tbuckley/cabot-search huggingface dataset:
Comparative analysis of nasal and oral mucosa dendritic cells
Authors: J.‐P. Allam, B. Niederhagen, M. Bücheler, T. Appel, H. Betten, T. Bieber, S. Bergé, N. Novak
Journal: Allergy (2005)

Mucosal dendritic cells (DC) play a crucial role in tolerance induction as seen in mucosal immunotherapy of atopic diseases. Nevertheless little is known about the phenotypical differences of oral and nasal mucosal DC (nmDC). Recently, we could show that oral mucosal myeloid CD1a(+) DC (omDC) differ from their skin counterparts especially by the expression of high affinity receptor for immunoglobulin E (IgE; FcepsilonRI). However, expression pattern of FcepsilonRI and phenotypical characteristics of CD1a(+) nmDC have not been elucidated in detailed yet.We performed detailed phenotypical comparison of nmDC and omDC of atopic and nonatopic individuals.As reported for omDC, FcepsilonRI on nmDC of atopic donors was elevated and mostly occupied by IgE while FcepsilonRI was present only in low amounts on nmDC of nonatopic donors. Nevertheless, the highest FcepsilonRI expression has been observed on omDC. Furthermore, significant amounts of costimulatory molecules CD40, CD80 and CD86 could be detected on nmDC that expressed more CD80 compared with omDC. Moreover, nmDC displayed less major histocompatability complex (MHC) class I and II molecules than omDC. In addition, nmDC expressed more C-type lectins CD205, CD206 as well as myeloid marker CD11b while omDC displayed increased expression of CD207 and lipopolysaccharide (LPS) receptor CD14.Together these data imply that nmDC phenotypical differ from omDC which might result in diverse functional properties and might be of relevance for selecting routes for immunotherapy of atopic diseases. Moreover these data provide a basis for further studies investigating immunological mechanisms underlying mucosal immunotherapy.
Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial: hope on the horizon for patients with severe systemic sclerosis
Authors: J M van Laar
Journal: Annals of the Rheumatic Diseases (2005)

<b><i>Background:</i></b> Cerebral infarctions are common in older persons but their relationship with dementia and cognitive function remains controversial. <b><i>Methods:</i></b> Participants were 164 older Catholic nuns, priests, and brothers who underwent annual clinical evaluation and brain autopsy at death. The authors quantified number and volume of old cerebral infarctions on postmortem examination and determined the association with dementia and cognitive function proximate to death. Analyses controlled for age, sex, and education. <b><i>Results:</i></b> A total of 58 (35.4%) subjects had cerebral infarctions: 29 had one infarction and 29 had multiple infarctions. In logistic regression analyses, infarctions increased the odds of dementia twofold (OR 2.12; 95% CI 1.06 to 4.25). The odds of dementia increased by 2.67-fold for multiple infarctions (95% CI 1.08 to 6.61), whereas the odds of dementia with single infarctions increased by 69% (95% CI 0.70 to 4.09). In linear regression analyses, there was a trend for multiple infarctions to be associated with lower global cognitive scores (−0.44 standard units, <i>p</i> = 0.057). Multiple infarctions were related to perceptual speed, visuospatial skills, and working memory, but not to episodic or semantic memory. The authors found similar results with infarction volume. In secondary analyses, only infarctions that were clinically evident during life were associated with dementia and cognitive function. <b><i>Conclusion:</i></b> Cerebral infarctions are associated with a twofold increase in odds of dementia. Odds are higher in persons with multiple, large, or clinically evident infarctions. In addition, cerebral infarctions do not affect all cognitive systems equally, showing the strongest association with perceptual speed and the weakest with episodic memory.
A bibliometric evaluation of European Union research of the respiratory system from 1987–1998
Authors: F. García-Río, S. Serrano, A. Dorgham, R. Alvarez-Sala, A. Ruiz Peña, J.M. Pino, J.L. Alvarez-Sala, J. Villamor
Journal: European Respiratory Journal (2001)

This study analyses the evolution of the bibliometric indicators of productivity and repercussion of European Union (EU) research into the respiratory system during the period from 1987–1998, describing the geographical distribution. Using MedLine, a selection was made of those articles by EU authors published between 1987–1998 in 38 respiratory system journals (classification from the Institute for Scientific Information). The journals, country of origin, number of articles and the relation to socioeconomic data, productivity index, visibility index, expected impact factor (EIF) and relative impact factor (RIF) were all analysed. The number of EU publications in respiratory system journals experienced an exponential increase, going from 606 articles (14.3% of world production) in 1987, to 2,325 (33.2%) in 1998. During this same period, the EIF increased from 1,258 to 2,111. The greatest gross productivities were those of the UK, France, Italy and Germany, although when corrected for number of inhabitants, Sweden, the Netherlands, Belgium and Denmark headed the list. The countries with the greatest mean EIF were the Netherlands, the UK, Spain and Belgium. In conclusion, productivity and repercussions of European Union research of the respiratory system experienced an important increase during this period.
Epicardial/Mesothelial Cell Line Retains Vasculogenic Potential of Embryonic Epicardium
Authors: Aya M. Wada, Travis K. Smith, Megan E. Osler, David E. Reese, David M. Bader
Journal: Circulation Research (2003)

Recent work has demonstrated the importance of the epicardium in the development of the heart. During embryogenesis, these epithelial cells provide the progenitors for the epicardium, coronary smooth muscle, endothelium, and cardiac fibroblasts. The epicardium sends important signals to the developing myocardium. Still, analysis of these epithelial cells has lagged behind that of other cardiac cell types largely because of the lack of a defined experimental cell system in which epicardial cell differentiation can be studied. The present report examines the developmental potential of a cell line derived from rat epicardial mesothelial cells. These analyses demonstrate that the cell line retains many characteristics of the intact epithelium, including the ability to form a polarized epithelium and express many epicardial genes. Our data show for the first time that these cells retain the ability to produce mesenchyme in response to specific growth factors and, importantly, to generate smooth muscle cells. Thus, this study provides evidence that these cells can serve as an important model system for the analysis of the cellular and molecular mechanisms that govern epicardial development and function.
Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study
Authors: Jaana Lindström, Pirjo Ilanne-Parikka, Markku Peltonen, Sirkka Aunola, Johan G Eriksson, Katri Hemiö, Helena Hämäläinen, Pirjo Härkönen, Sirkka Keinänen-Kiukaanniemi, Mauri Laakso, Anne Louheranta, Marjo Mannelin, Merja Paturi, Jouko Sundvall, Timo T Valle, Matti Uusitupa, Jaakko Tuomilehto
Journal: The Lancet (2006)
Abstract A10: In silico design of biomarker-optimized drug combinations in ERBB2+ cancers
Authors: Jinyan Du, Daniel Kirouac, Johanna Lahdenranta, Ryan Overland, Matthew Onsum, Charlotte McDonagh
Journal: Cancer Research (2013)

Abstract Crosstalk and compensatory circuits within cancer signaling networks fundamentally limit the activity of targeted therapies. Combination drug regimens are thus required to fully inhibit an oncogenic network. However, rationally designing optimal combinations, given the large number of targeted agents available remains a challenge. Previously, we developed a multi-scale systems model of ERBB2-high breast cancer to quantitatively interrogate relationships between biomarkers (proxies for the mode of network activation) and combination drug efficacy. We found that targeting the ERBB2-ERBB3 heterodimer with a combination of ERBB2 inhibitors (trastuzumab and lapatinib) and an ERBB3 inhibitor (MM-111) was more effective at inducing tumor regression than the combination of an AKT and MEK inhibitor (MK2206 and GSK1120212), and was significantly better tolerated. However, the model was parameterized based on data collected from one cell line. Here we have performed profiling of an 18-cell line panel to assess whether our model and results are extendable to other ERBB2-high cancers. We monitored cell viability and signaling events upon AKT and MEK inhibitor treatments in the presence or absence of the ERBB3 ligand heregulin in these cell lines. While all cells were ERBB2+, we observed widely variable phenotypic and signaling dependencies on the PI3K/AKT and MAPK/ERK pathway activities across the panel. At the phenotypic level, cells primarily depend on either AKT or ERK signaling in basal conditions. Interestingly, upon heregulin stimulation some cells lines switch pathway dependency from AKT to ERK. Adaptive feedback circuits downstream of ERK and AKT were identified in all cell lines, though the identity and strength vary extensively. ERBB3 signaling and total AKT were consistently up-regulated to various degrees upon AKT inhibitor treatment. In contrast, multiple ERBB receptors as well as other RTKS, AKT signaling, and total ERK were upregulated in the response to MEK inhibition. While it is plausible that signaling pathways beyond AKT and ERK are modulating cell viability, we are able to quantitatively describe cell growth regulation based on AKT and ERK pathway activity using quantitative logic-based modeling framework. Our results will help us better understand how signaling events are decoded by cancer cells into phenotypic responses, and enable in silico drug combination screening across molecularly and functionally heterogeneous cancers. Citation Format: Jinyan Du, Daniel Kirouac, Johanna Lahdenranta, Ryan Overland, Matthew Onsum, Charlotte McDonagh. In silico design of biomarker-optimized drug combinations in ERBB2+ cancers. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A10.
SPECIFICITY OF THE IMMUNE RESPONSE TO THE 2, 4-DINITROPHENYL AND 2, 4, 6-TRINITROPHENYL GROUPS
Authors: J. Russell Little, Herman N. Eisen
Journal: The Journal of Experimental Medicine (1969)

THE PRINCIPAL RESULTS OF THE PRESENT STUDY ARE: (a) the failure to find an antibody subset that binds a cross-reacting ligand better than the comparable homologue in spite of the use of isolation methods that select for such antibody molecules; (b) the isolation of antibody subsets with virtually indistinguishable average intrinsic association constants for homologous and cross-reacting ligands, but which nevertheless have physical properties (Qmax and relative fluorescence coefficient) that readily distinguish these subsets according to their origin in response to antigenic stimulation with DNP- or with TNP-protein; (c) the demonstration, by precipitin reaction and measurement of association constants for homologous and cross-reacting haptens, of generally greater cross-reactivity among high affinity anti-DNP and anti-TNP antibodies, i.e. low affinity antibodies are generally more discriminating; (d) the selection of anti-DNP and anti-TNP antibody subsets that are distinctive in their ability to show spur formation in gel diffusion reactions with homologous and cross-reacting antigens. These results suggest that in the initial cellular response to antigenic stimulation, DNP-BgammaG and TNP-BgammaG stimulate virtually nonoverlapping sets of antigen-sensitive cells, despite the great similarity of these two immunogens. With prolonged stimulation this specificity wanes, giving rise to a more degenerate response evident in the greater cross-reactivity of the antibodies produced later in immunization.
Neonatal Diabetes With End-Stage Nephropathy
Authors: Enric Esmatjes, Amanda Jimenez, Gonzalo Diaz, Mireia Mora, Roser Casamitjana, G. Pérez de Nanclares, Luis Castaño, Maria José Ricart
Journal: Diabetes Care (2008)

OBJECTIVE—To describe the diagnosis of a patient with neonatal diabetes who had been misdiagnosed with type 1 diabetes and referred to our hospital for pancreas and kidney transplantation because of end-stage renal disease. RESEARCH DESIGN AND METHODS—A diagnosis of neonatal diabetes was made after a molecular genetic study revealed a mutation in exon 34 of the ABCC8 gene. Pancreas transplantation was ill-advised. RESULTS—The patient was switched from insulin to glibenclamide 4 months after kidney transplantation, confirming that pancreas transplantation would not have been a good decision. CONCLUSIONS—This is the first report of a patient with neonatal diabetes who developed diabetic nephropathy that progressed to end-stage renal disease. This report illustrates that careful endocrinological evaluation, including molecular genetic studies, if necessary, is mandatory before a decision to perform a pancreas transplant is made.
Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Thomas P. Cappola, David A. Kass, Gregory S. Nelson, Ronald D. Berger, Gisele O. Rosas, Zoulficar A. Kobeissi, Eduardo Marbán, Joshua M. Hare
Journal: Circulation (2001)

Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy.Patients (n=9; ejection fraction, 29+/-3%) were instrumented to assess myocardial oxygen consumption (MVO(2)), peak rate of rise of left ventricular pressure (dP/dt(max)), stroke work (SW), and efficiency (dP/dt(max)/MV O(2) and SW/MVO(2)) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in MVO(2) (peak effect, -16+/-5%; P<0.01; n=9) with no parallel decrease in dP/dt(max) or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dt(max)/MVO(2), 22+/-9%, n=9; SW/MVO(2), 40+/-17%, n=6; both P<0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and beta-blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot.These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.
Interleukin 1 receptor antagonist. A new member of the interleukin 1 family.
Authors: W P Arend
Journal: Journal of Clinical Investigation (1991)

This review has summarized recent information derived from many laboratories on the discovery, characteristics, and properties of a new member of the IL-1 family, IL-1 receptor antagonist. In addition to information, an emphasis has been placed on unanswered questions and new concepts. The existence of this first-described naturally occurring specific cytokine receptor antagonist may lead to a different perspective on the cytokine network. A major unanswered question emphasized throughout this review, that now can be addressed more directly, concerns what are the physiological roles of members of the IL-1 family. Although IL-1 beta is presumed to function primarily as an extracellular cytokine, this molecule lacks a leader peptide, is synthesized and handled by the cells in a manner suggestive of a cytoplasmic (not secretory) protein, and may only be released after cellular injury. Furthermore, although IL-1ra possesses a leader sequence, 50% or more of this protein remains cell associated. Do these observations suggest that members of the IL-1 family possess important intracellular functions, as yet undetermined? IL-1 alpha may play an intracellular role in regulating senescence; an IL-1 alpha antisense oligodeoxynucleotide was shown to prolong the life span of cultured human endothelial cells. Whether intracellular IL-1ra plays a role in influencing life span has not been determined. The discovery of IL-1ra has led to a first level of assumptions that this molecule may be functioning in vivo to regulate the pleiotropic extracellular effects of IL-1 in physiological or pathophysiological processes. Although enticing, these assumptions have not yet been proven to be true. Perhaps we need to look beyond, or within, and consider that IL-1ra and other members of the IL-1 family may have additional roles in normal or abnormal cell growth and development.
EGF Receptor Inhibition Radiosensitizes NSCLC Cells by Inducing Senescence in Cells Sustaining DNA Double-Strand Breaks
Authors: Meng Wang, Fabian Morsbach, David Sander, Liliana Gheorghiu, Akash Nanda, Cyril Benes, Malte Kriegs, Mechthild Krause, Ekkehard Dikomey, Michael Baumann, Jochen Dahm-Daphi, Jeffrey Settleman, Henning Willers
Journal: Cancer Research (2011)

The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR) sensitizes non-small cell lung cancer (NSCLC) cells to ionizing radiation remain poorly understood. We set out to characterize the radiosensitizing effects of the tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to pronounced cellular senescence but not apoptosis of irradiated cells, both in vitro and in vivo. Senescence was completely dependent on wild-type p53 and associated with a reduction in cell number as well as impaired clonogenic radiation survival. Study of ten additional NSCLC cell lines revealed that senescence is a prominent mechanism of radiosensitization in 45% of cell lines and occurs not only in cells with wild-type p53 but also in cells with mutant p53, where it is associated with an induction of p16. Interestingly, senescence and radiosensitization were linked to an increase in residual radiation-induced DNA double-strand breaks irrespective of p53/p16 status. This effect of EGFR inhibition was at least partially mediated by disruption of the MEK-ERK pathway. Thus, our data indicate a common mechanism of radiosensitization by erlotinib or cetuximab across diverse genetic backgrounds. Our findings also suggest that assays that are able to capture the initial proliferative delay that is associated with senescence should be useful for screening large cell line panels to identify genomic biomarkers of EGFR inhibitor-mediated radiosensitization.
Life history of eNOS: Partners and pathways
Authors: D DUDZINSKI, T MICHEL
Journal: Cardiovascular Research (2007)

The complex regulation of eNOS (endothelial nitric oxide synthase) in cardiovascular physiology occurs at multiple stages. eNOS mRNA levels are controlled both at the transcriptional and post-transcriptional phases, and epigenetic mechanisms appear to modulate tissue-specific eNOS expression. The eNOS enzyme reversibly associates with a diverse family of protein partners that regulate eNOS sub-cellular localization, catalytic function, and biological activity. eNOS enzyme activity and sub-cellular localization are intimately controlled by post-translational modifications including phosphorylation, nitrosylation, and acylation. The multiple extra-cellular stimuli affecting eNOS function coordinate their efforts through these key modifications to dynamically control eNOS and NO bioactivity in the vessel wall. This review will focus on the biochemical partners and perturbations of the eNOS protein as this vital enzyme undergoes modulation by diverse signal transduction pathways in the vascular endothelium.
Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis.
Authors: A Ireland, C H Mason, D P Jewell
Journal: Gut (1988)

One hundred and sixty four patients with ulcerative colitis in remission were entered into a double blind, double dummy trial comparing olsalazine 500 mg bd and sulphasalazine 1 g bd. Clinical examination, sigmoidoscopy and rectal biopsy were performed at 0, three, and six months. Sixteen of 82 (19.5%) patients relapsed on olsalazine and 10/82 (12.2%) relapsed on sulphasalazine. The difference was not statistically significant (p = 0.1632). Adverse events were minor and were similar in both groups. No haematological or biochemical abnormalities were detected. Thus, olsalazine is as effective as sulphasalazine for preventing a relapse of ulcerative colitis.
Apoptosis induction by nitric oxide in adult cardiomyocytes via cGMP-signaling and its impairment after simulated ischemia
Authors: G Taimor
Journal: Cardiovascular Research (2000)

Objective: Nitric oxide (NO) has been shown to induce apoptosis in cardiomyocytes under normoxic conditions. The ability of NO to induce apoptosis after ischemia–reperfusion, a situation of increased NO release in vivo, has not been investigated. The present study was undertaken to characterize the pathway of induction of apoptosis by NO and the influence of ischemia on this pathway in cardiomyocytes. Methods: The study was performed on isolated adult cardiomyocytes of the rat. Ischemia was simulated by anoxia in a glucose free medium, pH 6.4. Induction of apoptosis was detected (1) by annexinV-fluorescein isothiocyanate (annexinV-FITC) binding to cells under exclusion of propidium iodide and (2) by laddering of genomic DNA. Results: Incubation of cardiomyocytes with the NO-donor (±)-S-nitroso-N-acetylpenicillamine (SNAP, 100 μM) induced apoptosis in 14.1±1.9% of the cells and necrosis in 24.4±4.6%. The induction of apoptosis but not necrosis could be blocked by inhibition of soluble guanylyl cyclase or of protein kinase G. Apoptosis induction was mimicked by incubation of cardiomyocytes with 8-pCPT-cGMP (100 μM, 9.6±0.6% apoptotic cells) or YC-1 (75 μM, 14.6±2.8% apoptotic cells), a direct activator of soluble guanylyl cyclase. After 3 h of anoxia, cardiomyocytes were transiently protected against apoptosis induced by NO, but not by 8-pCPT-cGMP or YC-1 (8.9±0.7% or 13.4±2.4% apoptotic cells). A correlation of the apoptotic response to SNAP or YC-1 with an increased activity of soluble guanylyl cyclase, determined by measurements of intracellular cGMP contents, was found. Conclusions: NO induces apoptosis in a cGMP dependent manner in isolated adult cardiomyocytes whereas induction of necrosis seems cGMP-independent. After simulated in vitro ischemia the activation of soluble guanylyl cyclase by NO is transiently inhibited resulting in a transient anti-apoptotic protection.
Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer
Authors: Helmut Oettle, Stefan Post, Peter Neuhaus, Klaus Gellert, Jan Langrehr, Karsten Ridwelski, Harald Schramm, Joerg Fahlke, Carl Zuelke, Christof Burkart, Klaus Gutberlet, Erika Kettner, Harald Schmalenberg, Karin Weigang-Koehler, Wolf-Otto Bechstein, Marco Niedergethmann, Ingo Schmidt-Wolf, Lars Roll, Bernd Doerken, Hanno Riess
Journal: JAMA (2007)

ITH AN ESTIMATED NUMber of 232 000 new cases per year, pancreatic cancer is among the most common malignancies worldwide. 1Moreover, it is one of the most lethal cancers, as indicated by a mortality incidence ratio of 98%. 1 Pancreatic cancer is the fourth leading cause of death from cancer in the United States, with 32 300 deaths estimated in 2006. 2 Sur-See also p 311 and Patient Page.