tbuckley/cabot-search huggingface dataset:
c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1.
Authors: V S Shapiro, M N Mollenauer, W C Greene, A Weiss
Journal: The Journal of Experimental Medicine (1996)

T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-kappa B family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation approximately 17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.
Chronicity of rheumatoid arthritis affects the responsiveness of physical function, but not of disease activity measures in rheumatoid arthritis clinical trials
Authors: Daniel Aletaha, Farideh Alasti, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In previous studies it has been indicated that functional measures are less responsive in patients with established or late rheumatoid arthritis (RA) as compared with early RA, potentially because chronic irreversible functional damage is present. Therefore, they may not be useful as disease activity measures. We aimed to investigate whether this is specific to functional measures, or if it similarly also relates to other typical RA disease activity measures. <h3>Methods</h3> We performed a pooled analysis of patient level clinical trial data of patients with RA. We investigated the effects of duration of RA on the responsiveness of all RA core set measures by using logistic regression analysis. We performed a number of sensitivity analyses to support our findings. <h3>Results</h3> The probability of response in functional scores decreased from ∼60% in early disease to ∼30% in established/late disease (p=0.0023). No other core set variable or composite index behaved in this way. The effect of chronicity solely on functional responses was confirmed in all sensitivity analyses, particularly also when joint damage was used as a surrogate of chronicity, responsiveness decreased from &gt;60% in patients with little structural damage to &lt;20% in patients with severe joint damage (p&lt;0.001). <h3>Conclusions</h3> Physical function is among the most important outcomes of RA, but in contrast with other core set measures it is not a reliable measure for disease activity.
Differential Brain Metabolic Predictors of Response to Paroxetine in Obsessive-Compulsive Disorder Versus Major Depression
Authors: Sanjaya Saxena, Arthur L. Brody, Matthew L. Ho, Narineh Zohrabi, Karron M. Maidment, Lewis R. Baxter
Journal: American Journal of Psychiatry (2003)

Serotonin reuptake inhibitor (SRI) medications are effective in the treatment of both major depressive disorder and obsessive-compulsive disorder (OCD), but it is unknown whether the neural substrates of treatment response for the two disorders are the same or different. The authors sought to identify pretreatment cerebral glucose metabolic markers of responsiveness to SRI treatment in patients with OCD versus major depressive disorder and to determine whether the pretreatment patterns associated with improvement of OCD symptoms were the same as or different from those associated with improvement of major depressive disorder symptoms.[(18)F]Fluorodeoxyglucose positron emission tomography was used to measure cerebral glucose metabolism in 27 patients with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent OCD and major depressive disorder, who were all then treated with 30-60 mg/day of paroxetine for 8-12 weeks. Correlations were calculated between pretreatment regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms, depressive symptoms, and overall functioning.While improvement of OCD symptoms was significantly correlated with higher pretreatment glucose metabolism in the right caudate nucleus (partial r=-0.53), improvement of major depressive disorder symptoms was significantly correlated with lower pretreatment metabolism in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91).These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment.
Increasing Minority Participation in Cancer Clinical Trials: The Minority-Based Community Clinical Oncology Program Experience
Authors: Worta McCaskill-Stevens, Martha M. McKinney, Cynthia G. Whitman, Lori M. Minasian
Journal: Journal of Clinical Oncology (2005)

The National Cancer Institute's (NCI) Minority-Based Community Clinical Oncology Program (MBCCOP) seeks to enhance minority participation in cancer clinical trials by building clinical trials outreach and management capacity in healthcare institutions serving large numbers of minority cancer patients. This article examines temporal trends in MBCCOP accruals to cancer prevention and control (CP/C) and cancer treatment trials and the racial distribution of study participants, along with the major factors affecting minority enrollment.We used NCI databases to analyze temporal trends in overall accruals and accruals by race. We analyzed transcripts from an NCI-sponsored meeting with MBCCOP principal investigators and data from a follow-up survey to identify factors affecting minority enrollment.Between 1992 and 2003, annual patient accruals to treatment trials increased 39% despite little change in the number of MBCCOP grantees. During this same period, annual participant accruals to CP/C trials more than doubled. Between 1995 and 2003, minorities comprised 51% to 67% of the MBCCOP patients accrued to cooperative group treatment trials compared with < or = 23% of the patients accrued by other cooperative group members and affiliates. Major factors affecting minority enrollment include the availability of "clinically relevant" protocols, regulatory requirements, characteristics of the patient population, and the level of support from sponsoring institutions and community physicians.MBCCOPs have demonstrated their ability to facilitate the participation of racial/ethnic minorities in clinical trials. However, the contributions that they could make to the design and conduct of minority-focused research studies merit further exploration.
Executive Functioning, Treatment Adherence, and Glycemic Control in Children With Type 1 Diabetes
Authors: Kelly McNally, Jennifer Rohan, Jennifer Shroff Pendley, Alan Delamater, Dennis Drotar
Journal: Diabetes Care (2010)

OBJECTIVE The primary aim of the study was to investigate the relationship among executive functioning, diabetes treatment adherence, and glycemic control. RESEARCH DESIGN AND METHODS Two hundred and thirty-five children with type 1 diabetes and their primary caregivers were administered the Diabetes Self-Management Profile to assess treatment adherence. Executive functioning was measured using the Behavior Rating Inventory of Executive Functioning and glycemic control was based on A1C. RESULTS Structural equation modeling indicated that a model in which treatment adherence mediated the relationship between executive functioning and glycemic control best fit the data. All paths were significant at P &amp;lt; 0.01. CONCLUSIONS These results indicate that executive functioning skills (e.g., planning, problem-solving, organization, and working memory) were related to adherence, which was related to diabetes control. Executive functioning may be helpful to assess in ongoing clinical management of type 1 diabetes.
Results and Long-Term Predictors of Adverse Clinical Events After Elective Percutaneous Interventions on Unprotected Left Main Coronary Artery
Authors: Takuro Takagi, Goran Stankovic, Leo Finci, Konstantinos Toutouzas, Alaide Chieffo, Vassilis Spanos, Francesco Liistro, Carlo Briguori, Nicola Corvaja, Remo Albero, Ginevra Sivieri, Rossella Paloschi, Carlo Di Mario, Antonio Colombo
Journal: Circulation (2002)

Background — The safety and efficacy of percutaneous coronary intervention of de novo lesions in unprotected left main coronary arteries remains an unresolved issue. Methods and Results — We analyzed 67 consecutive patients treated with the following devices: 39 with stents, 12 with rotational atherectomy plus stents, 13 with directional coronary atherectomy plus stents (a total of 64 patients were treated with stents), and 3 patients with directional coronary atherectomy only. The reference vessel size was 3.78±0.73 mm and lesion length was 6.6±3.0 mm. In-hospital complications were 2 coronary artery bypass grafts (CABGs) (3.0%), 2 Q-wave myocardial infarctions (MIs) (3.0%), and 3 non-Q-wave MIs (4.5%); there were no deaths. The estimated cardiac survival at 3 years was 91%. The cardiac mortality rate was higher in patients with Parsonnet score &gt;15 versus ≤15 (21.4% versus 4.2%, P =0.02) at 3 years. The independent covariate of cardiac death was preserved left ventricular ejection fraction; for combined cardiac events (cardiac death, MI, repeat revascularization) it was large reference vessel size. Follow-up angiography at 5±2 months in 85% of eligible patients revealed 31.4% restenosis. Extending the follow-up to 31±23 months (19 patients with follow-up beyond 3 years) the cumulative event rates were 11 deaths (16.4%), 8 of them cardiac (11.9%), 2 (3.0%) MI, and 16 (23.9%) repeat revascularizations (CABG in 5 patients). Conclusions — Elective percutaneous coronary intervention of de novo lesions in left main coronary arteries is feasible, with low procedural risk. The long-term follow-up revealed a high rate of angiographic restenosis and repeat revascularization, with a relatively high incidence of cardiac death. Reference vessel size and left ventricular function are the most important predictors of favorable follow-up.
Changing Trends of Inborn Errors in Reye's Syndrome: Rarity Is Relative
Authors: Edward Y. Hsia
Journal: Hepatology (1990)

Genetic disorders were identified infrequently among children presenting with Reye's syndrome in the past. During a two–year period, we evaluated four consecutive patients referred for intensive care of Reye's syndrome. A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase. None had experienced a previous episode of Reye's syndrome, and three of the four had been entirely healthy in the past. Our experience suggests that as the incidence of Reye's syndrome has decreased, patients with its clinical features are now more likely to have manageable inborn errors of metabolism (e. g. disorders of ureagenesis, ketogenesis, and branched–chain amino acids).
The Relationship Between Insulin Resistance and Incidence and Progression of Coronary Artery Calcification
Authors: Michael J. Blaha, Andrew P. DeFilippis, Juan J. Rivera, Matthew J. Budoff, Ron Blankstein, Arthur Agatston, Moyses Szklo, Susan G. Lakoski, Alain G. Bertoni, Richard A. Kronmal, Roger S. Blumenthal, Khurram Nasir
Journal: Diabetes Care (2011)

OBJECTIVE We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up. RESULTS Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components. CONCLUSIONS HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.
Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials
Authors: P. Meier, G. Knapp, U. Tamhane, S. Chaturvedi, H. S Gurm
Journal: BMJ (2010)

<b>Objective</b> To evaluate the relative short term safety and intermediate term efficacy of carotid endarterectomy versus carotid artery stenting. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> BIOSIS, Embase, Medline, the Cochrane central register of controlled trials, International Pharmaceutical Abstracts database, ISI Web of Science, and Google scholar and bibliographies, from 1 January 1990 to 25 July 2009. <b>Study selection</b> Randomised controlled trials comparing carotid endarterectomy with carotid artery stenting in patients with carotid artery stenosis with or without symptoms. <b>Data extraction</b> Primary end point was a composite of mortality or stroke. Secondary end points were death, stroke, myocardial infarction, or facial neuropathy (as individual end points), and mortality or disabling stroke (as a composite end point). <b>Data synthesis</b> 11 trials were included (4796 patients); 10 reported on short term outcomes (n=4709) and nine on intermediate term outcomes (1-4 years). The periprocedural risk of mortality or stroke was lower for carotid endarterectomy (odds ratio 0.67, 95% confidence interval 0.47 to 0.95; P=0.025) than for carotid stenting, mainly because of a decreased risk of stroke (0.65, 0.43 to 1.00; P=0.049), whereas the risk of death (1.14, 0.56 to 2.31; P=0.727) and the composite end point mortality or disabling stroke (0.74, 0.53 to 1.05; P=0.088) did not differ significantly. The odds of periprocedural myocardial infarction (2.69, 1.06 to 6.79; P=0.036) or cranial nerve injury (10.2, 4.0 to 26.1; P&lt;0.001) was higher in the carotid endarterectomy group than in the carotid stenting group. In the intermediate term, the two treatments did not differ significantly for stroke or death (hazard ratio 0.90, 95% confidence interval 0.74 to 1.1; P=0.314). <b>Conclusions</b> Carotid endarterectomy was found to be superior to carotid artery stenting for short term outcomes but the difference was not significant for intermediate term outcomes; this difference was mainly driven by non-disabling stroke. Significantly fewer cranial nerve injuries and myocardial infarctions occurred with carotid artery stenting.
Angiotensin II–Induced Leukocyte Adhesion on Human Coronary Endothelial Cells Is Mediated by E-Selectin
Authors: Michael Gräfe, Wolfgang Auch-Schwelk, Andreas Zakrzewicz, Vera Regitz-Zagrosek, Petra Bartsch, Kristof Graf, Matthias Loebe, Peter Gaehtgens, Eckart Fleck
Journal: Circulation Research (1997)

Clinical data suggest a link between the activation of the renin-angiotensin system and cardiovascular ischemic events. Leukocyte accumulation in the vessel wall is a hallmark of early atherosclerosis and plaque progression. E-Selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are adhesion molecules participating in mediating interactions between leukocytes and endothelial cells and have been found to be expressed in athero-sclerotic plaques. We investigated whether angiotensin II, the effector of the renin-angiotensin system, influences the endothelial expression of E-selectin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from explanted human hearts, angiotensin II (10(-11) to 10(-5) mol/L) induced a concentration-dependent increase in E-selectin expression. The effect was measured by cell ELISA and duplex reverse-transcription polymerase chain reaction (RT-PCR) and reached its maximum at 10(-7) mol/L. Angiotensin II induced only a small increase in E-selectin expression in cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of angiotensin II-induced E-selectin expression on leukocyte adhesion was quantified under flow conditions. Angiotensin II (10(-7) mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumor necrosis factor-alpha at a wall shear stress of 2 dyne/cm2. This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT1-receptor, but not AT2-receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.
Formation of lipoprotein-X. Its relationship to bile compounds.
Authors: E Manzato, R Fellin, G Baggio, S Walch, W Neubeck, D Seidel
Journal: Journal of Clinical Investigation (1976)

In this study we have demonstrated that in native bile, lipids are organized in the form of a lipoprotein (bile LP) carrying albumin as apoprotein. The lipid composition of bile LP is almost identical to lipoprotein-X (LP-X, the characteristic lipoprotein of cholestasis). However, it differs from LP-X inits protein/lipid ratio and immunological and electrophoretic characteristics. Bile lipoprotein can be converted into "LP-X-like" material in vitro by adding albumin or serum to native bile. The LP-X-like material formed in vitro has physicochemical and chemical characteristics similar or identical to LP-X isolated from serum. As bile lipoprotein can be converted into LP-X-like material by the addition of albumin to bile, LP-X can be converted into bile-LP-like particles by adding bile salts to a LP-X-positive serum. Furthermore, experimental connection of the common bile duct to the vena cava is followed after a few hours by the appearance of LP-X-like material in the plasma. These facts taken together strongly suggest that bile LP is a precursor lipoprotein for LP-X and that it refluxes into the plasma pool under cholestatic conditions.
The Electrophysiology of Acute Myocardial Ischemia
Authors: H A Fozzard, J C Makielski
Journal: Annual Review of Medicine (1985)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
The Merck Manual of Diagnosis and Therapy
Authors: C. W. Buckley
Journal: Annals of the Rheumatic Diseases (1950)

This report of the proceedings at a conference held by the British Rheumatism Association opens with addresses by well known authorities on the treatment and general management of rheumatoid arthritis, which may be read with profit by the laity, since they bring the newest remedies into due perspective and correct erroneous ideas.The problem of the rural patient living often at a distance from any centre for treatment was thoroughly discussed and the need for physiotherapists in the smaller towns and villages emphasized.This is a matter which might well receive consideration as a part of the National Health Service, the available directories of physiotherapists seem to suggest that in many large towns there are far more than can make a living while in the smaller centres there are none.This is probably because the amount of work would be insufficient to provide a reasonable income, and a car might be a necessity and some form of subsidy or salary would be required, some arrangement of the kind would certainly relieve the strain on the ambulance service in many districts and thus effect an economy.The patient who is housebound, either from the degree of crippling or the burden of domestic duties, might find a visiting physiotherapist a great boon.Rehabilitation, the provision for employment of those who are crippled, and the work ofexisting voluntary organizations furnish the material for other addresses and discussions, and indicate how wide is the field for the further work which the British Rheumatic Association is seeking to do.
In situ immunophenotyping study of endothelial cells of the human hepatic sinusoid: Results and functional implications
Authors: Jean-Yves Scoazec, Gérard Feldmann
Journal: Hepatology (1991)

Hepatic sinusoids are highly specialized capillary vessels characterized by the presence of resident macrophages adhering to the endothelial lining. Although it is likely that sinusoidal endothelial cells have specific adaptations, little is known about the roles that they actually play in vivo. We therefore designed an in situ immunophenotyping study of sinusoidal endothelial cells in normal human liver to compare this population with those of the other vascular compartments of the liver and to determine whether it expresses molecules involved in the following physiological processes: scavenging and nonspecific immune functions, antigen presentation and endothelialleukocyte adhesion. Our study showed that sinusoidal endothelial cells displayed a highly distinctive immunophenotype characterized by the expression of several molecules not found in the other vascular compartments of the liver. A first group of molecules restricted to sinusoidal endothelial cells were: the receptors II and III for the Fc fragment of IgG; the CD14 molecule, serving as a receptor for the lipopolysaccharide-binding protein; and aminopeptidase N. The presence of those molecules suggests that sinusoidal endothelial cells contribute to the scavenger and nonspecific immune functions of hepatic sinusoids. No direct evidence for an antigenpresenting function of this cell population was obtained. Another group of proteins restricted to sinusoidal endothelial cells comprised the leukocyte adhesion molecules CD4 and intercellular adhesion molecule–1, which may be involved in the adhesion of Kupffer cells to the sinusoidal wall. Therefore our immunophenotyping study makes it possible to provide an in situ demonstration of the phenotypical and functional diversity of endothelial cells in normal human liver. The distinctive phenotype of sinusoidal endothelial cells is likely to correlate with specific functional adaptations to their particular microenvironments. (HEPATOLOGY 1991;14:789–797).