tbuckley/cabot-search huggingface dataset:
Effect of Age on Allergen-induced Structural Airway Changes in Brown Norway Rats
Authors: Els Palmans, Nele J. Vanacker, Romain A. Pauwels, Johan C. Kips
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

It remains to be fully established whether allergen-induced airway inflammation and remodeling are influenced by age. The aim of the present study was to compare allergen-induced airway changes in young and adult rats. Brown Norway rats were sensitized at 4 weeks of age (young) or 13 weeks of age (adult) and exposed to aerosolized ovalbumin (OA) or phosphate-buffered saline for 2 weeks. In both age groups OA exposure induced an increase in OA-specific Immunoglobulin E and in the number of peribronchial eosinophils. OA-challenged animals also developed an increase in total airway wall area, enhanced fibronectin deposition, and goblet cell hyperplasia. Both inflammatory and structural alterations were more pronounced in the airways of young compared with adult OA-exposed rats. The number of peribronchial eosinophils was increased in young animals (685.4 +/- 75.0 versus 389.9 +/- 37.8/mm2 in adult rats; p < 0.001). A higher degree of goblet cell hyperplasia was observed in young rats (65.37 +/- 4.68 versus 34.74 +/- 3.68/mm basement membrane in adult rats; p < 0.001) and area of fibronectin deposition in the airway wall was higher in young compared with adult animals (5.08 +/- 0.46 versus 3.62 +/- 0.29 microm2/microm basement membrane; p < 0.005). In conclusion, in young rats airways are more susceptible to allergen-induced inflammatory and structural airway changes.
Sustained Benefit of Supportive Intervention for Depressive Symptoms in Caregivers of Patients With Alzheimer’s Disease
Authors: Mary S Mittelman, David L Roth, David W Coon, William E Haley
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The long-term effect of counseling and support on symptoms of depression was examined in spouse-caregivers of patients with Alzheimer's disease. METHOD: The participants were 406 spouse-caregivers of Alzheimer's disease patients who lived at home at baseline. The caregivers were randomly assigned to either a group receiving enhanced counseling and support treatment or a group receiving usual care (control group). Caregivers in the enhanced treatment group were provided with six sessions of individual and family counseling, agreed to join support groups 4 months after enrollment, and received ongoing ad hoc counseling. The Geriatric Depression Scale was administered at baseline and at regular follow-up intervals for as long as the caregiver participated in the study. RESULTS: After baseline differences were controlled for, caregivers in the enhanced treatment group had significantly fewer depressive symptoms after the intervention than did the control subjects. These effects were sustained for 3.1 years after baseline, similar across gender and patient severity level, and sustained after nursing home placement or death of the patient. CONCLUSIONS: Counseling and support lead to sustained benefits in reducing depressive symptoms in spouse-caregivers of Alzheimer's disease patients and should be widely available to provide effective, evidence-based intervention for family caregivers.
Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys
Authors: Sieghart Sopper, Dagmar Nierwetberg, Astrid Halbach, Ursula Sauer, Carsten Scheller, Christiane Stahl-Hennig, Kerstin Mätz-Rensing, Frank Schäfer, Thomas Schneider, Volker ter Meulen, Justus G. Müller
Journal: Blood (2003)
Knockout Mouse Models of Iron Homeostasis
Authors: Robert E. Fleming, Qi Feng, Robert S. Britton
Journal: Annual Review of Nutrition (2011)

Murine models have made valuable contributions to our understanding of iron metabolism. Investigation of mice with inherited forms of anemia has led to the discovery of novel proteins involved in iron homeostasis. A growing number of murine models are being developed to investigate mitochondrial iron metabolism. Mouse strains are available for the major forms of hereditary hemochromatosis. Findings in murine models support the concept that the pathogenesis of nearly all forms of hereditary hemochromatosis involves inappropriately low expression of hepcidin. The availability of mice with floxed iron-related genes allows the study of the in vivo consequences of cell-selective deletion of these genes.
Degradation of Basement Membrane by Murine Tumor Cells2
Authors: Lance A. Liotta, Jerome Kleinerman, Phillip Catanzaro, Donald Rynbrandt
Journal: JNCI Journal of the National Cancer Institute (1977)

Tumor cells from the murine T241 fibrosarcoma, which rapidly and reproducibility produces pulmonary metastases, were tested in vitro for their ability to degrade isolated pulmonary basement membrane. Degradation of basement membrane substrate was quantified by the culture of the substrate with tumor cells and measurement of the solubilized hydroxyproline and hexose glycoprotein at neutral pH. It was found that tumor cells collected in the tumor venous drainage were associated with a significantly greater solubilization of basement membrane than were tumor cells obtained from the primary tumor mass. Tumor cells were also assayed for their ability to solubilize type I collagen purified from human dura. Venous effluent tumor cells solubilized collagen to a significantly greater level than primary tumor cells, spleen cells, or liver cells. These findings raised the possibility that metastasizing tumor cells may be a distinct tumor subpopulation with regard to invasive potential.
Chronotropic Effect of Cardiac Glycosides in Cats, Dogs, and Rabbits
Authors: Robert E. Ten Eick, Brian F. Hoffman
Journal: Circulation Research (1969)

We have tested the widely accepted hypothesis that digitalis, in nontoxic concentration, can act directly on cells of the sinoatrial pacemaker to cause slowing. The effect of autonomic nerves on sinoatrial cells was eliminated either by chronic cardiac denervation or by use of autonomic blocking agents such as atropine, 0.5 mg/kg, and propranolol, 2 mg/kg, or MJ-1999, 3 mg/kg. When the effects of autonomic nerves were eliminated, acetylstrophanthidin, 0.120 mg/kg, failed to cause slowing of sinus rate in the anesthetized cat and the anesthetized dog. Similarly, ouabain, 5 x 10 -7 M, and acetylstrophanthidin, 1.5 µg/ml, after prior administration of autonomic blocking agents failed to cause slowing of the isolated rabbit right atrium perfused with Tyrode's solution. These results indicate that the sinus slowing caused by cardiac glycosides may be mediated entirely by alteration of the neural control of the heart and that the drug, in nontoxic concentration, does not have a direct negative chronotropic action on the mammalian sinoatrial node.
Comparative Effectiveness of Cardiac Resynchronization Therapy With an Implantable Cardioverter-Defibrillator Versus Defibrillator Therapy Alone
Authors: Frederick A. Masoudi, Xiaojuan Mi, Lesley H. Curtis, Pamela N. Peterson, Jeptha P. Curtis, Gregg C. Fonarow, Stephen C. Hammill, Paul A. Heidenreich, Sana M. Al-Khatib, Jonathan P. Piccini, Laura G. Qualls, Adrian F. Hernandez
Journal: Annals of Internal Medicine (2014)

Trials comparing implantable cardioverter-defibrillator (ICD) therapy with cardiac resynchronization therapy with a defibrillator (CRT-D) are limited to selected patients treated at centers with extensive experience.To compare outcomes after CRT-D versus ICD therapy in contemporary practice.Retrospective cohort study using the National Cardiovascular Data Registry's ICD Registry linked with Medicare claims.780 U.S. hospitals implanting both CRT-D and ICD devices.7090 propensity-matched patients older than 65 years with reduced left ventricular ejection fraction (&lt;0.35) and prolonged QRS duration on electrocardiography (≥120 ms) having CRT-D or ICD implantation between 1 April 2006 and 31 December 2009.Risks for death, readmission, and device-related complications over 3 years.Compared with ICD therapy, CRT-D was associated with lower risks for mortality (cumulative incidence, 25.7% vs. 29.8%; adjusted hazard ratio [HR], 0.82 [99% CI, 0.73 to 0.93]), all-cause readmission (cumulative incidence, 68.6% vs. 72.8%; adjusted HR, 0.86 [CI, 0.81 to 0.93]), cardiovascular readmission (cumulative incidence, 45.0% vs. 52.4%; adjusted HR, 0.80 [CI, 0.73 to 0.88]), and heart failure readmission (cumulative incidence, 24.3% vs. 29.4%; adjusted HR, 0.78 [CI, 0.69 to 0.88]). It was also associated with greater risks for device-related infection (cumulative incidence, 1.9% vs. 1.0%; adjusted HR, 1.90 [CI, 1.07 to 3.37]). The lower risks for heart failure readmission associated with CRT-D compared with ICD therapy were most pronounced among patients with left bundle branch block or a QRS duration at least 150 ms and in women.Patients were not randomly assigned to treatment groups, and few patients could be propensity-matched. The findings may not extend to younger patients or those outside of fee-for-service Medicare.In older patients with reduced left ventricular ejection fraction and prolonged QRS duration, CRT-D was associated with lower risks for death and readmission than ICD therapy alone.Agency for Healthcare Research and Quality.
Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study
Authors: G.F. Fleming, V.L. Filiaci, R.C. Bentley, T. Herzog, J. Sorosky, L. Vaccarello, H. Gallion
Journal: Annals of Oncology (2004)
Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration
Authors: Irving Kirsch, Brett J Deacon, Tania B Huedo-Medina, Alan Scoboria, Thomas J Moore, Blair T Johnson
Journal: PLoS Medicine (2008)

Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.
Mononuclear Infiltrates in Osteosarcoma and Chemokine Receptor Expression
Authors: Irene von Luettichau, Michaela Nathrath, Stefan Burdach, Ralf Huss, Stephan Segerer, Peter J. Nelson
Journal: Clinical Cancer Research (2006)

To the Editor: Laverdiere et al. recently reported the expression of a series of chemokine receptors in osteosarcoma ([1][1]). The authors used real time PCR analysis to characterize the expression of chemokine receptors in osteosarcoma tumor tissue. The expression of CXCR4, CCR7 and CCR10 was
Chronic Q fever: Review of the literature and a proposal of new diagnostic criteria
Authors: M.C.A. Wegdam-Blans, L.M. Kampschreur, C.E. Delsing, C.P. Bleeker-Rovers, T. Sprong, M.E.E. van Kasteren, D.W. Notermans, N.H.M. Renders, H.A. Bijlmer, P.J. Lestrade, M.P.G. Koopmans, M.H. Nabuurs-Franssen, J.J. Oosterheert
Journal: Journal of Infection (2011)
In vivo gene delivery in the mouse lung with lactosylated polyethylenimine, questioning the relevance of in vitro experiments
Authors: Stéphanie Grosse, Guiti Thévenot, Yolande Aron, Eric Duverger, Mohamed Abdelkarim, Annie-Claude Roche, Michel Monsigny, Isabelle Fajac
Journal: Journal of Controlled Release (2008)
Abnormal Glucose Metabolism in the Mediodorsal Nucleus of the Thalamus in Schizophrenia
Authors: Erin A Hazlett, Monte S Buchsbaum, Eileen Kemether, Rachel Bloom, Jimcy Platholi, Adam M Brickman, Lina Shihabuddin, Cheuk Tang, William Byne
Journal: American Journal of Psychiatry (2004)

Three thalamic nuclei--the mediodorsal nucleus, pulvinar, and centromedian nucleus--each have unique reciprocal circuitry with cortical and subcortical areas known to be affected in schizophrenia. To determine if the disorder is also associated with dysfunction in the mediodorsal nucleus, pulvinar, and centromedian nucleus, relative glucose metabolism in these regions was measured in a large group of unmedicated patients with schizophrenia.[18F]-deoxyglucose positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) scans were obtained for 41 unmedicated patients with schizophrenia and 60 age- and sex-matched healthy subjects. The PET and MRI images for each subject were coregistered, and the whole thalamus, mediodorsal nucleus, pulvinar, and centromedian nucleus were traced on the MRI image. Relative glucose metabolism in these regions was assessed.Patients with schizophrenia showed significantly lower relative glucose metabolism in the mediodorsal nucleus and the centromedian nucleus and significantly higher relative glucose metabolism in the pulvinar, compared with the healthy subjects. Lower relative glucose metabolism in the total thalamus, mediodorsal nucleus, and pulvinar was associated with greater overall clinical symptoms as measured by the Brief Psychiatric Rating Scale. Lower relative glucose metabolism in the pulvinar was associated with more hallucinations and more positive symptoms, while lower relative glucose metabolism in the mediodorsal nucleus was associated with more negative symptoms.The findings suggest that patients with schizophrenia exhibit dysfunction in thalamic subdivisions with distinct cortical connections and that these thalamic subdivisions have specific associations with clinical symptoms.
Pathologic and Molecular Features Correlate With Long-Term Outcome After Adjuvant Therapy of Resected Primary GI Stromal Tumor: The ACOSOG Z9001 Trial
Authors: Christopher L. Corless, Karla V. Ballman, Cristina R. Antonescu, Violetta Kolesnikova, Robert G. Maki, Peter W.T. Pisters, Martin E. Blackstein, Charles D. Blanke, George D. Demetri, Michael C. Heinrich, Margaret von Mehren, Shreyaskumar Patel, Martin D. McCarter, Kouros Owzar, Ronald P. DeMatteo
Journal: Journal of Clinical Oncology (2014)

Purpose The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. Patients and Methods There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis. Results RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model–adjusted P &lt; .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. Conclusion Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.
Clinical outcome measures in rheumatoid arthritis
Authors: P. L C M van Riel
Journal: Annals of the Rheumatic Diseases (2000)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with peripheral synovitis as its main manifestation. The presentation of the disease and the course during time are highly variable both within as well as between individuals.The symptoms and signs of RA may vary from joint complaints like pain, stiffness, swelling and functional impairment, to more constitutional complaints like fatigue and loss of general health. Because of this variety in disease expression a huge number of outcome variables have been used in the past decades to evaluate interventions in clinical trials.1 

Many efforts have been taken in the past years to standardise the assessment of RA aiming at making study results interchangeable. Consensus has been reached about a minimal set of disease activity variables to be measured in clinical trials.2 3 As a following step response criteria based on these core set variables have been developed by the European League Against Rheumatism (EULAR),4 and the American College of Rheumatology (ACR).5 The recent introduction of new, very effective, antirheumatic agents has forced many researchers to modify these response criteria.6 7 The validity of several of them however is questionable and gives rise to as yet unsolved problems, which will be discussed in this paper.

The two most widely used sets of improvement criteria have been developed following different routes: the preliminary ACR improvement criteria are using all seven core set variables while the EULAR response criteria are based on the Disease Activity Score (DAS), an index using only three or four core set variables. It turned out that including more variables in a combined index did not increase the validity of it.8 These two criteria sets also differ in respect to the way they were developed (the ability to discriminate from a placebo reponse, high versus …
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Authors: Simon Yona, Ki-Wook Kim, Yochai Wolf, Alexander Mildner, Diana Varol, Michal Breker, Dalit Strauss-Ayali, Sergey Viukov, Martin Guilliams, Alexander Misharin, David A. Hume, Harris Perlman, Bernard Malissen, Elazar Zelzer, Steffen Jung
Journal: Immunity (2012)
Persephin, a Novel Neurotrophic Factor Related to GDNF and Neurturin
Authors: Jeffrey Milbrandt, Frederic J de Sauvage, Timothy J Fahrner, Robert H Baloh, Melanie L Leitner, Malú G Tansey, Patricia A Lampe, Robert O Heuckeroth, Paul T Kotzbauer, Kelli S Simburger, Judith P Golden, Jamie A Davies, Richard Vejsada, Ann C Kato, Mary Hynes, Daniel Sherman, Merry Nishimura, Li-Chong Wang, Richard Vandlen, Barbara Moffat, Robert D Klein, Kris Poulsen, Christa Gray, Alain Garces, Christopher E Henderson, Heidi S Phillips, Eugene M Johnson
Journal: Neuron (1998)
Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8
Authors: M Fujimura, Q Xiu, M Tsujiura, H Tachibana, S Myou, T Matsuda, K Matsushima
Journal: European Respiratory Journal (1998)

Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5 microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3 weeks. One day after the last administration, animals were anaesthetized and artificially ventilated through tracheal cannulae, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[-1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057, but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil accumulation in guinea-pigs in vivo. In part this appears to be due to release of leukotriene B4, whereas it may not be mediated by neutrophil elastase.
A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes.
Authors: J Shellito, V V Suzara, W Blumenfeld, J M Beck, H J Steger, T H Ermak
Journal: Journal of Clinical Investigation (1990)

Pulmonary infections with Pneumocystis carinii are an important cause of morbidity and mortality in patients with AIDS. P. carinii infections are seen in patients with decreased numbers of helper T lymphocytes, suggesting that these cells are important in preventing infection. To test this hypothesis, we sought to establish experimental infection with P. carinii in mice selectively depleted of helper T lymphocytes. Weekly injections of a monoclonal anti-CD4 antibody produced sustained depletion of helper T lymphocytes from blood and lymphoid organs. To establish pulmonary infection, lymphocyte-depleted mice were then given intratracheal inoculations of P. carinii organisms derived from the lungs of chronically infected athymic mice. Pulmonary infection with P. carinii was demonstrable in the antibody-treated mice and was centered around the conducting airways. Infection was persistent for up to 3 mo with continued antibody treatments, and yet could be cleared from the lungs if antibody treatments were discontinued. This experimental model of P. carinii infection permits the study of infection associated with a specific immune defect and implicates the helper T lymphocyte as a critical cell in host defense against this pathogen.