tbuckley/cabot-search huggingface dataset:
Summary of the British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults
Authors: I A Du Rand, J Blaikley, R Booton, N Chaudhuri, V Gupta, S Khalid, S Mandal, J Martin, J Mills, N Navani, N M Rahman, J M Wrightson, M Munavvar
Journal: Thorax (2013)

Flexible bronchoscopy is an essential, established and expanding tool in respiratory medicine. Its practice, however, needs to be safe, effective and for the right indications to maximise clinical utility. This guideline is based on the best available evidence and is a revised update of the British Thoracic Society guideline on diagnostic flexible bronchoscopy.
Critical Role of Peroxisome Proliferator-Activated Receptor γ on Anoikis and Invasion of Squamous Cell Carcinoma
Authors: Tomotake Masuda, Koichiro Wada, Atsushi Nakajima, Masaya Okura, Chiho Kudo, Takashi Kadowaki, Mikihiko Kogo, Yoshinori Kamisaki
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) plays a important role in various physiological functions. We examined whether PPARγ is expressed in primary squamous cell carcinoma and lymph node metastasis and whether PPARγ is a potential target for tumor therapy. Experimental Design and Results: A high-level expression of PPARγ was observed in tumor cells of human primary squamous cell carcinoma, lymph node metastasis, and squamous cell carcinoma cell lines. Treatment with PPARγ-specific antagonists, but not agonists, caused apoptotic cell death on squamous cell carcinoma cell lines in a concentration-dependent manner. Small interfering RNA for PPARγ also inhibited cell adhesion and growth of squamous cell carcinomas. The phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with PPARγ antagonists, and resulted in decreases in phosphorylation of Erk and mitogen-activated protein kinase. Furthermore, PPARγ antagonists decreased the adhesion of squamous cell carcinomas into fibronectin-coated plates, indicating the inhibition of interaction between squamous cell carcinomas and fibronectin. Expression of integrin α5, a counter adhesion molecule for fibronectin, was inhibited by the treatment with PPARγ antagonists. These results indicate that the decrease in integrin α5 and following inhibition of cell adhesion may cause the inhibition of FAK signaling pathways. PPARγ antagonists also strongly inhibited invasion of squamous cell carcinoma via down-regulation of CD151 expression. Conclusions: The cell death caused by the PPARγ antagonists was a result of direct interference with cell adhesion “anoikis” involving intracellular FAK signaling pathways. These results imply a potentially important and novel role for the inhibition of PPARγ function via the use of specific antagonists in the treatment of squamous cell carcinoma and the prevention of tumor invasion and metastasis.
Biomarkers of Acute Kidney Injury
Authors: Vishal S. Vaidya, Michael A. Ferguson, Joseph V. Bonventre
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside.
Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival
Authors: Richard Fux, Matthias Schwab, Klaus-Peter Thon, Christoph H. Gleiter, Peter Fritz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and adenoma tissue seems to be higher than in normal mucosa. However, data about the relation between COX-2 expression and patient survival are inconclusive as yet. Therefore, we studied COX-2 expression in surgery tissue and survival time in a cohort of 747 colorectal cancer patients. Experimental Design: Surgical specimens of primary colorectal cancer from 747 individuals were immunostained for COX-2 and evaluated under a transmission light microscope. COX-2 expression was scored according to intensity and extent of staining, resulting in the COX-2 immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were analyzed for a relation between COX-2 expression and patient survival. Results: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2. The survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8% (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In the multivariable analysis, only node and metastasis were significantly related to overall patient survival. Similar results were obtained when stage IV and rectal cancer patients were excluded from the analysis. Conclusions: COX-2 expression in tumor epithelial cells does not seem to be related to survival of colorectal cancer patients. Besides COX-2, there are several targets, such as the peroxisome proliferator–activated receptors, that are involved in carcinogenesis and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are needed to determine their prognostic relevance.
Myocardial Gene Transfer and Overexpression of β <sub>2</sub> -Adrenergic Receptors Potentiates the Functional Recovery of Unloaded Failing Hearts
Authors: Hendrik T. Tevaearai, Andrea D. Eckhart, G. Brant Walton, Janelle R. Keys, Katrina Wilson, Walter J. Koch
Journal: Circulation (2002)

Background — Mechanical assistance of the failing left ventricle (LV) can lead to functional recovery after a period of unloading, including restoration of β-adrenergic receptor (βAR) inotropic reserve. We tested whether prolonged LV unloading of failing rabbit hearts by use of a heterotopic transplantation technique could lead to recovery and whether adenoviral gene transfer of a β 2 AR transgene (Adv-β 2 AR) could alter this process. Methods and Results — Heart failure was induced by coronary artery ligation in adult New Zealand White rabbits. After 4 weeks, failing hearts were heterotopically transplanted into recipient rabbits, allowing normal coronary perfusion but complete LV unloading. We also placed an LV latex balloon for remote access and in vivo physiological analysis. We found that there was reversal of signaling and functional abnormalities after 30 days of unloading. In another set of failing hearts, we randomly delivered, at the time of transplantation, either 2×10 11 viral particles of Adv-β 2 AR or saline via the coronary arteries. Sham-operated animals with nonfailing hearts served as controls. After 5 days of unloading, in vivo LV contractility (LV dP/dt max ) and relaxation (LV dP/dt min ) were significantly decreased in saline-treated failing hearts compared with control nonfailing hearts ( P &lt;0.05). In failing hearts treated with Adv-β 2 AR, however, LV dP/dt max and LV dP/dt min were improved in response to higher preloads ( P &lt;0.05) and βAR stimulation ( P &lt;0.01). Conclusions — Heterotopic transplantation in the rabbit does allow recovery of the failing heart, and β 2 AR overexpression acutely enhances this functional improvement. Accordingly, genetic manipulation of βAR signaling may represent a novel molecular adjunct to mechanical assistance to facilitate functional myocardial recovery.
Effect of Automated Bio-Behavioral Feedback on the Control of Type 1 Diabetes
Authors: Boris P. Kovatchev, Pamela Mendosa, Stacey Anderson, Jeffrey S. Hawley, Lee M. Ritterband, Linda Gonder-Frederick
Journal: Diabetes Care (2011)

To test the effect of an automated system providing real-time estimates of HbA(1c), glucose variability, and risk for hypoglycemia.For 1 year, 120 adults with type 1 diabetes (69 female/51 male, age = 39.1 [14.3] years, duration of diabetes 20.3 [12.9] years, HbA(1c) = 8.0 [1.5]), performed self-monitoring of blood glucose (SMBG) and received feedback at three increasingly complex levels, each continuing for 3 months: level 1--routine SMBG; level 2--adding estimated HbA(1c), hypoglycemia risk, and glucose variability; and level 3--adding estimates of symptoms potentially related to hypoglycemia. The subjects were randomized to feedback sequences of either levels 1-2-3 or levels 2-3-1. HbA(1c), symptomatic hypoglycemia, and blood glucose awareness were evaluated at baseline and at the end of each level.For all subjects, HbA(1c) was reduced from 8.0 to 7.6 from baseline to the end of study (P = 0.001). This effect was confined to subjects with baseline HbA(1c) >8.0 (from 9.3 to 8.5, P < 0.001). Incidence of symptomatic moderate/severe hypoglycemia was reduced from 5.72 to 3.74 episodes/person/month (P = 0.019), more prominently for subjects with a history of severe hypoglycemia (from 7.20 to 4.00 episodes, P = 0.008) and for those who were hypoglycemia unaware (from 6.44 to 3.71 episodes, P = 0.045). The subjects' ratings of the feedback were positive, with up to 89% approval of the provided features.Feedback of SMBG data and summary SMBG-based measures resulted in improvement in average glycemic control and reduction in moderate/severe hypoglycemia. These effects were most prominent in subjects who were at highest risk at the baseline.
ANTITHROMBOTIC POTENCY OF TICAGRELOR VERSUS CLOPIDOGREL, WHEN ADMINISTERED WITH BIVALIRUDIN
Authors: Mohammad Urooj Zafar, David Vorchheimer, Mita P. Tewar, Chiara Giannarelli, Matteo Crippa, Samantha Sartori, David Rodriguez, Christina M. Gestal, Usman Baber, Juan Badimon
Journal: Journal of the American College of Cardiology (2014)
Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin
Authors: Bernard Tardy, Thomas Lecompte, Françoise Boelhen, Brigitte Tardy-Poncet, Ismaïl Elalamy, Pierre Morange, Yves Gruel, Martine Wolf, Dominique François, Evelyne Racadot, Philippe Camarasa, Marie Thérèse Blouch, Françoise Nguyen, Sylvie Doubine, Fabienne Dutrillaux, Martine Alhenc-Gelas, Isabelle Martin-Toutain, Anne Bauters, Patrick Ffrench, Emmanuel de Maistre, Lélia Grunebaum, Christine Mouton, Marie G. Huisse, Michèle Gouault-Heilmann, Veronique Lucke
Journal: Blood (2006)
Interaction of bretylium tosylate with rat cardiac muscarinic receptors. Possible pharmacological relevance to antiarrhythmic action.
Authors: G Schreiber, M Friedman, M Sokolovsky
Journal: Circulation Research (1984)

The interaction of the antifibrillatory antiarrhythmic drug, bretylium tosylate, with the muscarinic receptor in tissue homogenates from regions of rat brain and heart was investigated. Competition-binding experiments were carried out with the highly specific tritiated antagonist N-methyl-4-piperidyl benzilate. Bretylium tosylate competitively displaced the labeled antagonist from the muscarinic receptor. The binding of the drug to the two brain preparations was found to be best fitted by a one-site model in each case. On the other hand, in the case of both heart preparations, a two-site model yielded a significantly better fit for the binding data than that given by a single-site model. The low affinity-binding constants in the atrium and the ventricle were similar (approximately 10 microM) to those in the brain regions examined, namely, the cortex and the medullapons. Sites with relatively higher affinity for the drug were detected in the heart only, with equilibrium-binding constants of 0.24 +/- 0.12 microM and 0.97 +/- 0.27 microM for the atrium and the ventricle, respectively. The drug also exerted anti-acetylcholine activity (K1 = 14 +/- 2 microM) measured physiologically in the guinea pig atrium, which correlated well with the concentration of the drug observed to be efficacious clinically (approximately 10 microM).
Trastuzumab-Mediated Antibody-Dependent Cellular Cytotoxicity against Esophageal Squamous Cell Carcinoma
Authors: Kousaku Mimura, Koji Kono, Mitsuhiko Hanawa, Mirei Kanzaki, Atsuhito Nakao, Akishi Ooi, Hideki Fujii
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2–expressing esophageal SCC cell lines. Experimental Design: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. Results: Trastuzumab induced ADCC against HER-2–expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-β–producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-β. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2–expressing esophageal SCC. Conclusion: HER-2–expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.
Perinatal Environmental Exposures Affect Mammary Development, Function, and Cancer Risk in Adulthood
Authors: Suzanne E. Fenton, Casey Reed, Retha R. Newbold
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Puberty is an important transition that enables reproduction of mammalian species. Precocious puberty, specifically early thelarche (the appearance of breast "buds"), in girls of multiple ethnic backgrounds is a major health problem in the United States and other countries. The cause for a continued decrease in the age of breast development in girls is unknown, but environmental factors likely play a major role. Laboratory and epidemiological studies have identified several individual environmental factors that affect breast development, but further progress is needed. Current research needs include increased attention to and recording of prenatal and neonatal environmental exposures, testing of marketed chemicals for effects on the mammary gland, and understanding of the mammary gland-specific mechanisms that are altered by chemicals. Such research is required to halt the increasing trend toward puberty at earlier ages.
Haplotypic analysis of the TNF locus by association efficiency and entropy
Authors: Hans Ackerman, Stanley Usen, Richard Mott, Anna Richardson, Fatoumatta Sisay-Joof, Pauline Katundu, Terrie Taylor, Ryk Ward, Malcolm Molyneux, Margaret Pinder, Dominic P Kwiatkowski
Journal: Genome biology (2003)

Abstract Background To understand the causal basis of TNF associations with disease, it is necessary to understand the haplotypic structure of this locus. We genotyped 12 single-nucleotide polymorphisms (SNPs) distributed over 4.3 kilobases in 296 healthy, unrelated Gambian and Malawian adults. We generated 592 high-quality haplotypes by integrating family- and population-based reconstruction methods. Results We found 32 different haplotypes, of which 13 were shared between the two populations. Both populations were haplotypically diverse (gene diversity = 0.80, Gambia; 0.85, Malawi) and significantly differentiated ( p &lt; 10 -5 by exact test). More than a quarter of marker pairs showed evidence of intragenic recombination (29% Gambia; 27% Malawi). We applied two new methods of analyzing haplotypic data: association efficiency analysis (AEA), which describes the ability of each SNP to detect every other SNP in a case-control scenario; and the entropy maximization method (EMM), which selects the subset of SNPs that most effectively dissects the underlying haplotypic structure. AEA revealed that many SNPs in TNF are poor markers of each other. The EMM showed that 8 of 12 SNPs (Gambia) and 7 of 12 SNPs (Malawi) are required to describe 95% of the haplotypic diversity. Conclusions The TNF locus in the Gambian and Malawi sample is haplotypically diverse and has a rich history of intragenic recombination. As a consequence, a large proportion of TNF SNPs must be typed to detect a disease-modifying SNP at this locus. The most informative subset of SNPs to genotype differs between the two populations.
A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97.
Authors: K S Furukawa, K Furukawa, F X Real, L J Old, K O Lloyd
Journal: The Journal of Experimental Medicine (1989)

Analysis of antibodies present in the serum of melanoma patient FD has shown that they detect a unique tumor epitope present only on the autologous melanoma cell line SK-MEL-131. Previous results had shown that the unique FD epitope is carried on a common glycoprotein of approximately 90 kD, widely expressed on melanoma and a few other cell types. We now show by sequential radioimmunoprecipitation and partial amino acid sequencing that this common molecule is a previously recognized melanoma antigen, originally identified by mouse mAbs, designated gp95 or p97 (and also known as melanotransferrin). Thus, FD is the first of the class I (unique) melanoma antigens that has been characterized and related to a known cell surface molecule.
Genetic aspects in sarcoidosis
Authors: M. Luisetti, A. Beretta, L Casali
Journal: European Respiratory Journal (2000)

Sarcoidosis is an immune-mediated, multiorgan, granulomatous disorder thought to be triggered by an intricate combination of environmental and genetic factors. Two robust lines of evidence support the hypothesis of a genetic component in the pathogenesis of sarcoidosis: racial variation in its epidemiology and familial clustering of cases. The relationship between epidemiology and environmental factors affecting variations in sarcoidosis incidence/prevalence and presentation are reviewed, as well as strategies to be pursued in the search for susceptibility genes for the disorder. Pathogenic processes leading to sarcoid granuloma formation and maintenance have prompted investigators interested in the genetics of sarcoidosis to focus mainly on major histocompatibility complex genes, and indeed a remarkable amount of data has been accumulated during the last two decades. Whilst in contrast with some autoimmune disorders a clear association between human leukocyte antigen (HLA) and sarcoidosis is still a controversial issue, there is, however, a general agreement that some HLA genes are related to phenotypic variations of the disease. Some genetic investigators have focused on T-cell receptor genes, immunoglobulin genes, angiotensin converting enzyme gene, chemokine genes and others. From a review of studies performed in different racial and ethnic groups, a reasonable suggestion arises that genetic factors are the major determinant in the racial variations in the epidemiology of the disorder. This assumption is, however, so far limited by lack of studies considering both genetic and environmental factors simultaneously.
Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)
Authors: John K Ramage, A Ahmed, J Ardill, N Bax, D J Breen, M E Caplin, P Corrie, J Davar, A H Davies, V Lewington, T Meyer, J Newell-Price, G Poston, N Reed, A Rockall, W Steward, R V Thakker, C Toubanakis, J Valle, C Verbeke, A B Grossman
Journal: Gut (2011)

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.
Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells
Authors: Matthew J. Frontini, Caroline O'Neil, Cynthia Sawyez, Bosco M.C. Chan, Murray W. Huff, J. Geoffrey Pickering
Journal: Circulation Research (2009)

A vital role of vascular smooth muscle cells (SMCs) is to stabilize the artery wall by elaborating fibrils of type I collagen. This is especially important in atherosclerotic lesions. However, SMCs in these lesions can be laden with lipids and the impact of this modification on collagen fibril formation is unknown. To address this, we converted human vascular SMCs to a foam cell state by incubating them with either LDL or VLDL. Biochemical markers of a SMC phenotype were preserved. However, microscopic tracking revealed a profound perturbation in the ability of the cells to assemble collagen fibrils, reducing assembly by up to 79%. This dysfunction was mirrored by an inability of smooth muscle foam cells to assemble fibronectin. Lipid-loaded SMCs did not display a generalized defect in the actin cytoskeleton and the formation of vinculin-containing focal adhesion complexes was preserved. However, lipid-loaded SMCs were unable to assemble fibrillar adhesion complexes and clustering of tensin and alpha5beta1 integrin was disordered. Moreover, phosphorylation of tensin, required for fibrillar adhesion complex formation, was suppressed by up to 57%, with a concomitant decrease in activation of Src and FAK and restriction of activated Src to the cell edges. Forced activation of Src-FAK signaling in lipid-engorged SMCs rescued both fibrillar adhesion formation and fibrillogenesis. We conclude that lipid accumulation by SMCs disables the machinery for collagen and fibronectin assembly. This previously unknown relationship between atherogenic lipids and integrin-based signaling could underlie plaque vulnerability.