tbuckley/cabot-search huggingface dataset:
IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway
Authors: Lin Wang, Tangsheng Yi, Marcin Kortylewski, Drew M. Pardoll, Defu Zeng, Hua Yu
Journal: The Journal of Experimental Medicine (2009)

Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17−/− mice but drastically accelerated in IFN-γ−/− mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4+ T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6–Stat3 pathway.
Gaps in policy-relevant information on burden of disease in children: a systematic review
Authors: Igor Rudan, Joy Lawn, Simon Cousens, Alexander K Rowe, Cynthia Boschi-Pinto, Lana Tomašković, Walter Mendoza, Claudio F Lanata, Arantxa Roca-Feltrer, Ilona Carneiro, Joanna A Schellenberg, Ozren Polašek, Martin Weber, Jennifer Bryce, Saul S Morris, Robert E Black, Harry Campbell
Journal: The Lancet (2005)
Allergic airway inflammation induces a pro-secretory epithelial ion transport phenotype in mice
Authors: P. Anagnostopoulou, L. Dai, J. Schatterny, S. Hirtz, J. Duerr, M.A. Mall
Journal: European Respiratory Journal (2010)

The airway epithelium is a central effector tissue in allergic inflammation and T-helper cell (Th) type 2-driven epithelial responses, such as mucus hypersecretion contribute to airflow obstruction in allergic airway disease. Previous in vitro studies demonstrated that Th2 cytokines also act as potent modulators of epithelial ion transport and fluid secretion, but the in vivo effect of allergic inflammation on airway ion transport remains unknown. We, therefore, induced allergic inflammation by intratracheal instillation of Aspergillus fumigatus extract or interleukin-13 in mice and determined effects on ion transport in native tracheal and bronchial tissues. We demonstrate that allergic inflammation enhanced basal Cl - secretion in both airway regions and inhibited epithelial Na + channel (ENaC)-mediated Na + absorption and increased Ca 2+ -dependent Cl - secretion in bronchi. Allergen-induced alterations in bronchial ion transport were associated with reduced transcript levels of α-, β- and γENaC, and were largely abrogated in signal transducer and activator of transcription (Stat)6 -/- mice. Our studies demonstrate that Th2-dependent airway inflammation produced a pro-secretory ion transport phenotype in vivo , which was largely Stat6-dependent. These results suggest that Th2-mediated fluid secretion may improve airway surface hydration and clearance of mucus that is hypersecreted in allergic airway diseases such as asthma, and identify epithelial Stat6 signalling as a potential therapeutic target to promote mucus hydration and airway clearance.
Diaphragmatic function in severely malnourished patients with anorexia nervosa. Effects of renutrition.
Authors: D Murciano, D Rigaud, S Pingleton, M H Armengaud, J C Melchior, M Aubier
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The effects of malnutrition and refeeding on nutritional indices, pulmonary function, and diaphragmatic contractile properties were studied in severely malnourished patients with anorexia nervosa. Fifteen patients were evaluated upon hospital admission (Day 0) and on Days 7, 30, and 45 after starting feeding. Spirometry, lung volumes, and arterial blood gases were measured at each time interval, as were contractile properties of the diaphragm as assessed by transdiaphragmatic pressure generated during electrical phrenic nerve stimulation (Pdistim) and a maximal sniff maneuver (Pdisniff). Anthropomorphic and biochemical measurements were performed at each time interval. Patients were severely malnourished upon admission; mean body weight was 37.1 +/- 4.7 kg (63% ideal body weight). During nutritional support, body weight increased significantly to 42.9 +/- 4.6 kg on Day 45 (p < 0.01), as did muscle mass: 11.2 +/- 4.1 kg on Day 0, to 16.6 +/- 4.9 kg on Day 45 (p < 0.01). Vital capacity and FEV1 increased significantly by Day 30 (p < 0.05). Lung volumes were unchanged. Mean arterial blood gas values were also within the normal range at Day 0; PaO2, 92.6 +/- 2.4 mm Hg and PacO2, 41.0 +/- 1.5 mm Hg. Four patients, however, had an increased PacO2 (> 42 mm Hg) at Day 0, which returned to normal by Day 30. Diaphragmatic contractility was severely depressed initially; Pdistim, 15.9 +/- 1.4 cm H2O; Pdisniff, 65.4 +/- 5 cm H2O; but it significantly increased with nutritional support by Day 30 to 22.5 +/- 1.9 and 84.6 +/- 4.7 cm H2O, respectively. We conclude that diaphragmatic function is severely impaired in malnuorished patients free of other coexisting
Synergistic Activity of Fenretinide and the Bcl-2 Family Protein Inhibitor ABT-737 against Human Neuroblastoma
Authors: Hua Fang, Theresa M. Harned, Ondrej Kalous, Vanessa Maldonado, Yves A. DeClerck, C. Patrick Reynolds
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Fenretinide (4-HPR) is a cytotoxic retinoid with minimal systemic toxicity that has shown clinical activity against recurrent high-risk neuroblastoma. To identify possible synergistic drug combinations for future clinical trials, we determined whether ABT-737, a small-molecule BH3-mimetic that inhibits most proteins of the antiapoptotic Bcl-2 family, could enhance 4-HPR activity in neuroblastoma. Experimental Design: Eleven neuroblastoma cell lines were tested for the cytotoxic activity of 4-HPR and ABT-737 as single agents and in combination using the DIMSCAN fluorescence digital imaging cytotoxicity assay. The effect of these agents alone and in combination on mitochondrial membrane depolarization and apoptosis (by flow cytometry), cytochrome c release, caspases, Bax-α, t-Bid, and Bak activation, and subcutaneous xenografts in nu/nu mice was also determined. Results: Multilog synergistic cytotoxicity was observed for the drug combination in all of the 11 neuroblastoma cell lines tested, including MDR lines and those insensitive to either drug as single agents. 4-HPR + ABT-737 induced greater mitochondrial membrane depolarization and mitochondrial cytochrome c release, greater activation of caspases, Bax-α, t-Bid, and Bak, and a higher level of apoptosis than either drug alone. In vivo, 4-HPR + ABT-737 increased the event-free survival of the MDR human neuroblastoma line CHLA-119 implanted subcutaneously in nu/nu mice (194.5 days for the combination vs. 68 days for ABT-737 and 99 days for 4-HPR). Conclusion: Thus, the combination of 4-HPR with a BH3-mimetic drug warrants clinical trials in recurrent neuroblastoma. Clin Cancer Res; 17(22); 7093–104. ©2011 AACR.
Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens
Authors: Brian Alexander, Jennifer Warner-Schmidt, Therese M. Eriksson, Carol Tamminga, Margarita Arango-Lievano, Subroto Ghose, Mary Vernov, Mihaela Stavarache, Sergei Musatov, Marc Flajolet, Per Svenningsson, Paul Greengard, Michael G. Kaplitt
Journal: Science Translational Medicine (2010)

Reduction of the 5-HT 1B receptor–binding protein p11 in the mouse nucleus accumbens induces depression-like behaviors, and gene therapy to restore p11 expression in this region reverses depression-like behaviors.
What happens when cardiac Na channel function is compromised? 2. Numerical studies of the vulnerable period in tissue altered by drugs
Authors: C Starmer
Journal: Cardiovascular Research (2003)

The fate of an impulse arising from stimulation is determined by the ability of the wave front to recruit sufficient Na channels from adjacent cells. Previous numerical studies of mutant Na channels revealed both the velocity of a conditioning wave and the recruiting capacity of the front as determinants of the vulnerable period (VP), an interval within which excitation results in unidirectional conduction. Drugs that block excitatory Na channels in a voltage dependent manner, such as antiarrhythmics, abused substances and antidepressants, slow the restoration of Na conductance trailing an action potential and are associated with proarrhythmia and sudden cardiac death. We hypothesized that drug-induced slowing of Na conductance recovery would flatten the Na conductance restoration gradient thereby reducing the recruiting capacity of a front, extending the VP and increasing the probability of unidirectional propagation.In a cable of ventricular cells, we explored the sensitivity of the VP to voltage-dependent blockade. While varying the unbinding time constant from 100 ms to 5 s, we measured the Na conductance restoration gradient, the liminal length, the refractory period (RP) and the VP.Reducing the rate of drug unbinding flattened the restoration gradient, diminished the recruiting capacity of a premature impulse and extended the liminal length, RP and the VP. The VP was linearly dependent on the drug unbinding time constant. Rapidly unbinding drugs (time constant <1 s) reduced the liminal length below that of a quiescent cable.Slowing the unbinding rate of voltage-dependent drug block of Na channels extended the RP and the VP. Drugs with unbinding time constants greater than 1 s dramatically increased the probability of unidirectional propagation, reflecting increases in both the RP and the VP. This study provides a new mechanism linking Na channel function, compromised by voltage-dependent Na channel drug block, with proarrhythmic conditions that can lead to sudden cardiac death following premature stimulation.
Postradiation Carcinoma Of Male Breast Bilaterally
Authors: S. Kirby Orme
Journal: JAMA (1967)

To the Editor:—  A 24-year-old white man entered the clinical center and said,  suspect I have breast cancer. At age 12 the patient had noted button-like enlargement of both breasts associated with intermittent sharp pain. A physician recommended surgical excision or x-ray therapy, and the latter was chosen. Both nipples, areolae, and small perimeters of adjacent skin were irradiated twice weekly for several months. During treatment, the cone of the x-ray machine rested on a lead shield which protected other parts of the thorax. The amount of irradiation given is unknown as the records have been destroyed. After these treatments, the patient noted that his nipples became abnormally red and tender following exposure to sunlight.  No abnormalities were found on physical examination performed upon entering and leaving the armed services at ages 17 and 21, respectively. At age 23, eight months before admission, intermittent sharp pains and a growing
Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Authors: Tohru Uchida, Takehiro Nakamura, Naoko Hashimoto, Tomokazu Matsuda, Ko Kotani, Hiroshi Sakaue, Yoshiaki Kido, Yoshitake Hayashi, Keiichi I Nakayama, Morris F White, Masato Kasuga
Journal: Nature Medicine (2005)
TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy
Authors: Jeffrey P Marcoe, James R Lim, Keri L Schaubert, Nassima Fodil-Cornu, Marsel Matka, Alexandra L McCubbrey, Alexander R Farr, Silvia M Vidal, Yasmina Laouar
Journal: Nature Immunology (2012)
Cardiac magnetic resonance imaging for the assessment of the heart and pulmonary circulation in pulmonary hypertension
Authors: L. E. R. McLure, A. J. Peacock
Journal: European Respiratory Journal (2009)

Pulmonary hypertension is a disease of the pulmonary arteries resulting in a progressive increase in pulmonary vascular resistance, ultimately leading to right ventricular failure and death. The functional capacity of the right ventricle is a major prognostic determinant. Our understanding of right ventricle performance in pulmonary hypertension has been hindered by the lack of techniques that give a reliable picture of right ventricle morphology and function. Cardiac magnetic resonance (CMR) imaging enables a unique combination of morphological and functional assessment of the right ventricle and pulmonary circulation. In this review article, we introduce the technique of CMR imaging, review its use in imaging of the heart and pulmonary circulation and discuss its current and future application to the management of patients with pulmonary hypertension. There have been recent major advances in our understanding of the mechanism of disease development, in the diagnostic process, and in the treatment of pulmonary hypertension. Therapeutic advances in the management have reinforced the requirement for noninvasive, accurate and reproducible methods of assessment to act as “end-points” to measure the effects of treatment. We anticipate CMR imaging will increasingly be utilised as the primary modality for combined anatomic and functional assessments that enable more complete and efficient evaluation of pulmonary hypertension patients.
Biological Consequences of Gene Regulation After Ionizing Radiation Exposure
Authors: R. R. Weichselbaum, D. E. Hallahan, V. Sukhatme, A. Dritschilo, M. L. Sherman, D. W. Kufe
Journal: JNCI Journal of the National Cancer Institute (1991)

Ionizing radiation is a ubiquitous environmental mutagen and carcinogen widely used in cancer therapy. However, little is known about the induction of cellular signaling events and specific gene expression after radiation exposure. We review the accumulating evidence that ionizing radiation induces signal transduction pathways involving activation of protein kinase C and a program of genetic events that may contribute to the biological effects of x rays.
Exposure–Response Relationship Between Paternal Smoking and Children's Pulmonary Function
Authors: SCOTT A. VENNERS, XIAOBIN WANG, CHANGZHONG CHEN, BINYAN WANG, JIATONG NI, YONGTANG JIN, JIANHUA YANG, ZHIAN FANG, SCOTT T. WEISS, XIPING XU
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We conducted a cross-sectional study to investigate paternal smoking and children's pulmonary function in rural communities of Anqing, China. Our analysis included 1,718 children 8 to 15 yr of age whose mothers were never-smokers. Multiple linear regression models were used to estimate the effect of paternal smoking on children's pulmonary function, with adjustment for children's age, sex, weight, height, square of height, asthma, and father's education. When compared with children of never-smoking fathers, children of smoking fathers had small, but detectable deficits in FEV(1) (-36 ml, SE = 20) and FVC (-37 ml, SE = 22). When children of smoking fathers were subdivided into two subgroups, father smoked < 30 cigarettes/day and >/= 30 cigarettes/day, we found that children whose fathers smoked >/= 30 cigarettes/day had the largest deficits in both FEV(1) (-79 ml, SE = 30) and FVC (-71 ml, SE = 34). This monotonic exposure-response relationship remained in all strata when we further stratified our analysis by children's sex and asthma status. Our data also suggested that the relationship was greatest among nonasthmatic girls, although neither sex nor asthma interaction terms were statistically significant. We conclude that there is a monotonic exposure-response relationship between paternal smoking and decline of pulmonary function in children in this rural Chinese population.
523 Patterns and correlations of ALT in a large sample of children with chronic HCV infection
Authors: E. Bortolotti, L. Zancan, A. Giannattasio, M. Marcellini, M. Resti, C. Barberas, M.G. Marazzi, E. Vajro, G. Verucchi, R. Giacchino, R. Iorio
Journal: Journal of Hepatology (2006)
Sexual Attitudes of Medical Students: Some Implications for Medical Education
Authors: SHERWYN M. WOODS, JOSEPH NATTERSON
Journal: American Journal of Psychiatry (1967)

A study of senior medical students indicated that nearly half experienced anxiety or conflict in at least one category of sexual behavior This anxiety, combined with a lack of knowledge, resulted in a sense of inadequacy about their ability to treat the sexual problems of their patients in a medical practice. The authors recommend small group seminars as the most appropriate method for sex education of medical students.
Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives
Authors: Willem M. Lijfering, Jan-Leendert P. Brouwer, Nic J. G. M. Veeger, Ivan Bank, Michiel Coppens, Saskia Middeldorp, Karly Hamulyák, Martin H. Prins, Harry R. Büller, Jan van der Meer
Journal: Blood (2009)
Chromatin Assembly Factor-1, a Marker of Clinical Value to Distinguish Quiescent from Proliferating Cells
Authors: Sophie E. Polo, Stamatios E. Theocharis, Jerzy Klijanienko, Alexia Savignoni, Bernard Asselain, Philippe Vielh, Geneviève Almouzni
Journal: Cancer Research (2004)

Abstract Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P &amp;lt; 0.0001); Ki-67 (r = 0.94, P &amp;lt; 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions.
How Outcomes Are Defined in Clinical Trials of Mechanically Ventilated Adults and Children
Authors: Bronagh Blackwood, Mike Clarke, Danny F. McAuley, Peter J. McGuigan, John C. Marshall, Louise Rose
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Systematic reviews have considerable potential to provide evidence-based data to aid clinical decision-making. However, there is growing recognition that trials involving mechanical ventilation lack consistency in the definition and measurement of ventilation outcomes, creating difficulties in combining data for meta-analyses. To address the inconsistency in outcome definitions, international standards for trial registration and clinical trial protocols published recommendations, effectively setting the “gold standard” for reporting trial outcomes. In this Critical Care Perspective, we review the problems resulting from inconsistent outcome definitions and inconsistent reporting of outcomes (outcome sets). We present data highlighting the variability of the most commonly reported ventilation outcome definitions. Ventilation outcomes reported in trials over the last 6 years typically fall into four domains: measures of ventilator dependence; adverse outcomes; mortality; and resource use. We highlight the need, first, for agreement on outcome definitions and, second, for a minimum core outcome set for trials involving mechanical ventilation. A minimum core outcome set would not restrict trialists from measuring additional outcomes, but would overcome problems of variability in outcome selection, measurement, and reporting, thereby enhancing comparisons across trials.
Treatment of Obsessive Compulsive Disorder
Authors: Martin E. Franklin, Edna B. Foa
Journal: Annual Review of Clinical Psychology (2011)

Obsessive compulsive disorder (OCD) is characterized by the presence of intrusive, anxiety-provoking thoughts, images, or impulses along with repetitive behaviors or mental acts designed to reduce obsessional distress. OCD is associated with significant functional impairment, psychiatric comorbidity, and compromised quality of life. Fortunately, substantive progress has been made in the past several decades in the development and empirical evaluation of treatments for OCD across the developmental spectrum. The current review begins with a discussion of the clinical presentation of OCD and psychological theories regarding its etiology and maintenance. A detailed discussion follows of exposure plus response prevention, the psychosocial treatment that has garnered the most evidence for its efficacy. A summary of the extant treatment outcome literature related to exposure plus response prevention as well as cognitive therapies, pharmacotherapies, and combined approaches is then presented. Recommendations for future clinical and research directions are then provided.