tbuckley/cabot-search huggingface dataset:
Variation in the <i>ICAM1–ICAM4–ICAM5</i> locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries
Authors: Kwangwoo Kim, Elizabeth E Brown, Chan-Bum Choi, Marta E Alarcón-Riquelme, Jennifer A Kelly, Stuart B Glenn, Joshua O Ojwang, Adam Adler, Hye-Soon Lee, Susan A Boackle, Lindsey A Criswell, Graciela S Alarcón, Jeffrey C Edberg, Anne M Stevens, Chaim O Jacob, Gary S Gilkeson, Diane L Kamen, Betty P Tsao, Juan-Manuel Anaya, Joel M Guthridge, Swapan K Nath, Bruce Richardson, Amr H Sawalha, Young Mo Kang, Seung Cheol Shim, Chang-Hee Suh, Soo-Kon Lee, Chang-sik Kim, Joan T Merrill, Michelle Petri, Rosalind Ramsey-Goldman, Luis M Vilá, Timothy B Niewold, Javier Martin, Bernardo A Pons-Estel, Timothy J Vyse, Barry I Freedman, Kathy L Moser, Patrick M Gaffney, Adrienne Williams, Mary Comeau, John D Reveille, Judith A James, R Hal Scofield, Carl D Langefeld, Kenneth M Kaufman, John B Harley, Changwon Kang, Robert P Kimberly, Sang-Cheol Bae
Journal: Annals of the Rheumatic Diseases (2012)

Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR(meta)=1.16, 95% CI 1.11 to 1.22; p=4.88×10(-10) and OR(meta)=1.67, 95% CI 1.55 to 1.79; p=3.32×10(-46), respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10(-5)).These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE.
A spline for the time
Authors: J. Schwartz
Journal: Thorax (2011)

Recipients of organ transplants are at increased risk for infection owing to their immunosuppressed state and the possibility of contamination of the donor organ. We report a case of multidrug resistant tuberculosis (MDR) transmission via a donor lung. After medical treatment with four drugs had failed, the patient underwent right upper lobectomy. There were no signs of disease on follow up more than 2 years later. To our knowledge, this is the first report of MDR tuberculosis in a lung transplant recipient. The need for a non-conservative approach, including pulmonary resection, to eradicate the infection is emphasised.
Hypoplasia of the aortic root : The problem of aortic valve replacement
Authors: R. Nicks, T. Cartmill, L. Bernstein
Journal: Thorax (1970)

We report a technique for the enlargement of a hypoplastic aortic root by an operation whereby the hypoplastic aortic root has been so enlarged by the insertion of a Dacron fabric gusset that it will accommodate a size 9A or larger Starr-Edwards prosthesis. Our experience in five patients is described. No matter what type of valve is used for replacement of a diseased aortic valve, and no matter what improved designs of valvular prosthesis are ultimately developed, it will be necessary (in the particular group described) to enlarge the aortic ring to accommodate a size which will function correctly without causing left ventricular outflow obstruction.
Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans
Authors: Chiara Luberto, Beatriz Martinez-Mariño, Daniel Taraskiewicz, Benjamin Bolaños, Pasquale Chitano, Dena L. Toffaletti, Gary M. Cox, John R. Perfect, Yusuf A. Hannun, Edward Balish, Maurizio Del Poeta
Journal: Journal of Clinical Investigation (2003)

Cryptococcus neoformans is a fungal pathogen that, after inhalation, can disseminate to the brain. Host alveolar macrophages (AMs) represent the first defense against the fungus. Once phagocytosed by AMs, fungal cells are killed by a concerted mechanism, involving the host-cellular response. If the cellular response is impaired, phagocytosis of the fungus may be detrimental for the host, since C. neoformans can grow within macrophages. Here, we identified a novel cryptococcal gene encoding antiphagocytic protein 1 (App1). App1 is a cryptococcal cytoplasmic protein that is secreted extracellularly and found in the serum of infected patients. App1 does not affect melanin production, capsule formation, or growth of C. neoformans. Treatment with recombinant App1 inhibited phagocytosis of fungal cells through a complement-mediated mechanism, and Δapp1 mutant is readily phagocytosed by AMs. Interestingly, the Δapp1 mutant strain showed a decreased virulence in mice deficient for complement C5 (A/Jcr), but it was hypervirulent in mice deficient for T and NK cells (Tgε26). This study identifies App1 as a novel regulator of virulence for C. neoformans, and it highlights that internalization of fungal cells by AMs increases the dissemination of C. neoformans when the host cellular response is impaired.
The Biochemical Pharmacology of Atrial Peptides
Authors: P Needleman, E H Blaine, J E Greenwald, M L Michener, C B Saper, P T Stockmann, H E Tolunay
Journal: The Annual Review of Pharmacology and Toxicology (1989)

A schematic overview is presented as a framework for the more com­ prehensive review of the atrial peptide system that follows (Figure 1). An expanded discussion of the specific details and references is detailed in the subsequent section. Briefly, granules located in the atria (but not the ventri­ cles) contain the 126-amino acid prohormone termed atrial natriuretic factor (ANF) , atrial natriuretic peptide (ANP) , cardionatrin or atriopeptin (AP). cDNA probes have been used to characterize the amino acid sequence of a 152-amino acid rat atrial preprohormone. Non-atrial sites of AP synthesis have also been discovered in the central nervous system and the cardiac ventricle, which only expresses AP biosynthesis during fetal and neonatal development and during cardiac hypertrophy. Recently, Flynn and colleagues announced (at the Third International Congress on Biologically Active Atrial Peptides, New York, June 25-26, 1988) the isolation and sequencing from rat atrial extracts of a unique atriopeptin-like peptide termed iso-rANP (rat atrial natriuretic peptide) (Fig-
An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units
Authors: Gabriel T. Bosslet, Thaddeus M. Pope, Gordon D. Rubenfeld, Bernard Lo, Robert D. Truog, Cynda H. Rushton, J. Randall Curtis, Dee W. Ford, Molly Osborne, Cheryl Misak, David H. Au, Elie Azoulay, Baruch Brody, Brenda G. Fahy, Jesse B. Hall, Jozef Kesecioglu, Alexander A. Kon, Kathleen O. Lindell, Douglas B. White
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsRecommendation 1Recommendation 2Recommendation 3Recommendation 4ReferencesCITING ARTICLES
Plasma HIV Viral Load in Patients with Hemophilia and Late-Stage HIV Disease: A Measure of Current Immune Suppression
Authors: Eric A. Engels, Philip S. Rosenberg, Thomas R. O'Brien, James J. Goedert
Journal: Annals of Internal Medicine (1999)

Background: For patients infected with HIV, plasma HIV viral load in early disease predicts long-term prognosis. However, the implications of viral load measurements late in HIV disease are uncertain. Objective: To evaluate the relation between plasma HIV viral load and subsequent risk for disease progression in patients with late-stage HIV disease. Design: Retrospective cohort study. Setting: 16 treatment centers for patients with hemophilia. Patients: 389 patients with hemophilia and late-stage HIV disease (CD4 count < 200 cells/mm3). Measurements: Plasma HIV viral load was measured at baseline. Patients were followed for AIDS-related illnesses (primary outcome) and, specifically, Pneumocystis carinii pneumonia (secondary outcome). Results: HIV viral load strongly predicted AIDS-related illness. For patients with viral loads less than 4.00 log10 copies/mL, the 1-year actuarial risk was 0% and the 5-year risk was 25%. For patients with viral loads of at least 6.00 log10 copies/mL, the 1-year actuarial risk was 42% and the 5-year risk was 78%. A linear relation existed between viral load and risk for AIDS-related illness (hazard ratio, 2.37 per log10 copies/mL; P < 0.001). In addition, viral load most strongly predicted risk for illness immediately after viral load testing; this predictive relation attenuated over time (P = 0.002). These findings changed little after adjustment for CD4 cell counts that were updated during follow-up. In the first year after viral load was measured, it predicted occurrence of P. carinii pneumonia (hazard ratio, 4.69 per log10 copies/mL; P < 0.001). Conclusions: In patients with hemophilia and late-stage HIV disease, viral load predicts disease progression independently of CD4 cell counts. Because viral load most strongly predicts progression immediately after load is measured, it seems to reflect the current level of immunosuppression.
Influence of High Levels of Dietary Fats and Cholesterol on Atherosclerosis and Lipid Distribution in Swine
Authors: RAYMOND REISER, MARY FRANCES SORRELS, MARY CARR WILLIAMS
Journal: Circulation Research (1959)

The degree of incorporation of injected 1-C 14 -acetate into tissue cholesterol on cholesterol free diets was much higher in the liver and plasma of swine ingesting saturated than unsaturated fat. The levels of cholesterol in all tissues increased with the presence of fat or cholesterol in the diet. In most cases, especially in the presence of cholesterol, cholesterol levels were highest in the presence of unsaturated fat. The combination of unsaturated fat with cholesterol in the diet produced the greatest degree of typical atheromatosis and the highest levels of cholesterol in the tissues, while saturated fat with cholesterol produced diffuse atypical lesions.
An official European Respiratory Society statement on physical activity in COPD
Authors: Henrik Watz, Fabio Pitta, Carolyn L. Rochester, Judith Garcia-Aymerich, Richard ZuWallack, Thierry Troosters, Anouk W. Vaes, Milo A. Puhan, Melissa Jehn, Michael I. Polkey, Ioannis Vogiatzis, Enrico M. Clini, Michael Toth, Elena Gimeno-Santos, Benjamin Waschki, Cristobal Esteban, Maurice Hayot, Richard Casaburi, Janos Porszasz, Edward McAuley, Sally J. Singh, Daniel Langer, Emiel F.M. Wouters, Helgo Magnussen, Martijn A. Spruit
Journal: European Respiratory Journal (2014)

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 “Rehabilitation and Chronic Care” determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically ( e.g. every 5–8 years).
Plasma ADMA Predicts Restenosis of Arteriovenous Fistula
Authors: Chih-Cheng Wu, Szu-Chi Wen, Chung-Wei Yang, Shih-Yun Pu, Kuei-Chin Tsai, Jaw-Wen Chen
Journal: Journal of the American Society of Nephrology (2009)

Plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide production, correlate with endothelial dysfunction and the development of cardiovascular events in patients with uremia. It is not known whether endothelial dysfunction contributes to the dysfunction of arteriovenous fistulas (AVFs) in hemodialysis patients. Here, we studied the predictive value of baseline plasma ADMA for symptomatic restenosis of an AVF after percutaneous transluminal angioplasty in dialysis patients. We obtained baseline plasma ADMA levels before percutaneous transluminal angioplasty in 100 consecutive patients with dysfunctional AVFs. Patients were followed up clinically for up to 6 mo after angioplasty for recurrent dysfunction. During the 6 mo after angioplasty, 46 patients experienced recurrent dysfunction of their AVF; of these, follow-up fistulography showed restenosis at the same location in 41, new stenosis at different locations in two, and no significant stenosis in three patients. Up to 60% of the patients with high levels of ADMA (&gt;0.910 μM) had target lesion restenosis compared with 25% of those with low levels (&lt;0.910 μM; <i>P</i> &lt; 0.001). In multivariate analysis, plasma ADMA independently nearly tripled the risk for recurrent symptomatic stenosis of an AVF after percutaneous transluminal angioplasty (hazard ratio 2.65; 95% confidence interval 1.33 to 5.28). These results suggest a role for ADMA in the progression of symptomatic restenoses of AVFs after percutaneous transluminal angioplasty and call for preventive strategies that target ADMA and/or endothelial dysfunction to decrease the risk for AVF restenosis.
Immunity in taeniasis-cysticercosis I. Vaccination against Taenia taeniaeformis in rats using purified antigen.
Authors: B H Kwa, F Y Liew
Journal: The Journal of Experimental Medicine (1977)

Artificial immunization of rats against Taenia taeniaeformis was studied using somatic antigen (Som-Ag) and excretory-secretory antigen (ES-Ag). It was found that both Som-Ag and ES-Ag stimulated immediate-type hypersensitivity and delayed-type hypersensitivity reactions of similar levels. Antibody levels rose from the 2nd wk and peaked around the 6th and 7th wk. Both IgM and IgG were detectable from the 2nd wk onwards, with IgG at a considerably higher level compared to IgM. It terms of protection, 90-100% reduction in cyst counts were detected if the rats were challenged 10 days or more after immunization. In all cases, no significant difference was observed between immunization with either Som-Ag or ES-Ag were purified and characterized using Sephadex G-200 chromatography, double immunodiffusion, and disk acrylamide gel electrophoresis. A purified antigen (mol wt, 140,000 daltons) was obtained, and highly significant protection against infection resulted with injections of 50, 10, or 1 mug doses of this antigen with complete Freund's adjuvant.
Epoxyeicosatrienoic Acids Activate K <sup>+</sup> Channels in Coronary Smooth Muscle Through a Guanine Nucleotide Binding Protein
Authors: Pin-Lan Li, William B. Campbell
Journal: Circulation Research (1997)

Abstract Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K + channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca 2+ -activated K + channel (K Ca ) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the K Ca channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the K Ca channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the K Ca channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-β-S (100 μmol/L). In outside-out patches, 11,12-EET also increased the K Ca channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-G S α antibody (100 nmol/L) in the pipette solution completely blocked the activation of the K Ca channels induced by 11,12-EET. An anti-Gβγ or anti-G i α antibody was without effect. We conclude that 11,12-EET activates the K Ca channels by a G S α-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.
Effect of a Mental Health “Carve-Out” Program on the Continuity of Antipsychotic Therapy
Authors: Wayne A. Ray, James R. Daugherty, Keith G. Meador
Journal: New England Journal of Medicine (2003)

On July 1, 1996, as a cost-containment strategy, Tennessee's expanded Medicaid program, TennCare, rapidly shifted the provision of mental health services to a fully capitated, specialty "carve-out" program, TennCare Partners. We studied the effect of this transition on the continuity of antipsychotic therapy among patients with severe mental illness who had previously adhered to treatment.Study patients were 21 to 64 years of age, were enrolled throughout the study period, and had adhered to antipsychotic therapy during a 6-month base-line period that preceded the 12 months of study follow-up. The study population included 4507 patients whose follow-up began on the day the change was implemented (the post-transition cohort) and 3644 patients whose follow-up began one year earlier (the pretransition cohort). We compared the two cohorts in terms of the loss of continuity of antipsychotic therapy (missed treatment for more than 60 days during follow-up) and the mean number of days of antipsychotic therapy during follow-up.As compared with the pretransition cohort, the post-transition cohort had increased odds of loss of continuity (a multivariate odds ratio of 1.18 [95 percent confidence interval, 1.07 to 1.30], P=0.001) and a shorter mean duration of antipsychotic therapy (a mean reduction of 4.2 days [95 percent confidence interval, 1.7 to 6.7], P=0.001) during follow-up. This difference was most pronounced among high-risk patients (those requiring the administration of extended-release [depot] injections of antipsychotic medications or who had been hospitalized for psychosis) at base line, for whom continuity was most important (odds ratio for loss of continuity, 1.79 [95 percent confidence interval, 1.45 to 2.22]; P<0.001; mean reduction in the number of days of antipsychotic therapy, 14.4 days [95 percent confidence interval, 9.4 to 19.4]; P<0.001). These patients had decreased use of antipsychotic drugs immediately after the transition; the lower level persisted throughout the 12 months of follow-up.These findings underscore the need to ensure that shifts to widely used carve-out programs, which are designed primarily to contain costs, do not adversely affect clinical outcomes.
To Share or Not To Share: That Is Not the Question
Authors: Lucila Ohno-Machado
Journal: Science Translational Medicine (2012)

There is an increasing awareness of the power of integrating multiple sources of data to accelerate biomedical discoveries. Some even argue that it is unethical not to share data that could be used for the public good. However, the challenges involved in sharing clinical and biomedical data are seldom discussed. I briefly review some of these challenges and provide an overview of how they are being addressed by the scientific community.
Adverse Intrauterine Conditions Diminish the Fetal Defense Against Acute Hypoxia by Increasing Nitric Oxide Activity
Authors: David S. Gardner, Abigail L. Fowden, Dino A. Giussani
Journal: Circulation (2002)

The incidence of perinatal morbidity arising from birth hypoxia or asphyxia has not changed significantly in recent years despite marked improvements in labor management. Perinatal mortality in these circumstances may therefore reflect antenatal compromise and subsequent alteration of the fetal capacity to respond to episodes of hypoxia that may occur during labor. Hence, we have investigated the effects of fetal pre-exposure to a period of adverse intrauterine conditions on the mechanisms mediating the fetal defense response to a subsequent episode of acute hypoxia in sheep.Sixteen fetal sheep were chronically instrumented at 118+/-2 days for recording of blood pressure, heart rate, and femoral and umbilical blood flows. In 8 of these fetuses, umbilical blood flow was reduced by 30% for 3 days (between days 125 and 128). The remaining 8 fetuses acted as sham-operated controls. Between 2 and 7 days after umbilical cord/sham compression, all fetuses were exposed to 2 episodes of acute hypoxemia on separate days during infusion with either saline or treatment with a combination of N(G)-nitro-L-arginine methyl ester and sodium nitroprusside. We show that previous fetal exposure to a period of adverse intrauterine conditions, such as that induced by compression of the umbilical cord, elevates nitric oxide activity and results in a markedly diminished cardiovascular defense response to subsequent acute hypoxia.The data imply that pre-exposure to adverse antenatal conditions may render the fetus more susceptible to the acute hypoxia or asphyxia that can accompany relatively uncomplicated labor and delivery.
Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits
Authors: M Gupta
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Surfactant protein B (SP-B) is an essential component of pulmonary surfactant, but shorter SP-B sequences may exert equivalent surface activity. <h3>METHODS</h3> We synthesised a peptide based on the amino-terminal domain of SP-B (SP-B1–25), a full length SP-B1–78, and a full length palmitoylated SP-C peptide (SP-C1–35) and compared the in vivo function and sensitivity to plasma inhibition of preparations consisting of mixtures of phospholipids with SP-B1–25 or SP-B1–78 and/or SP-C1–35 to Survanta. Preterm rabbits born at 27 days of gestation were treated at birth with surfactant and ventilated for 60 minutes. At 15 minutes half of them received plasma intratracheally. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured to define lung mechanics. <h3>RESULTS</h3> Dynamic compliance and postmortem lung volumes were highest after treatment with a surfactant consisting of an SP-B peptide and SP-C1–35 or Survanta. Plasma instillation decreased dynamic compliance and lung volumes sharply, but the most effective activity was by prior instillation of surfactants containing SP-B1–25. <h3>CONCLUSION</h3> These experiments suggest that the N-terminal domain of SP-B (SP-B1–25) exhibits in vitro and in vivo surface activity and is relatively insensitive to plasma inhibition.