tbuckley/cabot-search huggingface dataset:
Contact investigation for tuberculosis: a systematic review and meta-analysis
Authors: Gregory J. Fox, Simone E. Barry, Warwick J. Britton, Guy B. Marks
Journal: European Respiratory Journal (2012)

Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control in high-income countries, and is increasingly being considered in resource-limited settings. This review was commissioned for a World Health Organization Expert Panel to develop global contact investigation guidelines. We performed a systematic review and meta-analysis of all studies reporting the prevalence of TB and latent TB infection, and the annual incidence of TB among contacts of patients with TB. After screening 9,555 titles, we included 203 published studies. In 95 studies from low- and middle-income settings, the prevalence of active TB in all contacts was 3.1% (95% CI 2.2–4.4%, I 2 =99.4%), microbiologically proven TB was 1.2% (95% CI 0.9–1.8%, I 2 =95.9%), and latent TB infection was 51.5% (95% CI 47.1–55.8%, I 2 =98.9%). The prevalence of TB among household contacts was 3.1% (95% CI 2.1–4.5%, I 2 =98.8%) and among contacts of patients with multidrug-resistant or extensively drug-resistant TB was 3.4% (95% CI 0.8–12.6%, I 2 =95.7%). Incidence was greatest in the first year after exposure. In 108 studies from high-income settings, the prevalence of TB among contacts was 1.4% (95% CI 1.1–1.8%, I 2 =98.7%), and the prevalence of latent infection was 28.1% (95% CI 24.2–32.4%, I 2 =99.5%). There was substantial heterogeneity among published studies. Contacts of TB patients are a high-risk group for developing TB, particularly within the first year. Children &lt;5 yrs of age and people living with HIV are particularly at risk. Policy recommendations must consider evidence of the cost-effectiveness of various contact tracing strategies, and also incorporate complementary strategies to enhance case finding.
A Negative Feedback of the HIF-1α Pathway via Interferon-Stimulated Gene 15 and ISGylation
Authors: Yen-Hsiu Yeh, Yu-Chen Yang, Mei-Yi Hsieh, Yen-Cheng Yeh, Tsai-Kun Li
Journal: Clinical Cancer Research (2013)

The IFN-stimulated gene 15 (ISG15)- and ubiquitin-conjugation pathways play roles in mediating hypoxic and inflammatory responses. To identify interaction(s) between these two tumor microenvironments, we investigated the effect of ISG15 on the activity of the master hypoxic transcription factor HIF-1α.IFN and desferoxamine treatments were used to induce the expression of ISGs and HIF-1α, respectively. Interactions between HIF-1α and the ISG15 and ISGylation system were studied using knockdown of mRNA expression, immunoblotting, coimmunoprecipitation, and pull-down analyses. Effects of the ISG15 and ISGylation system on the HIF-1α-directed processes were examined using reporter, reverse transcription polymerase chain reaction (RT-PCR), and tumorigenic growth assays.We found that the level of the free form of HIF-1α is differentially regulated by IFN treatment, and that the free ISG15 level is lower under hypoxia. Mechanism-directed studies have shown that HIF-1α not only interacts physically with ISG15, but is also ISGylated in multiple domains. ISG15 expression disrupts the functional dimerization of HIF-1α and -1β. Subsequently, expression of the ISG15 and/or ISGylation system attenuates HIF-1α-mediated gene expression and tumorigenic growth.In summary, our results revealed cross-talk between inflammatory and hypoxic pathways through the ISGylation of HIF-1α. On the basis of these results, we propose a novel negative feedback loop for the HIF-1α-mediated pathway involving the regulation of HIF-1α via IFN-induced ISGylation.
DISAPPEARANCE AND REAPPEARANCE OF ISLET CELL CYTOPLASMIC ANTIBODIES IN CYCLOSPORIN-TREATED INSULIN-DEPENDENT DIABETICS
Authors: T. Mandrup-Poulsen, C.R. Stiller, G. Bille, R. Martell, P.A. Keown, N.W. Rodger, B.V. Graffenried, J. Nerup, B. Marner, D. Heinrichs, J. Dupre, M.R. Jenner, B. Wolfe, C. Binder
Journal: The Lancet (1985)
Serum Cystatin C as a Determinant of Fasting Total Homocysteine Levels in Renal Transplant Recipients with a Normal Serum Creatinine
Authors: ANDREW G. BOSTOM, REGINALD Y. GOHH, LINDA BAUSSERMAN, DAVID HAKAS, PAUL F. JACQUES, JACOB SELHUB, LANCE DWORKIN, IRWIN H. ROSENBERG
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels ( i.e. , ≤ 1.5 mg/dl), serum cystatin C, a more sensitive indicator of GFR, would better predict fasting total homocysteine levels compared with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B 12 , and pyridoxal 5′-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 28 consecutive renal transplant recipients (mean age 47 ± 14 yr; 60.7% men) with stable allograft function, whose serum creatinine was ≤1.5 mg/dl. General linear modeling with analysis of covariance revealed that serum cystatin C was independently predictive (partial R = 0.494; P = 0.023) of fasting total homocysteine levels after adjustment for age, gender, vitamin status, albumin, and creatinine levels. In contrast, creatinine levels were not predictive of fasting total homocysteine levels in this model ( P = 0.110) or an identical model that excluded cystatin C ( P = 0.131). Serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable renal transplant recipients with a normal serum creatinine.
The effects of maximum steady state pace training on running performance.
Authors: J W Priest, R D Hagan
Journal: British Journal of Sports Medicine (1987)

Maximum aerobic power (VO2 max), maximum anaerobic power (AP max), submaximal exercise heart rate (HRsub), and performance times for distances of 15m, 600 m, 3.22 km, and 10 km were evaluated in 12 male runners prior to and after 7 weeks of a running programme at each individual's maximum steady-state (MSS) pace. MSS pace, a running speed at which blood lactate is believed to equal 2.2 mmol . l-1, was calculated from weekly 3.22 km runs utilising the regression equation of LaFontaine et al (1981). During the training period, the mean MSS pace increased 11.3% from 3.76 to 4.19 m.s.-1. Body weight and maximal exercise heart rate were unaffected by MSS training. However, MSS training was associated with increases (p less than 0.05) in absolute VO2 max (8.9%) and VO2 max relative to body weight (8.1%), absolute AP max (3.7%) and AP max, relative to body weight (4.3%); decreases in resting HR (5.4%) and HRsub (6.9%); and decreases in performance times for runs of 15m (1.8%), 600 m (4.4%), 3.22 km (9.6%), and 10 km (12.1%). MSS paces determined prior to the pre- and post-training 10 km races were significantly related to the pre-training (r = 0.98) and post-training 10 km (r = 0.95) performance paces. Pretraining MSS pace, maximal aerobic power, and performance times for the 3.22 km and 10 km distances were highly related to improvements in MSS pace and performance times for the 3.22 km and 10 km runs. Our findings indicate that training at MSS pace is an effective method to increase maximal aerobic and anaerobic power, and decrease performance times for short- and middle-distance running events. Pre-training running performance may predict the magnitude of improvement due to MSS pace training.
Clinical and Physiological Effects of an Acute α-1 Adrenergic Agonist and a β-1 Adrenergic Antagonist in Chronic Orthostatic Intolerance
Authors: Julian M. Stewart, Jose Munoz, Amy Weldon
Journal: Circulation (2002)

Adrenergic agents are commonly used in the treatment of chronic orthostatic intolerance with postural tachycardia syndrome (POTS). POTS may be associated with increased limb blood flow ("high flow") and defective orthostatic vasoconstriction or decreased limb blood flow ("low flow") and potentially with small blood volume.We investigated the consequences of short-term intravenous administration of an alpha-1 adrenergic agonist, phenylephrine, and a beta-1 adrenergic antagonist, esmolol, in 14 patients with POTS aged 13 to 19 years. Indices of heart rate and blood pressure variability, peripheral blood flow, and arterial resistance were assessed, and the capacitance relation was computed for every subject using venous occlusion plethysmography. Patients were tilted to 35 degrees upright while medicated and while unmedicated, and measurements were repeated. Phenylephrine improved orthostatic tolerance and normalized hemodynamics and indices of heart rate/blood pressure variability while supine and while upright, producing significant peripheral vasoconstriction and venoconstriction (20% capacitance change). Esmolol did not improve orthostatic tolerance or hemodynamics. A subgroup of low-flow POTS patients had exaggerated venoconstriction to phenylephrine (50% capacitance change) but others had no response.Phenylephrine, but not esmolol, improves orthostatic tolerance and hemodynamics in POTS. This lends support to the use of oral alpha-1 agonists in the treatment of patients with chronic orthostatic intolerance.
LSC 2014 abstract - The ability of lung parenchymal fibroblasts to interact with T cells
Authors: Andrew Hutton, Tom Wilkinson, Jane Warner
Journal: European Respiratory Journal (2014)

Lung fibroblasts are one of the most numerous mesenchymal cells, located directly beneath the epithelia. Fibroblasts secrete the extracellular matrix and provide the structural means for immune cells to move within the tissue. However there is now a growing appreciation of their ability to influence immune cells during inflammation. Successful interaction with T cells typically involves expression of the molecules of the immune synapse as well as uptake of exogenous material into vesicles. Human lung fibroblast were grown out from explants of resected tissue and were exposed to varying levels of IFN-γ (0-1000U) and the expression of immune synapse molecules HLA-DR/DP/DQ, ICAM-1 and CD80/86 measured via flow cytometry at 48 hours. Fibroblasts were shown to express HLA and ICAM-1, with HLA increasing 6-foldb (N=10, P<0.0001) and ICAM-1 3-fold(N=11,P<0.005) following exposure to IFN-γ. CD80/86 were not initially expressed and were not upregulated by IFN-γ. Co-culture assays further demonstrated that activated T cells (5ug PHA, 48 hours) have a greater adherence to lung fibroblasts than inactive T cells and stimulating the fibroblasts with IFN-γ further increases adhesion. Blocking experiments with anti-ICAM-1 antibody reduced adhesion. Using a combination of flow cytometry and confocal microscopy, fibroblasts were shown to internalize exogenous particles into vesicles. The current study highlights that lung fibroblasts have the potential to interact with immune cells, via immune synapse molecules HLA and ICAM-1, promote T cell adhesion within tissues, and have the capability to internalize environmental proteins, a trait of antigen presenting cells.
Compensation for time delays is better achieved in time than in space
Authors: Myrka Zago, Francesco Lacquaniti
Journal: Behavioral and Brain Sciences (2008)

Abstract Mechanisms of visual prediction based on spatial extrapolation work only for targets moving at constant speed, but do not easily accommodate accelerating or decelerating motion. We argue that mechanisms based on temporal extrapolation deal with both uniform and non-uniform motion. We provide behavioural examples from interception of falling objects and suggest possible neurophysiological substrates of time extrapolation.
Additional Value of Whole-Body Positron Emission Tomography With Fluorine-18-2-Fluoro-2-deoxy-<scp>d</scp>-glucose in Recurrent Colorectal Cancer
Authors: Patrick Flamen, Sigrid Stroobants, Eric Van Cutsem, Patrick Dupont, Guy Bormans, Nancy De Vadder, Freddy Penninckx, Lieven Van Hoe, Luc Mortelmans
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess the additional value of the whole-body [ 18 F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan as a staging modality complementing conventional diagnostic methods (CDM) in patients suspected of having recurrent colorectal adenocarcinoma. PATIENTS AND METHODS: In 103 patients, the discordances between FDG-PET and CDM results were identified and related to the final diagnosis obtained by histopathology or clinical follow-up (&gt; 1 year). All FDG-PET studies were reviewed with full knowledge of the CDM findings. RESULTS: In a region-based analysis, discordances between CDM and FDG-PET findings were found in 40 of 412 regions (10%). In these, FDG-PET had additional diagnostic value in 14 of 16 locoregional, six of seven hepatic, seven of eight abdominal, and eight of nine extra-abdominal regions. In a patient-based analysis, CDM categorized a subgroup of 60 patients as having resectable recurrent disease limited to the liver (n = 37) or locoregional region (n = 23). In 13 of these patients, there were discordant FDG-PET findings, detecting additional tumor sites in nine patients and excluding disease in three patients and yielding an additional diagnostic value in 20% of the patients. A second subgroup consisted of 13 patients with inconclusive CDM findings (n = 5) or with elevated plasma carcinoembryonic antigen levels and an otherwise negative conventional work-up (n = 8). In these patients, FDG-PET results were correct in eight of nine discordances, yielding a positive additional diagnostic value in 62% of the patients. CONCLUSION: Whole-body FDG-PET can have a clear impact on the therapeutic management in the follow-up of patients with colorectal cancer.
Testosterone Induces Cytoprotection by Activating ATP-Sensitive K <sup>+</sup> Channels in the Cardiac Mitochondrial Inner Membrane
Authors: Fikret Er, Guido Michels, Natig Gassanov, Francisco Rivero, Uta C. Hoppe
Journal: Circulation (2004)

Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent experimental data postulate a benefit of testosterone for recovery of myocardial function after ischemia/reperfusion injury. Thus, we examined whether testosterone might improve myocardial tolerance to ischemia due to activation of mitochondrial (mitoK(ATP)) and/or sarcoplasmatic (sarcK(ATP)) K(ATP) channels.In a cellular model of ischemia, testosterone significantly decreased the rate of ischemia-induced death of cardiomyocytes that could be prevented by 5-hydroxydecainoic acid but was unaffected by the sarcK(ATP) blocker HMR1098 and the testosterone receptor antagonist flutamide. To index mitoK(ATP), mitochondrial flavoprotein fluorescence was measured. Testosterone induced a highly significant increase in mitochondrial flavoprotein fluorescence in intact myocytes and isolated mitoplasts that could be abolished by 5-hydroxydecainoic acid. Testosterone-mediated flavoprotein oxidation of mitoplasts was K+ dependent and ATP sensitive. In mitoplast-attached single-channel recordings, testosterone directly activated an ATP-sensitive K+ channel of the inner mitochondrial membrane. Addition of the K(ATP) channel opener diazoxide and pinacidil to the cytosolic solution activated the ATP-sensitive K+ current comparable to testosterone, whereas 5-hydroxydecainoic acid and glibenclamide inhibited the testosterone-induced current. Patch-clamp experiments of intact myocytes in whole-cell configuration did not demonstrate any effect of testosterone on sarcK(ATP) channels.Our results provide direct evidence for the existence of cardiac mitoK(ATP) and a link between testosterone-induced cytoprotection and activation of mitoK(ATP). Endogenous testosterone might play a more important role in recovery after myocardial infarction than is currently assumed.
Effects of Cortisone, Hydrocortisone and Corticotropin on Lipemia, Glycemia and Atherogenesis in Cholesterol-Fed Chicks
Authors: JEREMIAH STAMLER, RUTH PICK, LOUIS N. KATZ
Journal: Circulation (1954)

Hydrocortisone markedly affected carbohydrate, protein, lipid and electrolyte metabolism of cholesterol-fed cockerels (intact, alloxanized and depancreatized). Despite steroid-induced diabetes and hyperadrenalism, associated with enhancement of hypercholesterolemic hyperlipemia, no hypertension or intensification of atherogenesis (aortic or coronary artery) supervened. Corticotropin (ACTH) produced similar effects. Cortisone was relatively inactive as a glycocorticoid in this avian species. Despite its apparently slight metabolic activity, however, it moderately elevated blood pressure and intensified atherogenesis.
Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation
Authors: Maria M Bartholomew, Robert W Jansen, Lennox J Jeffers, K Rajender Reddy, Lance C Johnson, Hartwig Bunzendahl, Lynn D Condreay, Andreas G Tzakis, Eugene R Schiff, Nathaniel A Brown
Journal: The Lancet (1997)

BackgroundOrthotopic liver transplantation for end-stage hepatitis-B-virus (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a cytosine nucleoside analogue, has been shown to suppress HBV infection. We report the development of resistance to lamivudine in three patients who underwent transplantation for end-stage liver disease secondary to hepatitis B.MethodsTwo of the patients received lamivudine for recurrent HBV infection after transplantation, whereas the third patient began treatment 1 month before transplantation in an attempt to prevent HBV recurrence after transplantation. The three patients initially responded well to treatment, but viral recurrence occurred after 9–10 months of treatment in all patients. HBV DNA was amplified from serum and sequenced through a conserved polymerase domain—the tyrosine, methionine, aspartate, aspartate (YMDD) locus. We assessed the susceptibility of HBV to lamivudine by infecting primary human hepatocytes with serum taken before the start of treatment and after recurrence in varying concentrations of lamivudine.FindingsDNA sequencing showed a common mutation within the YMDD locus of the HBV polymerase gene in all patients during lamivudine treatment. In hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were reduced to less than 6% of those in control cultures by addition of lamivudine in concentrations as low as 0·03 μol/ L. By contrast, in cultures treated with serum taken after recurrence, HBV DNA concentrations did not fall below 20% of control values, even with lamivudine at 30 μmol/ L.InterpretationResistance to lamivudine has been reported in HIV patients with mutations in the YMDD locus of the polymerase gene. Our findings indicate a common mechanism of lamivudine resistance for HIV and HBV that involves similar point mutations in homologous domains of the viral polymerases.
Dopamine D<sub>4</sub> Gene 7-Repeat Allele and Attention Deficit Hyperactivity Disorder
Authors: Stephen V. Faraone, Joseph Biederman, Barbara Weiffenbach, Tim Keith, Monica P. Chu, Alix Weaver, Thomas J. Spencer, Timothy E. Wilens, Jean Frazier, Mario Cleves, Jun Sakai
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat al­leles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.
Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis
Authors: Antoni Torres, Catia Cillóniz, Miquel Ferrer, Albert Gabarrús, Eva Polverino, Santiago Villegas, Francesc Marco, Josep Mensa, Rosario Menéndez, Michael Niederman
Journal: European Respiratory Journal (2015)

The sensitivity of blood cultures in the diagnosis of bacteraemia for community-acquired pneumonia is low. Recommendations, by guidelines, to perform blood cultures are discordant. We aimed to determine the incidence, microbial aetiology, risk factors and outcomes of bacteraemic patients with community-acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A prospective, observational study was undertaken on consecutive adult patients admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community-acquired pneumonia and blood cultures were obtained. Of the 2892 patients included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP (multidrug-resistant Streptococcus pneumoniae , methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa , and an extended spectrum of beta-lactamase producing Enterobacteriaceae ). In multivariate analyses, pleuritic pain, C-reactive protein ≥21.6 mg·dL −1 and intensive care unit admissions were independently associated with bacteraemia, while prior antibiotic treatment and pneumococcal vaccine were protective factors. The risk factors for ARP bacteraemia were previous antibiotics and C-reactive protein &lt;22.2 mg·dL −1 , while pleuritic pain was the only protective factor in the multivariate analysis. Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease, arterial oxygen tension/inspiratory oxygen fraction &lt;250, pneumonia severity index risk classes IV and V, and intensive care unit admission were independently associated with a 30-day hospital mortality in the multivariate analysis. Inappropriate therapy was more frequent in ARP bacteraemia, compared with other bacteraemias (27% versus 3%, respectively, p&lt;0.001). Antibiotic therapy protected against bacteraemia, but increased specifically the risk of bacteraemia from ARP due to the inappropriate coverage of these pathogens. Identifying patients at risk of ARP bacteraemia would help in deciding appropriate empiric antimicrobial therapy. The results from this study provide evidence concerning community-acquired pneumonia patients in whom blood cultures should not be performed.