tbuckley/cabot-search huggingface dataset:
Hormone-Dependent Mammary Tumors in Strain GR/A Mice. III. Effectiveness of Supplementary Hormone Treatments in Inducing Tumorous Phase Growth2
Authors: Bruce D. Aidells, Charles W. Daniel
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Hormone-Dependent Mammary Tumors in Strain GR/A Mice. III. Effectiveness of Supplementary Hormone Treatments in Inducing Tumorous Phase Growth Get access Bruce D. Aidells, Bruce D. Aidells Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles W. Daniel Charles W. Daniel 5 5Address reprint requests to Dr. Daniel. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 3, September 1976, Pages 527–537, https://doi.org/10.1093/jnci/57.3.527 Published: 01 September 1976 Article history Received: 06 August 1975 Revision received: 30 January 1976 Accepted: 23 February 1976 Published: 01 September 1976
Preferential differentiation of T cell receptor specificities based on the MHC glycoproteins encountered during development. Evidence for positive selection.
Authors: S Marusić-Galesić, D L Longo, A M Kruisbeek
Journal: The Journal of Experimental Medicine (1989)

T cells recognize foreign antigens together with those MHC glycoproteins they have encountered during their development in the thymus. How the repertoire of antigen-specific TCRs is selected has not yet been fully defined. We have investigated the T cell repertoire specificities of CD4-CD8+ cytotoxic T cells developing under conditions where one of the class I MHC-encoded molecules is blocked, while other class I-MHC glycoproteins are still expressed. We show that antigen-specific T cells restricted to the blocked class I fail to develop, while generation of other class I-specific T cell proceeds undisturbed. This highly selective perturbation of the T cell receptor repertoire demonstrates that development of CD4-CD8+ T cells with a certain TCR specificity requires expression of particular alleles of class I MHC. Thus, TCR-MHC interactions provide signals essential to the differentiation of precursor T cells.
Human lung mast cells alter asthmatic airway epithelial cell function
Authors: Hatem Alkhouri, Janette Burgess, Carol Armour, J. Margaret Hughes
Journal: European Respiratory Journal (2013)

In asthma, the airway epithelial cell layer is fragile and mucus production is increased. As mast cells are often in close proximity with the epithelial cells we hypothesised they may affect the integrity of the epithelial layer and contribute to asthma pathophysiology.  Aim: To examine the effects of human lung mast cell (HLMC) products on asthmatic and non-asthmatic airway epithelial cell function.  Methods: HLMC were stimulated with IgE/anti-IgE and their supernatants (SN) collected after 2 and 24h. Calu-3 cell line or primary bronchial epithelial cells (PBEC) obtained from people with and without asthma were grown in air-liquid interface before adding HLMC SN. Epithelial layers were then evaluated for transepithelial electrical resistance (TEER), mucus secretion and wound healing within 48h.  Results: In all epithelial cells tested, both 2 and 24h HLMC SN significantly reduced TEER while only the 2h SN increased mucus production. The responses of asthmatic and non-asthmatic PBEC were not different. In Calu-3 control cells only 10% of the wound area remained open after 48h, but 2h HLMC SN reduced this closure by 28%. In contrast, the 24h HLMC SN increased the rate of wound closure, such that it was complete within 30 hours.  Conclusion: Granule derived (2h) and newly synthesised (24h) HLMC products differentially modulated airway epithelial cell function. Some effects of newly synthesized products may be protective by inducing wound healing. Thus mast cells have the capacity to regulate epithelial cell functions in asthma.  Funded by: NHMRC of Australia.
Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.
Authors: M J Rosen, K Clayton, R F Schneider, W Fulkerson, A V Rao, J Stansell, P A Kvale, J Glassroth, L B Reichman, J M Wallace, P C Hopewell
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.
DIE WIRKUNG VON BRADYKININ‐AEROSOL AUF DIE ATMUNG DES MENSCHEN UND DES MEER‐SCHWEINCHENS UND DER EINFLUSS VER‐SCHIEDENER SUBSTANZEN AUF DEN EXPERI‐MENTELLEN BRADYKININ‐BRONCHOSPASMUS
Authors: E. STRESEMANN
Journal: Allergy (1963)
DNA Methylation Markers Predict Outcome in Node-Positive, Estrogen Receptor-Positive Breast Cancer with Adjuvant Anthracycline-Based Chemotherapy
Authors: Oliver Hartmann, Frédérique Spyratos, Nadia Harbeck, Dimo Dietrich, Anne Fassbender, Manfred Schmitt, Serenella Eppenberger-Castori, Vincent Vuaroqueaux, Florence Lerebours, Katrin Welzel, Sabine Maier, Achim Plum, Stephan Niemann, John A. Foekens, Ralf Lesche, John W.M. Martens
Journal: Clinical Cancer Research (2008)

We have shown that DNA methylation of the PITX2 gene predicts risk of distant recurrence in steroid hormone receptor-positive, node-negative breast cancer. Here, we present results from a multicenter study investigating whether PITX2 and other candidate DNA methylation markers predict outcome in node-positive, estrogen receptor-positive, HER-2-negative breast cancer patients who received adjuvant anthracycline-based chemotherapy.Using a microarray platform, we analyzed DNA methylation in regulatory regions of PITX2 and 60 additional candidate genes in 241 breast cancer specimens. Using Cox regression analysis, we assessed the predictive power of the individual marker/marker panel candidates. Clinical endpoints were time to distant metastasis, disease-free survival, and overall survival. A nested bootstrap/cross-validation strategy was applied to identify and validate marker panels.DNA methylation of PITX2 and 14 other genes was correlated with clinical outcome. In multivariate models, each methylation marker added significant information to established clinical factors. A four-marker panel including PITX2, BMP4, FGF4, and C20orf55 was identified that resulted in improvement of outcome prediction compared with PITX2 alone.This study provides further evidence for the PITX2 biomarker, which has now been successfully confirmed to predict outcome among different breast cancer patient populations. We further identify new DNA methylation biomarkers, three of which can be combined into a panel with PITX2 to increase the outcome prediction performance in our anthracycline-treated primary breast cancer population. Our results show that a well-defined panel of DNA methylation markers enables outcome prediction in lymph node-positive, HER-2-negative breast cancer patients treated with anthracycline-based chemotherapy.
Cytomegalovirus-induced haemolytic anaemia after cardiac surgery.
Authors: S Holt, N Kirkham
Journal: Thorax (1976)

A patient, who underwent aortic valve replacement, developed a transient, autoimmune haemolytic anaemia in association with a significant rise in titre of antibodies against cytomegalovirus. A serological survey of blood donors indicated that the source of infection was fresh blood transfused during and shortly after surgery. A number of cases of short-lived haemolytic anaemia after large volume blood transfusion with cardiac surgery may be explained by this mechanism. It may be preferable to use only blood that has been screened for evidence of recent cytomegalovirus infection if post-perfusion complications of this disease are to be avoided.
Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function
Authors: Kyung-Sun Heo, Nhat-Tu Le, Hannah J. Cushman, Carolyn J. Giancursio, Eugene Chang, Chang-Hoon Woo, Mark A. Sullivan, Jack Taunton, Edward T.H. Yeh, Keigi Fujiwara, Jun-ichi Abe
Journal: Journal of Clinical Investigation (2015)

Disturbed blood flow (d-flow) causes endothelial cell (EC) dysfunction, leading to atherosclerotic plaque formation. We have previously shown that d-flow increases SUMOylation of p53 and ERK5 through downregulation of sentrin/SUMO-specific protease 2 (SENP2) function; however, it is not known how SENP2 itself is regulated by d-flow. Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis. In an LDLR-deficient murine model of atherosclerosis, EC-specific overexpression of p90RSK increased EC dysfunction and lipid accumulation in the aorta compared with control animals; however, these pathologic changes were not observed in atherosclerotic mice overexpressing dominant negative p90RSK (DN-p90RSK). Moreover, depletion of SENP2 in these mice abolished the protective effect of DN-p90RSK overexpression. We propose that p90RSK-mediated SENP2-T368 phosphorylation is a master switch in d-flow–induced signaling, leading to EC dysfunction and atherosclerosis.
Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique for obtaining high-quality synovial tissue from both large and small joints in early arthritis patients
Authors: S Kelly, F Humby, A Filer, N Ng, M Di Cicco, R E Hands, V Rocher, M Bombardieri, M A D'Agostino, I B McInnes, C D Buckley, P C Taylor, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To determine the tolerability, safety and yield of synovial tissue in an early arthritis cohort using a minimally invasive, ultrasound (US)-guided, synovial biopsy technique in small, medium and large joints. <h3>Methods</h3> 93 sequential biopsy procedures were assessed from a total of 57 patients (baseline and 36 repeat biopsies at 6 months) recruited as part of the 'Pathobiology of Early Arthritis Cohort' study. Patients completed a tolerability questionnaire prior to and following the synovial biopsy procedure. The synovial biopsy was performed under US guidance with US images of the joint recorded prior to each procedure. Synovial tissue was harvested for immunohistochemistry and RNA extraction. <h3>Results</h3> Five different joint sites were biopsied (knee, elbow, wrist, metacarpal phalangeal and proximal interphalangeal). No significant complications were reported following the procedure. No difference in pain, swelling and stiffness of the biopsied joint from before and after the procedure was demonstrated. A median of 14 biopsy samples was retrieved from each procedure with 93% of biopsy procedures yielding good quality tissue. RNA yield was good in all joints and in repeat biopsies. Multivariant analysis demonstrated a significantly greater yield of RNA and graded tissue in relation to a high prebiopsy, grey-scale synovitis score (0–3, semiquantitative). <h3>Conclusions</h3> A minimally invasive approach to synovial tissue harvesting, using US guidance, is both safe and well-tolerated by patients. Tissue quality/RNA yield is preserved in subsequent biopsies following therapeutic intervention. A high US grey-scale synovitis score is a predictor of good quality/quantity of tissue and RNA.
Plasma insulin response to oral glycaemic stimulus in lichen planus
Authors: P.K. Nigam, G. Singh, J.K. Agrawal
Journal: British Journal of Dermatology (1988)

Journal Article Plasma insulin response to oral glycaemic stimulus in lichen planus Get access P.K. Nigam, P.K. Nigam Department of Dermato‐venereology and Leprosy Institute of Medical Sciences Banaras Hindu University Varanasi‐221005, India Search for other works by this author on: Oxford Academic Google Scholar G. Singh, G. Singh Department of Dermato‐venereology and Leprosy Institute of Medical Sciences Banaras Hindu University Varanasi‐221005, India Search for other works by this author on: Oxford Academic Google Scholar J.K. Agrawal J.K. Agrawal Department of Dermato‐venereology and Leprosy Institute of Medical Sciences Banaras Hindu University Varanasi‐221005, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue 1, 1 July 1988, Pages 128–129, https://doi.org/10.1111/j.1365-2133.1988.tb07115.x Published: 01 July 1988
Antioxidant Supplements to Prevent Mortality
Authors: Goran Bjelakovic, Dimitrinka Nikolova, Christian Gluud
Journal: JAMA (2013)

Are antioxidant supplements associated with higher or lower all-cause mortality?Antioxidant supplements are not associated with lower all-cause mortality. Beta carotene, vitamin E, and higher doses of vitamin A may be associated with higher all-cause mortality.
Effects of acute supplementation with<i>Rhodiola rosea</i>and L-carnitine on exercise performance, cognitive function and cortisol in healthy active volunteers
Authors: D Muñiz-Pumares, A Lage-Guede, A Firth-Clark, J Allgrove
Journal: British Journal of Sports Medicine (2011)

Rhodiola rosea (RR) is an adaptogenic herb suggested to improve exercise and cognitive performance and reduce stress responses. Further, some evidence reports that L-carnitine (LC) can alter metabolism during exercise and improve performance. This study examined the effects of acute ingestion of a commercially available RR beverage (250 mg, 3% Rosavin) with and without LC (500 mg) on exercise performance, cognitive function and salivary cortisol. In a double-blind, randomised, crossover-design, 18 healthy, active men and women (age, 21±6 years; maximal oxygen uptake, VO 2 max 43±9 ml/min/kg) consumed 250 ml of a RR-LC, RR and placebo beverage 45 min before a cycle to fatigue at 77±11% of VO 2 max. Immediately before and after exercise, computerised cognitive tasks of Rapid Visual Information Processing (RVP), Visual Recognition Memory (VRM) and Stroop Colour-Word (Stroop) were completed. Expired gas and heart rate were recorded continuously during exercise. Capillary blood samples were taken for lactate analysis 2 min after cycling and saliva samples were collected before beverage ingestion, before and immediately after cognitive tests for cortisol analysis. Data were analysed using repeated measures ANOVAs with significance set at P &lt;0.05. Time to fatigue, physiological and cognitive variables did not differ between treatments. Cortisol increased ( P =0.028) after tests, but there was no effect of treatment on this response. However, exercise elicited higher RVP sustained attention ( P &lt;0.05), a faster response time in Stroop ( P &lt;0.05), but VRM was reduced. These findings suggest that acute RR-LC ingestion does not alter cognitive function, exercise performance or salivary cortisol. However, chronic supplementation or greater dosage might affect these results. These results show that exhaustive exercise reduces reaction time and increases attention, but memory outcomes become decreased.
Patterns of Immunodominance in HIV-1–specific Cytotoxic T Lymphocyte Responses in Two Human Histocompatibility Leukocyte Antigens (HLA)-identical Siblings with HLA-A*0201 Are Influenced by Epitope Mutation
Authors: P.J.R. Goulder, A.K. Sewell, D.G. Lalloo, D.A. Price, J.A. Whelan, J. Evans, G.P. Taylor, G. Luzzi, P. Giangrande, R.E. Phillips, A.J. McMichael
Journal: The Journal of Experimental Medicine (1997)

Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201–restricted SLYNTVATL and HLA-A3–restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201–restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71%) generated responses to the Gag epitope. In the 29% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. We concluded that HLA class I genotype determines epitope selection initially but that mutation in immunodominant epitopes can profoundly alter the pattern of CTL response.
626 ELEVATED LEVELS OF VON WILLEBRAND FACTOR ARE ASSOCIATED WITH MAINTAINED NORMAL PRIMARY HAEMOSTASIS IN THROMBOCYTOPENIC PATIENTS WITH LIVER CIRRHOSIS
Authors: A. Wannhoff, O.J. Müller, K.H. Weiss, H.A. Katus, W. Stremmel, D. Gotthardt
Journal: Journal of Hepatology (2013)
Functional impairment of natural killer cells in active ulcerative colitis: reversion of the defective natural killer activity by interleukin 2.
Authors: L Manzano, M Alvarez-Mon, L Abreu, J Antonio Vargas, E de la Morena, F Corugedo, A Durantez
Journal: Gut (1992)

We have studied the functional characteristics and clinical importance of the natural killer (NK) cytotoxicity of peripheral blood mononuclear cells (PBMNC) from patients with ulcerative colitis. Normal NK activity was observed in PBMNC from patients with inactive disease, but a pronounced decrease was found in those with active disease. Clinical change from active to inactive disease was associated with enhancement of the depressed NK activity. The impairment of NK cytotoxicity found in patients with active disese could not be ascribed to a deficient number of NK cells as the amounts of HNK-1+, CD16+ (Leu 11), and CD11b (OKM1) cells in PBMNC were within normal ranges. This defective cytotoxic PBMNC activity was normalised by short term (18 hour) incubation with recombinant interleukin 2 (rIL-2). Moreover, long term (5 day) incubation of these effector cells with rIL-2 induced strong cytotoxic activity against NK resistant and NK sensitive target cells in patients with active and inactive disease. We also found that both precursors and effectors of cytotoxic activity promoted by short term and long term incubation with rIL-2 of PBMNC from the patients showed the phenotype of NK cells (CD16+, CD3-). Taken together, these results show that active ulcerative colitis is associated with a defective function of NK cells that is found to be normal in the inactive stage of the disease. The possible pathogenic and therapeutic implications of these findings are discussed.
Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer
Authors: Rade Injac, Martina Perse, Manica Cerne, Nejka Potocnik, Natasa Radic, Biljana Govedarica, Aleksandar Djordjevic, Anton Cerar, Borut Strukelj
Journal: Biomaterials (2008)
Critical Role of the Stress Chaperone GRP78/BiP in Tumor Proliferation, Survival, and Tumor Angiogenesis in Transgene-Induced Mammary Tumor Development
Authors: Dezheng Dong, Min Ni, Jianze Li, Shigang Xiong, Wei Ye, Jenilyn J. Virrey, Changhui Mao, Risheng Ye, Miao Wang, Ligaya Pen, Louis Dubeau, Susan Groshen, Florence M. Hofman, Amy S. Lee
Journal: Cancer Research (2008)

Abstract The unfolded protein response (UPR) is an evolutionarily conserved mechanism that activates both proapoptotic and survival pathways to allow eukaryotic cells to adapt to endoplasmic reticulum (ER) stress. Although the UPR has been implicated in tumorigenesis, its precise role in endogenous cancer remains unclear. A major UPR protective response is the induction of the ER chaperone GRP78/BiP, which is expressed at high levels in a variety of tumors and confers drug resistance in both proliferating and dormant cancer cells. To determine the physiologic role of GRP78 in in situ–generated tumor and the consequence of its suppression on normal organs, we used a genetic model of breast cancer in the Grp78 heterozygous mice where GRP78 expression level was reduced by about half, mimicking anti-GRP78 agents that achieve partial suppression of GRP78 expression. Here, we report that Grp78 heterozygosity has no effect on organ development or antibody production but prolongs the latency period and significantly impedes tumor growth. Our results reveal three major mechanisms mediated by GRP78 for cancer progression: enhancement of tumor cell proliferation, protection against apoptosis, and promotion of tumor angiogenesis. Importantly, although partial reduction of GRP78 in the Grp78 heterozygous mice substantially reduces the tumor microvessel density, it has no effect on vasculature of normal organs. Our findings establish that a key UPR target GRP78 is preferably required for pathophysiologic conditions, such as tumor proliferation, survival, and angiogenesis, underscoring its potential value as a novel therapeutic target for dual antitumor and antiangiogenesis activity. [Cancer Res 2008;68(2):498–505]