tbuckley/cabot-search huggingface dataset:
Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats.
Authors: D J Sheridan, P A Penkoske, B E Sobel, P B Corr
Journal: Journal of Clinical Investigation (1980)

Alpha compared to beta adrenergic contributions to dysrhythmias induced by left anterior descending coronary occlusion and by reperfusion were assessed in chloralose-anesthetized cats (n = 96). Alpha receptor blockade with either phentolamine or prazosin significantly reduced the number of premature ventricular complexes during coronary reperfusion (321 +/- 62-14 +/- 10 premature ventricular complexes, P less than 0.001), abolished early ventricular fibrillation (from 25% in controls to 0%), and prevented the increase in idioventricular rate seen with coronary reperfusion. However, beta-receptor blockade was without effect. Ventricular dysrhythmias induced by coronary occlusion alone (without reperfusion) were attenuated markedly by alpha-receptor blockade under conditions in which perfusion (measured with radiolabeled microspheres) within ischemic zones was not affected. Alternative sympatholytic interventions including pretreatment with 6-hydroxydopamine to deplete myocardial norepinephrine from 8.8 +/- 1.4 to 0.83 +/- 0.2 ng/mg protein and render the heart unresponsive to tyramine (120 microgram/kg) attenuated dysrhythmias induced by both coronary occlusion and reperfusion in a fashion identical to that seen with alpha-receptor blockade. Although efferent sympathetic activation induced by left stellate nerve stimulation increased idioventricular rate from 66 +/- 6 to 144+/- 7 beats/min (P less than 0.01) before coronary occlusion, this response was blocked by propranolol but not by phentolamine. In contrast, during reperfusion the increase in idioventricular rate induced by left stellate nerve stimulation (to 203 +/- 14) was not inhibited by propranolol but was abolished by phentolamine (79 +/- 10). Intracoronary methoxamine (0.1 microM) in animals depleted of myocardial catecholamines by 6-hydroxydopamine pretreatment did not affect idioventricular rate before coronary occlusion. However, early after coronary reperfusion, methoxamine increased idioventricular rate from 33 +/- 7 to 123 +/- 21 beats/min (P less than 0.01). Thus, enhanced alpha-adrenergic responsiveness occurs during myocardial ischemia and appears to be primary mediator of the electrophysiological derangements and resulting malignant dysrhythmias induced by catecholamines during myocardial ischemia and reperfusion.
Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis
Authors: Christoph Stettler, Simon Wandel, Sabin Allemann, Adnan Kastrati, Marie Claude Morice, Albert Schömig, Matthias E Pfisterer, Gregg W Stone, Martin B Leon, José Suarez de Lezo, Jean-Jacques Goy, Seung-Jung Park, Manel Sabaté, Maarten J Suttorp, Henning Kelbaek, Christian Spaulding, Maurizio Menichelli, Paul Vermeersch, Maurits T Dirksen, Pavel Cervinka, Anna Sonia Petronio, Alain J Nordmann, Peter Diem, Bernhard Meier, Marcel Zwahlen, Stephan Reichenbach, Sven Trelle, Stephan Windecker, Peter Jüni
Journal: The Lancet (2007)
Alteration of Skin in Gross Leukemia. IV. Test of Allograft Hypothesis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: T. Mariani, Y. Maruyama, R. A. Good
Journal: JNCI Journal of the National Cancer Institute (1972)

To test the hypothesis that an immunologic response underlies the rejection of skin from syngeneic tumor-bearing animals, (C3H/Bi × DBA/2)F1 recipients were given 400 R total-body X irradiation, neonatally thymectomized, or both irradiated and thymectomized. These animals were grafted with syngeneic skin from mice bearing Gross passage A tumors for 4, 7, or 11 days. The rates of graft rejection, tumor development at the graft site, and survival time for these immunosuppressed animals did not differ from those of immunologically intact recipients. By contrast, allogeneic skin was not rejected by animals treated with the same immunosuppressive manipulations. These experiments indicate that syngeneic skin-graft rejection, the “heterogenization phenomenon,” is not of immunologic origin.
An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor
Authors: Pilar Delgado, Balbino Alarcón
Journal: The Journal of Experimental Medicine (2005)

Exit from the endoplasmic reticulum (ER) is an important checkpoint for proper assembly of multimeric plasma membrane receptors. The six subunits of the T cell receptor (TCR; TCRα, TCRβ, CD3γ, CD3δ, CD3ε, and CD3ζ) are each endowed with ER retention/retrieval signals, and regulation of its targeting to the plasma membrane is therefore especially intriguing. We have studied the importance of the distinct ER retention signals at different stages of TCR intracellular assembly. To this end, we have characterized first the presence of ER retention signals in CD3γ. Despite the presence of multiple ER retention signals in CD3γ, εγ dimers reach the cell surface when the single CD3ε ER retention signal is deleted. Furthermore, inclusion of this CD3ε mutant promoted plasma membrane expression of incomplete αβγε and αβδε complexes without CD3ζ. It therefore appears that the CD3ε ER retention signal is dominant and that it is only overridden upon the incorporation of CD3ζ. We propose that the stepwise assembly of the TCR complex guarantees that all assembly intermediates have at least one functional ER retention signal and that only a full signaling-competent TCR complex is expressed on the cell surface.
Tumor Galectin-1 Mediates Tumor Growth and Metastasis through Regulation of T-Cell Apoptosis
Authors: Alice Banh, Jing Zhang, Hongbin Cao, Donna M. Bouley, Shirley Kwok, Christina Kong, Amato J. Giaccia, Albert C. Koong, Quynh-Thu Le
Journal: Cancer Research (2011)

Galectin-1 (Gal-1), a carbohydrate-binding protein whose secretion is enhanced by hypoxia, promotes tumor aggressiveness by promoting angiogenesis and T-cell apoptosis. However, the importance of tumor versus host Gal-1 in tumor progression is undefined. Here we offer evidence that implicates tumor Gal-1 and its modulation of T-cell immunity in progression. Comparing Gal-1-deficient mice as hosts for Lewis lung carcinoma cells where Gal-1 levels were preserved or knocked down, we found that tumor Gal-1 was more critical than host Gal-1 in promoting tumor growth and spontaneous metastasis. Enhanced growth and metastasis associated with Gal-1 related to its immunomodulatory function, insofar as the benefits of Gal-1 expression to Lewis lung carcinoma growth were abolished in immunodeficient mice. In contrast, angiogenesis, as assessed by microvessel density count, was similar between tumors with divergent Gal-1 levels when examined at a comparable size. Our findings establish that tumor rather than host Gal-1 is responsible for mediating tumor progression through intratumoral immunomodulation, with broad implications in developing novel targeting strategies for Gal-1 in cancer.
Part 9: Post–Cardiac Arrest Care
Authors: Mary Ann Peberdy, Clifton W. Callaway, Robert W. Neumar, Romergryko G. Geocadin, Janice L. Zimmerman, Michael Donnino, Andrea Gabrielli, Scott M. Silvers, Arno L. Zaritsky, Raina Merchant, Terry L. Vanden Hoek, Steven L. Kronick
Journal: Circulation (2010)

The goal of immediate post-cardiac arrest care is to optimize systemic perfusion, restore metabolic homeostasis, and support organ system function to increase the likelihood of intact neurological survival. The post-cardiac arrest period is often marked by hemodynamic instability as well as metabolic abnormalities. Support and treatment of acute myocardial dysfunction and acute myocardial ischemia can increase the probability of survival. Interventions to reduce secondary brain injury, such as therapeutic hypothermia, can improve survival and neurological recovery. Every organ system is at risk during this period, and patients are at risk of developing multiorgan dysfunction. The comprehensive treatment of diverse problems after cardiac arrest involves multidisciplinary aspects of critical care, cardiology, and neurology. For this reason, it is important to admit patients to appropriate critical-care units with a prospective plan of care to anticipate, monitor, and treat each of these diverse problems. It is also important to appreciate the relative strengths and weaknesses of different tools for estimating the prognosis of patients after cardiac arrest.
Structure and Function of Human and Murine Receptors for IgG
Authors: J C Unkeless, E Scigliano, V H Freedman
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Manganese superoxide dismutase is increased in the airways of smokers' lungs
Authors: T. Harju, R. Kaarteenaho-Wiik, R. Sirviö, P. Pääkkö, J.D. Crapo, T.D. Oury, Y. Soini, V.L. Kinnula
Journal: European Respiratory Journal (2004)

Oxidant stress is a key mechanism for smoking-induced chronic obstructive pulmonary disease (COPD). Smoking has been shown to upregulate several antioxidant enzymes, with potential effects on the prevention of the disease and/or its progression. Superoxide dismutases (SOD)s are the only enzymes capable of consuming superoxide radicals. The purpose of the present study was to investigate SODs in the lungs of nonsmokers, smokers and COPD patients. Manganese superoxide dismutase (MnSOD), copper zinc SOD (CuZnSOD), and extracellular SOD (ECSOD), were investigated by immunohistochemistry in the airways of 13 nonsmokers, 20 smokers and 22 COPD patients with mild-to-moderate disease. Lung tissue homogenates of three nonsmokers and four smokers were used for Western blot and enzyme activity analysis. The expression of MnSOD was higher in the central bronchial epithelium of smokers with COPD and in the alveolar epithelium of smokers without or with COPD than innonsmokers. Lung MnSOD immunoreactivity, evaluated by Western blotting and specific activity, were 33% and 51% higher, respectively, in smokers than in nonsmokers. No major changes could be observed in lung CuZnSOD or ECSOD immunoreactivities. Manganese superoxide dismutase is elevated in the alveolar epithelium of cigarette smokers, probably due to the increased oxidant burden in smokers' lungs.
Radiologic Features of Diagnostic Importance
Authors: Richard H. Marshak
Journal: JAMA (1974)

ADENOCARCINOMA of the duodenum or small bowel is a rare lesion. Peripapillary carcinomas are usually polypoid, ulcerated, nonobstructive, and immediately adjacent to the papilla of Vater. In the remainder of the duodenum, primary carcinoma is difficult to distinguish from metastatic disease or extension of tumor from the pancreas. In the mesenteric small bowel, primary carcinoma occurs more frequently in the jejunum than in the ileum. The roentgenographic findings are usually a short, fairly sharply demarcated filling defect associated with an eccentric and irregular channel and with overhanging edges. The mucosa is ulcerated and partial obstruction is common.<sup>1</sup> In recent years, a number of cases of adenocarcinoma of the small bowel have been reported in association with long-standing regional enteritis or in surgically excluded loops.<sup>2</sup>The diagnosis is very difficult to establish preoperatively because the presence of multiple strictures with intervening segments of dilated bowel obscures the associated malignant
Respiratory health of California rice farmers.
Authors: S A McCurdy, T J Ferguson, D F Goldsmith, J E Parker, M B Schenker
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Rice farmers are occupationally exposed to agents that may affect respiratory health, including inorganic dusts and smoke from burning of agricultural waste. To assess respiratory health of this occupational group, we conducted a cross-sectional study, including a self-administered health and work questionnaire, spirometry, and chest radiography among 464 male California rice farmers. Mean age +/- SD was 48.3 +/- 15.2 yr; mean duration of rice farming was 25.7 +/- 14.3 yr. Prevalences for respiratory symptoms were: chronic bronchitis (6.3%), physician-diagnosed asthma (7.1%), and persistent wheeze (8.8%). Chronic cough was reported by 7.1% of respondents and was associated with reported hours per year burning rice stubble. Mean FEV1 and FVC were at expected values. FEV1 was inversely associated with years working in rice storage and use of heated rice dryers. Mean FEF25-75 was 93% of expected and was inversely associated with rice storage activities involving unheated rice driers. ILO profusion scores > or = 1/0 for small irregular opacities were seen in 18 (10.1%) of 178 chest radiographs. Study findings suggest increased asthma prevalence among California rice farmers. Radiologic findings consistent with dust or fiber exposure were increased compared with those of the general population, although no associations with specific farming activities were identified.
The Orphan Nuclear Receptor Nur77 Suppresses Endothelial Cell Activation Through Induction of IκBα Expression
Authors: Bei You, Yuan-Ying Jiang, Shaoping Chen, Guijun Yan, Jianxin Sun
Journal: Circulation Research (2009)

Endothelial inflammation plays a critical role in the development and progression of cardiovascular disease, albeit the mechanisms need to be fully elucidated. Nur77 is highly expressed in vascular endothelial cells (ECs) and plays a role in the regulation of cell proliferation and angiogenesis; its role in vascular inflammation, however, remains unknown. Treatment of human umbilical vein ECs (HUVECs) with tumor necrosis factor (TNF)-alpha substantially increased the transcription and protein expression of Nur77 in a dose and time-dependent manner, as determined by Northern blot and Western blot analysis. Adenovirus mediated overexpression of Nur77 markedly increased the intracellular levels of IkappaBalpha by approximately 4-fold, whereas overexpression of dominant negative Nur77 (DN-Nur77), which lacks its transactivation domain, had no effect on IkappaBalpha expression, suggesting that Nur77 is an important transcriptional factor in controlling IkappaBalpha expression in ECs. Furthermore, overexpression of Nur77 significantly increased IkappaBalpha promoter activity via directly binding to a Nur77 response element in the IkappaBalpha promoter. Importantly, overexpression of Nur77, but not DN-Nur77, protected ECs against the TNF-alpha- and interleukin-1beta-induced endothelial activation, as characterized by attenuation in the nuclear factor kappaB activation, expression of adhesion molecules ICAM-1 and VCAM-1, and monocytic adherence to ECs. These results indicate that Nur77 negatively regulates the TNF-alpha- and interleukin-1beta-induced vascular EC activation by transcriptionally upregulation of IkappaBalpha expression.
Low-Dose Paclitaxel Prior to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth
Authors: Hua Zhong, Baohui Han, Irina L. Tourkova, Anna Lokshin, Alan Rosenbloom, Michael R. Shurin, Galina V. Shurin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The main goal of this study was to provide the “proof-of-principle” that low-dose paclitaxel is able to change the tumor microenvironment and improve the outcome of intratumoral dendritic cell vaccine in a murine lung cancer model. Experimental Design: We evaluated the antitumor potential and changes in the intratumoral milieu of a combination of low-dose chemotherapy and dendritic cell vaccine in the Lewis lung carcinoma model in vivo. Results: The low-dose paclitaxel, which induced apoptosis in ∼10% of tumor cells, was not toxic to bone marrow cells and dendritic cells and stimulated dendritic cell maturation and function in vitro. Although tumor cells inhibited dendritic cell differentiation in vitro, this immunosuppressive effect was abrogated by the pretreatment of tumor cells with low-dose paclitaxel. Based on these data, we next tested whether pretreatment of tumor-bearing mice with low-dose paclitaxel in vivo would improve the antitumor potential of dendritic cell vaccine administered intratumorally. Significant inhibition of tumor growth in mice treated with low-dose paclitaxel plus intratumoral dendritic cell vaccine, associated with increased tumor infiltration by CD4+ and CD8+ T cells and elevated tumor-specific IFN-γ production by draining lymph node cells, was revealed. Using a novel intratumoral microdialysis technique and Luminex technology for collecting and characterizing soluble factors released within the tumor bed for several days in live freely moving animals, we showed that low-dose paclitaxel altered the cytokine network at the tumor site. Conclusions: Our data indicate that low-dose chemotherapy before intratumoral delivery of dendritic cells might be associated with beneficial alterations of the intratumoral microenvironment and thus support antitumor immunity.
Assessment of hepatic iron overload in thalassemic patients by magnetic resonance spectroscopy
Authors: Ruth M. Dixon, Peter Styles, Faris N. Al-Refaie, Graham J. Kemp, Sarah M. Donohue, Beatrix Wonke, Victor A. Hoffbrand, George K. Radda, Bheeshma Rajagopalan
Journal: Hepatology (1994)

The transverse relaxation time of water protons is shortened by the presence of iron. This shortening depends on the amount and the environment of iron in the sample. We have developed a method for measuring short transverse relaxation time noninvasively by magnetic resonance spectroscopy. To evaluate magnetic resonance spectroscopy as a means of assessing hepatic iron content in patients with transfusional iron overload, we compared the results obtained with this method with those obtained by other means of assessing total body iron content. The correlation between the liver biopsy iron concentration and 1/transverse relaxation time was highly significant (r = 0.95, p < 0.004, n = 6) for iron loads up to 3% dry weight. The correlation between serum ferritin and 1/transverse relaxation time was also significant, but the correlation coefficient was much lower (r = 0.67, p < 0.002, n = 20). The correlation between 24-hr urinary iron excretion and 1/transverse relaxation time was not significant, nor was that between AST and 1/transverse relaxation time. We conclude that magnetic resonance spectroscopic determination of the transverse relaxation time of hepatic water is an accurate method of measuring liver iron content, especially when the iron content is below 3%. Because it is a noninvasive method that is associated with negligible side effects, it could provide clinicians with an excellent means of assessing the effectiveness of the various therapeutic strategies used in the management of patients with iron overload.
Hepatitis B vaccination in children with juvenile idiopathic arthritis
Authors: O Kasapçopur, F Cullu, A Kamburoğlu-Goksel, H Cam, E Akdenizli, S Calýkan, L Sever, N Arýsoy
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To evaluate the responsiveness of children with juvenile idiopathic arthritis (JIA) to hepatitis B vaccination and to determine the most useful vaccination schedule. <b>Methods:</b> 39 children with JIA were enrolled in the study; all were in remission and negative to serological testing for hepatitis B surface antigen (HbsAg). The control group consisted of 41 healthy children. There were two different vaccination schedules: <i>group I</i> was vaccinated at 0, 1, and 3 months; <i>group II</i> was vaccinated at 0, 1, and 6 months. Positive responsiveness to the vaccine was defined as an anti-hepatitis B antibody titre above 10 mIU/ml. <b>Results:</b> All the children except one with systemic JIA developed an antibody response. None of the JIA patients experienced a flare up or clinical deterioration related to the vaccination. The antibody levels in children with JIA were significantly lower than in the healthy controls. Comparison of the antibody levels between the two vaccination schedules showed no statistical difference in the controls; in the JIA subjects the group II schedule resulted in a trend to a greater response than the group I schedule (p&lt;0.07). Vaccine responsiveness was not influenced by either methotrexate or prednisolone treatment. <b>Conclusions:</b> Children with JIA had an adequate response to hepatitis B vaccination and the response was not affected by immunosuppressive treatment. A vaccination schedule at 0, 1, and 6 months seems to be preferable to 0, 1, and 3 months.
Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy
Authors: K Pavelka, K Jarosova, D Suchy, L Senolt, K Chroust, L Dusek, J Vencovsky
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective:</h3> To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. <h3>Methods:</h3> 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease &gt;1.2) but who were not in remission (DAS28 &gt;2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). <h3>Results:</h3> There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). <h3>Conclusions:</h3> In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.
Plasma Lipoprotein Subpopulation Distribution in Caucasian and African-American Women With Gestational Diabetes
Authors: Joseph F. Bower, Hamid Hadi, Hisham A. Barakat
Journal: Diabetes Care (2001)

Lettersnondiabetic siblings of type 1 diabetic patients and therefore correlated with plasma concentrations of Lp(a) and fibrinogen.Cases of hyponatremia have been correlated with inflammation ( 14) and increased plasma interleukin Ϫ6 concentration (15).These findings are consistent with our hypothesis of an association among inflammatory markers, oxidative stress, and susceptibility to type 1 diabetes.Moreover, the familiarly overactive NHE could be viewed independently as further evidence for the presence in these families of a redox disequilibrium in which oxidation seems to be dominant.
IKKβ/NF-κB and the miscreant macrophage
Authors: Anjuli M. Timmer, Victor Nizet
Journal: The Journal of Experimental Medicine (2008)

Macrophage activation relies on complex intracellular signaling processes that integrate the need for rapid inflammatory responses to pathogens with the need to resolve inflammation without permanent harm to normal tissues. Patterns of aberrant macrophage activation characterize and sustain disorders of chronic inflammation, infection, and cancer. New studies now show a role for the NF-κB activator IKKβ in promoting an alternative, immunosuppressive pattern of macrophage activation, which limits the cell's tumoricidal and bactericidal capacities. As cancers and pathogens may have evolved multiple mechanisms to manipulate macrophages for their own survival, is there anything we can do about it?