tbuckley/cabot-search huggingface dataset:
A Novel System for Simultaneous<b><i>in Vivo</i></b>Tracking and Biological Assessment of Leukemia Cells and<b><i>ex Vivo</i></b>Generated Leukemia-Reactive Cytotoxic T Cells
Authors: Martin G. Sauer, Marna E. Ericson, Brenda J. Weigel, Michael J. Herron, Angela Panoskaltsis-Mortari, Betsy T. Kren, Bruce L. Levine, Jon S. Serody, Carl H. June, Patricia A. Taylor, Bruce R. Blazar
Journal: Cancer Research (2004)

Abstract To determine the mechanisms by which adoptive immunotherapy could reduce lethality to acute myelogenous leukemia (AML), a novel technique was developed to track both leukemic blasts and adoptively transferred cytotoxic T cells (CTLs) independently and simultaneously in mice. To follow the fate of ex vivo generated anti-AML-reactive CTLs, splenocytes obtained from enhanced green fluorescent protein transgenic mice were cocultured with AML lysate-pulsed dendritic cells, which subsequently were expanded by exposure to anti-CD3/CD28 monoclonal antibody-coated magnetic microspheres. To track AML cells, stable transfectants of C1498 expressing DsRed2, a red fluorescent protein, were generated. Three factors related to CTLs correlated with disease-free survival: (a) CTL l-selectin expression. l-Selectin high fractions resulted in 70% disease-free survival, whereas l-selectin low-expressing CTLs resulted in only 30% disease-free survival. (b) Duration of ex vivo expansion (9 versus 16 days). Short-term expanded CTLs could be found at high frequency in lymphoid organs for longer than 4 weeks after transfer, whereas long-term expanded CTLs were cleared from the system after 2 weeks. Duration of expansion correlated inversely with l-selectin expression. (c) CTL dose. A higher dose (40 versus 5 × 106) resulted in superior disease-free survival. This survival advantage was achieved with short-term expanded CTLs only. The site of treatment failure was mainly the central nervous system where no CTLs could be identified at AML sites.
Gene therapy for collateral vessel development
Authors: Guido Melillo, Marco Scoccianti, Imre Kovesdi, Jorge Safi, Teresa Riccioni, Maurizio C Capogrossi
Journal: Cardiovascular Research (1997)

Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application.
Rhinovirus-induced interferon production is not deficient in well controlled asthma
Authors: Annemarie Sykes, Jonathan Macintyre, Michael R Edwards, Ajerico del Rosario, Jennifer Haas, Vera Gielen, Onn Min Kon, Mark McHale, Sebastian L Johnston
Journal: Thorax (2013)

Defective rhinovirus (RV)-induced interferon (IFN)-β and IFN-λ production and increased RV replication have been reported in primary human bronchial epithelial cells (HBECs) from subjects with asthma. How universal this defect is in asthma is unknown. Additionally, the IFN subtypes induced by RV infection in primary HBECs have not been comprehensively investigated.To study RV induction of IFN-α, IFN-β and IFN-λ and RV replication in HBECs from subjects with atopic asthma and healthy controls.HBECs were obtained from subjects with asthma and healthy controls and infected with RV16 and RV1B, and cells and supernatants harvested at 8, 24 and 48h. IFN proteins were analysed by ELISA and IFN mRNA and viral RNA expression by quantitative PCR. Virus release was assessed in cell supernatants.IFN-β and IFN-λ were the only IFNs induced by RV in HBECs and IFN-λ protein induction was substantially greater than IFN-β. Induction of IFN-λ1 mRNA by RV16 at 48h was significantly greater in HBECs from subjects with asthma; otherwise there were no significant differences between subjects with asthma and controls in RV replication, or in induction of type I or III IFN protein or mRNA.IFN-λ and, to a lesser degree, IFN-β are the major IFN subtypes induced by RV infection of HBECs. Neither defective IFN induction by RV nor increased RV replication was observed in the HBECs from subjects with well controlled asthma reported in this study.
Modulation of Orphan Nuclear Receptor Nur77-Mediated Apoptotic Pathway by Acetylshikonin and Analogues
Authors: Jie Liu, Wen Zhou, Shao-Shun Li, Zhe Sun, Bingzhen Lin, Yuan-Yuan Lang, Jia-You He, Xihua Cao, Tingdong Yan, Li Wang, Jiongming Lu, Young-Hoon Han, Yu Cao, Xiao-kun Zhang, Jin-Zhang Zeng
Journal: Cancer Research (2008)

Abstract Shikonin derivatives, which are the active components of the medicinal plant Lithospermum erythrorhizon, exhibit many biological effects including apoptosis induction through undefined mechanisms. We recently discovered that orphan nuclear receptor Nur77 migrates from the nucleus to the mitochondria, where it binds to Bcl-2 to induce apoptosis. Here, we report that certain shikonin derivatives could modulate the Nur77/Bcl-2 apoptotic pathway by increasing levels of Nur77 protein and promoting its mitochondrial targeting in cancer cells. Structural modification of acetylshikonin resulted in the identification of a derivative 5,8-diacetoxyl-6-(1′-acetoxyl-4′-methyl-3′-pentenyl)-1,4-naphthaquinones (SK07) that exhibited improved efficacy and specificity in activating the pathway. Unlike other Nur77 modulators, shikonins increased the levels of Nur77 protein through their posttranscriptional regulation. The apoptotic effect of SK07 was impaired in Nur77 knockout cells and suppressed by cotreatment with leptomycin B that inhibited Nur77 cytoplasmic localization. Furthermore, SK07 induced apoptosis in cells expressing the COOH-terminal half of Nur77 protein but not its NH2-terminal region. Our data also showed that SK07-induced apoptosis was associated with a Bcl-2 conformational change and Bax activation. Together, our results show that certain shikonin derivatives act as modulators of the Nur77-mediated apoptotic pathway and identify a new shikonin-based lead that targets Nur77 for apoptosis induction. [Cancer Res 2008;68(21):8871–80]
The Renal Handling of Parathyroid Hormone
Authors: Kevin J. Martin, Keith A. Hruska, Jane Lewis, Charles Anderson, Eduardo Slatopolsky
Journal: Journal of Clinical Investigation (1977)

The mechanisms of uptake of parathyroid hormone (PTH) by the kidney was studied in anesthetized dogs before and after ureteral ligation. During constant infusion of bovine PTH (b-PTH 1-84), the renal arteriovenous (A-V) difference for immunoreactive PTH (i-PTH) was 22±2%. After ureteral ligation and no change in renal plasma flow, A-V i-PTH fell to 15±1% (P < 0.01), indicating continued and significant uptake of i-PTH at peritubular sites and a lesser role of glomerular filtration (GF) in the renal uptake of i-PTH. Since, under normal conditions, minimal i-PTH appears in the final urine, the contribution of GF and subsequent tubular reabsorption was further examined in isolated perfused dog kidneys before and after inhibition of tubular reabsorption by potassium cyanide. Urinary i-PTH per 100 ml GF rose from 8±4 ng/min (control) to 170±45 ng/min after potassium cyanide. Thus, i-PTH is normally filtered and reabsorbed by the tubular cells. The physiological role of these two mechanisms of renal PTH uptake was examined by giving single injections of b-PTH 1-84 or synthetic b-PTH 1-34 in the presence of established ureteral ligation. After injection of b-PTH 1-84, renal A-V i-PTH was 20% only while biologically active intact PTH was present (15-20 min). No peritubular uptake of carboxyl terminal PTH fragments was demonstrable. In contrast, after injection of synthetic b-PTH 1-34, renal extraction of N-terminal i-PTH after ureteral ligation (which was 13.4±0.6% vs. 19.6±0.9% in controls) continued for as long as i-PTH persisted in the circulation. These studies indicate that both GF and peritubular uptake are important mechanisms for renal PTH uptake. Renal uptake of carboxyl terminal fragments of PTH is dependent exclusively upon GF and tubular reabsorption, whereas peritubular uptake can only be demonstrated for biologically active b-PTH 1-84 and synthetic b-PTH 1-34.
Angiopoietin-1 Guides Directional Angiogenesis Through Integrin α <sub>v</sub> β <sub>5</sub> Signaling for Recovery of Ischemic Retinopathy
Authors: Junyeop Lee, Kyung Eun Kim, Dong-Kyu Choi, Jeon Yeob Jang, Ji-Jung Jung, Hiroshi Kiyonari, Go Shioi, Woohyok Chang, Toshio Suda, Naoki Mochizuki, Yoshikazu Nakaoka, Issei Komuro, Ook-Joon Yoo, Gou Young Koh
Journal: Science Translational Medicine (2013)

Angiopoietin-1 supplementation stimulates guided angiogenesis and promotes the formation of a healthy vascular network in a mouse model of ischemic retinopathy.
Targeted impairment of innate antiviral responses in the liver of chronic hepatitis C patients
Authors: Loubna Jouan, Laurent Chatel-Chaix, Pierre Melançon, Ian-Gaël Rodrigue-Gervais, Valerie-Ann Raymond, Subajini Selliah, Marc Bilodeau, Nathalie Grandvaux, Daniel Lamarre
Journal: Journal of Hepatology (2011)
Effect of Glutamate Carboxypeptidase II and Reduced Folate Carrier Polymorphisms on Folate and Total Homocysteine Concentrations in Dialysis Patients
Authors: Manuela Födinger, Jutta Dierkes, Sonja Skoupy, Claudia Röhrer, Wolfgang Hagen, Heidi Puttinger, Anna-Christine Hauser, Andreas Vychytil, Gere Sunder-Plassmann
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (<i>RFC1</i> 80G&gt;A) and the glutamate carboxypeptidase 2 (<i>GCP2</i> 1561C&gt;T) gene on total homocysteine (tHcy) plasma level and folate status in 120 chronic dialysis patients. Red blood cell folate concentration was higher in patients with the <i>GCP2</i> CT or TT genotype (ANOVA, <i>P</i> = 0.04). Among patient groups with different <i>RFC1</i> genotypes, red blood cell folate level was not significantly different. A multivariate analysis confirmed that the <i>GCP2</i> 1561C&gt;T genotype (<i>P</i> = 0.011) had a significant influence on the red blood cell folate concentration. Overall, serum folate, creatinine, and the <i>GCP2</i> polymorphism explained nearly 50% of the variance of red blood cell folate. A linear multivariate regression analysis showed that red blood cell folate (<i>P</i> &lt; 0.001), creatinine (<i>P</i> &lt; 0.001), and the 5,10-methylenetetrahydrofolate reductase (<i>MTHFR</i>) 677T allele (<i>P</i> = 0.013) are independent predictors of tHcy plasma level explaining 49% of the variance of tHcy plasma concentration. <i>GCP2</i> 1561C&gt;T and <i>RFC1</i> 80G&gt;A showed no effect on tHcy and folate plasma level. In conclusion, <i>GCP2</i> 1561C&gt;T, but not <i>RFC1</i> 80G&gt;A, is a predictor of red blood cell folate level in chronic dialysis patients. Both polymorphisms have no major effect on tHcy plasma concentration in end-stage renal disease patients. E-mail: Gere.Sunder-Plassmann@univie.ac.at
Heterochromatin, Satellite DNA, and Transformed Neoplastic Cells
Authors: N.C. Popescu, J. A. DiPaolo
Journal: JNCI Journal of the National Cancer Institute (1972)

Chromosome preparations of control Balb/3T3 cells stained to show heterochromatin had dark areas associated only with the centromeric regions. Two chemically transformed lines and one line transformed by simian virus 40 (SV40), all with subtetraploid modes, stained only in the centromeric heterochromatin. One SV40-transformed line and an SV40 tumor line, both with subdiploid chromosome modes, possessed, in addition to the characteristic centromeric heterochromatin, one chromosome with interstitial heterochromatin on both arms. The interstitial heterochromatin may represent induced host DNA as a result of viral infection.
Altered glycosylation of leukosialin, CD43, in HIV-1-infected cells of the CEM line.
Authors: J C Lefebvre, V Giordanengo, M Limouse, A Doglio, M Cucchiarini, F Monpoux, R Mariani, J F Peyron
Journal: The Journal of Experimental Medicine (1994)

CD43 (leukosialin, gpL115, sialophorin) is a major sialoglycoprotein widely expressed on hematopoietic cells that is defective in the congenital immunodeficiency Wiskott-Aldrich syndrome. It is thought to play an important role in cell-cell interactions and to be a costimulatory molecule for T lymphocyte activation. Using a metabolic 35SO4(2-) radiolabeling assay or biotinylation of cell surface proteins, we describe here that CD43 are sulfated molecules the glycosylation of which is altered in human immunodeficiency virus type 1 (HIV-1)-infected leukemic T cells of the CEM line. Hyposialylation of O-glycans and changed substitution on N-acetylgalactosamine residues are observed. The glycosylation defect is associated with an impairment of CD43-mediated homotypic aggregation which can be restored by resialylation. The hyposialylation of CD43 on HIV-1+ cells may explain the high prevalence of autoantibodies directed against nonsialylated CD43 that have been detected in HIV-1-infected individuals. A defect in glycosylation of important molecules such as CD43 or, as we recently described, CD45 may explain alterations of T cell functions and viability in HIV-1-infected individuals. In addition, a possible implication of hyposialylation in the HIV-1-infected cells entrapment in lymph nodes could be envisioned.
Chloroquine and proguanil prophylaxis in travellers to Kenya
Authors: A. Zumla, Duncan Churchill, Robert Davidson, Kieran O'Flynn, Wolfgang Kox, LeonardoK. Basco, Jacques Le Bras, Guy Charmot, Jean-Louis Vilde, Francois Vachon, Jean-Pierre Coulaud, R.H. Behrens
Journal: The Lancet (1992)
General Practitioners' Telephones
Authors: A. G. Grossett
Journal: BMJ (1971)

that I should function better if eased of some of the burden and so make use of various facilities including the Emergency Treatment Service.My experience with this excellent service does not correspond with Dr. Grant's.Admittedly the staff there will not divulge the bypass number, but if the reason for Dr. Grant's or anyone else's call is made clear and is reasonable the nurse on duty will call the general practitioner-if available-and through her switchboard effect contact.I have received several calls both professional and personal in this way, and it really is as simple as that.If, however, Dr.
Obesity and the reproductive system disorders: epigenetics as a potential bridge
Authors: Ana B. Crujeiras, Felipe F. Casanueva
Journal: Human Reproduction Update (2014)

Obesity and overweight are significantly involved in several reproductive pathologies contributing to infertility in men and women. In addition, several cancers of the reproductive system, such as endometrial, ovarian, breast, testicular and prostate cancers, are strongly influenced by obesity. However, the molecular mechanisms involved in the association between obesity and reproductive disorders remain unclear. Our proposal is to review the current scientific evidence regarding the effect of obesity-related factors as the core of the collective mechanisms directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effect of the obesity state microenvironment on the epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders. A PubMed search was performed using keywords related to obesity and adipose-related factors and epigenetics and associated with keywords related to reproduction. Full-text articles and abstracts in the English language published prior to 31 December 2013 were reviewed. The obesity state notably contributes to a reproductive dysfunction in both men and women, ranging from infertility to oncological outcomes. Several epidemiological and experimental studies demonstrate that factors secreted by the adipose tissue and gut in an obesity state can directly induce reproductive disturbances. Relevantly, these same factors are able to alter the epigenetic regulation of genes, a dynamic and reversible mechanism by which the organism responds to environmental pressures critical to the reproductive function. This review outlines the evidence showing that the association between the reproductive pathologies and obesity is not inevitable but is potentially preventable and reversible. The epigenetic marks related to obesity could constitute a therapeutic target for the reproductive disorders associated with obesity.
Meta-analysis: Erythropoiesis-Stimulating Agents in Patients With Chronic Kidney Disease
Authors: Suetonia C. Palmer
Journal: Annals of Internal Medicine (2010)

Background: Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease (CKD) increases the risk for death. Additional randomized trials have been recently completed. Purpose: To summarize the effects of ESA treatment on clinical outcomes in patients with anemia and CKD. Data Sources: MEDLINE (January 1966 to November 2009), EMBASE (January 1980 to November 2009), and the Cochrane database (to March 2010) were searched without language restriction. Study Selection: Two authors independently screened reports to identify randomized trials evaluating ESA treatment in people with CKD. Hemoglobin target trials or trials of ESA versus no treatment or placebo were included. Data Extraction: Two authors independently extracted data on patient characteristics, study risks for bias, and the effects of ESA therapy. Data Synthesis: 27 trials (10 452 patients) were identified. A higher hemoglobin target was associated with increased risks for stroke (relative risk [RR], 1.51 [95% CI, 1.03 to 2.21]), hypertension (RR, 1.67 [CI, 1.31 to 2.12]), and vascular access thrombosis (RR, 1.33 [CI, 1.16 to 1.53]) compared with a lower hemoglobin target. No statistically significant differences in the risks for mortality (RR, 1.09 [CI, 0.99 to 1.20]), serious cardiovascular events (RR, 1.15 [CI, 0.98 to 1.33]), or end-stage kidney disease (RR, 1.08 [CI, 0.97 to 1.20]) were observed, although point estimates favored a lower hemoglobin target. Treatment effects were consistent across subgroups, including all stages of CKD. Limitations: The evidence for effects on quality of life was limited by selective reporting. Trials also reported insufficient information to allow analysis of the independent effects of ESA dose on clinical outcomes. Conclusion: Targeting higher hemoglobin levels in CKD increases risks for stroke, hypertension, and vascular access thrombosis and probably increases risks for death, serious cardiovascular events, and end-stage renal disease. The mechanisms for harm remain unclear, and meta-analysis of individual-patient data and trials on fixed ESA doses are recommended to elucidate these mechanisms. Primary Funding Source: None.
Cardiac Na <sup>+</sup> Current Regulation by Pyridine Nucleotides
Authors: Man Liu, Shamarendra Sanyal, Ge Gao, Iman S. Gurung, Xiaodong Zhu, Georgia Gaconnet, Laurie J. Kerchner, Lijuan L. Shang, Christopher L.-H. Huang, Andrew Grace, Barry London, Samuel C. Dudley
Journal: Circulation Research (2009)

Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na+ current (I(Na)) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in NAD-dependent energy metabolism.Therefore, we tested whether NAD(H) could regulate human cardiac sodium channels (Na(v)1.5).HEK293 cells stably expressing Na(v)1.5 and rat neonatal cardiomyocytes were used. The influence of NADH/NAD+ on arrhythmic risk was evaluated in wild-type or SCN5A(+/-) mouse heart. A280V GPD1-L caused a 2.48+/-0.17-fold increase in intracellular NADH level (P<0.001). NADH application or cotransfection with A280V GPD1-L resulted in decreased I(Na) (0.48+/-0.09 or 0.19+/-0.04 of control group, respectively; P<0.01), which was reversed by NAD+, chelerythrine, or superoxide dismutase. NAD+ antagonism of the Na+ channel downregulation by A280V GPD1-L or NADH was prevented by a protein kinase (PK)A inhibitor, PKAI(6-22). The effects of NADH and NAD+ were mimicked by a phorbol ester and forskolin, respectively. Increasing intracellular NADH was associated with an increased risk of ventricular tachycardia in wild-type mouse hearts. Extracellular application of NAD+ to SCN5A(+/-) mouse hearts ameliorated the risk of ventricular tachycardia.Our results show that Na(v)1.5 is regulated by pyridine nucleotides, suggesting a link between metabolism and I(Na). This effect required protein kinase C activation and was mediated by oxidative stress. NAD+ could prevent this effect by activating PKA. Mutations of GPD1-L may downregulate Na(v)1.5 by altering the oxidized to reduced NAD(H) balance.
Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Authors: M. M. Bridgeman, M. Marsden, W. MacNee, D. C. Flenley, A. P. Ryle
Journal: Thorax (1991)

N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.