tbuckley/cabot-search huggingface dataset:
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
Authors: Irving I. Gottesman, Todd D. Gould
Journal: American Journal of Psychiatry (2003)

Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
The Anterior Pituitary-Grafted Rat: A Valid Model of Chronic Hyperprolactinemia*
Authors: ROBERT A. ADLER
Journal: Endocrine Reviews (1986)

TRANSPLANTATION of the rat anterior pituitary gland to the kidney capsule results in a state of chronic hyperprolactinemia. For more than 35 yr two versions of this model have been used to study the functions of PRL. Autotransplantation of the pituitary to the kidney capsule induces hyperprolactinemia, but growth, GH secretion, and other anterior pituitary functions are diminished. Nonhypophysectomized rats implanted with anterior pituitary glands from littermate donors also have excess circulating PRL levels, but growth, GH secretion, and thyroid function remain normal. In the intact pituitary-grafted male rat, gonadal testosterone secretion is maintained despite diminished gonadotropin secretion. One shortcoming of the intact pituitary-grafted rat is glucocorticoid excess, the mechanism of which is unclear. However, adrenalectomy with adrenal steroid replacement of pituitary-grafted rats provides an animal model that appears to have one abnormality only, excess PRL secretion. This animal preparation compares favorably with other models used to study the many actions of PRL.
Clinical Aspects and Prognosis of Brugada Syndrome in Children
Authors: Vincent Probst, Isabelle Denjoy, Paola G. Meregalli, Jean-Christophe Amirault, Fréderic Sacher, Jacques Mansourati, Dominique Babuty, Elisabeth Villain, Jacques Victor, Jean-Jacques Schott, Jean-Marc Lupoglazoff, Philippe Mabo, Christian Veltmann, Laurence Jesel, Philippe Chevalier, Sally-Ann B. Clur, Michel Haissaguerre, Christian Wolpert, Hervé Le Marec, Arthur A.M. Wilde
Journal: Circulation (2007)

Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and augmented risk of sudden cardiac death. Little is known about the clinical presentation and prognosis of this disease in children.Thirty children affected by Brugada syndrome who were <16 years of age (mean, 8+/-4 years) were included. All patients displayed a type I ECG pattern before or after drug provocation challenge. Diagnosis of Brugada syndrome was made under the following circumstances: aborted sudden death (n=1), syncope of unexplained origin (n=10), symptomatic supraventricular tachycardia (n=1), suspicious ECG (n=1), and family screening for Brugada syndrome (n=17). Syncope was precipitated by fever in 5 cases. Ten of 11 symptomatic patients displayed a spontaneous type I ECG. An implantable cardioverter-defibrillator was implanted in 5 children; 4 children were treated with hydroquinidine; and 1 child received a pacemaker because of symptomatic sick sinus syndrome. During a mean follow-up of 37+/-23 months, 1 child experienced sudden cardiac death, and 2 children received an appropriate implantable cardioverter-defibrillator shock; all of them were symptomatic and had manifested a type I ECG spontaneously. One child had a cardioverter-defibrillator infection that required explantation of the defibrillator.In the largest population of children affected by Brugada syndrome described to date, fever represented the most important precipitating factor for arrhythmic events, and as in the adult population, the risk of arrhythmic events was higher in previously symptomatic patients and in those displaying a spontaneous type I ECG.
Some properties of antisera to serum amyloid A protein (SAA): inhibition of precipitation by complexing of SAA to albumin.
Authors: E C Franklin
Journal: The Journal of Experimental Medicine (1976)

Three potent rabbit antisera to human serum amyloid A protein (SAA) appear to be directed exclusibely to the carboxy terminal region not shared with the tissue amyloid A protein. Since binding to albumin completely blocks the reaction of these antisera with the antigen, and since SAA exists in serum complexed to albumin, the anti-SAA cannot be used to detect or quantitate this serum component. The possibility that similar problems will be encountered with immunoassays for molecules that exist complexed to other proteins is discussed.
Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis
Authors: Xavier Paoletti, Koji Oba, Yung-Jue Bang, Harry Bleiberg, Narikazu Boku, Olivier Bouché, Paul Catalano, Nozomu Fuse, Stefan Michiels, Markus Moehler, Satoshi Morita, Yasuo Ohashi, Atsushi Ohtsu, Arnaud Roth, Philippe Rougier, Junichi Sakamoto, Daniel Sargent, Mitsuru Sasako, Kohei Shitara, Peter Thuss-Patience, Eric Van Cutsem, Tomasz Burzykowski, Marc Buyse
Journal: JNCI Journal of the National Cancer Institute (2013)

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R (2) between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer.
Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors.
Authors: L Shou, S A Schwartz, R A Good
Journal: The Journal of Experimental Medicine (1976)

Pretreatment of normal human peripheral blood lymphocytes with the plant lectin, concanavalin A (Con A), results in inhibition of blast transformation and [3H]thymidine incorporation by untreated allogeneic lymphocytes from healthy volunteers donors in one-way mixed leukocyte culture. Similarly, responses to mitogens, certain microbial antigens, and allogeneic lymphocytes are inhibited by Con A-treated allogeneic cells. Con A pretreated autologous lymphocytes can also be induced to manifest suppressor activities. This antimitotic effect occurs without evidence of cytotoxicity and is active on de novo lymphocyte responses and does not require prior sensitization of the cells being tested. Suppression of the lymphocyte response to pokeweed mitogen, a potent B-cell stimulator, by Con A-pretreated suppressor cells was not as consistent as was inhibition of response to other mitogens, including phytohemagglutinin and Con A. Furthermore, suppression of lymphocyte transformation to the microbial antigens, tuberculin purified protein derivative, and Canadida albicans extracts could be similarly induced by Con A pretreatment of either allogeneic or autologous cells. Induction of autologous suppressor activity in lymphocytes from healthy donors is compatible with a model that includes a role for suppressor cells in the modulation of the normal immune response.
Correction of Postkidney Transplant Anemia Reduces Progression of Allograft Nephropathy
Authors: Gabriel Choukroun, Nassim Kamar, Bertrand Dussol, Isabelle Etienne, Elisabeth Cassuto-Viguier, Olivier Toupance, François Glowacki, Bruno Moulin, Yvon Lebranchu, Guy Touchard, Maïté Jaureguy, Nicolas Pallet, Yannick Le Meur, Lionel Rostaing, Frank Martinez
Journal: Journal of the American Society of Nephrology (2011)

Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0–15.0 g/dl, n=63) compared with partial correction of anemia (10.5–11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin <11.5 g/dl and an estimated creatinine clearance (eCrCl) <50 ml/min per 1.73 m2. After 2 years, the mean hemoglobin was 12.9 and 11.3 g/dl in the normalization and partial correction groups, respectively (P<0.001). From baseline to year 2, the eCrCl decreased by a mean 2.4 ml/min per 1.73 m2 in the normalization group compared with 5.9 ml/min per 1.73 m2 in the partial correction group (P=0.03). Furthermore, fewer patients in the normalization group progressed to ESRD (3 versus 13, P<0.01). Cumulative death-censored graft survival was 95% and 80% in the normalization and partial correction groups, respectively (P<0.01). Complete correction was associated with a significant improvement in quality of life at 6 and 12 months. The number of cardiovascular events was low and similar between groups. In conclusion, this prospective study suggests that targeting hemoglobin values ≥13 g/dl reduces progression of chronic allograft nephropathy in kidney transplant recipients.
Symptom Prevalence, Intensity, and Distress in Patients With Inoperable Lung Cancer in Relation to Time of Death
Authors: Carol Tishelman, Lena-Marie Petersson, Lesley F. Degner, Mirjam A.G. Sprangers
Journal: Journal of Clinical Oncology (2007)

Purpose To examine symptom prevalence, intensity, and association with distress in patients with inoperable lung cancer (LC), using time to death as point of reference. Patients and Methods A consecutive sample of 400 patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 plus a 13-item LC-specific scale and the Thurstone Scale of Symptom Distress–Lung Cancer at six time points during the first year after diagnosis. Patients were divided into subgroups, using data from the time point closest to death (&lt; 1; 1 to 2; &gt; 2 to 3; &gt; 3 to 6; &gt; 6 to 12; and &gt; 12 months before death) for analysis. Results More than 50% of patients in all subgroups reported problems related to physical, role, and emotional functioning; fatigue; dyspnea; and cough. In general, functional levels were lower and symptoms higher in subgroups closer to death. Notably, clinically relevant differences were also found in role and social functioning and appetite loss between the two groups furthest from death. A consistent pattern was found among the six subgroups, with breathing, pain, and fatigue rated as the symptoms most associated with distress. Conclusion High prevalence of symptoms was found in all subgroups, with higher intensity in subgroups closer to death, indicating a need for prophylactic and proactive symptom management. Less concordance was found among symptom prevalence, intensity, and association with distress in subgroups further from death. Future studies should investigate longitudinal associations between symptoms with low intensity and high distress, and examine their clinical implications.
Hospital admissions, age, and death: retrospective cohort study
Authors: Tracy Dixon, Mary Shaw, Stephen Frankel, Shah Ebrahim
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> Ageing of the population brings the possibility of increased burdens for acute hospital services because of the marked increase in many common diseases with age. We aimed to examine the relation between age and use of acute services in hospitals in the period before death in a national sample of deaths in hospital. <b>Design</b> Retrospective cohort analysis of English hospital episode statistics database. <b>Setting</b> All NHS hospitals in England. <b>Data set</b> All post-neonatal deaths occurring in English NHS hospitals during financial year 1999-2000, with episodes of care in the previous three years determined through matching on sex, date of birth, and postcode. <b>Main outcome measures</b> Total bed days, mean and median length of stay. <b>Results</b> 253 799 in-hospital deaths were identified, representing about 45% of all deaths occurring in 1999-2000. Patients who died in hospital spent a median of 23 days in hospital in the three years before death; the median rose with age up to 45 years, but was fairly stable for ages 45 and above. The number of admissions to NHS hospitals in the three years before death averaged 3.6; this peaked at 10.4 in patients aged 5-9 years and decreased with age to 2.2 in those aged 85 and over. <b>Conclusions</b> The average number of bed days spent in hospital in the period before death does not increase with increasing age.
Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.
Authors: S J Klebanoff, H Rosen
Journal: The Journal of Experimental Medicine (1978)

Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system.
Widening the field: The process of language acquisition
Authors: Edith L. Bavin
Journal: Behavioral and Brain Sciences (2009)

Abstract Evans &amp; Levinson (E&amp;L) argue against Universal Grammar on the basis of language diversity. A related and fundamental issue is whether the language input provides sufficient information for a child to acquire it. I briefly discuss the more integrated approaches to language acquisition which focus on the mechanisms, and research showing that input cues provide valuable information for the language learner.
Mechanism of histamine actions in human coronary arteries.
Authors: N Toda
Journal: Circulation Research (1987)

Helical strips of human coronary arteries contracted in response to histamine concentration dependently, they relaxed with low concentrations and contracted with high concentrations. Treatment with cimetidine potentiated contraction in the strips with intact and damaged endothelium to a similar extent and attenuated relaxation. Removal of endothelium abolished relaxation and potentiated contraction in the cimetidine-treated strips. Methylene blue increased the contractile response to histamine in the strips with endothelium but did not alter the response in the damaged-endothelium strips. Histamine-induced relaxations in the intact strips were suppressed or abolished by treatment with ETYA, AA861, a lipoxygenase inhibitor, and by chlorpheniramine but were unaffected by indomethacin. Chlorpheniramine also abolished amine-induced contraction. It may be concluded that histamine-induced contraction in human coronary arteries is mediated by H1 receptors in smooth muscle, and relaxation is mediated by H2 receptors in smooth muscle and H1 receptors in endothelium. Also, stimulation of the endothelial H1 receptor liberates vasodilator substance and possibly activates smooth muscle guanylate cyclase to accumulate cellular cyclic guanosine monophosphate.
Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study
Authors: Joost Daemen, Peter Wenaweser, Keiichi Tsuchida, Linda Abrecht, Sophia Vaina, Cyrill Morger, Neville Kukreja, Peter Jüni, Georgios Sianos, Gerrit Hellige, Ron T van Domburg, Otto M Hess, Eric Boersma, Bernhard Meier, Stephan Windecker, Patrick W Serruys
Journal: The Lancet (2007)
A Neu View of Invasive Lobular Breast Cancer
Authors: Ron Bose
Journal: Clinical Cancer Research (2013)

Genome sequencing of relapsed, invasive lobular breast cancer identified actionable mutations in 86% of the cases. HER2 alterations occur in 27% of the cases, including 4 cases with activating HER2 mutations and 1 with a novel HER2-GRB7 gene fusion. This fusion links the HER2 tyrosine kinase domain to the GRB7 src homology 2 (SH2) domain.
Augmented cardiopulmonary baroreflex control of forearm vascular resistance in young athletes.
Authors: A Takeshita, S Jingu, T Imaizumi, Y Kunihiko, S Koyanagi, M Nakamura
Journal: Circulation Research (1986)

The aim of this study was to examine the effect of exercise training on reflex control of vascular resistance in human males. Forearm vascular responses to lower body negative pressure (LBNP) at -10 and -40 mm Hg were compared between highly trained young athletes (21.5 +/- 0.5 years old, n = 14) and age-matched nonathletes (20.7 +/- 0.5 years old, n = 16). Resting heart rate was lower in athletes than in nonathletes. Resting blood pressure, central venous pressure, forearm blood flow, and forearm vascular resistance were not different between the two groups. The magnitude of reflex forearm vasoconstriction in response to LBNP at -10 mm Hg, which decreased central venous pressure but did not alter blood pressure or heart rate, was greater in athletes than in nonathletes. The slope of the regression line relating changes in central venous pressure and forearm vascular resistance was steeper in athletes than in nonathletes. Vasoconstrictive responses to intraarterially administered norepinephrine and angiotensin II did not differ between athletes and nonathletes. These results suggest that the tonic inhibitory influence of the cardiopulmonary receptors is augmented in athletes. This augmentation may contribute to some of cardiovascular and endocrine adaptations that occur with exercise training.
Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model
Authors: I. Saga, S. Shibao, J. Okubo, S. Osuka, Y. Kobayashi, S. Yamada, S. Fujita, K. Urakami, M. Kusuhara, K. Yoshida, H. Saya, O. Sampetrean
Journal: Neuro-Oncology (2014)

The metabolic preference of malignant glioma for glycolysis as an energy source is a potential therapeutic target. As a result of the cellular heterogeneity of these tumors, however, the relation between glycolytic preference, tumor formation, and tumor cell clonogenicity has remained unknown. To address this issue, we analyzed the metabolic profiles of isogenic glioma-initiating cells (GICs) in a mouse model.GICs were established by overexpression of H-Ras(V12) in Ink4a/Arf-null neural stem cells. Subpopulations of these cells were obtained by single-cell cloning, and clones differing in extracellular acidification potential were assessed for metabolic characteristics. Tumors formed after intracranial implantation of these clones in mice were examined for pathological features of glioma and expression of glycolytic enzymes.Malignant transformation of neural stem cells resulted in a shift in metabolism characterized by an increase in lactic acid production. However, isogenic clonal populations of GICs manifested pronounced differences in glucose and oxygen consumption, lactate production, and nucleoside levels. These differences were paralleled by differential expression of glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2, with this differential expression also being evident in tumors formed by these clones in vivo.The metabolic characteristics of glioma cells appear early during malignant transformation and persist until the late stages of tumor formation. Even isogenic clones may be heterogeneous in terms of metabolic features, however, suggesting that a more detailed understanding of the metabolic profile of glioma is imperative for effective therapeutic targeting.
Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat
Authors: S. Flottorp
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>:To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat <b>Design</b>:Unblinded, cluster randomised pretest-post-test trial <b>Setting</b>:142 general practices in Norway <b>Participants</b>:72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection. <b>Interventions</b>:Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants <b>Main outcome measures</b>:Changes in rates of use of antibiotics, laboratory tests, and telephone consultations <b>Results</b>:Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practicesin the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures <b>Conclusions</b>:Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice