tbuckley/cabot-search huggingface dataset:
The inflammasome and danger molecule signaling: at the crossroads of inflammation and pathogen persistence in the oral cavity
Authors: Özlem Yilmaz, Kyu Lim Lee
Journal: Periodontology 2000 (2015)

Abstract Inflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase‐1‐dependent maturation and the subsequent secretion of inflammatory interleukin‐1beta and interleukin‐18 cytokines in response to a ‘danger signal’ in vertebrates. The assessment of their significance continues to grow rapidly as the complex biology of various chronic inflammatory conditions is better dissected. Increasing evidence strongly links inflammasomes and host‐derived small ‘danger molecule ATP ’ signaling with the modulation of the host immune response by microbial colonizers as well as with potential altering of the microbiome structure and intermicrobial interactions in the host. All of these factors eventually lead to the destructive chronic inflammatory disease state. In the oral cavity, a highly dynamic and multifaceted interplay takes place between the signaling of endogenous danger molecules and colonizing microbes on the mucosal surfaces. This interaction may redirect the local microenvironment to favor the conversion of the resident microbiome toward pathogenicity. This review outlines the major components of the known inflammasome complexes/mechanisms and highlights their regulation, in particular, by oral microorganisms, in relation to periodontal disease pathology. Better characterization of the cellular and molecular biology of the inflammasome will probably identify important potential therapeutic targets for the treatment and prevention of periodontal disease, as well as for other debilitating chronic diseases.
The additional diagnostic value of interferon gamma release assay to the tuberculin skin test in Greek health care workers (a preliminary study)
Authors: Alexandros Charisis, Athanasios Konstantinidis, Constantina Gartzonika, Dimitra Archimandriti, Athena Gogali, Christos Katsanos, Athanasios Kostoulas, Stamatis Katsenos, George Daskalopoulos, Stamatina Leveidiotou-Stefanou, Anestis Mavridis, Stavros Constantopoulos
Journal: European Respiratory Journal (2011)

Introduction:  Health care workers (HCWs) are at increased risk of Mycobacterium tuberculosis infection. The tuberculin skin test (TST) can be positive (among others) after vaccination with bacille Calmette-Guerin (BCG) creating confusion in countries where this is still compulsory, like Greece. Interferon gamma release assays (IGRAs) are used to solve this problem since they are more specific than TST and usually do not become positive after BCG vaccination.   Aims and objectives:  This is a preliminary study aiming to evaluate the additional diagnostic value of Quanti-FERON®-TB Gold In-Tube (QFT-GIT) to the tuberculin skin test (TST) in Greek HCWs.   Methods:  A cross-sectional study of TST and QFT-GIT was carried out among 275 immuno-competent HCWs at a 900-bed Greek tertiary referral University Hospital. TST was performed on all participants, while QFT-GIT was performed in all subjects with TST ≥10 mm.   Results:  Among the 275 study subjects, 124 (45.1%) had TST indurations of ≥10 mm, 96 of them were BCG vaccinated. None had clinical or radiologic evidence of active tuberculosis. From these 124 HCWs, 69 (age 20-67, mean 48,2) agreed to have the QFT-GIT test which was positive in only 9/69 (13%).   Conclusion:  Based on IGRA9s results, in the majority of Greek HCWs of our study, positive TST was not due to latent tuberculosis infection but to previous BCG vaccination or other unidentified reasons, like exposure to non-tuberculous mycobacteria. This is in agreement with a previous study of our Department in a younger age group of Greek Army recruits (S. Katsenos et al. Int J Tuberc Lung Dis 14(5):545–550).
Differences in Cell Surface Antigens of Tumor Metastases and Those of the Local Tumor2
Authors: Mina Fogel, Eliezer Gorelik, Shraga Segal, Michael Feldman
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Differences in Cell Surface Antigens of Tumor Metastases and Those of the Local Tumor Get access Mina Fogel, Mina Fogel 3Department of Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eliezer Gorelik, Eliezer Gorelik 3Department of Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shraga Segal, Shraga Segal 4 3Department of Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. 4Address reprint requests to Dr. Segal. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Feldman Michael Feldman 3Department of Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. 5The technical assistance of E. Vadai and Z. Gadassi is greatly appreciated. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 3, March 1979, Pages 585–588, https://doi.org/10.1093/jnci/62.3.585 Published: 01 March 1979 Article history Received: 26 April 1978 Accepted: 11 September 1978 Published: 01 March 1979
Body Mass Index as a Predictor of Cancer in Men&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Nomura, L K Heilbrun, G N Stemmermann
Journal: JNCI Journal of the National Cancer Institute (1985)

In this prospective study 8,006 Japanese men, age 45-68 years, were examined between 1965 and 1968. Their height and weight were measured and they were asked for their weight at age 25. After a surveillance period of almost 15 years, 646 incident cases of the following cancers were identified: 104 stomach, 101 colon, 101 lung, 96 prostate, 63 rectum, and 181 cancers of other sites. Body mass index (BMI = weight/height2) at time of examination and weight gain since age 25 were positively associated with an increased risk for colon cancer in subjects age 55 or older at the time of examination. No other cancer had a significant positive association with either BMI at the time of examination or with weight gain since age 25. In contrast, a low BMI at examination and weight loss since age 25 were associated with an increased risk for stomach cancer, whereas only weight loss since age 25 was associated with an increased risk for lung cancer. These two cancers accounted for the overall significant association of weight loss with total cancer incidence.
The New Zealand respiratory health survey- rationale, methodology and response rate
Authors: James Fingleton, Justin Travers, Mark Weatherall, Richard Beasley
Journal: European Respiratory Journal (2013)

Previous cluster analyses have reported candidate phenotypes of asthma and COPD, however the validity and response to medication of different phenotypes is not known. The NZRHS was designed to address this. Here we report the study design and Phase 1 results.   Aims   To describe clinical phenotypes of adults with symptoms of airways disease recruited from a random sample of New Zealand adults and compare the response to bronchodilators and inhaled corticosteroids (ICS) between phenotypes.    Methods   The NZRHS had 3 phases:   Phase 1  A random population sample of adults aged 18-75yrs was drawn from the electoral roll and a brief respiratory questionnaire posted to all participants.   Phase 2  Detailed characterisation of airways disease and response to salbutamol and ipratropium was performed on 451 participants with symptoms of wheeze and breathlessness.   Phase 3  Steroid naive participants from Phase 2 were offered a 12 week trial of ICS to assess response to treatment.   Results of Phase 1   Questionnaires were posted to 16,459 adults. 11,397 responses were received (69.2%) and are summarised in Tables 1 & 2.   Conclusions   The NZRHS has demonstrated a high symptom burden amongst adults in NZ. Phases 2 & 3 will allow description of candidate phenotypes and comparison of their response to medication.
CD45 and the immune response.
Authors: J A Donovan, G A Koretzky
Journal: Journal of the American Society of Nephrology (1993)

CD45 is a major transmembrane glycoprotein expressed on all nucleated hematopoietic cells. Eight isoforms of CD45 are distributed through the immune system according to cell type and degree of cellular differentiation. Heterogeneity among the isoforms is found entirely in the extracellular domain, arising from the differential splicing of up to four exons of a single gene. The control of isoform expression suggests that the extracellular domain may participate in protein-protein interactions with isoform-specific ligands. The intracellular domain of CD45 is large (approximately 700 amino acids), identical for all isoforms, and highly conserved across species. Two nonidentical intracellular sequences of about 240 amino acids that are homologous with a tyrosine phosphatase consensus sequence have been identified. Studies with purified CD45 have shown that all isoforms possess enzymatic activity in in vitro assays. In several T and B cell lines and in natural killer cells, it appears that CD45 is required for optimal signal transduction after stimulation through a number of surface receptors. Although an in vivo substrate has not been identified conclusively, one model suggests that CD45 functions to dephosphorylate a negative-regulatory tyrosine residue on one or more protein tyrosine kinases involved in receptor-mediated second messenger formation. In T cells, the src family kinases, lck and fyn, are candidates for this regulated kinase. In this review, some of the structural and functional aspects of CD45 and its role in signal transduction in the immune system are discussed.
Cardiac Natriuretic Peptides Inhibit TRPC6-Mediated Prohypertrophic Signaling
Authors: Hideyuki Kinoshita, Koichiro Kuwahara, Ryuji Inoue, Motohiro Nishida, Hitoshi Kurose, Shigeki Kiyonaka, Yasuo Mori, Masaki Harada, Masao Murakami, Yasuaki Nakagawa, Shinji Yasuno, Satoru Usami, Masataka Fujiwara, Yoshihiro Kuwabara, Takeya Minami, Yuko Yamada, Kenji Ueshima, Kazuwa Nakao
Journal: Circulation Research (2009)
Evaluation of outpatient infections in lung cancer patients treated with chemotherapy and/or radiotherapy
Authors: Vasileios Kouranos, Emily Tsaroucha, Antonis Vassias, John Arapis, John Gkiozos, Konstantinos Syrigos
Journal: European Respiratory Journal (2012)

Introduction: Infections are important causes of morbidity and mortality in lung cancer patients. The myelotoxicity caused by the administration of either the chemotherapeutic regimens or the radiotherapy increases the risk of potentially life-threatening infection.  Methods: This prospective study included all patients with lung cancer who referred with signs or symptoms of infection between September 2009 and October 2011. Data concerning patient9s history, disease9s diagnosis, management and therapy and infection9s signs, symptoms and documentation were collected.  Results: Seventy one patients with lung cancer were enrolled with febrile episodes and/or microbiologically or otherwise documented infection. Forty six patients (64.8%) presented with non-small cell lung carcinoma, while 22/71 patients (31%) and 3/71 patients (4.2%) had small cell lung cancer and mesothelioma respectively. Fifteen patients (21.1%) presented with FN and totally 43/71 (60.6%) patients required hospitalization for parenteral therapy upon admission. The predominant site of the infections was the lung in 59/71 patients (83.1%). In the hospitalized setting 3 episodes of bacteremia with Staphylococcus aureus were reported and microbiologically documented infections accounted for 26.7% of the hospitalized patients. The overall mortality rate was 9.8%, while only 1 patient died in the outpatient setting despite the antibiotic therapy.  Conclusion: This study showed that the early detection and control of infection in lung cancer patients receiving therapy may improve their survival. Recognition of predisposing factors for infections and possible therapy toxicities should be evaluated carefully.
A temporal effect of EGFR tyrosine kinase inhibitor in lymphoepithelioma-like carcinoma of lung
Authors: Kuoliang Chiu, Kuochin Chiu, Tzu-Sheng Chen
Journal: European Respiratory Journal (2012)

Introduction: Primary lymphoepithelioma-like carcinoma (LELC) is a rare in lung. Recent studies suggested a prevalent mutation on epidermal growth factor receptor (EGFR) in LELC of lung. However, the therapeutic effect of EGFR tyrosine kinase inhibitor (TKI) has not been tested. We hereby report an effect of EGFR TKI on LELC of lung.

Case report: A 70-year-old woman presented to have a lung tumor, 6.1x5.1x5.0 cm, over left upper lobe. CT-guided core-needle biopsy of lung tumor confirmed the diagnosis of LELC, and a clinical stage of T4N3M0, stage IIIB, was met. The patient had a partial response after completing 6 cycles of 1st-line chemotherapy (C/T) with gemcitabine plus cisplatin, and 4 cycles of 2nd-line C/T with docetaxel.

![Figure][1] 



After having a progression, she went on a TKI therapy. The tumor kept shrinking through 6 months, until progressing after 9-month TKI treatment.

![Figure][1] 



Discussions: This is the first report demonstrating a therapeutic effect of EGFR TKI on LELC of lung, as a 3rd-line therapy in this case. The case report suggests EGFR TKI, at least erlotinib, may be beneficial for patients with LELC of lung, at least for a significant period of time.

 [1]: pending:yes
Lung Clearance Index (LCI) and FEV1 on the evaluation of the effect of tobramycin solution for inhalation (TIS) among patients with cystic fibrosis
Authors: Elpis Hatziagorou, Vasiliki Avramidou, Asterios Kampouras, Fotis Kirvasillis, John Tsanakas
Journal: European Respiratory Journal (2014)

Background:   Several outcome measures to assess the efficacy of therapeutic interventions in patients with cystic fibrosis (CF) have been used.   Objective:  To assess the ability of LCI to detect a treatment response to inhaled tobramycin (tobramycin inhaled solution, TIS) in paediatric patients with CF colonized with pseudomonas aeruginosa.   Method:  Multiple breath washout and spirometry were performed by 15 children and adolescents with mild CF prior and post a four – week course of TIS.   Results:   Mean age of the study population was 11.7 years, mean baseline FEV 1  was 99.1% predicted (±15), while mean LCI was 10.3 (±3.1). Mean LCI improved significantly after a four-week course of TIS and deteriorated following a four-week off medication (mean change after TIS: -1.38, p:0.015; mean change after washout period: +1.75; p:0.000). Mean FEV 1  did not change significantly after TIS or after discontinuation of treatment (p: 0.638 and p: 0.783, respectively).   Conclusions:  Lung clearance index, but not FEV 1  was able to detect a treatment effect from TIS inhalation in patients with CF.
Do obese patients lose weight with pulmonary rehabilitation
Authors: Elliot W. Bone, Samantha S.C. Kon, Amy L. Clark, Jane L. Canavan, Claire M. Nolan, Sarah E. Jones, William D.-C. Man
Journal: European Respiratory Journal (2013)

Background  Obesity is abnormal fat accumulation that may impair health, defined as a BMI ≥ 30. Reduction in physical activity and sedentary lifestyles are now recognised as a major cause. Recent data suggest that obesity does not affect the response to pulmonary rehabilitation (PR) (Greening 2012). However it is not known whether PR can help with weight loss in obese patients.   Methods  234 patients (BMI ≥ 30) who completed an 8-week outpatient PR programme were recruited. All were provided with dietary advice leaflets and attended an hour lecture with a dietician. Weight, MRC, Chronic Respiratory Disease Questionnaire (CRQ), incremental shuttle walk (ISW) and body composition (Bodystat 1500) were measured pre and post PR. Fat free mass was calculated (Steiner 2002). Paired t-tests or Wilcoxon Signed rank tests were used to compare outcomes pre and post PR.   Results  Baseline characteristics mean (standard deviation) or median (25 th , 75 th  percentiles); Age 68 years (62,75), FEV 1  % pred 58 (22), MRC 4 (3,5), BMI 35.5 (5.5). Disease classifications (n): COPD (145), interstitial lung disease (23), asthma (28), obesity hypoventilation (14), bronchiectasis (10), extrathoracic restriction (9) and thoracic surgery for lung cancer (2). There was a significant change in all standard PR outcome measures (MRC, CRQ and ISW, all p 2  respectively, which was statistically significant (p=0.01 and p   Conclusion   Obese patients undergoing supervised exercise training as part of a PR lose weight which can be attributed to loss of fat mass. However, it is debatable whether these changes are clinically significant.
Subclinical small airway involvement in children with seasonal allergic rhinitis
Authors: Sotirios Fouzas, Argyro Lioliou, Ioanna Vassilopoulou, Michael Anthracopoulos, Maria Triga
Journal: European Respiratory Journal (2011)

Background:  Allergic rhinitis (AR) has been incriminated as a relevant risk factor for asthma onset in children and young adults. The aim of this study was to examine the presence of subclinical reversible airflow obstruction in non-asthmatic children suffering from seasonal AR.   Methods:  Twenty five children with seasonal AR and pollen allergens sensitization were compared during the pollen season with 25 matched for age healthy controls. All participants had no prior history of asthma, asthma-related symptoms or use of asthma medication. Forced spirometry indices (FEV 1 , FVC, FEV 1 /FVC, FEF 25-75 ), as well as respiratory resistance (Rrs) and reactance (Xrs) at frequencies of 4, 6, 8, and 10 Hz (forced oscillation technique), were determined before and 15 minutes after bronchodilator (BD) administration (salbutamol 500μg). Baseline values and relative changes were calculated and compared between children with and without AR.   Results:  There were no significant differences in baseline values of the studied indices between the two groups. Children with AR presented a significantly greater BD response compared to controls for FEF 25-75  (29±12% vs 18±10%; P (4Hz)  (18±8% vs 12±5%; P (6Hz)  (14±8% vs 9±5%; P  (4Hz)  (26±12% vs 17±8%; P (6Hz)  (28±15% vs 20±12%; P   Conclusion:  Small airway bronchodilator responsiveness was increased in children with AR. These data suggest that a subclinical small airway involvement is present in non-asthmatic children with seasonal AR.
ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development
Authors: Lekun Fang, Weisi Lu, Hyun Ho Choi, Sai-Ching J. Yeung, Jung-Yu Tung, Chwan-Deng Hsiao, Enrique Fuentes-Mattei, David Menter, Chuangqi Chen, Lei Wang, Jianping Wang, Mong-Hong Lee
Journal: Cancer Cell (2015)
Assessment of nutritional status in patients with primary lung cancer
Authors: Fatma Chermiti Ben Abdallah, Amel Chtourou, Sofia Taktak, Imène Bachouch, Soraya Fenniche
Journal: European Respiratory Journal (2014)

Background:  Lung cancer is the leading cause of cancer-related mortality worldwide. Malnutrition is a common problem among patients with cancer, affecting up to 85% of patients with certain cancers and represents a risk factor for poor prognosis.   Aim:  evaluate nutritional status in patients with lung cancer before and during treatment using nutritional risk index.   Patients and Methods : it9s a prospective study conducted in pneumology IV department in Abderahman Mami hospital, from January to May 2011. 30 male patients with a lung cancer were included. Nutritional status was assessed before and during treatment based on anthropometric measures, biological markers and nutritional risk index (NRI).   Results:  Mean age of patients was 58 ± 12 years, ranging from 19 to 82 years. 29 patients had non small cell lung cancer and one patient had small cell cancer. Malnutrition was noted in 14 patients (47%) before treatment according to the NRI. It was noted in 23 patients (77%) after three cycles of chemotherapy with severe malnutrition in 8 patients. Relationship between body mass index (BMI) and the NRI was linear, but NRI tends to evaluate more objectively risk of malnutrition in patients with lung cancer.   Conclusion:  Nutritional assessment in patient with lung cancer should be performed systematically, early and repeatedly. Several markers can be used such as BMI and NRI. Nutritional support will reduce morbidity and improve quality of life in patients with lung cancer.   Key-words: Lung cancer, malnutrition, treatment, Nutritional risk index.
Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction
Authors: José González-Santamaría, María Villalba, Oscar Busnadiego, Marina M. López-Olañeta, Pilar Sandoval, Jessica Snabel, Manuel López-Cabrera, Janine T. Erler, Roeland Hanemaaijer, Enrique Lara-Pezzi, Fernando Rodríguez-Pascual
Journal: Cardiovascular Research (2015)

After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross-links. This study investigates the contribution of LOX family members to the heart response to MI.Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI, and this response was accompanied by a significant accumulation of mature collagen fibres in the infarcted area. LOX expression was observed in areas of extensive remodelling, partially overlapping with α-smooth muscle actin-expressing myofibroblasts. Tumour growth factor-β as well as hypoxia-activated pathways contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post-infarction treatment with the broadband LOX inhibitor β-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also resulted in reduced ventricular dilatation and improved cardiac function.LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery.
Role of independent data-monitoring committees in randomized clinical trials sponsored by the National Cancer Institute.
Authors: M A Smith, R S Ungerleider, E L Korn, L Rubinstein, R Simon
Journal: Journal of Clinical Oncology (1997)

To describe the rationale for independent data monitoring committees (DMCs) for National Cancer Institute (NCI)-sponsored phase III cooperative group clinical trials.We review the necessity for interim monitoring of outcome data during the course of randomized clinical trials and summarize the reasons for establishing DMCs with requisite expertise and with appropriate independence from study investigators.The important components of the policy for cooperative group DMCs are described with a focus on the makeup of these bodies and on the complementary roles of study committee leadership and DMCs in protecting patient safety during the conduct of randomized clinical trials.The cooperative group DMCs that are independent of the study committees and that have the requisite expertise to examine accumulating data and to base decisions on monitoring guidelines that are specified in advance by the study committee provide a body able to protect patient safety, to protect the integrity of the clinical experiments on which patients have consented to participate, and to assure the public that conflicts of interest do not compromise either patient safety or trial integrity.