tbuckley/cabot-search huggingface dataset:
Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses.
Authors: A Bender, L K Bui, M A Feldman, M Larsson, N Bhardwaj
Journal: The Journal of Experimental Medicine (1995)

Inactivated or subunit virus preparations have been excellent vaccines for inducing antibody responses. Generation of cytolytic T cell responses, however, is thought to require replicating virus, primarily to provide sufficiently large amounts of cytoplasmic proteins for processing and presentation on major histocompatibility complex class I molecules by antigen-presenting cells. Potent human CD8+ cytolytic T cell responses to live replicating influenza A virus are generated when dendritic cells are used as the antigen-presenting cells. Here, we demonstrate that dendritic cells pulsed with poorly replicating, heat- or ultraviolet-inactivated influenza virus, induce equally strong CD8+ cytolytic T lymphocyte responses. The cytotoxic T lymphocytes are generated in the apparent absence of CD4+ helper cells or exogenous cytokines. Active viral protein synthesis is not required to charge class I molecules on dendritic cells. When pulsed with inactivated virus, &amp;lt; 1% of dendritic cells express nonstructural protein 1, which is only synthesized in the infectious cycle. To be optimally effective, however, the inactivated virus must retain its fusogenic activity, and presumably access the cytoplasm of dendritic cells. The data indicate, therefore, that dendritic cells require only small amounts of viral protein to charge class I molecules, most likely via traditional class I processing pathways. These results reopen the potential use of inactivated virus preparations as immunogens for cytotoxic T lymphocyte responses.
Measuring mitral regurgitation predicts clinical outcome of treatment
Authors: Scott Gottlieb
Journal: BMJ (2005)

Quantitative grading of mitral regurgitation, based on the effective regurgitant orifice of the valve and the regurgitated volume of blood, is a powerful predictor of the clinical outcome of medical management in asymptomatic patients. Patients with an effective regurgitant orifice of 40 mm2 or more should be considered for surgical repair.

The prognostic power of this quantitative classification superseded that of all other semiquantitative indexes, say the authors of the new study. They accurately determined the rates of death from any cause, death from cardiac causes, and cardiac events with the use of medical management based …
Coronary Artery Bypass Grafting in Patients 50 Years or Younger
Authors: Magnus Dalén, Torbjörn Ivert, Martin J. Holzmann, Ulrik Sartipy
Journal: Circulation (2015)

Background— There are limited data regarding long-term results after coronary artery bypass grafting (CABG) in young adults. We performed a nationwide population-based cohort study to analyze long-term survival, major adverse cardiovascular events, and factors associated with elevated risk in young adults undergoing CABG. Methods and Results— We included all adult patients ≤50 years of age who underwent primary isolated CABG in Sweden between 1997 and 2013 from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) register. Patient data were linked from national Swedish health data registers to create a study database. We identified 4086 young adults with a mean age of 46 years and 18% women. During a median follow-up time of 10.9 years (interquartile range, 6.4–14.1) 490 (12%) patients died. Survival at 5, 10, and 15 years was 96% (95% CI, 95–96), 90% (95% CI, 89–91), and 82% (95%CI, 80–83), respectively, which was significantly better in comparison with patients aged 51 to 70 years and &gt;70 years who underwent CABG during the same period. The cumulative incidence of death or a major adverse cardiovascular event during 17 years after CABG was mainly driven by myocardial infarction or the need for repeat revascularization. The most important risk factors for all-cause mortality were chronic kidney disease, reduced left ventricular ejection fraction, peripheral vascular disease, or chronic obstructive pulmonary disease. Conclusions— Long-term survival and freedom from major cardiovascular events after CABG was better in young adults than in older patients. Factors significantly associated with an elevated long-term risk of death or adverse outcome were similar to well-known risk factors for older age groups following CABG. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02276950.
Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX
Authors: S. Aebi, Z. Sun, D. Braun, K.N. Price, M. Castiglione-Gertsch, M. Rabaglio, R.D. Gelber, D. Crivellari, J. Lindtner, R. Snyder, P. Karlsson, E. Simoncini, B.A. Gusterson, G. Viale, M.M. Regan, A.S. Coates, A. Goldhirsch
Journal: Annals of Oncology (2011)
Children’s Urinary Phthalate Metabolites and Fractional Exhaled Nitric Oxide in an Urban Cohort
Authors: Allan C. Just, Robin M. Whyatt, Rachel L. Miller, Andrew G. Rundle, Qixuan Chen, Antonia M. Calafat, Adnan Divjan, Maria J. Rosa, Hanjie Zhang, Frederica P. Perera, Inge F. Goldstein, Matthew S. Perzanowski
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined.We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with Fe(NO) and that these associations would be stronger among children with seroatopy or wheeze.In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as Fe(NO) measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations.Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5-13.1%) and 8.7% (95% CI, 1.9-16.0%) increase in Fe(NO), respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and Fe(NO). There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016).Independent associations between exposures to DEP and BBzP and Fe(NO) in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.
A novel genetic marker of liver disease aetiology in hepatocellular carcinoma: culling the metabolic syndrome
Authors: Elizabeth M Brunt
Journal: Gut (2012)

Paradis et al 1 describe the work in which they identified CUL7 as a unique target gene in metabolic syndrome-related hepatocellular carcinoma (HCC). The increased worldwide prevalence and incidence of liver disease related to metabolic syndrome2 are noted as factors in the changing epidemiology and demographics of HCC, especially in otherwise ‘low-risk’ regions.3–5 Although this highly lethal malignancy remains most commonly associated with underlying cirrhosis secondary to viral hepatitis C or B,6 ,7 or alcohol,7 there is growing acceptance of the role of non-alcoholic steatohepatitis as another chronic liver disease that may predispose to the subsequent genetic and molecular aberrations that result in malignancy. Furthermore, investigators are showing the existence of an alarming trend in the evolution of HCC in the presence of metabolic syndrome before advanced fibrosis or cirrhosis.3 ,8 The implications for clinical management are apparent.

The group of Paradis et al ,1 started with a comparative genomic hybridisation analysis that showed amplification in 6p21.1. Another gene that resides in the …
Bile salt metabolism in patients with gallstones in functioning gallbladders
Authors: E. W. Pomare, K. W. Heaton
Journal: Gut (1973)

Isotopic bile salt studies were carried out in eight middle-aged women with radiolucent galstones in functioning gallbladders and in 10 matched controls. In the gallstone patients the size of the bile salt pool was reduced by 37% to 1·79 g, but there was considerable overlap with the normal subjects. The cholate and chenodeoxycholate pools were reduced, but the deoxycholate pool was normal in size. There were changes in bile salt metabolism which resembled those found after cholecystectomy but were less marked. This suggests that in gallstone disease the storage capacity of the gallbladder is impaired. This may contribute to the small bile salt pool, but it is unlikely to be the sole or even the major cause.
Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53
Authors: C. Zhang, Y. Feng, S. Qu, X. Wei, H. Zhu, Q. Luo, M. Liu, G. Chen, X. Xiao
Journal: Cardiovascular Research (2011)

Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of clinical antineoplastic activity, but increased apoptosis has been implicated in its cardiotoxicity. Resveratrol (RES) was shown to harbour major health benefits in diseases associated with oxidative stress. In this study, we aimed to determine the effect of RES on DOX-induced myocardial apoptosis in mice. Male Balb/c mice were randomized to one of the following four treatments: saline, RES, DOX, or RES plus DOX (10 mice in each group). DOX treatment markedly depressed cardiac function, decreased the heart weight, the body weight, and the ratio of heart weight to body weight, but inversely increased the level of protein carbonyl, malondialdehyde, and serum lactate dehydrogenase, and induced mitochondrial cytochrome c release and cardiomyocyte apoptosis. However, these effects of DOX were ameliorated by its combination with RES. Further studies with a co-immunoprecipitation assay revealed an interaction between p53 and Sirtuin 1 (SIRT1). It was found by western blot and electrophoretic mobility shift assay that DOX treatment increased p53 protein acetylation and cytochrome c release from mitochondria, activated p53 binding at the Bax promoter, and up-regulated Bax expression, but supplementation with RES could weaken all these effects. The protective effect of RES against DOX-induced cardiomyocyte apoptosis is associated with the up-regulation of SIRT1-mediated p53 deacetylation.
Is avoiding post-mastectomy radiotherapy justified for patients with four or more involved axillary nodes and endocrine-responsive tumours? Lessons from a series in a single institution
Authors: O Gentilini, E Botteri, N Rotmensz, M Intra, G Gatti, L Silva, N Peradze, R.C. Sahium, L.B. Gil, A Luini, P Veronesi, V Galimberti, S Gandini, A Goldhirsh, U Veronesi
Journal: Annals of Oncology (2007)
Map fragmentation in two- and three-dimensional environments
Authors: Homare Yamahachi, May-Britt Moser, Edvard I. Moser
Journal: Behavioral and Brain Sciences (2013)

Abstract The suggestion that three-dimensional space is represented by a mosaic of neural map fragments, each covering a small area of space in the plane of locomotion, receives support from studies in complex two-dimensional environments. How map fragments are linked, which brain circuits are involved, and whether metric is preserved across fragments are questions that remain to be determined.
Out-of-Pocket Costs and Diabetes Preventive Services
Authors: Andrew J. Karter, Mark R. Stevens, William H. Herman, Susan Ettner, David G. Marrero, Monika M. Safford, Michael M. Engelgau, J. David Curb, Arleen F. Brown
Journal: Diabetes Care (2003)

OBJECTIVE—Despite the increased shifting of health care costs to consumers, little is known about the impact of financial barriers on health care utilization. This study investigated the effect of out-of-pocket expenditures on the utilization of recommended diabetes preventive services. RESEARCH DESIGN AND METHODS—This was a survey-based observational study (2000–2001) in 10 managed care health plans and 68 provider groups across the U.S. serving ∼180,000 patients with diabetes. From 11,922 diabetic survey respondents, we studied the occurrence of self-reported annual dilated eye exams and diabetes health education and among insulin users, daily self-monitoring of blood glucose (SMBG). Conditional probabilities were estimated for outcomes at each level of self-reported out-of-pocket expenditure by using hierarchical logistic regression models with random intercepts. RESULTS—Conditional probabilities of utilization (95% CI) varied by expenditure for dilated eye exam [no cost 78% (75–82), copay 79% (75–82), and full price 70% (64–75); P &amp;lt; 0.0001]; diabetes health education [no cost 29% (23–36), copay 29% (23–36), and full price 19% (14–25); P &amp;lt; 0.0001]; and daily SMBG [no cost 75% (68–81), copay 68% (60–75), and full price 59% (49–68); P &amp;lt; 0.0001]. Extensive adjustment for patient factors had no discernible effect on the estimates or their significance, and cost-utilization relationships were similar across income levels and other patient characteristics. CONCLUSIONS—Benefit packages structured to derive greater fiscal contribution from the health plan membership result in suboptimal use of diabetes preventive services and may thus lead to poorer clinical outcomes, greater future costs, and lower health plan quality ratings.
Persistence of chronic myelocytic leukemia despite deletion of rearranged bcr/c-abl sequences in blast crisis.
Authors: C R Bartram, J W Janssen, R Becher, A de Klein, G Grosveld
Journal: The Journal of Experimental Medicine (1986)

We report on a Ph+ chronic myelocytic leukemia (CML) case, cytogenetically characterized by the occurrence of a second Philadelphia (Ph) chromosome in lymphoid blast crisis of T cell lineage. In situ hybridization analyses showed a deletion of translocated c-abl sequences, present on the Ph during chronic state, from both Ph in acute state. Moreover, Southern blot analyses of blastic cells exhibited a rearrangement within bcr, but a deletion of 5' bcr sequences, and Northern blots failed to detect the hybrid 8.5 kb bcr/c-abl transcript usually observed in Ph+ CML.
Inhibition of Protein Kinase Cα Prevents Endothelial Cell Migration and Vascular Tube Formation In Vitro and Myocardial Neovascularization In Vivo
Authors: Aihong Wang, Motohiro Nomura, Sybill Patan, J. Anthony Ware
Journal: Circulation Research (2002)

Although protein kinase C (PKC) activation is required for endothelial cell (EC) growth, migration, adhesion, and vessel formation, the role of individual PKC isoenzymes in these events is not defined. Because PKCalpha has been previously linked with enhanced EC migration and response to angiogenic growth factors, we characterized a specific phosphorothioate-modified 21-mer antisense PKCalpha (AS-PKCalpha). AS-PKCalpha (500 nmol/L) prevented the expression of PKCalpha protein by 90% in human ECs and did not reduce the expression of any other PKC isoenzyme. AS-PKCalpha reduced human EC migration by 64% compared with its control oligonucleotide in a "scratch" wounding assay, and AS-PKCalpha reduced human EC adhesion to the extracellular matrix protein vitronectin by 18%. Phosphorylation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) induced by vascular endothelial growth factor was inhibited by 30% in human ECs transfected with AS-PKCalpha. Compared with control, AS-PKCalpha also reduced the number of EC tubes formed in a 3D type I collagen gel assay by 37.5%. Finally, using an osmotic minipump, we infused AS-PKCalpha into mice in which myocardial infarction was induced by coronary ligation and found that the oligonucleotide was primarily taken up by intramyocardial blood vessels. Compared with the results with control oligonucleotide, AS-PKCalpha oligonucleotide inhibited the number of anti-PKCalpha-stained blood vessels by 48% and reduced the total vessel number by 72% as well. In conclusion, the expression of PKCalpha is required for full EC migration, adhesion to vitronectin, vascular endothelial growth factor-induced extracellular signal-regulated kinase activation, and tube formation and is likely to be of importance in myocardial angiogenesis in vivo after ischemia.
Urinary proteoglycan degradation product excretion in patients with rheumatoid arthritis and osteoarthritis.
Authors: J Krajickova, J Macek
Journal: Annals of the Rheumatic Diseases (1988)

The excretion of sugar components of glycosaminoglycans in the urine was investigated in 19 healthy controls, 27 patients with rheumatoid arthritis, and 24 with osteoarthritis. Both groups of patients excreted significantly more glucosamine, galactosamine, and mannose than the controls. The total uronic acid excretion, also, was higher in the two groups than in the healthy subjects. The possibility of using this method for the long term follow up of rheumatoid arthritis and osteoarthritis and the response to treatment is discussed.
Weight-Related Quality of Life, Health Utility, Psychological Well-Being, and Satisfaction With Exenatide Once Weekly Compared With Sitagliptin or Pioglitazone After 26 Weeks of Treatment
Authors: Jennie H. Best, Richard R. Rubin, Mark Peyrot, Yan Li, Ping Yan, Jaret Malloy, Louis P. Garrison
Journal: Diabetes Care (2011)

OBJECTIVE To assess change in patient-reported outcomes in subjects with type 2 diabetes treated with exenatide once weekly compared with those treated with sitagliptin or pioglitazone. RESEARCH DESIGN AND METHODS In this 26-week randomized, multicenter, double-dummy study, 491 subjects received 2 mg of exenatide once weekly or maximum daily doses of sitagliptin (100 mg) or pioglitazone (45 mg) on a background of metformin. Weight-related quality of life, health utility, psychological well-being, and diabetes treatment satisfaction were assessed at baseline and week 26. Mean group changes from baseline to week 26 were estimated by ANCOVA. RESULTS Weight-related quality of life total scores improved significantly in the exenatide once weekly and sitagliptin arms only; the exenatide once weekly group experienced significantly greater improvement than the pioglitazone group in weight-related quality of life total scores and in several domain scores. Health utility scores improved significantly for exenatide once weekly and sitagliptin groups (P &amp;lt; 0.05) with no significant difference between the exenatide once weekly group and either comparison group. All groups experienced significant improvements on the psychological well-being global scale and all six domain scores, with no significant difference between the exenatide once weekly group and either comparator. All groups experienced significant improvements in total diabetes treatment satisfaction scores. The exenatide once weekly group experienced greater improvement than the sitagliptin group in treatment satisfaction total scores. CONCLUSIONS In combination with clinical outcomes from this study, these results indicate it is possible for patients treated with metformin to initiate exenatide therapy with potential benefits in both clinical and patient-reported outcomes.
Uterine stem cells: What is the evidence?
Authors: C.E. Gargett
Journal: Human Reproduction Update (2006)

The mucosal lining (endometrium) of the human uterus undergoes cyclical processes of regeneration, differentiation and shedding as part of the menstrual cycle. Endometrial regeneration also follows parturition, almost complete resection and in post-menopausal women taking estrogen replacement therapy. In non-menstruating species, there are cycles of endometrial growth and apoptosis rather than physical shedding. The concept that endometrial stem/progenitor cells are responsible for the remarkable regenerative capacity of endometrium was proposed many years ago. However, attempts to isolate, characterize and locate endometrial stem cells have only been undertaken in the last few years as experimental approaches to identify adult stem/progenitor cells in other tissues have been developed. Adult stem cells are defined by their functional properties rather than by marker expression. Evidence for the existence of adult stem/progenitor cells in human and mouse endometrium is now emerging because functional stem cell assays are being applied to uterine cells and tissues. These fundamental studies on endometrial stem/progenitor cells will provide new insights into the pathophysiology of various gynaecological disorders associated with abnormal endometrial proliferation, including endometrial cancer, endometrial hyperplasia, endometriosis and adenomyosis.
The future role of CD4 cell count for monitoring antiretroviral therapy
Authors: Nathan Ford, Graeme Meintjes, Anton Pozniak, Helen Bygrave, Andrew Hill, Trevor Peter, Mary-Ann Davies, Beatriz Grinsztejn, Alexandra Calmy, N Kumarasamy, Praphan Phanuphak, Pierre deBeaudrap, Marco Vitoria, Meg Doherty, Wendy Stevens, George K Siberry
Journal: The Lancet Infectious Diseases (2014)
Independent relationship between circulating resistin concentrations and endothelial activation in rheumatoid arthritis
Authors: Patrick H Dessein, Gavin R Norton, Angela J Woodiwiss, Ahmed Solomon
Journal: Annals of the Rheumatic Diseases (2013)

Resistin is an adipokine that may contribute to the link between inflammation and cardiovascular disease.1 In rheumatoid arthritis (RA), resistin forms part of the inflammatory cascade and indeed colocalises with inflammatory cells in synovial tissue and upregulates cytokine production.2–6 Herein, we examined the associations of metabolic risk factors, systemic inflammation and disease characteristics with resistin concentrations as well as the independent relationship of resistin concentrations with endothelial activation in 217 African patients (112 black and 105 white patients) with established RA7 that form part of an ongoing study on cardiovascular risk.8 

All patients were employing disease modifying agents for rheumatic disease that included tumour necrosis factor-α inhibition and rituximab in 3.7% and 0.5% of them. The study was approved by the Witwatersrand University Ethics Committee (Human Subjects) and each participant gave informed written consent. Concentrations of interleukin-6, a major circulating cytokine in …