tbuckley/cabot-search huggingface dataset:
Inducible Co-Stimulator Null MRL-Fas lpr Mice
Authors: Geraldine C Zeller, Junichi Hirahashi, Andreas Schwarting, Arlene H Sharpe, Vicki R Kelley
Journal: Journal of the American Society of Nephrology (2005)

MRL/MpJ-Tnfrsf6lpr (MRL-Faslpr) mice develop a spontaneous T cell-dependent autoimmune disease that shares features with human lupus, including fatal nephritis, systemic pathology, and autoantibodies (autoAb). The inducible co-stimulator (ICOS) is upregulated on activated T cells and modulates T cell-mediated responses. To investigate whether ICOS has an essential role in regulating autoimmune lupus nephritis and the systemic illness in MRL-Faslpr mice, ICOS null (-/-) MRL Faslpr and ICOS intact (+/+) MRL-Faslpr strains (wild-type [WT]) were generated and compared. It was determined that in ICOS-/- MRL-Faslpr as compared with the WT strain, (1) there is a significant reduction in circulating IgG and double-stranded DNA autoantibody isotype titers, and (2) there is an amplification of the frequency of intrarenal T cells generating IFN-gamma and TNF-alpha in ICOS-/- versus WT mice. Of note, eliminating ICOS in the MRL-Faslpr strain does not alter renal pathology or function. Despite the reduction in circulating IgG and autoantibody isotypes (G1, G2a, and G2b), the amount of these IgG isotypes depositing in kidneys is similar. Furthermore, the systemic illness (skin, salivary and lacrimal glands, lungs, lymphadenopathy, and splenomegaly) is equivalent in ICOS-/- MRL-Faslpr and WT mice. These findings highlight the danger of relying on individual parameters, such as quantitative serum Ig levels and T cell functions, as prognostic indicators of lupus.
Climate change and respiratory disease: European Respiratory Society position statement
Authors: J. G. Ayres, B. Forsberg, I. Annesi-Maesano, R. Dey, K. L. Ebi, P. J. Helms, M. Medina-Ramón, M. Windt, F. Forastiere
Journal: European Respiratory Journal (2009)

Climate change will affect individuals with pre-existing respiratory disease, but the extent of the effect remains unclear. The present position statement was developed on behalf of the European Respiratory Society in order to identify areas of concern arising from climate change for individuals with respiratory disease, healthcare workers in the respiratory sector and policy makers. The statement was developed following a 2-day workshop held in Leuven (Belgium) in March 2008. Key areas of concern for the respiratory community arising from climate change are discussed and recommendations made to address gaps in knowledge. The most important recommendation was the development of more accurate predictive models for predicting the impact of climate change on respiratory health. Respiratory healthcare workers also have an advocatory role in persuading governments and the European Union to maintain awareness and appropriate actions with respect to climate change, and these areas are also discussed in the position statement.
Biochemical and immunological characterization of the extracellular nucleases of group B streptococci.
Authors: P Ferrieri, E D Gray, L W Wannamaker
Journal: The Journal of Experimental Medicine (1980)

Nearly all group B streptococcal strains representing the five major serotypes were found to produce extracellular nucleases by screening with an agar-well-diffusion technique in DNA-methyl green agar plates. Three different nucleases have been isolated and partially purified by DEAE-and carboxymethyl-cellulose chromatography. They possessed different mobilities on polyacrylamide gel electrophoresis and different molecular weights. These nucleases, designated I, II, and III, are optimally activated by cations of calcium and manganese and exhibited RNase as well as DNase activity. Despite differences in their physical and biochemical properties, nucleases II and III appear antigenically similar, but distinct from nuclease I. These group B streptococcal nucleases are immunologically different from the nucleases of group A streptococci. Neutralizing activity, probably antibody, to nucleases II and III was found in human sera, and was most prevalent in sera of pregnant women colonized with group B streptococci and in their newborn infants.
Dengue: defining protective versus pathologic immunity
Authors: Alan L. Rothman
Journal: Journal of Clinical Investigation (2004)

Dengue is an expanding public health problem, and an effective vaccine remains elusive. This review discusses how the significant influence of sequential infection with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine-induced immune responses.
Autonomic and cerebrovascular abnormalities in mild COPD are worsened by chronic smoking
Authors: L. Bernardi, G. Casucci, T. Haider, E. Brandstätter, E. Pocecco, I. Ehrenbourg, M. Burtscher
Journal: European Respiratory Journal (2008)

Patients with chronic obstructive pulmonary disease (COPD) may develop hypercapnia and hypoxia, two main determinants of cerebral blood flow. The current authors tested whether cerebrovascular regulation was altered in mild COPD, modified by manoeuvres acutely improving autonomic cardiovascular modulation or influenced by smoking habit. In 15 eucapnic normoxic mild COPD patients (eight smokers) and 28 age-matched controls (14 smokers), midcerebral artery blood flow velocity (MCFV), end-tidal carbon dioxide tension (P(ET,CO2)), arterial oxygen saturation (S(a,O2)), ECG and blood pressure at rest were monitored during progressive hypercapnic hyperoxia, isocapnic hypoxia, slow breathing and oxygen administration. MCFV, arterial baroreflex and dynamic MCFV-blood pressure relationships were compared by phase analysis. COPD and control smokers showed higher MCFV (when corrected for P(ET,CO2)), lower cerebrovascular resistance index and lower sensitivity to hypercapnia than nonsmokers, with equal sensitivity to S(a,O2) and similar phase analysis. Arterial baroreflex was depressed in all COPD patients. Slow breathing and oxygen administration improved baroreflex sensitivity and reduced MCFV in all COPD patients. Patients with mild chronic obstructive pulmonary disease show autonomic dysfunction. Chronic smoking induces cerebral vasodilation and impairs cerebrovascular control. All abnormalities can be partly corrected by improving the cardio- and cerebrovascular autonomic modulation, suggesting that functional autonomic abnormalities are already present at an early stage of disease.
Tumor LINE-1 Methylation Level and Microsatellite Instability in Relation to Colorectal Cancer Prognosis
Authors: Kentaro Inamura, Mai Yamauchi, Reiko Nishihara, Paul Lochhead, Zhi Rong Qian, Aya Kuchiba, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Seungyoun Jung, Xuehong Zhang, Kana Wu, Eunyoung Cho, Andrew T. Chan, Jeffrey A. Meyerhardt, Curtis C. Harris, Charles S. Fuchs, Shuji Ogino
Journal: JNCI Journal of the National Cancer Institute (2014)

Hypomethylation in long interspersed nucleotide element-1 (LINE-1) and high-degree microsatellite instability (MSI-high) in colorectal cancer (CRC) have been associated with inferior and superior survival, respectively; however, it remains uncertain whether the prognostic association of LINE-1 hypomethylation differs by MSI status. We hypothesized that the adverse prognostic association of LINE-1 hypomethylation might be stronger in MSI-high CRCs than in microsatellite stable (MSS) CRCs. Utilizing 1211 CRCs in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined patient survival according to LINE-1 hypomethylation status in strata of MSI status. A Cox proportional hazards model was used to compute multivariable CRC-specific mortality hazard ratios (HRs) for a 10% decrease in LINE-1 methylation level (range = 23.1–93.1%), adjusting for potential confounders, including CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. Statistical tests (log-rank test, chi-square test, and likelihood ratio test) were two-sided. In MSI-high cancers, the association of LINE-1 hypomethylation with higher mortality (HR = 2.45, 95% confidence interval [CI] = 1.64 to 3.66, P < .001) was stronger than that in MSS cancers (HR = 1.10, 95% CI = 0.98 to 1.24, P = .11) (Pinteraction < .001, between LINE-1 and MSI statuses). In MSI-high cases with CRC family history, the association of LINE-1 hypomethylation with higher mortality (HR = 5.13, 95% CI = 1.99 to 13.2; P < .001) was stronger than that in MSI-high cases without CRC family history (HR = 1.62, 95% CI = 0.89 to 2.94, P = .11) (Pinteraction = .02, between LINE-1 and CRC family history statuses). The association of LINE-1 hypomethylation with inferior survival is stronger in MSI-high CRCs than in MSS CRCs. Tumor LINE-1 methylation level may be a useful prognostic biomarker to identify aggressive carcinomas among MSI-high CRCs.
Decoy Receptors in the Regulation of T Helper Cell Type 2 Responses
Authors: Andrew N.J. McKenzie, Padraic G. Fallon
Journal: The Journal of Experimental Medicine (2003)

Th2-driven responses are instrumental in disease processes including allergies, asthma, and helminth infection, and are characterized by the production of the cytokines IL-4, IL-5, IL-9, and IL-13. These cytokines form a complex network of molecular and cellular interactions that mediate protective
Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
Authors: Yuxia Cui, Sandra J McBride, Windy A Boyd, Scott Alper, Jonathan H Freedman
Journal: Genome biology (2007)

Abstract Background Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. Results Using Caenorhabditis elegans , 290 genes were identified that are differentially expressed (&gt;1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1 , mtl-2 , cdr-1 and ttm-1 , confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek -1 (MAPKK)-dependent manner. Conclusion Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms.
Self-attaching and cell-attracting in-situ forming dextran-tyramine conjugates hydrogels for arthroscopic cartilage repair
Authors: Liliana S. Moreira Teixeira, Suzanne Bijl, Vishnu V. Pully, Cees Otto, Rong Jin, Jan Feijen, Clemens A. van Blitterswijk, Pieter J. Dijkstra, Marcel Karperien
Journal: Biomaterials (2012)
Nuancing should not imply neglecting
Authors: Howard Margolis
Journal: Behavioral and Brain Sciences (1996)

Abstract Koehler is right to argue for more nuanced interpretation of base rate anomalies. These anomalies are best understood in relation to a broader class of cognitive anomalies, which are important for theory and practice. Recognizing a need for more nuanced analysis should not be taken as a license for treating the effects as “explained away.”
Gain-of-function Lyn induces anemia: appropriate Lyn activity is essential for normal erythropoiesis and Epo receptor signaling
Authors: Neli S. Slavova-Azmanova, Nicole Kucera, Jiulia Satiaputra, Leah Stone, Aaron Magno, Mhairi J. Maxwell, Cathy Quilici, Wendy Erber, S. Peter Klinken, Margaret L. Hibbs, Evan Ingley
Journal: Blood (2013)
Thresholds of fibrillating leakage currents along intracardiac catheters: an experimental study
Authors: W. R. LEE, J. R. SCOTT
Journal: Cardiovascular Research (1973)

In dogs, with a normal acid-base and cation state, a 50 Hz electric shock passed between a ventricular cather and the right leg has a minimum fibrillation threshold of 130 uA. Severe metabolic acidosis decreases the threshold to 100 uA, but hypoxaemia has no effect.
Pathogenesis of Disseminated Intravascular Coagulation in Sepsis
Authors: Marcel Levi
Journal: JAMA (1993)

<h3>Objective.</h3> —To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention. <h3>Data Sources.</h3> —Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis. <h3>Study Selection.</h3> —Studies selected for detailed review were those reporting specifics about the mechanism of activation of coagulation and fibrinolysis in experimental human and animal models of sepsis. Data extraction guidelines for assessing data quality included validity of the model, quality of the laboratory assessment of activation of coagulation and fibrinolysis, and methodological considerations, such as the presence of control experiments and statistical analysis. <h3>Data Synthesis.</h3> —After the presence of endotoxin in the circulation, significant coagulation activation can be detected. This activation is preceded by an increase in the serum levels of various cytokines, such as tumor necrosis factor and interleukins. Inhibition of the increase in tumor necrosis factor results in inhibition of coagulation activation. Measurement of molecular markers for the activation of coagulation proteins at various levels indicates that the activation of coagulation is mediated by the tissue factor—dependent pathway, which is further confirmed by experiments in which the inhibition of the tissue factor—dependent pathway resulted in complete inhibition of coagulation activation. The activation of coagulation seems to be amplified by impaired function of the protein C—protein S inhibitory pathway. An imbalance between coagulation and fibrinolysis, ultimately leading to plasminogen activator inhibitor type 1—mediated inhibition of fibrinolysis, may further promote the procoagulant state. <h3>Conclusion.</h3> —The increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in sepsis may have therapeutic implications; however, their efficacy needs to be assessed in appropriate clinical trials. (<i>JAMA</i>. 1993;270:975-979)
Apical left ventricular aneurysm without atrio‐ventricular block due to a lamin A/C gene mutation
Authors: Jean‐François Forissier, Gisèle Bonne, Christiane Bouchier, Laetitia Duboscq‐Bidot, Pascale Richard, Claudine Wisnewski, Sylvain Briault, Claude Moraine, Olivier Dubourg, Ketty Schwartz, Michel Komajda
Journal: European Journal of Heart Failure (2003)
C-reactive protein levels in community-acquired pneumonia
Authors: E. García Vázquez, J.A. Martínez, J. Mensa, F. Sánchez, M.A. Marcos, A. de Roux, A. Torres
Journal: European Respiratory Journal (2003)

The diagnostic value of C-reactive protein (CRP) admission serum levels as an indicator of the aetiology of community-acquired pneumonia (CAP) was evaluated. A cohort of 1,222 patients with CAP was assessed. CRP levels were analysed in 258 patients with a single aetiological diagnosis. The mean CRP values in patients with pyogenic, atypical, viral and Legionella pneumophila pneumonia were: 16 mg x dL(-1), 13 mg x dL(-1), 14 mg x dL(-1) and 25 mg x dL(-1), respectively. CRP levels were not significantly different among patients outcome research team (PORT) groups (19 mg x dL(-1) in groups I-II, 16 mg x dL(-1) in group III and 16 mg x dL(-1) in groups IV-V). A cut-off point of 25 mg x dL(-1) had a sensibility, specificity, positive predictive value and negative predictive value of 0.6, 0.83, 0.3, and 0.94, respectively. After controlling for age and PORT score, the odds of having a CRP level >25 mg x dL(-1) was 6.9 times higher in patients with L. pneumophila pneumonia than in those with non-L. pneumophila pneumonia. Patients with Legionella pneumophila pneumonia had higher C-reactive protein levels than those with pneumonia of any other aetiology, independently of severity of infection. Being a cheap and readily available test, C-reactive protein may be a useful adjunctive procedure in the diagnosis of community-acquired pneumonia.
A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome
Authors: Carolin E. Sadowski, Svjetlana Lovric, Shazia Ashraf, Werner L. Pabst, Heon Yung Gee, Stefan Kohl, Susanne Engelmann, Virginia Vega-Warner, Humphrey Fang, Jan Halbritter, Michael J. Somers, Weizhen Tan, Shirlee Shril, Inès Fessi, Richard P. Lifton, Detlef Bockenhauer, Sherif El-Desoky, Jameela A. Kari, Martin Zenker, Markus J. Kemper, Dominik Mueller, Hanan M. Fathy, Neveen A. Soliman, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2014)

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of ESRD in the first two decades of life. Effective treatment is lacking. First insights into disease mechanisms came from identification of single-gene causes of SRNS. However, the frequency of single-gene causation and its age distribution in large cohorts are unknown. We performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with SRNS. We then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. We detected a single-gene cause in 29.5% (526 of 1783) of families with SRNS that manifested before 25 years of age. The fraction of families in whom a single-gene cause was identified inversely correlated with age of onset. Within clinically relevant age groups, the fraction of families with detection of the single-gene cause was as follows: onset in the first 3 months of life (69.4%), between 4 and 12 months old (49.7%), between 1 and 6 years old (25.3%), between 7 and 12 years old (17.8%), and between 13 and 18 years old (10.8%). For PLCE1, specific mutations correlated with age of onset. Notably, 1% of individuals carried mutations in genes that function within the coenzyme Q10 biosynthesis pathway, suggesting that SRNS may be treatable in these individuals. Our study results should facilitate molecular genetic diagnostics of SRNS, etiologic classification for therapeutic studies, generation of genotype-phenotype correlations, and the identification of individuals in whom a targeted treatment for SRNS may be available.
Leprosy reactional states and their treatment
Authors: D.S. JOLLIFFE
Journal: British Journal of Dermatology (1977)

Journal Article Leprosy reactional states and their treatment Get access D.S. JOLLIFFE D.S. JOLLIFFE Department of Dermatology, Royal Free Hospital, London NW3 2QG Dr D.S.Jolliffe, Department of Dermatology, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 3, 1 September 1977, Pages 345–352, https://doi.org/10.1111/j.1365-2133.1977.tb15196.x Published: 01 September 1977
Predictors of Coronary Stent Thrombosis
Authors: Jochem W. van Werkum, Antonius A. Heestermans, A. Carla Zomer, Johannes C. Kelder, Maarten-Jan Suttorp, Benno J. Rensing, Jacques J. Koolen, B.R. Guus Brueren, Jan-Henk E. Dambrink, Raymond W. Hautvast, Freek W. Verheugt, Jurriën M. ten Berg
Journal: Journal of the American College of Cardiology (2009)

This study sought to comprehensively identify predictors of stent thrombosis (ST). Given the devastating consequences of ST, efforts should be directed toward risk stratification to identify patients at highest risk for ST. Consecutive patients with angiographic ST were enrolled. Patients who did not suffer from a ST were randomly selected in a 2:1 ratio and were matched for: 1) percutaneous coronary intervention (PCI) indication; 2) same date of index PCI; and 3) same interventional center. Of 21,009 patients treated with either a bare-metal or drug-eluting stent, 437 patients (2.1%) presented with a definite ST. A total of 140 STs were acute, 180 were subacute, 58 were late, and 59 were very late. Undersizing of the coronary stent, Thrombolysis In Myocardial Infarction flow grade <3, present malignancy, presence of intermediate coronary artery disease proximal and distal to the culprit lesion, dissection, lack of aspirin, bifurcation lesions, ejection fraction <30%, and younger age were associated with ST. The lack of clopidogrel therapy at the time of ST in the first 30 days after the index PCI (hazard ratio [HR]: 36.5, 95% confidence interval [CI]: 8.0 to 167.8), between 30 days and 6 months after the index PCI (HR: 4.6, 95% CI: 1.4 to 15.3), and beyond 6 months (HR: 5.9, 95% CI: 1.7 to 19.8) after the index PCI was strongly associated with ST. Important correlates of ST were identified. Discontinuation of clopidogrel, undersizing of the coronary stent, present malignancy, and intermediate (≥50% to <70% stenosis) coronary artery disease proximal to the culprit lesion were the strongest predictors of ST.
Innate immunity in paediatric viral wheezers is virus specific and not interferon dependent
Authors: Sejal Saglani
Journal: Thorax (2014)

Up to a third of all children develop virus induced wheezing, but we still do not understand why some children wheeze with viral colds and others do not. We also do not know why only some viral wheezers progress to develop asthma and others do not. Data from the Childhood Origins of Asthma Study (COAST) have shown that children with at least one atopic parent who wheeze with viral infections in the first 3 years of life have a significantly increased risk of developing asthma.1 Specifically, wheezing with human rhinovirus (HRV) in the third year of life was associated with up to 30-fold higher risk. However, this association did not delineate whether virus infection caused asthma, or underlying susceptibility to asthma or early sensitisation resulted in altered immune responses to viral infections which subsequently resulted in an asthma phenotype. We now know that an underlying susceptibility is an important determinant since variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses in COAST and another unrelated high risk birth cohort.2 Moreover, allergic sensitisation precedes HRV induced wheezing and asthma development.3 However, we still know very little about the nature of the immune responses to viral infection in susceptible children who may go on to develop asthma compared with those who are likely to outgrow their symptoms. A consequence of our limited understanding of the mechanisms underlying virus associated wheezing is that currently therapeutic options remain limited …