tbuckley/cabot-search huggingface dataset:
Cigarette Smoking and Variations in Systemic Immune and Inflammation Markers
Authors: Meredith S. Shiels, Hormuzd A. Katki, Neal D. Freedman, Mark P. Purdue, Nicolas Wentzensen, Britton Trabert, Cari M. Kitahara, Michael Furr, Yan Li, Troy J. Kemp, James J. Goedert, Cindy M. Chang, Eric A. Engels, Neil E. Caporaso, Ligia A. Pinto, Allan Hildesheim, Anil K. Chaturvedi
Journal: JNCI Journal of the National Cancer Institute (2014)

A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease. Levels of 78 inflammation, immune, and metabolic markers were measured using multiplex immune assays in 1819 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) participants aged 55 to 74 years from three existing nested case-control studies. These data were made representative of the entire PLCO screening arm through reweighting with weights estimated in logistic regression models. We assessed associations between smoking status, cigarettes smoked per day, and time since quitting with dichotomized marker levels using adjusted weighted logistic regression models. Current smoking was associated with 10 inflammation markers after correcting for multiple testing, encompassing several components of the immune/inflammation response. Levels of seven of these markers (interleukin [IL]-15, IL-1RA, IL-1β, IL-16, stem cell factor, soluble interleukin 6 receptor, and soluble vascular endothelial growth factor receptor 3) were lower among current smokers (n = 414) when compared with never smokers (n = 548), with odds ratios (ORs) ranging from 0.44 to 0.27, while levels of CC motif ligand (CCL)/thymus and activation regulated chemokine (CCL17/TARC) (OR = 4.08, 95% confidence interval [CI] = 2.01 to 8.25), CCL11/EOTAXIN (OR = 2.57, 95% CI = 1.45 to 4.55), and C-reactive protein (CRP) (OR = 2.54, 95% CI = 1.29 to 4.98) were elevated. These markers were not associated with cigarettes per day among current smokers, but there were trends in IL-15, IL-1RA, IL-1β, CCL17/TARC, CCL11/EOTAXIN, and CRP levels across categories of years since quitting smoking. Smoking is associated with a broad range of alterations in systemic immune and inflammation marker levels among older, long-term smokers. Smoking cessation may result in marker levels reverting back to those of never smokers over time.
Abstract 4591: The folate receptor-targeted agents, vintafolide and etarfolatide, are not substrates for the reduced folate carrier or the proton-coupled folate transporter
Authors: Nikki Parker, Christina Cherian, Larry Matherly, Christopher P. Leamon
Journal: Cancer Research (2014)

Abstract Vintafolide (EC145), a folate-targeted small molecule drug conjugate (SMDC) of desacetylvinblastine hydrazide (DAVLBH), and etarfolatide (EC20), a folate-targeted companion imaging agent, are currently being evaluated in global phase 2 and 3 studies for the selection and treatment of patients with folate receptor (FR)-positive tumors. Both of these compounds have been shown to bind with high affinity and specificity to the FR, which is known to be internalized via endocytosis. Though the FR is the major route for delivery of folic acid (an oxidized folate congener) into a cell at physiological pH, two other transporters, the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT), play key roles in transporting folates and antifolates across the cell membrane at neutral and acidic pH, respectively. It is not known, however, if these two transporters play any role in the uptake of folic acid-based SMDCs. Therefore, this study was designed to determine whether vintafolide and/or etarfolatide are substrates for active transport by the RFC or PCFT, or whether their cellular uptake is specific only to the FR. To achieve this, we utilized a set of isogenic Chinese hamster ovary cell lines which have been engineered from transporter-null R2 cells to express the RFC, PCFT, or FR-α, to evaluate cellular uptake of 3H-vintafolide and 3H-etarfolatide:Re. The results of the uptake studies showed that no RFC or PCFT-specific transport of either SMDC occurred under the optimal conditions for transporter activity (pH 7.2 for RFC, and pH 5.5 for PCFT). Conversely, 3H-MTX, a known RFC and PCFT substrate, showed significant uptake by both the RFC and PCFT-expressing cells, and uptake was blocked by PT523 (specific inhibitor for RFC) and AG94 (specific inhibitor for PCFT). Though levels of 3H-vintafolide uptake by the RFC-expressing PC43 cells were similar to that of 3H-MTX, no inhibition of 3H-vintafolide uptake was seen with PT523 suggesting that this uptake is not mediated by the RFC. As expected, very high 3H-vintafolide and 3H-etarfolatide:Re binding and uptake was seen in the FRα-expressing RT-16 cells, and this uptake was competable with excess FA indicating that the interaction was specific to the FR. Collectively, these results show that vintafolide and etarfolatide are specifically transported via the FR and are not substrates for the RFC or PCFT. Citation Format: Nikki Parker, Christina Cherian, Larry Matherly, Christopher P. Leamon. The folate receptor-targeted agents, vintafolide and etarfolatide, are not substrates for the reduced folate carrier or the proton-coupled folate transporter. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4591. doi:10.1158/1538-7445.AM2014-4591
Effect of anticonvulsant drugs on the rate of folate catabolism in mice.
Authors: D Kelly, D Weir, B Reed, J Scott
Journal: Journal of Clinical Investigation (1979)

An increase in folate catabolism has been suggested as the cause of the folate deficiency observed in many clinical conditions, including chronic anticonvulsant therapy. Previous studies have shown that the radioactive catabolites, excreted after an equilibration period of 3 d, consisted exclusively of folates that had been cleaved to produce pteridines and p-aminobenzoylglutamate, most of which was excreted as acetamidobenzoylglutamate. We have developed an experimental animal model using mice to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of [3H]p-aminobenzoylglutamate and [3H]acetamidobenzoylglutamate in urine. Administration of diphenylhydantoin at three different doses (0.5, 20, and 50 mg/kg) significantly increased the rate of catabolism as measured by an increase in both the mean daily excretion and the cumulative excretion of these catabolites. Administration of intramuscular phenobarbitone on the other hand, did not affect the rate of catabolism, when compared with controls.
115. Whole Genome Analysis Shows That AAV Integrates at Chromosome 19 AAV-S1 Sites and Other Chromosomal Sites That Frequently Share GGTC Micro-Homology with the AAV P5 Promoter
Authors: Horace R. Drew, Linda J. Lockett, Gerald W. Both
Journal: Molecular Therapy (2006)

Adeno associated virus undergoes Rep-mediated integration into the AAV-S1 region of human chromosome 19 during latent infection but recombinant AAV (rAAV) vectors are missing essential viral components and lack such site-specificity. This was best shown recently by strategies that monitor rAAV integration events at the level of the whole eukaryotic genome. However, whole-genome analyses have not been used to analyse integration by wild-type AAV. We have used ligation-mediated PCR (LM-PCR) to monitor AAV integration under both latent and replication-permissive conditions of infection. Sequence analysis of fifty-two clones that met pre-determined criteria showed that, during replication, AAV integrated into many chromosomal sites via sequence microhomology that frequently involved a GGTC motif located within the AAV p5 element, with one site preferred. No clones containing specific AAV/AAV-S1 junctions were identified among authentic LM-PCR clones, although such clones were readily obtained using junction-specific PCR primers; suggesting that AAV-S1 integration events constituted only a small portion of the total integration product. During latent AAV infection, GGTC-mediated integration was significantly reduced, but such micro-homology-determined chromosomal junctions were still obtained in excess over AAV-S1 specific products. This new mechanism for the integration of AAV sequences into human chromosomes has a |[ldquo]|signature|[rdquo]| that suggests it may occur independently of Rep, although the detailed mechanism remains to be elucidated. Finally, since others have shown that the p5 element is necessary and sufficient for AAV-S1 chromosomal integration, in view of our new findings, the specificity of new rAAV vectors that include p5-region sequences for improved Repmediated integration should be closely monitored, especially by whole-genome approaches.
Identification of USP18 as an Important Regulator of the Susceptibility to IFN-α and Drug-Induced Apoptosis
Authors: Harish Potu, Andrea Sgorbissa, Claudio Brancolini
Journal: Cancer Research (2010)

Gene products that modify the apoptotic susceptibility of cancer cells may offer novel drug response markers or therapeutic targets. In this study, we probed the contribution of 53 different isopeptidases to apoptosis triggered by bortezomib and etoposide. USP18, a type I IFN-induced protein that deconjugates the ubiquitin-like modifier ISG15 from target proteins, was found to limit apoptotic susceptibility to IFN-alpha or bortezomib. Ablating USP18 in cells treated with IFN-alpha increased tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) production; upregulated expression of transcription factors IFN-regulatory factor (IRF)-1, IRF-7, and IRF-9; and promoted the extrinsic pathway of apoptosis. The proapoptotic effects of ablating USP18 were abrogated by FLIP overexpression or TRAIL silencing. However, in bortezomib-treated cells, weak spontaneous signaling from type I IFNs was implicated in the proapoptotic effect of USP18 ablation. Ectopic USP18 repressed apoptotic signaling by IFN-alpha, TRAIL, or bortezomib. Similar effects were produced by a catalytically inactive USP18 mutant, indicating that the antiapoptotic function of USP18 is independent of its catalytic activity. These findings suggest that USP18 may significantly limit operation of the extrinsic apoptotic pathway triggered by type I IFN and drugs.
Echocardiographic Study of the Abnormal Motion of the Posterior Left Ventricular Wall during Angina Pectoris
Authors: ALAN M. FOGELMAN, ABDUL S. ABBASI, MORTON L. PEARCE, ALBERT A. KATTUS
Journal: Circulation (1972)

Echocardiographic waves from the posterior left ventricular endocardium were recorded in 30 normal subjects and in nine patients during 13 anginal episodes. At rest the normal maximal systolic endocardial velocity (SEVM) was 6.2 ± 1.4 cm/sec, the mean systolic endocardial velocity (SEV) was 4.1 ± 0.7 cm/sec, and the systolic endocardial excursion (SEE) was 1.4 ± 0.3 cm. The maximal diastolic endocardial velocity (DEVM) was 18 ± 3 cm/sec, and the mean early diastolic endocardial velocity (DEV) was 9.4 ± 1.7 cm/sec. Exercise in 20 normals caused a significant increase in SEVM, SEV, DEVM, and DEV, but not SEE. In no instance did any of these values fall below the resting levels. The angina patients differed significantly from the normals having at rest a slower DEVM (15 ± 4 cm/sec) ( P &lt; 0.025) and DEV (8.4 ± 0.8 cm/sec) ( P &lt; 0.025). During exercise, but before angina, there was a significant increase in SEVM and SEV but not SEE, DEVM, or DEV. In no instance did any of these values fall below the resting levels. During angina SEVM and SEV reacted variably and together with SEE were not significantly different from the resting values. In contrast, there was a remarkable slowing of DEVM (8.2 ± 3.2 cm/sec) ( P &lt; 0.001) and DEV (5.7 ± 2.2 cm/sec) ( P &lt; 0.001). Five minutes after the pain and S-T-segment depression disappeared, the endocardium moved as it did before exercise.
Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease
Authors: J. Beecroft, J. Duffin, A. Pierratos, C. T. Chan, P. McFarlane, P. J. Hanly
Journal: European Respiratory Journal (2006)

Although sleep apnoea is very common in patients with end-stage renal disease, the physiological mechanisms for this association have not yet been determined. The current authors hypothesised that altered respiratory chemo-responsiveness may play an important role. In total, 58 patients receiving treatment with chronic dialysis were recruited for overnight polysomnography. A modified Read rebreathing technique, which is used to assess basal ventilation, ventilatory sensitivity and threshold, was completed before and after overnight polysomnography. Patients were divided into apnoeic (n = 38; apnoea/hypopnoea index (AHI) 35±22 events·h -1 ) and nonapnoeic (n = 20; AHI 3±3 events·h -1 ) groups, with the presence of sleep apnoea defined as an AHI &gt;10 events·h -1 . While basal ventilation and the ventilatory recruitment threshold were similar between groups, ventilatory sensitivity during isoxic hypoxia (partial pressure of oxygen ( P O 2 ) 6.65 kPa) and hyperoxia ( P O 2 19.95 kPa) was significantly greater in apnoeic patients. Overnight changes in chemoreflex responsiveness were similar between groups. In conclusion, these data indicate that the responsiveness of both the central and peripheral chemoreflexes is augmented in patients with sleep apnoea and end-stage renal disease. Since increased ventilatory sensitivity to hypercapnia destabilises respiratory control, the current authors suggest this contributes to the pathogenesis of sleep apnoea in this patient population.
Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor
Authors: Frank Breitenbuecher, Susanne Schnittger, Rebekka Grundler, Boyka Markova, Birgit Carius, Alexandra Brecht, Justus Duyster, Torsten Haferlach, Christoph Huber, Thomas Fischer
Journal: Blood (2008)
Lupus Nephritis and Renal Biopsy
Authors: DAVID M. ROXE
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 October 1982Lupus Nephritis and Renal BiopsyDAVID M. ROXE, M.D., FRANCESCO DEL GRECO, M.D.DAVID M. ROXE, M.D.Search for more papers by this author, FRANCESCO DEL GRECO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-4-615_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Whiting-O'Keefe and colleagues (1, 2) have thoughtfully illuminated an important issue, but have omitted data a nephrologist would value. Their before biopsy model does not include kidney size, hypertension, or rate of change in hypertension, and would be strengthened if this information were included. Although "urinalysis" is included, they do not include leukocyte counts or casts of any type, both of which would be part of a nephrologist's evaluation. Nor is there an indiction of how often biopsy data differ from the clinical prediction for improvement or worsening. If the biopsy results never change the clinical...References1. WHITING-O'KEEFEHENKESHEARNHOPPERBIAVAEPSTEIN QJMJCW. The information content from renal biopsy in systemic lupus erythematosus: stepwise linear regression analysis. Ann Intern Med. 1982;96(6 Pt 1):718-23. LinkGoogle Scholar2. WHITING-O'KEEFERICCARDIHENKESHEARNHOPPEREPSTEIN QPJMJW. Recognition of information in renal biopsies of patients with lupus nephritis. Ann Intern Med. 1982;96(6 Pt 1):723-7. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Section of Nephrology/Hypertension Northwestern University Medical School Chicago, IL 60611 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1982Volume 97, Issue 4Page: 615-615KeywordsBiopsyHypertensionKidneysLupus nephritis Issue Published: 1 October 1982 PDF DownloadLoading ...
The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation
Authors: Gaurav Kumar Pandey, Sanhita Mitra, Santhilal Subhash, Falk Hertwig, Meena Kanduri, Kankadeb Mishra, Susanne Fransson, Abiarchana Ganeshram, Tanmoy Mondal, Sashidhar Bandaru, Malin Östensson, Levent M. Akyürek, Jonas Abrahamsson, Susan Pfeifer, Erik Larsson, Leming Shi, Zhiyu Peng, Matthias Fischer, Tommy Martinsson, Fredrik Hedborg, Per Kogner, Chandrasekhar Kanduri
Journal: Cancer Cell (2014)
P02.07 * INTERFERON- MODULATES THE INNATE IMMUNE RESPONSE AGAINST GLIOBLASTOMA INITIATING CELLS
Authors: F. Wolpert, C. Happold, P. Roth, G. Reifenberger, M. Weller, G. Eisele
Journal: Neuro-Oncology (2014)

The prognosis of glioblastoma remains dismal. Immunotherapy is a promising approach with the need of well-defined targets and potent adjuvants. Glioma-initiating cells (GIC) with stem cell properties are such an attractive target for immunotherapy. However, the immunogenicity of GIC seems limited. Interferon (IFN)-β exerts immune-activating effects like enhanced antigen processing, up-regulation of co-stimulatory molecules and enhanced natural killer (NK) cell activity and thus might enhance an immune response against GIC. Moreover, IFN-β exerts direct anti-GIC cell activities. Thus, IFN-β warrants being further evaluated as an adjuvant for anti-glioblastoma immunotherapies. Here we define the net effect of IFN-β treatment on the innate immunogenicity of GIC. Employing Affymetrix-based transcriptomic profiling, we identified alterations in the expression of several immune regulatory genes in a panel of well-defined GIC lines upon treatment with IFN-β. The up-regulation of immunosuppressive human leukocyte antigen (HLA)-E was contrasted by enhanced surface levels of immune activating nectin-2 while the level of NKG2D ligands remained largely unaltered. In NK cell lysis assays, the immunogenicity of 2 of 3 GIC lines was increased upon IFN-β treatment and further enhanced upon gene silencing of HLA-E using RNA interference. Our data indicate that treatment with IFN-β alters the innate immunogenicity of GIC by increased expression of nectin-2, reverted in part by the concurrent upregulation of HLA-E.
Chronic lung disease and pulmonary hypertension: yes or no to NO?
Authors: N. Curzen, S. Archer
Journal: Thorax (1997)

diVusible through cell membranes but highly reactive. It is a vasodilator, this eVect being achieved following ac- and abnormal lungs. They found that inhaled NO at a concentration of 40 ppm precipitated small but significant tivation of soluble guanylyl cyclase after binding to its haem moiety, with a resultant increase in intracellular cyclic reductions in arterial oxygen tension (TcPo2) in both healthy volunteers and in patients with chronic obstructive
Recent Developments in Nonspecific Inflammatory Bowel Disease
Authors: Joseph B. Kirsner, Roy G. Shorter
Journal: New England Journal of Medicine (1982)

THE "nonspecific" inflammatory bowel diseases include ulcerative colitis and proctitis and Crohn's disease of the gastrointestinal tract. Their causes and precise relations remain obscure, and their designation as nonspecific reflects our continuing lack of knowledge of their pathogenesis.1 , 2 The incidence of the nonspecific inflammatory bowel diseases, especially of Crohn's disease, has increased worldwide,3 and they have emerged as one of the important biomedical problems of our time.*DefinitionsUlcerative colitis is a recurrent inflammatory and ulcerative disease of the colon and rectum, characterized clinically by rectal bleeding, diarrhea, cramping abdominal pain, anorexia, and weight loss. The diffuse tissue reaction (including . . .
Identification of an innate T helper type 17 response to intestinal bacterial pathogens
Authors: Kaoru Geddes, Stephen J Rubino, Joao G Magalhaes, Catherine Streutker, Lionel Le Bourhis, Joon Ho Cho, Susan J Robertson, Connie J Kim, Rupert Kaul, Dana J Philpott, Stephen E Girardin
Journal: Nature Medicine (2011)
209 COMBINED MYCOPHENOLATE MOFETIL AND MINIMAL DOSE CALCINEURIN INHIBITOR IN STABLE LIVER TRANSPLANT PATIENTS IS NEPHRO- AND HEPATOPROTECTIVE
Authors: V.R. Cicinnati, Z. Yu, C.G. Klein, G. Sotiropoulos, F. Sahner, G. Gerken, S. Beckebaum
Journal: Journal of Hepatology (2008)
Abstract 5417: Improved tumor targeting by BLD1-ELP
Authors: Eun-A Cho, Vijaya Devi Sarangthem, Byung-Heon Lee, In-San Kim, Rang-Woon Park
Journal: Cancer Research (2014)

Abstract Elastin-like polypeptide (ELP) is a promising class of recombinant biopolymers for drug delivery to solid tumors. It is a thermally responsive polypeptide derived from mammalian elastin and consists of repeating pentapeptide sequence, Val-Pro-Gly-X-Gly, where X can be any amino acid except proline. ELPs conjugated to targeting peptide and drugs would enable enhanced targeting for drug delivery to solid tumors. BLD1 is a peptide which can selectively bind to bladder tumor cells. Not only for overcoming its rapid elimination from circulation and short half-life, but also enhancing tumor targeting efficiency, we introduced multiple BLD1 into the ELP (BLD1-ELP). Transition temperature (Tt) of BLD1-ELP was approximately 39 °C. BLD1-ELP showed superior cell binding ability than BLD1 peptide alone with 5637 and HT-1376 bladder tumor cell lines. The confocal microscopic imaging further confirmed that BLD1-ELP polymer efficiently bound to 5637 cells and HT-1376 cells compare to HEK293 embryonic kidney epithelial cells. The cellular uptake of BLD1-ELP was also much higher in 5637 cells and HT-1376 cells than in HT-29 colon cancer cells and HEK293 cells. In in vivo imaging analysis, tumor targeting of intravenously injected BLD1-ELP was observed in 5637 tumor xenograft model. These data suggest that BLD1-ELP can be developed as an effective tumor targeting, drug delivery system for diagnosis and therapy. Citation Format: Eun-A Cho, Vijaya Devi Sarangthem, Byung-Heon Lee, In-San Kim, Rang-Woon Park. Improved tumor targeting by BLD1-ELP. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5417. doi:10.1158/1538-7445.AM2014-5417
Treatment of Intrahepatic Lithiasis Using the Choledochofiberscope
Authors: N. Murata, T. Beppu, Y. Bandai, J. Izeki, K. Arai, T. Ito, M. Sasago, G. Watanabe, S. Futagawa, K. Ushiyama, T. Wada
Journal: Endoscopy (1981)

Our experience with choledochoscopic extraction of intrahepatic calculi in eleven cases is presented. In three cases, the intrahepatic bile duct containing multiple stones was punctured under the guidance of ultrasonography, and the stones were removed choledochoscopically through the percutaneous transhepatic cholangial drainage (PTCD) tract which was dilated with catheters of increasing diameter.
Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model
Authors: K. Tanabe, Y. Maeshima, K. Ichinose, H. Kitayama, Y. Takazawa, K. Hirokoshi, M. Kinomura, H. Sugiyama, H. Makino
Journal: Kidney International (2006)
Comment on: Chang et al. A 25-Year Longitudinal Evaluation of Gastric Emptying in Diabetes. Diabetes Care 2012;35:2594–2596
Authors: Ketan Dhatariya
Journal: Diabetes Care (2013)

I read the article by Chang et al. (1) with some interest. However, there are several aspects of their article that I believe need further explanation.

The authors have previously published data on the same cohort of patients reporting no change in symptoms over a 12-year period (2). Out of their original cohort of 86 subjects, current data are only presented on 15% or 13 subjects. While the authors admit that there has been an attrition rate in follow-up due to the expected mortality and morbidity, to suggest that these 13 subjects somehow represented the entire original cohort maybe stretching things. The authors report that …