tbuckley/cabot-search huggingface dataset:
Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis.
Authors: H W Murray, J S Cervia, J Hariprashad, A P Taylor, M Y Stoeckle, H Hockman
Journal: Journal of Clinical Investigation (1995)

GM-CSF induces three effects potentially beneficial in visceral leishmaniasis: blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. To determine the experimental role and effect of GM-CSF in this intracellular infection, livers from Leishmania donovani-infected BALB/c mice were tested for GM-CSF mRNA expression and mice were treated with anti-GM-CSF antiserum or GM-CSF. L. donovani infection upregulated hepatic GM-CSF mRNA expression by 10-fold, and anti-GM-CSF treatment exacerbated visceral infection and tripled liver parasite burdens 4 wk after challenge. In euthymic mice with established infection, treatment with 1-5 micrograms/d murine GM-CSF induced three dose-related effects: peripheral blood leukocytosis, preferential accumulation of myelomonocytic cells at visceral foci of infection, and leishmanicidal activity comparable to that achieved by IFN-gamma. These effects were either largely or entirely T cell dependent. Treatment with human GM-CSF also induced anti-leishmanial activity but with little effect on peripheral leukocyte number or tissue myelomonocytic cell influx; human G-CSF stimulated marked peripheral granulocytosis and neutrophil tissue accumulation but induced little antileishmanial effect. These results identify a role for endogenous GM-CSF in the initial host defense response to L. donovani, reemphasize the influxing monocyte as an effector cell, and indicate that GM-CSF can be used as an antileishmanial treatment.
T-bet is essential for encephalitogenicity of both Th1 and Th17 cells
Authors: Yuhong Yang, Jeffrey Weiner, Yue Liu, Alan J. Smith, David J. Huss, Ryan Winger, Haiyan Peng, Petra D. Cravens, Michael K. Racke, Amy E. Lovett-Racke
Journal: The Journal of Experimental Medicine (2009)

The extent to which myelin-specific Th1 and Th17 cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) is controversial. Combinations of interleukin (IL)-1β, IL-6, and IL-23 with transforming growth factor β were used to differentiate myelin-specific T cell receptor transgenic T cells into Th17 cells, none of which could induce EAE, whereas Th1 cells consistently transferred disease. However, IL-6 was found to promote the differentiation of encephalitogenic Th17 cells. Further analysis of myelin-specific T cells that were encephalitogenic in spontaneous EAE and actively induced EAE demonstrated that T-bet expression was critical for pathogenicity, regardless of cytokine expression by the encephalitogenic T cells. These data suggest that encephalitogenicity of myelin-specific T cells appears to be mediated by a pathway dependent on T-bet and not necessarily pathway-specific end products, such as interferon γ and IL-17.
Insulinlike growth factor I regulation of growth hormone gene transcription in primary rat pituitary cells.
Authors: S Yamashita, S Melmed
Journal: Journal of Clinical Investigation (1987)

We have previously shown that insulinlike growth factor I (IGF-I) inhibits growth hormone (GH) secretion and messenger RNA (mRNA) levels in pituitary cells. The effects of IGF-I on new GH mRNA synthesis rates in primary monolayer rat pituitary cells were therefore examined by nuclear runoff transcription assays. IGF-I (1.3 nM) treatment for 1 h inhibited GH gene transcription to 60% of controls. IGF-I (3.25 nM) maximally suppressed GH gene transcription to 30% of control values after 4 h. After 24 h treatment, GH transcription was suppressed to 48% of controls by 3.25 nM IGF-I. IGF-I (3.25 nM) also inhibited the twofold growth hormone-releasing hormone (GHRH) (10 nM)-stimulated GH gene transcription by 30% after 4 h. Transcription of the prolactin (PRL) gene was not suppressed in these cells by IGF-I. Relatively high doses of insulin (200 nM) also suppressed GH gene transcription, but epidermal growth factor and fibroblast growth factor did not change GH mRNA synthesis. The results show that IGF-I exerts a rapid and selective suppression of basal and GHRH-stimulated GH gene transcription. These data indicate a role for IGF-I in negative feedback of GH gene expression and provide evidence for the direct transcriptional regulation of the GH gene by IGF-I in primary rat anterior pituitary cells.
Orthodeoxia and postural orthostatic tachycardia in patients with pulmonary arteriovenous malformations: a prospective 8-year series
Authors: V Santhirapala, B Chamali, H McKernan, H C Tighe, L C Williams, J T Springett, H R Bellenberg, A J Whitaker, C L Shovlin
Journal: Thorax (2014)

Postural changes in 258 patients with pulmonary arteriovenous malformations (PAVMs) reviewed between 2005 and 2013 were evaluated prospectively using validated pulse oximetry methods. Of the 257 completing the test, 75 (29%) demonstrated orthodeoxia with an oxygen saturation fall of at least 2% on standing. None described platypnoea (dyspnoea on standing). The heart rate was consistently higher in the erect posture: 74 (29%) had a postural orthostatic tachycardia of ≥20 min<sup>−1</sup>, and in 25 (10%) this exceeded 30 min<sup>−1</sup>. Orthostatic tachycardia was more pronounced in PAVM patients than controls without orthodeoxia (age-adjusted coefficient 5.5 (95% CIs 2.6, 8.4) min<sup>−1</sup>, p&lt;0.001). For PAVM patients, the age-adjusted pulse rise was 0.79 min<sup>−1</sup> greater for every 1% greater drop in oxygen saturation on standing (p&lt;0.001). In contrast to the postural orthostatic tachycardia syndrome, in this population, there was a trend for more pronounced orthostatic tachycardia to be associated with better exercise tolerance.
Review of research on aboriginal populations in Canada: relevance to their health needs
Authors: T K. Young
Journal: BMJ (2003)

To determine if research has adequately examined the health needs of the aboriginal population of Canada.Review.Medline search of journal articles published during 1992-2001. The search terms used were "Canada" and various synonyms and categories for Canadian aboriginal people. Each paper was categorised according to the aboriginal group, age-sex group, comparison group, geographic location, and type of research topic (health determinant, health status, or health care).Of 352 citations found, 254 were selected after elimination of those without abstracts, not containing data on Canada, or not focusing on health issues. The proportion of papers does not reflect the demographic composition of aboriginal people in Canada, with severe under-representation of Métis, urban aboriginal people, and First Nations people not living on reserves and over-representation of the Inuit. Children and women received less attention proportional to their share of the population. A few prolific research groups have generated a disproportionate amount of publications from a few communities and regions. 174 papers dealt with health determinants (for example, genetics, diet, and contaminants), 173 with health status, and 75 with health care. Injuries, which account for a third of all deaths, were studied in only 8 papers. None of the health care papers examined rehabilitation.Researchers have not adequately examined several important health needs of the aboriginal population.
Lithium rescues synaptic plasticity and memory in Down syndrome mice
Authors: Andrea Contestabile, Barbara Greco, Diego Ghezzi, Valter Tucci, Fabio Benfenati, Laura Gasparini
Journal: Journal of Clinical Investigation (2012)

Down syndrome (DS) patients exhibit abnormalities of hippocampal-dependent explicit memory, a feature that is replicated in relevant mouse models of the disease. Adult hippocampal neurogenesis, which is impaired in DS and other neuropsychiatric diseases, plays a key role in hippocampal circuit plasticity and has been implicated in learning and memory. However, it remains unknown whether increasing adult neurogenesis improves hippocampal plasticity and behavioral performance in the multifactorial context of DS. We report that, in the Ts65Dn mouse model of DS, chronic administration of lithium, a clinically used mood stabilizer, promoted the proliferation of neuronal precursor cells through the pharmacological activation of the Wnt/β-catenin pathway and restored adult neurogenesis in the hippocampal dentate gyrus (DG) to physiological levels. The restoration of adult neurogenesis completely rescued the synaptic plasticity of newborn neurons in the DG and led to the full recovery of behavioral performance in fear conditioning, object location, and novel object recognition tests. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult DS mice rescues hippocampal plasticity and memory and implicate adult neurogenesis as a promising therapeutic target to alleviate cognitive deficits in DS patients.
Effects of physical activity on exercise tests and respiratory function
Authors: Y J Cheng, C A Macera, C L Addy, F S Sy, D Wieland, S N Blair
Journal: British Journal of Sports Medicine (2003)

Background: Exercise is an important component of pulmonary rehabilitation for patients with chronic lung disease. Objective: To explore the role of physical activity in maintaining cardiac and respiratory function in healthy people. Methods: Cardiorespiratory fitness was measured by a maximal treadmill test (MTT), and respiratory function was tested by spirometry. The cross sectional study included data from 24 536 healthy persons who were examined at the Cooper Clinic between 1971 and 1995; the longitudinal study included data from 5707 healthy persons who had an initial visit between 1971 and 1995 and a subsequent visit during the next five years. All participants were aged 25–55 years and completed a cardiorespiratory test and a medical questionnaire. Results: In the cross sectional study, after controlling for covariates, being active and not being a recent smoker were associated with better cardiorespiratory fitness and respiratory function in both men and women. In the follow up study, persons who remained or became active had better MTT than persons who remained or became sedentary. Men who remained active had higher forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) than the other groups. Smoking was related to lower cardiorespiratory fitness and respiratory function. Conclusions: Physical activity and non-smoking or smoking cessation is associated with maintenance of cardiorespiratory fitness. Change in physical activity habits is associated with change in cardiorespiratory fitness, but respiratory function contributed little to this association during a five year follow up.
Alpha-secretase inhibition reduces human glioblastoma stem cell growth in vitro and in vivo by inhibiting Notch
Authors: Desiree H. Floyd, Benjamin Kefas, Oleksandr Seleverstov, Olga Mykhaylyk, Charli Dominguez, Laurey Comeau, Christian Plank, Benjamin Purow
Journal: Neuro-Oncology (2012)

The Notch pathway is dysregulated and a potential target in glioblastoma multiforme (GBM). Currently available Notch inhibitors block γ-secretase, which is necessary for Notch processing. However, Notch is first cleaved by α-secretase outside the plasma membrane, via a disintegrin and metalloproteinase–10 and –17. In this work, we used a potent α-secretase inhibitor (ASI) to test inhibition of glioblastoma growth and inhibition of Notch and of both novel and known Notch targets. Featured in this study are luciferase reporter assays and immunoblot, microarray analysis, chromatin immunoprecipitation (ChIP), quantitative real-time PCR, cell number assay, bromodeoxyuridine incorporation, plasmid rescue, orthotopic xenograft model, and local delivery of treatment with convection-enhanced delivery using nanoparticles, as well as survival, MRI, and ex vivo luciferase assay. A CBF1-luciferase reporter assay as well as an immunoblot of endogenous Notch revealed Notch inhibition by the ASI. Microarray analysis, quantitative real-time PCR, and ChIP of ASI and γ-secretase inhibitor (GSI) treatment of GBM cells identified known Notch pathway targets, as well as novel Notch targets, including YKL-40 and leukemia inhibitory factor. Finally, we found that local nanoparticle delivery of ASIs but not GSIs increased survival time significantly in a GBM stem cell xenograft treatment model, and ASI treatment resulted in decreased tumor size and Notch activity. This work indicates α-secretase as an alternative to γ-secretase for inhibition of Notch in GBM and possibly other cancers as well, and it identifies novel Notch targets with biologic relevance and potential as biomarkers.
Expression of Epiregulin and Amphiregulin and <i>K-ras</i> Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab
Authors: Shirin Khambata-Ford, Christopher R. Garrett, Neal J. Meropol, Mark Basik, Christopher T. Harbison, Shujian Wu, Tai W. Wong, Xin Huang, Chris H. Takimoto, Andrew K. Godwin, Benjamin R. Tan, Smitha S. Krishnamurthi, Howard A. Burris, Elizabeth A. Poplin, Manuel Hidalgo, Jose Baselga, Edwin A. Clark, David J. Mauro
Journal: Journal of Clinical Oncology (2007)

The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab.One hundred ten patients with metastatic colorectal cancer were enrolled onto a cetuximab monotherapy trial. Transcriptional profiling was conducted on RNA from mandatory pretreatment metastatic biopsies to identify genes whose expression correlates with best clinical responses. EGFR and K-ras mutation analyses and EGFR gene copy number analyses were performed on DNA from pretreatment biopsies.Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (EREG, P = .000015; AREG, P = .000025). Additionally, patients whose tumors do not have K-ras mutations have a significantly higher disease control rate than patients with K-ras mutations (P = .0003). Furthermore, patients with tumors that have high expression of EREG or AREG also have significantly longer progression-free survival (PFS) than patients with low expression (EREG: P = .0002, hazard ratio [HR] = 0.47, and median PFS, 103.5 v 57 days, respectively; AREG: P < .0001, HR = 0.44, and median PFS, 115.5 v 57 days, respectively).Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy.
CD8β Increases CD8 Coreceptor Function and Participation in TCR–Ligand Binding
Authors: Valery Renard, Pedro Romero, Eric Vivier, Bernard Malissen, Immanuel F. Luescher
Journal: The Journal of Experimental Medicine (1996)

To study the role of CD8 beta in T cell function, we derived a CD8 alpha/beta-(CD8-/-) T cell hybridoma of the H-2Kd-restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8 alpha alone or together with CD8 beta. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd-peptide derivative complexes, though CD8 alpha/beta cells did so more efficiently than CD8 alpha/alpha and especially CD8-/- cells. More strikingly, only CD8 alpha/beta cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab' fragments of the anti-Kd alpha 3 monoclonal antibody SF1-1.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR-ligand binding on CD8 alpha/beta cells was approximately 5- and 20-fold more avid than on CD8 alpha/a and CD8-/- cells, respectively. SF1-1.1.1 Fab' or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8 alpha/beta cells to approximately the same low levels observed on CD8-/- cells. These results indicate that CD8 alpha/beta is a more efficient coreceptor than CD8alpha/alpha, because it more avidly strengthens TCR-ligand binding.
Basophil histamine release and lymphocyte proliferation tests in latex contact urticaria
Authors: K. Turjanmaa, L. Räsänen, M. Lehto, S. Mäkinen‐Kiljunen, T. Reunala
Journal: Allergy (1989)

Basophil histamine release and lymphocyte proliferation tests were examined with latex allergen prepared from surgical gloves in 15 patients with latex contact urticaria. The basophil histamine release test (BHRT) yielded positive results in 13/14 (93%) patients, whereas commercial latex RAST was positive in only 9/15 (60%) patients. Lymphocyte proliferation test (LPT) was positive in 3/15 (20%) patients, suggesting that cell‐mediated immune reactions may also occur in latex allergy. However, patch tests to latex were negative and neither were epidermal Langerhans cells able to present latex antigen to T lymphocytes in vitro.
Viability of<i>Pseudomonas aeruginosa</i>in cough aerosols generated by persons with cystic fibrosis
Authors: Luke D Knibbs, Graham R Johnson, Timothy J Kidd, Joyce Cheney, Keith Grimwood, Jacqueline A Kattenbelt, Peter K O'Rourke, Kay A Ramsay, Peter D Sly, Claire E Wainwright, Michelle E Wood, Lidia Morawska, Scott C Bell
Journal: Thorax (2014)

<h3>Background</h3> Person-to-person transmission of respiratory pathogens, including <i>Pseudomonas aeruginosa</i>, is a challenge facing many cystic fibrosis (CF) centres. Viable <i>P aeruginosa</i> are contained in aerosols produced during coughing, raising the possibility of airborne transmission. <h3>Methods</h3> Using purpose-built equipment, we measured viable <i>P aeruginosa</i> in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured. <h3>Results</h3> Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with <i>P aeruginosa</i>, and 10 healthy controls, 26.5 (8.7) years, participated. Viable <i>P aeruginosa</i> were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of <i>P aeruginosa</i> aerosol colony counts was seen and correlated strongly (r=0.73–0.90) with sputum bacterial loads. Modelling decay of viable <i>P aeruginosa</i> in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room. <h3>Conclusions</h3> Viable <i>P aeruginosa</i> in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.
Optic neuritis associated with tumor necrosis factor-alfa antagonists for the treatment of psoriasis
Authors: Adèle de Masson, Benoît Ben Said, Josiane Parier, Edouard Begon, Frédéric Augey, Catherine Goujon, Karima Dahel, Jean-François Nicolas, Frédéric Bérard, Hervé Bachelez, Martine Bagot, Jean-David Bouaziz
Journal: Journal of the American Academy of Dermatology (2012)
Tissue transglutaminase-induced alterations in extracellular matrix inhibit tumor invasion
Authors: Lingegowda S Mangala, Banu Arun, Aysegul A Sahin, Kapil Mehta
Journal: Molecular Cancer (2005)

The molecular mechanisms underlying the acquisition of resistance to the antiestrogen Faslodex are poorly understood, although enhanced expression and activity of nuclear factor kappaB (NFkappaB) have been implicated as a critical element of this phenotype. The purpose of this study was to elucidate the mechanism by which NFkappaB up-regulation contributes to Faslodex resistance and to determine whether pharmacologic inhibition of NFkappaB by the small molecule parthenolide could restore Faslodex-mediated suppression of cell growth. Basal expression of multiple NFkappaB-related molecules in MCF7-derived LCC1 (antiestrogen-sensitive) and LCC9 (antiestrogen-resistant) breast cancer cells was determined, and cells were treated with Faslodex or parthenolide. The effect of these drugs either singly or in combination was assessed by cell proliferation, estrogen receptor (ER)-dependent transcriptional activation, cell cycle analysis, and apoptosis assays. Expression of the p65 NFkappaB subunit and the upstream NFkappaB regulator IkappaB kinase gamma/NFkappaB essential modulator were increased in the resistant MCF7/LCC9 cells (P=0.001 and 0.04, respectively). Whereas MCF7/LCC9 cells were unresponsive to Faslodex alone, parthenolide effectively inhibited MCF7/LCC9 cell proliferation and the combination of Faslodex and parthenolide resulted in a 4-fold synergistic reduction in cell growth (P=0.03). This corresponded to a restoration of Faslodex-induced apoptosis (P=0.001), with no observable changes in ER-dependent transcription or cell cycle phase distribution. Because parthenolide has shown safety in Phase I clinical trials, these findings have direct clinical relevance and provide support for the design of clinical studies combining antiestrogens and parthenolide in ER-positive breast cancer.
Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Philip C. Amrein, Eyal C. Attar, Tak Takvorian, Ephraim P. Hochberg, Karen K. Ballen, Kathleen M. Leahy, David C. Fisher, Ann S. LaCasce, Eric D. Jacobsen, Philippe Armand, Robert P. Hasserjian, Lillian Werner, Donna Neuberg, Jennifer R. Brown
Journal: Clinical Cancer Research (2011)

Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we tested the activity of dasatinib in patients with relapsed CLL.
Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study
Authors: Elise Cuyvers, Arne De Roeck, Tobi Van den Bossche, Caroline Van Cauwenberghe, Karolien Bettens, Steven Vermeulen, Maria Mattheijssens, Karin Peeters, Sebastiaan Engelborghs, Mathieu Vandenbulcke, Rik Vandenberghe, Peter P De Deyn, Christine Van Broeckhoven, Kristel Sleegers
Journal: The Lancet Neurology (2015)
Acute Renal Failure and Cardiac Surgery
Authors: Ravindra L. Mehta
Journal: Journal of the American Society of Nephrology (2004)

Acute renal failure (ARF) after cardiac surgery is a well recognized complication that generally occurs in 1 to 10% of patients ([1][1]–[4][2]). Patients who develop ARF have higher rates of mortality and resource utilization, with the worst values seen in dialyzed patients ([5][3],[6][4]).