tbuckley/cabot-search huggingface dataset:
Anti-inflammatory properties of a prostaglandin antagonist, a corticosteroid and indomethacin in experimental contact dermatitis
Authors: NICHOLAS J. LOWE, FRANK VIRGADAMO, RICHARD B. STOUGHTON
Journal: British Journal of Dermatology (1977)

The topical effects of N0164 (a phenyl phosphonate derivative which is a partially selective antagonist of prostaglandin E2), indomethacin and triamcinolone acetonide have been shown to reduce the erythema and ear weight gain from inflammation induced by experimental contact allergic eczema. Oxazolone sensitized Swiss Webster mice were used, ear erythema and ear weights being used as a measure of the anti‐inflammatory response to the drugs. N0164 was also shown to have systemic anti‐inflammatory activity after intraperitoneal injection.
Hemodynamics and left ventricular mass regression following implantation of the Toronto SPV® valve
Authors: D.S. Bach, T. David, M. Yacoub, J. Pepper, B. Goldman, J. Wood, E. Verrier, M. Petracek, V. Aldrete, M. Rosenbloom, S. Goldman, H. Azar, W. Cheng, H. Rakowski
Journal: Journal of the American College of Cardiology (1998)
Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial
Authors: L. Bjermer
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. <b>Design and setting</b> A 52 week, two period, double blind, multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol. <b>Participants</b> Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for ≥ 1 year, a baseline forced expiratory volume in one second (FEV 1) value 50-90% predicted, and a β agonist improvement of ≥ 12% in FEV 1. <b>Main outcome measures</b> The primary end point was the percentage of patients with at least one asthma exacerbation. <b>Results</b> 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19.1% in the group receiving salmeterol and fluticasone; the difference was 1% (95% confidence interval -3.1% to 5.0%). With a risk ratio (montelukast-fluticasone/salmeterol-fluticasone) of 1.05 (0.86 to 1.29), treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone. Salmeterol and fluticasone significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone (P ≤ 0.001), whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups. Montelukast and fluticasone significantly (P = 0.011) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone. Both treatments were generally well tolerated. <b>Conclusion</b> The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol.
Neural Correlates of Stress-Induced and Cue-Induced Drug Craving: Influences of Sex and Cocaine Dependence
Authors: Marc N. Potenza, Kwang-ik Adam Hong, Cheryl M. Lacadie, Robert K. Fulbright, Keri L. Tuit, Rajita Sinha
Journal: American Journal of Psychiatry (2012)

Activity in brain regions linked to substance abuse was greater in cocaine-dependent women than in non-substance-abusing women after stress but not after exposure to drug-related cues. For men with cocaine dependence, the pattern was reversed: more widespread hyperactivation after drug-related cues than after stress. Clinical possibilities include targeted treatment for cocaine dependence: stress reduction for women and 12-step or cognitive-behavioral approaches for men.
A High Incidence of Selection on Physiologically Important Genes in the Three-Spined Stickleback, Gasterosteus aculeatus
Authors: Y. Shimada, T. Shikano, J. Merila
Journal: Molecular Biology and Evolution (2010)

Genome scan approaches to detect footprints of directional selection in the genomes of wild animal and plant populations have become popular tools to study local adaptation and speciation at the molecular level. Most studies thus far have used random molecular markers and found footprints of directional selection at, on average, 5% (range: 1–15%) of the examined loci. We focused on physiologically important genes that exhibit transcriptional responses to specific environmental or developmental conditions and assessed if these genes have been subject to directional selection and are responsible for local adaptation in the three-spined stickleback (Gasterosteus aculeatus). Using microsatellite markers located within or closely linked to (<6 kb) target genes, we investigated footprints of directional selection for 157 genes with known physiological functions in three marine and six freshwater populations. A high incidence (16.6%) of footprints of directional selection for these genes was revealed by four different outlier tests. In a subset of four populations screened with both physiologically important and random genes, footprints of directional selection were more frequent in physiologically important genes (13.4%) as compared with random genes (2.4%). In general, our findings indicate strong selective pressures on physiologically important genes, suggesting that these genes have significant functions in evolutionary adaptation to environmental heterogeneity.
Systems Pathology Approach for the Prediction of Prostate Cancer Progression After Radical Prostatectomy
Authors: Michael J. Donovan, Stefan Hamann, Mark Clayton, Faisal M. Khan, Marina Sapir, Valentina Bayer-Zubek, Gerardo Fernandez, Ricardo Mesa-Tejada, Mikhail Teverovskiy, Victor E. Reuter, Peter T. Scardino, Carlos Cordon-Cardo
Journal: Journal of Clinical Oncology (2008)

Purpose For patients with prostate cancer treated by radical prostatectomy, no current personalized tools predict clinical failure (CF; metastasis and/or androgen-independent disease). We developed such a tool through integration of clinicopathologic data with image analysis and quantitative immunofluorescence of prostate cancer tissue. Patients and Methods A prospectively designed algorithm was applied retrospectively to a cohort of 758 patients with clinically localized or locally advanced prostate cancer. A model predicting distant metastasis and/or androgen-independent recurrence was derived from features selected through supervised multivariate learning. Performance of the model was estimated using the concordance index (CI). Results We developed a predictive model using a training set of 373 patients with 33 CF events. The model includes androgen receptor (AR) levels, dominant prostatectomy Gleason grade, lymph node involvement, and three quantitative characteristics from hematoxylin and eosin staining of prostate tissue. The model had a CI of 0.92, sensitivity of 90%, and specificity of 91% for predicting CF within 5 years after prostatectomy. Model validation on an independent cohort of 385 patients with 29 CF events yielded a CI of 0.84, sensitivity of 84%, and specificity of 85%. High levels of AR predicted shorter time to castrate prostate-specific antigen increase after androgen deprivation therapy (ADT). Conclusion The integration of clinicopathologic variables with imaging and biomarker data (systems pathology) resulted in a highly accurate tool for predicting CF within 5 years after prostatectomy. The data support a role for AR signaling in clinical progression and duration of response to ADT.
Osteopontin Expression in Fetal and Mature Human Kidney
Authors: KELLY L. HUDKINS, CECILIA M. GIACHELLI, None YAN CUI, WILLIAM G. COUSER, RICHARD J. JOHNSON, CHARLES E. ALPERS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Osteopontin is a secreted phosphoprotein that is expressed by normal kidney, and has been associated with a number of functions including cell adhesion, migration, signaling, and biomineralization. Although there is a vast literature detailing osteopontin localization in various rodent models of both development and disease, this article presents the first comprehensive description of osteopontin localization in human kidney. In this study, immunohistochemistry, immunoelectron microscopy, in situ hybridization, and Northern blotting are used to analyze osteopontin protein and mRNA expression in human fetal and normal mature renal tissue. Osteopontin is expressed in the human embryonic renal tubular epithelium beginning on approximately day 75 to 80 of gestation. In the fetal kidney, osteopontin can also be seen occasionally expressed in the ureteric buds and in some interstitial cells. As localized at the protein and mRNA level, the tubular expression of osteopontin increases with increasing gestational age and persists into adulthood. In the normal adult kidney, osteopontin is localized primarily to the distal nephron and is strongly expressed by the thick ascending limb of the loops of Henle. Osteopontin expression can also be observed in some collecting duct epithelium. In cases that exhibit foci of interstitial fibrosis and an associated influx of interstitial macrophages, osteopontin expression is significantly upregulated in all tubular segments, including proximal tubules.
Non-alcoholic fatty liver disease in patients with HCV genotype 4
Authors: A El-Zayadi, M Attia, E M F Barakat, K Zalata, A Saeid, H Hamdy, A El-Nakeeb
Journal: Gut (2007)

with persistently low platelet counts for many months.Moreover, the second episode of thrombocytopenia 1 week after the adalimumab infusion is consistent with the typical picture of onset of thrombocytopenia after rechallenge.Monoclonal antibodies against TNFa are used for the treatment of patients with autoimmune disorders who have had an inadequate response to conventional treatment. 2 3In patients with Crohn's disease, TNFa is a key proinflammatory cytokine and infliximab is an established treatment for patients resistant to conventional therapy.Infliximab is a chimeric monoclonal antibody because it is manufactured with mouse binding VK and VH domains and human constant Fc domains.In contrast, adalimumab is constructed from a fully human monoclonal antibody but shares the same Fc domain with infliximab.Both antibodies bind to the same region of TNFa, preventing it from activating TNF receptors and inducing downregulation of inflammatory reactions associated with autoimmune diseases.4][5][6] Although the mechanisms underlying them are unknown, autoantibodies produced during apoptosis could play a role in the pathogenesis of this phenomenon.We hypothesise the possible contribution of such a mechanism, or even the involvement of antibodies against infliximab that later recognise the Fc domain of adalimumab.The temporal relation between the initiation of anti-TNFa monoclonal antibodies and the onset of thrombocytopenia, in addition to the effects of the discontinuation and resumption of anti-TNFa monoclonal antibodies, are definite evidence of anti-TNFa-induced thrombocytopenia in our case.In patients with a suspicion of immune side effects after infliximab treatment, the use of other antibodies against TNFa should therefore be discouraged.
Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis
Authors: J. B. van Woensel, T. F. Wolfs, W. M. van Aalderen, P. L. Brand, J. L. Kimpen
Journal: Thorax (1997)

BACKGROUND: Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. METHODS: A randomised double blind trial was conducted in children up to two years of age admitted to hospital with RSV bronchiolitis to compare prednisolone (1 mg/ kg/day orally for seven days) with placebo. Variables used for the efficacy analysis were a daily symptom score and the length of time in hospital in the non-ventilated patients, and the duration of mechanical ventilation and the length of time in hospital in the ventilated patients. RESULTS: Fifty four patients were included in the trial, 40 of whom were non-ventilated (20 in each group) and 14 were ventilated (seven in each group). During the first three days of treatment the symptom score decreased significantly faster in the prednisolone group than in the placebo group (mean (SE) decrease -1.2 (0.2) points/day versus -0.6 (0.2) points/day; mean (95% confidence interval (CI)) for difference = -0.6 (-0.1 to -1.2); p = 0.02). The mean duration of hospital stay of all 40 non-ventilated patients was not significantly different between the two groups. In the ventilated patients the duration of mechanical ventilation was not significantly different, but the length of time in hospital was six days shorter in the prednisolone group than in the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI) difference = 7.0 (1.8 to 10.2) days; p &lt; 0.01). CONCLUSIONS: These results suggest that prednisolone may be effective in accelerating the clinical recovery of children admitted to hospital with RSV bronchiolitis.
Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress
Authors: Vishnu Chintalgattu, Di Ai, Robert R. Langley, Jianhu Zhang, James A. Bankson, Tiffany L. Shih, Anilkumar K. Reddy, Kevin R. Coombes, Iyad N. Daher, Shibani Pati, Shalin S. Patel, Jennifer S. Pocius, George E. Taffet, L. Maximillian Buja, Mark L. Entman, Aarif Y. Khakoo
Journal: Journal of Clinical Investigation (2010)

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-beta signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-beta was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-beta is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.
Verification and Unmasking of Widely Used Human Esophageal Adenocarcinoma Cell Lines
Authors: Jurjen J. Boonstra, Ronald van Marion, David G. Beer, Lin Lin, Paula Chaves, Catarina Ribeiro, A. Dias Pereira, Lúcia Roque, S. Jane Darnton, Nasser K. Altorki, David S. Schrump, David S. Klimstra, Laura H. Tang, James R. Eshleman, Hector Alvarez, Yutaka Shimada, Herman van Dekken, Hugo W. Tilanus, Winand N. M. Dinjens
Journal: JNCI Journal of the National Cancer Institute (2010)

For decades, hundreds of different human tumor type–specific cell lines have been used in experimental cancer research as models for their respective tumors. The veracity of experimental results for a specific tumor type relies on the correct derivation of the cell line. In a worldwide effort, we verified the authenticity of all available esophageal adenocarcinoma (EAC) cell lines. We proved that the frequently used cell lines SEG-1 and BIC-1 and the SK-GT-5 cell line are in fact cell lines from other tumor types. Experimental results based on these contaminated cell lines have led to ongoing clinical trials recruiting EAC patients, to more than 100 scientific publications, and to at least three National Institutes of Health cancer research grants and 11 US patents, which emphasizes the importance of our findings. Widespread use of contaminated cell lines threatens the development of treatment strategies for EAC.
Surgery for lung cancer
Authors: S W FOUNTAIN
Journal: Thorax (1998)

Although the profile of lung cancer has been raised recently, specifically1 and in the context of the general re-organisation of cancer services,2 concerns remain about the process of management3 and the delays in treatment which result.4 There is virtually uniform acceptance of the fact that, for patients with non-small cell lung cancer (NSCLC) at least, the best chance of cure is surgery5 and that successful surgery depends on diagnosis at an early stage in the disease process.6 Some evidence exists to suggest that, in Europe7 and the United States,8 almost 30% of patients with NSCLC undergo surgery. Although isolated reports from the UK quote operability rates of 20%,9 the overall resection rate is essentially static10 at 10% or less of the total number of new cases reported each year.11 Case selection and long term survival are, however, very similar in this and other countries.12 While it is …
Characterization of a Zinc-Finger Protein and Its Association With Apoptosis in Prostate Cancer Cells
Authors: G. T. G. Chang
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The transition from androgen-dependent to androgen-independent prostate cancer is not fully understood but appears to involve multiple genetic changes. We have identified a gene, GC79, that is more highly expressed in androgen-dependent LNCaP-FGC human prostate cancer cells than in androgen-independent LNCaP-LNO human prostate cancer cells. Physiologic levels (0.1 nM) of androgens repress expression of GC79 messenger RNA (mRNA) in LNCaP-FGC cells. To determine the role of GC79, we cloned its complementary DNA (cDNA) and functionally characterized its product. Methods: The differentially expressed GC79 gene was cloned from human prostate cDNA libraries, sequenced, and transfected into mammalian cells to study its function. Expression of GC79 was analyzed in various adult and fetal human tissues and in prostate glands of castrated rats. The association of GC79 expression and apoptosis was investigated in COS-1 and LNCaP cells transfected with GC79 cDNA. All statistical tests are two-sided. Results: Sequence analysis indicates that GC79 encodes a large, complex, multitype zinc-finger protein, containing nine C2H2-type zinc-finger domains, a cysteine-rich region, and a GATA C4-type zinc-finger domain. Castration-induced androgen withdrawal increased the expression of GC79 mRNA in the regressing rat ventral prostate, suggesting that the expression of GC79 mRNA is associated with the process of apoptotic cell death in the rat ventral prostate. Transfection and induction of GC79 cDNA in both COS-1 and LNCaP prostate cancer cells led to an apoptotic index that was eightfold higher (P<.001, two-sided Student's t test) than that observed in uninduced transfected cells. Conclusions: We have cloned an androgen-repressible gene, GC79, that is potentially involved in apoptosis. This finding may have implications for the development of androgen-independent prostate cancer and, ultimately, for the treatment of prostate cancer.
Baseline Characteristics, Natural History, and Risk Factors to Progression in Eyes with Stage 2 Macular Holes
Authors: Jung W. Kim, William R. Freeman, Wael El-Haig, Albert M. Maguire, J. Fernando Arevalo, Stanley P. Azen
Journal: Ophthalmology (1995)

Purpose: The purpose of this study is (1) to determine baseline characteristics and natural history of immature full-thickness macular holes, (2) to describe progression and resolution, and (3) to present new aspects of pathogenesis of idiopathic macular hole. Methods: The authors analyzed 41 eyes with stage 2 macular holes (37 patients) in a multicentered prospective randomized trial; 19 eyes were randomized to observation (versus surgery) and had more than 12 months of follow-up, allowing determination of the natural course. Baseline and subsequent examinations included best-refracted visual acuity (Early Treatment of Diabetic Retinopathy Study, potential acuity meter, Pelli-Robson contrast sensitivity, and Bailey-Lovie reading vision), of clinical examinations, photography, and fluorescein angiography. Result: Mean Snellen visual acuity was 20/66 at baseline. Centric holes usually had a small break (201 μm average mean diameter) with a dark yellow ring and without significant retinal elevation. Eccentric holes had a high maximum/minimum diameter ratio (mean, 1.88 ± 0.7) and an incomplete cuff of subretinal fluid or yellow ring. Posterior vitreous detachment prevalence was 32% (8/25) in the centric hole group and 0% (0/16) in the eccentric hole group (P < 0.05). For the 19 eyes with 12 months of follow-up, progression rate to stage 3 (or 4) was 74% (n = 14). The diameter of the stage 2 holes increased significantly between baseline and 12 months (P < 0.001). Progression rate to stage 3 was 100% (8/8) in the eyes with pericentral hyperfluorescence (PCH) and 55% (6/11) in eyes without PCH (P < 0.05). Enlargement occurred in 100% of eccentric holes and 60% of centric holes (P = 0.09). Different progression patterns in eccentric and centric holes suggest different mechanisms of pathogenesis. Conclusion: Eccentric and centric stage 2 macular holes may have a different pathogenesis. Most stage 2 macular holes, especially with PCH (P < 0.05) or eccentric holes, progressed to stage 3 or 4. In addition to purely tangential traction, some component of obliquely oriented anteroposterior vitreous traction component may be important for pathogenesis of senile macular holes, particularly eccentric stage 2 macular holes.
Signaling Pathways Controlling Second Heart Field Development
Authors: Francesca Rochais, Karim Mesbah, Robert G. Kelly
Journal: Circulation Research (2009)

Insight into the mechanisms underlying congenital heart defects and the use of stem cells for cardiac repair are major research goals in cardiovascular biology. In the early embryo, progenitor cells in pharyngeal mesoderm contribute to the rapid growth of the heart tube during looping morphogenesis. These progenitor cells constitute the second heart field (SHF) and were first identified in 2001. Direct or indirect perturbation of SHF addition to the heart results in congenital heart defects, including arterial pole alignment defects. Over the last 3 years, a number of studies have identified key intercellular signaling pathways that control the proliferation and deployment of SHF progenitor cells. Here, we review data concerning Wnt, fibroblast growth factor, bone morphogenetic protein, Hedgehog, and retinoic acid signaling that have begun to identify the ligand sources and responding cell types controlling SHF development. These studies have revealed the importance of signals from pharyngeal mesoderm itself, as well as critical inputs from adjacent pharyngeal epithelia and neural crest cells. Proliferation is emerging as a central checkpoint in the regulation of SHF development. Together, these studies contribute to defining the niche of cardiac progenitor cells in the early embryo, and we discuss the implications of these findings for the regulation of resident stem cell populations in the fetal and postnatal heart. Characterization of signals that maintain, expand, and regulate the differentiation of cardiac progenitor cells is essential for understanding both the etiology of congenital heart defects and the biomedical application of stem cell populations for cardiac repair.