tbuckley/cabot-search huggingface dataset:
Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells specific for a blood-borne self-antigen.
Authors: T Zal, A Volkmann, B Stockinger
Journal: The Journal of Experimental Medicine (1994)

Transgenic mice expressing a major histocompatibility complex class II-restricted T cell receptor with specificity for a natural self-antigen, the fifth component of complement, were generated to analyze the mechanism of tolerance induction to a blood-borne self-protein. In the absence of C5 protein thymocytes from T cell receptor transgenic mice develop into mature CD4 single positive cells which emigrate into the periphery and mount C5-specific T cell responses upon immunization with C5. In the presence of circulating C5 protein, CD4 single positive thymocytes do not develop. Negative selection occurs late in thymic ontogeny leaving the bulk of CD4+8+ thymocytes unaffected. This phenotype may be due to a delay in contact with self-antigen presentation which, under physiological conditions, is inefficient in the cortex of C5+ mice, and therefore does not affect most immature double positive thymocytes. In contrast, in vitro exposure to C5(-)-presenting dendritic cells or in vivo injection of C5 peptide results in deletion of double positive thymocytes. C5+ transgenic mice are tolerant in vivo, but contain T cells in spleen and lymph nodes that secrete interleukin 2 and interferon gamma in response to C5 activation in vitro. When crossed onto a Rag1-/- background to prevent endogenous T cell receptor rearrangements, these peripheral potentially autoreactive cells do not appear. This indicates that endogenous T cell receptor rearrangements possibly leading to the expression of two receptors might be a prerequisite for their survival and export into the periphery.
The measurement of thrombin in clotting blood by radioimmunoassay.
Authors: M A Shuman, P W Majerus
Journal: Journal of Clinical Investigation (1976)

We have developed a radioimmunoassay for human thrombin using rabbit anti-human thrombin IgG. The assay can measure 2 ng thrombin/ml plasma, 500-fold more sensitive than clotting assays. Human prothrombin is less reactive in the assay than thrombin by at least four orders of magnitude, and there is no demonstrable cross-reactivity with human factor Xa, the clotting factor structurally most similar to thrombin. The assay does not detect thrombin bound to anthithrombin III. Using the assay, we have demonstrated that plasma from 20 normal subjects does not contain detectable thrombin. We measured thrombin generation in clotting blood in polypropylene tubes and observed that thrombin appears (approximately equal to 3 ng/ml) within 45 S-5 min after venipuncture. This material is thrombin, not intermediates of prothrombin activation, since it disappears after addition of heparin, which promotes thrombin antithrombin III complex formation. After a plateau of 2-10 min, there is further thrombin generation, which results in clotting after 15-27 min at a level of 40-50 ng thrombin/ml. The thrombin generated 9-25 min before clotting may activate factors V and VIII and stimulate platelet aggregation and release. In contrast, the cascade hypothesis assigns a role for thrombin only late in blood clotting. Radioimmunoassay of thrombin and other clotting factors will be useful for clinical and physiological studies of blood clotting especially since the assay seems specific for thrombin and is independent of other activities that affect bioassays.
Risk of developing a mitochondrial DNA deletion disorder
Authors: Patrick F Chinnery, Salvatore DiMauro, Sara Shanske, Eric A Schon, Massimo Zeviani, Caterina Mariotti, Fanco Carrara, Anne Lombes, Pascal Laforet, Heléne Ogier, Michaela Jaksch, Hanns Lochmüller, Rita Horvath, Marcus Deschauer, David R Thorburn, Laurence A Bindoff, Joanna Poulton, Robert W Taylor, John NS Matthews, Douglass M Turnbull
Journal: The Lancet (2004)
Reduced Expression of Lipoic Acid Synthase Accelerates Diabetic Nephropathy
Authors: Xianwen Yi, Longquan Xu, Sylvia Hiller, Hyung-Suk Kim, Volker Nickeleit, Leighton R. James, Nobuyo Maeda
Journal: Journal of the American Society of Nephrology (2011)

Oxidative stress contributes to the pathogenesis of diabetic nephropathy. In mitochondria, lipoic acid synthase produces α-lipoic acid, an antioxidant and an essential cofactor in α-ketoacid dehydrogenase complexes, which participate in glucose oxidation and ATP generation. Administration of lipoic acid abrogates diabetic nephropathy in animal models, but whether lower production of endogenous lipoic acid promotes diabetic nephropathy is unknown. Here, we crossed mice heterozygous for lipoic acid synthase deficiency (Lias(+/-)) with Ins2(Akita/+) mice, a well characterized model of type 1 diabetes. Double mutant mice had more overt diabetic nephropathy, including microalbuminuria, glomerular basement thickening, mesangial matrix expansion, and hypertension, compared with Lias(+/+)Ins2(Akita/+) controls. We also identified proximal tubules as a major site for generation of superoxide anions during diabetic nephropathy. Mitochondria in proximal tubular cells were particularly sensitive to damage in diabetic mice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.
A Critical Review of Theory in Breast Cancer Screening Promotion across Cultures
Authors: Rena J. Pasick, Nancy J. Burke
Journal: Annual Review of Public Health (2007)

This article reviews the contribution and potential of widely used health behavior theories in research designed to understand and redress the disproportionate burden of breast cancer borne by diverse race/ethnic, immigrant, and low-income groups associated with unequal use of mammography. We review the strengths and limitations of widely used theories and the extent to which theory contributes to the understanding of screening disparities and informs effective intervention. The dominant focus of most theories on individual cognition is critically assessed as the abstraction of behavior from its social context. Proposed alternatives emphasize multilevel ecological approaches and the use of anthropologic theory and methods for more culturally grounded understandings of screening behavior. Common and alternative treatments of fatalism exemplify this approach, and descriptive and intervention research exemplars further highlight the integration of screening behavior and sociocultural context.
Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNF treatment
Authors: C. Veltkamp, M. Anstaett, K. Wahl, S. Moller, S. Gangl, O. Bachmann, M. Hardtke-Wolenski, F. Langer, W. Stremmel, M. P. Manns, K. Schulze-Osthoff, H. Bantel
Journal: Gut (2011)

Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient compensation of chronically activated T lymphocytes. This study was conducted to investigate whether increased apoptosis contributes to Treg cell deficiency in IBD and whether successful treatment with antitumour necrosis factor α (TNFα) is achieved by reducing of Treg cell apoptosis.Apoptosis of CD4(+)Foxp3(+) Treg cells in tissue sections of patients with active IBD was analysed by immunohistochemistry and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining. Apoptosis of peripheral blood CD4(+)CD25(+)Foxp3(+) Treg cells was investigated by flow cytometry and annexin-V staining. In addition, caspase activity and apoptosis were measured in sera of patients with IBD treated with anti-TNFα by a luminometric caspase enzyme assay.It is demonstrated that patients with active IBD revealed increased apoptosis of local CD4(+)Foxp3(+) Treg cells in the inflamed mucosa compared with non-inflamed control colon tissue. Moreover, in peripheral blood a reduced frequency and increased apoptosis of Treg cells were found and accompanied by elevated caspase activity in the serum. During anti-TNFα treatment, Treg cell apoptosis declined in close correlation with elevated peripheral Treg cell numbers and a decrease of caspase activation and disease activity.These data suggest that increased apoptosis of Treg cells plays a potentially important role in the pathogenesis of IBD and can be reversed by anti-TNFα treatment. Measurement of Treg cell apoptosis and serum caspase activity might therefore represent promising tools for monitoring disease activity and treatment response in patients with IBD.
Population-based trends in use of surgery for non-small cell lung cancer in a UK region, 1995-2006
Authors: M. McMahon, J. M. Barbiere, D. C. Greenberg, K. A. Wright, G. Lyratzopoulos
Journal: Thorax (2011)

To assess time trends in use of surgery in patients with non-small cell lung cancer (NSCLC) in a UK region.Cancer registration data for patients diagnosed with NSCLC between 1995 and 2006 in the East of England were analysed. Rates of surgery use for different age, gender, diagnosis period, tumour subtype and deprivation quintile groups were examined.The analysis included 18,767 patients with NSCLC. During the study period, 13% of patients were treated by surgery. Use of surgery decreased over time from 15% in 1995-1997 to 11% in 2004-2006 (p=0.022). Initial socioeconomic differences in surgery use narrowed significantly over time (p=0.028) and became non-apparent at the end of the study period.Use of surgery in patients with NSCLC decreased during the study period, possibly reflecting increasing quality of preoperative staging processes. Initial socioeconomic inequalities in surgery use became undetectable at the end of the study period. The findings provide baseline information to support comparisons with patterns of clinical management in more recent years.
Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis
Authors: I. Noth, S. M. Zangan, R. V. Soares, A. Forsythe, C. Demchuk, S. M. Takahashi, S. B. Patel, M. E. Strek, J. A. Krishnan, M. G. Patti, H. MacMahon
Journal: European Respiratory Journal (2011)

Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR disease and may contribute to idiopathic pulmonary fibrosis (IPF). We hypothesised that HH evaluated by computed tomography is more common in IPF than in asthma or chronic obstructive pulmonary disease (COPD), and correlates with abnormal GOR measured by pH probe testing. Rates of HH were compared in three cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter-observer agreement. In IPF, symptoms and anti-reflux medications were correlated with diffusing capacity of the lung for carbon monoxide (<i>D</i><sub>L,CO</sub>) and composite physiologic index (CPI). HH was correlated with pH probe testing in IPF patients (n=14). HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma (16.67%, p=0.0139). The HH inter-observer κ agreement was substantial in IPF (κ=0.78) and asthma (κ=0.86), and moderate in COPD (κ=0.42). In IPF, HH did not correlate with lung function, except in those on anti-reflux therapy, who had a better <i>D</i><sub>L,CO</sub> (p&lt;0.03) and CPI (p&lt;0.04). HH correlated with GOR as measured by DeMeester scores (p&lt;0.04). HH is more common in IPF than COPD or asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming abnormal acid GOR. Presence of HH alone was not associated with decreased lung function.
Remarks ON THE ETIOLOGY OF CARCINOMA. HAS IT A PHYSIOLOGICAL FUNCTION IN THE BODY?: Read before the Edinburgh Medico-Chirurgical Society
Authors: G. T. Beatson
Journal: BMJ (1905)

SOME recent utterances on the etiology of carcinoma strongly endorsed the view that we have to deal a microbic disease.This aspect of the question is aew this Society, as it has already been placed before it than one occasion, and notably so by Dr. W. Russell able and instructive paper.The lately published researches to which I refer are those of Professor Doyen, of t.hose of Drs.Ford Robertson and Wade, of
Race and Mortality after Acute Renal Failure
Authors: Sushrut S. Waikar, Gary C. Curhan, John Z. Ayanian, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2007)

Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference.
Regression Studies with Safflower Oil and Sitosterol in Rabbit Atherosclerosis
Authors: JONATHAN P. MILLER, G. FREDERICK LAMBERT, DOUGLAS V. FROST
Journal: Circulation Research (1959)

Hypercholesteremia with atherosclerosis was induced in male rabbits by feeding hydrogenated coconut oil as the only lipid in a purified diet. Replacing the hydrogenated coconut oil by safflower oil produccd a profound fall in plasma cholesterol in rabbits. Supplementing the safflower oil with βsitosterol at 3 per cent of the oil weight caused an even greater decrease in plasma cholesterol. Although in both cases the further development of aortic atheroma was arrested, there was no detectable regression of existing lesions, over 24 weeks. Hydrogenated coconut oil feeding produced high plasma and liver cholesterol levels in rabbits. When small amounts of safflower oil were fed in addition to the hydrogenated coconut oil, the elevation of plasma or liver cholesterol was much less.
From Intensive Care to Critical Care Medicine
Authors: Max Harry Weil, Wanchun Tang
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The evolution of Critical Care Medicine is traced in relationship to its predecessors, namely Intensive Care and Intensive Therapy. This commentary documents the initial physical care rendered by professional nurses in hospitals of the 19th century in locations close to the nursing stations. The development of incubators for newborns and life-support devices to support ventilation and renal function or to reverse fatal arrhythmias characterized Intensive Therapy of the early 20th century. In the most recent 50 years, Critical Care evolved for comprehensive, largely electronic monitoring and automated laboratory measurements to guide intensive therapy of multiorgan failures by critical care physicians and nurse specialists, pharmacists, and respiratory therapists using multiple life-support methodologies and devices.
Ciprofloxacin and pseudomembranous colitis
Authors: B.J. O'Keeffe, G.S. Tillotson, S.L. Chew, R. Daelemans, R.L. Lins, C.L. Golledge, G.L. O'Neill, C.F. Carson, R.A. Bowman, T.V. Riley, Nicola Low, Anthony Harries
Journal: The Lancet (1990)
Imaging experimental infective endocarditis with indium-111-labeled blood cellular components.
Authors: A L Riba, M L Thakur, A Gottschalk, V T Andriole, B L Zaret
Journal: Circulation (1979)

The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 (111In)-labeled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of 111In-platelets and in five after 111In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal 111In uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathological examination. 111In platelet uptake in vegetations from the 17 animals averaged 240 +/- 41 times greater than that in normal myocardium and 99 +/- 15 times greater uptake in blood. In contrast, 111In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracer administration and the lesion myocardium activity ratio was only 5 +/- 2 (3 +/- 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive 111In platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular 111In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that 111In platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation.
The paradox of NKp46<sup>+</sup>natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon α treatment
Authors: Tom Pembroke, Adam Christian, Emma Jones, Robert K Hills, Eddie C Y Wang, Awen M Gallimore, Andrew Godkin
Journal: Gut (2013)

Bilateral locked posterior fracture dislocation of the shoulders is one of the least common injuries of the shoulder, and this injury has been suggested to be pathognomonic of seizures when diagnosed in the absence of trauma. The authors present a case of idiopathic bilateral locked posterior fracture dislocations of the shoulder, along with a review of the medical literature. The authors also present the "triple E syndrome," describing the possible etiologies of this injury: epilepsy (or any convulsive seizure), electrocution, or extreme trauma.
Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda
Authors: Paul J Weidle, Nafuna Wamai, Peter Solberg, Cheryl Liechty, Sam Sendagala, Willy Were, Jonathan Mermin, Kate Buchacz, Prosper Behumbiize, Ray L Ransom, Rebecca Bunnell
Journal: The Lancet (2006)
Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD
Authors: Gerard J. Criner, John E. Connett, Shawn D. Aaron, Richard K. Albert, William C. Bailey, Richard Casaburi, J. Allen D. Cooper, Jeffrey L. Curtis, Mark T. Dransfield, MeiLan K. Han, Barry Make, Nathaniel Marchetti, Fernando J. Martinez, Dennis E. Niewoehner, Paul D. Scanlon, Frank C. Sciurba, Steven M. Scharf, Don D. Sin, Helen Voelker, George R. Washko, Prescott G. Woodruff, Stephen C. Lazarus
Journal: New England Journal of Medicine (2014)

Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial.
Control of Gammaherpesvirus Latency by Latent Antigen-Specific Cd8+ T Cells
Authors: Edward J. Usherwood, Douglas J. Roy, Kim Ward, Sherri L. Surman, Bernadette M. Dutia, Marcia A. Blackman, James P. Stewart, David L. Woodland
Journal: The Journal of Experimental Medicine (2000)

The contribution of the latent antigen-specific CD8(+) T cell response to the control of gammaherpesvirus latency is currently obscure. Some latent antigens induce potent T cell responses, but little is known about their induction or the role they play during the establishment of latency. Here we used the murine gammaherpesvirus system to examine the expression of the latency-associated M2 gene during latency and the induction of the CD8(+) T cell response to this protein. M2, in contrast to the M3 latency-associated antigen, was expressed at day 14 after infection but was undetectable during long-term latency. The induction of the M2(91-99)/K(d) CD8(+) T cell response was B cell dependent, transient, and apparently induced by the rapid increase in latently infected cells around day 14 after intranasal infection. These kinetics were consistent with a role in controlling the initial "burst" of latently infected cells. In support of this hypothesis, adoptive transfer of an M2-specific CD8(+) T cell line reduced the initial load of latently infected cells, although not the long-term load. These data represent the first description of a latent antigen-specific immune response in this model, and suggest that vaccination with latent antigens such as M2 may be capable of modulating latent gammaherpesvirus infection.
Generic Biologics May Be Coming to the Marketplace If Legislation Passes In Congress
Authors: J. B. Finkelstein
Journal: JNCI Journal of the National Cancer Institute (2007)

Legislation currently moving through the Senate would allow the U.S. Food and Drug Administration to regulate generic biologic agents, an industry potentially worth billions of dollars a year. But it would also establish protections that favor the original developers, giving them 12 years without direct competition. Although a relatively young fi eld, there are already a handful of blockbuster biologic agents, especially in oncology, where these treatments promise a more targeted ap proach to the disease. Everything from blood and blood products to cellular and gene therapies falls under the FDA’s defi nition of protein