tbuckley/cabot-search huggingface dataset:
Autocrine Secretion of Interferon γ Negatively Regulates Homing of Immature B Cells
Authors: Liat Flaishon, Rami Hershkoviz, Frida Lantner, Ofer Lider, Ronen Alon, Yoram Levo, Richard A. Flavell, Idit Shachar
Journal: The Journal of Experimental Medicine (2000)

The mechanism by which immature B cells are sequestered from encountering foreign antigens present in lymph nodes or sites of inflammation, before their final maturation in the spleen, has not been elucidated. We show here that immature B cells fail to home to the lymph nodes. These cells can actively exclude themselves from antigen-enriched sites by downregulating their integrin-mediated adhesion to the extracellular matrix protein, fibronectin. This inhibition is mediated by interferon γ secretion. Perturbation of interferon γ activity in vivo leads to the homing of immature B cells to the lymph nodes. This is the first example of autocrine regulation of immune cell migration to sites of foreign antigen presentation.
Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath
Authors: Roberto F. Machado, Daniel Laskowski, Olivia Deffenderfer, Timothy Burch, Shuo Zheng, Peter J. Mazzone, Tarek Mekhail, Constance Jennings, James K. Stoller, Jacqueline Pyle, Jennifer Duncan, Raed A. Dweik, Serpil C. Erzurum
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. Objectives: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. Methods: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. Main Results: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. Conclusion: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.
Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo
Authors: K. Ezzedine, A. Diallo, C. Léauté-Labrèze, J. Séneschal, S. Prey, F. Ballanger, K. Alghamdi, M. Cario-André, T. Jouary, Y. Gauthier, A. Taieb
Journal: British Journal of Dermatology (2011)

Background Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. Objectives The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. Patients and methods This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Results One hundred and twenty-seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients' disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment > 1% [odds ratio (OR) 15·14, P = 0·002], the presence of halo naevi (OR 24·82, P = 0·0001) and leukotrichia (OR 25·73, P = 0·0009). Conclusions Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.
Cytotoxic-lnduced Ovarian Failure in Hodgkin's Disease
Authors: Ramona M. Chapman
Journal: JAMA (1979)

Chemotheraphy for Hodgkin's disease produces ovarian failure in young women. The consequences of this are emotional distress, sexual dysfunction, and the disruption of families and friendships. These previously unappreciated side effects of cytotoxic therapy had developed in 25 of 41 patients, among whom we conducted a retrospective study.
A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood
Authors: Océane Albert, Bernard Jégou
Journal: Human Reproduction Update (2013)

BACKGROUNDA very large proportion of the literature on the endocrine disruptors categorized as anti-androgens deals with phthalates, which are produced in large amounts for use as plastic emollients and additives. In this review, we bring together and analyse work on the effects of phthalates in animals and humans at different stages of their development to assess whether or not their possible anti-androgenic properties represent a significant threat to human health.
The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough
Authors: C Advenier, V Lagente, E Boichot
Journal: European Respiratory Journal (1997)

Several recent observations suggest that tachykinins, such as substance P and neurokinin A, might be involved in the pathogenesis of bronchopulmonary alterations. Progress in investigations on the physiological and pathological roles of tachykinins has been greatly facilitated by the availability of a number of highly selective nonpeptide antagonists for tachykinin neurokinin 1, 2 and 3 (NK1, NK2 and NK3) receptors. The use of selective tachykinin NK2 receptor antagonists suggests that tachykinin NK2 receptor stimulation plays an important role in the development of airway hyperresponsiveness in the guinea-pig. Others studies have also indicated that tachykinin NK1-receptors are involved in immediate or delayed neurogenic inflammation including microvascular leakage and the subsequent increase in plasma protein extravasation. A role for the sensory neuropeptide system has also been proposed in cough, as shown by the observation that the antitussive effect of tachykinin NK2 receptor antagonists has clearly been demonstrated in several experimental conditions, but the effect of tachykinin NK1 receptor antagonists is still debated. Taken together, the results obtained with the various selective receptor antagonists provide pharmacological evidence that tachykinins play a role in delayed bronchopulmonary alterations and suggest that tachykinin receptor antagonists may be useful for investigating mechanisms and possibly reducing airway functional alterations in asthmatic patients.
Early Clinical Observations in Prospectively Followed Patients With Fungal Meningitis Related to Contaminated Epidural Steroid Injections
Authors: Thomas M. Kerkering, Marissa L. Grifasi, Anthony W. Baffoe-Bonnie, Ekta Bansal, Dorothy C. Garner, Jean A. Smith, Deborah D. Demicco, Charles J. Schleupner, Rabia A. Aldoghaither, Vipul A. Savaliya
Journal: Annals of Internal Medicine (2013)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Chinese translation Background: Administration of epidural steroid injections (ESIs) with contaminated methylprednisolone resulted in an outbreak of fungal meningitis in many locations in the United States. Objective: To characterize early clinical findings and initial response to treatment. Design: Case series with standardized observation studied from 4 October to 31 October 2012. Setting: An 800-bed hospital in Virginia. Patients: 172 patients who presented to the hospital with exposure to contaminated ESI. Intervention: Standardized approach to screening, case definition, treatment, and data collection. Measurements: Clinical findings, cerebrospinal fluid (CSF) values, magnetic resonance imaging (MRI), serum and CSF voriconazole concentrations, and clinician assessment of response to therapy. Results: Of 172 patients presenting to the hospital who had had ESI, 131 had lumbar puncture because of symptoms or signs consistent with central nervous system disease. Twenty-five (19%) had neutrophilic meningitis. All were started on voriconazole therapy alone. Three patients developed stroke during treatment. Ten patients had arachnoiditis, another had an epidural abscess, and 9 had urine retention. Fifteen continued to receive voriconazole, and 10 were switched to amphotericin B. Cerebrospinal fluid leukocyte counts began to decrease by day 13 of treatment. Findings on MRI included ventriculitis, leptomeningeal enhancement, infarction, hemorrhage, and arachnoiditis. Serum voriconazole levels varied, and CSF concentrations of voriconazole were approximately 50% those of serum. Exserohilum rostratum and Cladosporium species have been cultured. Limitations: This is an observational study of an evolving outbreak. Not all exposed patients presented for evaluation. Follow-up is too short to determine final outcomes. Conclusion: Meningitis after receipt of contaminated ESI has been diagnosed in many exposed patients presenting to 1 hospital. Most patients have improved on receipt of empirical voriconazole therapy. The full natural history and long-term sequelae of this infection are currently unknown. Primary Funding Source: None.
Pulmonary infection in Wegener granulomatosis and idiopathic pulmonary fibrosis
Authors: A G Richter, R A Stockley, L Harper, D R Thickett
Journal: Thorax (2009)

Wegener granulomatosis (WG) has previously been associated with increased nasal carriage of Staphylococcus aureus, but no studies have investigated the occurrence of pathogen growth in the lower airways.To culture bronchoalveolar lavage fluid (BALF) from patients with WG, patients with idiopathic pulmonary fibrosis (IPF) and normal controls.33 patients with WG, 22 with IPF and 8 normal controls underwent bronchoscopy and bronchoalveolar lavage. Quantitative culture established bacterial levels in the lower airways. Culture experiments were designed to investigate whether BALF is a supportive environment for S aureus growth. BALF cytokines were measured by ELISA.Pathogens were commonly grown from BALF of patients with WG and those with IPF. S aureus was particularly associated with patients with WG both in relapse and in remission. BALF levels of interleukin 1 receptor antagonist (IL1ra) were statistically significantly elevated in those patients who grew a pathogen from lavage fluid. BALF from patients with WG and IPF stimulated S aureus growth compared with normal lavage fluid.Pathogens are more commonly isolated from BALF from patients with WG than from that of patients with IPF or normal controls, and with a different culture profile. IL1ra was associated with pathogen growth in WG and IPF. WG BALF is a trophic environment for S aureus growth. Pulmonologists treating patients with acute or relapsing WG should consider bronchoscopic microbiological sampling and consider antibiotics with antistaphylococcal activity.
TIMI Risk Score for ST-Elevation Myocardial Infarction: A Convenient, Bedside, Clinical Score for Risk Assessment at Presentation
Authors: David A. Morrow, Elliott M. Antman, Andrew Charlesworth, Richard Cairns, Sabina A. Murphy, James A. de Lemos, Robert P. Giugliano, Carolyn H. McCabe, Eugene Braunwald
Journal: Circulation (2000)

Background —Considerable variability in mortality risk exists among patients with ST-elevation myocardial infarction (STEMI). Complex multivariable models identify independent predictors and quantify their relative contribution to mortality risk but are too cumbersome to be readily applied in clinical practice. Methods and Results —We developed and evaluated a convenient bedside clinical risk score for predicting 30-day mortality at presentation of fibrinolytic-eligible patients with STEMI. The Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI was created as the simple arithmetic sum of independent predictors of mortality weighted according to the adjusted odds ratios from logistic regression analysis in the Intravenous nPA for Treatment of Infarcting Myocardium Early II trial (n=14 114). Mean 30-day mortality was 6.7%. Ten baseline variables, accounting for 97% of the predictive capacity of the multivariate model, constituted the TIMI risk score. The risk score showed a &gt;40-fold graded increase in mortality, with scores ranging from 0 to &gt;8 ( P &lt;0.0001); mortality was &lt;1% among patients with a score of 0. The prognostic discriminatory capacity of the TIMI risk score was comparable to the full multivariable model (c statistic 0.779 versus 0.784). The prognostic performance of the risk score was stable over multiple time points (1 to 365 days). External validation in the TIMI 9 trial showed similar prognostic capacity (c statistic 0.746). Conclusions —The TIMI risk score for STEMI captures the majority of prognostic information offered by a full logistic regression model but is more readily used at the bedside. This risk assessment tool is likely to be clinically useful in the triage and management of fibrinolytic-eligible patients with STEMI.
Endothelial PGC-1α Mediates Vascular Dysfunction in Diabetes
Authors: Naoki Sawada, Aihua Jiang, Fumihiko Takizawa, Adeel Safdar, Andre Manika, Yevgenia Tesmenitsky, Kyu-Tae Kang, Joyce Bischoff, Hermann Kalwa, Juliano L. Sartoretto, Yasutomi Kamei, Laura E. Benjamin, Hirotaka Watada, Yoshihiro Ogawa, Yasutomi Higashikuni, Chase W. Kessinger, Farouc A. Jaffer, Thomas Michel, Masataka Sata, Kevin Croce, Rica Tanaka, Zolt Arany
Journal: Cell Metabolism (2014)
Lower education and living in countries with lower wealth are associated with higher disease activity in rheumatoid arthritis: results from the multinational COMORA study
Authors: Polina Putrik, Sofia Ramiro, Andras P Keszei, Ihsane Hmamouchi, Maxime Dougados, Till Uhlig, Tore K Kvien, Annelies Boonen
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To investigate the relationship of socioeconomic status (SES) on an individual and country level with disease activity in rheumatoid arthritis (RA) and explore the mediating role of uptake of costly biological disease-modifying antirheumatic drugs (bDMARDs) in this relationship. Methods Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of individual socioeconomic factors and country of residence to disease activity score with 28-joint assessment (DAS28) was explored in regression models, adjusting for relevant clinical confounders. Next, country of residence was replaced by gross domestic product (GDP) (low vs high) to investigate the contribution of SES by comparing R 2 (model fit). The mediating role of uptake of bDMARDs in the relationship between education or GDP and DAS28 was explored by testing indirect effects. Results In total, 3920 patients with RA were included (mean age 56 (SD 13) years, 82% women, mean DAS28 3.7 (1.6)). After adjustment, women (vs men) and low-educated (vs university) patients had 0.35 higher DAS28. Adjusted country differences in DAS28, compared with the Netherlands (lowest DAS28), varied from +0.2 (France) to +2.4 (Egypt). Patients from low GDP countries had 0.98 higher DAS28. No interactions between individual-level and country-level variables were observed. A small mediation effect of uptake of bDMARDs in the relationship between education and DAS28 (7.7%) and between GDP and DAS28 (6.7%) was observed. Conclusions Female gender and lower individual or country SES were independently associated with DAS28, but did not reinforce each other. The association between lower individual SES (education) or lower country welfare (GDP) with higher DAS28 was partially mediated by uptake of bDMARDs.
Positive pre-resection pleural lavage cytology is associated with increased risk of lung cancer recurrence in patients undergoing surgical resection: a meta-analysis of 4450 patients
Authors: Srdjan Saso, Christopher Rao, Hutan Ashrafian, Sadaf Ghaem-Maghami, Ara Darzi, Thanos Athanasiou
Journal: Thorax (2012)

<h3>Introduction</h3> The value of pleural lavage cytology (PLC) in assessing the prognosis of early stage lung cancer is still controversial. No systematic review has investigated the relationship between PLC and lung cancer recurrence. Our primary goal was to investigate the association between positive pre-resection PLC and pleural, distant and overall tumour recurrence in patients undergoing surgical resection. <h3>Methods</h3> Medline, EMBASE and Google Scholar databases were searched up to 2011. All studies reporting relevant outcomes in both patient groups were included. Data were extracted for the following outcomes of interest: overall, local and distant recurrence; and freedom from death (survival—overall and patients with stage I disease only). Random effects meta-analysis was used to aggregate the data. Sensitivity and heterogeneity analysis were performed. <h3>Results</h3> A meta-analysis of eight studies at maximum follow-up demonstrated a significant association between positive pre-resection PLC and increased risk of post-resection overall recurrence (OR 4.82, 95% CI 2.45 to 9.51), pleural recurrence (OR 9.89, 95% CI 5.95 to 16.44) and distant cancer recurrence (OR 3.18, 95% CI 1.57 to 6.46). Furthermore, a meta-analysis of 17 studies suggested that positive pre-resection PLC was also associated with unfavourable survival (HR 2.08, 95% CI 1.71 to 2.52). These findings were supported by sensitivity analysis. <h3>Discussion</h3> Positive pre-resection PLC is associated with higher overall, distant and local tumour recurrence and unfavourable patient survival outcomes. This technique may therefore act as a predictor of tumour recurrence and adverse survival. Furthermore, its role in including adjuvant chemotherapy to the management protocol should be investigated within randomised controlled trials.
Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities
Authors: Char-Chang Shieh, Michael Coghlan, James P. Sullivan, Murali Gopalakrishnan
Journal: Pharmacological Reviews (2000)

Potassium channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Over 50 human genes encoding various K(+) channels have been cloned during the past decade, and precise biophysical properties, subunit stoichiometry, channel assembly, and modulation by second messenger and ligands have been elucidated to a large extent. Recent advances in genetic linkage analysis have greatly facilitated the identification of many disease-producing loci, and naturally occurring mutations in various K(+) channels have been identified in diseases such as long-QT syndromes, episodic ataxia/myokymia, familial convulsions, hearing and vestibular diseases, Bartter's syndrome, and familial persistent hyperinsulinemic hypoglycemia of infancy. In addition, changes in K(+) channel function have been associated with cardiac hypertrophy and failure, apoptosis and oncogenesis, and various neurodegenerative and neuromuscular disorders. This review aims to 1) provide an understanding of K(+) channel function at the molecular level in the context of disease processes and 2) discuss the progress, hurdles, challenges, and opportunities in the exploitation of K(+) channels as therapeutic targets by pharmacological and emerging genetic approaches.
Carcinosarcoma of the oesophagus
Authors: I. Lichter, E. R. Smith, J. F. Gwynne
Journal: Thorax (1968)

The clinical and pathological details relating to a case of carcinosarcoma of the oesophagus are presented. Evidence for the true mixed nature of the lesion is demonstrated and criteria for distinguishing this from pleomorphic carcinoma are put forward. The literature relating to this rare lesion is reviewed and the problems of identifying its true pathological nature are discussed.
Multiple drug hypersensitivity: normal Treg cell function but enhanced <i>in vivo</i> activation of drug‐specific T cells
Authors: B. Daubner, M. Groux‐Keller, O. V. Hausmann, T. Kawabata, D. J. Naisbitt, B. K. Park, T. Wendland, M. Lerch, W. J. Pichler
Journal: Allergy (2011)

To cite this article: Daubner B, Groux‐Keller M, Hausmann OV, Kawabata T, Naisbitt DJ, Park BK, Wendland T, Lerch M, Pichler WJ. Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug‐specific T cells. Allergy 2012; 67 : 58–66. Abstract Background: Up to 10% of patients with severe immune‐mediated drug hypersensitivity reactions have tendencies to develop multiple drug hypersensitivities (MDH). The reason why certain individuals develop MDH and the underlying pathomechanism are unclear. We investigated different T cell subpopulations in MDH patients and compared them with patients allergic to a single drug and with healthy controls (HC). Methods: We analyzed the in vitro reactivity of peripheral blood mononuclear cells from MDH patients ( n = 7), patients with hypersensitivity to a single drug (monoallergic, n = 6), and healthy controls (HD) ( n = 6) to various drugs (mainly antibiotics and antiepileptics). By depleting and selectively re‐adding CD4 + CD25 bright T cells (T regulatory cells, Treg), their effect on drug‐specific T cell reactivity was analyzed. The phenotype of reacting T cells was determined ex vivo by staining for markers of activation (CD38) and cell exhaustion (PD‐1). Results: No functional deficiency of Treg cells was observed in all drug‐allergic patients. Drug‐reactive T cells from MDH patients were found in the CD4 + CD25 dim T cell fraction and showed enhanced CD38 and PD‐1 expression, while those from monoallergic patients reside in the resting CD4 + CD25 neg T cell fraction. Conclusion: In patients with MDH, the drug‐reactive T cells are contained in an in vivo pre‐activated T cell fraction. Therefore, they may show a lower threshold for activation by drugs. The reason for this in vivo T cell pre‐activation needs further investigations.