tbuckley/cabot-search huggingface dataset:
Itk Negatively Regulates Induction of T Cell Proliferation by CD28 Costimulation
Authors: X. Charlene Liao, Sylvie Fournier, Nigel Killeen, Arthur Weiss, James P. Allison, Dan R. Littman
Journal: The Journal of Experimental Medicine (1997)

CD28 is a cell surface molecule that mediates a costimulatory signal crucial for T cell proliferation and lymphokine production. The signal transduction mechanisms of CD28 are not well understood. Itk, a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells, has been implicated in the CD28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD28 upon cross-linking of the cell surface molecule. To determine whether Itk plays a functional role in CD28 signaling, we compared T cells from Itk-deficient mice and control mice for their responses to CD28 costimulation. T cells defective in Itk were found to be fully competent to respond to costimulation. Whereas the CD3-mediated proliferative response was severely compromised in the absence of Itk, the calcineurin-independent CD28-mediated response was significantly elevated when compared with cells from control animals. The augmented proliferation was not due to increased production of interleukin-2. The results suggest that Itk has distinct roles in the CD3 versus the CD28 signaling pathways. By negatively regulating the amplitude of signaling upon CD28 costimulation, Itk may provide a means for modulating the outcome of T cell activation during development and during antigen-driven immune responses.
Nitric Oxide Synthase (NOS2) Mutation in Dahl/Rapp Rats Decreases Enzyme Stability
Authors: Wei-Zhong Ying, Hongli Xia, Paul W. Sanders
Journal: Circulation Research (2001)

The pathogenesis of salt-sensitive hypertension remains poorly defined, but a role for nitric oxide (NO) has been suggested. The Dahl/Rapp salt-sensitive rat possesses a defect in NO synthesis that is overcome by supplementation with l -arginine, which increases NO and cGMP production and prevents salt-sensitive hypertension. An S714P mutation of inducible NO synthase (NOS2) was subsequently identified. The current report examined the functional significance of an S714P mutation in NOS2. COS-7 cells were transiently transfected with cDNA of wild-type NOS2 and S714P and S714A mutants of NOS2, and enzyme function was determined. Whereas steady-state mRNA levels did not differ, immunoblot analysis demonstrated decreased levels of NOS2 protein. Metabolic labeling experiments confirmed a reduced half-life of the S714P mutation. Nitrite production, which was dependent on the concentration of l -arginine in the medium, was diminished in cells transfected with the S714P mutant, compared with the wild type and the S714A mutant. These data provide a biochemical explanation of the physiological abnormalities of NOS2 in the Dahl/Rapp salt-sensitive rat and suggest that a posttranslational mechanism involving the proteasome may be responsible for the diminished NO production observed in response to increased dietary salt intake in these animals.
Trends in mortality after diagnosis of hepatitis C virus infection: An international comparison and implications for monitoring the population impact of treatment
Authors: Esther J. Aspinall, Sharon J. Hutchinson, Naveed Z. Janjua, Jason Grebely, Amanda Yu, Maryam Alavi, Janaki Amin, David J. Goldberg, Hamish Innes, Matthew Law, Scott R. Walter, Mel Krajden, Gregory J. Dore
Journal: Journal of Hepatology (2014)
The Effect of Insulin Infusion on the Metabolites in Cerebral Tissues Assessed With Proton Magnetic Resonance Spectroscopy in Young Healthy Subjects With High and Low Insulin Sensitivity
Authors: Monika Karczewska-Kupczewska, Eugeniusz Tarasów, Agnieszka Nikołajuk, Magdalena Stefanowicz, Natalia Matulewicz, Elżbieta Otziomek, Maria Górska, Marek Strączkowski, Irina Kowalska
Journal: Diabetes Care (2013)

OBJECTIVE Insulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy (1H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity. RESEARCH DESIGN AND METHODS We studied 16 healthy young men. 1H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity. RESULTS Baseline neurometabolic substrates were not different between the groups. Insulin infusion resulted in an increase in frontal NAA/Cr and NAA/H2O and frontal and temporal Glx/Cr and Glx/H2O and a decrease in frontal Cho/Cr and temporal Cho/H2O and myo-inositol/H2O (all P &amp;lt; 0.05, except temporal Glx/H2O, P = 0.054, NS) in the high-IS, but not in the low-IS, group. Insulin sensitivity correlated positively with frontal NAA/Cr and NAA/H2O and temporal Glx/H2O and negatively with temporal myo-inositol/Cr and myo-inositol/H2O assessed during the second 1H-MRS (all P &amp;lt; 0.05). CONCLUSIONS Insulin might influence cerebral metabolites, and this action is impaired in subjects with low whole-body insulin sensitivity. Thus, our results provide a potential link between insulin resistance and altered metabolism of the central nervous system.
Shattered Mirrors: Our Search for Identity and Community in the AIDS Era
Authors: David Michael Levin
Journal: JAMA (1990)

As the acquired immunodeficiency syndrome (AIDS) epidemic spreads its devastation and makes increasingly urgent—and increasingly difficult—demands on our social and political institutions, the number of books on AIDS also continues to increase. This new book, by the dean of the Benjamin Cardozo School of Law at Yeshiva University, is not only intelligent, but compelling in its honesty, its willingness to examine the problems we must face without flinching and without compromise. If it seemed, at first, that AIDS would mainly challenge the science and practice of medicine, it is now becoming increasingly clear that the infectious nature of the disease has also set in motion, at the same time, one of the greatest tests our legal system has ever had to confront: how to protect lives without violating and nullifying basic civil rights and freedoms. As Price observes in his prologue, "The challenge to the public's health is creating a
Anemia in Hodgkin's Lymphoma: The Role of Interleukin-6 and Hepcidin
Authors: Stefan Hohaus, Giuseppina Massini, Manuela Giachelia, Barbara Vannata, Valentina Bozzoli, Annarosa Cuccaro, Francesco D'Alo', Luigi Maria Larocca, Reinier A.P. Raymakers, Dorine W. Swinkels, Maria Teresa Voso, Giuseppe Leone
Journal: Journal of Clinical Oncology (2010)

Purpose Cytokines play a pivotal role in Hodgkin's lymphoma (HL). Because interleukin-6 (IL-6) induces expression of hepcidin, one of the principal regulators of iron metabolism, we studied the contribution of hepcidin in anemia in HL at diagnosis. Patients and Methods Plasma samples from 65 patients with HL were analyzed for hepcidin levels using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry; cytokine levels were analyzed using enzyme-linked immunosorbent assays and parameters of iron metabolism and acute-phase reaction. Results Hepcidin plasma levels were significantly higher in HL patients when compared with controls, independent of the presence of anemia (P = .001). In the subset of patients with anemia, hepcidin levels inversely correlated with hemoglobin levels (P = .01). Analyzing parameters of iron metabolism, hepcidin levels showed a positive correlation with ferritin (P &lt; .001) and an inverse correlation to iron and iron-binding capacity. Hepcidin strongly correlated to IL-6 levels (P &lt; .001) but not to IL-10 or thymus and activation-regulated cytokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) levels. In a multivariate regression analysis, IL-6 and fibrinogen levels were independently associated with hepcidin. Higher hepcidin levels were observed in patients with more aggressive disease characteristics: stage IV disease (P = .01), presence of B symptoms (P = .03), and International Prognostic Score &gt; 2 (P = .005). Conclusion Our findings suggest that in HL, hepcidin is upregulated by IL-6. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic inflammation, although hepcidin-independent mechanisms contribute to development of anemia in HL.
The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis.
Authors: Joseph F Ryan, Patrick M Burton, Maureen E Mazza, Grace K Kwong, James C Mullikin, John R Finnerty
Journal: Genome biology (2006)

Abstract Background Homeodomain transcription factors are key components in the developmental toolkits of animals. While this gene superclass predates the evolutionary split between animals, plants, and fungi, many homeobox genes appear unique to animals. The origin of particular homeobox genes may, therefore, be associated with the evolution of particular animal traits. Here we report the first near-complete set of homeodomains from a basal (diploblastic) animal. Results Phylogenetic analyses were performed on 130 homeodomains from the sequenced genome of the sea anemone Nematostella vectensis along with 228 homeodomains from human and 97 homeodomains from Drosophila . The Nematostella homeodomains appear to be distributed among established homeodomain classes in the following fashion: 72 ANTP class; one HNF class; four LIM class; five POU class; 33 PRD class; five SINE class; and six TALE class. For four of the Nematostella homeodomains, there is disagreement between neighbor-joining and Bayesian trees regarding their class membership. A putative Nematostella CUT class gene is also identified. Conclusion The homeodomain superclass underwent extensive radiations prior to the evolutionary split between Cnidaria and Bilateria. Fifty-six homeodomain families found in human and/or fruit fly are also found in Nematostella , though seventeen families shared by human and fly appear absent in Nematostella . Homeodomain loss is also apparent in the bilaterian taxa: eight homeodomain families shared by Drosophila and Nematostella appear absent from human (CG13424, EMXLX, HOMEOBRAIN, MSXLX, NK7, REPO, ROUGH, and UNC4), and six homeodomain families shared by human and Nematostella appear absent from fruit fly (ALX, DMBX, DUX, HNF, POU1, and VAX).
THE NEUROBIOLOGY OF THE ASCIDIAN TADPOLE LARVA: Recent Developments in an Ancient Chordate
Authors: Ian A. Meinertzhagen, Patrick Lemaire, Yasushi Okamura
Journal: Annual Review of Neuroscience (2004)

With little more than 330 cells, two thirds within the sensory vesicle, the CNS of the tadpole larva of the ascidian Ciona intestinalis provides us with a chordate nervous system in miniature. Neurulation, neurogenesis and its genetic bases, as well as the gene expression territories of this tiny constituency of cells all follow a chordate plan, giving rise in some cases to frank structural homologies with the vertebrate brain. Recent advances are fueled by the release of the genome and EST expression databases and by the development of methods to transfect embryos by electroporation. Immediate prospects to test the function of neural genes are based on the isolation of mutants by classical genetics and insertional mutagenesis, as well as by the disruption of gene function by morpholino antisense oligo-nucleotides. Coupled with high-speed video analysis of larval swimming, optophysiological methods offer the prospect to analyze at single-cell level the function of a CNS built on a vertebrate plan.
An Integrated View of Humoral Innate Immunity: Pentraxins as a Paradigm
Authors: Barbara Bottazzi, Andrea Doni, Cecilia Garlanda, Alberto Mantovani
Journal: Annual Review of Immunology (2009)

The innate immune system consists of a cellular and a humoral arm. Pentraxins (e.g., the short pentraxin C reactive protein and the long pentraxin PTX3) are key components of the humoral arm of innate immunity which also includes complement components, collectins, and ficolins. In response to microorganisms and tissue damage, neutrophils, macrophages, and dendritic cells are major sources of fluid-phase pattern-recognition molecules (PRMs) belonging to different molecular classes. Humoral PRMs in turn interact with and regulate cellular effectors. Effector mechanisms of the humoral innate immune system include activation and regulation of the complement cascade; agglutination and neutralization; facilitation of recognition via cellular receptors (opsonization); and regulation of inflammation. Thus, the humoral arm of innate immunity is an integrated system consisting of different molecules and sharing functional outputs with antibodies.
Autoimmune hepatitis in childhood: A 20-year experience
Authors: G V Gregorio, B Portmann, F Reid, P T Donaldson, D G Doherty, M McCartney, A P Mowat, D Vergani, G Mieli-Vergani
Journal: Hepatology (1997)

To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2–15] years) anti–nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8–14] years) liver/kidney microsomal antibody (LKM–1) positive, with median follow–up of 5 years (range 0.3–19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM–1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM–1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P &lt; .001). Of six (5 LKM–1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM–1 positive) died with no remission and 4 (2 LKM–1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM–1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM–1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long–term outcome.
Cold Agglutinins and Cold-Agglutinin Disease
Authors: M M Frank, J P Atkinson, J Gadek
Journal: Annual Review of Medicine (1977)

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
Embolic Protection Devices
Authors: Sripal Bangalore, Deepak L. Bhatt
Journal: Circulation (2014)

M anipulation of atherosclerotic lesions with wires, cath- eters, balloons, stents, and other intravascular devices during invasive procedures releases atherosclerotic plaque, resulting in distal embolization.This plaque debris leads to no or slow flow as a result of a multitude of factors, including mechanical obstruction of macrovascular and microvascular channels, local platelet adhesion, platelet activation, and thrombosis attributable to release of tissue factors and microvascular spasm by release of thromboxane.The clinical manifestation of this shower of atherosclerotic debris depends on the characteristics: the amount of debris, the size of particles, and the sensitivity of the organ perfused.Distal embolization during percutaneous coronary intervention (PCI) results in decreased distal perfusion, leading to myocardial ischemia or infarction.Manipulation of the aortic arch during coronary, cerebral, or valvular procedures can cause microembolization to the cerebral circulation that may manifest as a transient ischemic attack or stroke.Distal embolization is seen during intervention of all vascular beds, including peripheral, renal, and mesenteric arteries, but the clinical manifestation varies and depends on the sensitivity of the organ perfused and the metric used to assess end-organ damage.Embolic protection devices (EPDs) prevent or reduce plaque debris from reaching the distal bed and thereby have the potential to reduce adverse clinical events.They are commonly used in saphenous vein graft (SVG) interventions and during carotid artery stenting procedures.They are also being tested in other vascular beds such as the renal arteries, but their utility at reducing clinically significant outcomes in these vascular beds has yet to be established.Hyperlinked to this article is a video demonstrating the use of EPDs.Downloadable slides about EPD are available in the onlineonly Data Supplement. Types of EPDsEPDs can be divided into 3 distinct types based on their mechanism of operation: distal occlusion aspiration devices, distal filters, and proximal occlusion aspiration devices.
Leukaemia linked to eating disorders.
Authors: A Nishizono-Maher, H Sakamaki, H Mizukami, T Kuraki, K Minakawa, Y Masuda
Journal: BMJ (1993)

implications for staff training and morale as well as for more frequent medical assessment.'8Finally, both health authorities and local authorities are firmly committed to a policy of supporting older people in their own homes for as long as possible.Surprisingly, the results of this third census in Leicestershire show that the proportion of older people in some form of residential care increased little over the past decade.The greater absolute numbers of elderly people have been absorbed by the growing private sector despite a simultaneous collapse of long term provision in the NHS, and this has been widely attributed to the impact of the central government funding system for private residential care.This remains the situation that social service departments will inherit in April 1993, when social services assume responsibility for private care.Managing this situation while at the same time implementing the organisational, funding, and cultural changes that are required must be regarded as one of the foremost challenges facing local authorities.We thank all the nursing and care staff working in NHS hospitals and homes, local authority homes, and in the private and voluntary care sectors.We were given invaluable help by the directors of nursing services in the NHS hospital units: Miss B Wallam,
Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation
Authors: P. H. Brekke, T. Omland, S. H. Holmedal, P. Smith, V. Søyseth
Journal: European Respiratory Journal (2007)

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated. From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000-2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT >/=0.04 mug.L(-1) were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses. After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15-2.34). In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.
Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels
Authors: Jens Derbinski, Jana Gäbler, Benedikt Brors, Sascha Tierling, Sunitha Jonnakuty, Manfred Hergenhahn, Leena Peltonen, Jörn Walter, Bruno Kyewski
Journal: The Journal of Experimental Medicine (2005)

The role of central tolerance induction has recently been revised after the discovery of promiscuous expression of tissue-restricted self-antigens in the thymus. The extent of tissue representation afforded by this mechanism and its cellular and molecular regulation are barely defined. Here we show that medullary thymic epithelial cells (mTECs) are specialized to express a highly diverse set of genes representing essentially all tissues of the body. Most, but not all, of these genes are induced in functionally mature CD80hi mTECs. Although the autoimmune regulator (Aire) is responsible for inducing a large portion of this gene pool, numerous tissue-restricted genes are also up-regulated in mature mTECs in the absence of Aire. Promiscuously expressed genes tend to colocalize in clusters in the genome. Analysis of a particular gene locus revealed expression of clustered genes to be contiguous within such a cluster and to encompass both Aire-dependent and –independent genes. A role for epigenetic regulation is furthermore implied by the selective loss of imprinting of the insulin-like growth factor 2 gene in mTECs. Our data document a remarkable cellular and molecular specialization of the thymic stroma in order to mimic the transcriptome of multiple peripheral tissues and, thus, maximize the scope of central self-tolerance.
PRESSURE-VOLUME CHARACTERISTICS OF THE HUMAN COLON
Authors: Martin Lipkin, Thomas Almy, Bertrand M. Bell
Journal: Journal of Clinical Investigation (1962)

The activity of the muscular lining of the human colon has customarily been measured in terms of phasic variations of the intraluminal pressure, and less commonly in terms of changes in volume of inlying balloons. By such means, alterations of wave patterns have been recorded in abnormal physiological states, after the administration of pharmacologic agents, and in diseases of the colon. Estimates made from such recordings of the tonus or level of sustained contractions of the muscular wall have been widely regarded as unsatisfactory. With such limitations of our knowledge of colonic motility, additional parameters would appear desirable. In the present study, changes produced by distension in the pressure and volume of a segment of the human sigmoid colon were recorded simultaneously. Mathematical analysis of the data has provided measurements of the rate of distension and accommodation of the colonic wall to the stretching force. The relationships of these parameters to muscular activity are indicated by alterations resulting from the action of pharmacologic agents.