tbuckley/cabot-search huggingface dataset:
Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma
Authors: J K Shute
Journal: Thorax (2004)

The most characteristic structural change evident in endobronchial biopsies in asthma, even in mild disease, is subepithelial collagen deposition within the lamina reticularis. This has been associated with progressive loss of lung function and the persistence of airway hyperresponsiveness, and has been linked to airway fibroblast proliferation. A potent fibroproliferative factor in bronchoalveolar lavage fluid in asthma is fibroblast growth factor-2 (FGF-2). FGF-2 is a member of a family of heparin binding growth factors that bind to heparan sulphate proteoglycans (HSPG), an important determinant of FGF-2 activity. This study compared the level of expression and distribution of FGF-2 in relation to HSPG in bronchial tissue from normal and asthmatic subjects.The distribution of FGF-2 and HSPG in intact and cleaved forms in endobronchial biopsies from normal and asthmatic subjects was examined using an immunohistochemical approach. A novel ELISA based method was developed to detect solubilisation of FGF-2 following addition of heparin and heparitinase to bronchial tissue slices.Immunohistochemical analysis showed that FGF-2 was co-localised to HSPG in epithelial and endothelial basement membranes. Epithelial FGF-2, but not HSPG, was significantly more abundant in patients with mild asthma than in normal subjects. In vitro experiments indicated that FGF-2 was released from binding sites in the tissue by heparin and heparitinase I.FGF-2 is bound by HSPG in bronchial tissue. The mast cell, through the release of heparin and endoglycosidase, may make a unique contribution to tissue remodelling in allergic asthma.
Persistent B19 Parvovirus Infection in Patients Infected with Human Immunodeficiency Virus Type 1 (HIV-1): A Treatable Cause of Anemia in AIDS
Authors: N Frickhofen, J L Abkowitz, M Safford, J M Berry, J Antunez-de-Mayolo, A Astrow, R Cohen, I Halperin, L King, D Mintzer
Journal: Annals of Internal Medicine (1990)

Objective: To determine the role of B19 parvovirus in red cell aplasia of patients infected with human immunodeficiency virus type 1 (HIV-1). Design: Uncontrolled clinical trial, with assay of serum, peripheral blood cells, and bone marrow for virus using DNA hybridization and immunocytochemistry techniques; these assays were then correlated with clinical findings, results of immunoassays for antivirus antibodies, and with immunoglobulin (Ig) therapy. Setting: Government medical referral center, and university and private hospitals. Patients: Seven patients with pure red cell aplasia and serologic evidence of infection with HIV-1. Measurements and Main Results: All patients had giant pronormoblasts in the bone marrow (present in transient aplastic crisis caused by acute B19 parvovirus infection). High concentrations of B19 parvovirus were demonstrated in sera, in several cases in samples separated by weeks or months. Viral DNA and capsid protein were present in the bone marrow of three patients studied, and active viral replication was detected by southern analysis. There was no antivirus IgG in capture immunoassay and no or very low levels of antivirus IgM. The patients did not have symptoms of fifth disease, the illness caused by this virus in immunologically normal persons. Six patients were treated with a regimen of intravenous commercial immunoglobulin. In all cases, this therapy resulted in rapid reduction in serum virus concentrations and full recovery of erythropoiesis. Relapses in two cases were predicted by DNA hybridization studies, and these cases were successfully retreated. Conclusions: The B19 parvovirus is a remediable cause of severe chronic anemia in HIV-infected patients. Recognition of and therapy for parvovirus in this population will avoid erythrocyte transfusion and should prevent transmission of the virus to other persons, including immunosuppressed persons and women of child-bearing age.
Screening for tuberculosis: the port of arrival scheme compared with screening in general practice and the homeless
Authors: G H Bothamley
Journal: Thorax (2002)

Tuberculosis is increasing in London, especially in those recently entering the UK from an area of high incidence. Screening through the port of arrival scheme has a poor yield and has been considered discriminatory.A study was undertaken to compare the yield and costs of screening new entrants in a hospital based new entrants' clinic (1262 referrals from the port of arrival), general practice (1311 new registrations), and centres for the homeless (267 individuals) using a symptom questionnaire and tuberculin testing if indicated. Clinical outcome measures were cases of tuberculosis, tuberculin reactors requiring chemoprophylaxis and BCG vaccinations. Cost outcomes were cost per individual screened and cost per individual per case of tuberculosis prevented.Verbal screening limited tuberculin testing to 16% of those in general practice; most were tested at the other two locations. Intervention (BCG vaccination, chemoprophylaxis or treatment) occurred in 27% of those who received tuberculin testing. Attendance for screening was 17% of the port of arrival notifications (63% had registered with a GP), 54% in primary care, and 67% in the homeless (42% registered with a GP). Costs for screening an individual in general practice, hostels for the homeless, and the new entrants' clinic were 1.26 pounds sterling, 13.17 pounds sterling and 96.36 pounds sterling, respectively, while the cost per person screened per case of tuberculosis prevented was 6.32 pounds sterling, 23.00 pounds sterling, and 10.00 pounds sterling, respectively. The benefit of screening was highly sensitive to the number of cases of tuberculosis identified and case holding during treatment.Screening for tuberculosis in primary care is feasible and could replace hospital screening of new arrivals for those registered with a GP.
A Coupled SYSTEM of Intracellular Ca <sup>2+</sup> Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker
Authors: Edward G. Lakatta, Victor A. Maltsev, Tatiana M. Vinogradova
Journal: Circulation Research (2010)

Abstract: Ion channels on the surface membrane of sinoatrial nodal pacemaker cells (SANCs) are the proximal cause of an action potential. Each individual channel type has been thoroughly characterized under voltage clamp, and the ensemble of the ion channel currents reconstructed in silico generates rhythmic action potentials. Thus, this ensemble can be envisioned as a surface “membrane clock” (M clock). Localized subsarcolemmal Ca 2+ releases are generated by the sarcoplasmic reticulum via ryanodine receptors during late diastolic depolarization and are referred to as an intracellular “Ca 2+ clock,” because their spontaneous occurrence is periodic during voltage clamp or in detergent-permeabilized SANCs, and in silico as well. In spontaneously firing SANCs, the M and Ca 2+ clocks do not operate in isolation but work together via numerous interactions modulated by membrane voltage, subsarcolemmal Ca 2+ , and protein kinase A and CaMKII-dependent protein phosphorylation. Through these interactions, the 2 subsystem clocks become mutually entrained to form a robust, stable, coupled-clock system that drives normal cardiac pacemaker cell automaticity. G protein–coupled receptors signaling creates pacemaker flexibility, ie, effects changes in the rhythmic action potential firing rate, by impacting on these very same factors that regulate robust basal coupled-clock system function. This review examines evidence that forms the basis of this coupled-clock system concept in cardiac SANCs.
Superoxide dismutase: Master and Commander?
Authors: E. K. Weir, Z. Hong, Y. Chen
Journal: European Respiratory Journal (2010)

Inhaled nitric oxide (NO) has long been known to be an effective pulmonary vasodilator in the normal pulmonary vasculature. In the classical NO signalling pathway, it activates soluble guanylate cyclase in the cytoplasm of pulmonary artery smooth muscle cells, leading to the production of cyclic guanosine monophosphate (cGMP), which then activates protein kinase G (PKG). PKG, acting through several downstream targets, causes vasodilatation. In addition, NO acts through induction of post-translational changes, such as S -nitrosylation of proteins with reactive thiols. NO levels are decreased in idiopathic pulmonary arterial hypertension (IPAH) 1, 2, in patients with PAH secondary to anorectic agents 3 and in infants with persistent pulmonary hypertension of the newborn (PPHN) 4. In part, NO is decreased because of the reduced endothelial NO synthase (eNOS) that has been reported in PAH and in PPHN 5, 6. More recently, an additional mechanism has been described. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and IPAH patients have increased levels of ADMA in their blood and lungs 7. ADMA is metabolised by dimethylarginine dimethylaminohydrolase (DDAH) 1 or DDAH2, two enzymes encoded by different genes. Although solid evidence supporting a role for DDAH2 in the degradation of lung ADMA is not available, DDAH1 gene deletion in vascular endothelial cells causes accumulation of ADMA in the lung tissue of mice 8. Similarly, monocrotaline injection causes a decrease in lung DDAH1 expression and DDAH activity, leading to the accumulation of ADMA in rats, which may then contribute to the development of pulmonary hypertension 9. The increased ADMA levels provide another mechanism to explain the decreased NO levels in PAH. It is also worth noting that in IPAH patients, higher ADMA plasma levels correlate with …
Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults
Authors: Edward D. Siew, Lorraine B. Ware, Tebeb Gebretsadik, Ayumi Shintani, Karel G. M. Moons, Nancy Wickersham, Frederick Bossert, T. Alp Ikizler
Journal: Journal of the American Society of Nephrology (2009)

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has shown promise as a biomarker for the early detection of acute kidney injury (AKI) in fixed models of injury, but its ability to predict AKI and provide prognostic information in critically ill adults is unknown. We prospectively studied a heterogeneous population of 451 critically ill adults, 64 (14%) and 86 (19%) of whom developed AKI within 24 and 48 h of enrollment, respectively. Median uNGAL at enrollment was higher among patients who developed AKI within 48 h compared with those who did not (190 versus 57 ng/mg creatinine, P < 0.001). The areas under the receiver operating characteristic curves describing the relationship between uNGAL level and the occurrence of AKI within 24 and 48 h were 0.71 (95% Confidence Intervals [CI]: 0.63 to 0.78) and 0.64 (95% CI: 0.57 to 0.71), respectively. Urine neutrophil gelatinase-associated lipocalin remained independently associated with the development of AKI after adjustment for age, serum creatinine closest to enrollment, illness severity, sepsis, and intensive care unit (ICU) location, although it only marginally improved the predictive performance of the clinical model alone. A Cox proportional hazards model using time to first dialysis, adjusted for APACHE II score, suggested that uNGAL independently predicts severe AKI during hospitalization [HR 2.60, 95% CI:1.55 to 4.35]. In summary, although a single measurement of uNGAL exhibited moderate predictive utility for the development and severity of AKI in a heterogeneous ICU population, its additional contribution to conventional clinical risk predictors appears limited.
Expression of CD1a cells and VCAM in large airways and thoracic lymph nodes of fatal asthma
Authors: Erika Cagnoni, Diogenes Ferreira, Luiz Fernando Silva, Ana Laura Carvalho, Angela Santos, Maria Cristina Medeiros, Marisa Dolhnikoff, Klauss Rabe, Thais Mauad
Journal: European Respiratory Journal (2013)

Introduction: Dendritic cells (DCs) are initiators of the immune response in asthma and represent a heterogeneous class of antigen presenting cells. Little information is known about the expression of CD1a DCs in the airways and lymph nodes (LNs) of humans with asthma. VCAM (vascular cell adhesion molecule) mediates leukocyte accumulation in tissues and is induced by pro-inflammatory cytokines such as TNF-α, IL-1 and IL-4. Our objective was to study the expression of CD1a cells and VCAM in mediastinal LNs and in the airways of patients that have died of asthma.

Methods: We studied 10 non-smoker fatal asthma patients (FA) and 8 non-smoker individuals that died of non-pulmonary causes (controls, CTRLs). Immunohistochemistry was performed with antibodies against CD1a and VCAM. The total area stained with CD1a and VCAM antibodies was measured on the cortical area of the LNs and on the internal, airway smooth muscle and external layers of the cartilaginous airways.

Results: CD1a and VCAM stained in the airways and LNs of FA and CTRLs. No differences were found in the areas stained with CD1a and VCAM between FA and CTRLs. In fatal asthma CD1a+ stained area in the LNs correlated inversely with CD1a+ stained area in the internal (r = -0.697 p = 0.025) layer of the airways.

Conclusions: A fatal asthma episode is not associated with an increased expression of CD1 cells and VCAM in cartilaginous airways or thoracic LNs. In asthma however, CD1a DC cell traffic between the airway mucosa and LNs seems to be unidirectional.
The person as moralist account and its alternatives
Authors: Joshua Knobe
Journal: Behavioral and Brain Sciences (2010)

Abstract The commentators offer helpful suggestions at three levels: (1) explanations for the particular effects discussed in the target article; (2) implications of those effects for our understanding of the role of moral judgment in human cognition; and (3) more theoretical questions about the overall relationship between ordinary cognition and systematic science. The present response takes up these three issues in turn.
Clinical Correlates and Prognostic Significance of Six-minute Walk Test in Patients with Primary Pulmonary Hypertension
Authors: SHOICHI MIYAMOTO, NORITOSHI NAGAYA, TORU SATOH, SHINGO KYOTANI, FUMIO SAKAMAKI, MASATOSHI FUJITA, NORIFUMI NAKANISHI, KUNIO MIYATAKE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The six-minute walk test is a submaximal exercise test that can be performed even by a patient with heart failure not tolerating maximal exercise testing. To elucidate the clinical significance and prognostic value of the six-minute walk test in patients with primary pulmonary hypertension (PPH), we sought (1) to assess the relation between distance walked during the six-minute walk test and exercise capacity determined by maximal cardiopulmonary exercise testing, and (2) to investigate the prognostic value of the six-minute walk test in comparison with other noninvasive parameters. The six-minute walk test was performed in 43 patients with PPH, together with echocardiography, right heart catheterization, and measurement of plasma epinephrine and norepinephrine. Symptom-limited cardiopulmonary exercise testing was performed in a subsample of patients (n = 27). Distance walked in 6 min was significantly shorter in patients with PPH than in age- and sex-matched healthy subjects (297 ± 188 versus 655 ± 91 m, p < 0.001). The distance significantly decreased in proportion to the severity of New York Heart Association functional class. The distance walked correlated modestly with baseline cardiac output (r = 0.48, p < 0.05) and total pulmonary resistance (r = − 0.49, p < 0.05), but not significantly with mean pulmonary arterial pressure. In contrast, the distance walked correlated strongly with peak V˙ o 2 (r = 0.70, p < 0.001), oxygen pulse (r = 0.57, p < 0.01), and V˙ e-Vco 2 slope (r = − 0.66, p < 0.001) determined by cardiopulmonary exercise testing. During a mean follow-up period of 21 ± 16 mo, 12 patients died of cardiopulmonary causes. Among noninvasive parameters including clinical, echocardiographic, and neurohumoral parameters, only the distance walked in 6 min was independently related to mortality in PPH by multivariate analysis. Patients walking < 332 m had a significantly lower survival rate than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.01). These results suggest that the six-minute walk test, a submaximal exercise test, reflects exercise capacity determined by maximal cardiopulmonary exercise testing in patients with PPH, and it is the distance walked in 6 min that has a strong, independent association with mortality. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, Nakanishi N, Miyatake K. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: comparison with cardiopulmonary exercise testing.
ANCA antibodies in Graves' disease
Authors: M Guma
Journal: Annals of the Rheumatic Diseases (2002)

Several drugs have been associated with antineutrophil cytoplasmic antibodies (ANCA) positivity—namely, hydralazine, penicillamine, allopurinol, and propylthiouracil.1

Although propylthiouracil is often implicated in the induction of ANCA positive vasculitis,2,3 other antithyroid drugs, such as carbimazole and thiamazole, have been linked.4,5 Furthermore, ANCA positivity has been described in the course of Graves' disease without vasculitis.6

This study aimed at determining the frequency and specificity of ANCA in a series of patients with Graves' disease.

We retrospectively examined 35 serum samples from patients with Graves' disease. Diagnosis of the disease was based on typical signs and symptoms of hyperthyroidism, raised serum …
Nuclear Factor-κB, an Unappreciated Tumor Suppressor
Authors: Fei Chen, Vince Castranova
Journal: Cancer Research (2007)

Abstract The notion that nuclear factor-κB (NF-κB) is a tumor-promoting transcription factor has become a widely accepted dogma in biology. However, recent findings suggest an inhibitory role for NF-κB in carcinogenesis and tumorigenesis. Although the tumor suppressor–like effect of NF-κB remains to be rigorously established by further studies using cellular and animal models, these latest findings warrant caution with respect to blockage of NF-κB activation as a broad strategy in treating cancers. [Cancer Res 2007;67(23):11093–8]
Association of Improved Air Quality with Lung Development in Children
Authors: W. James Gauderman, Robert Urman, Edward Avol, Kiros Berhane, Rob McConnell, Edward Rappaport, Roger Chang, Fred Lurmann, Frank Gilliland
Journal: New England Journal of Medicine (2015)

Air-pollution levels have been trending downward progressively over the past several decades in southern California, as a result of the implementation of air quality-control policies. We assessed whether long-term reductions in pollution were associated with improvements in respiratory health among children.As part of the Children's Health Study, we measured lung function annually in 2120 children from three separate cohorts corresponding to three separate calendar periods: 1994-1998, 1997-2001, and 2007-2011. Mean ages of the children within each cohort were 11 years at the beginning of the period and 15 years at the end. Linear-regression models were used to examine the relationship between declining pollution levels over time and lung-function development from 11 to 15 years of age, measured as the increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) during that period (referred to as 4-year growth in FEV1 and FVC).Over the 13 years spanned by the three cohorts, improvements in 4-year growth of both FEV1 and FVC were associated with declining levels of nitrogen dioxide (P<0.001 for FEV1 and FVC) and of particulate matter with an aerodynamic diameter of less than 2.5 μm (P= 0.008 for FEV1 and P<0.001 for FVC) and less than 10 μm (P<0.001 for FEV1 and FVC). These associations persisted after adjustment for several potential confounders. Significant improvements in lung-function development were observed in both boys and girls and in children with asthma and children without asthma. The proportions of children with clinically low FEV1 (defined as <80% of the predicted value) at 15 years of age declined significantly, from 7.9% to 6.3% to 3.6% across the three periods, as the air quality improved (P = 0.001).We found that long-term improvements in air quality were associated with statistically and clinically significant positive effects on lung-function growth in children. (Funded by the Health Effects Institute and others.).
TRANSMISSION OF SIMIAN AIDS WITH TYPE D RETROVIRUS ISOLATE
Authors: Maneth Gravell, WilliamT. London, RebeccaS. Hamilton, JohnL. Sever, AlbertZ. Kapikian, Gopal Murti, LarryO. Arthur, RaymondV. Gilden, KentG. Osborn, PrestonA. Marx, RoyV. Henrickson, MurrayB. Gardner
Journal: The Lancet (1984)
Oral Administration of Tetrahydrobiopterin Prevents Endothelial Dysfunction and Vascular Oxidative Stress in the Aortas of Insulin-Resistant Rats
Authors: Kazuya Shinozaki, Yoshihiko Nishio, Tomio Okamura, Yuichi Yoshida, Hiroshi Maegawa, Hideto Kojima, Masahiro Masada, Noboru Toda, Ryuichi Kikkawa, Atsunori Kashiwagi
Journal: Circulation Research (2000)

We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(-)) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH(4) on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for 8 weeks significantly increased the BH(4) content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. The BH(4) treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats. The BH(4) treatment of control rats did not have any significant effects on these parameters. These results indicate that BH(4) augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.