tbuckley/cabot-search huggingface dataset:
Stimulation of Lung Innate Immunity Protects against Lethal Pneumococcal Pneumonia in Mice
Authors: Cecilia G. Clement, Scott E. Evans, Christopher M. Evans, David Hawke, Ryuji Kobayashi, Paul R. Reynolds, Seyed J. Moghaddam, Brenton L. Scott, Ernestina Melicoff, Roberto Adachi, Burton F. Dickey, Michael J. Tuvim
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The lungs are a common site of serious infection in both healthy and immunocompromised subjects, and the most likely route of delivery of a bioterror agent. Since the airway epithelium shows great structural plasticity in response to inflammatory stimuli, we hypothesized it might also show functional plasticity.To test the inducibility of lung defenses against bacterial challenge.Mice were treated with an aerosolized lysate of ultraviolet-killed nontypeable (unencapsulated) Haemophilus influenzae (NTHi), then challenged with a lethal dose of live Streptococcus pneumoniae (Spn) delivered by aerosol.Treatment with the NTHi lysate induced complete protection against challenge with a lethal dose of Spn if treatment preceded challenge by 4 to 24 hours. Lesser levels of protection occurred at shorter (83% at 2 h) and longer (83% at 48-72 h) intervals between treatment and challenge. There was also some protection when treatment was given 2 hours after challenge (survival increased from 14 to 57%), but not 24 hours after challenge. Protection did not depend on recruited neutrophils or resident mast cells and alveolar macrophages. Protection was specific to the airway route of infection, correlated in magnitude and time with rapid bacterial killing within the lungs, and was associated with increases of multiple antimicrobial polypeptides in lung lining fluid.We infer that protection derives from stimulation of local innate immune mechanisms, and that activated lung epithelium is the most likely cellular effector of this response. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value.
The Stoke CNEP Saga – the Government enquiry in retrospect*
Authors: Rod Griffiths
Journal: Journal of the Royal Society of Medicine (2010)

Sustained media coverage of allegations about the CNEP trial created pressure on the Department of Health. The responsible minister quite rightly stuck to the line that appropriate mechanisms already existed to investigate matters of individual care (the NHS complaints process) or individual professional misconduct (the GMC and other professional regulators) but this was not enough to make the problem go away. Eventually the minister came to the conclusion that one aspect that was not being investigated was the framework through which research was supervised in the North Staffordshire NHS Trust. The review thus covered research governance, though many have mistakenly assumed that it was about misconduct. Had it been about research misconduct I might well have refused to lead it.
Successful vaccination with intradermal hepatitis B vaccine in hemodialysis patients previously nonresponsive to intramuscular hepatitis B vaccine.
Authors: N M Waite, L G Thomson, M B Goldstein
Journal: Journal of the American Society of Nephrology (1995)

Seventy-seven chronic hemodialysis patients were vaccinated against hepatitis B virus with an intramuscular (im) hepatitis B vaccine (HBV), 40 micrograms at 0, 1, 2, and 6 months. Fifty-seven patients (74%) developed antibodies (anti-HBs). The im-responsive patients were significantly younger than the nonresponsive patients (P < 0.05). Nineteen of the 20 im nonresponders received HBV intradermally (id), 5 micrograms every 2 wk until anti-HBs developed; the 20th patient died before receiving the id vaccine. Three patients were lost to follow-up. Fifteen (94%) of the 16 developed anti-HBs after 5.2 +/- 4.7 months. The peak anti-HBs titers were 726 +/- 426 (im) and 211 +/- 260 (id) IU/L (P < 0.05). Twelve (21%) of the 57 im-responsive patients and 8 (53%) of the 15 id-responsive patients had anti-HBs less than 20 IU/L at 18 and 8 months postvaccination, respectively (P < 0.05). Further preliminary data indicate that more prolonged id vaccination can increase both the titer and the duration of anti-HBs in im-nonresponsive patients.
Defective Peyer's patch organogenesis in mice lacking the 55-kD receptor for tumor necrosis factor.
Authors: B Neumann, A Luz, K Pfeffer, B Holzmann
Journal: The Journal of Experimental Medicine (1996)

Lymphotoxin alpha (LT-alpha) may form secreted homotrimers binding to p55 and p75 tumor necrosis factor (TNF) receptors or cell surface-bound heterotrimers with LT-beta that interact with the LT-beta receptor. Genetic ablation of LT-alpha revealed that mutant mice have no detectable lymph nodes or Peyer's patches and that the organization of the splenic white pulp in T and B cell areas is disturbed. In this report we describe a novel function for the p55 TNF receptor during ontogeny and demonstrate that mice deficient for p55 completely lack organized Peyer's patches. In contrast, lymph nodes and spleen are present in p55-deficient mice and lymphocytes segregate normally into B and T cell areas in these organs. Lamina propria and intraepithelial lymphocytes of the small intestine were detected in normal number and distribution in p55 mutant mice. Lymphocytes and endothelial cells from p55-deficient mice express normal levels of adhesion molecules considered important for lymphocyte migration to mucosal organs; this indicates that the lack of Peyer's patches does not result from a defect in lymphocyte homing. In summary, the p55 receptor for TNF selectively mediates organogenesis of Peyer's patches throughout ontogeny, suggesting that the effects of LT-alpha on the development of lymphoid organs may be mediated by distinct receptors, each functioning in an organ-specific context.
Midkine Promotes Neuroblastoma through Notch2 Signaling
Authors: Satoshi Kishida, Ping Mu, Shin Miyakawa, Masatoshi Fujiwara, Tomoyuki Abe, Kazuma Sakamoto, Akira Onishi, Yoshikazu Nakamura, Kenji Kadomatsu
Journal: Cancer Research (2012)

Midkine is a heparin-binding growth factor highly expressed in various cancers, including neuroblastoma, the most common extracranial pediatric solid tumor. Prognosis of patients with neuroblastoma in which MYCN is amplified remains particularly poor. In this study, we used a MYCN transgenic model for neuroblastoma in which midkine is highly expressed in precancerous lesions of sympathetic ganglia. Genetic ablation of midkine in this model delayed tumor formation and reduced tumor incidence. Furthermore, an RNA aptamer that specifically bound midkine suppressed the growth of neuroblastoma cells in vitro and in vivo in tumor xenografts. In precancerous lesions, midkine-deficient MYCN transgenic mice exhibited defects in activation of Notch2, a candidate midkine receptor, and expression of the Notch target gene HES1. Similarly, RNA aptamer-treated tumor xenografts also showed attenuation of Notch2-HES1 signaling. Our findings establish a critical role for the midkine-Notch2 signaling axis in neuroblastoma tumorigenesis, which implicates new strategies to treat neuroblastoma.
In Vivo expression of two novel tumor-associated antigens and their use in immunolocalization of human hepatocellular carcinoma
Authors: Hiroshi Takahashi, Mehmet Ozturk, Byron Wilson, Atsuhiko Maki, Kazue Ozawa, Mitsuru Koizumi, Keigo Endo, William Strauss, Daniel Shouval, Jack Wands
Journal: Hepatology (1989)

We are investigating the antigenic changes on the cell surface of human hepatocytes that distinguish the normal from the transformed phenotype using monoclonal antibodies. In vivo expression of antigens has been directly assessed by in situ radioimmunohistology. This technique allows one to determine the distribution and density of antigen expression at the individual cellular level on fresh hepatoma and adjacent uninvolved liver tissue. We have found two antigens recognized by monoclonal antibodies XF-8 and AF-20 that are uniformly present on 15/15 hepatocellular carcinomas tested thus far. Most if not all tumor cells highly express these antigens. Such antigens were not evident on adjacent normal liver and the XF-8 epitope was not found on other normal human tissues. AF-20 antigen distribution revealed low-level expression on a subpopulation of cells in the zona glomerulosa of the adrenal gland and on crypt cells of the small intestinal tract. We have studied the capability of radiolabeled XF-8 and AF-20 monoclonal antibodies when administered either alone or in combination to localize a hepatitis B virus-related hepatocellular carcinoma cell line (FOCUS) grown as subcutaneous tumors in nude mice. Biodistribution experiments demonstrated an excellent localization to tumor of 15 to 22% of the injected dose of 125 I-labeled antibodies. Indeed, it was possible to enhance the delivery of 125 I to the tumor cell surface by the use of XF-8 and AF-20 in combination. Nuclear imaging studies showed sharp visualization of tumor and demonstrate that these monoclonal antibodies have sufficient specificity and sensitivity to be strongly considered as immunotargeting agents.
Bronchial Secretory Immunoglobulin A Deficiency Correlates With Airway Inflammation and Progression of Chronic Obstructive Pulmonary Disease
Authors: Vasiliy V. Polosukhin, Justin M. Cates, William E. Lawson, Rinat Zaynagetdinov, Aaron P. Milstone, Pierre P. Massion, Sebahat Ocak, Lorraine B. Ware, Jae Woo Lee, Russell P. Bowler, Alexey V. Kononov, Scott H. Randell, Timothy S. Blackwell
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown.
Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case–control study
Authors: G. Gorini, E. Stagnaro, V. Fontana, L. Miligi, V. Ramazzotti, D. Amadori, S. Rodella, R. Tumino, P. Crosignani, C. Vindigni, A. Fontana, P. Vineis, A. Seniori Costantini
Journal: Annals of Oncology (2006)
Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats
Authors: A Deten
Journal: Cardiovascular Research (2002)

Objective: The proinflammatory cytokines interleukin (IL)-1β and IL-6 are supposed to be involved in various cardiovascular diseases including reperfusion injury and cardiac hypertrophy. Methods and results: In the present study, we have examined the cytokine expression from 3 h up to 12 weeks after permanent coronary artery occlusion in rats. In the first 3–12 h, there was a strong induction in IL-1β and IL-6 mRNA expression in the infarct area (up to 50-fold) as well as in the non-infarcted myocardium (up to 15-fold). From day 3 onwards the cytokine expression was not significantly altered compared to sham-operated controls. In addition, the expression of C/AATT-enhancer binding protein-β was about fourfold elevated in the first hours after myocardial infarction, but not thereafter. Furthermore, the expression of gp130 and IL-6 receptor increased significantly in the infarct area. The elevation in cytokine expression preceded the increase in matrix-metalloproteinase-9 in the infarct area as well as the increase in ANP and collagen expression in the non-infarcted myocardium. Conclusions: We suggest that IL-6 and IL-1β act synergistically in promoting resorption of the necrotic tissue, matrix remodeling and wound healing. Furthermore, they may be involved in the early induction of fibrosis and compensatory cardiac hypertrophy of the non-infarcted myocardium, but seem not to play a key role in long-term cardiac remodeling in chronic heart failure after myocardial infarction.
Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity.
Authors: R C Frederich, B Löllmann, A Hamann, A Napolitano-Rosen, B B Kahn, B B Lowell, J S Flier
Journal: Journal of Clinical Investigation (1995)

The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, M. Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425). The encoded protein and to represent and "adipostat" signal reflecting the state of energy stores. We confirm that the adipocyte is the source of ob mRNA and that the predicted 16-kD ob protein is present in rodent serum as detected by Western blot. To evaluate the hypothesis that it might represent an adipostat, we assessed serum levels of ob protein and expression of ob mRNA in adipose cells and tissue of rodents in response to a variety of perturbations which effect body fat mass. Both ob protein and ob mRNA expression are markedly increased in obesity. The levels of ob protein are approximately 5-10-fold elevated in serum of db/db mice, in mice with hypothalamic lesions caused by neonatal administration of monosodium glutamate (MSG), and in mice with toxigene induced brown fat ablation, (UCP-DTA). Very parallel changes are observed in adipocyte ob mRNA expression in these models and in ob/ob mice. As predicted however, no serum ob protein could be detected in the ob/ob mice. By contrast to obesity, starvation of normal rats and mice for 1-3 d markedly suppresses ob mRNA abundance, and this is reversed with refeeding. Similarly, ob protein concentration in normal mice falls to undetectable levels with starvation. In the ob/ob, UCP-DTA and MSG models, overexpression of ob mRNA is reversed by caloric restriction. These data support the hypothesis that expression of ob mRNA and protein are regulated as a function of energy stores, and that ob serves as a circulating feedback signal to sites involved in regulation of energy homeostasis.
Overexpression of TOSO in CLL is triggered by B-cell receptor signaling and associated with progressive disease
Authors: Christian Philipp Pallasch, Alexandra Schulz, Nadine Kutsch, Janine Schwamb, Susanne Hagist, Hamid Kashkar, Alfred Ultsch, Claudia Wickenhauser, Michael Hallek, Clemens-Martin Wendtner
Journal: Blood (2008)
Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen
Authors: Michele L. Caton, Matthew R. Smith-Raska, Boris Reizis
Journal: The Journal of Experimental Medicine (2007)

Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.
Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases
Authors: Chrisoula Hatzara, Emilia Hadziyannis, Anna Kandili, Christos Koutsianas, Anastasia Makris, Georgios Georgiopoulos, Dimitrios Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To determine the rate of tuberculosis (TB) screening test conversion during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with negative baseline screening. <h3>Methods</h3> This was a prospective study of rheumatic patients with negative baseline TB screening (tuberculin skin test (TST): &lt;5 mm, and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray) treated with anti-TNF agents. All patients underwent re-screening for TB with all assays 1 year later. Factors associated with TB test conversion were analysed and compared between 'converters' and 'non-converters'. <h3>Results</h3> Seventy patients (mean age 50.6±15.5 years) with rheumatic disease (33 with rheumatoid arthritis, 33 with spondyloarthropathies and 4 with other conditions) were enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14 etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty patients (29%) displayed conversion of at least one screening assay 12 months after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7 (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more than one screening test. Univariate and multivariate analysis revealed that only infliximab was associated with a decreased rate of TB screening assay conversion (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid therapy) developed active TB during follow-up (27±12 months). <h3>Conclusions</h3> Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.
Clinical practice guideline on diagnosis and treatment of hyponatraemia
Authors: Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen, Evi Nagler
Journal: Intensive Care Medicine (2014)
Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma
Authors: K. Tobinai, T. Igarashi, K. Itoh, Y. Kobayashi, M. Taniwaki, M. Ogura, T. Kinoshita, T. Hotta, K. Aikawa, K. Tsushita, A. Hiraoka, Y. Matsuno, S. Nakamura, S. Mori, Y. Ohashi
Journal: Annals of Oncology (2004)
National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening
Authors: Alexa B. Kimball, Dafna Gladman, Joel M. Gelfand, Kenneth Gordon, Elizabeth J. Horn, Neil J. Korman, Gretchen Korver, Gerald G. Krueger, Bruce E. Strober, Mark G. Lebwohl
Journal: Journal of the American Academy of Dermatology (2008)
Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials
Authors: Karim Raza, Tajvur P Saber, Tore K Kvien, Paul P Tak, Danielle M Gerlag
Journal: Annals of the Rheumatic Diseases (2012)

The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a 'window of opportunity' is now well established and considerable attention has been paid to when it might close. However, in order to study how long the window of opportunity lasts, the timing of its opening must be precisely defined. An analysis of definitions of 'onset' in clinical studies reveals imprecision and heterogeneity, making accurate assessment of this important concept of the 'window of opportunity' very difficult. In this paper we propose that, in clinical trials in early RA, data on durations since onset of symptoms and onset of joint swelling as well as disease duration based on fulfilment of classification criteria should be routinely presented.
A role for sensory nerves in the late asthmatic response
Authors: Kristof Raemdonck, Jorge de Alba, Mark A Birrell, Megan Grace, Sarah A Maher, Charles G Irvin, John R Fozard, Paul M O'Byrne, Maria G Belvisi
Journal: Thorax (2011)

<h3>Background</h3> In allergic asthma, exposure to relevant antigens leads to an early asthmatic response (EAR) followed, in certain subjects, by a late asthmatic response (LAR). Although many subjects with asthma consider LAR to be one of the defining symptoms of their disease, and despite its widespread use in the clinical assessment of new therapeutic entities, the mechanism underlying the LAR remains unclear. <h3>Method</h3> A study was undertaken using ovalbumin-sensitised and challenged Brown Norway rat and C57BL/6J mouse models which recapitulate phenotypic features of allergic asthma including the LAR and its susceptibility to clinically effective agents. <h3>Results</h3> In conscious animals an EAR was followed by a LAR. The LAR was subjectively evidenced by audible (wheeze) and visual signs of respiratory distress associated with quantifiable changes in non-invasive lung function assessment. Treatments that attenuated the EAR failed to impact on the LAR and, while anaesthesia did not impact on EAR, it abolished LAR. A key role for airway sensory neuronal reflexes in the LAR was therefore hypothesised, which was confirmed by the blockade observed after administration of ruthenium red (non-selective cation channel blocker), HC-030031 (TRPA1 inhibitor) and tiotropium bromide (anticholinergic) but not JNJ-17203212 (TRPV1 inhibitor). <h3>Conclusion</h3> These results suggest that LAR involves the following processes: allergen challenge triggering airway sensory nerves via the activation of TRPA1 channels which initiates a central reflex event leading to a parasympathetic cholinergic constrictor response. These data are supported by recent clinical trials suggesting that an anticholinergic agent improved symptoms and lung function in patients with asthma.
Short-term in vivo exposure to cigarette-smoke increases the fluorescence in rat alveolar macrophages
Authors: CM Skold, K Andersson, J Hed, A Eklund
Journal: European Respiratory Journal (1993)

Alveolar macrophages (AMs) from human smokers exhibit a strong intracellular fluorescence. In order to study the mechanisms behind the fluorescence, we wanted to determine whether it could be induced by short term exposure to smoke. We therefore exposed rats for either one or five days to cigarette smoke. AMs were recovered by bronchoalveolar lavage (BAL), and their fluorescence was quantified by flow cytofluorometry. AMs from rats exposed to two cigarettes, on a single occasion, showed an increased fluorescence compared to controls. The fluorescence was further enhanced by exposing rats to two cigarettes, for five consecutive days. Larger and more granular/complex AMs were more fluorescent than smaller and less granular/complex cells. Smoke-exposed rats (five consecutive days) lavaged immediately after the exposure, had less cells in their BAL fluid than control animals. However, when rats were lavaged three smoke-free days after the exposure, the cell recovery increased, probably due to less airway obstruction. In conclusion, we found that a short-term in vivo exposure to cigarette smoke results in an increased AM fluorescence. The findings can be one explanation for the strong fluorescence seen in AMs from human smokers, possibly due to endocytosis of fluorescent material.
ANALOGUES OF GROWTH-HORMONE RELEASE-INHIBITING HORMONE
Authors: D.C. Evered, A. Gomez-Pan, W.M.G. Tunbridge, R. Hall, T. Lind, G.M. Besser, C.H. Mortimer, M.O. Thorner, A.V. Schally, A.J. Kastin, D.H. Coy
Journal: The Lancet (1975)