tbuckley/cabot-search huggingface dataset:
Vaccination against CD99 inhibits atherogenesis in low-density lipoprotein receptor-deficient mice
Authors: E. J.A. van Wanrooij, P. de Vos, M. G. Bixel, D. Vestweber, T. J.C. van Berkel, J. Kuiper
Journal: Cardiovascular Research (2008)

Murine CD99 was recently found to be expressed on leukocytes and endothelial cells, where it is concentrated at inter-endothelial contacts. Blockade of CD99 by specific antibodies inhibits leukocyte extravasation to inflamed sites in vivo. The aim of the present study is to show the role of CD99 in atherosclerosis using a CD99 vaccination protocol to block the function of CD99 during atherosclerosis. We constructed a DNA vaccine against CD99 by cloning the extracellular domain of murine CD99 into pcDNA3. Vaccination was performed by oral administration of attenuated Salmonella typhimurium transformed with pcDNA3-CD99. This vaccination results in a CD99-specific, CD8-mediated cytotoxic response and subsequent reduction of CD99-expressing cells. We showed that CD99 is expressed on vascular endothelium overlying atherosclerotic plaques and found that CD99 expression is upregulated during western-type diet feeding. CD99 vaccination induced the formation of CD8-positive T cells that were cytotoxic against cells transfected with pcDNA3-CD99. Activation of CD8+ T cells was demonstrated by a 30% increase in CD8+CD69+ double-positive T cells in spleen and mediastinal lymph nodes. Furthermore, lymphocytes isolated from CD99-vaccinated mice specifically lysed CD99-expressing cells. More importantly, vaccination against CD99 attenuated atherosclerotic lesion formation in the aortic valve leaflets by 38% and in the carotid artery by 69% compared with mice that were vaccinated with a control vector. Furthermore, a lower number of cells were found in atherosclerotic lesions, implying that fewer leukocytes were recruited to these sites. These observations were accompanied by a decrease in CD99 expression on leukocytes. We conclude that vaccination against CD99 decreases atherogenesis by the selective removal of CD99-expressing cells, which could reduce leukocyte recruitment into atherosclerotic lesions and attenuate atherogenesis.
Urinary eicosanoid and tyrosine derivative concentrations in patients with vasculitides
Authors: Noritaka Higashi, Haruhisa Mita, Masami Taniguchi, Naomi Turikisawa, Ai Higashi, Yoshinori Ozawa, Shigeto Tohma, Kimiyoshi Arimura, Kazuo Akiyama
Journal: Journal of Allergy and Clinical Immunology (2004)
Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies
Authors: J. Creaney, B. W. S. Robinson
Journal: Thorax (2014)

Dr Blyth raises some important issues regarding the interpretation of malignant pleural mesothelioma (MPM) biomarker studies. First, the effects of confounders, including healing and/or inflammatory factors on biomarker levels; second, the reproducibility of biomarker results between centres.

In our independent evaluation of the proposed MPM biomarker fibulin-3, we considered some of the confounders he suggests—for instance, body mass index and renal function—which were not significant determinants of the diagnostic use of fibulin-3; and the neutrophil to lymphocyte ratio, which was reported and adjusted for in multivariate models. We agree that timing with respect to talc pleurodesis should be acknowledged in papers because of the potential effects …
Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function
Authors: K. Ansarin, J.M. Chatkin, I.M. Ferreira, C.A. Gutierrez, N. Zamel, K.R. Chapman
Journal: European Respiratory Journal (2001)

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use. In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung ( D L,CO ) and resting oxygen saturation ( S a,O 2 ) were measured. Median eNO was significantly higher among patients with COPD than among healthy volunteers (p=0.003) but lower than among patients with asthma (p&lt;0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25–75% range 16–54) than among asthma patients who did not (51 ppb; 32–87) (p=0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second, D L,CO and S a,O 2 , and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found. Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.
Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects
Authors: Cristina Lara-Castro, Bradley R Newcomer, Jennifer Rowell, Penny Wallace, Sara M Shaughnessy, A Julian Munoz, Alanna M Shiflett, Dana Y Rigsby, Jeannine C Lawrence, Daryl E Bohning, Steven Buchthal, W Timothy Garvey
Journal: Metabolism (2007)
Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation
Authors: Ramjay S Vatsan, Peter F Bross, Ke Liu, Marc Theoret, Angelo R De Claro, Jinhua Lu, Whitney Helms, Brian Niland, Syed R Husain, Raj K Puri
Journal: Journal for ImmunoTherapy of Cancer (2013)

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development.
The effect of recombinant mast cell growth factor on purified murine hematopoietic stem cells.
Authors: P de Vries, K A Brasel, J R Eisenman, A R Alpert, D E Williams
Journal: The Journal of Experimental Medicine (1991)

Pluripotent hematopoietic stem cells (PHSC) are very rare cells whose functional capabilities can only be analyzed indirectly. For a better understanding and possible manipulation of mechanisms that regulate self-renewal and commitment to differentiation of PHSC, it is necessary to purify these cells and to develop assays for their growth in vitro. In the present study, a rapid and simple, widely applicable procedure to highly purify day 14 spleen colony-forming cells (day 14 CFU-S) is described. Low density bone marrow cells (rho less than or equal to 1.078 g/cm3) were enriched by two successive light-activated cell sorting procedures. In the first sort, cells within a predetermined light scatter (blast cell) window that are wheat germ agglutinin/Texas Red (WGA/TxR) positive and mAb 15-1.4.1/fluorescein isothiocyanate negative (granulocyte-monocyte marker) were selected. In the second sort, cells were selected on the basis of retention of the supravital dye rhodamine 123 (Rh123). Cells that take up little Rh123 (Rh123 dull cells) and those that take up more Rh123 (Rh123 bright cells) were 237-fold and 132-fold enriched, respectively, for day 14 CFU-S. Both Rh123 fractions were cultured for various time periods in vitro in the presence of mast cell growth factor (MGF), with or without interleukin 3 (IL-3) or IL-1 alpha. Both Rh123 fractions proliferated in response to MGF alone as determined by a [3H]TdR assay or by counting nucleated cells present in the cultures over time. MGF also acted synergistically with both IL-3 and IL-1 alpha to promote stem cell proliferation. Stimulation of both Rh123 fractions with MGF alone did not result in a net increase of day 14 CFU-S. Stimulation with MGF + IL-3 or MGF + IL-alpha resulted in a 4.4- or 2.6-fold increase of day 14 CFU-S in the Rh123 dull fraction, and an 11.6-fold or 2.6-fold increase of day 14 CFU-S in the Rh123 bright fraction, respectively. The data presented in this paper indicate that in vitro MGF acts on primitive hematopoietic stem cells by itself and also is a potent synergistic factor in combination with IL-3 or IL-1 alpha.
American Thoracic Society/European Respiratory Society Statement on Pulmonary Rehabilitation
Authors: Linda Nici, Claudio Donner, Emiel Wouters, Richard Zuwallack, Nicolino Ambrosino, Jean Bourbeau, Mauro Carone, Bartolome Celli, Marielle Engelen, Bonnie Fahy, Chris Garvey, Roger Goldstein, Rik Gosselink, Suzanne Lareau, Neil MacIntyre, Francois Maltais, Mike Morgan, Denis O'Donnell, Christian Prefault, Jane Reardon, Carolyn Rochester, Annemie Schols, Sally Singh, Thierry Troosters
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Linda Nici, Claudio Donner, Emiel Wouters, Richard Zuwallack, Nicolino Ambrosino, Jean Bourbeau, Mauro Carone, Bartolome Celli, Marielle Engelen, Bonnie Fahy, Chris Garvey, Roger Goldstein, Rik Gosselink, Suzanne Lareau, Neil MacIntyre, Francois Maltais, Mike Morgan, Denis O’Donnell, Christian Prefault, Jane Reardon, Carolyn Rochester, Annemie Schols, Sally Singh, and Thierry Troosters, on behalf of the ATS/ERS Pulmonary Rehabilitation Writing Committee
Early T2 changes predict onset of radiographic knee osteoarthritis: data from the osteoarthritis initiative
Authors: Hans Liebl, Gabby Joseph, Michael C Nevitt, Nathan Singh, Ursula Heilmeier, Karupppasamy Subburaj, Pia M Jungmann, Charles E McCulloch, John A Lynch, Nancy E Lane, Thomas M Link
Journal: Annals of the Rheumatic Diseases (2014)

To evaluate whether T2 relaxation time measurements obtained at 3 T MRI predict the onset of radiographic knee osteoarthritis (OA).We performed a nested case-control study of incident radiographic knee OA in the Osteoarthritis Initiative cohort. Cases were 50 knees with baseline Kellgren-Lawrence (KL) grade of 0 that developed KL grade of 2 or more over a 4-year period. Controls were 80 knees with KL grade of 0 after 4 years of follow-up. Baseline T2 relaxation time measurements and laminar analysis of T2 in deep and superficial layers were performed in all knee compartments. The association of T2 values with incident OA was assessed with logistic regression and differences in T2 values by case-control status with linear regression, adjusting for age, sex, body mass index (BMI) and other covariates.Baseline T2 values in all compartments except the medial tibia were significantly higher in knees that developed OA compared with controls and were particularly elevated in the superficial cartilage layers in all compartments. There was an increased likelihood of incident knee OA associated with higher baseline T2 values, particularly in the patella, adjusted OR per 1 SD increase in T2 (3.37 (95% CI 1.72 to 6.62)), but also in the medial femur (1.90 (1.07 to 3.39)), lateral femur (2.17 (1.11 to 4.25)) and lateral tibia (2.23 (1.16 to 4.31)).These findings suggest that T2 values assessed when radiographic changes are not yet apparent may be useful in predicting the development of radiological tibiofemoral OA.
Postoperative irinotecan in resected stage II–III rectal cancer: final analysis of the French R98 Intergroup trial
Authors: C. Delbaldo, M. Ychou, A. Zawadi, J.Y. Douillard, T. André, V. Guerin-Meyer, P. Rougier, O. Dupuis, R. Faroux, A. Jouhaud, E. Quinaux, M. Buyse, P. Piedbois
Journal: Annals of Oncology (2015)
ANTIPLATELET ACTION OF CLOPIDOGREL AND PRASUGREL IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK
Authors: Martin Orban, Isabell Bernlochner, Mathias Orban, Katharina Mayer, Martin Hadamitzky, Siegmund Braun, Joerg Hausleiter, Karl-Ludwig Laugwitz, Klaus Tiroch, Steffen Massberg, Julinda Mehilli, Dirk Sibbing, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2013)
Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study
Authors: Stewart Goldman, Eric Bouffet, Paul G. Fisher, Jeffrey C. Allen, Patricia L. Robertson, Paul J. Chuba, Bernadine Donahue, Cynthia S. Kretschmar, Tianni Zhou, Allen B. Buxton, Ian F. Pollack
Journal: Journal of Clinical Oncology (2015)

Purpose This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. Patients and Methods Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. Results The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. Conclusion Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. This regimen should be included as a backbone for further studies.
Tivantinib (ARQ197) Displays Cytotoxic Activity That Is Independent of Its Ability to Bind MET—Letter
Authors: Lorenza Rimassa, Jordi Bruix, Massimo Broggini, Armando Santoro
Journal: Clinical Cancer Research (2013)

We read with interest the article by Basilico and colleagues ([1][1]), testing the in vitro activity of tivantinib.

The article ignores highly suggestive clinical evidence supporting the conclusion that the principal mechanism of action of tivantinib is the inhibition of MET, as shown in a double-
Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion
Authors: C-F. Su, D. D. Liu, S. J. Kao, H. I. Chen
Journal: European Respiratory Journal (2007)

Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung. I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-alpha and interleukin-1beta in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue. Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg.kg(-1) body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.
Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma
Authors: J Pijpe
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjögren's syndrome (SS) and associated MALT lymphoma. <b>Case report:</b> The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and the hard palate. Four infusions of rituximab (375 mg/m<sup>2</sup>) weekly resulted in complete remission of the lymphoma. An incision biopsy of the parotid gland before and after treatment showed improvement of the (immuno)histopathological characteristics of SS, with possible regeneration of salivary gland tissue. Furthermore, salivary analysis showed decreased inflammatory characteristics and increased stimulated salivary flow. <b>Discussion:</b> Rituximab is a promising agent in the treatment of SS associated MALT lymphoma. In addition to the effect on MALT lymphoma, B cell depletion by rituximab may also attenuate the activity of SS. This case report is the first to describe the effect of rituximab on histological and sialometric/chemical characteristics of SS. The efficacy of rituximab in the treatment of SS warrants further investigation.
Selective blockade of mGlu5 metabotropic glutamate receptors protects rat hepatocytes against hypoxic damage
Authors: Marianna Storto, Ugo de Grazia, Thomas Knöpfel, Pier Luigi Canonico, Agata Copani, Plinio Richelmi, Ferdinando Nicoletti, Mariapia Vairetti
Journal: Hepatology (2000)

Western blot analysis of protein extracts from rat liver revealed the presence of the mGlu5 receptor, one of the G-protein-coupled receptors activated by glutamate (named "metabotropic glutamate receptors" or mGlu receptors). mGlu5 expression was particularly high in extracts from isolated hepatocytes, where levels were comparable with those seen in the rat cerebral cortex. The presence of mGlu5 receptors in hepatocytes was confirmed by reverse-transcription polymerase chain reaction (RT-PCR) analysis, immunohistochemistry in neonate or adult rat liver, as well as by immunocytochemical analysis in HepG2 hepatoma cells, where the receptor appeared to be preferentially distributed in cell membranes. Interestingly, mGlu1 receptors (which are structurally and functionally homologous to mGlu5 receptors) were never found in rat liver or hepatocytes. In hepatocytes exposed to anoxic conditions for 90 minutes, glutamate, (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD) and quisqualate, which all activate mGlu5 receptors, accelerated the onset and increased the extent of cell damage, while 4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of mGlu2/3 receptors, was inactive. 2-methyl-6-(2-phenyl-1-ethynyl)-pyridine (MPEP), a novel, noncompetitive, highly selective mGlu5 receptor antagonist, not only abolished the toxic effect of 1S,3R-ACPD, but, unexpectedly, was protective by itself against anoxic damage. This suggests that hepatocytes express mGlu5 receptors and that activation of these receptors by endogenous glutamate facilitates the development of anoxic damage in hepatocytes.
The mosaic nature of the eukaryotic nucleus
Authors: S Ribeiro, G B Golding
Journal: Molecular Biology and Evolution (1998)

The phylogenies for each of the protein-coding genes from the Methanococcus jannaschii genome were surveyed to determine the history of the major groups of life. For each gene, homologous sequences from other archaea, eucarya, and Gram-positive and Gram-negative bacteria were collected and aligned, and a phylogeny was reconstructed with a maximum-likelihood algorithm. The majority of significant phylogenies favor the eucarya and the archaca as sister groups. A smaller, but still substantial, portion of these significant phylogenies favor an eucarya/Gram-negative clade. These results indicate that support for the early history of life is not unequivocal. A chimeric origin of eukaryotes or an ancient, massive horizontal transfer of genes from Gram-negative bacteria to eucarya can explain many of the observed phylogenies.
GE-05 * STUDY OF EPIGENETIC DEREGULATION OF A NOVEL DEUBIQUITYLASE IN MEDULLOBLASTOMA
Authors: R. Hatcher, C. Das, J. Fangusaro, V. Rajaram, R. Lulla, S. Goldman, S. Khatua, G. Sbardella, V. Gopalakrishnan
Journal: Neuro-Oncology (2015)

A major goal of our work is to study medulloblastoma biology to facilitate the development of targeted therapy. Here, we have dissected the contribution of epigenetics to tumor development. Epigenetic perturbations are pharmacologically reversible and may have therapeutic potential. The RE1-Silencing Transcription Factor (REST) is an epigenetic modulator, and a repressor of neuronal differentiation genes. Its expression is significantly elevated in human medulloblastomas, and is associated with poor prognosis. REST is a driver of medulloblastoma in mouse orthotopic models. To understand REST's contribution to tumor development, we created a novel genetically engineered mouse model in which REST transgene is conditionally elevated in the cerebellar granule progenitors (GNPs), the cells of origin of some medulloblastoma. Transgene induction caused GNP hyperproliferation, accompanied by a failure to express the cell cycle regulator-p27. Using genetic and biochemical approaches, we attributed the lack of p27 expression to direct REST-mediated repression of a novel deubiquitylase, USP37. We also identified a role for USP37 in p27 protein stabilization, and terminal cell cycle exit. USP37 and p27 levels were significantly correlated in patient samples, and their loss was associated with poor overall patient survival. Importantly, constitutive USP37 expression blocked the tumorigenic potential of high-REST human medulloblastomas, suggesting a tumor suppressive function for USP37. REST binding to the USP37 promoter caused increased histone H3 lysine (K)-9 tri-methylation, an epigenetic mark associated with gene silencing. The histone methyl-transferase G9a, which promotes this modification, is a known REST co-repressor. Importantly, genetic ablation of G9a or pharmacological inhibition of its activity upregulated USP37 expression in a REST-dependent manner, and blocked tumor growth in mice. Our work has provided the first link between epigenetic deregulation of the proteasome and medulloblastoma development, and supports the manipulation of the REST-epigenome for future therapeutic application.