tbuckley/cabot-search huggingface dataset:
Regulation of thymocyte development through CD3. II. Expression of T cell receptor beta CD3 epsilon and maturation to the CD4+8+ stage are highly correlated in individual thymocytes.
Authors: C N Levelt, R Carsetti, K Eichmann
Journal: The Journal of Experimental Medicine (1993)

Recent studies have shown that maturation of CD4-8- double negative (DN) thymocytes to the CD4+8+ double positive (DP) stage is dependent on expression of the T cell receptor (TCR)-beta polypeptide. The exact mechanism by which the TCR-beta chain regulates this maturation step remains unknown. Previous experiments had suggested that in the presence of some TCR+ thymocytes, additional DN thymocytes not expressing a TCR-beta chain may be recruited to mature to the DP stage. The recent demonstration of an immature TCR-beta-CD3 complex on early thymocytes lead to the alternative hypothesis that signal transduction through an immature TCR-CD3 complex may induce maturation to the DP stage. In the latter case, maturation to the DP stage would depend on the expression of TCR-beta-CD3 in the same cell. We examined these two hypotheses by studying the expression of the intra- and extracellular CD3 epsilon, CD3 zeta, and TCR-beta polypeptides in intrathymic subpopulations during embryogenesis. CD3 epsilon and CD3 zeta were expressed intracellularly 2 and 1 d, respectively, before intracellular expression of the TCR-beta chain, potentially allowing immediate surface expression of an immature TCR-beta-CD3 complex as soon as functional rearrangement of a TCR-beta gene locus has been accomplished. Calcium mobilization could be induced by stimulation with anti-CD3 epsilon mAb as soon as intracellular TCR-beta was detectable, suggesting that a functional TCR-beta-CD3 complex is indeed expressed on the surface of early thymocytes. From day 17 on, most cells were in the DP stage, and over 95% of the DP cells expressed on the TCR-beta chain intracellularly. At day 19 of gestation, extremely low concentrations of TCR-beta chain and CD3 epsilon were detectable on the cell surface of nearly all thymocytes previously thought to be TCR-CD3 negative. These findings strongly support the hypothesis that maturation to the DP stage depends on surface expression of and subsequent signal transduction through an immature TCR-beta-CD3 complex and suggest that maturation to the DP stage by recruitment, if it occurs at all, is of minor relevance.
P35 Long-term remission is achievable in autoimmune hepatitis using Tacrolimus or Mycophenolate mofetil and results in regression of fibrosis
Authors: R. Scott, J. White, G. Atwal, N. Taylor, G. Mortimore, J. Freeman, A. Lawson, A. Austin
Journal: Gut (2011)

<h3>Introduction</h3> 10–20% of patients do not respond to conventional treatment of autoimmune hepatitis, or are intolerant of azathioprine. There is no established second line treatment. Experience with transplant immunosuppressive agents such as Tacrolimus (TAC) and mycophenolate mofetil (MMF) is limited to small numbers and short-term follow-up. <h3>Aim</h3> To describe the progress of all patients who had failed conventional therapy and were treated with second line agents with at least 12-month follow-up. <h3>Method</h3> An audit of patients identified who received second line agents for at least 12 months on maintenance dose &lt;10 mg prednisolone. Patient records were reviewed and treatment endpoints based on aminotransferase changes defined as; Complete response (CR) - sustained normalisation for at least 12 months, partial response (PR) - improvement by &gt;50% but not always normal over a 12-month period. Where applicable, interval histology was reviewed by a single pathologist to assess ISHAK fibrosis scores at the start and at least 18 months after commencing second line agents. <h3>Results</h3> A total of 26 patients were identified. 9 were treated with TAC for a median 81 months (21–137), 16 with MMF for a median 81 months (30–114) and one on a combination of TAC and MMF. Median age is 56 (28–68) and 64 (40–79) respectively. The median dose of TAC is 3.5 mg/day (1–6) and MMF 1 g/day (1–2). All patients on TAC achieved CR. Two patients discontinued treatment; one renal impairment and one rationalising treatment after 27 months CR. 11/16 patients on MMF achieved CR, 5/16 achieved PR. Five patients no longer take MMF; two due to toxicity (recurrent chest infections at 60 months, GI disturbance at 78 months), one successfully withdrew treatment after 39 months CR, one switched to TAC as a treatment failure of MMF after 103 months and one was withdrawn after a diagnosis of larynx SCC. The combination patient achieved CR and has received 50 months dual treatment with confirmed histological remission. Four patients on TAC and five on MMF had interval biopsies. 3/4 patients on TAC (median 87 months) exhibited stable or reduced grades of fibrosis compared to 2/5 patients on MMF (median 101 months). <h3>Conclusion</h3> Effective long-term maintenance of remission at 10 years is achievable on MMF and TAC in the absence of significant toxicity. Achieving prolonged CR seems to confer disease control and can result in histological regression of fibrosis.
Blood Pressure, C-Reactive Protein, and Risk of Future Cardiovascular Events
Authors: Gavin J. Blake, Nader Rifai, Julie E. Buring, Paul M Ridker
Journal: Circulation (2003)

Background— Accumulating data suggest a link between blood pressure and vascular inflammation. Methods and Results— We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure &lt;120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and ≥160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively ( P for trend &lt;0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (≥3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure ≥160/95 mm Hg and CRP levels ≥3 mg/L was 8.31 (95% CI, 4.44 to 15.55, P &lt;0.0001) compared with those with blood pressure &lt;120/75 and CRP levels &lt;3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (&lt;3 or ≥3 mg/L) and blood pressure levels (&lt;130/85 or ≥130/85), the risk factor–adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure, 1.87 ( P =0.002); low CRP/high blood pressure, 2.54 ( P &lt;0.0001); and high CRP/high blood pressure, 3.27 ( P &lt;0.0001). Conclusions— CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive.
Sinoatrial-Node Entrance Block
Authors: BRUCE N. GOLDREYER, ANTHONY N. DAMATO
Journal: Circulation (1971)

Sinus-node function was characterized in 13 patients during cardiac catheterization by the introduction of progressively premature atrial depolarizations. Curves relating the extent of sinus-node depression following these premature depolarizations and their degree of prematurity were constructed. The maximum extent of sinus-node depression following premature depolarizations and A-V-nodal and atrial refractoriness were determined. Maximum sinus-node depression could be demonstrated to be independent of sinus rate. In six patients "early" atrial premature depolarizations demonstrated entrance block into the sinus-node pacemaker. Sinoatrial (SA) node entrance block could be clearly distinguished from atrial echoes and repetitive atrial firing subsequent to stimulation during the atrial relative refractory period. Prolonged refractoriness of tissues conducting impulses between atrium and sinus node was unrelated to parameters of sinus-node automaticity (sinus rate or maximum depression following premature atrial depolarizations) or to the refractoriness of the atrium itself.
Fibronectin fragments containing the RGDS cell-binding domain mediate monocyte migration into the rabbit lung. A potential mechanism for C5 fragment-induced monocyte lung accumulation.
Authors: D E Doherty, P M Henson, R A Clark
Journal: Journal of Clinical Investigation (1990)

Many inflammatory processes are characterized by an early phase of neutrophil migration and a later phase of monocyte migration into the inflammatory site. Mechanisms that govern the transition between phases are the subject of these investigations. Acute lung inflammation induced by C5 fragments in the rabbit leads to an initial neutrophil influx and plasma leakage into the alveolar space, followed by monocyte influx that we have previously shown to be dependent on prior emigration of neutrophils. Neutrophil enzymes are known to cleave intact fibronectin into fragments that are monocyte chemotaxins in vitro. Accordingly, generation of appropriate fibronectin fragments in situ by proteolytic enzymes from infiltrating neutrophils might represent a potential mechanism for attraction of monocytes into the lung. The studies reported herein demonstrate that a 120-kD fragment of fibronectin containing the RGDS fibroblast cell-binding domain induced monocyte migration into the rabbit lung in vivo. Intact fibronectin was inactive. A significant proportion of the monocyte migration was neutrophil independent. Intact fibronectin was present in bronchoalveolar lavage fluid from C5 fragment-treated animals rendered neutropenic, but absent in lavage from normal C5 fragment-treated animals. Fibronectin fragments were present in bronchoalveolar lavage fluid from both C5 fragment-treated and control rabbits. In addition, the amount of fibronectin was significantly increased in lavage of C5 fragment-treated normal but not neutropenic animals. Monoclonal antibodies directed against an epitope of fibronectin containing the RGDS cell-binding domain significantly inhibited the C5 fragment-induced monocyte migration, but not neutrophil migration. These studies suggest that chemotactic fibronectin fragments may in part be responsible for the recruitment of monocytes into areas of acute lung inflammation.
Workgroup II: the screening process. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002)
Authors: S. Winawer, J. Faivre, J. Selby, L. Bertaro, T. H.-H. Chen, O. Kroborg, B. Levin, J. Mandel, C. O'Morain, M. Richards, G. Rennert, A. Russo, H. Saito, B. Semigfnovsky, B. Wong, R. Smith
Journal: Annals of Oncology (2004)
Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44–GeparQuinto)
Authors: G. von Minckwitz, S. Loibl, M. Untch, H. Eidtmann, M. Rezai, P.A. Fasching, H. Tesch, H. Eggemann, I. Schrader, K. Kittel, C. Hanusch, J. Huober, C. Solbach, C. Jackisch, G. Kunz, J.U. Blohmer, M. Hauschild, T. Fehm, V. Nekljudova, B. Gerber, K. Gnauert, B. Heinrich, T. Prätz, U. Groh, H. Tanzer, C. Villena, A. Tulusan, B. Liedtke, J.-U. Blohmer, K. Kittel, C. Mau, J. Potenberg, J. Schilling, M. Just, E. Weiss, U. Bückner, M. Wolfgarten, R. Lorenz, G. Doering, S. Feidicker, P. Krabisch, U. Deichert, D. Augustin, G. Kunz, K. Kast, G. von Minckwitz, C. Nestle-Krämling, M. Rezai, C. Höß, J. Terhaag, P. Fasching, P. Staib, B. Aktas, T. Kühn, F. Khandan, V. Möbus, C. Solbach, H. Tesch, E. Stickeler, G. Heinrich, H. Wagner, A. Abdallah, T. Dewitz, G. Emons, A. Belau, V. Rethwisch, T. Lantzsch, C. Thomssen, U. Mattner, A. Nugent, V. Müller, T. Noesselt, F. Holms, T. Müller, J.-U. Deuker, I. Schrader, D. Strumberg, C. Uleer, E. Solomayer, I. Runnebaum, H. Link, O. Tomé, H.-U. Ulmer, B. Conrad, G. Feisel-Schwickardi, H. Eidtmann, C. Schumacher, T. Steinmetz, I. Bauerfeind, S. Kremers, D. Langanke, U. Kullmer, A. Ober, D. Fischer, A. Kohls, W. Weikel, J. Bischoff, K. Freese, M. Schmidt, W. Wiest, M. Sütterlin, M. Dietrich, M. Grießhammer, D.-M. Burgmann, C. Hanusch, B. Rack, C. Salat, D. Sattler, J. Tio, E. von Abel, B. Christensen, U. Burkamp, C.-H. Köhne, W. Meinerz, S.-T. Graßhoff, T. Decker, F. Overkamp, I. Thalmann, A. Sallmann, T. Beck, T. Reimer, G. Bartzke, M. Deryal, M. Weigel, J. Huober, P. Weder, C.-C. Steffens, S. Lemster, A. Stefek, F. Ruhland, M. Hofmann, J. Schuster, W. Simon, U. Kronawitter, M. Clemens, T. Fehm, W. Janni, K. Latos, W. Bauer, A. Roßmann, L. Bauer, D. Lampe, V. Heyl, G. Hoffmann, F. Lorenz-Salehi, J. Hackmann, R. Schlag
Journal: Annals of Oncology (2014)
17β-Estradiol-induced interaction of ERα with NPPA regulates gene expression in cardiomyocytes
Authors: Shokoufeh Mahmoodzadeh, Thi Hang Pham, Arne Kuehne, Britta Fielitz, Elke Dworatzek, Georgios Kararigas, George Petrov, Mercy M. Davidson, Vera Regitz-Zagrosek
Journal: Cardiovascular Research (2012)

17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not fully elucidated. To gain better understanding of E2-induced ERα action in the human heart, we aimed to identify and functionally analyse interaction partners of ERα. Using yeast two-hybrid assays with a human heart cDNA library, we identified atrial natriuretic peptide precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERα interaction partner interacting in an E2-dependent manner. Mutation analyses and immunofluorescence data indicated that the LXXLL motif within NPPA is necessary for its E2-induced interaction with ERα, its action as a co-repressor of ERα, and its translocation into the nucleus of human and rat cardiomyocytes. Expression analysis and chromatin immunoprecipitation assays in a human left ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with E2/ERα, suppressing the transcriptional activity of ERα on E2-target genes, such as NPPA, connexin43, αactinin-2, nuclear factor of activated T-cells, and collagens I and III. We characterize for the first time an E2-regulated interaction of NPPA with ERα in cardiomyocytes, that may be crucial in physiological and/or pathological cardiac processes, thereby representing a potential therapeutic target.
The Falun Gong, organ transplantation, the holocaust and ourselves
Authors: Tom Treasure
Journal: Journal of the Royal Society of Medicine (2007)

The numbers of organ transplants performed in China and the speed with which organs become available has raised international concern about the source of organs. It is publicly declared that organs come from executed criminals and that consent is given. However, there are allegations of an even more macabre scenario—that prisoners are systematically subjected to surgery specifically to remove their organs for transplantation. In this essay I explore the plausibility of this claim against our knowledge of doctors’ complicity with the events leading to the holocaust and the practicalities of contemporary organ transplantation. Organ transplantation has increased in China at a
A Randomized Trial of Urodynamic Testing before Stress-Incontinence Surgery
Authors: Charles W. Nager, Linda Brubaker, Heather J. Litman, Halina M. Zyczynski, R. Edward Varner, Cindy Amundsen, Larry T. Sirls, Peggy A. Norton, Amy M. Arisco, Toby C. Chai, Philippe Zimmern, Matthew D. Barber, Kimberly J. Dandreo, Shawn A. Menefee, Kimberly Kenton, Jerry Lowder, Holly E. Richter, Salil Khandwala, Ingrid Nygaard, Stephen R. Kraus, Harry W. Johnson, Gary E. Lemack, Marina Mihova, Michael E. Albo, Elizabeth Mueller, Gary Sutkin, Tracey S. Wilson, Yvonne Hsu, Thomas A. Rozanski, Leslie M. Rickey, David Rahn, Sharon Tennstedt, John W. Kusek, E. Ann Gormley
Journal: New England Journal of Medicine (2012)

Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes.
Progressive mechanical impairment associated with progressive but reversible electrocardiographic ischaemic changes during repeated brief coronary artery occlusions in pigs
Authors: J. FIGUERAS, J. CINCA, G. SENADOR, J. RIUS
Journal: Cardiovascular Research (1986)

Journal Article Progressive mechanical impairment associated with progressive but reversible electrocardiographic ischaemic changes during repeated brief coronary artery occlusions in pigs Get access JAIME FIGUERAS, JAIME FIGUERAS From the Experimental Laboratory, Coronary Unit, Cuidad Sanitaria Valle de Hebron de la Seguridad Social, Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar JUAN CINCA, JUAN CINCA From the Experimental Laboratory, Coronary Unit, Cuidad Sanitaria Valle de Hebron de la Seguridad Social, Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar GUSTAVO SENADOR, GUSTAVO SENADOR From the Experimental Laboratory, Coronary Unit, Cuidad Sanitaria Valle de Hebron de la Seguridad Social, Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar JORGE RIUS JORGE RIUS From the Experimental Laboratory, Coronary Unit, Cuidad Sanitaria Valle de Hebron de la Seguridad Social, Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 20, Issue 11, November 1986, Pages 797–806, https://doi.org/10.1093/cvr/20.11.797 Published: 01 November 1986
Emergency cardiac care in the athletic setting: from schools to the Olympics
Authors: Brett Toresdahl, Ron Courson, Mats Börjesson, Sanjay Sharma, Jonathan Drezner
Journal: British Journal of Sports Medicine (2012)

Medical providers at sporting events must be well-trained in the care of cardiac emergencies. Optimal outcomes are most likely achieved through comprehensive emergency planning that ensures prompt and appropriate care. The diversity of athletic venues, as well as the age and competition level of different athlete populations, present challenges to the provision of appropriate emergency care in sport. An efficient and coordinated medical response to cardiac emergencies requires an established emergency action plan, training of potential first responders in cardiopulmonary resuscitation and use of an automated external defibrillator, coordinating communication and transportation systems, and ensuring access to appropriate medical equipment and supplies. Prompt recognition and early defibrillation are critical in the management of athletes suffering sudden cardiac arrest. This article reviews emergency planning and cardiac care in athletics, with special considerations presented for the school, large arena, mass event and Olympic settings.
Nitric oxide in essential and renal hypertension.
Authors: R MacAllister, P Vallance
Journal: Journal of the American Society of Nephrology (1994)

L-Arginine-derived nitric oxide (NO) maintains the systemic and renal vasculature in a state of active vasodilation. Inhibition of NO synthesis increases renal vascular tone, reducing RBF and GFR. Similar effects reproduced in other vascular beds result in systemic hypertension. In addition, NO modulates natriuresis by a direct effect on renal tubular function. Abnormalities of the L-arginine:NO pathway occur in experimental hypertension and renal disease and could contribute to alterations in vascular tone; similar abnormalities are seen in essential hypertension in humans. In dialysis-dependent renal failure, the accumulation of endogenous compounds that inhibit NO synthase could exacerbate renal hypertension by inhibiting vascular and renal tubular NO synthesis and might provoke atherogenesis.
Metabolic Syndrome: Risk factor distribution and 18-year mortality in the Multiple Risk Factor Intervention Trial
Authors: L. E. Eberly
Journal: Diabetes Care (2006)

To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD).A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference.At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]).Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.
STUDIES ON THE MECHANISM OF THE SHWARTZMAN PHENOMENON
Authors: Lewis Thomas, Chandler A. Stetson
Journal: The Journal of Experimental Medicine (1949)

Rabbit skin which is prepared for the Shwartzman phenomenon by an intradermal injection of meningococcal toxin exhibits, in vitro, a high degree of aerobic glycolysis. This metabolic abnormality is reflected, in vivo, by a measurable increase in the concentration of lactic acid in the prepared skin. Some increase in anaerobic glycolysis also occurs in prepared skin; this is of less degree than the increase in aerobic glycolysis. The respiratory quotient of prepared skin tends to be somewhat higher than that of normal skin, although the oxygen uptake is not significantly altered. Gross hemorrhagic lesions which resemble the Shwartzman phenomenon are produced by the intradermal injection of papain into rabbits which have received an intravenous injection of meningococcal toxin 1 hour previously. Such hemorrhagic reactions are not observed when papain is injected into normal rabbit skin. Similarly, hemorrhagic lesions are produced by the intradermal injection of cysteine and BAL, following an intravenous injection of meningococcal toxin. An hypothesis to explain the Shwartzman phenomenon, which implicates tissue protease in the damage to the blood vessels of the skin, is proposed.
Private health sector could face reduced business as NHS tightens its belt
Authors: A. O'Dowd
Journal: BMJ (2011)

Private sector mental health and specialist care providers could face tough times in the short term as the NHS tightens its financial belt and focuses on inhouse provision, according to new report.

A report from healthcare intelligence analysts Laing & Buisson says that public spending cuts will mean pressure for non-NHS independent specialist providers in the next three years, but the situation could improve in the medium to long term.

Mental Health and Specialist Care Services UK Market Report provides an analysis of the market in England for the independent mental health and specialist care sector, which provides services in mental health hospitals; care homes and non-residential care for learning …