross sectional observations. Smokers whose skin test responses are positive appear more likely to give up smoking.
Potentiated adherence of sickle erythrocytes to endothelium infected by virus.
Authors: R P Hebbel, M R Visser, J L Goodman, H S Jacob, G M Vercellotti
Journal: Journal of Clinical Investigation (1987)

Systemic viral infection is a known precipitant of vasocclusive crisis in sickle patients, but the mechanism underlying this clinical observation is unknown. In the present studies, human umbilical vein endothelial cells were infected with Herpes simplex virus type 1 (HSV) to model systemic viral disease. The already abnormal adherence of sickle erythrocytes to control endothelium is enhanced 1.8 +/- 0.4-fold to HSV-infected endothelium (P less than 0.001). This component of potentiated adherence is eliminated by maneuvers that block Fc receptors, it is prevented by tunicamycin, and it is not seen using a mutant HSV that is unable to express the Fc receptor glycoprotein. Thus, the incremental adherence seen here occurs due to expression of Fc receptor activity on HSV-infected endothelium and the consequent recognition of abnormal amounts of IgG on sickle erythrocytes. We conclude that systemic viral infection potentially can induce a novel mechanism for enhancement of erythrocyte adherence to endothelium and that this may increase the likelihood of vasocclusion during viral infection.
Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus
Authors: Christoph Welsch, Francisco S Domingues, Simone Susser, Iris Antes, Christoph Hartmann, Gabriele Mayr, Andreas Schlicker, Christoph Sarrazin, Mario Albrecht, Stefan Zeuzem, Thomas Lengauer
Journal: Genome biology (2008)

The inhibitor telaprevir (VX-950) of the hepatitis C virus (HCV) protease NS3-4A has been tested in a recent phase 1b clinical trial in patients infected with HCV genotype 1. This trial revealed residue mutations that confer varying degrees of drug resistance. In particular, two protease positions with the mutations V36A/G/L/M and T54A/S were associated with low to medium levels of drug resistance during viral breakthrough, together with only an intermediate reduction of viral replication fitness. These mutations are located in the protein interior and far away from the ligand binding pocket.Based on the available experimental structures of NS3-4A, we analyze the binding mode of different ligands. We also investigate the binding mode of VX-950 by protein-ligand docking. A network of non-covalent interactions between amino acids of the protease structure and the interacting ligands is analyzed to discover possible mechanisms of drug resistance. We describe the potential impact of V36 and T54 mutants on the side chain and backbone conformations and on the non-covalent residue interactions. We propose possible explanations for their effects on the antiviral efficacy of drugs and viral fitness. Molecular dynamics simulations of T54A/S mutants and rotamer analysis of V36A/G/L/M side chains support our interpretations. Experimental data using an HCV V36G replicon assay corroborate our findings.T54 mutants are expected to interfere with the catalytic triad and with the ligand binding site of the protease. Thus, the T54 mutants are assumed to affect the viral replication efficacy to a larger degree than V36 mutants. Mutations at V36 and/or T54 result in impaired interaction of the protease residues with the VX-950 cyclopropyl group, which explains the development of viral breakthrough variants.
Ventriculoatrial Intervals: Diagnostic Use in Paroxysmal Supraventricular Tachycardia
Authors: DAVID G. BENDITT
Journal: Annals of Internal Medicine (1979)

Reciprocating tachycardias due to reentry either within the atrioventricular (AV) node or using an accessory AV pathway are a common cause of paroxysmal supraventricular tachycardia in humans. Unfortunately, although of potential therapeutic value, differentiation of these forms of reciprocating tachycardia may be difficult and require detailed electrophysiologic study. To develop diagnostic criteria that permit exclusion of participation of an accessory AV pathway in reciprocating tachycardia without extensive laboratory testing, results of electrophysiologic studies were examined in 50 patients with Wolff-Parkinson-White syndrome, 15 patients with accessory AV pathways that conducted only in the ventriculoatrial direction, and 15 patients with reentry within the AV node. The interval between onset of ventricular activation and both earliest recorded atrial activity (V-Amin) and high lateral right atrial electrogram (V-HRA) was measured during tachycardia. A V-Amin of 61 ms or less or V-HRA of 95 ms or less did not occur in patients with accessory AV pathways, but occurred frequently (12 of 15 and seven of eight, respectively) in patients with reentry within the AV node. Therefore, in patients with paroxysmal reciprocating tachycardias, V-A interval measurements provide a screening test capable of excluding participation of an accessory AV pathway.
Extrapituitary prolactin promoter polymorphism in Czech patients with systemic lupus erythematosus and rheumatoid arthritis
Authors: M. Fojtikova, M. Cerna, P. Cejkova, S. Ruzickova, C. Dostal
Journal: Annals of the Rheumatic Diseases (2007)

Prolactin (PRL) and its production by lymphocytes have been suggested to play a distinct role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).1,2 PRL acts as a cytokine and influences the maturation and differentiation of immune cells.3,4 Extrapituitary PRL synthesis is regulated by an alternative promoter,5 which contains a single-nucleotide polymorphism (SNP) at the region −1149 G/T. Higher PRL mRNA expression is associated with the G allele in lymphocytes.6 High frequency of the G allele was described in patients with SLE,7 but was not confirmed in other work.8

We investigated −1149 G/T SNP in 156 patients with SLE and 173 patients with RA, and in 123 healthy individuals (control group). Patients …
Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis
Authors: G J Wolbink
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). <b>Methods:</b> Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. <b>Results:</b> After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders (median (interquartile range) 0.5 (0.2–2.2) <i>v</i> 3.6 (1.4–8.2) mg/l; p&lt;0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment (Spearman rank correlation <i>r</i><sub>s</sub> = −0.43, p&lt;0.001). <b>Conclusion:</b> Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing intervals.
Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease
Authors: York Pei, Young-Hwan Hwang, John Conklin, Jamie L. Sundsbak, Christina M. Heyer, Winnie Chan, Kairong Wang, Ning He, Anand Rattansingh, Mostafa Atri, Peter C. Harris, Masoom A. Haider
Journal: Journal of the American Society of Nephrology (2014)

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.
Phospholipase A2 Receptor Autoantibodies and Clinical Outcome in Patients with Primary Membranous Nephropathy
Authors: Elion Hoxha, Ina Thiele, Gunther Zahner, Ulf Panzer, Sigrid Harendza, Rolf A.K. Stahl
Journal: Journal of the American Society of Nephrology (2014)

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A2 receptor (PLA2R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA2R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA2R antibodies who had not received immunosuppressive therapy. Patients were followed ≤24 months. PLA2R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA2R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA2R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA2R antibody levels achieved remission of proteinuria significantly later than patients with low PLA2R antibody levels. PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA2R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary MN.
Senate Examines Improper Medicare and Medicaid Payments
Authors: Julie A. Jacob
Journal: JAMA (2015)

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Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure.
Authors: M R Bristow, R Ginsburg, V Umans, M Fowler, W Minobe, R Rasmussen, P Zera, R Menlove, P Shah, S Jamieson
Journal: Circulation Research (1986)

We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists.
A prospective study on dinghy sailors’ training habits and injury incidence with a comparison between elite sailor and club sailor during a 12-month period
Authors: Lena Bøymo-Having, Magnus Grävare, Karin Grävare Silbernagel
Journal: British Journal of Sports Medicine (2013)

Background Sailing is an Olympic sport practiced by both men and women of all ages. Despite being a popular sport, we have found no prospective studies investigating the injury incidence and training quantity such as found for other sports. The purpose of this study was to do an inventory over dinghy sailors’ training habits, injury incidence and type of injury. Methods In this prospective cohort study, 45 sailors (17 women and 28 men), age 17–31 years, were included. 24 sailors belonged to the SWE Sailing Team and 21 were club sailors. All the participants kept a training diary, and once a month for 12 months they reported their training and injuries through a web-based questionnaire. Each time a sailor reported an injury, they were contacted by the researchers and an injury form was completed. Results The SWE Sailing Team performed significantly (p=0.006) more physical training than the club sailor. There was no significant difference (p=0.7) in hours of sail training. A total of 144 injuries were reported. The most common injury location was the knee (19%), followed by the lower leg (13%) and shoulder (12%). 30% of the injuries occurred during physical training, 17% during sail training and 12% during sail racing. Conclusions The most common injury location was the knee. The largest proportion of injuries occurred during physical training and unspecified activities. The least number of injuries occurred during sail racing. The injury location was different between the older more experienced sailor (more upper extremity injuries) compared with the younger sailors (more trunk injuries).
Evaluating Health Research Capacity Building: An Evidence-Based Tool
Authors: Imelda Bates, Alex Yaw Osei Akoto, Daniel Ansong, Patrick Karikari, George Bedu-Addo, Julia Critchley, Tsiri Agbenyega, Anthony Nsiah-Asare
Journal: PLoS Medicine (2006)

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