tbuckley/cabot-search huggingface dataset:
Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection. Protection by T cells is MHC-restricted and MHC-regulated; a model for MHC-disease associations.
Authors: W M Kast, A M Bronkhorst, L P de Waal, C J Melief
Journal: The Journal of Experimental Medicine (1986)

The in vivo importance of class I MHC regulation of the Tc response to a natural pathogenic agent of high virulence was studied on the basis of our previous demonstration of a major difference in the capacity to generate a Sendai virus-specific Tc response between C57BL/6 (B6, H-2b) mice and H-2Kb mutant B6.C-H-2bm1 (bm 1) mice. These two mouse strains differ from each other only in three amino acids in the crucial H-2Kb restriction element for this response. bm 1 mice, in contrast to B6 mice, are Tc nonresponders against this virus, but show Sendai-specific T cell proliferation, antibody production, and DTH reactions, as well as NK cell activity, equal to those of B6 mice. B6, Sendai Tc-deficient bm 1 and T cell-deficient B6 nu/nu mice differ from each other in susceptibility to lethal pneumonia induced by i.n. inoculation of virulent Sendai virus. The lethal dose (LD50) in B6 mice averaged 152 TCID50, in bm 1 mice, 14 TCID50 and in B6 nu/nu mice 0.5 TCID50. The importance of Tc was also shown by the complete protection of B6 nu/nu mice against infection with a lethal virus dose by i.v. injection of a Sendai virus-specific, IL-2-dependent and H-2Kb-restricted B6 Tc clone. In vivo protection by this Tc clone was H-2Kb-restricted. Apart from Tc, an important role for virus-specific Th cells is evident from the difference in susceptibility between bm 1 and B6 nu/nu mice. This conclusion was supported by the demonstration that the mean survival time of B6 nu/nu and bm 1 nu/nu mice could be significantly prolonged, in an I-Ab-restricted manner, by the injection of in vitro-propagated, Sendai-specific B6 or bm 1 Th clones after a lethal dose of Sendai virus, and by the demonstration that inoculation of these Th clones provided help to virus-specific Tc by means of IL-2 production. Strikingly, Th and Tc cooperate in anti-Sendai virus immunity, since permanent survival of lethally infected nu/nu mice was only achieved by inoculation of a mixture of Tc and Th clones or a mixture of a Tc clone and rIL-2. This study provides a unique model for the study of MHC-disease associations.
Opinions concerning euthanasia, life-sustaining treatment and acceleration of death: results of an Italian Association of Medical Oncology (AIOM) survey
Authors: C. Catania, V. Zagonel, V. Fosser, N. La Verde, O. Bertetto, C. Iacono, M. Venturini, D. Radice, L. Adamoli, F. Boccardo
Journal: Annals of Oncology (2008)
Effect of mechanical work load on the transmural distribution of glucose uptake in the isolated perfused rat heart, studied by regional deoxyglucose trapping.
Authors: T E Takala, I E Hassinen
Journal: Circulation Research (1981)

The applicability of the 2-deoxyglucose tracer method to the study of the transmural distribution of glucose uptake in the left ventricle of the isolated, Langendorff-perfused rat heart was validated for the myocardium. The total 2-deoxy[3H]glucose trapped in the myocardium was proportional to the glucose uptake which was varied by the mechanical work load and availability of other oxidizable substrates. When the mechanical work of the heart was eliminated by K+-induced arrest, the glucose uptake of 2.0 mumol/min per g protein was evenly distributed across the left ventricular wall. In the beating heart, glucose uptake averaged 4.7 mol/min per g protein, and was about 40% higher in the subendocardial layer than in the subepicardium (P less than 0.001). Measurement of the transmural distribution of coronary flow by the microsphere method indicated that there were no areas of underperfusion in the left ventricle. The transmural gradient in glucose uptake probably is caused by uneven distribution of the mechanical work load.
<i>In vivo</i>Model of Follicular Lymphoma Resistant to Rituximab
Authors: Stéphane Dalle, Sophie Dupire, Stéphanie Brunet-Manquat, Lina Reslan, Adriana Plesa, Charles Dumontet
Journal: Clinical Cancer Research (2009)

Follicular lymphoma (FL) is the most common subtype of indolent lymphomas. Rituximab is widely used alone or in combination therapy for the treatment of FL. Despite its well-established clinical efficacy, a subpopulation of patients does not respond to rituximab and most patients will relapse after therapy. The mechanisms of action and resistance to rituximab are not fully understood.To study these mechanisms we developed an in vivo model of FL resistant to rituximab. This model was developed using the human RL line, isolated from a patient with FL, grown as xenotransplants in severe combined immunodeficient mice, exposed weekly to rituximab in vivo, followed by serial reimplantation and reexposure to rituximab, until a resistant phenotype was obtained.RL-derived tumors unexposed to rituximab were grown as controls and compared with the resistant tumors. Although the expression of CD46 and CD55 antigens were not differently expressed in the resistant cells, the complement inhibitor CD59 was overexpressed in a subpopulation and CD20 was found to be expressed at a lower level in a minority of cells. Bcl-X(L) and YY1 were also found more highly expressed in rituximab-resistant cells.This model provides insight on potential in vivo resistance mechanisms to rituximab and could help contribute to the development of novel therapies in rituximab-refractory diseases.
Associations of PM<sub>10</sub> with Sleep and Sleep-disordered Breathing in Adults from Seven U.S. Urban Areas
Authors: Antonella Zanobetti, Susan Redline, Joel Schwartz, Dennis Rosen, Sanjay Patel, George T. O'Connor, Michael Lebowitz, Brent A. Coull, Diane R. Gold
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood.We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older.Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects).In summer, increases in RDI or percentage of sleep time at less than 90% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5% (95% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5°F) in temperature.Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk.
Human Regulatory T Cells Do Not Suppress the Antitumor Immunity in the Bone Marrow: A Role for Bone Marrow Stromal Cells in Neutralizing Regulatory T Cells
Authors: Teun Guichelaar, Maarten E. Emmelot, Henk Rozemuller, Bianka Martini, Richard W.J. Groen, Gert Storm, Henk M. Lokhorst, Anton C. Martens, Tuna Mutis
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Regulatory T cells (Tregs) are potent tools to prevent graft-versus-host disease (GVHD) induced after allogeneic stem cell transplantation or donor lymphocyte infusions. Toward clinical application of Tregs for GVHD treatment, we investigated the impact of Tregs on the therapeutic graft-versus-tumor (GVT) effect against human multiple myeloma tumors with various immunogenicities, progression rates, and localizations in a humanized murine model. Experimental Design: Immunodeficient Rag2−/−γc−/− mice, bearing various human multiple myeloma tumors, were treated with human peripheral blood mononuclear cell (PBMC) alone or together with autologous ex vivo cultured Tregs. Mice were analyzed for the in vivo engraftment, homing of T-cell subsets, development of GVHD and GVT. In additional in vitro assays, Tregs that were cultured together with bone marrow stromal cells were analyzed for phenotype and functions. Results: Treatment with PBMC alone induced variable degrees of antitumor response, depending on the immunogenicity and the growth rate of the tumor. Coinfusion of Tregs did not impair the antitumor response against tumors residing within the bone marrow, irrespective of their immunogenicity or growth rates. In contrast, Tregs readily inhibited the antitumor effect against tumors growing outside the bone marrow. Exploring this remarkable phenomenon, we discovered that bone marrow stroma neutralizes the suppressive activity of Tregs in part via production of interleukin (IL)-1β/IL-6. We furthermore found in vitro and in vivo evidence of conversion of Tregs into IL-17–producing T cells in the bone marrow environment. Conclusions: These results provide new insights into the Treg immunobiology and indicate the conditional benefits of future Treg-based therapies. Clin Cancer Res; 19(6); 1467–75. ©2012 AACR.
Involvement of retinoic acid-inducible gene-I in the IFN- /STAT1 signalling pathway in BEAS-2B cells
Authors: T. Imaizumi, M. Kumagai, K. Taima, T. Fujita, H. Yoshida, K. Satoh
Journal: European Respiratory Journal (2005)

Bronchial epithelial cells play an important role in airway host defence, and interferon (IFN)-gamma controls immune reactions by regulating the expression of various genes in bronchial epithelial cells. Signal transducer and activator of transcription 1 (STAT1) is the key transcriptional factor in IFN-gamma signalling. Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box family of proteins and designated a putative RNA helicase. RNA helicases play diverse roles in regulation of gene expression and cellular functions, and RIG-I is implicated in antiviral responses. The aim of the present study was to investigate the effect of IFN-gamma on RIG-I expression in a cell line derived from human bronchial epithelial cells, BEAS-2B. Induction of RIG-I in response to IFN-gamma was found in BEAS-2B cells. Induction of RIG-I by IFN-gamma was also demonstrated in another pulmonary epithelial cell line, NCI-H292. Transfection of BEAS-2B cells with RIG-I complementary DNA resulted in the upregulation of STAT1. Induction of IFN-gamma-inducible protein 10 by IFN-gamma was enhanced in the cells overexpressing RIG-I. It is concluded that retinoic acid-inducible gene-I may play an important role in the regulation of immunological reactions in bronchial epithelial cells elicited by interferon-gamma.
KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
Authors: W. De Roock, H. Piessevaux, J. De Schutter, M. Janssens, G. De Hertogh, N. Personeni, B. Biesmans, J.-L. Van Laethem, M. Peeters, Y. Humblet, E. Van Cutsem, S. Tejpar
Journal: Annals of Oncology (2007)
Improved Estimates of Cancer-Specific Survival Rates From Population-Based Data
Authors: Nadia Howlader, Lynn A. G. Ries, Angela B. Mariotto, Marsha E. Reichman, Jennifer Ruhl, Kathleen A. Cronin
Journal: JNCI Journal of the National Cancer Institute (2010)

Accurate estimates of cancer survival are important for assessing optimal patient care and prognosis. Evaluation of these estimates via relative survival (a ratio of observed and expected survival rates) requires a population life table that is matched to the cancer population by age, sex, race and/or ethnicity, socioeconomic status, and ideally risk factors for the cancer under examination. Because life tables for all subgroups in a study may be unavailable, we investigated whether cause-specific survival could be used as an alternative for relative survival.We used data from the Surveillance, Epidemiology, and End Results Program for 2,330,905 cancer patients from January 1, 1992, through December 31, 2004. We defined cancer-specific deaths according to the following variables: cause of death, only one tumor or the first of multiple tumors, site of the original cancer diagnosis, and comorbidities. Estimates of relative survival and cause-specific survival that were derived by use of an actuarial method were compared.Among breast cancer patients who were white, black, or of Asian or Pacific Islander descent and who were older than 65 years, estimates of 5-year relative survival (107.5%, 106.6%, and 103.0%, respectively) were higher than estimates of 5-year cause-specific survival (98.6%, 95% confidence interval [CI] = 98.4% to 98.8%; 97.4%, 95% CI = 96.2% to 98.2%; and 99.2%, 95% CI = 98.4%, 99.6%, respectively). Relative survival methods likely underestimated rates for cancers of the oral cavity and pharynx (eg, for white cancer patients aged ≥65 years, relative survival = 54.2%, 95% CI = 53.1% to 55.3%, and cause-specific survival = 60.1%, 95% CI = 59.1% to 60.9%) and the lung and bronchus (eg, for black cancer patients aged ≥65 years, relative survival = 10.5%, 95% CI = 9.9% to 11.2%, and cause-specific survival = 11.9%, 95% CI = 11.2 % to 12.6%), largely because of mismatches between the population with these diseases and the population used to derive the life table. Socioeconomic differences between groups with low and high status in relative survival estimates appeared to be inflated (eg, corpus and uterus socioeconomic status gradient was 13.3% by relative survival methods and 8.8% by cause-specific survival methods).Although accuracy of the cause of death on a death certificate can be problematic for cause-specific survival estimates, cause-specific survival methods may be an alternative to relative survival methods when suitable life tables are not available.
Health Status in Obstructive Sleep Apnea
Authors: LESLEY S. BENNETT, CHARLES BARBOUR, BEVERLEY LANGFORD, JOHN R. STRADLING, ROBERT J. O. DAVIES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Section:ChooseTop of pageAbstract <<METHODSRESULTSDISCUSSIONCONCLUSIONSReferencesCITING ARTICLES
The <i>Gly82Ser</i> Polymorphism of the Receptor of Advanced Glycation End Product (RAGE) Gene Is Not Associated With Type 1 or Type 2 Diabetes in a Brazilian Population
Authors: Carolina L. Naka, Geraldo Picheth, Vânia Manfredini Alcântera, Rosangela R. Réa, Eleidi A. Chautard-Freire-Maia, Fábio de Oliveira Pedrosa, Tania Leme da Rocha Martinez, Emanuel M. Souza
Journal: Diabetes Care (2006)

In diabetes, the levels of advanced glycation end products (AGEs) increase as a result of chronic hyperglycemia (1). The best-characterized receptor for AGEs is RAGE. The AGE-RAGE interaction mediates activation and secretion of various cytokines via activation of factors such as the nuclear factor-κB, leading to a proinflammatory process (1). A guanine-to-adenine single nucleotide polymorphism at codon 82 (GGC→AGC) located in exon 3 of RAGE causes the amino acid change glycine to serine ( Gly82Ser or G82S polymorphism) within the putative ligand-binding domain of the protein (2). The RAGE Ser82 isoform has been suggested to upregulate the inflammatory response upon engagement of S100/calgranulins, thereby contributing to the enhancement of proinflammatory mechanisms (3). The aim of this study was to investigate the association of the RAGE polymorphism Gly82Ser with type 1 and type 2 diabetes in a Brazilian population compared with a nondiabetic sample.

The ethnic composition of this unrelated sample was 65.4% Euro Brazilian, 33.8% African Brazilian, and 0.8% Asians. The …
Angiosarcoma of the scalp: absence of vascular endothelial cadherin in primary and metastatic lesions
Authors: M. Tanioka, A. Ikoma, K. Morita, H. Fujii, K-I. Toda, K. Takahashi, T. Tanaka, C. Nishigori, G. Jin, S. Higashi, S. Toyokuni, Y. Miyachi
Journal: British Journal of Dermatology (2001)

A 73‐year‐old man with angiosarcoma of the scalp died about 1 year after disease onset, despite systemic and topical administration of recombinant interleukin‐2. Histopathology showed typical changes of endothelial cells with very sparse lymphocytic infiltration into the tumour. An autopsy revealed that the primary site penetrated cranial bone and invaded vertically into the subarachnoid space. Multiple metastases to lung, chest wall, vertebrae and ribs were also found. On immunofluorescence staining, the expression of vascular endothelial cadherin, which is present in normal endothelium, was absent from both primary and metastatic sites. This may have promoted local invasion and metastasis.
Primary Retroperitoneal Sarcomas: A Multivariate Analysis of Surgical Factors Associated With Local Control
Authors: Sylvie Bonvalot, Michel Rivoire, Marine Castaing, Eberhard Stoeckle, Axel Le Cesne, Jean Yves Blay, Agnès Laplanche
Journal: Journal of Clinical Oncology (2008)

To define the optimal initial management and the best extent of surgery that would optimize margins on primary retroperitoneal sarcomas (RPS).A total of 382 patients with primary RPS were analyzed. Sixty-five patients had a simple resection of the tumor, 120 patients had a complete compartmental resection (systematic resection of noninvolved contiguous organs), 130 patients had a contiguously involved organ resection, 21 patients had a systematic re-excision, 38 patients had an incomplete gross resection, and eight patients had a biopsy alone. Radiotherapy and chemotherapy were administered to 121 and 145 patients, respectively.One, 3-, and 5-year overall survival (OS) rates were 86% (95% CI, 0.82 to 0.89), 66% (95% CI, 0.61 to 0.71), and 57% (95% CI, 0.51 to 0.62), respectively. Median overall survival was 6 years. In the multivariate analysis, high grade, tumor rupture, gross residual disease, and positive margins were associated with decreased OS. Low grade, no tumor rupture, negative histologic margins, a high number of patients undergoing operation per center, and compartmental resection compared with standard procedures were associated with decreased abdominal recurrences. Compartmental resection is a significant variable, predicting a 3.29-fold lower rate of abdominal recurrence compared with simple complete resection.Complete compartmental surgery without tumor rupture should be performed when possible to achieve clear margins. This surgery should be performed in a high-volume center. The role of adjuvant treatments should be evaluated in a randomized trial in association with this optimal surgery.
Self-efficacy and quality of life in COPD patients
Authors: Marinella Sommaruga, Paola Gremigni, Vincenzo Zagà, Claudia Goti, Linda Bassi, Pierachille Santus
Journal: European Respiratory Journal (2012)

Background and purpose: Chronic obstructive pulmonary disease (COPD) is a complex chronic multi-component disease. Understanding the mechanisms of health related quality of life (HRQL) impairment should help identifying targets of pulmonary rehabilitation (PR). Research has shown positive correlations between efficacy expectations and outcome in patients with COPD (Kas¸ikci MK. Int J Nurs Practice 2011; 17:1–8; Arnold R et al., Behav Med, 2005 31:107-15). This study sought to evaluate the relative role of self-efficacy and socio-demographic variables in the prediction of HRQOL in COPD patients.  Methods: A total of 103 COPD patients (60% males, mean aged 70 ± 14 years) before entering a PR program, completed dimensional rating scales on self-efficacy (Perceived Health Competence Scale) and HRQOL (Airways Questionnaire 20). Regression analysis was performed to identify the impact of self-efficacy and demographic variables (gender, age, level of education, and marital status) on HRQOL.  Results: Stepwise multiple regression analysis revealed that age and self-efficacy were correlated with HRQOL (R²= 0.27). These findings suggest that the HRQOL is negatively correlated with age (b = -0.30) and positively correlated with self-efficacy (b = 0.36), independent of gender, level of education, and marital status.  Conclusions: In a chronic diseases such as COPD, it is important to work at improving confidence in the patient9s ability to follow a self-care regimen by increasing self-efficacy, especially in older patients, as it may positively affect quality of life. Therefore, clinicians should include careful assessment of self-efficacy in their routine evaluation of patients before entering a pulmonary rehabilitation program.
gdnf Activates Midline Repulsion by Semaphorin3B via NCAM during Commissural Axon Guidance
Authors: Camille Charoy, Homaira Nawabi, Florie Reynaud, Edmund Derrington, Muriel Bozon, Kevin Wright, Julien Falk, Françoise Helmbacher, Karine Kindbeiter, Valérie Castellani
Journal: Neuron (2012)
Impaired Diastolic Function After Exchange of Endogenous Troponin I With C-Terminal Truncated Troponin I in Human Cardiac Muscle
Authors: Nadiya A. Narolska, Nicoletta Piroddi, Alexandra Belus, Nicky M. Boontje, Beatrice Scellini, Sascha Deppermann, Ruud Zaremba, Rene J. Musters, Cris dos Remedios, Kornelia Jaquet, D. Brian Foster, Anne M. Murphy, Jennifer E. van Eyk, Chiara Tesi, Corrado Poggesi, Jolanda van der Velden, Ger J.M. Stienen
Journal: Circulation Research (2006)

The specific and selective proteolysis of cardiac troponin I (cTnI) has been proposed to play a key role in human ischemic myocardial disease, including stunning and acute pressure overload. In this study, the functional implications of cTnI proteolysis were investigated in human cardiac tissue for the first time. The predominant human cTnI degradation product (cTnI 1–192 ) and full-length cTnI were expressed in Escherichia coli , purified, reconstituted with the other cardiac troponin subunits, troponin T and C, and subsequently exchanged into human cardiac myofibrils and permeabilized cardiomyocytes isolated from healthy donor hearts. Maximal isometric force and kinetic parameters were measured in myofibrils, using rapid solution switching, whereas force development was measured in single cardiomyocytes at various calcium concentrations, at sarcomere lengths of 1.9 and 2.2 μm, and after treatment with the catalytic subunit of protein kinase A (PKA) to mimic β-adrenergic stimulation. One-dimensional gel electrophoresis, Western immunoblotting, and 3D imaging revealed that approximately 50% of endogenous cTnI had been homogeneously replaced by cTnI 1–192 in both myofibrils and cardiomyocytes. Maximal tension was not affected, whereas the rates of force activation and redevelopment as well as relaxation kinetics were slowed down. Ca 2+ sensitivity of the contractile apparatus was increased in preparations containing cTnI 1–192 (pCa 50 : 5.73±0.03 versus 5.52±0.03 for cTnI 1–192 and full-length cTnI, respectively). The sarcomere length dependency of force development and the desensitizing effect of PKA were preserved in cTnI 1–192 -exchanged cardiomyocytes. These results indicate that degradation of cTnI in human myocardium may impair diastolic function, whereas systolic function is largely preserved.