tbuckley/cabot-search huggingface dataset:
Enhancement of MEK/ERK signaling promotes glucocorticoid resistance in CD4+ T cells
Authors: Daphne C. Tsitoura, Paul B. Rothman
Journal: Journal of Clinical Investigation (2004)

Glucocorticoids have potent immunosuppressive properties, but their effects are often modulated by the conditions prevailing in the local immune milieu. In this study we determined whether the action of glucocorticoids is influenced by the degree of signaling during T cell activation. We found that dexamethasone (Dex) effectively suppressed T cell receptor–induced (TCR-induced) proliferation of naive CD4+ T cells, through a mechanism involving downregulation of c-Fos expression and inhibition of activator protein-1 (AP-1), nuclear factor of activated T cells (NF-AT), and NF-κB transcriptional activity. However, enhancement of TCR signaling by CD28- or IL-2–mediated costimulation abrogated the suppressive effect of Dex on c-Fos expression and AP-1 function and restored cellular proliferation. The amount of signaling through the MAPK pathway was critical in determining the effect of Dex on T cell activation. In particular, costimulatory signaling via MAPK kinase (MEK) and extracellular signal–regulated kinase (ERK) was essential for the development of T cell resistance to Dex. Selective blockade of MEK/ERK signal transduction abolished the costimulation-induced resistance. In contrast, transmission of IL-2 signals via STAT5 and CD28 signals via NF-κB remained inhibited by Dex. These results imply that the immune system, by regulating the degree of local costimulation through MEK/ERK, can modify the effect of glucocorticoids on T cells. Moreover, these findings suggest that MAPK inhibitors may offer a therapeutic solution for glucocorticoid resistance.
Deceleration Time in Ischemic Cardiomyopathy
Authors: Yongqi Yong, Sherif F. Nagueh, Sarah Shimoni, Kesavan Shan, Zuo-Xiang He, Michael J. Reardon, George V. Letsou, Jimmy F. Howell, Mario S. Verani, Miguel A. Quiñones, William A. Zoghbi
Journal: Circulation (2001)

Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. Methods and Results —Forty patients with ischemic cardiomyopathy underwent 201 Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 μg · kg −1 · min −1 ) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE ( r =0.72), scar perfusion defect by SPECT ( r =−0.69), and the change in ejection fraction (ΔEF) after surgery ( r =0.77) (all P &lt;0.01). DT &gt;150 ms effectively identified (sensitivity 79%, specificity 81%) patients with ΔEF ≥5%. The population was divided into 2 groups according to DT: group 1 (DT &gt;150 ms, n=21) and group 2 (DT ≤150 ms, n=19). At baseline, NYHA class, LV EF, age, and use of cardiovascular drugs were similar between the 2 groups. The number of viable segments by both DE and SPECT, however, was higher in group 1 (both P &lt;0.01), and only patients in group 1 had an increase in EF (29±4.8% to 40±8%, P &lt;0.01) after surgery. Death and heart transplantation occurred in 7 patients from group 2 and 1 patient from group 1 ( P =0.017). Conclusions —In patients with ischemic cardiomyopathy, the reduced amount of viable myocardium results in a restrictive mitral inflow pattern, which in turn predicts poor survival.
Case of Mesenteric Reticulosarcoma Associated with Gluten-sensitive Steatorrhoea
Authors: C. N. Best, P. B. Cook
Journal: BMJ (1961)

Ten cases of intussusception are reported.An adeno- virus was isolated from the faeces of six of these patients and herpes simplex from the faeces of one.Thirteen subjects of a similar age examined as controls were negative.The possible role of adenovirus in the aetiology of intussusception is discussed.I am indebted to the Child Health Department, Newcastle upon Tyne, and the clinicians at Sheriff Hill Hospital, Gateshead, from whom specimens were obtained.ADDENDUM.-Since this investigation was completed three further cases of intussusception have been examined; two were associated with adenovirus excretion.
Cardiac Arrhythmogenic Remodeling in a Rat Model of Long-Term Intensive Exercise Training
Authors: Begoña Benito, Gemma Gay-Jordi, Anna Serrano-Mollar, Eduard Guasch, Yanfen Shi, Jean-Claude Tardif, Josep Brugada, Stanley Nattel, Lluis Mont
Journal: Circulation (2010)

Background— Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias. Methods and Results— Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-β1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; P =0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation. Conclusions— In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, together with changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias.
Human peripheral blood lymphocytes as a cell model to evaluate the genotoxic effect of coal tar treatment.
Authors: S Pavanello, A G Levis
Journal: Environmental Health Perspectives (1994)

Peripheral blood lymphocytes (PBL) from psoriatic patients therapeutically exposed to polycyclic aromatic hydrocarbons (PAH) during coal tar (CT) treatment were used to evaluate the in vivo formation of benzo[a]pyrene diol epoxide(BaPDE)-DNA adducts by an ELISA technique and by the 32P-postlabeling method. Moreover, we controlled if the pretreatment with CT influences the formation of BaP-DNA adducts and the BaP metabolism in the PBL obtained from psoriatic patients, treated in vitro with BaP. Our data did not show any significant influence of the CT treatment on the levels of PAH-DNA adducts. Moreover, the use of PBL from psoriatic patients, treated in vitro with BaP, did not allow to detect significant modifications of the metabolic activation of BaP and of the ability of its metabolites to bind to DNA, before and after CT treatment. Thus, PBL do not seem to represent an useful cell model to evaluate the possible genotoxic effect of the exposure through the skin of psoriatic patients to the PAH contained in CT.
ATAD2 Is a Novel Cofactor for MYC, Overexpressed and Amplified in Aggressive Tumors
Authors: Marco Ciró, Elena Prosperini, Micaela Quarto, Ursula Grazini, Julian Walfridsson, Fraser McBlane, Paolo Nucifero, Giovanni Pacchiana, Maria Capra, Jesper Christensen, Kristian Helin
Journal: Cancer Research (2009)

The E2F and MYC transcription factors are critical regulators of cell proliferation and contribute to the development of human cancers. Here, we report on the identification of a novel E2F target gene, ATAD2, the predicted protein product of which contains both a bromodomain and an ATPase domain. The pRB-E2F pathway regulates ATAD2 expression, which is limiting for the entry into the S phase of the cell cycle. We show that ATAD2 binds the MYC oncogene and stimulates its transcriptional activity. ATAD2 maps to chromosome 8q24, 4.3 Mb distal to MYC, in a region that is frequently found amplified in cancer. Consistent with this, we show that ATAD2 expression is high in several human tumors and that the expression levels correlate with clinical outcome of breast cancer patients. We suggest that ATAD2 links the E2F and MYC pathways and contributes to the development of aggressive cancer through the enhancement of MYC-dependent transcription.
An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe−/− mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia
Authors: Paul J. Schmidt, Iva Toudjarska, Anoop K. Sendamarai, Tim Racie, Stuart Milstein, Brian R. Bettencourt, Julia Hettinger, David Bumcrot, Mark D. Fleming
Journal: Blood (2012)
GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration
Authors: Ethan A Winkler, Yoichiro Nishida, Abhay P Sagare, Sanket V Rege, Robert D Bell, David Perlmutter, Jesse D Sengillo, Sara Hillman, Pan Kong, Amy R Nelson, John S Sullivan, Zhen Zhao, Herbert J Meiselman, Rosalinda B Wenby, Jamie Soto, E Dale Abel, Jacob Makshanoff, Edward Zuniga, Darryl C De Vivo, Berislav V Zlokovic
Journal: Nature Neuroscience (2015)
EXCESSIVE ABDOMINAL DISTENTION AT HIGH ALTITUDES IN A CASE OF CONGENITAL MEGACOLON (HIRSCHSPRUNG'S DISEASE)
Authors: Leon H. Collins
Journal: JAMA (1941)

With the rapid increase in air transportation occurring in this country, the effects on certain disease processes of reduced barometric pressure take on growing clinical importance. The levels attained in commercial airline transportation today at times are sufficient to allow of a 50 to 100 per cent expansion of air or gas contained in one of the body cavities. It has long been recognized that reduced barometric pressure with its attendant reduction in the partial pressure of inspired oxygen affects unfavorably some pathologic states, particularly cardiac and pulmonary diseases. Especially interesting, however, have been those cases in which the expansion of air or gas at a reduced barometric pressure of itself has led to untoward symptoms. Lovelace and Hinshaw<sup>1</sup>have recently drawn attention to the hazards of air transportation to patients with pneumothorax. They point out that the expansion of the air introduced into the pleural cavity may cause
The pathophysiological role of platelets during myocardial ischaemia
Authors: N. A Flores, D. J Sheridan
Journal: Cardiovascular Research (1994)

Journal Article The pathophysiological role of platelets during myocardial ischaemia Get access Nicholas A Flores, Nicholas A Flores Academic Cardiology Unit, St Mary's Hospital Medical School, 10th Floor QEQM Wing, South Wharf Road, London W2 1NY, United Kingdom: N A Flores, D J Sheridan. Correspondence to Dr Flores. Search for other works by this author on: Oxford Academic PubMed Google Scholar Desmond J Sheridan Desmond J Sheridan Academic Cardiology Unit, St Mary's Hospital Medical School, 10th Floor QEQM Wing, South Wharf Road, London W2 1NY, United Kingdom: N A Flores, D J Sheridan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Pages 295–302, https://doi.org/10.1093/cvr/28.3.295 Published: 01 March 1994 Article history Received: 02 March 1993 Accepted: 05 November 1993 Published: 01 March 1994
A Novel HSP90 Inhibitor Delays Castrate-Resistant Prostate Cancer without Altering Serum PSA Levels and Inhibits Osteoclastogenesis
Authors: Francois Lamoureux, Christian Thomas, Min-Jean Yin, Hidetoshi Kuruma, Ladan Fazli, Martin E. Gleave, Amina Zoubeidi
Journal: Clinical Cancer Research (2011)

Prostate cancer responds initially to antiandrogen therapies; however, progression to castration-resistant disease frequently occurs. Therefore, there is an urgent need for novel therapeutic agents that can prevent the emergence of castrate-resistant prostate cancer (CRPC). HSP90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-Allylamino-17-demethoxy-geldanamycin (17-AAG) has been reported to inhibit tumor growth in various cancers; however, it induces tumor progression in the bone microenvironment.Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometric, and luciferase assays, respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay.PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell-cycle arrest at sub-G(1), and leads to apoptosis and increased caspase-3 activity. These biological events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-κB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared with controls. Surprisingly, PF-04929113 did not reduce serum prostate-specific antigen (PSA) levels in vivo; in parallel, these decrease in tumor volume.These data identify significant anticancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmacodynamic tool for this drug.
Activation of CDCA1-KNTC2, Members of Centromere Protein Complex, Involved in Pulmonary Carcinogenesis
Authors: Satoshi Hayama, Yataro Daigo, Tatsuya Kato, Nobuhisa Ishikawa, Takumi Yamabuki, Masaki Miyamoto, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura
Journal: Cancer Research (2006)

Abstract We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non–small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1398-416) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers. (Cancer Res 2006; 66(21): 10339-48)
Spontaneous Haematoma of the Rectus Abdominis Muscle in Pregnancy
Authors: V. Sheehan
Journal: BMJ (1951)

An increasing number of studies suggest the importance of antibodies in the pathogenesis of most systemic and organ-specific autoimmune diseases, although there is considerable controversy over the precise role of the autoantibodies involved. In humans, a major obstacle to progress is the identification and cloning of the relevant autoantibodies and autoantigens. Here, an approach based on the sequential use of antibody phage display and antigen expression libraries is developed and applied to a donor suffering from rheumatoid arthritis (RA), splenomegaly, and peripheral destruction of neutrophils leading to neutropenia (Felty9s syndrome). An antibody phage display library was constructed from bone marrow from the donor and a high-affinity human mAb, ANA15, selected by panning against fresh neutrophils and independently by panning against a fixed cell line. The antibody showed strong staining of neutrophils and a number of cell lines. Probing of a λgt11 expression library from an induced myelomonocytic cell line with the mAb ANA15 identified the eukaryotic elongation factor 1A-1 (eEF1A-1) as a novel autoantigen. The specificity of ANA15 was confirmed by reactivity with both purified and recombinant eEF1A-1. Screening of a large panel of sera revealed that 66% of patients with Felty9s syndrome had elevated levels of anti-eEF1A-1 antibodies. The cloning of this antibody–antigen pair should permit rational evaluation of any pathogenicity resulting from the interaction and its significance in neutropenia.
The Case for More Women in Medicine: The Stanford Program
Authors: John P. Bunker, Judith G. Pool
Journal: New England Journal of Medicine (1971)

In a recent action of its Faculty Senate, Stanford University School of Medicine has announced the goal of an increased proportion of women in its student body. The action expresses Stanford's clear conviction that more women are needed in medicine nationally. What are the reasons? The case for more women in medicine can be made on the basis of what medicine has to offer to women in search of a career but, equally compellingly, on the basis of what women have to offer to medicine.In response to the manpower crisis in health, the nation is attempting to increase the . . .
Immune Complexes in Cancer
Authors: Argyrios N. Theofilopoulos
Journal: New England Journal of Medicine (1982)

Antigen–antibody immune complexes can activate a variety of cell types, interact with humoral factors, and induce the release of biologically active mediators that participate directly in disease processes. Moreover, immune complexes have profound effects on immune responses, enhancing or suppressing them, depending on the molar ratio of the antigens and antibodies that they contain.1 Therefore, the role of immune complexes in tumor immunopathology and immunity has been subjected to extensive scrutiny.Tumor cells, expressing new antigens on their surface membranes, become foreign to the host and elicit both humoral and cellular immune responses. These responses should produce a condition that . . .
Validity of subjective assessment of changes in respiratory health status: a 30 year epidemiological study of workers in Paris
Authors: F Kauffmann, I Annesi, J Chwalow
Journal: European Respiratory Journal (1997)

The validity of scales used for subjective assessment of health, particularly transitional indices, is under discussion. The aim of the present study was to assess the concurrent and predictive validity of a simple estimate of long-term subjective assessment of respiratory health changes. A longitudinal study of 915 workers was conducted over 30 yrs, with both retrospective self-assessment of respiratory health changes and objective measurements of spirometric values 12 yrs apart. An assessment of the reason for death during the subsequent 20 yrs was performed. Subjective assessment of respiratory deterioration over 12 yrs was significantly related to both cross-sectional lung function values and longitudinal lung function changes (forced expiratory volume in one second (FEV1) decline), an association which remained after adjustment for FEV1 level. It was also related to the same risk factors as decline in FEV1 (smoking, occupational exposure). Self-evaluation of respiratory deterioration was significantly predictive of death from all causes, with the highest (but nonsignificant) rate ratio for respiratory causes. Asthmatics exhibited greater long-term variability (objective and subjective) than nonasthmatics. Independent of dyspnoea, self-assessment of respiratory health deterioration was significantly related to FEV1. Subjective assessment of long-term changes in respiratory health provides valid information.
Bariatric surgery: give more weight to bone loss
Authors: M. R. Laurent
Journal: BMJ (2014)

In their otherwise exhaustive review on bariatric surgery, Arterburn and Courcoulas fail to mention metabolic bone disorders among its complications.1 This is truly a missed opportunity, and I would like to draw attention to this problem.

It is a common misconception that obesity (which does not usually resolve after bariatric surgery) is protective for the skeleton. Several longitudinal studies show markedly …
THE TREATMENT OF DELIRIUM TREMENS
Authors: E. A. Cannon
Journal: JAMA (1942)

The problem of the treatment and care of patients with delirium tremens is well known. Usually large quantities of sedatives, drastic purgatives and frequent spinal taps are used. The patient remains strapped in bed, straining against his bonds and raising considerable disturbance. The difficulty of treating associated conditions such as lobar pneumonia, perforations of the bowel or fractures of all kinds are greatly prevented by the actions of the patient in delirium.  Many such problems occurred at St. Mary's Hospital. We would like to present our comparatively simple treatment used on a number of patients in recent months. We employ an intravenous injection of 50 cc. of 50 per cent dextrose, 8 cc. of vitamin B1 (approximately 25,000 units) and 25 units of insulin, all in one injection, as soon as the diagnosis is made. Sedation of any kind is not given. The straps are kept in readiness but have
The association of HLA-DQ7 with bullous pemphigoid is restricted to men
Authors: None Banfield, None Wojnarowska, None Allen, None George, None Venning, None Welsh
Journal: British Journal of Dermatology (1998)

This study examines in detail the HLA associations of 74 patients (40 women and 34 men) with bullous pemphigoid (BP) and compares their immunogenetic profile with that of 604 unrelated control subjects (238 women and 366 men). Correlations were sought between HLA antigens and the various BP disease parameters investigated. The presence of milia was the only clinical or laboratory finding which was linked with a specific HLA antigen, HLA-DQ6, in both men and women with BP (P < 0.01). BP has previously been linked with the HLA-DQ7 antigen and this association was confirmed in 39 of our patients (14 women and 25 men). Twelve of these patients (four women and eight men) were homozygous for HLA-DQ7. The association of HLA-DQ7 with BP was gender-restricted and only significant for men (P < 0.01). No equivalent HLA disease susceptibility risk factor could be identified for our female BP patients. This difference in HLA association between men and women with BP has not been reported previously, and its significance for disease pathogenesis is not known. No specific link could be found between HLA-DQ7 and BP for any of the clinical, immunofluorescence, western blotting, treatment or prognostic disease factors studied.
Induction of hepatic and intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone (SL)
Authors: Viviana A. Catania, Marcelo G. Luquita, Enrique J.Sanchez Pozzi, Jose M. Pellegrino, Justina E. Ochoa, Aldo D. Mottino
Journal: Journal of Hepatology (2002)