tbuckley/cabot-search huggingface dataset:
Up-regulation of Heat Shock Protein 27 Induces Resistance to 17-Allylamino-Demethoxygeldanamycin through a Glutathione-Mediated Mechanism
Authors: Andrea K. McCollum, Cynthia J. TenEyck, Brian M. Sauer, David O. Toft, Charles Erlichman
Journal: Cancer Research (2006)

Abstract 17-Allylamino-demethoxygeldanamycin (17-AAG), currently in phase I and II clinical trials as an anticancer agent, binds to the ATP pocket of heat shock protein (Hsp90). This binding induces a cellular stress response that up-regulates many proteins including Hsp27, a member of the small heat shock protein family that has cytoprotective roles, including chaperoning of cellular proteins, regulation of apoptotic signaling, and modulation of oxidative stress. Therefore, we hypothesized that Hsp27 expression may affect cancer cell sensitivity to 17-AAG. In colony-forming assays, overexpression of Hsp27 increased cell resistance to 17-AAG whereas down-regulation of Hsp27 by siRNA increased sensitivity. Because Hsp27 is known to modulate levels of glutathione (GSH), we examined cellular levels of GSH and found that it was decreased in cells transfected with Hsp27 siRNA when compared with control siRNA. Treatment with buthionine sulfoximine, an inhibitor of GSH synthesis, also sensitized cells to 17-AAG. Conversely, treatment of Hsp27 siRNA–transfected cells with N-acetylcysteine, an antioxidant and GSH precursor, reversed their sensitivity to 17-AAG. A cell line selected for stable resistance to geldanamycin relative to parent cells showed increased Hsp27 expression. When these geldanamycin- and 17-AAG-resistant cells were transfected with Hsp27 siRNA, 17-AAG resistance was dramatically diminished. Our results suggest that Hsp27 up-regulation has a significant role in 17-AAG resistance, which may be mediated in part through GSH regulation. Clinical modulation of GSH may therefore enhance the efficacy of Hsp90-directed therapy. (Cancer Res 2006; 66(22): 10967-75)
A.L.G. AFTER RENAL ALLOTRANSPLANTATION
Authors: AltonJ. Morris, D. Mears, J.H. Rogers, J.R. Johnson, J. Charlesworth, J.H. Stewart, A.G.R. Sheil, G.E. Kelly, B.G. Storey, J. May, S. Kalowski
Journal: The Lancet (1971)
A LABILE SERUM FACTOR CLOTTING DEFECT: ITS DEMONSTRATION BY THE THROMBOPLASTIN GENERATION TEST AND ITS CLINICAL SIGNIFICANCE*
Authors: William E. Connor, E. D. Warner, John R. Carter
Journal: Journal of Clinical Investigation (1961)

The thromboplastin generation test, originally described by Biggs and Douglas (2), has proved to be a valuable tool in the study and diagnosis of hemorrhagic disease. Several problems have arisen from its use, however. These have centered about the preparation of the reagents for the test and the implications of an abnormal test result. This test, which measures the rate of formation and the amount of plasma thromboplastin, may be performed with platelet factor 3 supplied by either a platelet suspension or an emulsion of phosphatides from soybeans or brain. In the routine performance of the test we have used a soybean phosphatide. Early in the course of our studies with the thromboplastin generation test, we occasionally found a serum factor deficiency different from deficiencies of PTC (factor IX) or Stuart factor (factor X). This labile serum factor defect was not evident in fresh serum but developed as the serum was aged from 3 to 24 hours. The abnormality was noted in some patients with undiagnosed bleeding whose other coagulation tests were normal. Patients with liver disease, patients with polycythemia vera, and newborn infants usually had this defect. It was sometimes found, combined with other defects, in patients receiving coumarin drugs. It occured in a few normal control subjects. Such defective thromboplastin generation could be corrected readily by the use of any one of the following in the test system: se
Oncogenic NRAS, Required for Pathogenesis of Embryonic Rhabdomyosarcoma, Relies upon the HMGA2–IGF2BP2 Pathway
Authors: Zhizhong Li, Yunyu Zhang, Krishnan Ramanujan, Yan Ma, David G. Kirsch, David J. Glass
Journal: Cancer Research (2013)

Embryonic rhabdomyosarcoma (ERMS) is the most common soft-tissue tumor in children. Here, we report the identification of the minor groove DNA-binding factor high mobility group AT-hook 2 (HMGA2) as a driver of ERMS development. HMGA2 was highly expressed in normal myoblasts and ERMS cells, where its expression was essential to maintain cell proliferation, survival in vitro, and tumor outgrowth in vivo. Mechanistic investigations revealed that upregulation of the insulin-like growth factor (IGF) mRNA-binding protein IGF2BP2 was critical for HMGA2 action. In particular, IGF2BP2 was essential for mRNA and protein stability of NRAS, a frequently mutated gene in ERMS. shRNA-mediated attenuation of NRAS or pharmacologic inhibition of the MAP-ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) effector pathway showed that NRAS and NRAS-mediated signaling was required for tumor maintenance. Taken together, these findings implicate the HMGA2-IGFBP2-NRAS signaling pathway as a critical oncogenic driver in ERMS.
What evidence exists for new strategies or technologies in the diagnosis of sports concussion and assessment of recovery?
Authors: Jeffrey Scott Kutcher, Paul McCrory, Gavin Davis, Alain Ptito, Willem H Meeuwisse, Steven P Broglio
Journal: British Journal of Sports Medicine (2013)

Objective The purpose of this critical review is to summarise the evidence for the following technologies/strategies related to diagnosing or managing sports-related concussion: quantitative EEG, functional neuroimaging, head impact sensors, telemedicine and mobile devices. Data sources MEDLINE, PubMed, Cochrane Controlled Trials Registers, SportDiscus, EMBASE, Web of Science and ProQuest databases. Primary search keywords were concussion, sports concussion and mild traumatic brain injury. The keywords used for secondary, topic specific searches were quantitative electroencephalography, qEEG, functionalMRI, magnetoencephalography, near-infrared spectroscopy, positron emission tomography, single photon emissionCT, accelerometer, impact sensor, telemetry, remote monitoring, robotic medicine, telemedicine, mobile device, mobile phone, smart phone and tablet computer. Results The primary search produced 8567 publications. The secondary searches produced nine publications that presented original data, included a comparison group in the study design and involved sports-related concussion. Four studies spoke to the potential of qEEG as a diagnostic or management tool, while five studies addressed the potential of fMRI to be used in the same capacity. Conclusions Emerging technologies and novel approaches that aid in sports concussion diagnosis and management are being introduced at a rapid rate. While some technologies show promise, their clinical utility remains to be established.
2-Methoxyestradiol, an Estradiol Metabolite, Inhibits Neointima Formation and Smooth Muscle Cell Growth via Double Blockade of the Cell Cycle
Authors: Federica Barchiesi, Edwin K. Jackson, Juergen Fingerle, Delbert G. Gillespie, Bernhard Odermatt, Raghvendra K. Dubey
Journal: Circulation Research (2006)

2-Methoxyestradiol (2-ME), an endogenous metabolite of estradiol with no affinity for estrogen receptors, is a potent anticarcinogenic agent (in phase II clinical trials) and mediates the inhibitory effects of estradiol on smooth muscle cell (SMC) growth. Here we studied the intracellular mechanisms by which 2-ME inhibits SMC growth and whether 2-ME prevents injury-induced neointima formation. 2-ME concentrations that inhibit proliferation of cycling human aortic SMCs by >or=50% blocked cell-cycle progression in G(0)/G(1) and in G(2)/M phase, as determined by flow cytometry. Consistent with the cell-cycle effects, at a molecular level (Western blots), 2-ME inhibited cyclin D(1) and cyclin B(1) expression; cyclin-dependent kinase (cdk)-1 and cdk-2 activity; and retinoblastoma protein (pRb), extracellular signal-regulated kinase (ERK) 1/2, and Akt phosphorylation. 2-ME also upregulated the Cdk inhibitor p27 and interfered with tubulin polymerization. Moreover, 2-ME augmented COX-2 expression, suggesting that it may also inhibit SMC growth via prostaglandin formation. In rats, treatment with 2-ME abrogated injury-induced neointima formation; decreased proliferating SMCs; downregulated expression of proliferating-cell nuclear antigen (PCNA), c-myc, cyclin D(1), cyclin B(1), phosphorylated Akt, phosphorylated ERK1/2, p21, and pRb; inhibited cdk-1 and cdk-4 activity; and upregulated expression of cyclooxygenase (COX)-2 and p27. Caspase-3 cleavage assay and fluorescence-activated cell-sorting (FACS) analysis showed no evidence of apoptosis in 2-ME-treated SMCs, and TUNEL staining in carotid segments showed no evidence of 2-ME-induced apoptosis in vivo. The antimitotic effects of 2-ME on SMCs are mediated by the inhibition of key cell-cycle regulatory proteins and effects on tubulin polymerization and COX-2 upregulation. These effects of 2-ME most likely contribute to the antivasoocclusive actions of this endogenous compound.
Echocardiographic Studies of Stented Fascia Lata Grafts in the Mitral Position
Authors: DAVID A. S. MARY, BROJESH C. PAKRASHI, ROGER W. CATCHPOLE, MARIAN I. IONESCU
Journal: Circulation (1974)

Nineteen patients with stented fascia lata grafts in the mitral position were studied by the reflected ultrasound technique. Eleven of these had competent grafts, two had minimal regurgitation and six had severe graft incompetence as judged by ventriculography and during surgery. The diastolic closure rate (E-F speed) of the cusps revealed significant correlation with the effective graft area derived by calculations from cardiac catheterization data ( P &lt; 0.01), and indicated only mild to moderate stenosis. The exhibited cusp mobility revealed an amplitude which was comparable with and similar to that measured in cusps from freshly prepared fascia lata valves. The demonstrated cusp mobility and E-F speed did not show a statistically significant difference between competent and incompetent grafts ( P &gt; 0.7 and P &gt; 0.4 respectively). Further evidence is presented supporting the role played by the mitral annulus mobility in the production of echocardiographic diastolic movement of the leaflet.
Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms
Authors: S. Fuschillo, A. De Felice, G. Balzano
Journal: European Respiratory Journal (2008)

Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders. The pathogenesis of bronchiectasis is poorly understood. Three distinct pathogenetic elements, namely infection, inflammation and enzymatic actions, which interact with each other, have been implicated in the pathophysiology of bronchiectasis. Some recent observations indicate that airway inflammation in bronchiectasis comes from a deregulated cytokine network independent of bacterial airway colonisation. In the present review, current knowledge about cellular and molecular inflammatory events in the dynamic process of host–pathogen interaction that are thought to play a relevant role in the pathogenic mechanisms of airway wall destruction leading to bronchiectasis are discussed.
Prevalences of scabies and pediculosis corporis among homeless people in the Paris region: results from two randomized cross‐sectional surveys (HYTPEAC study)
Authors: A. Arnaud, O. Chosidow, M.‐A. Détrez, D. Bitar, F. Huber, F. Foulet, Y. Le Strat, S. Vandentorren
Journal: British Journal of Dermatology (2015)

Journal Article Prevalences of scabies and pediculosis corporis among homeless people in the Paris region: results from two randomized cross‐sectional surveys (HYTPEAC study) Get access A. Arnaud, A. Arnaud Observatoire du Samusocial de Paris 35 Avenue Courteline 75012 Paris FranceFrench Institute for Public Health Surveillance Saint‐Maurice France Correspondence Amandine Arnaud. E‐mail: a.arnaud@samusocial-75.fr Search for other works by this author on: Oxford Academic Google Scholar O. Chosidow, O. Chosidow Department of Dermatology AP‐HP Hôpital Henri Mondor Créteil FranceUniversité Paris‐Est Créteil Val de Marne (UPEC) Créteil FranceCIC INSERM 1430 and EA EpiDermE (Epidemiology in Dermatology and Evaluation of Therapeutics) Créteil France Search for other works by this author on: Oxford Academic Google Scholar M.‐A. Détrez, M.‐A. Détrez Observatoire du Samusocial de Paris 35 Avenue Courteline 75012 Paris France Search for other works by this author on: Oxford Academic Google Scholar D. Bitar, D. Bitar French Institute for Public Health Surveillance Saint‐Maurice France Search for other works by this author on: Oxford Academic Google Scholar F. Huber, F. Huber Observatoire du Samusocial de Paris 35 Avenue Courteline 75012 Paris France Search for other works by this author on: Oxford Academic Google Scholar F. Foulet, F. Foulet Department of Dermatology AP‐HP Hôpital Henri Mondor Créteil France Search for other works by this author on: Oxford Academic Google Scholar Y. Le Strat, Y. Le Strat French Institute for Public Health Surveillance Saint‐Maurice France Search for other works by this author on: Oxford Academic Google Scholar S. Vandentorren S. Vandentorren Observatoire du Samusocial de Paris 35 Avenue Courteline 75012 Paris FranceFrench Institute for Public Health Surveillance Saint‐Maurice France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 1, 1 January 2016, Pages 104–112, https://doi.org/10.1111/bjd.14226 Published: 01 January 2016
Cerebral Glucose Metabolism in Obsessive-Compulsive Hoarding
Authors: Sanjaya Saxena, Arthur L Brody, Karron M Maidment, Erlyn C Smith, Narineh Zohrabi, Elyse Katz, Stephanie K Baker, Lewis R Baxter
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Compulsive hoarding and saving symptoms, found in many patients with obsessive-compulsive disorder (OCD), are part of a discrete clinical syndrome that includes indecisiveness, disorganization, perfectionism, procrastination, and avoidance and has been associated with poor response to medications and cognitive behavior therapy. The authors sought to identify cerebral metabolic patterns specifically associated with the compulsive hoarding syndrome using positron emission tomography (PET). METHOD: [18F]Fluorodeoxyglucose PET scans were obtained for 45 adult subjects who met DSM-IV criteria for OCD (12 of whom had compulsive hoarding as their most prominent OCD symptom factor) and 17 normal comparison subjects. All subjects had been free of psychotropic medication for at least 4 weeks. Regional cerebral glucose metabolism was compared between the groups. RESULTS: In relation to the comparison subjects, the patients with compulsive hoarding syndrome had significantly lower glucose metabolism in the posterior cingulate gyrus and cuneus, whereas the nonhoarding OCD patients had significantly higher glucose metabolism in the bilateral thalamus and caudate. In relation to nonhoarding OCD patients, compulsive hoarders had significantly lower metabolism in the dorsal anterior cingulate gyrus. Across all OCD patients, hoarding severity was negatively correlated with glucose metabolism in the dorsal anterior cingulate gyrus. CONCLUSIONS: OCD patients with the compulsive hoarding syndrome had a different pattern of cerebral glucose metabolism than nonhoarding OCD patients and comparison subjects. Obsessive-compulsive hoarding may be a neurobiologically distinct subgroup or variant of OCD whose symptoms and poor response to anti-obsessional treatment are mediated by lower activity in the cingulate cortex.
When is Cancer Care Cost-Effective? A Systematic Overview of Cost–Utility Analyses in Oncology
Authors: Dan Greenberg, Craig Earle, Chi-Hui Fang, Adi Eldar-Lissai, Peter J. Neumann
Journal: JNCI Journal of the National Cancer Institute (2010)

New cancer treatments pose a substantial financial burden on health-care systems, insurers, patients, and society. Cost-utility analyses (CUAs) of cancer-related interventions have received increased attention in the medical literature and are being used to inform reimbursement decisions in many health-care systems. We identified and reviewed 242 cancer-related CUAs published through 2007 and included in the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org). Leading cancer types studied were breast (36% of studies), colorectal (12%), and hematologic cancers (10%). Studies have examined interventions for tertiary prevention (73% of studies), secondary prevention (19%), and primary prevention (8%). We present league tables by disease categories that consist of a description of the intervention, its comparator, the target population, and the incremental cost-effectiveness ratio. The median reported incremental cost-effectiveness ratios (in 2008 US $) were $27,000 for breast cancer, $22,000 for colorectal cancer, $34,500 for prostate cancer, $32,000 for lung cancer, and $48,000 for hematologic cancers. The results highlight the many opportunities for efficient investment in cancer care across different cancer types and interventions and the many investments that are inefficient. Because we found only modest improvement in the quality of studies, we suggest that journals provide specific guidance for reporting CUA and assure that authors adhere to guidelines for conducting and reporting economic evaluations.
Eating disorders in college men
Authors: R Olivardia, H G Pope, B Mangweth, J I Hudson
Journal: American Journal of Psychiatry (1995)

This study was designed to assess the characteristics of men with eating disorders in the community.The authors recruited 25 men meeting DSM-IV criteria for eating disorders and 25 comparison men through advertisements in college newspapers. A second comparison group comprised 33 women with bulimia nervosa who were recruited and interviewed with virtually identical methods.The men with eating disorders closely resembled the women with eating disorders but differed sharply from the comparison men in phenomenology of illness, rates of comorbid psychiatric disorders, and dissatisfaction with body image. Homosexuality did not appear to be a common feature of men with eating disorders in the community. Childhood physical and sexual abuse appeared slightly more common among the eating-disordered men than among the comparison men.Eating disorders, although less common in men than in women, appear to display strikingly similar features in affected individuals of the two genders.
Adjuvant Ganglioside GM2-KLH/QS-21 Vaccination Versus Observation After Resection of Primary Tumor &gt; 1.5 mm in Patients With Stage II Melanoma: Results of the EORTC 18961 Randomized Phase III Trial
Authors: Alexander M.M. Eggermont, Stefan Suciu, Piotr Rutkowski, Jeremy Marsden, Mario Santinami, Philippa Corrie, Steinar Aamdal, Paolo A. Ascierto, Poulam M. Patel, Wim H. Kruit, Lars Bastholt, Lorenzo Borgognoni, Maria Grazia Bernengo, Neville Davidson, Larissa Polders, Michel Praet, Alan Spatz
Journal: Journal of Clinical Oncology (2013)

The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation.A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat.After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity.GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
Biophysical basis for monophasic action potential
Authors: V NESTERENKO, M KONDO, C ANTZELEVITCH
Journal: Cardiovascular Research (2005)

We welcome Dr. Franz's comments relative to our recent publication dealing with the monophasic action potential (MAP) [1].We agree and fully appreciate the fact that the Franz contact electrode technique has been successfully used for over 20 years by Dr. Franz and other investigators.This success stems from the fact that the two electrodes of the contact catheter are relatively close to each other so that their combined field of view is fairly localized.However, we do not agree that this success can be used as an argument against our conclusion that it is not the tip electrode that records the MAP.Our study investigated the physical principles behind the MAP recording.We started with a simple definition of voltage as the difference of potential between two points or two electrodes.To determine which of these two potentials carries time-dependent information, we placed the two electrodes at sites with different cellular activity and observed which activity is reflected in the MAP signal.The observations demonstrated in a very straightforward manner that the tip or inactivating electrode is not the recording electrode.This conclusion provides support for theories introduced as early as 1934 [2].
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1928)

The therapeutic effect of several antiparasitic chemicals on experimental verruga peruana is described. The drugs were administered by intravenous injection according as the nodules (1) were already developed to an approximate maximum, or (2) were still in the active period of growth. The effect of the drugs was different under the two circumstances of their administration. When they were given after the maturity of the nodules they hastened the regressive process, but when given during active growth of the lesions no action whatever was detected. Bartonella bacilliformis in culture is acted upon injuriously by a number of the chemicals employed in the therapeutic tests, the most active being formalin and neutroflavine.