tbuckley/cabot-search huggingface dataset:
Growth phase-dependent expression of ICAD-L/DFF45 modulates the pattern of apoptosis in human colonic cancer cells.
Authors: Laetitia Charrier, Anne Jarry, Claire Toquet, Chantal Bou-Hanna, Marie Chedorge, Marc Denis, Geneviève Vallette, Christian L. Laboisse
Journal: Cancer Research (2002)

The inhibitor of caspase-3-activated DNase (ICAD) is a caspase-3 substrate that controls nuclear apoptosis. ICAD has two isoforms: a functional isoform of  M  r  45,000, ICAD-L/DNA fragmentation factor (DFF) 45; and a  M  r  35,000 isoform, ICAD-S/DFF35. ICAD-deficient murine cells display resistance to apoptotic stimuli and absence of typical nuclear changes of apoptosis. Our aim was to: ( a ) characterize the ICAD expression in several human colonic cancer cell lines compared with human normal colonocytes; and ( b ) correlate the phenotypic features of apoptosis to the level of ICAD expression. ICAD expression was assessed by immunoblot analysis. Early markers of apoptosis of cultured cells included lactate dehydrogenase retention in dying cells, cytokeratin 18 cleavage, and caspase-3 activation. Nuclear markers of apoptosis were assessed by Hoechst staining of nuclei, electron microscopy, and DNA electrophoresis. Inhibition of caspases was performed using a broad-spectrum caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. ICAD expression was restricted to the functional ICAD-L/DFF45 isoform in colonic cancer cells as well as in human normal colonocytes. In a clonal derivative of HT29 cells (HT29-Cl.16E cells), ICAD expression was found to be down-regulated during the exponential phase of growth, and the cell death triggered by IFN-γ, anti-Fas antibody plus Adriamycin was characterized by the expression of early markers of apoptosis, whereas the key nuclear features of apoptosis were absent. In contrast, exposure of confluent cells to this treatment led to a typical apoptotic nuclear fragmentation. Both forms of apoptosis, in exponentially growing and confluent cells, were sensitive to the broad spectrum inhibitor of caspases, z-Val-Ala-Asp-fluoromethyl ketone. Our findings support the concept that the expression of ICAD is essential to the execution of full-blown apoptosis in colonic cancer cells. Altogether, our results point to ICAD as a potential target for restoring a normal apoptotic signal transduction pathway in colonic cancer cells.
HLA B8 and granuloma formation in Crohn's disease.
Authors: G Holdstock, B Macpherson, W L Beeken
Journal: Gut (1982)

In a retrospective survey, patients with Crohn's disease who were HLA B8 were found to have significantly fewer granulomas in rectal biopsies (p less than 0.002) and in resected bowel specimens (p less than 0.02) than non-HLA B8 patients. No statistically significant difference was found between HLA B12 and non-B12 patients. This in vivo evidence of differing immune response capabilities between HLA B8 and non-HLA B8 individuals is compatible with previously reported in vitro studies. Despite these differences, the clinical manifestations and disease course of the two groups of patients was similar, suggesting that neither the presence of HLA B8 nor the development of granuloma directly influence the course of Crohn's disease.
Propofol Is Associated with Favorable Outcomes Compared with Benzodiazepines in Ventilated Intensive Care Unit Patients
Authors: Nick W. Lonardo, Mary C. Mone, Raminder Nirula, Edward J. Kimball, Kyle Ludwig, Xi Zhou, Brian C. Sauer, Kevin Nechodom, Chiachen Teng, Richard G. Barton
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<MethodsResultsDiscussionConclusionsReferencesCITING ARTICLES
Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up Commentary: Progress on nicotine replacement therapy for smokers
Authors: T. Blondal, L. J. Gudmundsson, I. Olafsdottir, G. Gustavsson, A. Westin, J. Stapleton
Journal: BMJ (1999)

# Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up {#article-title-2} Objective : To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year. Design : Placebo controlled, double blind trial. Setting : Reykjavik health centre. Subjects : 237 smokers aged 22-66 years living in or around Reykjavik. Interventions : Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment. Main outcome measure : Sustained abstinence from smoking. Results : The log rank test for 6 years (χ2=8.5, P=0.004) shows a significant association between abstinence from smoking and type of treatment. Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (P=0.011 (χ 2), 95% confidence interval 1.17% to 3.32%), 37% v 25% after 3 months (P=0.045, 1.01% to 3.08%), 31% v 16% after 6 months (P=0.005, 1.27% to 4.50%), 27% v 11% after 12 months (P=0.001, 1.50% to 6.14%), and 16% v 9% after 6 years (P=0.077, 0.93% to 4.72%). Conclusions : Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch. # Commentary: Progress on nicotine replacement therapy for smokers {#article-title-20}
Impact of <i>EWS-ETS</i> Fusion Type on Disease Progression in Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: Prospective Results From the Cooperative Euro-E.W.I.N.G. 99 Trial
Authors: Marie-Cecile Le Deley, Olivier Delattre, Karl-Ludwig Schaefer, Sue A. Burchill, Gabriele Koehler, Pancras C.W. Hogendoorn, Thomas Lion, Christopher Poremba, Julien Marandet, Stelly Ballet, Gaelle Pierron, Samantha C. Brownhill, Michaela Nesslböck, Andreas Ranft, Uta Dirksen, Odile Oberlin, Ian J. Lewis, Alan W. Craft, Heribert Jürgens, Heinrich Kovar
Journal: Journal of Clinical Oncology (2010)

Purpose EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. Patients and Methods Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS-ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). Conclusion In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions.
Long pentraxin PTX3 is associated with mortality and disease severity in severe Leptospirosis
Authors: Jiri F.P. Wagenaar, Marga G.A. Goris, M. Hussein Gasem, Bambang Isbandrio, Federica Moalli, Alberto Mantovani, Kimberly R. Boer, Rudy A. Hartskeerl, Cecilia Garlanda, Eric C.M. van Gorp
Journal: Journal of Infection (2009)
Mirror neurons: From origin to function
Authors: Richard Cook, Geoffrey Bird, Caroline Catmur, Clare Press, Cecilia Heyes
Journal: Behavioral and Brain Sciences (2014)

Abstract This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action “goals”; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons (“wealth of the stimulus”); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.
Low-Dose Irradiation of Nontransformed Cells Stimulates the Selective Removal of Precancerous Cells via Intercellular Induction of Apoptosis
Authors: Daniel I. Portess, Georg Bauer, Mark A. Hill, Peter O'Neill
Journal: Cancer Research (2007)

Abstract An important stage in tumorigenesis is the ability of a precancerous cell to escape natural anticancer signals imposed on it by neighboring cells and its microenvironment. We have previously characterized a system of intercellular induction of apoptosis whereby nontransformed cells selectively remove transformed cells from coculture via cytokine and reactive oxygen/nitrogen species (ROS/RNS) signaling. We report that irradiation of nontransformed cells with low doses of either high linear energy transfer (LET) α-particles or low-LET γ-rays leads to stimulation of intercellular induction of apoptosis. The use of scavengers and inhibitors confirms the involvement of ROS/RNS signaling and of the importance of transformed cell NADPH oxidase in the selectivity of the system. Doses as low as 2-mGy γ-rays and 0.29-mGy α-particles were sufficient to produce an observable increase in transformed cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for γ-rays and 25 mGy for α-particles). The use of transforming growth factor-β (TGF-β) neutralizing antibody confirms a role for the cytokine in the radiation-induced signaling. The system may represent a natural anticancer mechanism stimulated by extremely low doses of ionizing radiation. [Cancer Res 2007;67(3):1246–53]
A Signal Peptide Derived from hsp60 Binds HLA-E and Interferes with CD94/NKG2A Recognition
Authors: Jakob Michaëlsson, Cristina Teixeira de Matos, Adnane Achour, Lewis L. Lanier, Klas Kärre, Kalle Söderström
Journal: The Journal of Experimental Medicine (2002)

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule which presents a restricted set of nonameric peptides, derived mainly from the signal sequence of other MHC class I molecules. It interacts with CD94/NKG2 receptors expressed on the surface of natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also presents a peptide derived from the leader sequence of human heat shock protein 60 (hsp60). This peptide gains access to HLA-E intracellularly, resulting in up-regulated HLA-E/hsp60 signal peptide cell-surface levels on stressed cells. Notably, HLA-E molecules in complex with the hsp60 signal peptide are no longer recognized by CD94/NKG2A inhibitory receptors. Thus, during cellular stress an increased proportion of HLA-E molecules may bind the nonprotective hsp60 signal peptide, leading to a reduced capacity to inhibit a major NK cell population. Such stress induced peptide interference would gradually uncouple CD94/NKG2A inhibitory recognition and provide a mechanism for NK cells to detect stressed cells in a peptide-dependent manner.
The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia
Authors: Boris C. Bastian
Journal: Annual Review of Pathology Mechanisms of Disease (2014)

Melanomas comprise multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ-line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain-of-function mutations in one of several primary oncogenes, which typically lead to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor-suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about the pathogenesis and clinical, histologic, and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework.
Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors
Authors: B. Geoerger, D. Hargrave, F. Thomas, A. Ndiaye, D. Frappaz, F. Andreiuolo, P. Varlet, I. Aerts, R. Riccardi, T. Jaspan, E. Chatelut, M.-C. Le Deley, X. Paoletti, C. Saint-Rose, P. Leblond, B. Morland, J.-C. Gentet, V. Meresse, G. Vassal
Journal: Neuro-Oncology (2010)

This multicenter phase I study aimed to establish the recommended dose (RD) of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, given as monotherapy or with radiotherapy to children with malignant brain tumors. Group 1 included patients with refractory or relapsing brain tumors receiving erlotinib alone, and group 2 included newly diagnosed patients with brainstem gliomas receiving radiotherapy and erlotinib. A conventional 3 + 3 dose escalation and a continual reassessment method, respectively, were utilized in 4 dose levels: 75, 100, 125, and 150 mg/m2 per day. Fifty-one children were enrolled (30 and 21, respectively); 50 received treatment. The RD of erlotinib was 125 mg/m2 per day as monotherapy or in combination with radiotherapy. Overall, 230 adverse events in 44 patients were possibly treatment related (216, grades 1 and 2; 9, grade 3; 1, grade 4; 4, grade 5). Dermatologic and neurologic symptoms were common; intratumoral hemorrhage was confirmed in 3 patients. In group 1, 8 of 29 patients (28%) had stable disease with tumor regression approaching 50% in a malignant glioma and an anaplastic oligoastrocytoma. In group 2, overall survival was 12.0 months. EGFR overexpression by immunohistochemistry was found in 17 of 38 (45%) tumor samples analyzed, with a partial gain of 7p11.2 in 1 glioblastoma; phosphate and tensin homolog loss was frequent in brainstem glioma (15 of 19). Mean (95% CI) apparent clearance and volume of distribution for erlotinib were 4.0 L/h (3.4–4.5 L/h) and 98.6 L (69.8–127.0 L), respectively, and were independent of the dose level; mean half-life was 16.6 hours. Thus, erlotinib 125 mg/m2 per day has an acceptable tolerability profile in pediatric patients with brain tumors and can be combined with radiotherapy.
Association of Coexisting Diabetes and Depression With Mortality After Myocardial Infarction
Authors: Mariska Bot, François Pouwer, Marij Zuidersma, Joost P. van Melle, Peter de Jonge
Journal: Diabetes Care (2012)

Diabetes and depression are both linked to an increased mortality risk after myocardial infarction (MI). Population-based studies suggest that having both diabetes and depression results in an increased mortality risk, beyond that of having diabetes or depression alone. The purpose of this study was to examine the joint association of diabetes and depression with mortality in MI patients.Data were derived from two multicenter cohort studies in the Netherlands, comprising 2,704 patients who were hospitalized for MI. Depression, defined as a Beck Depression Inventory score ≥10, and diabetes were assessed during hospitalization. Mortality data were retrieved for 2,525 patients (93%).During an average follow-up of 6.2 years, 439 patients died. The mortality rate was 14% (226 of 1,673) in patients without diabetes and depression, 23% (49 of 210) in patients with diabetes only, 22% (118 of 544) in patients with depression only, and 47% (46 of 98) in patients with both diabetes and depression. After adjustment for age, sex, smoking, hypertension, left ventricular ejection fraction, prior MI, and Killip class, hazard ratios for all-cause mortality were 1.38 (95% CI 1.00-1.90) for patients with diabetes only, 1.39 (1.10-1.76) for patients with depression only, and as much as 2.90 (2.07-4.07) for patients with both diabetes and depression.We observed an increased mortality risk in post-MI patients with both diabetes and depression, beyond the association with mortality of diabetes and depression alone.
THE LANGUAGE OF HEALTH CARE: Precision and the alienating language of health care
Authors: A Michael Davies
Journal: Journal of the Royal Society of Medicine (2007)

‘Language can educate and inform or confuse and mislead’, your editorial states (October 2006, JRSM), as it goes on to describe problems in medical care and patient-carer communication. I suggest that the major ‘alienating language of health care’ is the substitution of ‘health’ for ‘medical’. It is unlikely that the quest for health will be expedited by the confusion of health and treatment of the sick. Health of individuals and of groups is affected by many social, economic and environmental factors and the search for causes and the amelioration of differences between groups requires clear definition and measurement of the target. At present uses of the word health are exemplified by health care (i.e. care of the sick), health services, health insurance, health centres and so on, diverting attention from the promotion of health and leaving research into the nature and measurement of health and equity outside the purview of medicine.

‘Health’ is an OK word and confers added value to the descriptions on packages of the plants and nostrums of alternative treatments, on centres for physical exercise and on spas. Even the latest guide to membership services and benefits of the British Medical Association, which includes advice on careers and information on the new credit card, has the words ‘improving health’ on its cover.

Absence of an operational definition of health makes it difficult to measure and health status of nations and groups is inferred from rates of diagnosed disease or from self appraisal questionnaires with all the problems of personality, culture and education in interpreting such estimates. The World Health Organization definition of health, and others like it, are inspired but not quantifiable. Precision in language, with the necessary effort to achieve an agreed definition, could be a first step to objective measurement and scientific study of health itself.
Active Compression-Decompression
Authors: Todd J. Cohen, Kelly J. Tucker, Keith G. Lurie, Rita F. Redberg, John P. Dutton, Kathy A. Dwyer, Theresa M. Schwab, Michael C. Chin, Alan M. Gelb, Melvin M. Scheinman, Nelson B. Schiller, Michael L. Callaham
Journal: JAMA (1992)

<h3>Objective.</h3> —To describe and compare with standard cardiopulmonary resuscitation (CPR) in humans a new form of CPR that involves both active compression and active decompression of the chest. <h3>Design.</h3> —Patients in cardiac arrest in whom standard advanced cardiac life support failed were randomized to receive 2 minutes of either standard or active compression-decompression (ACD) CPR using a custom, hand-held suction device, followed by 2 minutes of the alternate technique. The ACD device was applied midsternum and used to perform CPR according to the guidelines of the American Heart Association: 80 compressions per minute, compression depth of 3.8 to 5 cm, 50% duty cycle, and constant-volume ventilation. Mechanical Thumper CPR was also compared in five patients. End-tidal carbon dioxide (ETco2) concentrations and hemodynamic variables were measured. Transesophageal Doppler echocardiography was used to assess contractility, the velocity time integral (an analogue of cardiac output), and diastolic myocardial filling times. <h3>Results.</h3> —Ten patients were enrolled. The mean±SD ETco2 was 4.3±3.8 mm Hg with standard CPR and 9.0±3.9 mm Hg with ACD CPR (<i>P</i>&lt;.0001). Systolic arterial pressure with standard CPR was 52.5±14.0 mm Hg and with ACD CPR, 88.9±24.7 mm Hg (<i>P</i>&lt;.003). The velocity time integral increased from 7.3±2.6 cm with standard CPR to 17.5±5.6 cm with ACD CPR (<i>P</i>&lt;.0001), and diastolic filling times increased from 0.23±09 seconds with standard CPR to 0.37±12 seconds with ACD CPR (<i>P</i>&lt;.004). Mechanical Thumper CPR consistently underperformed both standard and ACD CPR. Minute ventilation obtained in four patients during ACD CPR without endotracheal ventilation was 6.6±0.9 L/min. After 1 hour of standard CPR failed, three of 10 patients randomized to ACD CPR rapidly converted to a hemodynamically stable rhythm following 2 minutes of ACD CPR. <h3>Conclusion.</h3> —ACD CPR is a simple manual technique that improved cardiopulmonary circulation in 10 patients during cardiac arrest. Although ACD CPR may have produced a return of spontaneous circulation in three patients refractory to standard measures, its impact on survival when used early in cardiac arrest remains to be determined. (<i>JAMA</i>. 1992;267:2916-2923)