tbuckley/cabot-search huggingface dataset:
Psoriasis and the Risk of Depression in the US Population
Authors: Brandon E. Cohen, Kathryn J. Martires, Roger S. Ho
Journal: JAMA Dermatology (2015)

Psoriasis is a risk factor for depression. Depression may also trigger or exacerbate psoriasis. The relationship between psoriasis and depression, however, remains to be fully explored.To investigate the association between psoriasis and major depression in the US population.Population-based study using participants in the National Health and Nutrition Examination Survey from 2009 through 2012.Diagnosis of major depression based on the Patient Health Questionnaire-9.We identified 351 (2.8%) cases of psoriasis and 968 (7.8%) cases of major depression among 12,382 US citizens included in our study. Fifty-eight (16.5%) patients with psoriasis met criteria for a diagnosis of major depression. The mean (SD) Patient Health Questionnaire-9 score was significantly higher among patients with a history of psoriasis than those without psoriasis (4.54 [5.7] vs 3.22 [4.3], P < .001). Psoriasis was significantly associated with major depression, even after adjustment for sex, age, race, body mass index, physical activity, smoking history, alcohol use, history of myocardial infarction (MI), history of stroke, and history of diabetes mellitus (OR, 2.09 [95% CI, 1.41-3.11], P < .001). Interaction term analyses involving patients with a history of both psoriasis and a cardiovascular event, specifically MI or stroke, did not reveal a synergistically increased risk of major depression (psoriasis and MI: OR, 1.09 [95% CI, 0.28-3.60], P = .91; psoriasis and stroke: OR, 0.67 [95% CI, 0.12-3.66], P = .63). In adjusted multivariable models, the risk of major depression was not significantly different between patients with limited vs extensive psoriasis (OR, 0.66 [95% CI, 0.18-2.44], P = .53).Self-reported history of psoriasis was independently associated with major depression as assessed by a validated screening tool, even when controlling for comorbidities. History of cardiovascular event did not modify the risk of major depression for patients with psoriasis. The severity of psoriasis was unrelated to the risk of major depression. Therefore, all patients with psoriasis, regardless of severity, may be at risk for major depression.
Monoclonal Antibody Against Citrullinated Peptides Obtained From Rheumatoid Arthritis Patients Reacts With Numerous Citrullinated Microbial and Food Proteins
Authors: Reina Tsuda, Tatsuhiko Ozawa, Eiji Kobayashi, Hiroshi Hamana, Hirofumi Taki, Kazuyuki Tobe, Eiji Sugiyama, Masahiro Iwamoto, Johji Imura, Hiroyuki Kishi, Atsushi Muraguchi
Journal: Arthritis & Rheumatology (2015)

Objective To investigate the reactivity of monoclonal anti–citrullinated protein antibody (ACPA) obtained from peripheral blood B cells of rheumatoid arthritis (RA) patients with human autoantigens as well as environmental proteins by determining the essential epitope for the ACPA. Methods A human monoclonal ACPA (cyclic citrullinated peptide antibody 1 [CCP‐Ab1]) was obtained by screening peripheral blood lymphocytes from 31 patients with RA using a novel monoclonal antibody–secreting cell (ASC) screening system, the immunospot‐array assay on a chip. The essential epitope for CCP‐Ab1 was determined using epitope mapping. Then, human, microbial, and plant proteins that share the essential epitope identified were searched using BLAST. Finally, representative proteins identified by the search were produced in vitro, and their reactivity with CCP‐Ab1 was examined. Results CCP‐Ab1 bound CCP in a citrulline‐indispensable manner. In CCP, the 6 amino acid residues required for CCP‐Ab1 binding were identified. In the BLAST search, 38 human, 56 viral, 1,383 fungal, 547 bacterial, and 1,072 plant proteins were found to share the essential epitope, and CCP‐Ab1 reacted with all of the recombinant citrullinated proteins tested, which included the various environmental factors, such as various plant proteins that are part of the daily diet. Conclusion Our findings demonstrate, for the first time, that a monoclonal ACPA (CCP‐Ab1) derived from RA patients cross‐reacts not only with various autoantigens but also with numerous plant and microbial proteins. We propose that countless environmental factors, including microbes and diet, may trigger the generation of ACPAs that then cross‐react with various citrullinated human autoantigens through molecular mimicry to induce RA.
Successful treatment of acute fascioliasis with bithionol
Authors: Yannick Bacq, Jean-Marc Besnier, Thanh-Hai Duong, Guy Pavie, Etienne-Henri Metman, Patrick Choutet
Journal: Hepatology (1991)

Fascioliasis is the parasitic infestation of the liver and biliary tract related to Fasciola hepatica. Bithionol is proposed as the treatment of choice for human fascioliasis without major side effects. However, the efficacy of bithionol has been evaluated in chronic but not in acute fascioliasis. In this study we report on the success of treatment with bithionol in 10 patients with fascioliasis, 8 having acute fascioliasis. The criteria for the diagnosis of fascioliasis were hypereosinophilia, positive immunoelectrophoresis and indirect hemagglutination. Bithionol was given orally to hospitalized patients at the daily dose of 25 mg/kg body wt for 10 days. Three patients with acute fascioliasis received a second course of bithionol 2 or 3 mo after the first because of the recurrence of diarrhea and fatigue in one patient and persistent hypereosinophilia in two patients. All patients were cured. The follow-up period after the first course of treatment was between 16 and 47 mo. No major side effects were observed. We conclude that bithionol is the drug of choice for both acute and chronic fascioliasis. Moreover, its oral administration may allow treatment of fascioliasis in outpatients who do not have serious symptoms.
Efficacy of Low-Dose Interferon α2a 18 Versus 60 Months of Treatment in Patients With Primary Melanoma of ≥ 1.5 mm Tumor Thickness: Results of a Randomized Phase III DeCOG Trial
Authors: Axel Hauschild, Michael Weichenthal, Knuth Rass, Ruthild Linse, Carola Berking, Jörg Böttjer, Thomas Vogt, Konstanze Spieth, Thomas Eigentler, Norbert H. Brockmeyer, Annette Stein, Helmut Näher, Dirk Schadendorf, Peter Mohr, Martin Kaatz, Michael Tronnier, Rüdiger Hein, Gerold Schuler, Friederike Egberts, Claus Garbe
Journal: Journal of Clinical Oncology (2010)

PURPOSE Low-dose (LD) interferon (IFN) alfa (LDI) has demonstrated a consistent disease-free survival benefit for patients with clinically lymph node-negative melanoma in clinical trials. However, the optimal duration of treatment is still under discussion, and no previous trial has evaluated this question specifically. A prolongation of LDI from 18 months to 60 months might be of clinical benefit for patients with intermediate or high-risk melanoma. PATIENTS AND METHODS Eight hundred fifty patients with resected cutaneous melanoma of at least 1.5 mm tumor thickness were included in this prospective randomized, multicenter trial in Germany and Austria. Patients had to be clinically lymph node-negative, and sentinel node biopsy (SLNB) was performed in a majority of cases. They were randomly assigned to receive 3 MU IFNalpha2a three times a week subcutaneously for either 18 months (arm A) or 60 months (arm B). Results Of 850 randomly assigned patients, 840 were eligible for evaluation after a median follow-up of 4.3 years. Tumor thickness and other relevant prognostic factors were well balanced between both groups. SLNB was performed in 635 patients (75.6%), with a positivity rate of 18.0% in arm A and 17.5% in arm B. Neither relapse-free survival (arm A, 75.6% v arm B, 72.6%; P = .72; hazard ratio, 1.05; 95% CI, 0.80 to 1.39) nor distant-metastasis-free survival (81.9% v 79.7%; P = .56; HR, 1.10; 95% CI, 0.80 to 1.52) or overall survival (85.9% v 84.9%; P = .86; HR, 1.03; 95% CI, 0.71 to 1.50) showed significant differences. CONCLUSION A prolongation of conventional LDI therapy from 18 to 60 months showed no clinical benefit in patients with intermediate and high-risk primary melanoma.
T-cell inducer populations in cutaneous inflammation: a predominance of T helper-inducer lymphocytes (THi) in the infiltrate of inflammatory dermatoses
Authors: A.C. MARKEY, M.H. ALLEN, C. PITZALIS, D.M. MACDONALD
Journal: British Journal of Dermatology (1990)

The mononuclear infiltrate found in a variety of inflammatory dermatoses was characterized by a predominance of T helper-inducer lymphocytes (THi), CD4+/CD45RA-/CD45RO+, a population of cells responsible for maintaining and promoting immune reactions. Only small numbers of T-suppressor-inducer lymphocytes (TSi), CD4+/CD45RA+/CD45RO-, cells responsible for inducing CD8 suppressor-effector cells to 'down regulate' immune reactions, were seen. The predominance of CD4+ THi lymphocytes was common to all dermatoses studied and suggests a common final pathway in chronic cutaneous inflammation, irrespective of initial causative factors.
Oxidation contributes to low glutathione in the airways of children with cystic fibrosis
Authors: A. J. Kettle, R. Turner, C. L. Gangell, D. T. Harwood, I. S. Khalilova, A. L. Chapman, C. C. Winterbourn, P. D. Sly
Journal: European Respiratory Journal (2014)

Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques. The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis, whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage. The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age. Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset and progression of lung disease in cystic fibrosis.
Congenital H-ficolin deficiency in premature infants with severe necrotising enterocolitis
Authors: L. J. Schlapbach, S. Thiel, U. Kessler, R. A. Ammann, C. Aebi, J. C. Jensenius
Journal: Gut (2010)

In a recent issue of Gut , Muller et al reported on excessive colitis in a murine model of mannan-binding lectin (MBL) deficiency.1 They showed that absence of MBL can lead to uncontrolled intestinal inflammation detrimental to the host. MBL is a pattern-recognition molecule activating the complement system by the lectin pathway. H-ficolin is structurally closely related to MBL and can activate the lectin pathway of complement independently of MBL. While low levels of MBL occur in 10% of Caucasians, H-ficolin deficiency is extremely rare: studies involving over 100 000 adults found no case of H-ficolin deficiency, suggesting it exerts crucial functions for the human immune system.2 The first report on the so far only patient diagnosed with H-ficolin deficiency was published only recently,3 describing a patient with repeated infections who presented …
Elevated Troponin I Level on Admission Is Associated With Adverse Outcome of Primary Angioplasty in Acute Myocardial Infarction
Authors: Shlomo Matetzky, Tali Sharir, Michelle Domingo, Marko Noc, Kuang-Yuh Chyu, Sanjay Kaul, Neal Eigler, Prediman K. Shah, Bojan Cercek
Journal: Circulation (2000)

Background —In patients with acute myocardial infarction (AMI) undergoing thrombolytic therapy, an elevated troponin level on admission is associated with a lower reperfusion rate and a complicated clinical course. Whether an elevated troponin level on admission similarly predicts an adverse outcome in patients undergoing primary angioplasty is currently unknown and was investigated in the present study. Methods and Results —Cardiac troponin I (cTnI) was determined on admission in 110 consecutive patients with AMI associated with ST-segment elevation or left bundle branch block who underwent primary angioplasty. Fifty-four patients (49%) had an elevated cTnI (≥0.4 ng/mL) on admission. In patients with elevated cTnI, primary angioplasty was less likely to achieve TIMI 3 flow (as classified by the Thrombolysis in Myocardial Infarction trial) in univariate (76% versus 96%, P =0.03) or in multivariate (odds ratio 0.1, 95% CI 0.02 to 0.54) analysis. Patients with elevated cTnI were more likely to develop congestive heart failure (23% versus 9%, P &lt;0.05) and death, heart failure, or shock (30% versus 9%, P =0.006). Elevated cTnI remained a significant predictor of the composite end point after controlling for other clinical data that were available early in the course, including time to presentation and angiographic results (relative risk 5.2, 95% CI 1.03 to 26.3). During a follow-up of 426±50 days, elevated admission cTnI was a predictor of cardiac mortality (11% versus 0%, P =0.012), adverse cardiac events (cardiac mortality or nonfatal reinfarction; 19% versus 5.4%, P =0.04), and adverse cardiac events plus target vessel revascularization (32% versus 14%, P =0.054). Conclusions —In patients with ST-segment elevation AMI, an elevated cTnI on admission is associated with an increased risk of primary angioplasty failure and a more complicated clinical course.
Selective stimulation of colonic transit by the benzofuran 5HT<sub>4</sub> agonist, prucalopride, in healthy humans
Authors: E P Bouras, M Camilleri, D D Burton, S McKinzie
Journal: Gut (1999)

BACKGROUND Prucalopride (R093877) is a selective and specific 5HT 4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. AIMS To evaluate the effects of prucalopride on gastrointestinal and colonic transit. METHODS A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0.5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours. RESULTS There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p&lt;0.05) and proximal colonic emptying t 1/2 (p&lt;0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p&gt;0.5) or small bowel transit (overall p=0.12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. CONCLUSION Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation.
AXL Mediates Resistance to Cetuximab Therapy
Authors: Toni M. Brand, Mari Iida, Andrew P. Stein, Kelsey L. Corrigan, Cara M. Braverman, Neha Luthar, Mahmoud Toulany, Parkash S. Gill, Ravi Salgia, Randall J. Kimple, Deric L. Wheeler
Journal: Cancer Research (2014)

The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated, and tightly associated with EGFR expression in cells resistant to cetuximab (Ctx(R) cells). Using RNAi methods and novel AXL-targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation, and MAPK signaling in Ctx(R) cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in Ctx(R) cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft models, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab-resistant cancers. Cancer Res; 74(18); 5152-64. ©2014 AACR.
Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus
Authors: Julie A. Cakebread, Yunhe Xu, Chris Grainge, Valia Kehagia, Peter H. Howarth, Stephen T. Holgate, Donna E. Davies
Journal: Journal of Allergy and Clinical Immunology (2011)
Effects of antibiotics on protected specimen brush sampling in ventilator-associated pneumonia
Authors: E. Prats, J. Dorca, M. Pujol, L. Garcia, B. Barreiro, R. Verdaguer, F. Gudiol, F. Manresa
Journal: European Respiratory Journal (2002)

The effects of antibiotic treatment on the results of protected specimen brushing (PSB) in ventilator-associated pneumonia were prospectively assessed by performing this procedure before antibiotic treatment, and 12, 24, 48 and 72 h after initiation of antibiotic treatment, in 35 ventilated patients who developed pneumonia during mechanical ventilation. The number of micro-organisms isolated, their concentration (colony-forming units (cfu)·mL −1 ), and the number of cases with a positive PSB (≥10 3 cfu·mL −1 ) were evaluated. Within 12 h of the initiation of effective antibiotic treatment a rapid, significant decrease in the numbers of organisms isolated, their individual concentrations and the percentage of positive PSB results were observed. Certain bacterial species ( Streptococcus pneumoniae , Haemophilus influenzee ) appeared to be more vulnerable to antibiotics than others ( Staphylococcus aureus , Pseudomonas aeruginosa , Acinetobacter baumanni ). This data confirms that prior antibiotic treatment, even after only a few hours of activity, significantly decreases the sensitivity of protected brush specimen; this effect appears to be particularly marked among the species involved in early ventilator associated pneumonia.
Leukotriene B4-Driven Neutrophil Recruitment to the Skin Is Essential for Allergic Skin Inflammation
Authors: Michiko K. Oyoshi, Rui He, Yitang Li, Subhanjan Mondal, Juhan Yoon, Roshi Afshar, Mei Chen, David M. Lee, Hongbo R. Luo, Andrew D. Luster, John S. Cho, Lloyd S. Miller, Allison Larson, George F. Murphy, Raif S. Geha
Journal: Immunity (2012)
BRAF Mutations in Colorectal Cancer: Clinical Relevance and Role in Targeted Therapy
Authors: Rona Yaeger, Leonard Saltz
Journal: Journal of the National Comprehensive Cancer Network (2012)

Experts have long appreciated that the clinical entity we call colorectal cancer is a phenotype made up of numerous different genotypes, accounting for the wide variation in clinical course and responses to therapies experienced by different individuals.Observations reported by Khambata-Ford et al 1 and subsequently confirmed by Amado et al 2 have made the practicing community aware that activating mutations in exon 2 of the gene encoding for KRAS, a key signal transduction protein, result in primary resistance to anti-epidermal growth factor receptor (EGFR) agents by leading to EGFR-independent activation of mitogen-activated protein kinase (MAPK) signaling.BRAF is a signal transduction protein that is downstream of KRAS in the MAPK pathway.Approximately 5% to 10% of colorectal cancers harbor mutations in BRAF; the most common is the V600E mutation.The occurrence of these mutations in colorectal cancers raises 2 important questions: what are the clinical characteristics of a colorectal cancer with a V600E BRAF mutation, and can that mutation be targeted for therapeutic advantage?
Lung transplantation for pulmonary sarcoidosis
Authors: MA Judson
Journal: European Respiratory Journal (1998)

Patients with end-stage sarcoidosis have now undergone lung transplantation successfully with good short-term and intermediate-term results. Lung transplantation for sarcoidosis requires several considerations unique to this disease. Selection of pulmonary sarcoidosis patients for transplantation requires that medical therapy has been exhausted. This may involve the use of corticosteriods and alternative medications. Causes of pulmonary dysfunction other than pulmonary sarcoidosis, such as bronchiectasis and myocardial sarcoidosis, must be excluded before candidates are considered for transplantation. The extent and severity of extrapulmonary disease must also be assessed and may preclude lung transplantation. The presence of mycetomas is considered a relative contra-indication by some transplant centres and an absolute contra-indication by others. Relatively few patients with pulmonary sarcoidosis have undergone transplantation and, therefore, there are few data on outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur in sarcoidosis transplant recipients, although at present there is no evidence of an increased risk of obliterative bronchiolitis or increased mortality.