tbuckley/cabot-search huggingface dataset:
Intercohort Gene Expression Co-Analysis Reveals Chemokine Receptors as Prognostic Indicators in Ewing's Sarcoma
Authors: Idriss M. Bennani-Baiti, Aaron Cooper, Elizabeth R. Lawlor, Maximilian Kauer, Jozef Ban, Dave N.T. Aryee, Heinrich Kovar
Journal: Clinical Cancer Research (2010)

We report a novel analytic method, named intercohort co-analysis or Ican, which aids in the discovery of genes with predictive value for the progression or outcome of diseases from small-size cohorts. We tested this premise in Ewing's sarcoma (ES), a highly metastatic cancer of bone and soft tissues that lacks validated molecular metastasis and prognostic indicators.To uncover genes significantly expressed in ES patient subsets, we first determined a nonarbitrary gene expression significance cutoff based on expression levels in validated expressing and nonexpressing tissues. We next searched for genes that were consistently significantly expressed in several ES cohort and cell line datasets. Significantly expressed genes were independently validated by quantitative reverse transcription-PCR in an additional ES cohort.Analysis of ES cohorts revealed marked intercohort gene expression variability. After filtering out the intercohort variability, CXCR4 and CXCR7 were found to be consistently associated with specific ES subsets. Pairwise analyses showed CXCR4 to correlate with ES metastases, and CXCR4 and CXCR7 to patient survival, but not with several other clinicopathological variables.Ican is a powerful novel method to identifying genes consistently associated with particular disease states in cancers for which large cohorts are not available, currently the case of most cancers. We report for the first time that high CXCR4 expression preferentially associates with metastatic ES, and that of CXCR7 with poor patient survival.
NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor Growth Delay
Authors: Lisa A. Ridnour, Robert Y.S. Cheng, Jonathan M. Weiss, Sukhbir Kaur, David R. Soto-Pantoja, Debashree Basudhar, Julie L. Heinecke, C. Andrew Stewart, William DeGraff, Anastasia L. Sowers, Angela Thetford, Aparna H. Kesarwala, David D. Roberts, Howard A. Young, James B. Mitchell, Giorgio Trinchieri, Robert H. Wiltrout, David A. Wink
Journal: Cancer Research (2015)

Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In support of this observation, tumor irradiation induced a rapid increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR administration of L-NAME. In vivo suppression of IL10 using an antisense IL10 morpholino also extended the tumor growth delay induced by radiation in a manner similar to L-NAME. Further examination of this mechanism in cultured Jurkat T cells revealed L-NAME suppression of IR-induced IL10 expression, which reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10 expression in Jurkat T cells and ANA-1 macrophages, which further suggests that the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines, including IL2, IL12p40, and IFNγ, as well as activated CD8(+) T cells were elevated in tumors receiving post-IR L-NAME. Together, these results suggest that post-IR NOS inhibition improves radiation tumor response via Th1 immune polarization within the tumor microenvironment.
Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999
Authors: Charles Peters, Lawrence R. Charnas, Ye Tan, Richard S. Ziegler, Elsa G. Shapiro, Todd DeFor, Satkiran S. Grewal, Paul J. Orchard, Susan L. Abel, Anne I. Goldman, Norma K. C. Ramsay, Kathryn E. Dusenbery, Daniel J. Loes, Lawrence A. Lockman, Shunichi Kato, Patrick R. Aubourg, Hugo W. Moser, William Krivit
Journal: Blood (2004)
Transcranial magnetic stimulation and auditory hallucinations in schizophrenia
Authors: Ralph E Hoffman, Nashaat N Boutros, Sylvia Hu, Robert M Berman, John H Krystal, Dennis S Charney
Journal: The Lancet (2000)

12 patients with schizophrenia and auditory hallucinations received 1 Hz transcranial magnetic stimulation of left temporoparietial cortex. In a double-blind crossover trial, active stimulation significantly reduced hallucinations relative to sham stimulation.
Paediatric origins of adult lung diseases bullet 4: Tobacco related lung diseases begin in childhood
Authors: P N Le Souef
Journal: Thorax (2000)

Tobacco related diseases are the most important cause of respiratory morbidity and mortality in adults. Adult tobacco related respiratory disease may begin in childhood in two ways. Firstly, long term lung damage could occur due to passive exposure from tobacco products reaching the fetus via the placental circulation in utero, and through the air in infants and children. Secondly, most adult smokers begin to smoke while they are children so that factors associated with initiation of smoking and failure of cessation during childhood are of major importance in determining long term adult morbidity from active smoking. There are several strategies to minimise smoking that have been shown to be effective and these should be adopted by educational and governmental agencies. Tobacco companies have played a major role in promoting their products to children and in lobbying politicians to limit effective preventative strategies.

### EFFECTS OF IN UTERO EXPOSURE

If the mother smokes, the level of exposure of the fetus to tobacco products from the time of conception is at the same level as active smokers. A study examining exposure by measurement of maternal urinary cotinine levels at the time of the first clinic visit to a medical practitioner reported levels that were comparable to those found in active smokers.1 Since cotinine diffuses freely through body fluids, the fetus would be exposed to similar levels and these are likely to be comparable to exposure of active smokers. Fetal exposure to tobacco products that cross the placenta has important deleterious effects to the fetus including increased miscarriage,2 3 ectopic pregnancies,4congenital malformations,5 and impaired placental function.6 

### PULMONARY FUNCTION MEASUREMENTS IN NEONATES AND IN EARLY LIFE

Lung growth and function is also adversely affected by maternal smoking during pregnancy.7-12 In studies in neonates the respiratory pattern, as evaluated by the ratio of time to maximal tidal expiratory flow over total time of …
Bone oedema on MRI is highly associated with low bone mineral density in patients with early inflammatory back pain: results from the DESIR cohort
Authors: Karine Briot, Anne Durnez, Simon Paternotte, Corinne Miceli-Richard, Maxime Dougados, Christian Roux
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To assess bone mineral density (BMD) at lumbar spine and hip in a large cohort of patients with early inflammatory back pain (IBP) suggestive of axial spondyloarthritis (SpA), and to assess systemic and bone inflammation (according to MRI) as risk factors of low BMD. <h3>Patients and Methods</h3> 332 (52.4% male) patients with IBP suggestive of axial SpA defined by Calin or Berlin criteria were recruited; they had lumbar spine and hip BMD and body composition measurements. Low BMD was defined by Z≤−2 (at least one site). Clinical, biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in patients with and without low BMD (Z≤−2). Significant parameters in univariate analysis were tested in multivariate models. <h3>Results</h3> Patients (mean age 33.8 years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate logistic regression showed that parameters significantly associated with low BMD (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR 9.60, p=0.0004). <h3>Conclusions</h3> This study conducted in a large cohort of young adults with early IBP suggestive of SpA shows that 13.0% of patients have a low BMD and that the main risk factor associated with low BMD was inflammation on MRI.
High Serum Uric Acid as a Novel Risk Factor for Type 2 Diabetes
Authors: Giuseppe Lippi, Giovanni Targher, Martina Montagnana, Gian Luca Salvagno, Gian Cesare Guidi
Journal: Diabetes Care (2008)

We read with interest the recent article by Dehghan et al. (1), who suggest that serum uric acid might be a strong and independent risk factor for diabetes. In particular, it was reported that the age- and sex-adjusted hazard ratios for diabetes were 1.30 for the 2nd quartile, 1.63 for the 3rd quartile, and 2.83 for the 4th quartile of serum uric acid, in comparison with the 1st quartile. To further investigate the association between uric acid and glucose homeostasis, we performed a retrospective analysis on the database of the Laboratory Information System of the Clinical Chemistry Laboratory at the Verona University Hospital to retrieve results …
Granule-mediated Killing: Pathways for Granzyme B–initiated Apoptosis
Authors: Robert V. Talanian, XiaoHe Yang, Jane Turbov, Prem Seth, Tariq Ghayur, Carlos A. Casiano, Kim Orth, Christopher J. Froelich
Journal: The Journal of Experimental Medicine (1997)

We report that the serine protease granzyme B (GrB), which is crucial for granule-mediated cell killing, initiates apoptosis in target cells by first maturing caspase-10. In addition, GrB has a limited capacity to mature other caspases and to cause cell death independently of the caspases. Compared with other members, GrB in vitro most efficiently processes caspase-7 and -10. In a human cell model, full maturation of caspase-7 does not occur unless caspase-10 is present. Furthermore, GrB matured caspase-3 with less efficiency than caspase-7 or caspase-10. With the caspases fully inactivated by peptidic inhibitors, GrB induced in Jurkat cells growth arrest and, over a delayed time period, cell death. Thus, the primary mechanism by which GrB initiates cell death is activation of the caspases through caspase-10. However, under circumstances where caspase-10 is absent or dysfunctional, GrB can act through secondary mechanisms including activation of other caspases and direct cell killing by cleavage of noncaspase substrates. The redundant functions of GrB ensure the effectiveness of granule-mediated cell killing, even in target cells that lack the expression or function (e.g., by mutation or a viral serpin) of one or more of the caspases, providing the host with overlapping safeguards against aberrantly replicating, nonself or virally infected cells.
Targeting DNA Methylation
Authors: Jean-Pierre J. Issa, Hagop M. Kantarjian
Journal: Clinical Cancer Research (2009)

Abstract Two nucleoside inhibitors of DNA methylation, azacitidine and decitabine, are now standard of care for the treatment of the myelodysplastic syndrome, a deadly form of leukemia. These old drugs, developed as cytotoxic agents and nearly abandoned decades ago were resurrected by the renewed interest in DNA methylation. They have now provided proof of principle for epigenetic therapy, the final chapter in the long saga to provide legitimacy to the field of epigenetics in cancer. But challenges remain; we don't understand precisely how or why the drugs work or stop working after an initial response. Extending these promising findings to solid tumors faces substantial hurdles from drug uptake to clinical trial design. We do not know yet how to select patients for this therapy and how to move it from life extension to cure. The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. But the idea of stably changing gene expression in vivo has transformative potential in cancer therapy and beyond.
The role of bile salt composition in liver pathology of mdr2 (−/−) mice: differences between males and females
Authors: Carin M.J. van Nieuwerk, albert K. Groen, Roelof Ottenhoff, Michael van Wijland, Marius A. van den Bergh Weerman, Guido N.J. Tytgat, Johan J.A. Offerhaus, Ronald P.J. Oude Elferink
Journal: Journal of Hepatology (1997)
Whole-Body Glycolysis Measured by the Deuterated-Glucose Disposal Test Correlates Highly With Insulin Resistance In Vivo
Authors: Carine Beysen, Elizabeth J. Murphy, Tracey McLaughlin, Timothy Riiff, Cindy Lamendola, Holly C. Turner, Mohamad Awada, Scott M. Turner, Gerald Reaven, Marc K. Hellerstein
Journal: Diabetes Care (2007)

The purpose of this study was to compare an in vivo test of whole-body glycolysis, the deuterated-glucose disposal test (2H-GDT), with insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp and the steady-state plasma glucose (SSPG) test.The 2H-GDT consists of an oral glucose challenge containing deuterated glucose, followed by measurement of heavy water (2H2O) production, which represents whole-body glycolytic disposal of the glucose load. 2H2O production is corrected for ambient insulin concentration as an index of tissue insulin sensitivity. The 2H-GDT was compared with euglycemic-hyperinsulinemic glucose clamps in healthy lean subjects (n = 8) and subjects with the metabolic syndrome (n = 9) and with the SSPG test in overweight (n = 12) and obese (n = 6) subjects.A strong correlation with the clamp was observed for the 75-g and 30-g 2H-GDT (r = 0.95, P < 0.0001 and r = 0.88, P < 0.0001, respectively). The 2H-GDT and clamp studies revealed marked insulin resistance in subjects with metabolic syndrome compared with lean control subjects. The correlation with the clamp was maintained in each group (lean, r = 0.86, P < 0.01; metabolic syndrome, r = 0.81, P < 0.01) for the 75-g test. The 2H-GDT also correlated strongly with the SSPG test (r = -0.87, P < 0.0001) in overweight and obese subjects.The 2H-GDT, which measures whole-body glycolysis in humans in a quantitative manner, correlates highly with the euglycemic-hyperinsulinemic glucose clamp and the SSPG test. Impaired insulin-mediated whole-body glycolysis is a feature of insulin resistance, which provides a means of assessing insulin sensitivity in vivo.
Sensitization of Glioma Cells to Fas-Dependent Apoptosis by Chemotherapy-Induced Oxidative Stress
Authors: Shuli Xia, Eliot M. Rosen, John Laterra
Journal: Cancer Research (2005)

Abstract A prominent feature of glioblastoma is its resistance to death from Fas pathway activation. In this study, we explored the modulation of Fas-induced glioblastoma death with chemotherapeutic agents. Camptothecin significantly increased the glioblastoma cell death response to Fas receptor activation regardless of p53 status. Sublethal concentrations of camptothecin reduced the IC50 of agonistic anti-Fas antibody (CH-11) 10-fold, from 500 to 50 ng/mL, in human U87 glioblastoma cells (p53 wild-type). Cell viability in response to camptothecin, CH-11 alone, and the combination of camptothecin + CH-11 was found to be 84%, 85%, and 47% (P &amp;lt; 0.001), respectively. A similar pattern of relative cytotoxicity was found in U373 cells (p53 mutant). We further examined the pathways and mechanisms involved in this apparent synergistic cytotoxic response. Cell death was found to be predominantly apoptotic involving both extrinsic and intrinsic pathways as evidenced by annexin V staining, cleavage of caspases (3, 8, and 9), increased caspase activities, Smac release, and cytoprotection by caspase inhibitors. Expression of Fas-associated death domain, and not Fas, Fas ligand, or caspase proteins, increased following cell treatment with camptothecin + CH-11. Camptothecin treatment enhanced c-jun-NH2-kinase activation in response to CH-11, but inhibition of c-jun-NH2-kinase did not prevent cell death induced by the combination treatment. Reactive oxygen species, especially H2O2, were elevated following camptothecin treatment; and H2O2 enhanced cell death induced by CH-11. The antioxidants glutathione and N-acetyl-cysteine prevented cell death induced by camptothecin + CH-11. These findings show that camptothecin synergizes with Fas activation to induce glioblastoma apoptosis via a mechanism involving reactive oxygen species and oxidative stress pathways.
Long-Term Inhibition of RhoA Attenuates Vascular Contractility by Enhancing Endothelial NO Production in an Intact Rabbit Mesenteric Artery
Authors: Noriko Shiga, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Hajime Nawata, Hideo Kanaide
Journal: Circulation Research (2005)

RhoA plays a critical role in regulating NO production in cultured endothelial cells. To determine its role in in situ endothelial cells, we investigated the effects of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and a RhoA-binding domain of Rho-kinase (RB) on vascular contractility in the isolated rabbit mesenteric artery. Ex vivo treatment of the strips with 3×10 −5 mol/L simvastatin and fluvastatin for ≈24 to 30 hours significantly attenuated the contractile response to phenylephrine and high K + in the presence of endothelium. The addition of N ω -nitro- l -arginine methyl ester and the removal of endothelium abolished the attenuation of the contractile response. The cotreatment with geranylgeranyl pyrophosphate prevented the statin-induced attenuation of the contractile response, whereas geranylgeranyl transferase inhibitor mimicked the effect of simvastatin. Treatment with simvastatin enhanced the bradykinin-induced endothelium-dependent relaxation in the mesenteric artery, whereas it had no effect on the bradykinin-induced [Ca 2+ ] i elevation in endothelial cells of the aortic valves. Introduction of RB to the strips using a cell-penetrating peptide of Tat protein (TATHA-RB) attenuated the contractile responses in a NO-dependent manner. However, a Rac1/Cdc42-binding fragment of p21-activated protein kinase, RB without Tat peptide or TATHA-protein A had no effect. The in vivo treatment of rabbit with simvastatin and TATHA-RB attenuated the contractility in a NO-dependent manner. Simvastatin and TATHA-RB significantly upregulated eNOS in the rabbit mesenteric artery. The present study provides the first evidence that RhoA plays a physiological role in suppressing NO production in in situ endothelial cells.
Comparative Effectiveness of Collaborative Chronic Care Models for Mental Health Conditions Across Primary, Specialty, and Behavioral Health Care Settings: Systematic Review and Meta-Analysis
Authors: Emily Woltmann, Andrew Grogan-Kaylor, Brian Perron, Hebert Georges, Amy M. Kilbourne, Mark S. Bauer
Journal: American Journal of Psychiatry (2012)

Objective: Collaborative chronic care models (CCMs) improve outcome in chronic medical illnesses and depression treated in primary care settings. The effect of such models across other treatment settings and mental health conditions has not been comprehensively assessed. The authors performed a systematic review and meta-analysis to assess the comparative effectiveness of CCMs for mental health conditions across disorders and treatment settings. Method: Randomized controlled trials comparing CCMs with other care conditions, published or in press by August 15, 2011, were identified in a literature search and through contact with investigators. CCMs were defined a priori as interventions with at least three of the six components of the Improving Chronic Illness Care initiative (patient self-management support, clinical information systems, delivery system redesign, decision support, organizational support, and community resource linkages). Articles were included if the CCM effect on mental health symptoms or mental quality of life was reported. Data extraction included analyses of these outcomes plus social role function, physical and overall quality of life, and costs. Meta-analyses included comparisons using unadjusted continuous measures. Results: Seventy-eight articles yielded 161 analyses from 57 trials (depression, N=40; bipolar disorder, N=4; anxiety disorders, N=3; multiple/other disorders, N=10). The meta-analysis indicated significant effects across disorders and care settings for depression as well as for mental and physical quality of life and social role function (Cohen's d values, 0.20–0.33). Total health care costs did not differ between CCMs and comparison models. A systematic review largely confirmed and extended these findings across conditions and outcome domains. Conclusions: CCMs can improve mental and physical outcomes for individuals with mental disorders across a wide variety of care settings, and they provide a robust clinical and policy framework for care integration.
Primary brain CD30+ ALK1+ anaplastic large cell lymphoma (‘ALKoma’): the first case with a combination of ‘not common’ variants
Authors: M. Ponzoni, M.R. Terreni, F. Ciceri, A.J.M. Ferreri, S. Gerevini, N. Anzalone, M. Valle, S. Pizzolito, G. Arrigoni
Journal: Annals of Oncology (2002)
An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages
Authors: R de Marco
Journal: Thorax (2004)

<b>Background:</b> The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects "at risk" of developing the disease. <b>Methods:</b> In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20–44 years) were analysed. <b>Results:</b> The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II–III. Moderate to heavy smoking (⩾15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p&lt;0.001), with no difference between stage 0 and COPD. <b>Conclusions:</b> A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.