tbuckley/cabot-search huggingface dataset:
International Union of Pharmacology. XX. Current Status of the Nomenclature for Nicotinic Acetylcholine Receptors and Their Subunits
Authors: Ronald J. Lukas, Jean-Pierre Changeux, Nicolas le Novère, Edson X. Albuquerque, David J.K. Balfour, Darwin K. Berg, Daniel Bertrand, Vincent A. Chiappinelli, Paul B.S. Clarke, Allan C. Collins, John A. Dani, Sharon R. Grady, Kenneth J. Kellar, Jon M. Lindstrom, Michael J. Marks, Maryka Quik, Palmer W. Taylor, Susan Wonnacott
Journal: Pharmacological Reviews (1999)

Nicotinic acetylcholine receptors (nACh receptors2) in jawed vertebrates are prototypical members of the multisubunit, neurotransmitter-gated superfamily of ion channels (ionotropic neurotransmitter receptors; see Section IV for selected seminal papers, reviews, and collections). nACh receptors
Phenotypic characterisation of patients with intermediate sweat chloride values: towards validation of the European diagnostic algorithm for cystic fibrosis
Authors: C Goubau, M Wilschanski, V Skalicka, P Lebecque, K W Southern, I Sermet, A Munck, N Derichs, P G Middleton, L Hjelte, R Padoan, M Vasar, K De Boeck
Journal: Thorax (2009)

Background: In patients with symptoms suggestive of cystic fibrosis (CF) and intermediate sweat chloride values (30–60 mmol/l), extensive CFTR gene mutation analysis and nasal potential difference (NPD) measurement are used as additional diagnostic tests and a positive result in either test provides evidence of CFTR dysfunction. To define the phenotype of such patients and confirm the validity of grouping them, patients with intermediate sweat chloride values in whom either additional CF diagnostic test was abnormal were compared with subjects in whom this was not the case and patients with classic CF. Methods: The phenotypic features of four groups were compared: 59 patients with CFTR dysfunction, 46 with an intermediate sweat chloride concentration but no evidence of CFTR dysfunction (CF unlikely), 103 patients with CF and pancreatic sufficiency (CF-PS) and 62 with CF and pancreatic insufficiency (CF-PI). Results: The CFTR dysfunction group had more lower respiratory tract infections (p = 0.01), more isolation of CF pathogens (p<0.001) and clubbing (p = 0.001) than the CF unlikely group, but less frequent respiratory tract infections with CF pathogens than the CF-PS group (p = 0.05). Patients in the CF-PS group had a milder phenotype than those with PI. Many features showed stepwise changes through the patient groups. Conclusion: Patients with intermediate sweat chloride values and two CFTR mutations or an abnormal NPD measurement have a CF-like phenotype compatible with CFTR dysfunction and, as a group, differ phenotypically from patients with intermediate sweat chloride values in whom further CF diagnostic tests are normal as well as from CF-PS and CF-PI patients.
Hypoadiponectinemia and Proinflammatory State: Two Sides of the Same Coin?
Authors: Christian Herder, Hans Hauner, Burkhard Haastert, Karin Röhrig, Wolfgang Koenig, Hubert Kolb, Sylvia Müller-Scholze, Barbara Thorand, Rolf Holle, Wolfgang Rathmann
Journal: Diabetes Care (2006)

OBJECTIVE—Previous studies have yielded conflicting results on the association of adiponectin levels and inflammation. Low systemic concentrations of adiponectin, as well as elevated levels of immune mediators, represent risk factors for the development of type 2 diabetes and coronary artery disease. The major aim of this cross-sectional study was to investigate the interdependence of hypoadiponectinemia and low-grade systemic inflammation. RESEARCH DESIGN AND METHODS—The study sample consisted of 606 participants aged 55–74 years (244 with normal glucose tolerance, 242 with impaired glucose tolerance, and 120 with newly diagnosed type 2 diabetes) of the population-based KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4; 1999–2001). Systemic concentrations of adiponectin and a wide range of anthropometric, metabolic, and inflammatory variables were available for analyses. The association of adiponectin with 15 immunological markers, including leukocyte count, acute-phase proteins, cytokines, cytokine receptors, and chemokines, was assessed using univariable and multivariable models. RESULTS—No evidence for a significant correlation between adiponectin and all immunological parameters except eotaxin could be found after multivariable adjustments, whereas multiple strong correlations with obesity and metabolic factors were present. CONCLUSIONS—From these data, we conclude that hypoadiponectinemia and a proinflammatory state are largely independent from each other.
Fibroblast heterogeneity in the cancer wound
Authors: Daniel Öhlund, Ela Elyada, David Tuveson
Journal: The Journal of Experimental Medicine (2014)

Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy.
Psoriatic arthritis: epidemiology, clinical features, course, and outcome
Authors: D D Gladman, C Antoni, P Mease, D O Clegg, P Nash
Journal: Annals of the Rheumatic Diseases (2005)

Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.
Molecular epidemiology of tuberculosis in London 1995-7 showing low rate of active transmission
Authors: H Maguire
Journal: Thorax (2002)

<b>Background:</b> Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of <i>Mycobacterium tuberculosis</i> has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of <i>M tuberculosis</i> in London and subpopulations of the community with high rates of recent transmission. <b>Methods:</b><i>M tuberculosis</i> isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS<i>6110</i> restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable. <b>Results:</b> RFLP patterns were obtained for 2042 isolates with more than four copies of IS<i>6110</i>; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0–19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering. <b>Conclusions:</b> Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.
Association between Adrenal Insufficiency and Ventilator Weaning
Authors: Chung-Jen Huang, Horng-Chyuan Lin
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Adrenal insufficiency is a common disorder in critically ill patients with mechanical ventilation and is usually associated with higher mortality and poor clinical outcome.To determine whether stress dose corticosteroid supplementation can improve ventilator weaning and clinical outcome in patients with adrenal insufficiency.A prospective, randomized, placebo controlled, double-blinded study was conducted in the intensive care unit of a tertiary teaching hospital. A total of 93 mechanically ventilated patients were enrolled in the ventilator weaning trial. Adrenal function was assessed in all patients. Patients with adrenal insufficiency were randomized to the treatment group (50 mg intravenous hydrocortisone every 6 h) and the placebo group.The successful ventilator weaning percentage was significantly higher in the adequate adrenal reserve group (88.4%) and in the stress dose hydrocortisone treatment group (91.4%) than in the placebo group (68.6%). The weaning period was shorter in the hydrocortisone treatment group than in the placebo group. No significant adverse effects were observed in the corticosteroid treatment group.For patients with respiratory failure, early identification of adrenal insufficiency and appropriate supplementation with stress dose hydrocortisone increase the success of ventilator weaning and shortens the weaning period.
Reversible inhibition of mitochondrial complex IV activity in PBMC following acute smoking
Authors: J-R. Alonso, F. Cardellach, J. Casademont, Ò. Miró
Journal: European Respiratory Journal (2004)

Smoking causes a decrease of mitochondrial complex IV activity in chronic smokers. However, it is not known if this toxic effect is due to the acute effect of cigarette smoke itself or is a secondary phenomenon related to other smoking factors. The study assessed mitochondrial respiratory chain function in peripheral blood mononuclear cells of 15 healthy nonsmoker individuals before smoking (t 0 ), immediately after smoking five cigarettes in 45 min (t 1 ) and 24 h later (t 2 ). Blood carboxyhaemoglobin (COHb) and carbon monoxide concentrations in exhaled air (COEA) were determined to ascertain smoke inhalation status. After acute smoking, COHb increased from 0.5±0.3% to 3.3±1.5%, and COEA from 2.9±2.5 to 26.1±9.9 ppm. Complex II and III enzyme activities did not change along the study. Complex IV activity showed a 23% inhibition at t 1 but returned to initial (t 0 ) levels at t 2 . A decay in oxygen consumption was observed after the correction for mitochondrial content. Lipid peroxidation of cell membranes remained unchanged. Short-time smoking causes an acute and reversible mitochondrial complex IV inhibition in human mononuclear cells. These results suggest that smoke itself is one of the causes for the decrease of complex IV activity observed in chronic smokers.
A continuous mental task decreases the physiological response to soccer-specific intermittent exercise
Authors: Matt Greig, David Marchant, Richard Lovell, Peter Clough, Lars McNaughton
Journal: British Journal of Sports Medicine (2007)

Epidemiological findings of higher injury incidence during the latter stages of soccer match-play have been attributed to fatigue.To examine the interaction of physical and cognitive responses during soccer-specific intermittent exercise.Ten semi-professional soccer players completed a 90-minute laboratory-based treadmill protocol replicating the activity profile of soccer match-play. Two separate trials were performed in randomised order, with and without the added stressor of a continuous grid-based vigilance task. The exercise task comprised six repetitions of a 15 minute activity profile, separated by a passive 15 minute half-time interval. The vigilance task required continual attention and sporadic target response within a letter grid. Physical response (RPE, heart rate, blood lactate, salivary cortisol) and cognitive performance (response time, response accuracy) were quantified at 15 minute intervals.Completing the exercise task with the vigilance task resulted in decreased physiological (heart rate, blood lactate) response. This may be attributed to externally directed attention, resulting in association with the cognitive task and subsequent dissociation from the physical effort. Response speed generally improved with exercise duration, while there was evidence of impaired accuracy in the early stages of the first half and the latter stages of the second half.The interaction of physical and mental work was not additive in nature. The mental task had a masking effect on the physical response. Performing physical exercise tasks without due regard for appropriate psychological stimuli may therefore overestimate the physiological response.
Endotoxin and liver diseases. High titres of enterobacterial common antigen antibodies in patients with alcoholic cirrhosis.
Authors: U Turunen, M Malkamaki, V V Valtonen, U Larinkari, P Pikkarainen, M P Salaspuro, P H Makela
Journal: Gut (1981)

We have measured antibodies to the enterobacterial common antigen (ECA) in sera of 86 patients with various liver diseases. ECA is a component of the cell wall of all enteric bacteria, and ECA antibodies are a specific indication of the presence of enterobacterial components. Patients with alcoholic cirrhosis with or without signs of alcoholic hepatitis had significantly raised anti-ECA titres compared with healthy control subjects. Other groups of patients (alcoholic hepatitis and/or fatty liver, primary biliary cirrhosis, chronic active hepatitis, or liver metastases) did not differ significantly from controls in the height of their anti-ECA titres. The results support the concept that Gram-negative bacterial components may have some role in the pathophysiology of alcoholic cirrhosis.
Influence of Blood Temperature on the Pulmonary Circulation
Authors: PIERRE M. GALLETTI, PETER F. SALISBURY, ANDRE RIEBEN
Journal: Circulation Research (1958)

Innervated, nourished and ventilated dog lungs were perfused in situ with a technic which afforded adequate control of blood flow, pressures, pH and temperature. Variations of the pulmonary (hut not of the systemic) blood temperature was followed by pronounced changes of the pulmonary vascular resistance, believed to be attributable to pulmonary vasomotion.
Intratumor Heterogeneity: Evolution through Space and Time
Authors: Charles Swanton
Journal: Cancer Research (2012)

Recent technologic advances have permitted higher resolution and more rapid analysis of individual cancer genomes at the single-nucleotide level. Such advances have shown bewildering intertumor heterogeneity with limited somatic alterations shared between tumors of the same histopathologic subtype. Exacerbating such complexity, increasing evidence of intratumor genetic heterogeneity (ITH) is emerging, both within individual tumor biopsies and spatially separated between biopsies of the same tumor. Sequential analysis of tumors has also revealed evidence that ITH temporally evolves during the disease course. ITH has implications for predictive or prognostic biomarker strategies, where the tumor subclone that may ultimately influence therapeutic outcome may evade detection because of its absence or presence at low frequency at diagnosis or because of its regional separation from the tumor biopsy site. In this review, the implications of "trunk and branch" tumor evolution for drug discovery approaches and emerging evidence that low-frequency somatic events may drive tumor growth through paracrine signaling fostering a tumor ecologic niche are discussed. The concept of an "actionable mutation" is considered within a model of clonal dominance and heterogeneous tumor cell dependencies. Evidence that cancer therapeutics may augment ITH and the need to track the tumor subclonal architecture through treatment are defined as key research areas. Finally, if combination therapeutic approaches to limit the consequences of ITH prove challenging, identification of drivers or suppressors of ITH may provide attractive therapeutic targets to limit tumor evolutionary rates and adaptation.
Hidden autoantibodies against common serum proteins in murine systemic lupus erythematosus. Detection by in vitro plaque-forming cell assay.
Authors: P L Cohen, R G Rapoport, R A Eisenberg
Journal: The Journal of Experimental Medicine (1985)

The autoantibodies found in human and murine systemic lupus erythematosus (SLE) are generally directed against cells or components of cells such as nuclear antigens. This predilection may be due to the unusual immunogenicity of certain autoantigens, or to unusual patterns of antibody crossreactivity. Alternatively, the observed spectrum of reactivities may reflect the in vivo absorption of those autoantibodies directed against soluble antigens. To test whether hitherto undetected autoantibodies against serum proteins might exist in murine SLE, we developed assays that were independent of the possibility of absorption of autoantibodies by serum autoantigens; large numbers of plaque-forming cells (PFC) directed against mouse albumin and mouse transferrin were easily detected in the spleens of MRL/Mp-lpr/lpr, BXSB, and NZB mice. The secreted antibodies were relatively specific for the mouse proteins, since only limited cross-reactivity was seen with albumin and transferrins of other species in inhibition experiments. The production of these hidden antibodies could not be the result of diffuse polyclonal B cell activation, since the PFC to mouse transferrins and albumin were not always accompanied by comparable numbers of PFC against related albumins and transferrins. The results indicate that autoantibody production in murine lupus is a generalized phenomenon, not limited to the production of autoantibodies to nuclear or other cell-bound antibodies. However, the relative specificity of the autoantibodies for self-antigens indicates that diffuse polyclonal B cell activation cannot be the mechanism responsible, and argues that a selective mechanism, probably driven by antigen, accounts for production of autoantibodies in SLE.
Thrice-weekly maintenance therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS)
Authors: Josep Mallolas, Josep M. Gatell, Juan Luis Gómez-Sirvent, Elisabeth Buira, Laura Zamora, Jerusa Alecrim-Andrade, Alfredo Adán, Marta Morales, Josep M. Miró, Montserrat Loncá, Ana Guelar, Eladio Soriano
Journal: Clinical Microbiology and Infection (1996)
Roles of Idiotype-Specific T Cells in Myeloma Cell Growth and Survival: Th1 and CTL Cells Are Tumoricidal while Th2 Cells Promote Tumor Growth
Authors: Sungyoul Hong, Jianfei Qian, Jing Yang, Haiyan Li, Larry W. Kwak, Qing Yi
Journal: Cancer Research (2008)

Abstract Idiotype (Id) protein, secreted by myeloma cells, is a tumor-specific antigen. Id-based immunotherapy has been explored in patients with myeloma, and results were disappointing. Although previous studies have shown that Id-specific CTLs are able to lyse myeloma cells, it is unclear whether other types of Id-specific T cells, such as type-1 T-helper (Th1) and type-2 T-helper (Th2) cells, are also able to suppress or kill myeloma cells. Using a 5T murine myeloma model, we generated T-cell clones of different subsets and examined their function in the context of myeloma cells. Id-specific CTLs specifically lysed myeloma cells via MHC class I, perforin, and Fas ligand (FasL), and Th1, but not Th2, cells lysed the myeloma cells by FasL–Fas interaction. CTL and Th1 cells also suppressed the growth and function of myeloma cells, whereas Th2 cells promoted the proliferation and enhanced the secretion of Id protein and cytokines by myeloma cells. CTL and Th1, but not Th2, cells were able to eradicate established myeloma in vivo after adoptive transfer. These results show that Id-specific CTL and Th1 are promising effector cells, whereas Th2 provide no protection and may even promote tumor progression in vivo. [Cancer Res 2008;68(20):8456–64]
α-Melanocyte–stimulating Hormone Inhibits Lung Injury after Renal Ischemia/Reperfusion
Authors: Jiangping Deng, Xuzhen Hu, Peter S. T. Yuen, Robert A. Star
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock or visceral or renal ischemia. Alpha-melanocyte-stimulating hormone (alpha-MSH) is an antiinflammatory cytokine, which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if alpha-MSH inhibits acute lung injury after renal ischemia and to determine the early mechanisms of alpha-MSH action. Mice were subjected to renal ischemia treated with vehicle or alpha-MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for intracellular adhesion molecule-1 and tumor necrosis factor-alpha. Renal ischemia rapidly activated kidney and lung nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury. Alpha-MSH administration immediately before reperfusion significantly decreased kidney and lung injury and prevented activation of kidney and lung transcription factors and stress response genes, and lung intracellular adhesion molecule-1 and tumor necrosis factor-alpha at early time points after renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after renal ischemia. alpha-MSH protects against both kidney and lung damage after renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury.
Neuroendocrine Evidence That Clozapine's Serotonergic Antagonism Is Relevant to Its Efficacy in Treating Hallucinations and Other Positive Schizophrenic Symptoms
Authors: Hugh Jones, Vivienne A. Curtis, Padraig Wright, James V. Lucey
Journal: American Journal of Psychiatry (1998)

The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia.Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment.The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms.Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.