tbuckley/cabot-search huggingface dataset:
STUDIES IN IMMUNITY AND ANAPHYLAXIS
Authors: Richard M. Pearce, Howard T. Karsner, Arthur B. Eisenbrey
Journal: The Journal of Experimental Medicine (1911)

1. The sera of rabbits injected repeatedly with the nucleoproteins, globulins, and albumins of the liver and kidney of the dog give no evidence in vitro or in vivo experiments of organ affinity. The precipitin test offers no proof of the specificity of these sera for the proteins employed as antigens. 2. The anaphylaxis reaction applied to the same proteins indicates a slight relative organ affinity but no specificity as far as the respective protein fractions are concerned. The relative organ affinity resides, rather, in the globulin and albumin fractions than in the nucleoprotein fraction. Dog serum used both as a sensitizing and an intoxicating agent gives rise to very active cross reactions with organ proteins, thus failing to support the theory of organ or of protein specificity. 3. These results do not support the view put forward that nucleoproteins play an important part in the course of production of cytotoxic immune sera.
Suppression of Plasma Estrogen Levels by Letrozole and Anastrozole Is Related to Body Mass Index in Patients With Breast Cancer
Authors: Elizabeth J. Folkerd, J. Michael Dixon, Lorna Renshaw, Roger P. A'Hern, Mitch Dowsett
Journal: Journal of Clinical Oncology (2012)

To investigate whether suppression of plasma estradiol and estrone sulfate levels by the aromatase inhibitors (AIs) anastrozole and letrozole is related to body mass index (BMI) in postmenopausal women with early estrogen receptor (ER) -positive breast cancer. Recent studies have reported that the AI anastrozole has lower effectiveness than tamoxifen in women with high BMI. This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole.Plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay were available for 44 postmenopausal patients who received anastrozole (1 mg per day) for 3 months followed by letrozole (2.5 mg per day) for 3 months or the opposite sequence. Correlations between the estrogen suppression by each AI and BMI were assessed.Baseline values of estradiol and estrone sulfate were significantly correlated with BMI (r = 0.57; P < .001, and r = 0.38; P = .006, respectively). Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both AIs, but although this was significant with letrozole (r = 0.35; P = .013, and r = 0.30; P = .035 for estradiol and estrone sulfate, respectively), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study.The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.
Octreotide LAR for severe obscure-overt gastrointestinal haemorrhage in high-risk patients on anticoagulation therapy
Authors: J Molina-Infante, B Perez-Gallardo, G Gonzalez-Garcia, M Fernandez-Bermejo, J M Mateos-Rodriguez, P Robledo-Andres
Journal: Gut (2007)

We read with interest the letter by Krikis et al ( Gut 2005; 54 :171–2). We report on two patients with a poor clinical history (recurrent gastrointestinal haemorrhage, older age, severe comorbidity, anticoagulation, contraindication to β-blockers), successfully treated using only octreotide long-active release (LAR).

A 73-year-old man was admitted six times (32 days of hospital stay) in the previous six months because of recurrent episodes of melaena. Medical history included type 1 diabetes, three myocardial infarctions and multivessel disease treated by triple-bypass graft surgery (left ventricular ejection fraction 35%), ischaemic stroke due to total occlusion of the right carotid artery, surgically solved, and occlusion of the …
Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial
Authors: Marco Valgimigli, Andrea Gagnor, Paolo Calabró, Enrico Frigoli, Sergio Leonardi, Tiziana Zaro, Paolo Rubartelli, Carlo Briguori, Giuseppe Andò, Alessandra Repetto, Ugo Limbruno, Bernardo Cortese, Paolo Sganzerla, Alessandro Lupi, Mario Galli, Salvatore Colangelo, Salvatore Ierna, Arturo Ausiello, Patrizia Presbitero, Gennaro Sardella, Ferdinando Varbella, Giovanni Esposito, Andrea Santarelli, Simone Tresoldi, Marco Nazzaro, Antonio Zingarelli, Nicoletta de Cesare, Stefano Rigattieri, Paolo Tosi, Cataldo Palmieri, Salvatore Brugaletta, Sunil V Rao, Dik Heg, Martina Rothenbühler, Pascal Vranckx, Peter Jüni
Journal: The Lancet (2015)
Translating evidence-based sports medicine into clinical practice: time to point the finger at doctors as much as at patients with respect to knee arthroscopy
Authors: John Orchard
Journal: British Journal of Sports Medicine (2015)

When health practitioners bemoan the gap between the scientific evidence base and the real world, it is usually with a belief that patients or policymakers are failing to heed advice of established medical science. Occasionally, we need to concede that the medical profession can sometimes fall behind the scientifically established evidence base.

The most common orthopaedic procedure in the UK, the USA and elsewhere, is knee arthroscopy. This revolutionary 1980s procedure transformed knee surgery as it slashed surgical recovery time from months to weeks. It took 20 years for the first high-quality studies to assess whether knee arthroscopy was actually efficacious for its most common indications, and these results did not favour surgery.1 Multiple randomised controlled trials since, comparing knee arthroscopy in middle-aged arthritic knees (with or without meniscectomy) with another treatment (sham surgery or conservative treatment)2–5 have …
Altered N-myc Downstream-Regulated Gene 1 Protein Expression in African-American Compared with Caucasian Prostate Cancer Patients
Authors: Robert P. Caruso, Benjamin Levinson, Jonathan Melamed, Rosemary Wieczorek, Samir Taneja, David Polsky, Caroline Chang, Anne Zeleniuch-Jacquotte, Konstantin Salnikow, Herman Yee, Max Costa, Iman Osman
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds. Experimental Design: Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined. We studied 223 cases, including 157 African Americans and 66 Caucasians (T2, n = 144; ≥T3, n = 79; Gleason &amp;lt;7, n = 122; ≥7, n = 101). Three patterns of NDRG1 expression were identified in prostate cancer: (a) intense, predominately membranous staining similar to benign prostatic epithelium; (b) intense, nucleocytoplasmic localization; and (c) low or undetectable expression. We then examined the correlations between patients’ clinicopathological parameters and different NDRG1 expression patterns. Results: In this study of patients with equal access to care, African-American ethnic origin was an independent predictor of prostate-specific antigen recurrence (P &amp;lt; 0.05). We also observed a significant correlation between different patterns of NDRG1 expression and ethnic origin. Pattern 2 was less frequent in African Americans (21% versus 38%), whereas the reverse was observed for pattern 3 (60% in African Americans versus 44% in Caucasians; P = 0.03). This association remained significant after controlling for both grade and stage simultaneously (P = 0.02). Conclusions: Our data suggest that different NDRG1 expression patterns reflect differences in the response of prostatic epithelium to hypoxia and androgens in African-American compared with Caucasian patients. Further studies are needed to determine the contribution of NDRG1 to the disparity in clinical outcome observed between the two groups.
Cardiac sympathetic neuronal function in left ventricular volume and pressure overload
Authors: G.A. Somsen, E. A. Dubois, K. Brandsma, J. de Jong, P. A. van der Wouw, H. D. Batink, E. A. van Royen, K. I. Lie, P. A. van Zwieten
Journal: Cardiovascular Research (1996)

In heart failure cardiac sympathetic neuronal function and activity appear to be altered. Although these changes are widely accepted, controversy exists concerning the neurohormonal changes occurring in pressure and volume overloaded hearts. The present study in rabbits was performed to assess the effects of mechanical overload on cardiac sympathetic neuronal function and beta-adrenoceptor density, in relation to left ventricular function.In nine rabbits the aortic valve was perforated to induce left ventricular volume overload. Pressure overload was induced by suprarenal banding of the aorta abdominalis (group 1). Five animals were sham operated (group 2). Subanalysis of group 1 was performed for non-failing (n = 5) and failing (n = 4) hearts. Heart failure was defined as any reduction in left ventricular fractional shortening 2 weeks after the second operation compared to baseline.In animals with cardiac overload, left ventricular weight was higher compared with the control animals, 7.99 +/- 1.13 vs. 6.16 +/- 0.86 g (P < 0.02). Left ventricular end diastolic diameter increased from 1.35 +/- 0.16 to 1.57 +/- 0.15 cm (P < 0.005) after surgically induced overload. Left ventricular end systolic diameter and fractional shortening did not change significantly. Myocardial noradrenaline (NA) concentration and beta-adrenoceptor density were significantly lower in group 1 than in group 2, 1005 +/- 393 vs. 1643 +/- 109 ng/g (P < 0.02) and 167 +/- 36 vs. 224 +/- 36 fmol/mg protein (P < 0.03), respectively. Myocardial [123I]-MIBG uptake did not significantly differ between group 1 and 2, 2.1 +/- 0.58 vs. 1.8 +/- 0.44 (%ID/g x kg). A significant positive correlation between myocardial NA concentration and beta-adrenoceptor density was found (r = 0.66, P < 0.02). Myocardial NA concentration was inversely related to left ventricular weight (r =-0.75, P < 0.003).The present data indicate that in a condition of cardiac volume and pressure overload, sympathetic activity is enhanced as shown by myocardial noradrenaline depletion and beta-adrenoceptor downregulation. In contrast, no cardiac neuronal dysfunction is observed, even in the stage of early heart failure.
Patterns of Psychopathology and Dysfunction in High-Risk Children of Parents With Panic Disorder and Major Depression
Authors: Joseph Biederman, Stephen V. Faraone, Dina R. Hirshfeld-Becker, Deborah Friedman, Joanna A. Robin, Jerrold F. Rosenbaum
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The purpose of the study was to evaluate 1) whether an underlying familial predisposition is shared by all anxiety disorders or whether specific risks are associated with specific disorders, and 2) whether panic disorder and major depression have a familial link. METHOD: The study compared four groups of children: 1) offspring of parents with panic disorder and comorbid major depression (N=179), 2) offspring of parents with panic disorder without comorbid major depression (N=29), 3) offspring of parents with major depression without comorbid panic disorder (N=59), and 4) offspring of parents with neither panic disorder nor major depression (N=113). RESULTS: Parental panic disorder, regardless of comorbidity with major depression, was associated with an increased risk for panic disorder and agoraphobia in offspring. Parental major depression, regardless of comorbidity with panic disorder, was associated with increased risks for social phobia, major depression, disruptive behavior disorders, and poorer social functioning in offspring. Both parental panic disorder and parental major depression, individually or comorbidly, were associated with increased risk for separation anxiety disorder and multiple (two or more) anxiety disorders in offspring. CONCLUSIONS: These findings confirm and extend previous results documenting significant associations between the presence of panic disorder and major depression in parents and patterns of psychopathology and dysfunction in their offspring.
In vivo measurement of myocardial protein turnover using an indicator dilution technique.
Authors: J H Revkin, L H Young, W S Stirewalt, D M Dahl, R A Gelfand, B L Zaret, E J Barrett
Journal: Circulation Research (1990)

We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-[ring-2,6-3H]phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of [3H]phenylalanine was compared with L-[1-14C]leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl-tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation. This was addressed by improving the precision of both the measurements of phenylalanine concentration and phenylalanine specific activity using high-performance liquid chromatography. We conclude that the in vivo measurement of phenylalanine tracer exchange across the myocardium permits the nondestructive estimation of heart protein turnover in the intact animal.
Differentiation of Homicidal Child Molesters, Nonhomicidal Child Molesters, and Nonoffenders by Phallometry
Authors: Philip Firestone, John M. Bradford, David M. Greenberg, Kevin L. Nunes
Journal: American Journal of Psychiatry (2000)

The purpose of this study was to examine the ability of phallometry to discriminate among homicidal child molesters, nonhomicidal child molesters, and a comparison group of nonoffenders.Twenty-seven child molesters who had committed or had attempted a sexually motivated homicide, 189 nonhomicidal child molesters, and 47 nonoffenders were compared on demographic variables and psychometrically determined responses to aural descriptions of sexual vignettes. Two phallometric indexes were used: the pedophile index and the pedophile assault index. The pedophile index was computed by dividing the subject's highest response to an aural description of sex with a "consenting" child by his highest response to description of sex with a consenting adult. The pedophile assault index was computed by dividing the subject's highest response to an aural description of assault involving a child victim by his highest response to description of sex with a "consenting" child.Homicidal child molesters, nonhomicidal child molesters, and nonoffenders were not significantly different in age or IQ. Homicidal and nonhomicidal child molesters had significantly higher pedophile index scores than nonoffenders. Significantly more homicidal child molesters (14 [52%] of 27) and nonhomicidal child molesters (82 [46%] of 180) than nonoffenders (13 [28%] of 47) had pedophile index scores equal to or greater than 1.0, but homicidal and nonhomicidal child molesters did not differ from each other. Significantly more homicidal child molesters (17 [63%] of 27) than either nonhomicidal child molesters (71 [40%] of 178) or nonoffenders (17 [36%] of 47) had pedophile assault index scores equal to or greater than 1.0, and nonhomicidal child molesters and nonoffenders were not significantly different from each other. Within-group analyses revealed that of the three groups, only the nonhomicidal child molesters exhibited a significant difference between their pedophile index scores and their pedophile assault index scores; their pedophile index scores were higher.Consistent with past research, the authors found that the pedophile index is useful in differentiating homicidal and nonhomicidal child molesters from nonoffenders and that the pedophile assault index is able to differentiate homicidal child molesters from nonhomicidal child molesters and nonoffenders.
STUDIES ON THE CHEMOTHERAPY OF THE HUMAN MALARIAS. VIII. THE PHYSIOLOGICAL DISPOSITION OF PAMAQUINE 123
Authors: Charles G. Zubrod, Thomas J. Kennedy, James A. Shannon
Journal: Journal of Clinical Investigation (1948)

The recent appreciation (1,2) of the earlier studies on the curative activity of pamaquine in mosquito-transmitted vivax malaria (3) has pro- moted renewed interest in the chemotherapeutic potentialities of this compound and of several related derivatives of 8-aminoquinoline.Con- sequently, a report on the physiological disposition of pamaquine seemed desirable. METHODS AND MATERIALThe individuals used in these studies were, for the most part, patients with central nervous system syphilis.Cer- tain of the pharmacological studies were carried out in normal volunteers.Pamaquine disposition was usually studied prior to induction of therapeutic malaria or after convalescence had become well established.Some of the data on the relationship of dosage5 to plasma drug level, however, were obtained during the course of treatment for acute vivax or falciparum malaria.The chemical meth- ods used have been described elsewhere (4). RESULTS I. Physiological dispositionA. Absorption.The absorption of pamaquine from the gastro-intestinal tract cannot be -exam- ined by balance experiments since the compound 1 The work described in this paper was done under
Correspondence on the paper by Krauss–Etschmann S, Bush A, Bellusci S,<i>et al</i>.
Authors: J Bousquet, J M Anto, J Heinrich, T Keil, D S Postma, J Sunyer
Journal: Thorax (2013)

We have read with interest the paper of This is an important contribution to the current understanding of prenatal and early life events impacting chronic respiratory disease development and progression across the life cycle.A major challenge is to combine expertise in human conditions with complementary model systems. Btter understanding of these links should allow novel prevention strategies to promote healthy ageing.In its important final message, the authors propose a roadmap for integrative research.Since 2004, several initiatives funded under the EU Framework Programme for Research and Technological Development FP6-FP7 have attempted to identify, compare and evaluate pooling data from existing European birth cohorts with a major focus on respiratory and allergic diseases and their risk factors (GA²LEN: Global Allergy and European Network, FP6; ENRIECO: Environmental Health Risks in European Birth Cohorts, FP7; CHICOS: Developing a Child Cohort Research Strategy for Europe, FP7; and MeDALL: Mechanisms of the Development of ALLergy, FP7). 2 MeDALL emphasised the importance of multidisciplinary dialogue and integrative research to link molecular mechanisms with the populationbased distribution of allergic diseases from birth to adolescence. 2Developmental origins of ageing are in the EU research and political agenda.The Polish Priority of the EU Council (2011) promoted the recognition, prevention and management of chronic respiratory diseases in children to impact healthy ageing. 3The Cyprus Presidency of the EU Council (2012) identified research needs on birth cohorts to understand early determinants of chronic diseases. 4The previous initiatives are important in identifying research needs and strategies to be addressed in Horizon 2020 in Europe.Action Plan B3 (integrated care for chronic diseases) of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) includes health promotion and management with a life cycle perspective.To find novel health promotion strategies in chronic diseases, the results of FP6 and FP7 projects on prenatal and early life events, as well as epigenetics, will be
Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma
Authors: Jie Hong, Jose Behar, Jack Wands, Murray Resnick, Li Juan Wang, Ronald A DeLellis, David Lambeth, Rhonda F Souza, Stuart J Spechler, Weibiao Cao
Journal: Gut (2009)

Background and aims Mechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation. Methods Human Barrett's cell line BAR-T and OA cell line FLO were transfected by the Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H 2 O 2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation. Results NOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H 2 O 2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett's mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H 2 O 2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H 2 O 2 production and thymidine incorporation in FLO cells. Conclusions TDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. These data may provide potential targets to prevent and/or treat Barrett's OA.