tbuckley/cabot-search huggingface dataset:
Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo.
Authors: J de la Mata, H L Uy, T A Guise, B Story, B F Boyce, G R Mundy, G D Roodman
Journal: Journal of Clinical Investigation (1995)

Tumors frequently induce the multifunctional cytokine IL-6, which has been linked to several paraneoplastic syndromes, most notably cachexia. IL-6 stimulates osteoclast formation, causes mild hypercalcemia, and is produced by bone cells in vitro upon exposure to systemic hormones. Since IL-6 is produced together with parathyroid hormone-related protein (PTH-rP) in some patients with cancer, we tested the hypothesis that production of IL-6 potentiates the effects of PTH-rP on Ca2+ homeostasis and osteoclastic bone resorption and examined potential mechanisms for these interactions in vivo. Chinese hamster ovarian (CHO) cells stably transfected with cDNAs for IL-6 (CHO/IL-6) and PTH-rP sense (CHO/PTH-rP) or antisense (CHO/PTH-rP AS) were inoculated intramuscularly into nude mice. Experimental groups included CHO/IL-6 plus CHO/PTH-rP; CHO/IL-6 plus CHO/PTH-rP AS; CHO/IL-6 alone; and CHO/PTH-rP alone. Blood ionized Ca2+ was measured on days 0, 7, 10, 12, and 13. Three different developmental stages in the osteoclast lineage were examined at day 13: the early multipotential precursor, granulocyte macrophage colony-forming units (CFU-GM); more mature mononuclear osteoclast precursors, assessed by their capacity to form tartrate-resistant acid phosphatase-positive multinucleated cells in marrow cultures; and mature osteoclasts, assessed by histomorphometry. IL-6 increased CFU-GM but not bone resorption or Ca2+. In contrast, PTH-rP induced hypercalcemia and bone resorption and increased multinucleated osteoclasts and more mature precursors cells, but not CFU-GM. However, mice treated with both IL-6 and PTH-rP had very marked hypercalcemia and osteoclastosis as well as an increase in the number of both CFU-GM and mature osteoclast precursors. These data demonstrate that IL-6 enhances PTH-rP-mediated hypercalcemia and bone resorption, most likely by increasing the pool of early osteoclast precursors that in turn can differentiate to mature osteoclasts. We conclude that IL-6 stimulatory effects on osteoclast precursors may enhance the effects of other bone resorption factors that act at later stages in the osteoclast lineage.
Role of IL-1 and the Nlrp3/caspase-1/IL-1 axis in cigarette smoke-induced pulmonary inflammation and COPD
Authors: N.S. Pauwels, K.R. Bracke, L.L. Dupont, G.R. Van Pottelberge, S. Provoost, T. Vanden Berghe, P. Vandenabeele, B.N. Lambrecht, G.F. Joos, G.G. Brusselle
Journal: European Respiratory Journal (2011)

Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses. We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD. In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1β. Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers. These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.
CSF Norepinephrine Concentrations in Posttraumatic Stress Disorder
Authors: Thomas D. Geracioti, Dewleen G. Baker, Nosakhare N. Ekhator, Scott A. West, Kelly K. Hill, Ann B. Bruce, Dennis Schmidt, Barbara Rounds-Kugler, Rachel Yehuda, Paul E. Keck, John W. Kasckow
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD. METHOD: CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under baseline (unstressed) conditions. Severity of the patients' PTSD symptoms was assessed with the Clinician-Administered PTSD Scale. RESULTS: CSF norepinephrine concentrations were significantly higher in the men with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms. CONCLUSIONS: These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.
Impairment in Postischemic Neovascularization in Mice Lacking the CXC Chemokine Receptor 3
Authors: Ludovic Waeckel, Ziad Mallat, Stéphane Potteaux, Christophe Combadière, Michel Clergue, Micheline Duriez, Lu Bao, Craig Gerard, Barrett J. Rollins, Alain Tedgui, Bernard I. Levy, Jean-Sébastien Silvestre
Journal: Circulation Research (2005)

Inflammatory cell infiltration is a feature of postischemic neovascularization. However, mechanisms leading to leukocyte attraction to the site of neovascularization are still undefined. We hypothesized that the CXC chemokine receptor 3 (CXCR3) may contribute to leukocyte accumulation and subsequently to blood vessel growth in the ischemic area. Ischemia induced by femoral artery ligature improved the number of CXCR3-expressing cells and the level of its ligand, CXCL10. Angiographic score, blood flow recovery measurement, and capillary density analysis showed a significant decrease of ischemic/nonischemic leg ratio in CXCR3-deficient mice when compared with controls ( P &lt;0.05), at day 21 after ischemia. Interestingly, this impairment was as important as that observed in mice deficient for the well known CC-chemokine monocyte chemoattractant protein-1 (MCP-1). At day 7 of ischemic injury, the number of CD3-positive T cells and Mac-3–positive monocytes/macrophages was 38% and 45% lower, respectively, in the ischemic leg of CXCR3-deficient mice compared with the control group ( P &lt;0.05), suggesting an important role for CXCR3 in leukocyte recruitment into the ischemic area. VEGF protein content, a classical proangiogenic factor, was also markedly reduced (80% reduction) in ischemic leg of CXCR3-deficient mice ( P &lt;0.01). Injection of bone marrow–derived mononuclear cells (BM-MNCs) isolated from wild-type animals restored the neovascularization reaction in CXCR3-deficient mice whereas BM-MNCs from CXCR3-deficient mice was ineffective. In conclusion, CXCR3 plays a key role in neovascularization and provides novel information on the mechanisms leading to leukocyte infiltration in the vessel growth area.
Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease
Authors: Xuebin Liu, Stewart Leung, Chunxia Wang, Zhu Tan, Ji Wang, Taylor B Guo, Lei Fang, Yonggang Zhao, Bing Wan, Xia Qin, Limin Lu, Runsheng Li, Heng Pan, Mingjuan Song, Ailian Liu, Jian Hong, Hongtao Lu, Jingwu Z Zhang
Journal: Nature Medicine (2010)
Physiology of B cells in mice with X-linked immunodeficiency. II. Influence of the thymus and mature T cells on B cell differentiation.
Authors: J Sprent, J Bruce
Journal: The Journal of Experimental Medicine (1984)

Evidence is presented that the in vivo differentiation of B cells expressing X-linked immunodeficiency (xid) is controlled by mature T cells. Normal (C57BL/6 X CBA/J)F1 mice were thymectomized (ATx), heavily irradiated, and reconstituted with CBA/N (xid) or CBA/Ca (nondefective) marrow. In contrast to sham-operated mice, ATx recipients of xid marrow showed an almost total absence of Ig+ B cells in lymph nodes (LN) and thoracic duct lymph at 2 mo post-reconstitution ; B cells were markedly reduced in the spleen in some mice but only moderately in others. Addition of mature T cells soon after marrow reconstitution substantially abrogated the B cell depletion. In control experiments with nondefective B cells, the number of B cells developing in ATx irradiated recipients of normal (xid-) marrow cells was not detectably lower than in sham-operated recipients. These data imply that a subset of T-dependent B cells is either missing in normal mice or present in only very small numbers.
Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene
Authors: Maria Meehan, Laavanya Parthasarathi, Niamh Moran, Caroline A Jefferies, Niamh Foley, Elisa Lazzari, Derek Murphy, Jacqueline Ryan, Berenice Ortiz, Armida W M Fabius, Timothy A Chan, Raymond L Stallings
Journal: Molecular Cancer (2012)

Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD , indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.
Authors response. The chronic obstructive pulmonary disease (COPD) control panel: towards personalised medicine in COPD
Authors: Alvar Agusti, William MacNee
Journal: Thorax (2013)

We thank Dr Vishnivetsky et al 1 for their interest in our paper on the ‘COPD control panel’. We are happy to see that our proposal has generated some debate. In their letter, Dr Vishnivetsky and colleagues raise several important issues: (1) Relevance of comorbidities . We fully agree with their comments. Whether or not they should be ‘prioritised’ in the control panel proposed is open for debate. …
Bronchopulmonary Disease in Children with Cystic Fibrosis after Early or Delayed Diagnosis
Authors: Philip M. Farrell, Zhanhai Li, Michael R. Kosorok, Anita Laxova, Christopher G. Green, Jannette Collins, Hui-Chuan Lai, Michael J. Rock, Mark L. Splaingard
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Although early diagnosis of cystic fibrosis (CF) can lead to nutritional benefits, there has been uncertainty about pulmonary outcomes. Using a randomized controlled trial with unique unblinding/surveillance, we evaluated patients with CF who received similar treatment after being assigned to an early diagnosis (screened) group or to a standard diagnosis (control) group. When the youngest patient was 7 years of age, we compared outcomes using pulmonary function data and quantitative chest radiology. In the screened group (56 patients), diagnosis was made at a younger age of 12.4 weeks, compared with the diagnosis in control group (47 control patients) at the age of 95.8 weeks, but included a significantly greater proportion of patients with deltaF508 genotypes and pancreatic insufficiency. The first chest radiograph showed significantly fewer abnormalities in the screened group; but, over time, the two groups converged, and after 10 years of age the screened patients showed worse chest X-ray scores associated with earlier acquisition of Pseudomonas aeruginosa. No differences were detected in any measure of pulmonary dysfunction, which was generally mild in each group. Although CF neonatal screening provides a potential opportunity for better pulmonary outcomes, it appears that respiratory infections and pancreatic status are the dominant factors in pulmonary prognosis.
ABC of nutrition. Other nutritional deficiencies in affluent communities.
Authors: A S Truswell
Journal: BMJ (1985)

Iron is essential for haemoglobin formation.It is also part ofmyoglobin, ofsome enzymes required for neurotransmitter synthesis, and ofan important enzyme in DNA synthesis.In deficiency, sometimes before there is anaemia, reduced maximum muscular work capacity has been reported, 1333
Prevalence of Depression in Individuals With Impaired Glucose Metabolism or Undiagnosed Diabetes
Authors: Arie Nouwen, Giesje Nefs, Isabela Caramlau, Martin Connock, Kirsty Winkley, Cathy E. Lloyd, Mark Peyrot, François Pouwer
Journal: Diabetes Care (2011)

Meta-analyses have shown that the risk for depression is elevated in type 2 diabetes. Whether this risk in individuals with impaired glucose metabolism (IGM) or undiagnosed diabetes (UDD) is elevated relative to normal glucose metabolism (NGM) or decreased relative to previously diagnosed type 2 diabetes (PDD) has not been the subject of a systematic review/meta-analysis. This study examined the prevalence of depression in IGM and UDD subjects relative to each other and to NGM and PDD subjects by reviewing the literature and conducting a meta-analysis of studies on this topic.EMBASE and MEDLINE databases were searched for articles published up to May 2010. All studies that compared the prevalence of depression in subjects with IGM and UDD were included. Odds ratios (ORs) were calculated using fixed and random-effects models.The meta-analysis showed that the risk for depression was not increased in IGM versus NGM subjects (OR 0.96, 95% CI 0.85-1.08). Risk for depression did not differ between individuals with UDD and individuals with either NGM (OR 0.94, 95% CI 0.71-1.25) or IGM (OR 1.16, 95% CI 0.88-1.54). Finally, individuals with IGM or UDD both had a significantly lower risk of depression than individuals with PDD (OR 0.59, 95% CI 0.48-0.73, and OR 0.57, 95% CI 0.45-0.74, respectively).Results of this meta-analysis show that the risk of depression is similar for NGM, IGM, and UDD subjects. PDD subjects have an increased risk of depression relative to IGM and UDD subjects.
NGS-Logistics: federated analysis of NGS sequence variants across multiple locations
Authors: Amin Ardeshirdavani, Erika Souche, Luc Dehaspe, Jeroen Van Houdt, Joris Robert Vermeesch, Yves Moreau
Journal: Genome Medicine (2014)

As many personal genomes are being sequenced, collaborative analysis of those genomes has become essential. However, analysis of personal genomic data raises important privacy and confidentiality issues. We propose a methodology for federated analysis of sequence variants from personal genomes. Specific base-pair positions and/or regions are queried for samples to which the user has access but also for the whole population. The statistics results do not breach data confidentiality but allow further exploration of the data; researchers can negotiate access to relevant samples through pseudonymous identifiers. This approach minimizes the impact on data confidentiality while enabling powerful data analysis by gaining access to important rare samples. Our methodology is implemented in an open source tool called NGS-Logistics, freely available at https://ngsl.esat.kuleuven.be.
Staple line as a cause of unusual early internal hernia after appendectomy
Authors: Meenakshi Rajan, Fernando Dip, Samuel Szomstein, Antonio Zanghì, Andrea Cavallaro, Maria Di Vita, Francesco Cardì, Paolo Di Mattia, Alessandro Cappellani, Emanuele Lo Menzo, Raul Rosenthal
Journal: International Journal of Surgery (2014)
p56lck interacts via its src homology 2 domain with the ZAP-70 kinase.
Authors: P Duplay, M Thome, F Hervé, O Acuto
Journal: The Journal of Experimental Medicine (1994)

p56lck, a member of the src family of protein tyrosine kinases, is an essential component in T cell receptor (TCR) signal transduction. p56lck contains a src homology 2 (SH2) domain found in a number of proteins involved in intracellular signaling. SH2 domains have been implicated in protein-protein interactions by binding to sequences in target proteins containing phosphorylated tyrosine. Using an in vitro assay, we have studied specific binding of tyrosine-phosphorylated proteins to a recombinant p56lck SH2 domain. In nonactivated Jurkat cells, two tyrosine-phosphorylated proteins were detected. Stimulation with anti-CD3 monoclonal antibodies induced the binding of seven additional tyrosine-phosphorylated proteins to the SH2 domain of p56lck. We have identified the zeta-associated tyrosine kinase, ZAP-70, as one of these proteins. Evidence suggests that binding of ZAP-70 to p56lck SH2 is direct and not mediated by zeta. The significance of this interaction was further investigated in vivo. p56lck could be coprecipitated with the zeta/ZAP-70 complex and conversely, ZAP-70 was detected in p56lck immunoprecipitates of activated Jurkat cells. The physical association of p56lck and ZAP-70 during activation supports the recently proposed functional cooperation of these two tyrosine kinases in TCR signaling.
Hydroxycarbamide: a treatment for lichen sclerosus?
Authors: N. Tomson, J.C. Sterling
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, A 67‐year‐old woman was diagnosed with lichen sclerosus (LS) 10 years ago in our dermatology department. She presented with vulval itching and soreness and had shiny, white, atrophic plaques with telangiectasia and purpura on the labia minora, as well as erythema and fissuring at the posterior fourchette. Over the last 10 years, she has experienced vulval soreness daily. She was treated initially with clobetasone butyrate 0·05% (Trimovate®; GlaxoSmithKline, Uxbridge, U.K.) cream twice daily but has needed to use clobetasol propionate 0·05% (Dermovate®; GlaxoSmithKline) ointment frequently to control her symptoms. In November 2005, she was diagnosed with polycythaemia rubra vera following investigations for malaise. She was started on hydroxycarbamide (hydroxyurea) 1 g daily. Within a month she noticed that her vulval soreness and pruritus had improved, and was asymptomatic by January 2006. She has not used any treatment for her LS over the last 9 months and attributes the improvement in her vulval symptoms to the hydroxycarbamide that she continues to take. She remains asymptomatic with only mild scarring over the labia minora. To our knowledge this is the first case report of LS improving following the initiation of hydroxycarbamide.
A Teachable Moment for Oncologists: Cancer Survivors, 10 Million Strong and Growing!
Authors: Patricia A. Ganz
Journal: Journal of Clinical Oncology (2005)

During the last 25 years we have witnessed the remarkable transformation of cancer from an immediately fatal disease to one in which the majority of individuals receive highly effective treatments that result in long-term, diseasefree survivorship. 1 One need only think about the remarkable public achievements of cyclist Lance Armstrong to understand that life after cancer can permit continued high levels of physical and psychological performance. Although Armstrong’s achievements after cancer may not reflect the norm, they do represent one end of the spectrum for the quality of life after cancer treatment. More often, however, cancer patients are left with subtle and sometimes more overt sequelae from their cancer treatments that follow
Applying electrical impedance tomography to dynamically monitor retroperitoneal bleeding in a renal trauma patient
Authors: Fusheng You, Xuetao Shi, Wanjun Shuai, Hongyi Zhang, Wei Zhang, Feng Fu, Ruigang Liu, Canhua Xu, Tingyi Bao, Xiuzhen Dong
Journal: Intensive Care Medicine (2013)

Applying electrical impedance tomography to dynamically monitor retroperitoneal
Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study
Authors: Walter H Gotlieb, Frederic Amant, Suresh Advani, Chanchal Goswami, Hal Hirte, Diane Provencher, Naresh Somani, S Diane Yamada, Jean-Francois Tamby, Ignace Vergote
Journal: The Lancet Oncology (2011)
Cyclophilin-Mediated Pathways in the Effect of Cyclosporin A on Endothelial Cells
Authors: M. Victoria Alvarez-Arroyo, Susana Yagüe, Ronald M. Wenger, Daniel S. Pereira, Sonsoles Jiménez, Francisco R. González-Pacheco, M. Angeles Castilla, Juan José P. Deudero, Carlos Caramelo
Journal: Circulation Research (2002)

The relative importance of cyclophilin (CyP) versus calcineurin (Cn)-mediated mechanisms in the effect of cyclosporin A (CsA) on endothelial cells (ECs) is largely unknown. In cultured ECs, CsA was cytotoxic/proapoptotic or cytoprotective/antiapoptotic at high or low concentrations, respectively. CsA analogs (MeVal-4-CsA and MeIle-4-CsA), which bind to CyP but do not inhibit Cn, closely reproduced the CsA effects. Based on our previous data, the role of vascular endothelial growth factor (VEGF) as a mediator of CsA-induced cytoprotection was further analyzed. The actions of CsA and CsA analogs were shifted from a protective to a cell-damaging pattern in the presence of a specific anti-VEGF monoclonal antibody (mAb). This positive interaction was further supported by a transient increase in cytosolic free calcium concentration ([Ca 2+ ] i ) by VEGF after pretreatment with either CsA or MeVal-4-CsA and an increase in the expression and synthesis of VEGF receptor 2 (VEGFR2). Of functional importance, blockade of the interaction between VEGF and VEGFR2 by a VEGFR2 mAb abolished the cytoprotective effect of CsA. In addition, preconditioning with low concentrations of CsA or CsA analogs increased both cytoprotection and VEGFR2 mRNA expression when EC were exposed to higher concentrations of CsA. In summary, our results reveal that (1) the biphasic responses to CsA in EC are related to the interaction of CsA with CyP rather than with Cn and (2) VEGF is a critical factor in the cytoprotective effect of CsA, by a mechanism that involves VEGFR2.