tbuckley/cabot-search huggingface dataset:
An animal model for allergic penicilliosis induced by the intranasal instillation of viable Penicillium chrysogenum conidia
Authors: J D Cooley
Journal: Thorax (2000)

A study was undertaken to determine the consequences of long term intranasal instillation of Penicillium chrysogenum propagules in a mouse model.C57 Black/6 mice were inoculated intranasally each week for six weeks with 10(4) viable and non-viable P chrysogenum conidia. Cytokine levels and cellular responses in these animals were then measured.Compared with controls, mice inoculated intranasally each week for six weeks with 10(4) P chrysogenum conidia (average viability 25%) produced significantly more total serum IgE (mean difference 1823.11, lower and upper 95% confidence intervals (CI) 539.09 to 3107.13), peripheral eosinophils (mean difference 5.11, 95% CI 2.24 to 7.99), and airway eosinophilia (rank difference 11.33, 95% CI 9.0 to 20.0). With the exception of airway neutrophilia (mean difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intranasally with 10(4) non-viable conidia did not show significant changes in total serum IgE, peripheral or airway eosinophils. However, when compared with controls, this group (10(4) non-viable) had a significant increase in total serum IgG(2a) (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-gamma (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice inoculated intranasally with 10(4) viable P chrysogenum conidia had significantly increased levels of interleukin (IL)-4 (mean difference 285.28, 95% CI 108.73 to 461.82) and IL-5 (mean difference 16.61, 95% CI 11.23 to 21.99). The IgG(2a)/IgE ratio and the IFN-gamma/IL-4 ratio was lower in the group of mice inoculated intranasally with 10(4) viable conidia than in the 10(4) non-viable conidia group and the controls. When proteins were extracted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 10(4) viable group, significant increases in conidia-specific IgE and IgG(1) were observed compared with controls, while serum from the 10(4) non-viable group was similar to controls.These data suggest that long term inhalation of viable P chrysogenum propagules induces type 2 T helper cell mediated (Th2) inflammatory responses such as increases in total and conidia-specific serum IgE and IgG(1), together with BAL fluid levels of IL-4 and IL-5 and peripheral and airway eosinophilia, which are mediators of allergic reactions.
Switch to adalimumab in patients with Crohn's disease controlled by maintenance infliximab: prospective randomised SWITCH trial
Authors: Gert Van Assche, Séverine Vermeire, Vera Ballet, Frederik Gabriels, Maja Noman, Geert D'Haens, Christophe Claessens, Evelien Humblet, Niels Vande Casteele, Ann Gils, Paul Rutgeerts
Journal: Gut (2011)

<h3>Background</h3> Elective switching between anti-tumour necrosis factor (TNF) agents not necessarily dictated by efficacy or tolerability occurs in clinical practice. A study was undertaken to evaluate prospectively the impact of elective switching of patients with Crohn9s disease well controlled with intravenous infliximab to subcutaneous adalimumab in a controlled trial. <h3>Methods</h3> An open-label randomised single-centre trial recruited 73 patients with ongoing response to at least 6 months of scheduled maintenance infliximab. Patients were randomised to continue intravenous 5 mg/kg infliximab or to switch to subcutaneous adalimumab 80 mg at baseline followed by 40 mg every other week for 1 year. Dose optimisation was allowed for intermittent flares, and patients with loss of response or intolerance could cross over to the alternative treatment group. Tolerability, patient preference and efficacy of both treatment options were the primary outcomes. <h3>Results</h3> Dose optimisation or interruption of treatment occurred in 17/36 patients (47%) in the adalimumab group and in 6/37 patients (16%) in the infliximab group (p=0.006). One patient interrupted infliximab treatment and 10 patients interrupted adalimumab treatment (p=0.003), mostly for loss of tolerance. Overall, patients preferred adalimumab treatment. All five serious adverse events were related to complicated Crohn9s disease and occurred in patients randomised to adalimumab. Injection site reactions were more frequent than infusion reactions (8 vs 1, p=0.01), but only the latter caused cessation of further dosing. Anti-TNF serum levels were stable throughout the 1-year period in both groups. <h3>Conclusion</h3> Elective switching from infliximab to adalimumab is associated with loss of tolerance and loss of efficacy within 1 year. Adherence to the first anti-TNF agent is recommended.
Default Mode Network Activity and Connectivity in Psychopathology
Authors: Susan Whitfield-Gabrieli, Judith M. Ford
Journal: Annual Review of Clinical Psychology (2012)

Neuropsychiatric disorders are associated with abnormal function of the default mode network (DMN), a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks. In schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected. In schizophrenia this may relate to overly intensive self-reference and impairments in attention and working memory. In depression, DMN hyperactivity may be related to negative rumination. These findings are considered in terms of what is known about psychological functions supported by the DMN, and alteration of the DMN in other neuropsychiatric disorders.
A proposed classification system of central airway stenosis
Authors: L. Freitag, A. Ernst, M. Unger, K. Kovitz, C. H. Marquette
Journal: European Respiratory Journal (2007)

Tracheobronchial stenosis, a serious problem in adults and children, has multiple causes and has been treated in many ways. While developing an international multicentre study to evaluate efficacy of airway stents, it was realised that no adequate description of central airway stenosis regarding type, location and degree has been published. Thus, comparing results of different treatment modalities in different centres has been difficult due to a lack of uniformity of classification. Reports are typically descriptive and precise classification schemes have not adequately addressed either for the trachea or the main bronchi. A standardised classification scheme was proposed with descriptive images and diagrams for rapid and uniform classification of central airway stenosis. The present authors' system divides stenosis into structural and dynamic types and further classifies the disease by degree of stenosis, location and transition zone. Multiple sites can be described and each is transformed into a simple numerical scoring system prompted by a diagram, which can be easily captured for subsequent uniform analysis across sites. A pilot validation of the system, with 18 pulmonologists of varying training background, showed strong precision and agreement between observers. Such a system will enhance the ability to study the effectiveness of treatment modalities for central airway stenosis.
SPECIFICITY OF THE PRECIPITIN REACTION IN TOBACCO MOSAIC DISEASE
Authors: Helen Purdy Beale
Journal: The Journal of Experimental Medicine (1931)

1. Leaf extracts of Sudan grass, Hippeastrum equestre Herb., lily, and Abutilon striatum Dicks. (A. Thompsoni hort.), each affected with its respective mosaic disease, and peach affected with yellows disease, were tested for their ability to precipitate antiserum for virus extract of tobacco mosaic disease. No precipitate occurred. 2. Nicotiana glutinosa L., N. rustica L., and Martynia louisiana Mill. were added to the list of hosts of tobacco mosaic virus which have been tested with antiserum for the same virus in N. tabacum L. var. Turkish. The object was to determine the presence or absence of material reacting with the specific precipitins such as that already demonstrated in extracts of tomato, pepper, and petunia affected with the same virus. The presence of specific substances was demonstrated in every case. 3. The viruses of ringspot and cucumber mosaic diseases were multiplied in Turkish tobacco and leaf extracts of the affected plants were used in turn as antigens in precipitin tests with antiserum for tobacco mosaic virus extract of Turkish tobacco. A slight precipitation resulted in the tubes containing undiluted antiserum and virus extract such as occurs when juice from normal tobacco is used with undiluted antiserum. No precipitate was demonstrable that was specific for virus extracts of tobacco affected with either ringspot or cucumber mosaic disease. 4. The results favor the interpretation that the specific antigenic substance in virus extract of tobacco mosaic disease is foreign antigenic material, possibly virus itself, not altered host protein.
C-Reactive Protein for Cardiovascular Risk Assessment
Authors: Mona A. Kholeif
Journal: Diabetes Care (2005)

Malik et al. (1) report on the usefulness of C-reactive protein (CRP) in stratifying risk in patients with the metabolic syndrome and diabetes.

Studies on normal volunteers showed intraindividual variability, which in ∼50% of individuals was sufficient to change their CRP-related risk category (2).

Bogaty et al. (3) have also demonstrated what seems to be spontaneous fluctuation of CRP in stable patients with coronary artery disease …
Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis
Authors: Benfang Lei, Frank R. DeLeo, Nancy P. Hoe, Morag R. Graham, Stacy M. Mackie, Robert L. Cole, Mengyao Liu, Harry R. Hill, Donald E. Low, Michael J. Federle, June R. Scott, James M. Musser
Journal: Nature Medicine (2001)
Deep Brain Stimulation of the Midbrain Locomotor Region Improves Paretic Hindlimb Function After Spinal Cord Injury in Rats
Authors: Lukas C. Bachmann, Alina Matis, Nicolas T. Lindau, Petra Felder, Miriam Gullo, Martin E. Schwab
Journal: Science Translational Medicine (2013)

Stimulating the midbrain improves gait and locomotion in rats with chronic spinal cord injury.
Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes.
Authors: J Bastin, J Rothbard, J Davey, I Jones, A Townsend
Journal: The Journal of Experimental Medicine (1987)

The conserved epitopes of influenza nucleoprotein (NP) recognized by class I MHC-restricted CTL from CBA (H-2k) and C57BL/10 (H-2b) mice have been defined in vitro with synthetic peptides 50-63 and 365-379, respectively. Two Db-restricted clones were described that recognize different epitopes on peptide 365-379. Finally, the recognition of complete NP was shown to be approximately 200-fold less efficient than peptide in the cytotoxicity assay. These phenomena are closely related to results with class II-restricted T cells and they strengthen the hypothesis that influenza proteins are degraded in the infected cell before recognition by class I-restricted CTL.
Pesticides environmental exposure and respiratory health in schoolchildren
Authors: Ali Mamane, Emilie Berteaud, Ghislaine Bouvier, Isabelle Baldi, Chantal Raherison
Journal: European Respiratory Journal (2014)

Exposure to environmental factors may contribute to respiratory symptoms, in vulnerable subjects particularly children. In rural area, children9s pesticides exposure included usually residential proximity to farmland, and domestic exposure.  A pilot study was performed in rural area in south-west of France to evaluate the impact of pesticides used in vineyards culture, on respiratory health in schoolchildren during pesticides-treatment. Three hundred and ten schoolchildren were included in this study, (Means age [3-11 years old]). Parents answered a standardized questionnaire (ISAAC ) on respiratory symptoms and domestic pesticides use. Air Pesticides exposure at schools was measured by monitors in classrooms.  24.8% of children had ever wheeze, 29.1% had cough episodes during past year, and 17.6 % had asthma. 36.2% had rhinitis and 32.2% had rhino-conjunctivitis during past year. Three major pesticides were identified in schools : Folpel, CS2 and chlorpyriphos methyl. Children highly exposed to Folpel, had significantly more rhinoconjunctivitis (OR: 3.26 [1.14-9.29). Children highly exposed to CS2 had a higher risk of allergic conjunctivitis (OR: 3.04 [1.31-7.04]). Insecticide domestic use was associated with rhinitis (OR: 1.82 [0.99-3.5]). Lice killer lotion was associated with current rhinitis (OR: (3.56[0.99-12.59]), dyspnea episodes (OR: 3.84[1.18-12.46]) and allergic cough (OR: 2.12 [1.07-4.2). Any domestic pesticide exposure was associated with current rhinitis (OR: 3.67[1.47-9.1]) and allergic cough (OR: 2.37[1.08-5.1]).  Pesticides exposure had a significant impact for children in schools located near pesticides-treated lands.  Fundings : Fondation du souffle, ANSES.
Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity
Authors: Charlène Brault, Pierre Lévy, Sarah Duponchel, Maud Michelet, Aurèlie Sallé, Eve-Isabelle Pécheur, Marie-Laure Plissonnier, Romain Parent, Evelyne Véricel, Alexander V Ivanov, Münevver Demir, Hans-Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch
Journal: Gut (2014)

<h3>Objective</h3> Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed. <h3>Design</h3> The study was performed using a replicative in vitro HCV infection model and liver biopsies derived from two different CHC patient cohorts. <h3>Results</h3> A screen for HCV-induced peroxide scavengers identified GPx4 as a host factor required for HCV infection. The physiological role of GPx4 is the elimination of lipid peroxides from membranes or lipoproteins. GPx4-silencing reduced the specific infectivity of HCV by up to 10-fold. Loss of infectivity correlated with 70% reduced fusogenic activity of virions in liposome fusion assays. NS5A was identified as the protein that mediates GPx4 induction in a phosphatidylinositol-3-kinase-dependent manner. Levels of GPx4 mRNA were found increased in vitro and in CHC compared with control liver biopsies. Upon successful viral eradication, GPx4 transcript levels returned to baseline in vitro and also in the liver of patients. <h3>Conclusions</h3> HCV induces oxidative stress but controls it tightly by inducing ROS scavengers. Among these, GPx4 plays an essential role in the HCV life cycle. Modulating oxidative stress in CHC by specifically targeting GPx4 may lower specific infectivity of virions and prevent hepatocarcinogenesis, especially in patients who remain difficult to be treated in the new era of interferon-free regimens.
Obama to name Margaret Hamburg to head FDA
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

President Barack Obama is expected to name Margaret Hamburg, a former New York city health commissioner and a bioterrorism expert, to head the Food and Drug Administration and Joshua Sharfstein, Baltimore’s health commissioner, as her deputy, according to media reports.

The appointments are expected to be formally announced this week. Dr Hamburg’s appointment will need to be confirmed by the Senate. 

Dr Hamburg, aged 53, is a graduate of Harvard University and Harvard Medical School. She trained at New York Presbyterian Hospital and specialised in internal medicine. She later did neuroscience research at Rockefeller University in New York and at the National Institute of …
Hyperplastic growth of aortic smooth muscle cells in renovascular hypertensive rabbits is characterized by the expansion of an immature cell phenotype.
Authors: P Pauletto, A Chiavegato, L Giuriato, M Scatena, E Faggin, A Grisenti, R Sarzani, M V Paci, P D Fulgeri, A Rappelli
Journal: Circulation Research (1994)

Smooth muscle cells (SMCs) of rabbit aorta undergo marked changes in myosin isoform content during development. Analysis of nonmuscle myosin composition at the protein level has permitted the identification of three phases in the SMC differentiation process: fetal, postnatal, and adult. Using monoclonal antibodies specific for smooth muscle and nonmuscle myosins and extra domain A of fibronectin as well as cDNA probes for platelet-derived growth factors (PDGF) and various procollagens, we have evaluated the differentiation pattern of aortic SMCs in two-kidney, one-clip hypertensive rabbits. Morphometric and bromo-deoxyuridine studies indicate that hypertrophy of aortic media along with intimal thickening occurring in hypertensive animals is due to SMC hyperplasia. Western blotting experiments performed on aortic specimens from hypertensive animals with antimyosin antibodies revealed the appearance of a myosin isoform pattern of the "immature" type. Immunofluorescence tests showed that these cells are localized in the thickened intima or distributed in the underlying media (sparsely or in groups). Similarly, the fibronectin variant showing the extra domain A, peculiar to "phenotypically modulated" SMCs, appeared in intimal thickening, and its expression followed the time course of nonmuscle myosin expression. Counting of postnatal-type SMCs in the aortic media revealed that this cell population increases markedly with hypertension (2- up to 15-fold at 4 months) and then declines to near control level in 8-month hypertensive rabbits. Diminution of postnatal-type SMCs at later stages of hypertension was temporally correlated with the slowing down of aortic wall hypertrophy. Average levels of mRNAs, as determined by densitometric analysis in aortas from 1- and 2.5-month hypertensive rabbits, showed an increased expression for PDGF beta receptor (up to twofold), procollagen type I (alpha 1, threefold), procollagen type III (alpha 1, twofold), and fibronectin (up to threefold) compared with controls. Conversely, the steady-state levels of mRNAs for PDGF (A and B chain), PDGF alpha receptor, TGF-beta 1, and procollagen type IV (alpha 1) did not increase significantly. These results provide evidence that in adult renovascular hypertensive rabbits, the hyperplastic growth of aortic SMCs is accompanied by the expansion of an "immature" cell phenotype characteristic of the early stages of development.
Fetal Aortic Valve Stenosis and the Evolution of Hypoplastic Left Heart Syndrome
Authors: Kaarin Mäkikallio, Doff B. McElhinney, Jami C. Levine, Gerald R. Marx, Steven D. Colan, Audrey C. Marshall, James E. Lock, Edward N. Marcus, Wayne Tworetzky
Journal: Circulation (2006)

Background— Fetal aortic valvuloplasty may prevent progression of aortic stenosis (AS) to hypoplastic left heart syndrome (HLHS). Predicting which fetuses with AS will develop HLHS is essential to optimize patient selection for fetal intervention. The aim of this study was to define echocardiographic features associated with progression of midgestation fetal AS to HLHS. Methods and Results— Fetal echocardiograms were reviewed from 43 fetuses diagnosed with AS and normal left ventricular (LV) length at ≤30 weeks’ gestation. Of 23 live-born patients with available follow-up data, 17 had HLHS and 6 had a biventricular circulation. At the time of diagnosis, LV length, mitral valve, aortic valve, and ascending aortic diameter Z-scores did not differ between fetuses that ultimately developed HLHS and those that maintained a biventricular circulation postnatally. However, all of the fetuses that progressed to HLHS had retrograde flow in the transverse aortic arch (TAA), 88% had left-to-right flow across the foramen ovale, 91% had monophasic mitral inflow, and 94% had significant LV dysfunction. In contrast, all 6 fetuses with a biventricular circulation postnatally had antegrade flow in the TAA, biphasic mitral inflow, and normal LV function. With advancing gestation, growth arrest of left heart structures became evident in fetuses developing HLHS. Conclusions— In midgestation fetuses with AS and normal LV length, reversed flow in the TAA and foramen ovale, monophasic mitral inflow, and LV dysfunction are predictive of progression to HLHS. These physiological features may help refine patient selection for fetal intervention to prevent the progression of AS to HLHS.
Genotype-Guided Tamoxifen Dosing Increases Active Metabolite Exposure in Women With Reduced CYP2D6 Metabolism: A Multicenter Study
Authors: William J. Irvin, Christine M. Walko, Karen E. Weck, Joseph G. Ibrahim, Wing K. Chiu, E. Claire Dees, Susan G. Moore, Oludamilola A. Olajide, Mark L. Graham, Sean T. Canale, Rachel E. Raab, Steven W. Corso, Jeffrey M. Peppercorn, Steven M. Anderson, Kenneth J. Friedman, Evan T. Ogburn, Zeruesenay Desta, David A. Flockhart, Howard L. McLeod, James P. Evans, Lisa A. Carey
Journal: Journal of Clinical Oncology (2011)

We examined the feasibility of using CYP2D6 genotyping to determine optimal tamoxifen dose and investigated whether the key active tamoxifen metabolite, endoxifen, could be increased by genotype-guided tamoxifen dosing in patients with intermediate CYP2D6 metabolism.One hundred nineteen patients on tamoxifen 20 mg daily ≥ 4 months and not on any strong CYP2D6 inhibiting medications were assayed for CYP2D6 genotype and plasma tamoxifen metabolite concentrations. Patients found to be CYP2D6 extensive metabolizers (EM) remained on 20 mg and those found to be intermediate (IM) or poor (PM) metabolizers were increased to 40 mg daily. Eighty-nine evaluable patients had tamoxifen metabolite measurements repeated 4 months later.As expected, the median baseline endoxifen concentration was higher in EM (34.3 ng/mL) compared with either IM (18.5 ng/mL; P = .0045) or PM (4.2 ng/mL; P < .001). When the dose was increased from 20 mg to 40 mg in IM and PM patients, the endoxifen concentration rose significantly; in IM there was a median intrapatient change from baseline of +7.6 ng/mL (-0.6 to 23.9; P < .001), and in PM there was a change of +6.1 ng/mL (2.6 to 12.5; P = .020). After the dose increase, there was no longer a significant difference in endoxifen concentrations between EM and IM patients (P = .84); however, the PM endoxifen concentration was still significantly lower.This study demonstrates the feasibility of genotype-driven tamoxifen dosing and demonstrates that doubling the tamoxifen dose can increase endoxifen concentrations in IM and PM patients.
From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2011)

The WHO has indicated that in 2009, the most recent year for which data are available, approximately 250 million people were infected with malaria, and nearly one million of those patients succumbed to their infections. But without Youyou Tu (Institute of Materia Medica, Academy of Traditional Chinese Medicine and China Academy of Chinese Medical Sciences) (Figure ​(Figure1),1), many of those 249 million others may not have survived. This is the story of how Tu led a team that transformed an ancient Chinese method of using the herb qinghao into artemisinin, the most powerful antimalarial medicine that currently exists. And as the Chinese proverb has it, “He who plants a garden, plants happiness.” 



Figure 1

Youyou Tu, winner of the 2011 Lasker~DeBakey Clinical Medical Research Award.