tbuckley/cabot-search huggingface dataset:
Glucocorticoid receptor-mediated suppression of the interleukin 2 gene expression through impairment of the cooperativity between nuclear factor of activated T cells and AP-1 enhancer elements.
Authors: A Vacca, M P Felli, A R Farina, S Martinotti, M Maroder, I Screpanti, D Meco, E Petrangeli, L Frati, A Gulino
Journal: The Journal of Experimental Medicine (1992)

The immunosuppressant hormone dexamethasone (Dex) interferes with T cell-specific signals activating the enhancer sequences directing interleukin 2 (IL-2) transcription. We report that the Dex-dependent downregulation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and calcium ionophore-induced activity of the IL-2 enhancer are mediated by glucocorticoid receptor (GR) via a process that requires intact NH2- and COOH-terminal and DNA-binding domains. Functional analysis of chloramphenicol acetyltransferase (CAT) vectors containing internal deletions of the -317 to +47 bp IL-2 enhancer showed that the GR-responsive elements mapped to regions containing nuclear factor of activated T cells protein (NFAT) (-279 to -263 bp) and AP-1 (-160 to -150 bp) motifs. The AP-1 motif binds TPA and calcium ionophore-induced nuclear factor(s) containing fos protein. TPA and calcium ionophore-induced transcriptional activation of homo-oligomers of the NFAT element were not inhibited by Dex, while AP-1 motif concatemers were not stimulated by TPA and calcium ionophore. When combined, NFAT and AP-1 motifs significantly synergized in directing CAT transcription. Such a synergism was impaired by specific mutations affecting the trans-acting factor binding to either NFAT or AP-1 motifs. In spite of the lack of hormone regulation of isolated cis elements, TPA/calcium ionophore-mediated activation of CAT vectors containing a combination of the NFAT and the AP-1 motifs became suppressible by Dex. Our results show that the IL-2-AP-1 motif confers GR sensitivity to a flanking region containing a NFAT element and suggest that synergistic cooperativity between the NFAT and AP-1 sites allows GR to mediate the Dex inhibition of IL-2 gene transcription. Therefore, a Dex-modulated second level of IL-2 enhancer regulation, based on a combinatorial modular interplay, appears to be present.
US healthcare spending will reach 20% of GDP by 2024, says report
Authors: Michael McCarthy
Journal: BMJ (2015)

US healthcare spending will grow by an average of 5.8% a year from 2014 through to 2024, rising to $5.4 trillion (£3.46trn; €4.92trn) a year—nearly 20% of the nation’s gross domestic product—says a report by government economists.

The report was prepared by economists and actuaries in the Office of the Actuary at the Centers for Medicare and Medicaid Services, and it appeared in the August issue of …
A3.2 Five year survival rate and predictors of death and disease worsening in a single-center cohort of patients with systemic sclerosis
Authors: A Soare, C Mihai, R Dobrotă, AM Gherghe, C Vancea, M Gorga, R Ioniţescu, R Jurcuţ, Ş Magda, T Constantinescu, R Sfrenţ-Cornăţeanu, I Ancuţa, M Sasu, M Milicescu, L Macovei, C Ciofu, A Martin, A Shorab, M Bojincă, V Stoica
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic sclerosis (SSc) is associated with a significant reduction in survival in comparison to the general population. This is the first report on 5-year survival and its predictors in a Romanian cohort of SSc patients. <h3>Objective</h3> We aimed to assess the 5-year survival rate in a single-center cohort of SSc patients and to identify predictors of death and disease worsening. <h3>Methods</h3> All patients of the EUSTAR Center 100 enrolled before 2009 and who had at least 2 visits at a minimum interval of 5 years, or who died after at least 3 months of follow-up, were included. All patients were assessed according to current EUSTAR recommendations. A comparison was made between the surviving and the deceased patients regarding all MEDS baseline parameters. Using age-adjusted univariate logistic regression we identified predictors for death and for several outcomes considered as disease worsening: 20% reduction in forced vital capacity (FVC); 20% reduction in diffusing capacity of the lung for carbon monoxide (DLCO); development of pulmonary arterial hypertension (PAH) as assessed by power Doppler heart ultrasound; and digital ulcers (DUs) recurrent at prospective visits. <h3>Results</h3> Out of 68 patients enrolled before 01.01.2009, 40 met the inclusion criteria (82,5% females, 55% limited cutaneous subset, mean ± SD follow-up period 5.7 ± 2.1 years; mean ± SD age at first visit 49 ± 11.8 years; mean ± SD disease duration at first visit 4.4 ± 6.0 years). Throughout the 5-year follow-up period there were 7 deaths (including 3 SSc-related deaths), resulting in an overall 5-year survival rate of 82,5%. In survivors, lung function tests deteriorated significantly in 11% (FVC) and 52% (DLCO), while 20% developed PAH. Recurrent or newly appearing DUs occurred in 21% of all 42 patients. Significant predictors for death were the diffuse cutaneous subset, and the presence of DUs at presentation, with odd ratios [95% confidence interval] (OR[CI95%]) of 14,2 [1.3-151] and 38 [2.9-501] respectively. Conduction blocks on the baseline ECG predicted PAH with an OR [95% CI] of 12.8 [1.5-108]. Significant predictors for DUs were active DUs and calcinosis at presentation: OR [CI95%] 5.2 [1.1-26] and 6 [1.1-33] respectively. None of the parameters tested as potential predictors of the respiratory function decline achieved statistical significance. <h3>Conclusions</h3> The survival rate in our cohort was 82.5%, which is similar to other cohorts from developed countries. We identified diffuse cutaneous subset, active digital ulcers, and heart conduction blocks as predictors for a poor disease outcome.
Disseminated Tumor Cells in Lymph Nodes as a Determinant for Survival in Surgically Resected Non–Small-Cell Lung Cancer
Authors: B. Kubuschok, B. Passlick, J. R. Izbicki, O. Thetter, K. Pantel
Journal: Journal of Clinical Oncology (1999)

In recent years, the detection of even a few tumor cells in lymph nodes of patients with surgically resected non-small-cell lung cancer (NSCLC) became possible with immunohistochemical staining procedures. Tumor cells in lymph nodes have been shown to be associated with an increased rate of early recurrence. However, the prognostic significance of this minimal tumor cell spread for overall survival remains unclear.We used the epithelium-specific monoclonal antibody Ber-EP4, which recognizes the 17-1A antigen (also called EGP40 or Ep-CAM), to discover small tumor cell deposits (< or = three cells) in 565 regional lymph nodes judged as tumor-free by conventional histopathology in patients with NSCLC staged as pT1-4, pN0-2, M0, R0. In a prospective analysis, we studied the influence of the detected tumor cells on the cancer recurrence rate and survival of 117 patients.Ber-EP4-positive cells were found in 27 of 125 patients (21.6%). After an observation period of 64 months, patients with disseminated tumor cells had reduced disease-free survival (P < .0001) and overall survival (P = .0001) rates in univariate analyses (logrank test). Multivariate analysis (Cox model) showed a 2.7 times increased risk for tumor relapse and a 2.5 times increased risk for shorter survival in patients with disseminated tumor cells compared with patients without such cells. Patients without any evidence of histopathologic and immunohistochemical lymph node involvement had an overall survival rate of 78%.The immunohistochemical detection of disseminated tumor cells in lymph nodes of patients with completely resected NSCLC is an independent prognostic factor for overall survival.
Involvement of FAN in TNF-induced apoptosis
Authors: Bruno Ségui, Olivier Cuvillier, Sabine Adam-Klages, Virginie Garcia, Sophie Malagarie-Cazenave, Sophie Lévêque, Sylvie Caspar-Bauguil, Jérôme Coudert, Robert Salvayre, Martin Krönke, Thierry Levade
Journal: Journal of Clinical Investigation (2001)

TNF-alpha is a pleiotropic cytokine activating several signaling pathways initiated at distinct intracellular domains of the TNF receptors. Although the C-terminal region is believed to be responsible for apoptosis induction, the functions of more membrane-proximal domains, including the domain that couples to neutral sphingomyelinase activation, are not yet fully elucidated. The roles of this region and of the associated adapter protein FAN (factor associated with neutral SMase activation) in the cytotoxic response to TNF have been investigated. We have now shown that stable expression in human fibroblasts of a dominant negative form of FAN abrogates TNF-induced ceramide generation from sphingomyelin hydrolysis and reduces caspase processing, thus markedly inhibiting TNF-triggered apoptosis. However, the cytotoxic responses to daunorubicin and exogenous ceramide remain unaltered, as do the TNF-induced p42/p44 MAPK activation and CD54 expression. Fibroblasts from FAN-knockout mice also proved to be resistant to TNF toxicity. These findings highlight the previously unrecognized role of the adapter protein FAN in signaling cell death induction by TNF.
Injuries in national Olympic level judo athletes: an epidemiological study
Authors: Keun-Suh Kim, Ki Jun Park, Jaekoo Lee, Byung Yong Kang
Journal: British Journal of Sports Medicine (2015)

To present an epidemiological study of injuries found among South Korea's National level Judo athletes as a foundation for future injury prevention and skill enhancement in this group.This study is a prospective study on a 4-year injury assessment held from January 2010 to December 2013 at the training centre in South Korea for National Level athletes. Athlete's weight class, gender, injury location and injury grade (grade I=1-3 treatment days, grade II=4-7 treatment days, and grade III ≥8 treatment days) were analysed.There were a total of 782 injuries recorded during this period, equalling to four injuries per athlete annually. Almost half of these injuries (47%) were grade I injuries. Injury occurrence was the highest in the Lower body (44.2%). This was then followed by injuries in the upper body (29.8%), trunk (20.3%) and head and neck (5.6%). Men and women showed similar, non-significantly different trends in the proportion of body parts injured. Women experienced more grade III injuries than males (p=0.0228). Comparison between women in different weight classes also showed that heavyweights incurred more grade III injuries than lightweights (p=0.0087). Lightweights had a higher rate of injury than heavyweights in males and females, although this was statistically significant only among males (p<0.001).Many body regions are prone to injury in the elite judo population. Women, especially those in the heavyweight classification, were more prone to severe injuries. Lightweights experienced more injuries than heavyweights among male athletes. Specifically, further studies are needed to confirm these findings and to address the impact of rapid weight loss practices on injury risk to implement effective preventive measures.
Perioperative Reactions: Are They So Infrequent?
Authors: Claude M. Urbain, Alberto Lafuente, Gracia Javaloyes, Paula Cabrera-Freitag, Juan De La Borbolla Moran, M. Jose Goikoetxea, Rafael Moncada, Maria L. Sanz, Marta M. Ferrer, Gabriel Gastaminza
Journal: Journal of Allergy and Clinical Immunology (2014)
Occult gastro-intestinal cause of spastic paresis of the legs
Authors: V Verma, A Dhar, P F Chinnery
Journal: Gut (2008)

A 40-year-old man with diabetes presented with difficulty in walking and paresthesia affecting both feet. Examination revealed pes cavus (fig 1), lower limb hypertonia, sustained ankle clonus and symmetric hyper-reflexia. There was no muscle weakness and cerebellar signs were absent. …
What Erdelyi has repressed
Authors: Frederick Crews
Journal: Behavioral and Brain Sciences (2006)

Erdelyi's “unified theory of repression” attempts to rehabilitate psychoanalytic doctrine by exaggerating its compatibility with the findings of cognitive science. In addition, Erdelyi treats Freud's writings as holy writ, any portion of which can be quoted to prove a point. He also relies on a long-discredited account of Freud's “seduction theory” and ignores important links between Freudian assumptions and our recent recovered memory movement.
Moving From Political Declaration to Action on Reducing the Global Burden of Cardiovascular Diseases
Authors: Sidney C. Smith, Deborah Chen, Amy Collins, John G. Harold, Mariell Jessup, Staffan Josephson, Susanne Logstrup, Cand Jur, Ralph L. Sacco, Panos E. Vardas, David A. Wood, William A. Zoghbi
Journal: Circulation (2013)
Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE
Authors: J. Thariat, T. Schouman, A. Brouchet, J. Sarini, R.C. Miller, H. Reychler, I. Ray-Coquard, A. Italiano, C. Verite, S. Sohawon, E. Bompas, O. Dassonville, S. Salas, K. Aldabbagh, P. Maingon, T. de La MotteRouge, J.E. Kurtz, J. Usseglio, P. Kerbrat, G. Raoul, J.P. Lotz, G. Bar-Sela, L. Brugières, L. Chaigneau, E. Saada, G. Odin, P.Y. Marcy, A. Thyss, M. Julieron
Journal: Annals of Oncology (2012)
Germinal Center Formation and Local Immunoglobulin E (IgE) Production in the Lung after an Airway Antigenic Challenge
Authors: Yolande Chvatchko, Marie H. Kosco-Vilbois, Suzanne Herren, Jean Lefort, Jean-Yves Bonnefoy
Journal: The Journal of Experimental Medicine (1996)

Airway inflammation plays a central role in the pathogenesis of asthma. However, the precise contribution of all cell types in the development and maintenance of airway hyperreactivity and histopathology during allergic inflammation remains unclear. After sensitization of mice in the periphery, challenge by multiple intratracheal (i.t.) instillations of ovalbumin (OVA) results in eosinophilia, mononuclear cell infiltration, and airway epithelial changes analogous to that seen in asthma (Blyth, D.I., M.S. Pedrick, T.J. Savage, E.M. Hessel, and D. Fattah. 1996. Am. J. Respir. Cell Mol. Biol. 14:425-438). To investigate further the nature of the cellular infiltrate, lungs from OVA-versus saline-treated mice were processed for histology and immunohistochemistry. One of the most striking features observed was the formation of germinal centers within the parenchyma of the inflamed lungs. In addition, follicular dendritic cells (FDCs) bearing OVA on their plasma membranes appeared and, adjacent to these sites, OVA-specific IgG1-, IgE-, and IgA-producing plasma cells emerged. To confirm that antigen-specific immunoglobulins (Ig) were being produced within the parenchyma, plasma cell number and antibody production were quantitated in vitro after isolation of cells from the lung. These assays confirmed that the isotypes observed in situ were a secreted product. As IgE-dependent mechanisms have been implicated as being central to the pathogenesis of bronchial asthma, airway hyperresponsiveness was evaluated. The mice undergoing lung inflammation were hyperresponsive, while the control group remained at baseline. These data demonstrate that antigen-driven differentiation of B cells via induction of an FDC network and germinal centers occurs in the parenchyma of inflamed lungs. These germinal centers would then provide a local source of IgE-secreting plasma cells that contribute to the release of factors mediating inflammatory processes in the lung.
Epigenetic Status of Gdnf in the Ventral Striatum Determines Susceptibility and Adaptation to Daily Stressful Events
Authors: Shusaku Uchida, Kumiko Hara, Ayumi Kobayashi, Koji Otsuki, Hirotaka Yamagata, Teruyuki Hobara, Takayoshi Suzuki, Naoki Miyata, Yoshifumi Watanabe
Journal: Neuron (2011)

Stressful events during adulthood are potent adverse environmental factors that can predispose individuals to psychiatric disorders, including depression; however, many individuals exposed to stressful events can adapt and function normally. While stress vulnerability may influence depression, the molecular mechanisms underlying the susceptibility and adaptation to chronic stress within the brain are poorly understood. In this study, two genetically distinct mouse strains that exhibit different behavioral responses to chronic stress were used to demonstrate how the differential epigenetic status of the glial cell-derived neurotrophic factor (Gdnf) gene in the ventral striatum modulates susceptibility and adaptation to chronic stress. Our results suggest that the histone modifications and DNA methylation of the Gdnf promoter have crucial roles in the control of behavioral responses to chronic stress. Our data provide insights into these mechanisms, suggesting that epigenetic modifications of Gdnf, along with genetic and environmental factors, contribute to behavioral responses to stress.
Atopic dermatitis in 5–6‐year‐old Swedish children: cumulative incidence, point prevalence, and severity scoring
Authors: A. Broberg, Å Svensson, M. P. Borres, R. Berg
Journal: Allergy (2000)

Background: This study aimed to evaluate the cumulative incidence, point prevalence, and severity of atopic dermatitis (AD) in a pediatric population. We also aimed to identify differential diagnoses relevant to AD in this population. Methods: Children scheduled for a health visit at 5.5 years of age were selected consecutively during the period October 1997–March 1998 from two cities in southern Sweden (Göteborg and Kristianstad). Schultz Larsen's questionnaire was used to evaluate the cumulative incidence of AD. Clinical examination was performed by dermatologists (A.B. and Å.S.) for those children with active eczema. The UK working party's criteria were used for the clinical diagnosis of AD. The SCORAD index was used to evaluate the severity of eczema. This index includes evaluation of extent, intensity, and subjective symptoms to a maximum score of 103 points. Results: In Göteborg 1219 and in Kristianstad 742 questionnaires were answered regarding 1961 children, 1004 boys and 957 girls. The response rate was 89%. According to the answers to Schultz Larsen's questionnaire, the cumulative incidence of AD in the whole material was 20.7% (406/1961) (CI 95% 18.9–22.5). In Göteborg, 104 of the examined children fulfilled the UK working party's criteria, equivalent to a point prevalence of 8.5% (CI 95% 7.0–10.1). In Kristianstad, the corresponding point prevalence was 11.5% (CI 95% 9.2–13.8). The severity of AD was evaluated in all children with visible eczema. SCORAD evaluation was performed in 155 of the 157 children with visible eczema. The majority of children had mild or moderate eczema; mean value 20.5 (CI 95% 18.7–22.3), median 19.6. Of the 96 children who did not fulfil the criteria of AD, other skin disorders were diagnosed in 51 at the clinical examination. Dry skin was by far the most common differential diagnosis. Conclusions: We have used validated protocols to evaluate the cumulative incidence, point prevalence, and severity of AD in a population‐based study in southern Sweden The present study, involving a rural and urban pediatric population, shows that AD is common, usually classified as mild or moderate, and seems to increase over time.
Distinct Chromosomal Bias of Gene Expression Signatures in the Progression of Hepatocellular Carcinoma
Authors: Yutaka Midorikawa, Shuichi Tsutsumi, Kunihiro Nishimura, Naoko Kamimura, Makoto Kano, Hirohiko Sakamoto, Masatoshi Makuuchi, Hiroyuki Aburatani
Journal: Cancer Research (2004)

Abstract To identify the chromosomal aberrations associated with the progression of liver cancer, we applied expression imbalance map analysis to gene expression data from 31 hepatocellular carcinomas and 19 noncancerous tissues. Expression imbalance map analysis, which detects mRNA expression imbalance correlated with chromosomal regions, showed that expression gains of 1q21-23 (74%), 8q13-21 (48%), 12q23-24 (41%), 17q12-21(48%), 17q25 (25%), and 20q11 (22%) and losses of 4q13 (48%), 8p12-21 (32%), 13q14 (32%), and 17p13 (29%) were significantly associated with hepatocellular carcinoma. Most regions with altered expression identified by expression imbalance map were also identified in previous reports using comparative genomic hybridization. We demonstrated chromosomal copy number gain in 1q21-23 and loss in 17p13 by genomic quantitative PCR, suggesting that gene expression profiles reflect chromosomal alterations. Furthermore, expression imbalance map analysis revealed that more poorly differentiated hepatocellular carcinoma contain more chromosomal alterations, which are accumulated in a stepwise manner in the course of hepatocellular carcinoma progression: expression imbalance of 1q, 8p, 8q, and 17p occur as early events in hepatocarcinogenesis, and 12q, 17q25 and 20q occur as later events. In particular, expression gain of 17q12-21 and loss of 4q were seen to accumulate constantly through the dedifferentiation process. Our data suggest that gene expression profiles are subject to chromosomal bias and that expression imbalance map can correlate gene expression to gene loci with high resolution and sensitivity.
Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis
Authors: A McEntegart, E Morrison, H A Capell, M R Duncan, D Porter, R Madhok, E A Thomson
Journal: Annals of the Rheumatic Diseases (1997)

Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow.814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients.The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities.RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.