tbuckley/cabot-search huggingface dataset:
Increased levels of angiopoietin 1 & 2 in sputum supernatant in smoking asthma
Authors: Eleni Tseliou, Petros Bakakos, Konstantinos Kostikas, Vasiliki Petta, Davina Simoes, Goergios Hillas, Nikolaos Koulouris, Spyros Papiris, Stelios Loukides
Journal: European Respiratory Journal (2012)

Background: Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor.

Objective: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with smoking asthma and to investigate possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling process

Methods: Eighty-seven patients with asthma (42 smokers) and 28 healthy subjects (14 smokers) were studied. All subjects underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed.

Results: Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly higher in patients with smoking asthma compared to patients with non-smoking asthma and both smoking and non-smoking healthy subjects [median, interquartile ranges 24(13-37) vs. 10 (7-14) vs. 5.3(3.7-6.5) vs 4.6 (3.8-5.7) respectively, p<0.001; and 168 (132-203) vs 124 (82-152) vs 94(78-113) vs 100 (96-108) respectively, p<0.001]. Regression analysis showed a significant positive association for Ang-2 with AVP index, and VEGF in smoking asthma. A negative association was observed between Ang-1 and AVP index, MMP-2, sputum neutrophils and VEGF in smoking asthma.

Conclusions: Our results indicate that sputum Ang-1 and Ang-2 levels are higher in smoking asthma compared to non-smoking asthma and healthy subjects pointing towards a contribution of smoking through these mediators to the asthmatic angiogenesis process.
Maintaining Tumor Heterogeneity in Patient-Derived Tumor Xenografts
Authors: John W. Cassidy, Carlos Caldas, Alejandra Bruna
Journal: Cancer Research (2015)

Abstract Preclinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumor xenografts (PDX) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumor is governed by both cell-autonomous (e.g., genetic and epigenetic heterogeneity) and non–cell-autonomous (e.g., stromal heterogeneity) drivers. Although PDXs can largely recapitulate the polygenomic architecture of human tumors, they do not fully account for heterogeneity in the tumor microenvironment. Hence, these models have substantial utility in basic and translational research in cancer biology; however, study of stromal or immune drivers of malignant progression may be limited. Similarly, PDX models offer the ability to conduct patient-specific in vivo and ex vivo drug screens, but stromal contributions to treatment responses may be under-represented. This review discusses the sources and consequences of intratumor heterogeneity and how these are recapitulated in the PDX model. Limitations of the current generation of PDXs are discussed and strategies to improve several aspects of the model with respect to preserving heterogeneity are proposed. Cancer Res; 75(15); 2963–68. ©2015 AACR.
Chronic thromboembolic pulmonary hypertension associated with Klippel Trenaunay syndrome: A retrospective series of 5 patients
Authors: Andrei Seferian, Xavier Jaïs, David Montani, Sven Günther, Delphine Natali, Laurent Savale, Florence Parent, Dermot Steven O'Callaghan, Olivier Sitbon, Marc Humbert, Gerald Simonneau
Journal: European Respiratory Journal (2011)

Introduction:  Klippel Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the triad: (1) cutaneous capillary malformations; (2) soft tissue and bone hypertrophy; (3) multiple vascular malformations at arterial, venous and lymphatic level. KTS is associated with recurrent venous thromboembolism (VTE), that may lead to chronic thromboembolic pulmonary hypertension (CTEPH).   Patients and methods:  We retrospectively reviewed clinical and haemodynamical characteristics of 5 patients with CTEPH associated with KTS referred to our center between 1993 and 2010.   Results:  Four patients had a previous history of VTE. At diagnosis, 1 patient was in NYHA functional class (FC) II and 4 patients were in NYHA FC III. Pulmonary haemodynamics were: mean pulmonary artery pressure (mPAP)= 56.4±9.3 mmHg, cardiac index (CI)= 2.74±0.89 l/min/m 2  and total pulmonary resistance (TPR)= 20.2±12.4 Wood units. One patient had proximal CTEPH, underwent a pulmonary endarterectomy and normalized his pulmonary pressures after surgery. The other 4 patients had inoperable CTEPH due to distal lesions and were treated with specific pulmonary arterial hypertension (PAH) therapy. Two patients were clinically and haemodynamically improved by oral therapy with a mean reduction of 22% of the mPAP and 60% of the TPR after a mean follow-up of 50 months. One patient died after 34 months due to recurrent VTE complications and one patient needed a heart-lung transplantation after 15 years of follow up.   Conclusion:  CTEPH is a rare but severe complication of KTS. Careful monitoring of patients with KTS in a multidisciplinary setting is thus appropriate.
Abstract 13626: Sex Differences in Risk Factors, Treatment Patterns and Clinical Outcomes of Stroke Among Patients with Atrial Fibrillation
Authors: Meytal Avgil Tsadok, Cynthia Jackevicius, Elham Rahme, Karin H Humphries, Vidal Essebag, Mark J Eisenberg, Jack V Tu, Hassan Behlouli, Louise Pilote
Journal: Circulation (2011)

Background: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men, however the reason for this is uncertain. It has...
Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial
Authors: F. Sclafani, I. Chau, D. Cunningham, C. Peckitt, A. Lampis, J.C. Hahne, C. Braconi, J. Tabernero, B. Glimelius, A. Cervantes, R. Begum, D. Gonzalez De Castro, S. Hulkki Wilson, Z. Eltahir, A. Wotherspoon, D. Tait, G. Brown, J. Oates, N. Valeri
Journal: Annals of Oncology (2015)

Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC.
An in vitro resistance study of levofloxacin, ciprofloxacin, and ofloxacin using keratitis isolates of Staphylococcus aureus and Pseudomonas aeruginosa1 1The authors have no proprietary interest in any of the products presented in this study.
Authors: Regis P Kowalski, Angana N Pandya, Lisa M Karenchak, Eric G Romanowski, Roger C Husted, David C Ritterband, M.K Shah, Y.Jerold Gordon
Journal: Ophthalmology (2001)
Abstract 15724: Intermittent Hypoxia Induces Early Pro-Atherogenic Changes in Aortic Wall Macrophages in a Murine Model of Obstructive Sleep Apnea
Authors: Alex Gileles-Hillel, Isaac Almendros, Abdelnaby Khalyfa, Shelley Zhang, Yang Wang, David Gozal
Journal: Circulation (2014)

Background: OSA is a highly prevalent condition throughout the lifespan, and has emerged as an independent risk factor for atherosclerosis. Macrophages play a key role in the pathogenesis of atherosclerosis through shifts in the continuum between the pro-inflammatory M1 and the athero-protective M2. We hypothesized that Intermittent Hypoxia (IH) during the sleep period, a model for OSA, will induce shifts towards a pro-atherogenic state in the spectrum of macrophages within the aortic vascular wall. Methods: 8-week old male C57BL/6J mice were exposed to IH for 12-hr/day during the light period or to room air (RA) for 6 weeks and were kept on a regular low-fat chow. Following exposure, full-length aortas were dissected and enzymatically digested. Single cell suspensions were prepared and cells were incubated with antibodies for macrophage markers previously implicated in atherogenesis and metabolic dysregulation - CD11b, F4/80, Ly6c, CD36, and CD64, and analyzed by FACS. Results: Macrophages were defined as CD11b+/F4/80+ cells. Significant increases in the percentage of macrophages emerged in IH-exposed mice (6.4%±0.3 vs. 8%±0.3, p=0.003, n=19-20/group). Furthermore, IH induced shifts in the macrophage population toward an M1 pro-inflammatory phenotype. Specifically, IH group showed significantly higher expression of Ly6c, (MFI:522±23 vs. 699±43, p=0.004, n=12/group) and increased the percentage of Ly6c+(hi) cells (9.2% vs. 11.7%, p=0.03). Conversely, tissue-resident marker CD64 expression in the aortic macrophages was down-regulated following IH exposures (MFI:3207±453 vs. 2967±483, p=0.03, n=12/group), while scavenger receptor CD36 expression was increased in the IH-exposed group (MFI:1694±56 vs.2129±209, p=0.005). Conclusion: Intermittent hypoxia during the sleep period leads to early expansion of the macrophage population in the aortic wall in a relatively resistant animal model for development of atherosclerosis, i.e., in the absence of a high-fat diet or of high atherogenic risk predisposing gene knockout. Furthermore IH induces changes in macrophage phenotypes, including a shift towards a pro-inflammatory phenotype, and recruitment of bone-marrow derived macrophages expressing indicators of metabolic activation.
An effect of the home-based rehabilitation programme following the outpatient rehabilitation programme in patients with pulmonary sarcoidosis
Authors: Jakub Zatloukal, Katerina Neumannova, Vladimira Lostakova, Vitezslav Kolek
Journal: European Respiratory Journal (2012)

Background  Definition of the pulmonary rehabilitation (PR) precisely describes how such a programme should be established and what parts should be included. However, success in completing the programme should motivate patients to keep at it and thus to prolong the beneficial effect of it.  Aim  To evaluate an effect of a 6-week home-based PR following a 6-week outpatient PR on health status and health-related quality of life (HRQL) in patients with pulmonary sarcoidosis (PS).  Methods  There were 18 patients with PS (mean age 50.3±13.3) recruited to the PR programme. The assessments included lung function tests, maximal inspiratory (MIP) and expiratory (MEP) mouth pressures, chest expansion, 6-minute walk test (6MWT) and HRQL using the Sarcoidosis Health Questionnaire. Patients underwent a 6-week outpatient PR followed by a 6-week home-based PR programme, which both consisted of respiratory physiotherapy and regular physical activity training.  Results  Baseline data showed decreased breathing muscle strength (MIP 89 %, MEP 65 %), limited chest expansion and relatively normal results in 6MWT (105 % of predicted). Completing outpatient PR programme induced statistically significant changes in all measured parameters but lung function tests. Further significant improvement was observed in MIP during the following home-based PR programme.  Conclusion  Achieved improvements of the 6-week outpatient PR remained also after the 6-week home-based PR and therefore patients should be encouraged in continuing the PR programme at home.  Supported by grants of the Palacky University – FTK_2011:010, FTK_2012:023.
Calorie Restriction: Effect on Growth of Human Tumors Heterotransplanted in Nude Mice<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: B C Giovanella, R C Shepard, J S Stehlin, J M Venditti, B J Abbott
Journal: JNCI Journal of the National Cancer Institute (1982)

The presence of 4 human malignant tumors (1 breast, 1 lung, and 2 colon carcinomas) growing subcutaneously as heterotransplants in nude mice did not significantly affect the body weights of adult animals until the tumors reached very large dimensions (tumor wt greater than 15% of the body wt). However, a colon carcinoma (HT 29) induced a cessation of the natural rate of body weight increase when it grew in young adults (animals weighing approximately equal to 25 g which will gain 6 g or approximately equal to 25% body wt in 1 mo). Calorie restriction at all the levels tested (8, 6, 4, and 2 g/day/mouse) with standard pelletized mouse food produced both weight loss in the animals (with and without tumor) and a lowering of the growth rate of all the 4 tumors tested growing at a subcutaneous site and/or under the kidney capsule. Each tumor responded differently to the calorie restriction. The 4 tumors tested grew equally in both male and female nude mice. Young animals weighing 20 g inoculated with a fifth tumor (MeWo melanoma) exhibited tumor growth inhibition proportional to restriction of calorie intake. Their survival, however, did not improve.
Instrument variability in the measurement of respiratory resistance
Authors: Ellie Oostveen, K. De Soomer, J.A. Otte, A.-M. Vints, W. De Backer
Journal: European Respiratory Journal (2014)

Our aim was to quantify the accuracy of 5 forced oscillation devices (#1: custom made, #2: I2M [Chess mT, Belgium], #3: IOS [Jaeger, Germany], #4: TremoFlo [Thorasys, Canada] and #5: Resmon PRO FULL [Restech s.r.l., Italy]).  Methods: Respiratory resistance at 5 Hz (R5) of 80 subjects (20 controls, 60 patients with pulmonary disorders) was measured with all 5 setups, in random order. Additionally, the short-term repeatability of R5 on each device was assessed in another 25 subjects.  Results: The short-term, mean relative coefficient of repeatability of R5 was 21% (16%-23%). Bland-Altman analysis revealed that I2M (#2) slightly underestimated R5 while IOS (#3) slightly overestimated R5 compared to the other setups. More importantly, the between-setup differences were much larger than expected on the basis of the short-term repeatability (see table and figure).  Conclusion: Instrumentation is a non-negligable source of variability in the measurement of respiratory resistance.
Interactions between epithelial cells and neutrophils during pro-inflammatory conditions
Authors: Ida von Schéele, Kjell Larsson, Lena Palmberg
Journal: European Respiratory Journal (2011)

Inter-cellular communication is essential for defense and survival of the organism. The aim of the study was to find out whether there is an active cross-talk between cells constituting the first line of defense; alveolar epithelial cells (A549) and neutrophils, following activation with pro-inflammatory stimuli in vitro. Further, to explore whether this communication is altered in chronic obstructive pulmonary disease (COPD), a condition characterized by chronic airway and lung inflammation.

Blood neutrophils from healthy subjects and COPD-patients were co-cultured with A549 cells in medium and in medium containing lipopolysaccharide (LPS), peptidoglycan (PGN) or tumor necrosis factor (TNF). The expression of TLR2, TLR4 and CD14 on the cell surface of neutrophils was assessed by flow cytometry and CXCL8 (IL-8) and soluble CD14 (sCD14) in the supernatant were measured with ELISA.

On neutrophils, the surface expression of TLR2 was diminished following activation with all three pro-inflammatory stimuli and membrane bound (mCD14) and TLR4 expression were increased in co-cultures compared to single cell cultures, irrespective of pro-inflammatory stimulation. A strong correlation between CXCL8 and sCD14 was observed in LPS-stimulated co-cultured cells.

These data showed a down regulation of TLR2 on neutrophils induced by pro-inflammatory stimuli and is strongly suggesting an active cross-talk between A549 cells and blood neutrophils, both in unstimulated cells and following activation with pro-inflammatory stimuli, in vitro.
Cytotoxicity of a Factor Isolated From Human Spleen 2
Authors: Carmen B. Lozzio, Bismarck B. Lozzio
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Cytotoxicity of a Factor Isolated From Human Spleen Get access Carmen B. Lozzio, Carmen B. Lozzio The University of Tennessee Memorial Research Center and Hospital, Knoxville, Tennessee 37920 Search for other works by this author on: Oxford Academic PubMed Google Scholar Bismarck B. Lozzio Bismarck B. Lozzio The University of Tennessee Memorial Research Center and Hospital, Knoxville, Tennessee 37920 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 535–538, https://doi.org/10.1093/jnci/50.2.535 Published: 01 February 1973 Article history Received: 14 July 1972 Accepted: 13 October 1972 Published: 01 February 1973
Endothelial microparticles and progenitor cells in pulmonary arterial hypertension
Authors: Jéssica García-Lucio, Nuria Chamorro, Roberto del Pozo, Olga Tura-Ceide, Nuria Coll, Cristina Bonjoch, Isabel Crespo, Victor I. Peinado, Joan Albert Barberà
Journal: European Respiratory Journal (2014)

Rationale and aim: Endothelial dysfunction is crucial for the development of pulmonary arterial hypertension (PAH). The combined assessment of endothelial microparticles (EMPs) and progenitor cells (PCs) informs about endothelial impairment and endogenous repair capacity. Accordingly, we aimed to assess the number of circulating EMPs and PCs in PAH patients and investigate whether indices of PAH severity correlate with these cytometric measurements.

Methods: Circulating EMPs and PCs were determined in 53 controls (51±12y; 78% females) and 71 PAH patients (53±16y; 77% females; mPAP 46±12 mmHg) all of them under specific theraphy. Total (CD31+CD42b-), apoptotic (CD31+CD42b-AnnexinV+) and activated (CD31+CD42b-CD62E+) EMPs were determined by flow cytometry in platelet poor plasma. Circulating PCs (CD34+CD45+, CD34+CD133+ and c-Kit+ cells) were measured from mononuclear peripheral blood cells by flow cytometry.

Results: Total circulating EMPs were increased in PAH (median, 600 (IQR, 358-871) EMPs/μl) compared with controls (428 (299-633) EMPs/μl) (p<0.05). Apoptotic EMPs were also higher in PAH compared with controls (353 (212-588) vs 261 (195-367) EMPs/μl; p<0.05). No differences were observed in activated EMPs. The number of the three assessed circulating PCs were reduced in PAH compared with controls (p<0.05). No correlation was found between circulating EMPs and PCs numbers and with PAH severity.

Conclusions: Patients with PAH show endothelial impairment and reduced repair capacity, as shown by increased circulating EMPs and reduced PCs.

Supported by FIS PS12/00510. J. Garcia-Lucio is recipient of PFIS grant from ISCIII.
Deletion of Lkb1 in Renal Tubular Epithelial Cells Leads to CKD by Altering Metabolism
Authors: Seung Hyeok Han, Laura Malaga-Dieguez, Frank Chinga, Hyun Mi Kang, Jianling Tao, Kimberly Reidy, Katalin Susztak
Journal: Journal of the American Society of Nephrology (2015)

Renal tubule epithelial cells are high-energy demanding polarized epithelial cells. Liver kinase B1 (LKB1) is a key regulator of polarity, proliferation, and cell metabolism in epithelial cells, but the function of LKB1 in the kidney is unclear. Our unbiased gene expression studies of human control and CKD kidney samples identified lower expression of LKB1 and regulatory proteins in CKD. Mice with distal tubule epithelial-specific Lkb1 deletion (Ksp-Cre/Lkb1flox/flox) exhibited progressive kidney disease characterized by flattened dedifferentiated tubule epithelial cells, interstitial matrix accumulation, and dilated cystic-appearing tubules. Expression of epithelial polarity markers β-catenin and E-cadherin was not altered even at later stages. However, expression levels of key regulators of metabolism, AMP-activated protein kinase (Ampk), peroxisome proliferative activated receptor gamma coactivator 1-α (Ppargc1a), and Ppara, were significantly lower than those in controls and correlated with fibrosis development. Loss of Lkb1 in cultured epithelial cells resulted in energy depletion, apoptosis, less fatty acid oxidation and glycolysis, and a profibrotic phenotype. Treatment of Lkb1-deficient cells with an AMP-activated protein kinase (AMPK) agonist (A769662) or a peroxisome proliferative activated receptor alpha agonist (fenofibrate) restored the fatty oxidation defect and reduced apoptosis. In conclusion, we show that loss of LKB1 in renal tubular epithelial cells has an important role in kidney disease development by influencing intracellular metabolism.
The impact of rosacea on quality of life: effects of demographic and clinical characteristics and various treatment modalities
Authors: B. Aksoy, A. Altaykan-Hapa, D. Egemen, F. Karagöz, N. Atakan
Journal: British Journal of Dermatology (2010)

Background Rosacea has a major psychosocial impact on a patient's life. Objectives To determine the impact of rosacea on patient quality of life, the relationship of quality of life scores to clinical and demographic variables, and the change in quality of life following various treatments. Methods Patients' demographic and clinical characteristics were recorded at their initial examination and their response to treatment and side‐effects were recorded additionally at their follow‐up examination. Rosacea severity was scored for each of four signs from 0 to 3. Patients were requested to complete Dermatology Life Quality Index (DLQI) questionnaires. Results A total of 308 patients took part in this study. Mean ± SD DLQI total score at the initial visit was 6·93 ± 5·18 and was related to patients' age, sex, age at disease onset, subjective symptoms, triggering factors, previous treatments, rosacea severity scores and patients' self‐assessment of ease of living with rosacea. Of these 308 patients, 164 completed the DLQI following treatment. Mean ± SD post‐treatment DLQI score was 4·36 ± 4·82. Post‐treatment scores were also related to sex, type of treatment modality, development of side‐effects, improvement of rosacea, rosacea severity scores and patients' self‐reported ease of living with rosacea. Topical metronidazole, oral tetracycline and oral isotretinoin were observed to reduce signs and symptoms of rosacea and DLQI scores significantly at this repeat examination. Conclusions Rosacea affects patients' lives to a moderate extent, and this can be assessed by using DLQI. DLQI is also sensitive to quality of life changes brought about by treatment of rosacea. As a preliminary result we can say that topical metronidazole, oral tetracycline and oral isotretinoin seem to improve quality of life of patients by improving lesions of rosacea more efficiently than other therapeutic agents.