tbuckley/cabot-search huggingface dataset:
Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models
Authors: D. Edo-Matas, P. Lemey, J. A. Tom, C. Serna-Bolea, A. E. van den Blink, A. B. van 't Wout, H. Schuitemaker, M. A. Suchard
Journal: Molecular Biology and Evolution (2010)

The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically relevant populations. Similar inference problems are proliferating across many measurably evolving pathogens for which intrahost sequence samples are readily available. To this end, we propose novel hierarchical phylogenetic models (HPMs) that incorporate fixed effects to test for differences in dynamics across host populations in a formal statistical framework employing stochastic search variable selection and model averaging. To clarify the role of CCR5 host genetic background and disease progression on viral evolutionary patterns, we obtain gp120 envelope sequences from clonal HIV-1 variants isolated at multiple time points in the course of infection from populations of HIV-1–infected individuals who only harbored CCR5-using HIV-1 variants at all time points. Presence or absence of a CCR5 wt/Δ32 genotype and progressive or long-term nonprogressive course of infection stratify the clinical populations in a two-way design. As compared with the standard approach of analyzing sequences from each patient independently, the HPM provides more efficient estimation of evolutionary parameters such as nucleotide substitution rates and dN/dS rate ratios, as shown by significant shrinkage of the estimator variance. The fixed effects also correct for nonindependence of data between populations and results in even further shrinkage of individual patient estimates. Model selection suggests an association between nucleotide substitution rate and disease progression, but a role for CCR5 genotype remains elusive. Given the absence of clear dN/dS differences between patient groups, delayed onset of AIDS symptoms appears to be solely associated with lower viral replication rates rather than with differences in selection on amino acid fixation.
Ontogeny of culture-generated suppressor cells.
Authors: F M Rollwagen, O Stutman
Journal: The Journal of Experimental Medicine (1979)

Culture of murine lymphoid cells without added antigen results in the generation of cells which suppress a variety of in vitro immune responses, such as the mixed lymphocyte response (MLR) and the generation of alloreactive cytotoxic T cells (CTL). The ontogeny of this phenomenon was studied. Cells which suppressed the MLR after preculture were isolated from spleens and hematopoietic livers of fetal and young (less than 1 wk old) mice. On the other hand, the generation of alloreactive CTL could be suppressed only by precultured spleen cells taken from 1-w-old or older mice. The parallel between the development of the suppressor functions and the maturation of the responses they regulate, suggests a possible biological significance of the effect.
The ageing of lung function: cross-sectional and longitudinal studies of an Inuit community
Authors: A Rode, RJ Shephard
Journal: European Respiratory Journal (1994)

Three surveys (1969/1970, 1979/1980 and 1989/1990) have examined the impact of acculturation to a sedentary lifestyle on the pulmonary function of a circumpolar native Inuit community. The sample comprised more than 50% of those aged 20-60 yrs, most recently 119 males and 92 females. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MMEF) were measured by standard spirometric techniques, and information was obtained on smoking habits and health. Multiple regression equations showed that lung function was affected by height and age, but usually not by age squared. Cross-sectional age coefficients for FVC and FEV1 increased over the period 1969/1970 to 1989/1990. Parallel longitudinal trends were seen in FEV1 (males only). Multiple analysis of variance (MANOVA) showed age-decade*cohort effects for FVC and FEV1 (males but not females). Almost all of the population now smoke (mean +/- SD males 13 +/- 8 cigarettes.day-1; females 11 +/- 7 cigarettes.day-1). However, smoking bears little relationship to lung function perhaps due to limited variance in consumption. About a third of the community have physician-diagnosed and/or radiographically visible chest disease, but with little effect upon pulmonary function. We conclude that an apparent secular trend to a faster ageing of lung function in men is not explained by disease or domestic air pollution. Possible factors include increased lung volumes in young adults, greater pack-years of cigarette exposure, nonspecific respiratory disease, increased inspiration of cold air or altered chest mechanics due to operation of high-speed snowmobiles, and loss of physical fitness.
Mechanism Underlying Initiation of Paroxysmal Atrial Flutter/Atrial Fibrillation by Ectopic Foci
Authors: Yunfan Gong, Fagen Xie, Kenneth M. Stein, Alan Garfinkel, Calin A. Culianu, Bruce B. Lerman, David J. Christini
Journal: Circulation (2007)

Background— The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear. Methods and Results— We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte. At the single-cell level, upregulation of the L-type Ca 2+ current I Ca,L steepened restitution curves of action potential duration and conduction velocity compared with the control. Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated I Ca,L case. For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length. For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium. The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node. Conclusions— These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.
Locally rational decision-making
Authors: Richard M. Shiffrin
Journal: Behavioral and Brain Sciences (2003)

Colman shows that normative theories of rational decision-making fail to produce rational decisions in simple interactive games. I suggest that well-formed theories are possible in local settings, keeping in mind that a good part of each game is the generation of a rational approach appropriate for that game. The key is rationality defined in terms of the game, not individual decisions.
Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension
Authors: Michael J. Krowka, Robert P. Frantz, Michael D. McGoon, Cathy Severson, David J. Plevak, Russell H. Wiesner
Journal: Hepatology (1999)

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as “portopulmonary hypertension.” Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] ≥35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (−34% ± 18%), MPAP (−16% ± 10%), and cardiac output (CO) (+21 ± 18%), were statistically significant (P &lt; .01). Long-term use of epoprostenol further lowered PVR (−47% ± 12% from baseline and −31% ± 22% from the acute change; P &lt; .05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.
The Amount of Ferritin and Hemosiderin in the Livers of Patients with Iron-Loading Diseases
Authors: Floris M. J. Zuyderhoudt, Jan W. Sindram, Joannes J. M. Marx, George G. A. Jorning, Jacobus Van Gool
Journal: Hepatology (2007)

Depot iron, ferritin iron, and ferritin protein were measured in 34 liver needle biopsy specimens obtained from patients with primary and secondary iron-loading diseases. The patients were classified as idiopathic hemochromatosis (14), porphyria cutanea tarda (4), and iron-loading anemias (16). With accumulation of depot iron, the amount of liver ferritin protein increased, however, the ratio of ferritin protein to depot iron fell at concentrations of depot iron in excess of 1,000 m̈er gm of liver. The liver ferritin protein concentration was not influenced by the specific kind of the iron storage disorder. The mean iron content of ferritin molecules increased about 50% in profound iron overload. In low grade iron overload, the bulk of depot iron was present as ferritin; however, in subjects with heavy iron overload, depot iron consisted of approximately equal amounts of hemosiderin (nonferritin iron) and ferritin iron.
Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy
Authors: R. Dziadziuszko, B. Holm, B.G. Skov, K. Osterlind, M.V. Sellers, W.A. Franklin, P.A. Bunn, M. Varella-Garcia, F.R. Hirsch
Journal: Annals of Oncology (2006)
Effect of Nurse Case Management Compared With Usual Care on Controlling Cardiovascular Risk Factors in Patients With Diabetes
Authors: Areef Ishani, Nancy Greer, Brent C. Taylor, Laurie Kubes, Paula Cole, Melissa Atwood, Barbara Clothier, Nacide Ercan-Fang
Journal: Diabetes Care (2011)

To determine whether nurse case management with a therapeutic algorithm could effectively improve rates of control for hypertension, hyperglycemia, and hyperlipidemia compared with usual care among veterans with diabetes.A randomized controlled trial of diabetic patients that had blood pressure (BP) >140/90 mmHg, hemoglobin A(1c) (HbA(1c)) >9.0%, or LDL >100 mg/dL. Intervention patients received case management (n = 278) versus usual care (n = 278) over a 1-year period. The primary outcome was the percentage of patients achieving simultaneous control of all three parameters (defined by BP <130/80 mmHg, HbA(1c) <8.0%, and LDL <100 mg/dL) at 1 year. Secondary outcomes included improvements within each individual component of the composite primary outcome. Differences between groups were analyzed using t tests, Pearson χ(2) tests, and linear and logistic regression.A greater number of individuals assigned to case management achieved the primary study outcome of having all three outcome measures under control (61 [21.9%] compared with 28 [10.1%] in the usual care group [P < 0.01]). In addition, a greater number of individuals assigned to the intervention group achieved the individual treatment goals of HbA(1c) <8.0% (73.7 vs. 65.8%, P = 0.04) and BP <130/80 mmHg (45.0 vs. 25.4%, P < 0.01), but not for LDL <100 mg/dL (57.6 vs. 55.4%, P = 0.61), compared with those in the usual care group.In patients with diabetes, nurse case managers using a treatment algorithm can effectively improve the number of individuals with control of multiple cardiovascular risk factors at 1 year.
II. APLASIA OF MARROW AND FATAL INTOXICATION IN DOGS PRODUCED BY ROENTGEN RADIATION OF ALL BONES
Authors: Samuel S. Shouse, Stafford L. Warren, George H. Whipple
Journal: The Journal of Experimental Medicine (1931)

Constant findings were obtained in the acute reaction to the specified amount of heavily filtered radiation over the bony skeleton. 1. There develops without warning a short and fatal intoxication on the 8th or 9th day after the exposure to the radiation. 2. A profound leucopenia appears after 5 to 6 days and is maintained in the peripheral blood (200 white blood cells or less per c. mm.) for the 2 to 3 days before death. 3. The platelets suddenly disappear from the blood smears the day before death. This has some bearing on the life cycle of the platelet. 4. All of the organs and body structures present extensive and generalized capillary hemorrhage of recent origin. 5. The substance of the spleen and lymph nodes is greatly reduced and the germinal centers are visible only as remnants. 6. The red cell hematocrit reading drops from about 50 per cent or normal to approximately 40 per cent. 7. The bone marrow is depleted of all its cells except the connective tissue and fat cells, blood vessel endothelium, phagocytes filled with brown granules, and occasional normoblasts.
Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis.
Authors: N Odum, N Morling, P Platz, B Hofmann, L.P Ryder, C Heilmann, F.K Pedersen, L.P Nielsen, J Friis, A Svejgaard
Journal: Annals of the Rheumatic Diseases (1987)

The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 patients with active juvenile chronic arthritis (JCA), 10 patients with JCA in remission, and 11 age matched, healthy controls. In addition, the distribution of T 9helper/inducer9 (CD4+), T 9suppressor/inducer9 (CD4+, Leu8+), T 9suppressor/cytotoxic9 (CD8+), and 9natural killer9 (NK) cells (CD16+) was studied. Twenty patients and six controls were investigated for the capability to stimulate alloreactivated primed lymphocytes. The prevalence of VLA-1 positive, large cells was significantly increased to 5% (median value) in active JCA as compared with JCA in remission (2%, p less than 0.05) and controls (1%, p less than 0.05), whereas no significant difference between JCA in remission and controls was observed. Except for two patients with active JCA, less than 1% IL2 receptor bearing cells were found in patients with JCA and controls. No significant difference in the prevalence and expression of the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA, JCA in remission, and controls. The prevalence of T suppressor/inducer (CD4+,Leu8+) cells was higher in remission JCA (17%) than in active JCA (11%) and controls (10%). This increase, however, did not reach statistical significance. In conclusion, late stage but not early stage T cell activation antigens were increased in patients with active JCA as compared with patients with JCA in remission and control, whereas some patients in remission had an increased prevalence of T suppressor/inducer cells.
IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations <i>In Vivo</i>
Authors: David J. Jackson, Heidi Makrinioti, Batika M. J. Rana, Betty W. H. Shamji, Maria-Belen Trujillo-Torralbo, Joseph Footitt, None Jerico del-Rosario, Aurica G. Telcian, Alexandra Nikonova, Jie Zhu, Julia Aniscenko, Leila Gogsadze, Eteri Bakhsoliani, Stephanie Traub, Jaideep Dhariwal, James Porter, Duncan Hunt, Toby Hunt, Trevor Hunt, Luminita A. Stanciu, Musa Khaitov, Nathan W. Bartlett, Michael R. Edwards, Onn Min Kon, Patrick Mallia, Nikolaos G. Papadopoulos, Cezmi A. Akdis, John Westwick, Matthew J. Edwards, David J. Cousins, Ross P. Walton, Sebastian L. Johnston
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation.To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway.We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade.IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33.IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33-responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.
The modulation of attachment, growth and morphology of cancerous prostate cells by polyelectrolyte nanofilms
Authors: Nathalie Picollet-D'hahan, Sophie Gerbaud, Frédérique Kermarrec, Jean-Pierre Alcaraz, Patricia Obeid, Ricky Bhajun, Laurent Guyon, Eric Sulpice, Philippe Cinquin, Monika E. Dolega, Jayesh Wagh, Xavier Gidrol, Donald K. Martin
Journal: Biomaterials (2013)

The behaviour of cancerous epithelial prostatic cells (PC3) growing on polyelectrolytes (PE) coatings was compared to the behaviour of immortalized normal prostatic cells (PNT-2). The cell behaviour was evaluated and quantified in terms of initial cell attachment, growth, metabolic activity, morphometry, adhesion, apoptosis and stress related gene expression. Both the anionic PSS (poly(sodium 4-styrenesulphonate))-terminated surface and cationic PAH (poly(allylamine hydrochloride))-terminated surfaces were not cytotoxic. The initial attachment of cells was better on the PAH-terminated surface compared to fibronectin. However, the proliferation rate of PC3 cells was reduced on the PAH-terminated surface and slightly increased on the PSS coatings. Only PAH prevented the clustering phenotype of PC3 and reduced the number of focal adhesion points as compared to fibronectin or PSS coatings. In contrast, none of the PE surfaces significantly affected the biological responses of PNT-2 cells. PAH-terminating films provide a tool to preferentially modulate the growth of some cancerous phenotypes, in this case as a micro-environment that reduces the growth of metastatic PC3 cells.
Essential Role of the NADPH Oxidase Subunit p47 <sup>phox</sup> in Endothelial Cell Superoxide Production in Response to Phorbol Ester and Tumor Necrosis Factor-α
Authors: Jian-Mei Li, Adrian M. Mullen, Sheng Yun, Frans Wientjes, Gabi Y. Brouns, Adrian J. Thrasher, Ajay M. Shah
Journal: Circulation Research (2002)

A phagocyte-type NADPH oxidase complex is a major source of endothelial reactive oxygen species (ROS) production, but its biochemical function and regulation remain unclear. In neutrophils, the p47(phox) subunit is centrally involved in oxidase activation in response to agonists such as phorbol-12-myristate-13-acetate (PMA). We investigated the role of p47(phox) in endothelial cell ROS production in response to PMA or tumor necrosis factor-alpha (TNFalpha) stimulation. To specifically address the role of p47(phox), we studied coronary microvascular endothelial cells (CMECs) isolated from p47(phox-/-) mice and wild-type controls. p47(phox) was absent in hearts of knockout mice whereas the essential oxidase subunit, p22(phox), was expressed in both groups. In the absence of agonist stimulation, the lack of p47(phox) did not result in a reduction in NADPH-dependent ROS production in p47(phox-/-) CMECs compared with wild-type CMECs. Prestimulation with PMA (100 ng/mL) or TNFalpha (100 U/mL) for 10 minutes significantly increased NADPH-dependent O(2)(-) production in wild-type CMECs, assessed either by lucigenin (5 micromol/L) chemiluminescence or dichlorohydrofluorescein (DCF) fluorescence. This response was completely lost in p47(phox-/-) cells. Transfection of the full-length p47(phox) cDNA into p47(phox-/-) CMECs caused expression of p47(phox) protein and restoration of the O(2)(-) response to PMA and TNFalpha. In wild-type CMECs, transfection of antisense p47(phox) cDNA substantially reduced p47(phox) expression and caused loss of the O(2)(-) response to PMA and TNFalpha. These data show that endothelial cell p47(phox) is critical in the upregulation of NADPH oxidase activity by PMA and TNFalpha.
Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes
Authors: F HEINZEL, Y LUO, G DODONI, K BOENGLER, F PETRAT, F DILISA, H DEGROOT, R SCHULZ, G HEUSCH
Journal: Cardiovascular Research (2006)

Reactive oxygen species (ROS) play an ambivalent role in cardiomyocytes: low concentrations are involved in cellular signaling, while higher concentrations contribute to cellular injury. We studied ROS formation during increases in contraction frequency in isolated cardiomyocytes.Rat ventricular cardiomyocytes were loaded with dichlorodihydrofluorescein and electrically stimulated (37 degrees C). ROS formation was assessed by the rate of oxidation-dependent fluorescence increase (OxR). Oxygen consumption (VO(2)) and NAD(P)H autofluorescence were measured in parallel experiments.Increases in contraction frequency were accompanied by an increase in VO(2) and a decrease in NAD(P)H fluorescence. OxR increased to 124+/-4%, 146+/-8%, 204+/-25% and 256+/-29% of OxR at baseline during 1, 2, 3 and 4 Hz stimulation, and subsequently returned to baseline values with 0.2 Hz. The OxR increase was dose-dependently inhibited by the antioxidant NAC (10 and 100 mM), but unaffected by the NO synthase inhibitor l-NAME (200 microM and 10 mM). The OxR increase was attenuated when myosin ATPase activity was inhibited by butanedione monoxime (BDM; 5 mM).Increased contraction frequency induces ROS formation in rat cardiomyocytes.