tbuckley/cabot-search huggingface dataset:
Potent Inhibitory Effect of Sirolimus on Circulating Vascular Progenitor Cells
Authors: Daiju Fukuda, Masataka Sata, Kimie Tanaka, Ryozo Nagai
Journal: Circulation (2005)

Neointimal hyperplasia is the major cause of in-stent restenosis (ISR). The sirolimus-eluting stent (SES) has emerged as a promising therapy to prevent ISR; however, the exact mechanism by which locally delivered sirolimus, an immunosuppressive agent, prevents ISR remains unknown. Recent evidence suggests that circulating progenitor cells may contribute to neointimal formation.Mononuclear cells (MNCs) were isolated from peripheral blood of healthy human volunteers. Smooth muscle (SM)-like cells outgrew from the culture of MNCs (1x10(6)) in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas endothelial cell-like cells were obtained in the presence of vascular endothelial growth factor. Sirolimus potently inhibited SM-like cell outgrowth. The number of SM-like cells was significantly reduced at a concentration as low as 0.1 ng/mL (15.9+/-5.8% of control, P<0.001). Sirolimus also exerted an inhibitory effect on endothelial cell-like cells that originated from MNCs. Wire-mediated vascular injury was induced in femoral arteries of bone marrow chimeric mice. Either vehicle or sirolimus was administered locally to the perivascular area of the injured arteries. Sirolimus significantly reduced neointima hyperplasia at 4 weeks (intima/media ratio 2.0+/-0.3 versus 1.0+/-0.2, P<0.05) with a decreased number of bone marrow-derived SM-like cells and hematopoietic cells in the lesion. Reendothelialization was retarded in the arteries treated with sirolimus.The potent inhibitory effects of sirolimus on circulating smooth muscle progenitor cells may mediate the clinical efficacy of SES, at least in part. Sirolimus potentially may affect reendothelialization after stent implantation.
Cytochrome P4502A6 (CYP2A6) expression in human hepatocellular carcinoma
Authors: Hannu Raunio, Risto Juvonen, Markku Pasanen, Olavi Pelkonen, Paavo Pääkkö, Ylermi Soini
Journal: Hepatology (1998)

The hepatic cytochrome P4502A6 (CYP2A6) enzyme mediates the oxidative metabolism of several procarcinogens that have liver as their primary target. Mouse models indicate that liver tumors invariably overexpress CYP2A forms, and that inflammation and cirrhosis may regulate the CYP2A expression pattern. In this study, the distribution of the CYP2A6 protein was investigated in a series of 24 human hepatocellular carcinoma (HCC) samples by immunohistochemical analysis. A polyclonal antibody was raised in chicken against CYP2A5, the mouse orthologue of CYP2A6. The antibody was characterized and found to be specific for CYP2A members. In DBA/2 mouse liver, a strong increase of CYP2A5 protein amount, localized in the perivenous region, occurred in response to treatment with pyrazole. In human HCC samples, overexpression of CYP2A6 protein was associated with the presence of chronic inflammation and cirrhosis. CYP2A6 protein was observed in 9 of 16 (56%) of samples with non-neoplastic hepatocytes and in 10 of 24 (42%) HCC samples. The staining for CYP2A6 protein was very heterogeneous in tumor cells, suggesting that increased expression of CYP2A6 occurred in a distinct subpopulation of neoplastic cells. In Kaplan-Meyer survival analysis, there was a tendency toward a more favorable prognosis in patients with CYP2A6-positive tumors in comparison with patients with CYP2A6-negative tumors. These data suggest that, in human HCC, in contrast to mouse liver tumors, CYP2A6 overexpression is not an invariable phenotype.
A Randomized, Multi-Center, NIH/NIAID Funded Study To Assess The Immunogenicity Of Fluzone® Intradermal and Intramuscular Vaccines In Atopic Dermatitis
Authors: Donald Y.M. Leung, Lisa A. Beck, Jon M. Hanifin, Lynda C. Schneider, Amy Paller, Gloria David, Katherine Monti, Brett Jepson, Adriana Weinberg
Journal: Journal of Allergy and Clinical Immunology (2014)
Detection of immune complexes. The use of radioimmunoassays with Clq and monoclonal rheumatoid factor.
Authors: A Gabriel, V Agnello
Journal: Journal of Clinical Investigation (1977)

This study describes two sensitive, rapid, relatively simple, competitive inhibition radioimmunoassays for detecting immune complex. The tests are based on the inhibition of I125-Clq or I125-monoclonal rheumatoid factor (mRF) binding to an insoluble substrate, IgG-Sepharose. The assays can be performed in 5 h utilizing 10 micronl of serum. Heating of serum is not required and polyclonal rheumatoid factors do not interefere. With the two assays, a wide range of complexes of various size and complement fixing activity can be detected. The Clq test can detect complement fixing Ig complexes larger than 19S, while the mRF tests detect complexes of IgG as small as 8S irrespective of their complement fixing activity. Mouse, rabbit, and human aggregated IgG (agg IgG) can be detected in the Clq test, and human and rabbit agg IgG in the mRF test. As low as 4 microng/ml of isolated human agg IgG can be detected in the Clq test and 0.5 microng/ml in the rheumatoid factor test. Sensitivity is greater for mouse agg IgG. For pathologic sera which must be diluted to eliminate interfering factors, the sensitivity of the assay is approximately 10 times less. The Clq test showed marked inhibition by systemic lupus erythematosus sera with close correlation with CH50 levels and disease activity. The mRF test showed better correlation with rheumatoid arthritis sera. In addition, anionic macromolecules known to react with Clq and other Clq reactants that occur in pathologic sera such as the "low molecular weight" substances in systemic lupus erythematosus are also detected. These reactants are not detectable in the mRF test and can be eliminated in the Clq test by performing the test at higher ionic strength. The tests can be applied to the study of a variety of pathologic states where immune complexes appear to play a role.
Overexpression of the EMT Driver Brachyury in Breast Carcinomas: Association With Poor Prognosis
Authors: Claudia Palena, Mario Roselli, Mary T. Litzinger, Patrizia Ferroni, Leopoldo Costarelli, Antonella Spila, Francesco Cavaliere, Bruce Huang, Romaine I. Fernando, Duane H. Hamilton, Caroline Jochems, Kwong-Yok Tsang, Qing Cheng, H. Kim Lyerly, Jeffrey Schlom, Fiorella Guadagni
Journal: JNCI Journal of the National Cancer Institute (2014)

The epithelial–mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells. Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan–Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided. The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14×10−4) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01×10−4). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells. The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies.
Active Properties of Neuronal Dendrites
Authors: Daniel Johnston, Jeffrey C. Magee, Costa M. Colbert, Brian R. Christie
Journal: Annual Review of Neuroscience (1996)

Dendrites of neurons in the central nervous system are the principal sites for excitatory synaptic input. Although little is known about their function, two disparate perspectives have arisen to describe the activity patterns inherent to these diverse tree-like structures. Dendrites are thus considered either passive or active in their role in integrating synaptic inputs. This review follows the history of dendritic research from before the turn of the century to the present, with a primary focus on the hippocampus. A number of recent techniques, including high-speed fluorescence imaging and dendritic patch clamping, have provided new information and perspectives about the active properties of dendrites. The results support previous notions about the dendritic propagation of action potentials and also indicate which types of voltage-gated sodium and calcium channels are expressed and functionally active in dendrites. Possible roles for the active properties of dendrites in synaptic plasticity and integration are also discussed.
Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer
Authors: Eben L. Rosenthal, Jason M. Warram, Esther de Boer, Thomas K. Chung, Melissa L. Korb, Margie Brandwein-Gensler, Theresa V. Strong, Cecelia E. Schmalbach, Anthony B. Morlandt, Garima Agarwal, Yolanda E. Hartman, William R. Carroll, Joshua S. Richman, Lisa K. Clemons, Lisle M. Nabell, Kurt R. Zinn
Journal: Clinical Cancer Research (2015)

Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer.A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology.There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels.We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology.
Upregulation of Fas Ligand by Simian Immunodeficiency Virus—A <i>nef</i>-arious Mechanism of Immune Evasion?
Authors: R. Paul Johnson
Journal: The Journal of Experimental Medicine (1997)

AIDS is the end result of a prolonged dynamic war of attrition between virus and host, marked by prodigious rates of viral replication opposed by host immune responses and remarkable rates of T cell regeneration (([1][1]), ([2][2])). Understanding the ultimate failure of the host immune responses to
Atrial natriuretic peptide in primary pulmonary hypertension
Authors: AH Morice, J Pepke-Zaba, MJ Brown, PS Thomas, TW Higenbottam
Journal: European Respiratory Journal (1990)

Plasma levels of atrial natriuretic peptide (ANP) were determined during cardiac catheterization in nine patients with primary pulmonary hypertension (PPH) and the effect of prostacyclin infusion via a right heart catheter studied. The role of hypoxia on the release of ANP was investigated in a control group of six normal subjects who underwent an acute hypoxic challenge. Patients showed the typical haemodynamic changes of primary pulmonary hypertension with elevation of mean (SD) pulmonary artery pressure, 71.3 (13.8) mmHg, and low cardiac index, 1.9 (0.5) l.min-1.m-2. Plasma ANP was also elevated; mean pulmonary artery plasma ANP was 96.3 (77.6) pmol.l-1 in PPH patients compared with mean venous plasma ANP of 8.9 (5.6) pmol.l-1 in normal subjects. Prostacyclin infusion in PPH patients and hypoxic challenge in normal subjects did not significantly alter plasma ANP levels. The elevated levels of ANP in PPH are due to the altered haemodynamics secondary to increased pulmonary vascular resistance and may be responsible for the lack of peripheral oedema seen in this condition.
Mechanism for muscarinic inhibition of ICa(L) is determined by the path for elevating cyclic AMP in cardiac myocytes
Authors: Y Imai
Journal: Cardiovascular Research (2001)

Objective: Does carbachol (CCh) require NO/cGMP for inhibition of L-type calcium current (ICa(L)) when either adenylyl cyclase activation or phosphodiesterase suppression is used to raise cAMP? Methods: The effects of the NO donor SIN-1 (3-morpholino-sydnonimine), CCh and atrial natriuretic peptide (ANP) were evaluated when ICa(L) had been stimulated by isoproterenol (ISO) or 3-isobutyl-1-methylxanthine (IBMX) in guinea pig isolated ventricular myocytes (35°C). Results: Carbachol, SIN-1 or ANP did not affect basal ICa(L); each inhibited IBMX-stimulated ICa(L). Dialyzed (30–100 μM) ODQ (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one), a soluble guanylyl cyclase (sGC) inactivator, blocked inhibition of IBMX-stimulated ICa(L) by SIN-1 (10 μM) but not by CCh (1–100 μM) or ANP (100 nM). Dialysis with 3 μM LY83583 (6-anilino-5,8-quinolinedione), a particulate (pGC) and sGC inactivator, opposed muscarinic-, ANP- and SIN-1-induced inhibition of IBMX-stimulated ICa(L). Thus CCh can increase cGMP synthesis via pGC. Even with 100 μM [LY83583]pip, CCh inhibited ISO-stimulated ICa(L), an effect referable to suppression of adenylyl cyclase activity. However, 3 μM [LY83583]pip prevented inhibition of ISO-stimulated ICa(L) by ANP. [LY83583]pip did not affect inhibition by 8 bromo-cGMP (100 μM) of ISO- or IBMX-stimulated ICa(L). The observations indicate that: (1) myocytes have ODQ-sensitive sGC activated by NO and LY8353-sensitive pGC activated by ANP, (2) CCh does not inhibit ICa(L) via NO, (3) the mechanism for muscarinic inhibition depends upon the cAMP-elevating agent and (4) LY83583 distinguishes between two pathways for muscarinic inhibition. Conclusion: The nature of the stimulant pathway that increases cAMP determines intracellular transduction of muscarinic inhibition. This hypothesis accords with distinct cyclic nucleotide compartments for the differential expression of muscarinic inhibition of ICa(L).
OvMark: a user-friendly system for the identification of prognostic biomarkers in publically available ovarian cancer gene expression datasets
Authors: Stephen F Madden, Colin Clarke, Britta Stordal, Mark S Carey, Russell Broaddus, William M Gallagher, John Crown, Gordon B Mills, Bryan T Hennessy
Journal: Molecular Cancer (2014)

Ovarian cancer has the lowest survival rate of all gynaecologic cancers and is characterised by a lack of early symptoms and frequent late stage diagnosis. There is a paucity of robust molecular markers that are independent of and complementary to clinical parameters such as disease stage and tumour grade. We have developed a user-friendly, web-based system to evaluate the association of genes/miRNAs with outcome in ovarian cancer. The OvMark algorithm combines data from multiple microarray platforms (including probesets targeting miRNAs) and correlates them with clinical parameters (e.g. tumour grade, stage) and outcomes (disease free survival (DFS), overall survival). In total, OvMark combines 14 datasets from 7 different array platforms measuring the expression of ~17,000 genes and 341 miRNAs across 2,129 ovarian cancer samples. To demonstrate the utility of the system we confirmed the prognostic ability of 14 genes and 2 miRNAs known to play a role in ovarian cancer. Of these genes, CXCL12 was the most significant predictor of DFS (HR = 1.42, p-value = 2.42x10−6). Surprisingly, those genes found to have the greatest correlation with outcome have not been heavily studied in ovarian cancer, or in some cases in any cancer. For instance, the three genes with the greatest association with survival are SNAI3, VWA3A and DNAH12. OvMark is a powerful tool for examining putative gene/miRNA prognostic biomarkers in ovarian cancer (available at http://glados.ucd.ie/OvMark/index.html ). The impact of this tool will be in the preliminary assessment of putative biomarkers in ovarian cancer, particularly for research groups with limited bioinformatics facilities.
Vasomotor Responses in the Hindlimb of Newborn Calves
Authors: JOHN E. MILLIGAN, MARGOT R. ROACH, NORMAN S. TALNER
Journal: Circulation Research (1967)

The reflex control of the hindlimb circulation was examined in 9 newborn calves under chloralose anesthesia by measuring iliac arterial pressure-flow curves. Asphyxia always caused vasoconstriction which was abolished or greatly reduced by sciatic nerve section. Vasomotor tone was present a few hours from birth, as shown by an increase in flow on sciatic nerve section and by drug action. It is concluded that autonomic control of the systemic circulation is effective in this species at birth.
Lung transplantation in children and young adults: a 20-year single-centre experience
Authors: Saskia Gruber, Thomas Eiwegger, Edith Nachbaur, Kerstin Tiringer, Clemens Aigner, Peter Jaksch, Maya Keplinger, Walter Klepetko, György Lang, Shahrokh Taghavi, Alexandra Graf, Irmgard Eichler, Thomas Frischer, Zsolt Szépfalusi
Journal: European Respiratory Journal (2012)

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria. Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan-Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses. A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.
Gastroesophageal reflux with nasogastric tubes. Effect of nasogastric tube size.
Authors: R G Dotson, R G Robinson, S K Pingleton
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Pulmonary aspiration of gastric contents results initially from reflux of stomach contents into the esophagus. Small-bore enteral feeding tubes are thought to result in less pulmonary aspiration and less reflux. We prospectively investigated the effect of nasogastric tube size upon gastroesophageal (GE) reflux in normal volunteers in a randomized crossover trial. Reflux was assessed by gastroesophageal scintiscanning, a radioisotopic technique that detects and quantitates GE reflux. A total of 11 subjects were studied three times: control, no nasogastric tube, small-bore (8F) nasogastric tube, and large-bore (14F) nasogastric tube. Reflux was assessed in each subject under each experimental condition by provocative testing in which abdominal pressure was increased from 0 to 100 mm Hg by 20-mm Hg increments with an abdominal pressure device. GE reflux indices were calculated for each measurement and the groups compared. A positive indicator of reflux was defined as a > or = 4% reflux index. Gastroesophageal reflux was not detected at any level of abdominal pressure regardless of the presence or size of a nasogastric tube. With maximum 100 mm Hg abdominal pressure, the reflux index was control, 1.75 +/- 0.45%; small-bore tube, 1.67 +/- 0.28%; and large-bore tube, 1.88 +/- 0.35% (NS). The reflux index was not different between small-bore and large-bore nasogastric tubes. Our data suggest the size of a nasogastric tube is not an important determinant of GE reflux in normal subjects during short-term intubation. Large-bore tubes did not cause more reflux than small-bore tubes. The presence of a nasogastric tube did not cause reflux in normal subjects. These data suggest that factors other than the size of nasogastric tube are more important in GE reflux in normal subjects.
The effect of active and convalescent serum on the Kobner reaction in patients with active psoriasis
Authors: L. Stankler
Journal: British Journal of Dermatology (1974)

Journal Article The effect of active and convalescent serum on the Köbner reaction in patients with active psoriasis Get access L. Stankler L. Stankler Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Page 15, https://doi.org/10.1111/j.1365-2133.1974.tb12476.x Published: 01 July 1974
AN ELECTROPHORETIC DIFFERENCE BETWEEN SURFACE AND SECRETED I<scp>G</scp>M OF MURINE SPLENOCYTES
Authors: Ulrich Melcher, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1973)

µ-chains on the surface of murine splenocytes are more heterogeneous on SDS-polyacrylamide gel electrophoresis than both secreted and intracellular µ-chains labeled with [3H]tyrosine. No difference in heterogeneity among cell surface, secreted, or intracellular L chains was detected. The possible role of carbohydrate in µ-chain heterogeneity is discussed.
Effect of recombinant human insulin-like growth factor-1 on the inflammatory response to acute renal injury.
Authors: N Goes, J Urmson, D Vincent, V Ramassar, P F Halloran
Journal: Journal of the American Society of Nephrology (1996)

Renal ischemic injury evokes an inflammatory response with increased cytokine and major histocompatibility complex (MHC) expression and a mild interstitial infiltrate. This "injury response" could contribute to the tendency of ischemically injured renal transplants to reject. The studies presented here evaluated the ability of recombinant human insulin-like growth factor-1 (rhlGF-1) given after renal injury to prevent renal inflammation. The left renal pedicle of CBA and BALB/c mice was clamped for 60 min, and rhlGF-1 (25, 50, 100 micrograms) was administered sc at 2, 24, 48, 72, and 96 h after reflow. Cytokine and MHC expression was monitored in the injured kidney, compared with the contralateral kidney. In untreated mice, a single episode of injury induced the expression of MHC mRNA and products and tumor necrosis factor-alpha (TNF-alpha) mRNA, and depressed preproepidermal growth factor (ppEGF) mRNA, for up to 5 wk. With immunohistology, epithelial Class I and II MHC expression was shown to be increased for 2 wk, and Class II positive interstitial cells were shown to be increased for up to 5 wk. The ischemically injured kidneys from mice treated with rhlGF-1 and examined at 5 days showed a dose-dependent normalization of all of the changes of the injury response. This included prevention of the increased expression of MHC and cytokines and the Class II positive interstitial cells, and restoration of ppEGF mRNA. Thus the complex and long-lasting increase in proinflammatory cytokines and MHC expression that follow renal ischemia can be interrupted by treatment with rhlGF-1 beginning 2 h after the injury. This therapy may have applications to the injury response in renal transplants.