tbuckley/cabot-search huggingface dataset:
A novel inhibitor of vacuolar H+-ATPase, NIK-12192, potentiates the antitumor effect of topotecan in BCRP-expressing tumor systems.
Authors: Rosanna Supino, Giovanna Petrangolini, Anna C. Croce, Laura Dal Bo, Monica Tortoreto, Graziella Pratesi, Paola Misiano, Carlo Farina, Franco Zunino
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5422 

Tumor cells often exist in hypoxic microenvironment and produce acidic metabolites. Different types of intracellular pH regulatory mechanisms are known, including the vacuolar H+-ATPase (V-ATPase), which is functionally expressed in cellular membranes. V-ATPase is often overexpressed in P-gp multidrug resistant (MDR) cells and its modulation may affect drug-resistance. Its role in the drug resistance of tumor cells expressing breast cancer resistance protein (BCRP) remains to be elucidated. NIK-12192 is a small molecule indole derivative identified as a potent inhibitor of the osteoclasts V-ATPase. The aim of the study was to investigate the effect of NIK-12192 on the cytotoxicity of topotecan (TPT), a clinically used camptothecin known to be a BCRP substrate. The human HT29 colon carcinoma cell line and the BCRP-overexpressing HT29/Mit sub-line were employed. In cell cultures, the antiproliferative effect of TPT was enhanced by the concomitant exposure to NIK-12192 in both cell lines, particularly in HT29/Mit cells. The potentiation of TPT efficacy by NIK-12192 was documented in the same tumor models growing in vivo as tumor xenografts. Again, the enhancement of TPT activity was more evident in the TPT-resistant HT29/Mit model. While TPT alone localized mainly in mitochondria and endoplasmic compartment, the simultaneous presence of NIK-12192 resulted in a cytoplasmatic localization of TPT. Moreover, as evidenced by acridine orange staining, HT29/Mit cells treated with TPT presented a marked acidification, which was reverted by NIK-12192. In conclusion, the V-ATPase inhibitor NIK-12192 was able to potentiate the cytotoxic effect of TPT in a BCRP-overexpressing tumor, either in in vitro or in vivo systems, possibly by modifying the cellular pharmacokinetic of the drug.
T-cell release of granulysin contributes to host defense in leprosy
Authors: Maria-Teresa Ochoa, Steffen Stenger, Peter A. Sieling, Sybille Thoma-Uszynski, Shereen Sabet, Sungae Cho, Alan M. Krensky, Martin Rollinghoff, Euzenir Nunes Sarno, Anne E. Burdick, Thomas H. Rea, Robert L. Modlin
Journal: Nature Medicine (2001)
Fibroblast growth factor 9 (FGF9) modulates the phenotype of control and fibrotic human lung fibroblasts in vitro
Authors: Audrey Joannes, Joelle Marchal-Somme, Laura Giersch, Bruno Crestani, Arnaud Mailleux
Journal: European Respiratory Journal (2014)

Introduction: Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix (ECM) proteins and fibroblasts in the distal airways. Key developmental lung signalling pathways are reactivated in IPF. During lung development, FGF9 is produced by epithelial cells and controls mesenchyme proliferation and patterning during branching morphogenesis. We investigated the effects of FGF9 on proliferation, myofibroblastic differentiation, survival and migration of control and IPF human lung fibroblasts in vitro.  Methods: Control and IPF fibroblasts (N=6) were cultured with FGF9 (20ng/ml) (24 or 48 h).Growth rate was evaluated by cell count. FAS-ligand induced apoptosis was assayed by measuring caspase 3/7 activity.Expression of FGF receptors (FGFR) mRNA, and α-smooth muscle actin, collagen I and fibronectin was analyzed with qPCR and western blot. Migratory capacities were evaluated in a modified Boyden chamber.  Results:  Fgfr1IIIc, Fgfr3IIIc and Fgfr4  are the main FGFR expressed in control and IPF fibroblasts. FGF9 did not influence fibroblast proliferation or differentiation of control and IPF fibroblasts in presence or absence of TGF-b1 (1ng/ml). FGF9 decreased caspase 3/7 activity induced by Fas-ligand activation in control fibroblast (-25%) but not in IPF fibroblast. FGF9 increased the migratory capacity of control (4.1 fold) and IPF (3.5 fold) fibroblasts.  Conclusion: These results identify FGF9 as a potential pro-survival and pro-migratory growth factor on lung fibroblast that could contribute to lung fibrosis.   This work was supported by the Agence Nationale pour la Recherche (ANR-11-BSV1-0011), Boehringer Ingelheim and the LabEx Inflamex.
The human olfactory receptor repertoire
Authors: Sergey Zozulya, Fernando Echeverri, Trieu Nguyen
Journal: Genome biology (2001)

The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans.The strategy of our sequence database mining for full-length, functional candidate odorant receptor genes was based on the high overall sequence similarity and presence of a number of conserved sequence motifs in all known mammalian odorant receptors as well as the absence of introns in their coding sequences. We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors. A new nomenclature for human odorant receptors based on their chromosomal localization and phylogenetic analysis is proposed. We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors.The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction.
Nonoperative Management of Bilateral Adrenal Incidentalomas
Authors: Linwah Yip, Sally E. Carty
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder
Authors: K S Cadenhead, M A Geyer, D L Braff
Journal: American Journal of Psychiatry (1993)

Information processing measures that serve as biological markers for schizophrenia can help to define the boundaries of schizophrenia. Prepulse inhibition and habituation of the blink reflex component of startle, which are thought to reflect an individual's ability to screen out or "gate" irrelevant sensory stimuli, are impaired in patients with schizophrenia. These deficits in sensorimotor gating and habituation in schizophrenic patients may lead to sensory overload and, secondarily, cognitive fragmentation, disorganization, and thought disorder. The goal of this study was to test two hypotheses: 1) patients with schizotypal personality disorder would show a loss of sensorimotor gating reflected by impaired prepulse inhibition of the human startle response and 2) patients with schizotypal personality disorder would show deficits in startle habituation consistent with the deficits seen in patients with schizophrenia.Prepulse inhibition and habituation were assessed in 12 men and four women who met DSM-III-R criteria for schizotypal personality disorder and in 22 normal comparison subjects.Patients with schizotypal personality disorder had deficits in acoustic prepulse inhibition and habituation similar to the deficits observed in patients with schizophrenia. Although there were no differences between patients with schizotypal personality disorder and normal subjects in latency from acoustic startle stimuli to response, latency facilitation was produced by the prepulse in both groups.This pattern of changes in amplitude and latency of the startle response suggests that subjects with schizotypal personality disorder perceive the prepulse stimuli but still demonstrate deficient sensorimotor gating of amplitude. These findings support the importance of startle prepulse inhibition and startle habituation as biological markers for schizophrenia spectrum disorders.
Effects of Nurse-Managed Protocols
Authors: Michelle A. Lucatorto, Storm Morgan
Journal: Annals of Internal Medicine (2015)

Letters5 May 2015Effects of Nurse-Managed ProtocolsMichelle A. Lucatorto, APRN, DNP, FNP-BC and Storm Morgan, MSN, RN, MBAMichelle A. Lucatorto, APRN, DNP, FNP-BCFrom Veterans Health Administration, Washington, DC.Search for more papers by this author and Storm Morgan, MSN, RN, MBAFrom Veterans Health Administration, Washington, DC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5086 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Shaw and colleagues (1) do a nice job of quantifying clinical outcomes for patients who receive care by nurses using protocols. Jauhar and Battinelli's editorial asks whether nurses are the answer to the national problem of primary care physician shortages at a time when demand for services continues to rise. We suggest that nurses are not the sole answer to the challenges in primary care; the solution is the implementation of high-performing, team-based care. However, nursing is a vital and untapped component of this high-performing team.It literally takes a village to manage health care needs, including ...References1. Shaw RJ, McDuffie JR, Hendrix CC, Edie A, Lindsey-Davis L, Nagi A, et al. Effects of nurse-managed protocols in the outpatient management of adults with chronic conditions: a systematic review and meta-analysis. Ann Intern Med. 2014;161:113-21. [PMID: 25023250] doi:10.7326/M13-2567 LinkGoogle Scholar2. Mitchell P, Wynia M, Golden R, McNellis B, Okun S, Webb CE, et al. Institute of Medicine. Discussion Paper: Core Principles & Values of Effective Team-Based Health Care. Washington, DC: National Academies Pr; 2012. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Veterans Health Administration, Washington, DC.Disclaimer: The contents of this letter do not represent the views of the U.S. Department of Veterans Affairs or the U.S. government.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0495. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffects of Nurse-Managed Protocols in the Outpatient Management of Adults With Chronic Conditions Ryan J. Shaw , Jennifer R. McDuffie , Cristina C. Hendrix , Alison Edie , Linda Lindsey-Davis , Avishek Nagi , Andrzej S. Kosinski , and John W. Williams Jr. Effects of Nurse-Managed Protocols in the Outpatient Management of Adults With Chronic Conditions Ryan J. Shaw , Jennifer R. McDuffie , Cristina C. Hendrix , Alison Edie , Linda Lindsey-Davis , Avishek Nagi , Andrzej S. Kosinski , and John W. Williams Jr. Metrics 5 May 2015Volume 162, Issue 9Page: 669KeywordsDisclosureDrug therapyHealth careHealth promotionLegislationNursesNutritionPatientsPharmacists ePublished: 5 May 2015 Issue Published: 5 May 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Vaccine and Drug Dispensing
Authors: Tracy Hampton
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Applying results of randomised trials to patients
Authors: S. Senn
Journal: BMJ (1998)

Prognosis of symptoms that are medically unexplained Every neurology service should have access to specialist liaison psychiatryEditor-Crimlisk et al's report on the outcome of motor symptoms that were medically unexplained in a cohort first identified at the National Hospital for Nervous Diseases is welcomed by those interested in the psychiatry of physical illness. 1 Slater's work, based on cohorts recruited in the 1950s, overestimated the likelihood of misdiagnosis in modern neurology, 2 and his conclusions have dissuaded psychiatrists from becoming involved in the management of hysteria.O'Brien's editorial on Crimlisk et al's study could have sounded two cautionary notes. 3Firstly, the study was not based on a true inception cohort, and it was recruited from a highly specialised centre.Usually, these factors lead to the finding of a worse prognosis than if only incident cases were included and the sample was less prone to recruitment bias.In this case, however, the bias may have been in the other direction.Patients seen at the National Hospital are likely to have been more exhaustively investigated and observed for longer (either in this episode or before referral) than they would be in most hospitals, so that the chances of misdiagnosis are reduced.We should not generalise the study findings to hospitals where initial assessment may be undertaken with little or no access to specialist neurological opinion or investigations.Secondly, the negative message-that high rates of undetected neurological disease are not seen at follow up-has been allowed to obscure the important positive findings of the study.Even years later, the patients had disabling physical symptoms and substantial psychiatric problems.As in Slater's original study, preventable deaths occurred from suicide and the complications of immobility.Many people were apparently not referred for psychiatric help either at the time of the initial presentation or subsequently.The important conclusion of Crimlisk et al's study must be that every neurology service should have easy access to referral to specialist liaison psychiatry. 4This group of patients, who are difficult to treat, are often resistant to treatment, and have a poor prognosis, may then have a reasonable chance of obtaining appropriate treatment for their primary disorder.
Abstract 818: A Novel Electrophysiological Model Using Hybrid X-Ray/MRI and Non-Contact Mapping to Estimate Electrical Recruitability of Myocardial Tissue
Authors: Phani Chinchapatnam, Matthew R Ginks, Maxime Sermesant, Kawal Rhode, Simon Arridge, Pier D Lambiase, Julian Bostock, C A Rinaldi, Reza Razavi
Journal: Circulation (2008)

Introduction CRT is established therapy for patients with symptomatic heart failure, poor LV function &amp; evidence of dyssynchrony. Hypothesis CRT outcomes may be improved by understanding of patient-specific conduction through electrical recruitability (ER) maps of the LV which can be derived from LV electrical activation (EA) data &amp; electrophysiology (EP) models. Methods Patients scheduled for CRT underwent cardiac MRI in our hybrid X-ray/MRI (XMR) laboratory to delineate scar using late gadolinium enhancement (LE). An EP study was performed in the same procedure. An Eikonal EP model was used to predict propagation wavefronts in different pacing modes. ER was defined as the square of the tissue space constant of EA &amp; was estimated by an adaptive algorithm by matching the simulated to the recorded activation times. Activation maps were recorded in various pacing modes using non-contact mapping (NCM). Results Ten patients underwent combined MRI &amp; EP study. Fig 1a shows the estimated ER for a patient with activation recorded in sinus rhythm (SR) &amp; corresponding % thickness LE from cardiac MRI (Fig 1b ). The correspondence of low recruitability areas (blue) to positive LE areas is evident. Further, an endocardial paced isochronal map was then predicted using the EP model with the SR ER map (Fig 1c ) &amp; compared against NCM isochrones obtained (Fig 1d ) pacing in that position. Conclusion We have shown the proof of concept for estimating the electrical recruitability of myocardial tissue. Such maps may provide insights into the electrical properties of the tissue and assist in prediction of activation patterns resulting from pacing and may have a role in optimization of CRT pacing lead positions. Fig. 1. Bull’s eye plots for a patient with ischemic cardiomyopathy, posterolateral scar and LBBB. LV apex at centre of each diagram and basal segment on outside; anatomical orientation as indicated in (a) top left; Electrical recruitablility (units=mm 3 ) obtained in sinus rhythm (b) bottom left: percentage wall thickness of late enhancement (LE) (0=no LE; 1= full thickness LE) (c) top right; predicted isochronal map (earliest in red to latest in blue, units= msec) for LV endocardial pacing based on estimated recruitability and (d) bottom right corresponding measured activation pattern measured using NCM. (IVS: Interventricular septum)
Abstract 18807: Spatial Distribution of the Metabolically Active Pulmonary Circulation in Humans
Authors: Xavier Levac, Francois Harel, Vincent Finnerty, Quang Trinh Nguyen, Myriam Letourneau, Sophie Marcil, Alain Fournier, Jocelyn Dupuis
Journal: Circulation (2014)

Introduction: Human pulmonary perfusion is not homogeneously distributed. Analysis of pulmonary perfusion spatial distribution (SD) variations, could be useful in the evaluation of pulmonary disorders. We developed a new tracer called PulmoBind (PB), which binds to the adrenomedullin receptor abundantly expressed in the lung endothelium. Nowadays, all imagery methods rely on physical agents distributed within the pulmonary circulation and whose external signals are reflections of perfusion. There is no clinically validated imaging agent that relies on biologic functions of the endothelium properties and could quantitatively assess the spatial distribution of metabolic active pulmonary circulation (SDMAPC). The aim of this study was to determine the ability of the endothelial cell tracer PB to measure the SDMAPC in human. Methods: Healthy subjects (n=20) were included in the PB phase I trial (NCT01539889). SPECT imaging was performed in the supine position 90 min after injection. SD was determined as mean ...
Abstract 2624: Chronic Hypoxia Increases Bone Marrow-Derived Endothelial Cells of Non-Hematopoietic Stem Cell Origin, as Well as Macrophages of Hematopoietic Stem Cell Origin, in Pulmonary Vascular Lesions in Mice: Differential Roles of Bone Marrow-Derived Hematopoietic and Non-Hematopoietic Stem Cells in Pulmonary Hypertension
Authors: Taichi Kato, Hirofumi Sawada, Junko Maruyama, Masahiro Masuya, Eri Mityata, Shiho Nakamura, Yukiko Ikeyama, Takao Deguchi, Hideto Shimpo, Kazuo Maruyama, Yoshihiro Komada, Yoshihide Mitani
Journal: Circulation (2008)
Abstract 5492: Effect of GnRH analogues and pharmacoperone IN3 treatment in survival of prostatic cancer cells to radiation
Authors: Catherine A. Sanchez, Apolo Salgado, Enrique A. Castellon
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) is the second cause of cancer related death in men. Radiotherapy of localized tumours is highly effective and reduces the risk of urinary incontinence and impotence compared with radical surgery. Radiotherapy is more effective when associated with GnRH analogues (as leuprolide), which has been related with decreased circulating androgens due to hypophysis-testis axis blockade. We propose that GnRH analogues increase the cytotoxic effect of radiotherapy in PCa cells, effect that can be potentiated with IN3, a pharmacoperone that increases GnRH receptor (GnRHR) expression in cell membrane. To demonstrate our hypothesis, we stablished primary cell cultures from PCa samples from patients of our Institutional Hospital (n=12). Cells were treated during 24 hr with 1 ug/ml IN3 (Merck Sharp &amp; Dohme Corp., USA,) and then with different concentrations (20-80 ng/ml) of leuprolide (Sigma-Aldrich Co., USA) for 24 hr. Later, cells were irradiated at 3 Gy and we evaluated cell survival at 24 hr (through MTT), changes in cell cycle at 24 hr and apoptosis at 6 hr (through FACS). GnRHR expression in cell membrane after 24 hr of IN3 treatment was evaluated trough fluorescence microscopy. Results were evaluated using Anova and Kruskal-Wallis tests, followed by post-test of Dunn. P &amp;lt;0.05. As we previously described, we observed that leuprolide decreased PCa cell survival. When cells were pre-treated with IN3, GnRHR expression in cell membrane increased in about 60% and the effect of leuprolide treatment was higher. When cells were irradiated, cell survival decreased in 10%, this effect was higher when cells were previously treated with leuprolide (15%) and IN3/leuprolide (20%). This was related with an increase of 10% in apoptosis and cell cycle arrest in G2. The effect was dependant of leuprolide dose. At the dose used, IN3 had no effect in cell survival. We concluded that leuprolide sensitizes cells from PCa to radiation, and this effect was increased with pretreatment with IN3 due, at least in part, for the increase of GnRHR expression in cell membrane, a receptor that decreases its expression during PCa progression. In clinical practice, leuprolide has direct effect over PCa cells, decreasing cancer cell survival and improving the cytotoxic effect of radiation. The utility of IN3 as a potential adjuvant therapy needs to be addressed. Citation Format: Catherine A. Sanchez, Apolo Salgado, Enrique A. Castellon. Effect of GnRH analogues and pharmacoperone IN3 treatment in survival of prostatic cancer cells to radiation. [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 5492. doi:10.1158/1538-7445.AM2014-5492