tbuckley/cabot-search huggingface dataset:
Age at symptom onset in ankylosing spondylitis: is there a gender difference?
Authors: Adrian Ciurea, Almut Scherer, Ulrich Weber, Regula Neuenschwander, Giorgio Tamborrini, Pascale Exer, Jürg Bernhard, Peter M Villiger, Rudolf Kissling, Beat A Michel, Daniel Stekhoven
Journal: Annals of the Rheumatic Diseases (2014)

The impact of human leukocyte antigen (HLA)-B27 on the age at disease onset in patients with ankylosing spondylitis (AS) has consistently been shown in several cohorts.1–4 A potential gender difference with respect to age at symptom onset remains, however, controversial5–8 as the distribution of HLA-B27 within these populations is not known in all studies. While no sex differences with regard to disease onset were found in several cohorts from Europe,5 ,6 a later disease onset in men was reported in a North American investigation.7 We analysed this issue within the ongoing Swiss Clinical Quality Management cohort of patients with axial spondyloarthritis (axSpA).9 Ethics approval was given by the regional review boards. Informed consent was obtained from all patients.

From a total of 3046 spondyloarthritis patients recruited until June 2014, 2098 (1294 men, 804 women) were included in this analysis, as they fulfilled the Assessment in SpondyloArthritis International Society (ASAS) classification criteria, with the following minor modifications, as the cohort was initiated before the publication of these criteria.9 First, …
Increased Expression of Insulin-like Growth Factor-II Messenger RNA–Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer
Authors: Tatsuya Kato, Satoshi Hayama, Takumi Yamabuki, Nobuhisa Ishikawa, Masaki Miyamoto, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in a large proportion of non–small cell lung cancers (NSCLC) using a cDNA microarray representing 27,648 genes. Experimental Design: A gene encoding insulin-like growth factor-II mRNA-binding protein 1 (IMP-1) was selected as a candidate (≥3-fold expression than in normal lung tissue in about 70% of NSCLCs). Tumor tissue microarray was applied to examine expression of IMP-1 protein in archival lung cancer samples from 267 patients and investigated its clinicopathologic significance. A role of IMP-1 in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis. Results: Positive immunostaining of IMP-1 was correlated with male (P = 0.0001), tumor size (P = 0.0003), non-adenocarcinoma histology (P &amp;lt; 0.0001), smoking history (P = 0.0005), non–well-differentiated tumor grade (P = 0.0001), and poor prognosis (P = 0.0053). Suppression of IMP-1 expression with small interfering RNA effectively suppressed growth of NSCLC cells. In addition, we identified that exogenous expression of IMP-1 increased the migratory activity of mammalian cells. IMP-1 was able to bind to mRNAs encoding a variety of proteins involved in signal transduction, cell cycle progression, cell adhesion and cytoskeleton, and various types of enzymatic activities. Conclusions: These results suggest that IMP-1 expression is likely to play important roles in lung cancer development and progression, and that IMP-1 is a prognostic biomarker and a promising therapeutic target for lung cancer.
Effects of High versus Low Positive End-Expiratory Pressures in Acute Respiratory Distress Syndrome
Authors: Salvatore Grasso, Vito Fanelli, Aldo Cafarelli, Roberto Anaclerio, Marilisa Amabile, Giovanni Ancona, Tommaso Fiore
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 +/- 2 cm H2O) and higher (16 +/- 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 +/- 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 +/- 36 to 396 +/- 138), and reduction in static lung elastance (from 23 +/- 3 to 20 +/- 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 +/- 5 to 28 +/- 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume-pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.
JRSM Introduces Open Peer Review
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2006)

Some news is hard to ignore. In the UK it might be a roasting on the BBC's Today programme or disgrace on the front page of The Mail—according to the government's calculus it is the UK's most influential newspaper. In the USA you wouldn't need to look much further than the New York Times for its ability to inspire dread among the people and organizations it chooses to write about. Proper media rarely tell good news stories. So when the New York Times decides to devote an editorial lamenting the woeful state of US medical journals you can imagine a wave of humiliation—perhaps anger—sweeping through editorial offices and research departments.
Adoptive Transfer of Tumor-Reactive Transforming Growth Factor-β–Insensitive CD8+ T Cells: Eradication of Autologous Mouse Prostate Cancer
Authors: Qiang Zhang, Ximing Yang, Michael Pins, Borko Javonovic, Timothy Kuzel, Seong-Jin Kim, Luk Van Parijs, Norman M. Greenberg, Victoria Liu, Yinglu Guo, Chung Lee
Journal: Cancer Research (2005)

Transforming growth factor (TGF)-beta is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells may lead to tumor evasion from the host immune surveillance and tumor progression. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. The mouse TRAMP-C2 prostate cancer cells produced large amounts of TGF-beta1 and were used as an experimental model. C57BL/6 mice were primed with irradiated TRAMP-C2 cells. CD8+ T cells were isolated from the spleen of primed animals, were expanded ex vivo, and were rendered TGF-beta insensitive by infecting with a retrovirus containing dominant-negative TGF-beta type II receptor. Results of in vitro cytotoxic assay revealed that these CD8+ T cells showed a specific and robust tumor-killing activity against TRAMP-C2 cells but were ineffective against an irrelevant tumor line, B16-F10. To determine the in vivo antitumor activity, recipient mice were challenged with a single injection of TRAMP-C2 cells for a period up to 21 days before adoptive transfer of CD8+ T cells was done. Pulmonary metastasis was either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. Results of immunofluorescent studies showed that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis in tumor cells. Furthermore, transferred tumor-reactive TGF-beta-insensitive CD8+ T cells were able to persist in tumor-bearing hosts but declined in tumor-free animals. These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for cancer therapy.
Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes.
Authors: M Tanaka, H Ito, S Adachi, H Akimoto, T Nishikawa, T Kasajima, F Marumo, M Hiroe
Journal: Circulation Research (1994)

We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro. Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2 atmosphere to produce hypoxic conditions. DNA fragmentation into integer multiples of the internucleosomal DNA length was observed in cardiomyocytes as early as 12 hours, whereas nonmyocytes did not show fragmentation of DNA up to 72 hours. DNA fragmentation of cardiomyocytes induced by hypoxia was also confirmed by nick-end labeling in situ. Messenger RNA for Fas antigen, a mediator of apoptotic cell death, was expressed in both cardiomyocytes and nonmyocytes as revealed by Northern blotting and in situ hybridization. In hypoxic condition, Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over controls, whereas those of nonmyocytes were downregulated. These results indicate that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen may be associated with the mechanism of this apoptotic process.
Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project
Authors: HR Anderson, C Spix, S Medina, JP Schouten, J Castellsague, G Rossi, D Zmirou, G Touloumi, B Wojtyniak, A Ponka, L Bacharova, J Schwartz, K Katsouyanni
Journal: European Respiratory Journal (1997)

We investigated the short-term effects of air pollution on hospital admissions for chronic obstructive pulmonary disease (COPD) in Europe. As part of a European project (Air Pollution and Health, a European Approach (APHEA)), we analysed data from the cities of Amsterdam, Barcelona, London, Milan, Paris and Rotterdam, using a standardized approach to data eligibility and statistical analysis. Relative risks for daily COPD admissions were obtained using Poisson regression, controlling for: seasonal and other cycles; influenza epidemics; day of the week; temperature; humidity and autocorrelation. Summary effects for each pollutant were estimated as the mean of each city's regression coefficients weighted by the inverse of the variance, allowing for additional between-cities variance, as necessary. For all ages, the relative risks (95% confidence limits (95% CL)) for a 50 microg x m(-3) increase in daily mean level of pollutant (lagged 1-3 days) were (95% CL): sulphur dioxide 1.02 (0.98, 1.06); black smoke 1.04 (1.01, 1.06); total suspended particulates 1.02 (1.00, 1.05), nitrogen dioxide 1.02 (1.00, 1.05) and ozone (8 h) 1.04 (1.02, 1.07). The results confirm that air pollution is associated with daily admissions for chronic obstructive pulmonary disease in European cities with widely varying climates. The results for particles and ozone are broadly consistent with those from North America, though the coefficients for particles are substantially smaller. Overall, the evidence points to a causal relationship but the mechanisms of action, exposure response relationships and pollutant interactions remain unclear.
Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy
Authors: Diane V. Havlir
Journal: JAMA (2001)

PATIENTS INFECTED WITH HUMANimmunodeficiency virus (HIV), antiretroviral therapy (ART) is directed at achieving and maintaining HIV RNA levels below the limit of detection of currently approved assays. 1,2A lower nadir of HIV RNA in response to therapy is an independent predictor of long-term virologic suppression. 3In 1 study, 4 participants who achieved a viral load of less than 20 copies/mL had a 10-fold reduction in risk of virologic failure compared with those who did not.Once virologic suppression is achieved, sustaining suppression is critical for preventing the emergence of drug-resistant virus and subsequent virologic failure.Maintaining virologic suppression depends on a number of variables including regimen potency, adherence, and tolerability.6][7] However, transient smaller elevations in HIV RNA levels are also frequently observed in patients who maintain HIV RNA levels of less than 200 copies/mL
The Sony Ericsson WTA Tour 10 year age eligibility and professional development review
Authors: C L Otis, M Crespo, C T Flygare, P R Johnston, A Keber, D Lloyd-Kolkin, J Loehr, K Martin, B M Pluim, A Quinn, P Roetert, K A Stroia, P C Terry
Journal: British Journal of Sports Medicine (2006)

Concerns have long existed over the participation of adolescent athletes in professional sports. In 2004, the Sony Ericsson WTA Tour (WTA Tour) commissioned a Professional Development Advisory Panel (PDAP) to evaluate the WTA Tour’s age eligibility rule (AER) and professional development programmes (PDPs) for female tennis players since their inception in 1995. More than 75% of the 628 respondents supported the principles of the AER, and 90% indicated a need for PDPs. Statistical analysis of WTA Tour players’ careers found that premature retirements (players leaving the Tour at or before age 21) decreased significantly from 7% before the AER to less than 1% afterward, and median career length increased by 43%. The PDAP recommends that the WTA Tour continues a phased-in, developmentally appropriate AER, enhances the PDPs, and works with other sport governing bodies to coordinate rules and programmes at earlier ages to aid the transition of adolescents into adult sports.
Nitric Oxide Enhances Angiogenesis via the Synthesis of Vascular Endothelial Growth Factor and cGMP After Stroke in the Rat
Authors: Ruilan Zhang, Lei Wang, Li Zhang, Jieli Chen, Zhenping Zhu, Zhenggang Zhang, Michael Chopp
Journal: Circulation Research (2003)

We investigated the effects of NO on angiogenesis and the synthesis of vascular endothelial growth factor (VEGF) in a model of focal embolic cerebral ischemia in the rat. Compared with control rats, systemic administration of an NO donor, DETANONOate , to rats 24 hours after stroke significantly enlarged vascular perimeters and increased the number of proliferated cerebral endothelial cells and the numbers of newly generated vessels in the ischemic boundary regions, as evaluated by 3-dimensional laser scanning confocal microscopy. Treatment with DETANONOate significantly increased VEGF levels in the ischemic boundary regions as measured by ELISA. A capillary-like tube formation assay was used to investigate whether DETANONOate increases angiogenesis in ischemic brain via activation of soluble guanylate cyclase. DETANONOate -induced capillary-like tube formation was completely inhibited by a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). Blocking VEGF activity by a neutralized antibody against VEGF receptor 2 significantly attenuated DETANONOate -induced capillary-like tube formation. Moreover, systemic administration of a phosphodiesterase type 5 inhibitor (Sildenafil) to rats 24 hours after stroke significantly increased angiogenesis in the ischemic boundary regions. Sildenafil and an analog of cyclic guanosine monophosphate (cGMP) also induced capillary-like tube formation. These findings suggest that exogenous NO enhances angiogenesis in ischemic brain, which is mediated by the NO/cGMP pathway. Furthermore, our data suggest that NO, in part via VEGF, may enhance angiogenesis in ischemic brain.
Use of β-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study
Authors: Gitte Vrelits Sørensen, Patricia A. Ganz, Steven W. Cole, Lars A. Pedersen, Henrik Toft Sørensen, Deirdre P. Cronin-Fenton, Jens Peter Garne, Peer M. Christiansen, Timothy L. Lash, Thomas P. Ahern
Journal: Journal of Clinical Oncology (2013)

To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort.We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year.Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3).Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.
Transplantation of haemochromatosis liver and intestine into a normal recipient
Authors: P C ADAMS, G JEFFREY, K ALANEN, S CHAKRABARTI, R PRESHAW, W HOWSON, D GRANT
Journal: Gut (1999)

#### Background

Haemochromatosis is a common genetic disease leading to iron overload. Although the gene had been identified ( HFE ),1 the pathogenesis had not been fully elucidated.2 The inadvertent transplant of a C282Y homozygous liver and intestine provided a unique opportunity to study this problem.

##### Methods

A 19 year old man underwent orthotopic liver and intestinal transplantation in January 1997 for the treatment of short bowel syndrome secondary to a mid gut volvulus with resection and cholestatic liver disease resulting from total parenteral nutrition. The organ donor was an 18 year old woman posthumously discovered to be a C282Y homozygote for haemochromatosis.

##### Results

Preoperative recipient …
Stimulation of the soluble guanylate cyclase (sGC) inhibits fibrosis by blocking non-canonical TGFβ signalling
Authors: Christian Beyer, Christoph Zenzmaier, Katrin Palumbo-Zerr, Rossella Mancuso, Alfiya Distler, Clara Dees, Pawel Zerr, Jingang Huang, Christiane Maier, Milena L Pachowsky, Andreas Friebe, Peter Sandner, Oliver Distler, Georg Schett, Peter Berger, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2014)

Objectives We have previously described the antifibrotic role of the soluble guanylate cyclase (sGC). The mode of action, however, remained elusive. In the present study, we describe a novel link between sGC signalling and transforming growth factor β (TGFβ) signalling that mediates the antifibrotic effects of the sGC. Methods Human fibroblasts and murine sGC knockout fibroblasts were treated with the sGC stimulator BAY 41-2272 or the stable cyclic guanosine monophosphate (cGMP) analogue 8-Bromo-cGMP and stimulated with TGFβ. sGC knockout fibroblasts were isolated from sGCI fl/fl mice, and recombination was induced by Cre-adenovirus. In vivo, we studied the antifibrotic effects of BAY 41-2272 in mice overexpressing a constitutively active TGF-β1 receptor. Results sGC stimulation inhibited TGFβ-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFβ-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGFβ target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGFβ-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGFβ target gene expression, confirming that non-canonical TGFβ pathways mediate the antifibrotic sGC activity. Conclusions We elucidated the antifibrotic mode of action of the sGC that increases cGMP levels, blocks non-canonical TGFβ signalling and inhibits experimental fibrosis. Since sGC stimulators have shown excellent efficacy and tolerability in phase 3 clinical trials for pulmonary arterial hypertension, they may be further developed for the simultaneous treatment of fibrosis and vascular disease in systemic sclerosis.
Schistosoma japonicum egg antigen-specific T cell lines in man. Induction of helper and suppressor T cell lines and clones in vitro in a patient with chronic schistosomiasis japonica.
Authors: N Ohta, T Itagaki, M Minai, K Hirayama, Y Hosaka
Journal: Journal of Clinical Investigation (1988)

T cell lines (TCLs) specific for Schistosoma japonicum egg antigen were established from a patient with chronic schistosomiasis japonica to investigate the regulatory mechanism of S.japonicum egg antigen-driven T cell responses in man. All five TCLs tested were CD2+, CD4+, CD8-, and were strongly proliferative only to S. japonicum egg antigen in the absence of exogenous IL-2. All but one TCL produced IL-2-like lymphokines in vitro, indicating their helper T cell functions. One TCL, SjE-3, failed to produce IL-2-like lymphokines. Moreover, this TCL suppressed the specific proliferation of autologous peripheral blood lymphocytes to S. japonicum egg antigen. This TCL produced a soluble suppressor factor(s). These functional diversities among established TCLs were also confirmed by cloned T cells. Our observations might suggest that the regulatory system through helper and suppressor T-T interactions somehow involved in T cell responses to the egg antigen in human chronic schistosomiasis japonica.
134 CONSTITUTIVELY ACTIVE GP130 MUTANTS CAUSE INFLAMMATORY ADENOMAS IN LIVER (IHCA): FUNCTIONAL ANALYSIS AND IDENTIFICATION OF JANUS KINASE 1 AS A POTENTIAL THERAPEUTIC TARGET
Authors: M. Amessou, K. Poussin, G. Couchy, S. Rebouissou, J. Zucman-Rossi
Journal: Journal of Hepatology (2011)