tbuckley/cabot-search huggingface dataset:
Natural history of development of airflow limitation
Authors: Peter Lange, Jacob Louis Marott, Jørgen Vestbo
Journal: European Respiratory Journal (2014)

COPD develops mainly due to accelerated decline in FEV 1  from early adulthood throughout the middle-age ( fast FEV 1  decline trajectory ). However, low maximal level of FEV 1  in early adulthood may also be important ( low maximally attained FEV 1  trajectory ). In this study we investigated different trajectories leading to the development of airflow limitation.   Design:  Longitudinal study of individuals aged 20 to 40 yrs recruited from the general population in 1976-78 and followed with spirometry for 25 years (n = 1249) and with hospital admissions and mortality for 35 years (n= 2092).   Results:  At the final spirometry, 203 (16.1%) had airflow limitation. They differed significantly from those without airflow limitation with regard to smoking, respiratory symptoms and frequency of acute respiratory infections but not with regard to blood levels of inflammatory biomarkers, early life events like childhood asthma and bronchitis or parental smoking. Among those with airflow limitation, 132 (65%) had an initial FEV 1  g80% of predicted (mean 93%p), whereas 70 (35%) had initial FEV 1  below 80% of predicted (mean 70%p). These two groups differed significantly with regard to mean annual FEV 1  –decline (51 ml/yr (1.4%/yr)  versus  29 ml/yr (1.1%/yr)), but not with regard to other factors except for a higher frequency of respiratory infections in the group with low initial FEV 1 . The incidence of hospital admissions due to respiratory diseases was higher in the group with low initial FEV 1 , but respiratory mortality in this group was lower than in those with high initial FEV 1  and fast FEV 1  –decline.
Overexpression of Rho effector rhotekin promotes cytoskeleton reorganization and cell motility
Authors: Li-Yin Chen, Jeou-Yuan Chen
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5481 

Gastric cancer (GC) is highly prevalent and represents the second leading cause of cancer death worldwide. However, the mechanism underlying the pathogenic development of GC remains largely elusive. We have previously shown that rhotekin , the gene encoding Rho GTPase effector rhotekin (RTKN), is overexpressed in human GC, and its expression is correlated with disease progression (J. Biomed. Sci. 11:661, 2004). In this study, the function of RTKN involved in Rho-mediated cytoskeleton reorganization and cell migration was investigated. RTKN overexpression induced extensive cell surface protrusions with a concomitant decrease of stress fibers and focal adhesions. The fact that N-RTKN mutant which contains the Rho-binding domain-only region, but not the C-terminal regulatory domain-containing mutant, mimicked the full-length RTKN to induce morphological changes and such changes were suppressed when an active form of RhoA was co-expressed suggested that RTKN may interfere with Rho activity in regulating cytoskeleton reorganization. Our findings that the level of phosphorylated myosin light chain was reduced in RTKN-expressing cells confirmed that RTKN overexpression sequesters Rho from Rho/ROCK-mediated signaling pathway. In line with the notion that active Rho GTPase is secluded by overexpressed RTKN, Rac activity was increased in RTKN-overexpressing cells, providing a molecular basis for the presence of membrane ruffles and lamellipodia that were frequently observed in RTKN-expressing cells. Consistent with that cells overexpressing RTKN developed extended branching sprouts, RTKN-expressing cells also displayed increased motility as demonstrated by both time-lapse microscopy and trans-well assay. Based on these observations, we conclude that overexpression of RTKN promotes cytoskeleton reorganization and cell migration, and thus may contribute to tumor metastasis.
Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells
Authors: Anna Bunin, Vanja Sisirak, Hiyaa S. Ghosh, Lucja T. Grajkowska, Z. Esther Hou, Michelle Miron, Cliff Yang, Michele Ceribelli, Noriko Uetani, Laurence Chaperot, Joel Plumas, Wiljan Hendriks, Michel L. Tremblay, Hans Häcker, Louis M. Staudt, Peter H. Green, Govind Bhagat, Boris Reizis
Journal: Immunity (2015)
Long‐term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years
Authors: Marco Merlo, Alberto Pivetta, Bruno Pinamonti, Davide Stolfo, Massimo Zecchin, Giulia Barbati, Andrea Di Lenarda, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2013)
Abstract 2032: Mechanistic and Prognostic Implications of “Burst” Ventricular Arrhythmias and Their Precise Timing after TIMI 3 Reperfusion in Anterior ST Elevation Myocardial Infarction
Authors: Mohamed Majidi, Andrzej S Kosinski, Sana M Al-Khatib, Lilian Smolders, Miguel E Lemmert, Karen S Pieper, Harry J Crijns, Hein J Wellens, Anton P Gorgels, Mitchell W Krucoff
Journal: Circulation (2007)

BACKGROUND Burst ventricular arrhythmias in the presence of TIMI 3 epicardial flow may reflect quality of reperfusion at a cellular level and have previously been shown to correlate with infarct size. This study aims to determine if timing of burst ventricular arrhythmias relative to reperfusion further stratifies the degree of cellular damage. METHODS A total of 229 anterior STEMI pts with final TIMI 3 flow from the EMERALD and CASTEMI primary PCI trials had continuous 24-hr high fidelity 12-lead ECG + Holter monitoring starting prior to PCI. Ventricular ectopy (VPC) burst arrhythmias were defined as a sudden increase over patient-specific baseline VPC rates using statistical outlier detection methodology. The time from reperfusion (defined as attainment of &gt;50% ST recovery and TIMI 3 flow by angiography) to onset of VPC burst arrhythmias was correlated with infarct size by day 7 SPECT imaging. Continuous digital 12-lead ECG + Holter recordings, angiographic films, and SPECT images were analyzed in independent, blinded core labs. RESULTS Reperfusion VPC bursts were seen in 160/229 pts (70%). The presence of reperfusion VPC bursts was significantly associated with a larger infarct size (figure ). Delayed onset reperfusion VPC bursts following epicardial recanalization showed a non-significant trend towards a larger infarct size (figure ). CONCLUSIONS In anterior STEMI pts with successful restoration of TIMI 3 flow, reperfusion burst arrhythmias may be a unique biomarker of cellular injury with delayed burst arrhythmias signaling a worse cellular response to reperfusion. Further characterization of this unique biomarker is important to aid prognostication after reperfusion.
ANKL Is Strongly EBV-Related, Frequent In Chromosome Aberrations and Gene Mutations, LMP2A/LMP1-CDK6-MDM2-CD44-Positive and Might Be Sensitive To L-Asparaginase-Containing Regimen
Authors: Hongsheng Zhou, Yongjian Deng, Changxin Yin, Xiaolei Xue, Xiangzhao Li, Min Dai, Qiang Wang, Na Xu, Yongqiang Wei, Zhi Liu, Dan Xu, Fen Huang, Zhiping Fan, Yu Zhang, Qianli Jiang, Xiaofang Li, Ru Feng, Xiaoli Liu, Jing Sun, Qifa Liu, Bing Xu, Fanyi Meng
Journal: Blood (2013)
Abstract 10470: Nucleosome Positioning is a Mechanism of Global Chromatin Structural Remodeling in Cardiac Hypertrophy
Authors: Haodong Chen, Sarah Franklin, Zugen Chen, Stanley F Nelson, Scherise Mitchell-Jordan, Shuxun Ren, Yibin Wang, Thomas M Vondriska
Journal: Circulation (2011)

The re-expression of fetal cardiac genes during disease requires coordinated chromatin remodeling. Local chromatin packing around the nucleosome protein complex is understood with atomic resolution...
Abstract 1464: Patient-derived tumor xenograft are susceptible to formation of B-cell lymphoma after initial transplantation of human carcinoma to immunodeficient mice
Authors: Gennadiy Bondarenko, Andrey Ugolkov, Piotr Kulesza, Stephen M. Rohan, Oleksii Dubrovskyi, Demirkan Gursel, Jeremy V. Mathews, Thomas V. O'Halloran, Jian-Jun Wei, Andrew P. Mazar
Journal: Cancer Research (2015)

Abstract Patient-derived xenograft (PDX) tumor models have emerged as new and effective models for developing novel anticancer therapies and personalized use of chemotherapeutic drugs. The PDX approach is based on the transplantation of primary or metastatic human tumors into highly immunodeficient NOD scid gamma (NSG) mice followed by continuous propagation of the established engrafment in mice. Clinicians can evaluate the effects of cancer drugs on their patients’ personalized tumor grafts enabling them to select the best treatment for the cancer patient. Here, we report that PDX tumors engrafted in NSG mice are susceptible to formation of B-cell lymphomas. We xenografted primary or metastatic human tumor fragments into NSG mice and found that tumors generated from patients’ samples of breast (1 out 3 cases), colon (2 out of 6 cases), pancreatic (1 out of 3 cases), bladder (1 out of 2 cases) and renal (1 out of 2 cases) cancer were histologically similar to lymphoid neoplasm. Moreover, we found that the first passage (F1) of some breast and pancreatic cancer PDX tumors could grow as a lymphoid neoplasm in one mouse and as an adenocarcinoma in another mouse after initial transplantation of the pieces from the same human tumor graft (F0). Whereas subcutaneous PDX tumors resembling primary human carcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphoid neoplasms were fast growing and formed large metastatic lesions in lymph nodes, liver, lungs and spleen of the mouse. Immunohistochemical staining confirmed that lymphoma cells express human leucocyte common antigen CD45 and B-cell antigen CD19/20. By using Epstein-Barr Virus-encoded RNA (EBER) in situ hybridization, we found that PDX lymphoma cells were EBER-positive. Because B-cells are typically present in any solid malignant tumor, B-cell PDX lymphomas may evolve in a wide range of PDX tumor models. Our results suggest that histolopathological evaluation and lymphoid marker testing should be performed as part of the initial model characterization in order to exclude B-cell lymphomas during the development of PDX tumor model from solid human carcinoma. Citation Format: Gennadiy Bondarenko, Andrey Ugolkov, Piotr Kulesza, Stephen M. Rohan, Oleksii Dubrovskyi, Demirkan Gursel, Jeremy V. Mathews, Thomas V. O'Halloran, Jian-Jun Wei, Andrew P. Mazar. Patient-derived tumor xenograft are susceptible to formation of B-cell lymphoma after initial transplantation of human carcinoma to immunodeficient mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1464. doi:10.1158/1538-7445.AM2015-1464
Adolescent undiagnosed-wheeze; an unrecognised state associated with significant morbidity, tobacco and paracetamol use
Authors: Ramesh Kurukulaaratchy, Abid Raza, Hasan Arshad, Graham Roberts, Bernie Clayton, Jane Grundy
Journal: European Respiratory Journal (2011)

Background:  Adolescent undiagnosed-wheeze is poorly understood.   Aims:  We characterised adolescent undiagnosed-wheeze hypothesising associations with behaviour-linked exposures.   Methods:  The Isle of Wight Birth Cohort (UK) was recruited in 1989 (N=1456) and reviewed at 1, 2, 4, 10 and 18-years. At 18-years, “Asthma” was defined as “ever had asthma” plus either “wheezing in the last 12 months” or “asthma treatment in the last 12 months”, “Undiagnosed-wheeze” as “wheeze in the last 12 months” but “no” to “ever had asthma”, with remaining subjects termed “non-wheezers”. Testing included questionnaires, skin prick tests, spirometry, bronchodilator reversibility and methacholine bronchial challenge.   Results:  Undiagnosed-wheeze accounted for 22% of wheezing at 18-years. This was mostly adolescent onset with similar symptom frequency/severity to asthma. However, undiagnosed-wheezers had higher FEV 1 /FVC ratio (p=0.002) but lower bronchodilator reversibility (p   Conclusions:  Undiagnosed-wheeze occurred in 5% of adolescents. It had many distinctive characteristics from asthma plus strong associations to smoking and paracetamol use that merit further study.
Journal: Journal of Clinical Effectiveness
Authors: A. Liberati
Journal: BMJ (1999)

Eds Gifford Batstone, Mary Edwards Financial Times Healthcare, annual subscription £53 ISSN 1361 5874 Rating: ![Graphic][1]</img>![Graphic][2]</img> The promotion of evidence based practice is, at least in words, high on the agenda for reforming healthcare systems in different parts of the world. As has been recently pointed out by Trish Greenhalgh, “Evidence-based practice is more than the scholarly and rigorous interpretation and use of the best available information. It is a way of thinking.” This is why the current enthusiasm for evidence based practice should be regarded with scepticism if it is divorced from appropriate efforts to change the cultural and social basis on which health care is currently practised. Such a change requires adopting a systematic approach in which … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Abstract 13793: Role of Cardiac Autoantibodies for the Prediction of Recurrence Following Cryoballoon-based Lone Atrial Fibrillation Ablation
Authors: Muhammed U Yalcin, Kadri M Gurses, Duygu Kocyigit, Sacit A Kesikli, Hikmet Yorgun, Mehmet L Sahiner, Ergun B Kaya, Dicle Guc, Mehmet A Oto, Necla Ozer, Kudret Aytemir
Journal: Circulation (2014)

Introduction: Recent evidence have suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). Predictive value of pre-procedural autoantibodies against beta-1 adrenergic receptor (anti-β1-R) and M2-muscarinic acetylcholine receptor (anti-M2-R) for AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of pre-procedural anti-β1-R and anti-M2-R levels for AF recurrence in lone AF patients following cryoballoon-based PVI. METHODS: 80 patients (mean age 54.25±7.7 years; 40% males) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural anti-M2-R and anti-β1-R levels were measured with ELISA. RESULTS: At one-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model including number of antiarrhythmic drugs, early AF recurrence, anti-β1-R levels &gt;159.88 ng/mL, anti-M2-R levels &gt;277.65 ng/mL, AF duration and left atrial volume index; only anti-β1-R levels &gt;159.88 ng/mL (HR: 4.281, p=0.039) and anti-M2-R levels &gt;277.65 ng/mL (HR: 4.313, p=0.030) were found to be independent predictors of late AF recurrence. Anti-β1-R level &gt;159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%. CONCLUSION: Pre-procedural serum anti-β1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in lone AF patients. Detection of pre-procedural anti-β1-R and anti-M2-R levels may serve as a novel method for determination of lone AF patients who may not benefit from cryoballoon-based PVI.
Short communication: Public data mining shows extended linkage disequilibrium around ADAM33
Authors: M. Wjst
Journal: Allergy (2007)

Background: ADAM33 has been described to be the first positional cloned asthma gene. Consecutive association studies have found inconsistent results. At present no functional relevant variation is being known. Objective: Aim of the study was to test if genes in close physical distance could also be responsible for the observed linkage signal. Method: We downloaded three public single‐nucleotide polymorphism (SNP) data sets and tested if linkage disequilibrium extends beyond ADAM33. Results: Linkage disequilibrium extends upstream to a region including GDNF family receptor alpha (GFRA4), attractin (ATRN) and downstream to sialoadhesin (SN) with a peak recombinatory rate at ADAM33 exon S to V. Conclusion: Resequencing of the ADAM33 region including GFRA4, ATRN and SN is expedient.
Abstract 19575: Prevalence of Abnormal T-wave Inversions in European and American Athletes and its Association with Abnormal Echocardiogram
Authors: Dany Jacob, Anthony Magalski, Sanjaya Gupta, Marcia McCoy
Journal: Circulation (2014)

Background: Electrocardiographic (ECG) evaluation is one of the primary tools utilized to screen for increased risk of sudden cardiac death in athletes. Recent study by Sheikh et al. proposed a further refinement to the Seattle criteria, known as the refined criteria. The objective of this study was to compare the prevalence of abnormal T-wave inversions (TWI) using the refined criteria in an American and European cohort and to evaluate the association of abnormal TWI with abnormal echocardiogram in the American cohort. Methods: Collegiate athletes at a single university underwent prospective collection of medical history, physical examination, 12-lead ECG, and 2-dimensional echocardiography from 2004 to 2013. ECG analysis of 1755 athletes was performed to asses for TWI as outlined by the refined criteria. Subjects were further classified by race, gender and area of TWI on ECG and compared to 5505 European athletes. Results: Of the 1755 American athletes, 49% were males and 1.3% had abnormal TWI. European cohort included 79% males and 3.9% abnormal TWI. Higher prevalence of abnormal TWI were noted in black athletes compared to white athletes in the American cohort (2% and 1.1% respectively). European counterpart had similar findings with 6% of black athletes and 3.3% of white athletes having abnormal TWI. In the American cohort abnormal TWI were distributed unequally within the anterior, lateral and antero-lateral leads (30%, 4% and 65% respectively). Only one American athlete (3.5%) with abnormal TWI had an abnormal echocardiogram. Conclusion: Incorporation of ECG assessment has been proposed as part of the preparticipation screening of athletes in United States. Comparison of American and European athletes showed a 67% lower prevalence of abnormal TWI in the American athletes. Only one American athlete with abnormal TWI had an abnormal echocardiogram. We conclude that abnormal TWI alone has a weak association with an abnormal echocardiogram in American college athletes.
Progranulin Overproduction Due to Fli‐1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis
Authors: Yohei Ichimura, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono
Journal: Arthritis & Rheumatology (2015)

Objective Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long‐standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Methods Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription–polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene‐silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme‐linked immunosorbent assay. Results Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli‐1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli‐1 +/− mice and bleomycin‐treated wild‐type mice exhibited up‐regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C‐reactive protein level. Conclusion Progranulin overproduction due to Fli‐1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc.
Carriage of Rickettsia spp., Coxiella burnetii and Anaplasma spp. by endemic and migratory wild birds and their ectoparasites in Cyprus
Authors: I. Ioannou, D. Chochlakis, N. Kasinis, P. Anayiotos, A. Lyssandrou, B. Papadopoulos, Y. Tselentis, A. Psaroulaki
Journal: Clinical Microbiology and Infection (2009)
A memorable patient: A regular pain
Authors: C. Lanigan
Journal: BMJ (2001)

Ice cream and apple juice. They should not make a healthy 7 year old cry, should they? But she screamed. She had had an adenotonsillectomy that morning under the care of a senior colleague. Pethidine 25 mg had been given over 90 minutes ago. She screamed swallowing the “prn” paracetamol (500 mg dissolved in apple …
Abstract 1628: Direct anti-cancer effects of zoledronic acid on human cancer cell
Authors: Pengfei Jiang, Rajesh Mukthavavam, Natsuko Nomura, Sandeep C. Pingle, Santosh Kesari
Journal: Cancer Research (2014)

Abstract Zoledronic Acid (ZA) is a potent nitrogen-containing bisphosphonates (NBP) has been extensively used to limit bone turnover in a various diseases including tumors. Recently, clinical trails of Zoledronic Acid demonstrated direct anti-cancer effects as well as the known skeletal-related events. We investigated the effect of 4 NBPs on human tumor cells proliferation and found ZA is most potent for GBM cell, breast cell and GBM patients' stem-cell-like cells. ZA also effectively inhibited GBM tumor growth in mouse model. ZA stimulated strong autophagy but not apoptotic signals in all tested cells. One intermediate product of cholesterols synthesis pathway—-geranylgeranyl diphosphate (GGPP) rescued cell from the cytotoxicity of ZA. Knock-down RABGGTA, which encoded a subunit of the Rab geranylgeranyltransferase proteins, induced a similar effect as Zoledronic Acid in cancer cell lines. These data suggested great potential for Zoledronic Acid against human cancer. Note: This abstract was not presented at the meeting. Citation Format: Pengfei Jiang, Rajesh Mukthavavam, Natsuko Nomura, Sandeep C. Pingle, Santosh Kesari. Direct anti-cancer effects of zoledronic acid on human cancer cell. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1628. doi:10.1158/1538-7445.AM2014-1628