tbuckley/cabot-search huggingface dataset:
<i>Mycobacterium tuberculosis</i>–specific CD8<sup>+</sup>T Cells Preferentially Recognize Heavily Infected Cells
Authors: Deborah A. Lewinsohn, Amy S. Heinzel, James M. Gardner, Liqing Zhu, Mark R. Alderson, David M. Lewinsohn
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Both CD4+ and CD8+ T cells are important for successful immunity to tuberculosis and have redundant effector functions, such as cytolysis and release of potent antimycobacterial cytokines such as interferon-gamma and tumor necrosis factor-alpha. We hypothesized that CD8+ T cells play a unique role in host defense to Mycobacterium tuberculosis infection as well. Possibilities include preferential and/or enhanced release of granular constituents and/or preferential recognition of heavily infected cells. Utilizing human, Mycobacterium tuberculosis-specific, CD4+ and CD8+ T cell clones, we demonstrate that, after recognition of antigen-presenting cells displaying peptide antigen, CD4+ T cells preferentially release interferon-gamma, whereas CD8+ T cells preferentially lyse antigen-presenting cells. Furthermore, utilizing dendritic cells infected with Mycobacterium tuberculosis expressing green fluorescent protein, we show that CD8+ T cells preferentially recognize heavily infected cells that constitute the minority of infected cells. These data support the hypothesis that the central role of CD8+ T cells in the control of infection with Mycobacterium tuberculosis may be that of surveillance; in essence, recognition of cells in which the containment of Mycobacterium tuberculosis is no longer effective.
Simvastatin Rescues Rats From Fatal Pulmonary Hypertension by Inducing Apoptosis of Neointimal Smooth Muscle Cells
Authors: Toshihiko Nishimura, Laszlo T. Vaszar, John L. Faul, Guohua Zhao, Gerald J. Berry, Lingfang Shi, Daoming Qiu, Gail Benson, Ronald G. Pearl, Peter N. Kao
Journal: Circulation (2003)

Pulmonary vascular injury by toxins can induce neointimal formation, pulmonary arterial hypertension (PAH), right ventricular failure, and death. We showed previously that simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in pneumonectomized rats injected with the alkaloid toxin monocrotaline. The present study was undertaken to investigate the efficacy of simvastatin and its mechanism of reversing established neointimal vascular occlusion and pulmonary hypertension.Pneumonectomized rats injected with monocrotaline at 4 weeks demonstrated severe PAH at 11 weeks (mean pulmonary artery pressure [mPAP]=42 versus 17 mm Hg in normal rats) and death by 15 weeks. When rats with severe PAH received simvastatin (2 mg x kg(-1) x d(-1) by gavage) from week 11, there was 100% survival and reversal of PAH after 2 weeks (mPAP=36 mm Hg) and 6 weeks (mPAP=24 mm Hg) of therapy. Simvastatin treatment reduced right ventricular hypertrophy and reduced proliferation and increased apoptosis of pathological smooth muscle cells in the neointima and medial walls of pulmonary arteries. Longitudinal transcriptional profiling revealed that simvastatin downregulated the inflammatory genes fos, jun, and tumor necrosis factor-alpha and upregulated the cell cycle inhibitor p27Kip1, endothelial nitric oxide synthase, and bone morphogenetic protein receptor type 1a.Simvastatin reverses pulmonary arterial neointimal formation and PAH after toxic injury.
Reduced Mitochondrial Adenosine Triphosphate Synthesis in Skeletal Muscle in Patients With Child–Pugh Class B and C Cirrhosis
Authors: Esben Bjørn Jacobsen, Ole Hamberg, Bjørn Quistorff, Peter Ott
Journal: Hepatology (2001)

Patients with cirrhosis of the liver often complain of tiredness and a lack of strength at physical exercise. Other investigators have found that muscle strength, work capacity, and maximal oxygen consumption are reduced in cirrhosis. We hypothesized that mitochondrial maximal rate of ATP synthesis in skeletal muscle may be impaired in these patients. This was tested with (31)P nuclear magnetic resonance spectroscopy in anterior tibial muscle of cirrhotic patients and healthy controls at rest, during exercise, and subsequent recovery. In patients with Child-Pugh class B and C cirrhosis resting PCr/P(i) ratio (8.3 +/- 1.0; n = 7) was lower than in patients with Child-Pugh class A cirrhosis (12.1 +/- 2.1; n = 7) and controls (11. 7 +/- 1.1; n = 6; P =.03), while the resting P(i)/gammaATP ratio was higher in Child-Pugh class B and C patients (0.43, 0.30, and 0.27, respectively; P =.03). Maximal rate of mitochondrial adenosine triphosphate (ATP) synthesis (V(max)) as calculated from the initial rate of phosphocreatine (PCr) recovery after work was lower in Child-Pugh class B and C cirrhosis (0.189 mmol/L/s +/- 0.034) than in both Child-Pugh class A patients (0.402 mmol/L/s +/- 0.103) and controls (0.425 mmol/L/s +/- 0.064; P =.01). V(max) was significantly correlated to intracellular free [Mg(2+)] obtained from the (31)P nuclear magnetic resonance (NMR) spectra (P =.003). Insufficient oxygen delivery did not seem a likely cause of reduced ATP synthesis in the patients. These findings suggest either a decreased number of mitochondria in skeletal muscle of the cirrhotic patient in Child-Pugh class B and C or a defective mitochondrial function that could be related to low intracellular free [Mg(2+)].
Attachment theory underestimates the child
Authors: Judith Rich Harris
Journal: Behavioral and Brain Sciences (2009)

Abstract The problem with elaborations of attachment theory is attachment theory itself. How would a mind that works the way the theory posits have increased its owner's fitness in hunter-gatherer times? The child's mind is more capacious and discerning than attachment theorists give it credit for. Early-appearing, long-lasting personality characteristics, often mistaken for the lingering effects of early experiences, are more likely due to genetic influences on personality.
Effects of tamoxifen in relation to breast cancer.
Authors: V C Jordan
Journal: BMJ (1977)

It has been suggested that tamoxifen possesses estrogenic properties which may induce regression of mammary tumors in humans. However, it has been shown that tamoxifen inhibits the estradiol-stimulated changes in immature, ovariectomized, and mature rats. Whereas estradiol stimulates cell division, tamoxifen produces endometrial hypertrophy, even though it has been shown to bind to cytoplasmic estrogen receptors. In vitro experiments with human breast cancer cells have shown that tamoxifen has effects other than that of a simple estrogen antagonist. It is concluded that in addition to its antiestrogneic properties, it may act as a partial or a typical estrogen agonist, which may account for its antitumor activity in postmenopausal patients with breast cancer.
Repetitive Transcranial Magnetic Stimulation Versus Electroconvulsive Therapy: Efficacy of Treatment in Nonpsychotic Patients With Depression
Authors: PHILIP G. JANICAK, SHEILA DOWD, JEFFREY RADO, MARY JANE WELCH, LOUIS FOGG, JOHNNY O’REARDON, DAVID AVERY, C. EDWARD COFFEY, SHIRLENE SAMPSON, NASH BOUTROS
Journal: American Journal of Psychiatry (2007)
Non-invasive ventilation for ALS with respiratory failure in home care settings
Authors: Vasiliy Shtabnitskiy, Lev Brylev
Journal: European Respiratory Journal (2013)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease which ultimately leads to death. Non-invasive ventilation (NIV) can alleviate dyspnea, improve sleep, quality of life, and prognosis. Currently home care NIV and IV (invasive ventilation) is preferred way to provide respiratory support for ALS. We present one of the first experiences of ALS home care in Russia.  Aims and objective: To demonstrate first experience of ALS home care in Russia.  Methods: 54 patients with ALS were included. Functional state (ALSFRS scale), disease stage (Jose C. Rosche et al. classification), spirometry, respiratory muscle strength, sleep pulseoxymetry were assessed. NIV and IV were initiated according to current guidelines.  Results: Of 54 patients, 54% were IVB stage, III - 22%, IIB -15%, IIA - 9%. 26% were bulbar onset patients.  Mean VC on admission was 42.9±19.0, MIP (maximal inspiratory pressure) 14.5 (11-26), MEP (maximal expiratory pressure) 19.0 (14-25), dessaturation index 8 (5.6-15.1), mean saturation and minimal saturation were 92.1(90.1-95.0) and 81(74.5-87). ALSFRS negatively correlated with disease duration, VC% correlated with MIP and MEP. Mean saturation during sleep study related to age of the patient.35 patient were given respiratory support, with 28 ventilated non-invasively, and 7 with tracheotomy. Currently 11 patients died. Older age, low index of minimal saturation, and low MIP were related to risk of death. ALSFRS, VC, MEP and dessaturation index were not related to risk of death.  Conclusion: NIV can be provided in home care settings, VC, MIP, MEP, night pulseoxymetry can be effectively used to monitor disease progression in ALS home care.
Effect of air pollution on prevalence of chronic bronchitis symptoms-a cross-sectional analysis of 5 cohort studies
Authors: Yutong Cai, Tamara Schikowski, Andrea Vierkötter, Anne-Elie Carsin, Margaux Sanchez, Martin Adam, Alessandro Marcon, Raphaelle Varraso, Francine Kauffmann, Benedicte Jacquemin, Nicole Probst-Hensch, Ursula Krämer, Christian Schindler, Jordi Sunyer, Dirk Keidel, Nino Künzli, Anna L. Hansell
Journal: European Respiratory Journal (2013)

Background : Chronic bronchitis symptoms are associated with COPD and overall mortality. This study aims to assess effects of outdoor air pollution on prevalence of chronic bronchitis in five cohort studies (E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project.   Methods:  Annual average concentrations of particulate matter (PM) and NO 2 /NO x  and road traffic measures 2008-11, were assigned to home address at follow-up 2000-2011. Chronic bronchitis symptoms (³3 months for 2 or more years) were assessed as chronic cough and phlegm, chronic cough and chronic phlegm respectively. Cross-sectional multivariable logistic regression analyses were conducted at each cohort, adjusting for a confounder set common to all studies (age, sex, smoking, interview season, education) followed by random-effect meta-analysis.   Results:  13,758 and 8784 participants respectively were included in NO 2  and PM analyses.No consistent associations were observed between any exposure and prevalence of chronic bronchitis.Combined effect estimates for chronic cough and phlegm were (shown as OR (95%CI) per10ug/m 3 ): NO 2  0.96 (0.89-1.04) and PM 10  0.85 (0.53-1.39).Corresponding results for never smokers were: NO 2  0.99 (0.84-1.18) and PM 10  1.34 (0.93-1.93).Similar null associations were seen for chronic cough alone or chronic phlegm.   Conclusions:  In contrast to some previously published European studies, this study did not find consistent effects of current air pollution exposures level on chronic bronchitis symptoms. Further investigations including use of back-extrapolated air pollution values to actual year of questionnaire are needed.
Differential Colchicine Effects on the Transport of Membrane and Secretory Proteins in Rat Hepatocytes In Vivo : Bipolar Secretion of Albumin
Authors: Lucian Saucan, George E. Palade
Journal: Hepatology (1992)

We carried out a comparative investigation on the effects of colchicine (25 mumoles/100 gm body wt) on the intracellular transport, processing and discharge by secretion or proteolytic processing of a membrane protein (i.e., the polymeric IgA receptor) and a secretory protein (i.e., albumin) in rat hepatocytes. The results obtained indicated the following: (a) the transport and processing of polymeric IgA receptor is strongly inhibited and delayed, but the appearance of secretory component in the bile is not arrested; (b) polymeric IgA receptor reaches the sinusoidal plasmalemma in colchicine-treated specimens, as it does in controls; (c) albumin discharge into the plasma is strongly inhibited and markedly delayed in colchicine-treated as compared with control animals; (d) the reverse applies for albumin secretion in the bile, which is increased by a large factor; (e) newly synthesized albumin secreted directly from hepatocytes in control and in colchicine-treated animals is the major source of bile albumin; and (f) colchicine affects in different ways the polymeric IgA receptor and albumin arrival at the sinusoidal front and especially at the biliary front of the hepatocyte.
Complement Activation Regulates the Capacity of Proximal Tubular Epithelial Cell to Stimulate Alloreactive T Cell Response
Authors: Ke Li, Hetal Patel, Conrad A. Farrar, Roseanna E.G. Hargreaves, Steven H. Sacks, Wuding Zhou
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Tissue expression of C3 is an unexpected regulator of the alloimmune response in mouse kidney transplantation. It is unclear, however, whether a direct or an indirect action of complement on the host immune response is involved. Also unknown is which of the complement effector products, cleaved C3, cleaved C5, or C5b-9, is responsible. Proximal tubular epithelial cells (PTEC) not only constitute a major target of the alloimmune response but also produce substantial amounts of C3. This study investigated the property of mouse PTEC to stimulate alloreactive T cells in a complement-dependent manner. The proliferative and cytokine responses of primed alloreactive T cells were measured after exposure to donor-specific PTEC that had been pretreated with normal mouse serum, heat-inactivated mouse serum, or complement- deficient (C3, C5, or C6) mouse sera to differentially deposit complement components. PTEC were able to stimulate alloreactive T cells in an antigen-specific manner. Complement activation leading to the deposition of cleaved C3 on PTEC enhanced the alloreactive T cell response. This complement-mediated stimulation of the T cell response was dependent on C3 but not on C5 or C6. The primary influence of tissue-bound complement was on CD4+ T cells. Moreover, the effect of complement on alloreactive T cells was B7 dependent, shown by inhibition studies with CTLA4-Ig. These results suggest that donor epithelium-bound C3 can upregulate the alloimmune response. It is postulated that surface-bound C3 interacts with complement receptors on alloreactive T cells or on antigen presenting cells to increase allo-immune stimulation.
Fidaxomicin versus Vancomycin for<i>Clostridium difficile</i>Infection
Authors: Thomas J. Louie, Mark A. Miller, Kathleen M. Mullane, Karl Weiss, Arnold Lentnek, Yoav Golan, Sherwood Gorbach, Pamela Sears, Youe-Kong Shue
Journal: New England Journal of Medicine (2011)

Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Patients generally have a response to oral vancomycin or metronidazole; however, the rate of recurrence is high. This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection.Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry. We randomly assigned patients to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The primary end point was clinical cure (resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy). The secondary end points were recurrence of C. difficile infection (diarrhea and a positive result on a stool toxin test within 4 weeks after treatment) and global cure (i.e., cure with no recurrence).A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies.The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin. Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non–North American Pulsed Field type 1 strains. (Funded by Optimer Pharmaceuticals; ClinicalTrials.gov number, NCT00314951.)
Two Ly-2 T helper cell subsets distinguished by Qa-1 phenotype. The priming environment determines whether one or both subsets will be generated.
Authors: J S McDougal, F W Shen, S P Cort, J Bard
Journal: The Journal of Experimental Medicine (1982)

The Qa-1 cell surface phenotype reportedly distinguishes two Ly-1 T cell subsets conjointly required for T helper effector activity. Ly-1 cells, obtained from several different priming regimens, were negatively selected with anti-Qa-1 plus complement and compared with unselected Ly-1 cells for helper cell activity. Priming isolated T cells on antigen-pulsed macrophages in the absence of B cells favors the generation of the Ly-1:Qa1- subset, which is capable of efficient helper activity in the absence of the Ly-1:Qa-1+ subset. Priming T cells in an environment containing B cells generates both Ly-1:Qa-1- helper effector cells and Ly-1:Qa-1+ cells which contribute to the helper effect. Whether Ly-1:Qa-1+ cells are capable of independent helper activity cannot be determined, and, as such, Ly-1:Qa-1+ cells are more appropriately termed "help associated" rather than "helper effector." Our results assign a membrane phenotype, Qa-1, which distinguishes an Ly-1 help-associated B cell requiring subset in our system and may prove to be a general marker in a number of systems of Ly-1 inducer cell subsets which functionally require or recognize B cells or their products.
Press Releases by Academic Medical Centers: Not So Academic?
Authors: Steven Woloshin, Lisa M. Schwartz, Samuel L. Casella, Abigail T. Kennedy, Robin J. Larson
Journal: Annals of Internal Medicine (2009)

Background: The news media are often criticized for exaggerated coverage of weak science. Press releases, a source of information for many journalists, might be a source of those exaggerations. Objective: To characterize research press releases from academic medical centers. Design: Content analysis. Setting: Press releases from 10 medical centers at each extreme of U.S. News & World Report's rankings for medical research. Measurements: Press release quality. Results: Academic medical centers issued a mean of 49 press releases annually. Among 200 randomly selected releases analyzed in detail, 87 (44%) promoted animal or laboratory research, of which 64 (74%) explicitly claimed relevance to human health. Among 95 releases about primary human research, 22 (23%) omitted study size and 32 (34%) failed to quantify results. Among all 113 releases about human research, few (17%) promoted studies with the strongest designs (randomized trials or meta-analyses). Forty percent reported on the most limited human studies—those with uncontrolled interventions, small samples (<30 participants), surrogate primary outcomes, or unpublished data—yet 58% lacked the relevant cautions. Limitation: The effects of press release quality on media coverage were not directly assessed. Conclusion: Press releases from academic medical centers often promote research that has uncertain relevance to human health and do not provide key facts or acknowledge important limitations. Primary Funding Source: National Cancer Institute.
AB0959 Radiological and clinical profil of osteoarthritic patients undergoing total joint replacement
Authors: A. Neuprez, G. François, O. Bruyère, V. Kovats, W. Kurth, J.-P. Huskin, P. Gillet, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis is a major burden worldwide. <h3>Objectives</h3> Arthritic conditions are extremely painful for the patient and are associated with a significant reduction in health related quality of life (HRQOL), mainly in term of physical and functional impairment. Therefore, the demand for total joint replacement (TJR) is increasing. The objective of the present study was to access the radiological and clinical profil of osteoarthritic patients undergoing of total joint replacement. <h3>Methods</h3> We analyzed the preoperative radiologic and clinical status of 185 consecutive patients undergoing total joint replacement for symptomatic osteoarthritis of the lower limb. Specific HRQOL was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the pain with the EQ-VAS. These questionnaires were administered preoperatively. <h3>Results</h3> Our cohort included 75 men and 110 women aged from 33 to 86 years (mean 65.2±10.5). 102 of them received a total hip prosthesis and 83 of them a total knee prosthesis. The mean duration of OA was 3097.2±3281.5 (SD) days or 8,5±9 years They were all diagnosed with primary OA following the ACR criteria. 172 pre-operative X-ray assessments were available and analyzed. Out of the 172, 2,9% (n=5) were presenting with a KL-score of 1; 39,5% (n=68) were presenting with a KL-score of 2; 39,5% (n=68) with a KL-score of 3 and 18% (n=31) with a KL-score of 4. The mean value EQ-VAS pain was 62.4 (mean) ±17.2 (SD). The mean WOMAC score values were 10.8±3.8 for pain, 4.6±1.8 for stiffness, 36.1±13 for physical function. The total WOMAC score was 51.4±17.2 (0-96). <h3>Conclusions</h3> We concluded that patients undergoing total joint replacement in university setting, in Belgium, do present with a moderate to severe OA. <h3>Disclosure of Interest</h3> None Declared