tbuckley/cabot-search huggingface dataset:
A Clinical Index to Define Risk of Asthma in Young Children with Recurrent Wheezing
Authors: JOSÉ A. CASTRO-RODRÍGUEZ, CATHARINE J. HOLBERG, ANNE L. WRIGHT, FERNANDO D. MARTINEZ
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Because most cases of asthma begin during the first years of life, identification of young children at high risk of developing the disease is an important public health priority. We used data from the Tucson Children's Respiratory Study to develop two indices for the prediction of asthma. A stringent index included frequent wheezing during the first 3 yr of life and either one major risk factor (parental history of asthma or eczema) or two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). A loose index required any wheezing during the first 3 yr of life plus the same combination of risk factors described previously. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma between ages 6 and 13 than children with a negative loose index. Risk of having subsequent asthma increased to 4.3 to 9.8 times when a stringent index was used. We found that 59% of children with a positive loose index and 76% of those with a positive stringent index had active asthma in at least one survey during the school years. Over 95% of children with a negative stringent index never had active asthma between ages 6 and 13. We conclude that the subsequent development of asthma can be predicted with reasonable accuracy using simple, clinically based parameters.
Minimally Invasive Evaluation of Coronary Microvascular Function by Electron Beam Computed Tomography
Authors: Stefan Möhlenkamp, Lilach O. Lerman, Amir Lerman, Thomas R. Behrenbeck, Zvonimir S. Katušić, Patrick F. Sheedy, Erik L. Ritman
Journal: Circulation (2000)

Background —We previously demonstrated that in vivo electron-beam computed tomography (EBCT)–based indicator-dilution methods provide an estimate of intramyocardial blood volume (BV) and perfusion (F), which relate as BV=aF+b√F, where a characterizes the recruitable (exchange) and b the nonrecruitable (conduit) component of the myocardial microcirculation. In the present study, we compared BV and F with intracoronary Doppler ultrasound–based coronary blood flow (CBF) as a method for detecting and quantifying differential responses of these microvascular components to vasoactive drugs in normal (control) and hypercholesterolemic (HC) pigs. Methods and Results —BV and F values were obtained from contrast-enhanced EBCT studies in 14 HC and 14 control pigs. BV, F, and CBF values were obtained at baseline (intracoronary infusion of saline) and after 5 minutes each of intracoronary infusion of adenosine (100 μg · kg − 1 · min − 1 ) and nitroglycerin (40 μg/min). BV and CBF reserves in response to adenosine were attenuated in HC pigs compared with controls (90±36% versus 127±42%, P &lt;0.03, and 485±182% versus 688±160%, P &lt;0.01, respectively). The relationship between BV and F showed consistently lower recruitable BV in HC versus control pigs. Nonrecruitable BV reserve in response to adenosine was attenuated in HC compared with controls (77±20% versus 135±28%, P &lt;0.001). Our findings are consistent with HC-induced impairment of intramyocardial resistance vessel function. Conclusions —EBCT technology allows minimally invasive evaluation of intramyocardial microcirculatory function and permits assessment of microvascular BV distribution in different functional components. This method may be of value in evaluating the coronary microcirculation in pathophysiological states such as hypercholesterolemia.
Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin's lymphoma not achieving complete response after induction chemotherapy: the GEL/TAMO experience
Authors: J. Rodriguez, M.D. Caballero, A. Gutierrez, C. Solano, R. Arranz, J.J. Lahuerta, J. Sierra, M. Gandarillas, J.A. Perez-Simon, J. Zuazu, A. Lopez-Guillermo, A. Sureda, E. Carreras, J. Garcia-Laraña, J. Marin, J.C. Garcia, A. Fernandez de Sevilla, J. Rifon, R. Varela, I. Jarque, C. Albo, A. Leon, J. SanMiguel, E. Conde
Journal: Annals of Oncology (2004)
Alternative Therapies Used by Women With Breast Cancer in Four Ethnic Populations
Authors: M. M. Lee, S. S. Lin, M. R. Wrensch, S. R. Adler, D. Eisenberg
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND: Interest in alternative therapies is growing rapidly in the United States. We studied the types and prevalence of conventional and alternative therapies used by women in four ethnic groups (Latino, white, black, and Chinese) diagnosed with breast cancer from 1990 through 1992 in San Francisco, CA, and explored factors influencing the choices of their therapies. METHODS: Subjects (n = 379) completed a 30-minute telephone interview in their preferred language. Logistic regression models assessed factors associated with the use of alternative therapies after a diagnosis of breast cancer. RESULTS: About one half of the women used at least one type of alternative therapy, and about one third used two types; most therapies were used for a duration of less than 6 months. Both the alternative therapies used and factors influencing the choice of therapy varied by ethnicity. Blacks most often used spiritual healing (36%), Chinese most often used herbal remedies (22%), and Latino women most often used dietary therapies (30%) and spiritual healing (26%). Among whites, 35% used dietary methods and 21% used physical methods, such as massage and acupuncture. In general, women who had a higher educational level or income, were of younger age, had private insurance, and exercised or attended support groups were more likely to use alternative therapies. About half of the women using alternative therapies reported discussing this use with their physicians. More than 90% of the subjects found the therapies helpful and would recommend them to their friends. CONCLUSIONS: Given the high prevalence of alternative therapies used in San Francisco by the four ethnic groups and the relatively poor communication between patients and doctors, physicians who treat patients with breast cancer should initiate dialogues on this topic to better understand patients' choices with regard to treatment options.
Tanezumab for the Treatment of Pain from Osteoarthritis of the Knee
Authors: Nancy E. Lane, Thomas J. Schnitzer, Charles A. Birbara, Masoud Mokhtarani, David L. Shelton, Mike D. Smith, Mark T. Brown
Journal: New England Journal of Medicine (2010)

Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor.We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%).In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).
Depletion of Dendritic Cells Delays Ovarian Cancer Progression by Boosting Antitumor Immunity
Authors: Eduardo Huarte, Juan R. Cubillos-Ruiz, Yolanda C. Nesbeth, Uciane K. Scarlett, Diana G. Martinez, Ronald J. Buckanovich, Fabian Benencia, Radu V. Stan, Tibor Keler, Pablo Sarobe, Charles L. Sentman, Jose R. Conejo-Garcia
Journal: Cancer Research (2008)

Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenvironment and are required for the maintenance of tumor vasculature. Consequently, depletion of DCs in mice bearing established ovarian cancer by targeting different specific markers significantly delays tumor growth and enhances the effect of standard chemotherapies. Tumor growth restriction was associated with vascular apoptosis after DC ablation followed by necrosis, which triggered an antitumor immunogenic boost. Our findings provide a mechanistic rationale for selectively eliminating tumor-associated leukocytes to promote antitumor immunity while impeding tumor vascularization and to develop more effective DC vaccines based on a better understanding of the tumor microenvironment.
Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Lenègre disease
Authors: Vincent Probst, Florence Kyndt, Franck Potet, Jean-Noel Trochu, Guy Mialet, Sophie Demolombe, Jean-Jacques Schott, Isabelle Baró, Denis Escande, Hervé Le Marec
Journal: Journal of the American College of Cardiology (2003)
Tracking Chromatid Segregation to Identify Human Cardiac Stem Cells That Regenerate Extensively the Infarcted Myocardium
Authors: Jan Kajstura, Yingnan Bai, Donato Cappetta, Junghyun Kim, Christian Arranto, Fumihiro Sanada, Domenico D'Amario, Alex Matsuda, Silvana Bardelli, João Ferreira-Martins, Toru Hosoda, Annarosa Leri, Marcello Rota, Joseph Loscalzo, Piero Anversa
Journal: Circulation Research (2012)

According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening.Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration.Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs.The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the "mother" DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.
Endothelin-1-induced Bronchoconstriction in Asthma
Authors: GEORGE W. CHALMERS, STUART A. LITTLE, KANTILAL R. PATEL, NEIL C. THOMSON
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Endothelin-1 (ET-1) has been indirectly implicated in the pathophysiology of asthma, and it is a potent bronchoconstrictor both in vitro and by inhalation in animal models in vivo. We examined the effect of inhaled ET-1 on airway tone in comparison with methacholine in eight asthmatics and five healthy volunteers in a double-blind randomized fashion. After a screening methacholine challenge each asthmatic had two ET-1 (doubling dose range, 0.96 to 15.36 nmol) and one methacholine (doubling dose range, 0.33 to 21.0 μ mol) challenge, and normal subjects had a single ET-1 challenge. Inhalations were delivered using a dosimeter, and lung function measurements were made using constant-volume body plethysmography, with end points being a 35% fall in specific airway conductance (SGaw) and a 15% fall in FEV1. Samples for plasma ET-1 were taken before and after the inhalations, and pulse, blood pressure and oxygen saturation were monitored throughout the inhalations. All the asthmatic subjects displayed rapid-onset ( < 5 min) dose-dependent bronchconstriction to ET-1 across the dose range used, with mean (range) ET-1 PC35SGaw values of 5.15 (1.4 to 13.9) nmol, and 4.3 (1.2 to 8.3) nmol for the two ET-1 inhalations, and 0.42 (0.2 to 0.7) μ mol for methacholine. Albuterol completely and rapidly reversed ET-1-induced bronchoconstriction, and in two patients not given albuterol, bronchoconstriction lasted 60 to 90 min. No significant bronchoconstriction was observed in any of the healthy volunteers across the ET-1 dose range used (mean PC35SGaw > 15.36 nmol). Oxygen saturation did not alter in either group, and plasma ET-1 did not change after ET-1 inhalation. Noninvasive blood pressure measurements revealed a fall in systolic blood pressure in normal subjects, with no change in asthmatics. Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor potency around 100 times that of methacholine in asthma. Asthmatics exhibit bronchial hyperractivity to ET-1, and inhaled ET-1 can safely be given to asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol.
Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α
Authors: Nadia Elia, Maxime Tapponnier, Michael A. Matthay, Jürg Hamacher, Jean-Claude Pache, Marie-Anne Bründler, Martin Totsch, Patrick De Baetselier, Lucie Fransen, Norimasa Fukuda, Denis R. Morel, Rudolf Lucas
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Tumor necrosis factor-α (TNF-α) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-α receptor–dependent and –independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-α (mTNF-α) was functional in mice that were genetically deficient in both types of mTNF-α receptor, establishing the importance of mTNF-α receptor–independent effects in this species. In addition, we assessed the capacity of an mTNF-α–derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-α, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-α has a potential physiological role in the resolution of alveolar edema in rats and mice.
Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome
Authors: Jennifer A Ronesi, Katie A Collins, Seth A Hays, Nien-Pei Tsai, Weirui Guo, Shari G Birnbaum, Jia-Hua Hu, Paul F Worley, Jay R Gibson, Kimberly M Huber
Journal: Nature Neuroscience (2012)
Evaluating SafeClub: can risk management training improve the safety activities of community soccer clubs?
Authors: K Abbott, P Klarenaar, A Donaldson, S Sherker
Journal: British Journal of Sports Medicine (2007)

Objective: To evaluate a sports safety-focused risk-management training programme. Design: Controlled before and after test. Setting: Four community soccer associations in Sydney, Australia. Participants: 76 clubs (32 intervention, 44 control) at baseline, and 67 clubs (27 intervention, 40 control) at post-season and 12-month follow-ups. Intervention: SafeClub, a sports safety-focused risk-management training programme (3×2 hour sessions) based on adult-learning principles and injury-prevention concepts and models. Main outcome measures: Changes in mean policy, infrastructure and overall safety scores as measured using a modified version of the Sports Safety Audit Tool. Results: There was no significant difference in the mean policy, infrastructure and overall safety scores of intervention and control clubs at baseline. Intervention clubs achieved higher post-season mean policy (11.9 intervention vs 7.5 controls), infrastructure (15.2 vs 10.3) and overall safety (27.0 vs 17.8) scores than did controls. These differences were greater at the 12-month follow-up: policy (16.4 vs 7.6); infrastructure (24.7 vs 10.7); and overall safety (41.1 vs 18.3). General linear modelling indicated that intervention clubs achieved statistically significantly higher policy (p&lt;0.001), infrastructure (p&lt;0.001) and overall safety (p&lt;0.001) scores compared with control clubs at the post-season and 12-month follow-ups. There was also a significant linear interaction of time and group for all three scores: policy (p&lt;0.001), infrastructure (p&lt;0.001) and overall safety (p&lt;0.001). Conclusions: SafeClub effectively assisted community soccer clubs to improve their sports safety activities, particularly the foundations and processes for good risk-management practice, in a sustainable way.
OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis
Authors: Daniel Hirschhorn-Cymerman, Gabrielle A. Rizzuto, Taha Merghoub, Adam D. Cohen, Francesca Avogadri, Alexander M. Lesokhin, Andrew D. Weinberg, Jedd D. Wolchok, Alan N. Houghton
Journal: The Journal of Experimental Medicine (2009)

Expansion and recruitment of CD4(+) Foxp3(+) regulatory T (T reg) cells are mechanisms used by growing tumors to evade immune elimination. In addition to expansion of effector T cells, successful therapeutic interventions may require reduction of T reg cells within the tumor microenvironment. We report that the combined use of the alkylating agent cyclophosphamide (CTX) and an agonist antibody targeting the co-stimulatory receptor OX40 (OX86) provides potent antitumor immunity capable of regressing established, poorly immunogenic B16 melanoma tumors. CTX administration resulted in tumor antigen release, which after OX86 treatment significantly enhanced the antitumor T cell response. We demonstrated that T reg cells are an important cellular target of the combination therapy. Paradoxically, the combination therapy led to an expansion of T reg cells in the periphery. In the tumor, however, the combination therapy induced a profound T reg cell depletion that was accompanied by an influx of effector CD8(+) T cells leading to a favorable T effector/T reg cell ratio. Closer examination revealed that diminished intratumoral T reg cell levels resulted from hyperactivation and T reg cell-specific apoptosis. Thus, we propose that CTX and OX40 engagement represents a novel and rational chemoimmunotherapy.
The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells
Authors: Christina Halsey, Marie Docherty, Mhairi McNeill, Derek Gilchrist, Michelle Le Brocq, Brenda Gibson, Gerard Graham
Journal: Journal of Hematology & Oncology (2012)

Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL.