tbuckley/cabot-search huggingface dataset:
Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice
Authors: Rafael Prados-Rosales, Andres Baena, Luis R. Martinez, Jose Luque-Garcia, Rainer Kalscheuer, Usha Veeraraghavan, Carmen Camara, Joshua D. Nosanchuk, Gurdyal S. Besra, Bing Chen, Juan Jimenez, Aharona Glatman-Freedman, William R. Jacobs, Steven A. Porcelli, Arturo Casadevall
Journal: Journal of Clinical Investigation (2011)

Bacteria naturally release membrane vesicles (MVs) under a variety of growth environments. Their production is associated with virulence due to their capacity to concentrate toxins and immunomodulatory molecules. In this report, we show that the 2 medically important species of mycobacteria, Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guérin, release MVs when growing in both liquid culture and within murine phagocytic cells in vitro and in vivo. We documented MV production in a variety of virulent and nonvirulent mycobacterial species, indicating that release of MVs is a property conserved among mycobacterial species. Extensive proteomic analysis revealed that only MVs from the virulent strains contained TLR2 lipoprotein agonists. The interaction of MVs with macrophages isolated from mice stimulated the release of cytokines and chemokines in a TLR2-dependent fashion, and infusion of MVs into mouse lungs elicited a florid inflammatory response in WT but not TLR2-deficient mice. When MVs were administered to mice before M. tuberculosis pulmonary infection, an accelerated local inflammatory response with increased bacterial replication was seen in the lungs and spleens. Our results provide strong evidence that actively released mycobacterial vesicles are a delivery mechanism for immunologically active molecules that contribute to mycobacterial virulence. These findings may open up new horizons for understanding the pathogenesis of tuberculosis and developing vaccines.
Updating clinical recommendations for breast, colorectal and lung cancer treatments: an opportunity to improve methodology and clinical relevance
Authors: E. Parmelli, D. Papini, L. Moja, E. Bandieri, M. Belfiglio, G. Ciccone, R. De Palma, M. Leoni, G. Longo, N. Magrini, I. Moschetti, A. Liberati
Journal: Annals of Oncology (2010)
Differences in post-inflammatory hypersensitivity between splanchnic and pelvic afferents: mechanisms and implications for human disease
Authors: D. J Levinthal, K. Bielefeldt
Journal: Gut (2009)

Pain is common and strongly associated with poor quality of life and disability, constituting a major burden for affected individuals and for society as a whole. As gastroenterologists, we can appreciate this fact in our clinical practice: pain and discomfort are by far the most important causes for consultative visits. In the majority of cases, our diagnostic efforts do not identify an underlying cause, resulting in the diagnosis of a functional disease. Whether it is irritable bowel syndrome (IBS), functional dyspepsia or gastroparesis, a subgroup of patients will recall an acute event, typically infectious, preceding the onset of their chronic illness. Understanding how a transient process triggers lasting symptoms may thus provide important insight into mechanisms of visceral pain, which in turn could translate into better treatments. We cannot prospectively dissect the relationship between a sensitising event and the development of pain in humans. However, we can use animal models of human disease to obtain very detailed information about the effects of inflammation on the properties of afferent neurons. So, what can such animal models teach us about the physiology and pathophysiology of visceral sensation? In this issue of Gut , Hughes et al 1 (see page 1333) report an elegant series of experiments that convincingly demonstrate lasting increases in the excitability of afferent nerve fibres following transient colitis. Thus, we have hypersensitivity (more afferent input), which may well translate into hyperalgesia (more pain).

The results fit into a growing body of literature implicating hypersensitivity as a cause for chronic visceral …
What Makes Clinical Research Ethical?
Authors: E J Emanuel, D Wendler, C Grady
Journal: JAMA (2000)

Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.
Pan-Canadian Study of Mammography Screening and Mortality from Breast Cancer
Authors: Andrew Coldman, Norm Phillips, Christine Wilson, Kathleen Decker, Anna M. Chiarelli, Jacques Brisson, Bin Zhang, Jennifer Payne, Gregory Doyle, Rukshanda Ahmad
Journal: JNCI Journal of the National Cancer Institute (2014)

Screening with mammography has been shown by randomized controlled trials to reduce breast cancer mortality in women aged 40 to 74 years. Estimates from observational studies following screening implementation in different countries have produced varyied findings. We report findings for seven Canadian breast screening programs. Canadian breast screening programs were invited to participate in a study aimed at comparing breast cancer mortality in participants and nonparticipants. Seven of 12 programs, representing 85% of the Canadian population, participated in the study. Data were obtained from the screening programs and corresponding cancer registries on screening mammograms and breast cancer diagnoses and deaths for the period between 1990 and 2009. Standardized mortality ratios were calculated comparing observed mortality in participants to that expected based upon nonparticipant rates. A substudy using data from British Columbia women aged 35 to 44 years was conducted to assess the potential effect of self-selection participation bias. All statistical tests were two-sided. Data were obtained on 2796472 screening participants. The average breast cancer mortality among participants was 40% (95% confidence interval [CI] = 33% to 48%), lower than expected with a range across provinces of 27% to 59%. Age at entry into screening did not greatly affect the magnitude of the average reduction in mortality, which varied between 35% and 44% overall. The substudy found no evidence that self-selection biased the reported mortality results, although the confidence intervals of this assessment were wide. Participation in mammography screening programs in Canada was associated with substantially reduced breast cancer mortality.
Presence of covalently bound metabolites on rat hepatocyte plasma membrane proteins after administration of isaxonine, a drug leading to immunoallergic hepatitis in man
Authors: Jacqueline Loeper, Véronique Descatoire, Gilles Amouyal, Philippe Lettéron, Dominique Larrey, Dominique Pessayre
Journal: Hepatology (1989)

Isaxonine and several other drugs transformed by cytochrome P-450 into reactive metabolites apparently lead to immunoallergic hepatitis in man. Protein epitopes modified by the covalent binding of the metabolites have been proposed as possible targets for the immune response. The purpose of this work was to determine whether covalently bound metabolites are indeed present on hepatocyte plasma membrane proteins. In a first series of experiments, rats were killed 15 or 60 min after administration of [2- 14 C]isaxonine (0.2 mmole · kg −1 i.p.), and various fractions were prepared from isolated hepatocytes; microsomal contamination of the plasma membrane fraction was 1.2% or less. At 60 min, the amount of isaxonine metabolite covalently bound per mg of protein was similar in plasma membranes (0.42 nmole metabolite · mg protein −1 ) and in microsomes (0.38); both values were decreased by about 70% in rats pretreated with piperonyl butoxide, an inhibitor of cytochrome P-450. At 15 min, however, covalent binding to plasma membrane proteins (0.06 nmole metabolite · mg protein −1 ) was only half of that to microsomal proteins (0.12). In a second series of experiments, [2- 14 C] isaxonine (0.1 m M ) was incubated with NADPH, hepatic microsomes and plasma membranes. The reactive isaxonine metabolite became bound extensively to microsomal proteins, but not to plasma membrane proteins. These results show that administration of isaxonine leads to the presence of isaxonine adducts on the proteins of the hepatocyte plasma membrane. They are consistent with the in situ binding of a highly unstable metabolite in the endoplasmic reticulum, or its immediate vicinity, some of these proteins then migrating toward the plasma membrane in vivo .
Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML)
Authors: Giovanni Del Poeta, Adriano Venditti, Maria Ilaria Del Principe, Luca Maurillo, Francesco Buccisano, Anna Tamburini, Maria Christina Cox, Annibale Franchi, Antonio Bruno, Carla Mazzone, Paola Panetta, Giovanna Suppo, Mario Masi, Sergio Amadori
Journal: Blood (2003)
Formation of Heterotypic Gap Junction Channels by Connexins 40 and 43
Authors: Virginijus Valiunas, Robert Weingart, Peter R. Brink
Journal: Circulation Research (2000)

Gap junctions formed between transfected cells expressing connexin (Cx) 40 and Cx43 (Cx43-RIN, Cx40-HeLa, and Cx43-HeLa) revealed a relationship, g(j)=f(V(j)), at steady state, that is typified by a nonsymmetrical behavior similar to that previously reported for other heterotypic channels (gap junction conductance [g(j)]; transjunctional voltage [V(j)]). The unitary conductance of the channels was sensitive to the polarity of V(j). A main state conductance of 61 pS was found when the Cx43 cell was stepped positively or the Cx40 cell negatively (V(j)=70 mV); the reverse polarities yielded a conductance of 100 pS. These heterotypic channels were permeable to carboxyfluorescein. In addition, two other heterotypic forms are illustrated to demonstrate that endogenous Cx45 expression cannot explain the results. The demonstration of heterotypic Cx40-Cx43 channels may have implications for the propagation of the electrical impulse in heart. For example, they may contribute to the slowing of the impulse propagation through the junctions between Purkinje fibers and ventricular muscle.
Psychosocial Oncology Research Faces Uncertain Future in UK
Authors: Kate Travis
Journal: JNCI Journal of the National Cancer Institute (2009)

n November, the cancer charity Cancer Research UK announced its research strategy for the next 5 years.Included in it are goals to increase research on the early diagnosis of cancer; invest more in research on radiotherapy and surgery; and devote more research to cancers of the lung, pancreas, and esophagus.But for some researchers, the strategy is notable for what it doesn't include: Cancer Research UK has decided to discontinue funding research in several areas it has long supported, including psychosocial oncology.The decision has "created seismic shockwaves" throughout the psychosocial oncology research community, said Lesley Fallowfi eld, Ph.D., director of the
A Cytologic Assay for Diagnosis of Food Hypersensitivity in Patients With Irritable Bowel Syndrome
Authors: Antonio Carroccio, Ignazio Brusca, Pasquale Mansueto, Giuseppe Pirrone, Maria Barrale, Lidia Di Prima, Giuseppe Ambrosiano, Giuseppe Iacono, Maria Letizia Lospalluti, Stella M. La Chiusa, Gaetana Di Fede
Journal: Clinical Gastroenterology and Hepatology (2009)
Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: A phase II trial
Authors: L R Laufman, C H Spiridonidis, J Pritchard, R Roach, J Zangmeister, N Larrimer, T Moore, M Segal, J Jones, T Patel, L Gutterman, L Carman, D Colborn, J P Kuebler
Journal: Annals of Oncology (2001)

Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer.Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks.Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent.Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.
<i>CTLA4</i>gene polymorphisms are associated with chronic bronchitis
Authors: G. Zhu, A. Agusti, A. Gulsvik, P. Bakke, H. Coxson, D. A. Lomas, E. K. Silverman, S. G. Pillai
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation. Genetic association between nine CTLA4 single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort. Six CTLA4 SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079< or = p < or =0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325< or = p < or =0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses. Thus, CTLA4 is likely to be a genetic determinant of chronic bronchitis among COPD cases.
Restenosis after directional coronary atherectomy and balloon angioplasty: Comparative analysis based on matched lesions
Authors: Victor A. Umans, Walter Hermans, David P. Foley, Sipke Strikwerda, Marcel van den Brand, Peter de Jaegere, Pim J. de Feyter, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1993)
Genetic variation in TH17 pathway genes, childhood asthma, and total serum IgE levels
Authors: Maximilian Schieck, Sven Michel, Kathrin Suttner, Thomas Illig, Sonja Zeilinger, Andre Franke, Christian Vogelberg, Andrea von Berg, Albrecht Bufe, Andrea Heinzmann, Otto Laub, Ernst Rietschel, Burkhard Simma, Thomas Frischer, Jon Genuneit, Sebastian Kerzel, Michael Kabesch
Journal: Journal of Allergy and Clinical Immunology (2013)
Reduced Mammographic Density with Use of a Gonadotropin-Releasing Hormone Agonist–Based Chemoprevention Regimen in <i>BRCA1</i> Carriers
Authors: Jeffrey N. Weitzel, Saundra S. Buys, William H. Sherman, Anna Marie Daniels, Giske Ursin, John R. Daniels, Deborah J. MacDonald, Kathleen R. Blazer, Malcolm C. Pike, Darcy V. Spicer
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Women with a BRCA1 mutation (BRCA1mut) need risk reduction options beyond mastectomy and oophorectomy. We evaluated the efficacy, safety, and tolerability of hormonal chemoprevention with a gonadotropin-releasing hormone agonist (GnRHA) with low-dose add-back steroids in BRCA1mut carriers. Experimental Design: The 12-month open label clinical trial used the GnRHA deslorelin, ultra-low-dose estradiol (E2), and replacement testosterone, administered via daily intranasal spray in premenopausal women with a BRCA1mut, and intermittent oral medroxyprogesterone acetate. The end points included mammographic percent density, bone mineral density, endometrial hyperplasia, symptom inventory, and quality of life (Medical Outcomes SF-36 survey). Results: Six of eight BRCA1mut women (mean age, 30.3 years; range, 25-36 years) completed the study. Mammographic percent density was significantly reduced at 12 months (median absolute mammographic percent density decrease, 8.3%; P = 0.043), representing a 29.2% median reduction in mammographic percent density. Bone mineral density remained within reference limits for all participants; there were no cases of atypical endometrial hyperplasia and menses resumed within a median of 67 days (range, 35-110 days) after last drug treatment day. The treatment was well tolerated; hypoestrogenic side effects were minimal and transient; and there were no significant changes in quality of life. Conclusions: The GnRHA deslorelin, with low-dose add-back steroids, was well tolerated and significantly decreased mammographic percent density in BRCA1mut carriers. This regimen may reduce breast cancer risk and improve the usefulness of mammographic surveillance by reducing density. This is the first demonstration, to our knowledge, of a direct reduction of mammographic densities in young BRCA1mut carriers.
Lymph Node Staging by Positron Emission Tomography in Cervical Cancer: Relationship to Prognosis
Authors: Elizabeth A. Kidd, Barry A. Siegel, Farrokh Dehdashti, Janet S. Rader, David G. Mutch, Matthew A. Powell, Perry W. Grigsby
Journal: Journal of Clinical Oncology (2010)

PURPOSE A previous retrospective study demonstrated that positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) was more sensitive than computed tomography for lymph node staging in patients with cervical cancer; the findings on FDG-PET were strongly associated with progression-free survival. Therefore, a prospective cohort study was initiated to evaluate FDG-PET lymph node staging in a larger patient population. PATIENTS AND METHODS The study was conducted between July 2000 and March 2009. All 560 patients with cervical cancer underwent pretreatment FDG-PET lymph node staging. Treatment included surgery alone, surgery and postoperative radiation therapy, and definitive radiation or combination radiation and chemotherapy. PET findings were correlated with the risk of disease progression and with survival. Results Overall, 47% of patients had lymph node involvement by FDG-PET at diagnosis. The frequency of lymph node metastasis increased with clinical stage and was similar to that in historical surgical series. Within a stage, patients with PET-positive lymph nodes had significantly worse disease-specific survival than those with PET-negative lymph nodes (P < .001). Disease-specific survival was stratified into distinct groups based on the most distant level of PET-detected nodal disease (none, pelvic, para-aortic, or supraclavicular; P < .001). The hazard ratios for disease recurrence increased incrementally based on the most distant level of nodal disease: pelvic 2.40 (95% CI, 1.63 to 3.52), para-aortic 5.88 (95% CI, 3.80 to 9.09), and supraclavicular 30.27 (95% CI 16.56 to 55.34). CONCLUSION Nodal involvement detected by FDG-PET in cervical cancer relates to clinical stage, is comparable to historical data, and stratifies patient recurrence and survival outcomes.
MDR1 expression in poor-risk acute myeloid leukemia with partial or complete monosomy 7
Authors: MM van den Heuvel-Eibrink, EAC Wiemer, MJ de Boevere, RM Slater, EME Smit, MM van Noesel, B van der Holt, M Schoester, R Pieters, P Sonneveld
Journal: Leukemia (2001)
Chemoprevention of Breast Cancer by Fish Oil in Preclinical Models: Trials and Tribulations
Authors: Carina Signori, Karam El-Bayoumy, Jose Russo, Henry J. Thompson, John P. Richie, Terryl J. Hartman, Andrea Manni
Journal: Cancer Research (2011)

Despite the perception that omega-3 fatty acids (n-3 FA) protect against breast cancer, epidemiologic studies have yielded inconsistent results. Although preclinical data have been, in general, more supportive of a protective effect of n-3 FA on breast cancer, inconsistencies still remain, which preclude definite conclusions or in-depth mechanistic investigations despite 30 years of research in this area. In this review, we discuss key variables that may account for inconsistencies of results across preclinical studies and provide recommendations for future experiments testing the chemopreventive effect of n-3 FAs in breast cancer, as part of a multiagent approach under rigorously controlled conditions.
Early Events in the Embryogenesis of the Vertebrate Visual System: Cellular Determination and Pathfinding
Authors: W A Harris, C E Holt
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
The treatment of erythema multiforme major with systemic corticosteroids
Authors: S. Wright
Journal: British Journal of Dermatology (1991)

Journal Article The treatment of erythema multiforme major with systemic corticosteroids Get access S. Wright S. Wright Department of Dermatology, University of Zimbabwe Medical School, Harare, Zimbabwe Present address: Department of Dermatology, The Royal Free Hospital, Pond Street, London NW3 2QG, U. K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 6, 1 June 1991, Pages 612–613, https://doi.org/10.1111/j.1365-2133.1991.tb04965.x Published: 01 June 1991