tbuckley/cabot-search huggingface dataset:
Cellular FLICE-inhibitory protein is required for T cell survival and cycling
Authors: Hien Chau, Veronica Wong, Nien-Jung Chen, Huey-Lan Huang, Wen-Jye Lin, Christine Mirtsos, Alisha R. Elford, Madeleine Bonnard, Andrew Wakeham, Annick Itie You-Ten, Bénédicte Lemmers, Leonardo Salmena, Marc Pellegrini, Razq Hakem, Tak W. Mak, Pamela Ohashi, Wen-Chen Yeh
Journal: The Journal of Experimental Medicine (2005)

Fas-associated death domain (FADD) and caspase-8 are key signal transducers for death receptor–induced apoptosis, whereas cellular FLICE-inhibitory protein (cFLIP) antagonizes this process. Interestingly, FADD and caspase-8 also play a role in T cell development and T cell receptor (TCR)–mediated proliferative responses. To investigate the underlying mechanism, we generated cFLIP-deficient T cells by reconstituting Rag−/− blastocysts with cFLIP-deficient embryonic stem cells. These Rag chimeric mutant mice (rcFLIP−/−) had severely reduced numbers of T cells in the thymus, lymph nodes, and spleen, although mature T lymphocytes did develop. Similar to FADD- or caspase-8–deficient cells, rcFLIP−/− T cells were impaired in proliferation in response to TCR stimulation. Further investigation revealed that cFLIP is required for T cell survival, as well as T cell cycling in response to TCR stimulation. Interestingly, some signaling pathways from the TCR complex appeared competent, as CD3 plus CD28 cross-linking was capable of activating the ERK pathway in rcFLIP−/− T cells. We demonstrate an essential role for cFLIP in T cell function.
Abnormally High Degree Connectivity of the Orbitofrontal Cortex in Obsessive-Compulsive Disorder
Authors: Jan C. Beucke, Jorge Sepulcre, Tanveer Talukdar, Clas Linnman, Katja Zschenderlein, Tanja Endrass, Christian Kaufmann, Norbert Kathmann
Journal: JAMA Psychiatry (2013)

Neurobiological models of obsessive-compulsive disorder (OCD) predict hyperactivity in brain circuits involving the orbitofrontal cortex and the basal ganglia, but it is unclear whether these areas are also characterized by altered brain network properties.To determine regions of abnormal degree connectivity in patients with OCD and to investigate whether connectivity measures are affected by antidepressant medication in OCD.Case-control cross-sectional study using resting-state functional magnetic resonance imaging and a data-driven, model-free method to test for alterations in the degree of whole-brain, distant, and local connectivity in unmedicated patients with OCD compared with healthy controls.Outpatient clinic for OCD.Twenty-three patients with OCD (12 women, 11 men) receiving no medication, 23 patients with OCD (14 women, 9 men) treated with antidepressant medication, and 2 equally sized control samples matched for age, sex, handedness, educational level, and IQ.Statistical parametric maps testing the degree of distant and local functional connectivity of each voxel (hub analysis at voxel level) and OCD symptom severity.Unmedicated patients with OCD showed greater distant connectivity in the orbitofrontal cortex and subthalamic nucleus and greater local connectivity in the orbitofrontal cortex and the putamen. Furthermore, distant connectivity of the orbitofrontal cortex and the putamen positively correlated with global OCD symptom severity. Medicated patients with OCD showed reduced local connectivity of the ventral striatum compared with the unmedicated patients.Consistent with neurobiological models of OCD, the orbitofrontal cortex and the basal ganglia are hyperconnected in unmedicated patients. The finding of distant connectivity alterations of the orbitofrontal cortex and the basal ganglia represents initial evidence of greater connections with distant cortical areas outside of corticostriatal circuitry. Furthermore, these data suggest that antidepressant medication may reduce connectivity within corticobasal ganglia-thalamo-cortical circuits in OCD.
Morson and Dawson’s Gastrointestinal Pathology, 4th edn
Authors: N A Wright
Journal: Gut (2005)

Edited by D W Day, J R Jass, A B Price, et al . Massachusetts: Blackwell Publishing, 2003, £175.00, pp 692. ISBN 0-632-04204-4

Why do people buy s book such as this, which involves a not inconsiderable financial outlay (even if you box clever and make it tax deductible)? I think for two main reasons—firstly, for use as a bench book, and secondly, for information on the pathological basis of gastrointestinal disease for interest, teaching, or indeed …
Genetic diagnosis of lymph-node metastasis in colorectal cancer
Authors: N. Hayashi, I. Ito, Y. Nakamura, A. Yanagisawa, Y. Kato, S. Nakamori, S. Imaoka, H. Watanabe, N. Hayashi, M. Ogawa, Y. Nakamura
Journal: The Lancet (1995)
Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group
Authors: Miguel A. Sanz, Pau Montesinos, Edo Vellenga, Consuelo Rayón, Javier de la Serna, Ricardo Parody, Juan M. Bergua, Angel León, Silvia Negri, Marcos González, Concha Rivas, Jordi Esteve, Gustavo Milone, José D. González, Elena Amutio, Salut Brunet, J. García-Laraña, Dolors Colomer, María J. Calasanz, Carmen Chillón, Eva Barragán, Pascual Bolufer, Bob Lowenberg
Journal: Blood (2008)
THE INFLUENCE OF THE REDUCTION OF KIDNEY SUBSTANCE UPON NITROGENOUS METABOLISM
Authors: Richard M. Pearce
Journal: The Journal of Experimental Medicine (1908)

1. The removal of one half, two thirds and sometimes three quarters of the kidney substance in the dog causes no change in the general nitrogenous metabolism as determined by estimations of the total nitrogen, urea and ammonia elimination by the urine. 2. The removal of larger amounts, and sometimes of three quarters of the substance, leads to the metabolism condition of starvation. This, however, is apparently the result of the gastro-intestinal disturbance constantly associated with extensive kidney reduction and not of a disturbance of general nitrogenous metabolism. 3. The determination of the amount of faecal nitrogen indicates that the gastro-intestinal disturbance is not due to diminished absorption; and except in one instance there was no evidence of its being due to an increased elimination of nitrogenous substances into the intestine. 4. These experiments do not support the theory that the kidney furnishes an internal secretion having an important influence on general nitrogenous metabolism. At least, if such a function exists, it is not disturbed by the removal of three quarters of the kidney substance. 5. The metabolism in excessive kidney reduction is that of inanition dependent on gastro-intestinal disturbances presumably due to faulty chemical correlation. In this connection further knowledge concerning the elimination into the intestine of toxic substances is desirable.
On the Importance of Rest in the Treatment of Acute Phthisis
Authors: H. J. Campbell
Journal: BMJ (1897)

13, 89 than the latter, and seems to be present in what may be termed " passive " increase of intracranial pressure-that is, where the intracranial pressure is increased from alteration of th^circulation in the rest of the body.14.In some conditions the intracranial circulation seems to vary independently of the circulation elsewhere.This would tend to show that, although the blood vessels of the brain are not directly controlled from the general vasomotor centre, the e must be some local mechauism for altering their calibre.
Repair of articular cartilage defect with layered chondrocyte sheets and cultured synovial cells
Authors: Satoshi Ito, Masato Sato, Masayuki Yamato, Genya Mitani, Toshiharu Kutsuna, Toshihiro Nagai, Taku Ukai, Miyuki Kobayashi, Mami Kokubo, Teruo Okano, Joji Mochida
Journal: Biomaterials (2012)
Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
Authors: Sunil Verma, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, Mark Pegram, Do-Youn Oh, Véronique Diéras, Ellie Guardino, Liang Fang, Michael W. Lu, Steven Olsen, Kim Blackwell
Journal: New England Journal of Medicine (2012)

Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)–targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker.
The Effect of Insulin on Blood Levels of Infused Pentoses in Man
Authors: Stanton Segal, James B. Wyngaarden, Joseph Foley
Journal: Journal of Clinical Investigation (1957)

In 1931 Wierzuchowski (1) showed an influence of insulin on galactose tolerance of dogs.More recently, Levine, Goldstein, Huddlestun, Klein, and Henry (2, 3) demonstrated that insulin lowers the blood levels of D-galactose, D-xylose, and L-arabinose but not of D-arabinose or D-mannose, following their infusion into the eviscerated nephrectomized dog.The volume of distribution of the responsive sugars was increased from 45 to 70 per cent of body weight as a result of insulin administration.It was suggested that the insulin response represented a facilitation of transport of the sugar across the cell membrane into intra- cellular fluid.In all the responsive sugars the stereochemical structure of carbon atoms 1 to 3 was like that of D-glucose, and these authors sug- gested that these structural characteristics determined the insulin responsiveness of a sugar.Confirmatory evidence has appeared that insulin affects transport of D-galactose, D-xylose and L-arabinose across the cell membrane in the rat diaphragm (4-6), eviscerate rat (7), perfused rat heart (8) and intact cat (9).However, slow penetration of a number of sugars into muscle of nephrectomized and eviscerated rats has now also been demonstrated, and this slow penetration is increased by insulin for D-lyxose, D-ribose, D-mannose, D-fructose and D-fucose, as well as for D-xylose, D-galactose and L-arabinose (10,11).Although these results indicate that the concept of structural specificity in carbon atoms 1 to 3 for insulin responsiveness has proved to be too limited in scope, the lack of an effect of insulin upon in- tracellular entry of sorbitol, mannitol and raffinose is strong evidence that the action of insulin is not simply an acceleration of a process of physical diffusion (12).
Myocardial infarction in Mexican-Americans and non-Hispanic whites. The San Antonio Heart Study.
Authors: B D Mitchell, H P Hazuda, S M Haffner, J K Patterson, M P Stern
Journal: Circulation (1991)

Mexican-American men experience reduced cardiovascular mortality compared with non-Hispanic white men. There is no corresponding ethnic difference in cardiovascular mortality in women. The difference in men could result either from a lower incidence of cardiovascular disease or a lower case fatality rate among Mexican-Americans. Although the incidence of cardiovascular disease in Mexican-Americans is unknown, we have collected data on prevalence of myocardial infarction in 5,148 individuals examined in the San Antonio Heart Study, a population-based survey of cardiovascular disease conducted between 1979 and 1988 in Mexican-Americans and non-Hispanic whites aged 25-64 years. Myocardial infarction was assessed by Minnesota-coded electrocardiograms and by a self-reported history of a physician-diagnosed heart attack. For both end points, the age-adjusted prevalence of myocardial infarction was lower in Mexican-American men than in non-Hispanic white men. After adjustment for age and diabetes status (present/absent), the odds of a myocardial infarction, as defined by either criterion, was approximately one third lower in Mexican-American men than in non-Hispanic white men (p = 0.06). In women, the prevalence of both myocardial infarction end points was slightly higher in Mexican-Americans than in non-Hispanic whites, although neither of these differences was significant. Although the ethnic differences in prevalence in this study were not statistically significant, their pattern parallels the pattern in the mortality due to cardiovascular diseases. Therefore, the results support the hypothesis that the reduced cardiovascular mortality rate observed in Mexican-American men reflects a lower incidence of myocardial infarction rather than a reduced case fatality rate because the latter would result in a higher prevalence.
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial
Authors: John A Dormandy, Bernard Charbonnel, David JA Eckland, Erland Erdmann, Massimo Massi-Benedetti, Ian K Moules, Allan M Skene, Meng H Tan, Pierre J Lefèbvre, Gordon D Murray, Eberhard Standl, Robert G Wilcox, Lars Wilhelmsen, John Betteridge, Kåre Birkeland, Alain Golay, Robert J Heine, László Korányi, Markku Laakso, Marián Mokáň, Antanas Norkus, Valdis Pirags, Toomas Podar, André Scheen, Werner Scherbaum, Guntram Schernthaner, Ole Schmitz, Jan Škrha, Ulf Smith, Jan Tatoň
Journal: The Lancet (2005)
METHODOLOGICAL CONSIDERATION ON THIGH MARKER CLUSTERS ON KNEE VALGUS ANGLES IN SIDESTEP CUTTING AND VERTICAL DROP JUMPING
Authors: KM Mok, EK Kristianslund, T Krosshaug
Journal: British Journal of Sports Medicine (2014)

Background Ranking the athletes according to their knee valgus angle contributes to the development of screening tools for the risk of knee injury. However, studies used different thigh marker clusters to calculate knee valgus angle in marker-based motion analysis system. There is a methodological concern on the thigh marker cluster design which relates to the reliability of measurement. Objective To quantify the differences between six different thigh marker clusters in terms of the calculated knee valgus angles and the ranking of athletes according to the maximal knee valgus angle and knee valgus angle at initial contact. Design A methodological study. Setting A marker-based motion analysis system (Oqus, Qualisys, Gothenburg, Sweden) with 480 Hz frame rate was used. Six different marker clusters was put on the thigh of subjects. Subjects performed sidestep cutting and vertical drop jumping motions while being filmed with a skin marker-based motion capture system. The knee valgus angles from six different thigh marker clusters were calculated based on the dynamic trials. Participants 19 elite female handball players and 22 elite female football players (n=41). Main outcome measurements The calculated knee valgus angles and the resulting ranking of athletes from six different thigh marker clusters. Results There was a discrepancy in knee valgus angles between the six marker sets up to 13.9° of peak valgus angle. The rank correlation coefficient varied from 0.505 to 0.974. Conclusions The present study demonstrated that the choice of thigh marker clusters in analyses of drop jumps and sidestep cutting affected the magnitude of knee valgus angle, as well as the ranking of athletes. A standardized thigh marker cluster setup would facilitate the reliability of measurement, especially for a study on risk factor . Table 1: Thigh skin marker cluster. Marker cluster Skin marker component Number of markers Design I LE, AT, GT 3 Ford et al . (2003), Howett et al. (2005) II LE, DAT, GT 3 McLean et al . (1999) III LE, DAT, LT 3 Distal thigh + GT V LE,DAT,LT,GT 4 Distal thigh + GT VI LE,DAT,LT,HJC 4 Distal thigh + HJC VI LE,DAT,LT,HJC,GT 5 Kristianslumnd et al . (2012) Table 2: The mean (SD) of the outcome variables on different thigh marker clusters. Task Marker cluster I II III IV V VI Sidestep cutting Valgus at 1C (deg) 0.7 (3.3) 3.5 (2.6) 2.4 (3.0) 5.0 (3.1) 6.2 (3.4) 5.0 (3.4) Peak valgus (deg) 9.0 (4.0) 10.5 (4.1) 10.6 (4.5) 13.5 (4.6) 13.7 (5.4) 11.6 (5.5) Vertical drop jumping Valgus at IC (deg) -5.0 (3.5) 0.24 (3.0) 0.9 (3.2) 2.1 (3.0) 1.0 (3.5) -1.0 (3.6) Peak valgus (deg) 1.9 (2.8) 9.5 (5.0) 11.6 (5.4) 15.8 (5.8) 12.0 (5.3) 6.9 (5.3)
Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells
Authors: Andrei Ivanov, Stephen A. Beers, Claire A. Walshe, Jamie Honeychurch, Waleed Alduaij, Kerry L. Cox, Kathleen N. Potter, Stephen Murray, Claude H.T. Chan, Tetyana Klymenko, Jekaterina Erenpreisa, Martin J. Glennie, Tim M. Illidge, Mark S. Cragg
Journal: Journal of Clinical Investigation (2009)

mAbs are becoming increasingly utilized in the treatment of lymphoid disorders. Although Fc-FcgammaR interactions are thought to account for much of their therapeutic effect, this does not explain why certain mAb specificities are more potent than others. An additional effector mechanism underlying the action of some mAbs is the direct induction of cell death. Previously, we demonstrated that certain CD20-specific mAbs (which we termed type II mAbs) evoke a nonapoptotic mode of cell death that appears to be linked with the induction of homotypic adhesion. Here, we reveal that peripheral relocalization of actin is critical for the adhesion and cell death induced by both the type II CD20-specific mAb tositumomab and an HLA-DR-specific mAb in both human lymphoma cell lines and primary chronic lymphocytic leukemia cells. The cell death elicited was rapid, nonapoptotic, nonautophagic, and dependent on the integrity of plasma membrane cholesterol and activation of the V-type ATPase. This cytoplasmic cell death involved lysosomes, which swelled and then dispersed their contents, including cathepsin B, into the cytoplasm and surrounding environment. The resulting loss of plasma membrane integrity occurred independently of caspases and was not controlled by Bcl-2. These experiments provide what we believe to be new insights into the mechanisms by which 2 clinically relevant mAbs elicit cell death and show that this homotypic adhesion-related cell death occurs through a lysosome-dependent pathway.
Diagnosis and management of menopause: summary of NICE guidance
Authors: G. Sarri, M. Davies, M. A. Lumsden
Journal: BMJ (2015)

#### What you need to know

The average age of menopause in the United Kingdom is 51 years, although 1% of women experience premature ovarian insufficiency (menopause before the age of 40 years). Eight out of 10 women experience perimenopausal symptoms, most commonly hot flushes and night sweats (figure⇓), which typically last about four years.1 Quality of life may be severely affected.2



Perimenopausal symptoms. FSH=follicle stimulating hormone; GNRH=gonadotrophin releasing hormone; LH=luteinising hormone 



Services and information available for menopausal women in the UK are variable.3 The use of hormone replacement therapy has been highly controversial.4 5

#### What’s new in this guidance 

This article summarises the most recent recommendations on the diagnosis and management of menopause from …
Heterogeneity of the <i>MYCN</i> Oncogene in Neuroblastoma
Authors: Jessica Theissen, Marc Boensch, Ruediger Spitz, David Betts, Sabine Stegmaier, Holger Christiansen, Felix Niggli, Freimut Schilling, Manfred Schwab, Thorsten Simon, Frank Westermann, Frank Berthold, Barbara Hero
Journal: Clinical Cancer Research (2009)

MYCN amplification is an important therapy-stratifying marker in neuroblastoma. Fluorescence in situ hybridization with signal detection on the single-cell level allows a critical judgement of MYCN intratumoral heterogeneity.The MYCN status was investigated by fluorescence in situ hybridization at diagnosis and relapse. Heterogeneity was defined as the simultaneous presence of amplified cells (>/=5 cells per slide) and nonamplified cells within one tumor or sequential change of the amplification status during the course of the disease. Likewise, heterogeneity can be detected between primary tumor and metastasis.From 1,341 patients analyzed, 1,071 showed no amplification, 250 showed homogeneous amplification, and 20 patients showed MYCN heterogeneity. Of the patients with heterogeneity, 12 of 20 had clusters of MYCN amplifications, 3 of 20 had amplified single cells, 3 of 20 showed MYCN amplifications in the bone marrow but not in the primary tumor, and 2 of 20 acquired MYCN amplification during the course of the disease. All stage 4 patients were treated according to high-risk protocols; 7 of 8 later progressed. Four patients with localized disease were treated according to high-risk protocol because of MYCN-amplified clusters; 1 of 4 later progressed. One patient treated with mild chemotherapy experienced progression. Seven patients with localized/4S disease underwent no chemotherapy: 4 of 5 patients with MYCN heterogeneity at diagnosis remained disease-free, and 1 of 5 experienced local progression. Two patients had normal MYCN status at diagnosis but acquired MYCN amplification during the course of the disease.MYCN heterogeneity is rare. Our results suggest that small amounts of MYCN-amplified cells are not correlated to adverse outcomes. More patients with heterogeneity are warranted to clarify the role of MYCN heterogeneity for risk classification.
Small-Cell Cancers, and an Unusual Reaction to Chemotherapy
Authors: Uzair B. Chaudhary, Jason D. Taksey, R. Duren Johnson, David N. Lewin
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.06.165 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12805346 Small-Cell Cancers, and an Unusual Reaction to Chemotherapy CASE 3. SMALL-CELL CARCINOMA OF THE STOMACH Uzair B. ChaudharyxUzair B. ChaudharySearch for articles by this author , Jason D. TakseyxJason D. TakseySearch for articles by this author , R. Duren JohnsonxR. Duren JohnsonSearch for articles by this author , David N. LewinxDavid N. LewinSearch for articles by this author Show More Departments of Medicine and Pathology, Medical University of South Carolina, Charleston, SC https://doi.org/10.1200/JCO.2003.06.165 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Using New Technologies to Improve the Prevention and Management of Chronic Conditions in Populations
Authors: Brian Oldenburg, C. Barr Taylor, Adrienne O'Neil, Fiona Cocker, Linda D. Cameron
Journal: Annual Review of Public Health (2015)

Lifestyle factors are important in the development of chronic diseases, such as heart disease, respiratory disease, and diabetes, and chronic disease risk can be reduced by changes in lifestyle behaviors linked to these conditions. The use of mass media and community-wide strategies targeting these behaviors has been extensively evaluated since the 1970s. This review summarizes some examples of interventions and their use of media conducted within the old communications landscape of the 1970s and 1980s and the key lessons learned from their design, implementation, and evaluation. We then consider the potential and evidence base for using contemporary technology applications and platforms-within the new communications landscape-to improve the prevention and management of lifestyle-related chronic diseases in the future. We discuss the implications and adaptation of lessons derived from the ways in which new technologies are being used in commercial and political contexts and their relevance for public health. Finally, we consider some recent examples of applying new technologies to public health issues and consider some of the challenges in this rapidly developing field.