tbuckley/cabot-search huggingface dataset:
Abstract 5270: Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer
Authors: Jaeku Kang, Sun Young Kim
Journal: Cancer Research (2011)

Abstract Histone deacetylases (HDACs) are associated with the development and progression of cancer, but which HDAC isoforms play important roles in breast cancer metastasis is not known. Here, we identify the specific HDAC isoforms that are necessary for invasion and/or migration in human breast cancer cell lines. MDA-MB-231 cells were significantly more invasive and expressed higher levels of matrix metalloproteinase-9 (MMP-9) than MCF-7 cells. We compared the expression of HDAC isoforms between MCF-7 and MDA-MB-231 cells and found greater expression of HDAC4, 6 and 8 in MDA-MB-231 by RT-PCR and Western blot analyses. In addition, apicidin, a histone deacetylase inhibitor, was shown to attenuate the invasion, migration and MMP-9 expression in MDA-MB-231 cells. Using specific siRNAs directed against HDAC1, 4, 6 and 8, we show that inhibition of HDAC1, 6 and 8, but not HDAC4, are responsible for invasion and MMP-9 expression in MDA-MB-231 cells. We analyzed the invasiveness of MCF-7 cells overexpressing HDAC1, 4, 6 or 8 and found that overexpression of HDAC1, 6 or 8 increased invasion and MMP-9 expression. By developing HDAC isoforms as potential biomarkers for breast cancer metastasis, the present study can be extended to developing therapies for breast cancer invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2011-5270
Abstract 2909: Doxorubicin-loaded zirconium phosphate nanoparticles for intracellular anticancer drug delivery to breast cancer cells
Authors: Millie L. González, Agustin Diaz, Jennifer Cabán, Jorge Colón, Adriana Báez
Journal: Cancer Research (2012)

Abstract Purpose: Doxorubicin (DOX), is an anthracycline antibiotic widely used for the treatment of several solid tumors but its usage is limited by serious side effects to healthy tissues. The purpose of this study was to explore the effectiveness of zirconium phosphate nanoparticles (ZrP) as carrier of anticancer agents (ie. DOX) to tumor cells and potentially reduce side effects to healthy tissue. Methods: Confocal Microscopy (CM) was used to assess internalization and localization of doxorubicin-loaded ZrP nanoparticles (DOX:ZrP) in MCF-7 breast cancer cell line. The cytotoxicity of ZrP and DOX:ZrP in MCF-7 and MCF-10A cells was studied using MTT assay. Results: Co-internalization of DOX and ZrP nanoparticles into the cytoplasm and nucleus of MCF-7 cells was detected using CM. A high fluorescence in cell nucleus demonstrated DOX release from ZrP nanoparticles. ZrP alone is non-toxic to MCF-7 and MCF-10A cells. After a 48-hour treatment of MCF-7 cells with DOX:ZrP or DOX alone the IC50 obtained was 23µM and 24 µM, respectively. DOX cytotoxicity to MCF-7 cells after 72-hour treatment was three times higher than DOX:ZrP with IC50 of 0.74 µM and 3.15 µM, respectively. Conclusion: ZrP nanoparticles are internalized and can effectively deliver DOX to the interior of cancer cells. ZrP nanoparticles might provide a versatile platform for transportation of anticancer agents resulting in improved cancer therapy by reducing the side effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2909. doi:1538-7445.AM2012-2909
Medicare Coverage of Investigational Devices
Authors: P. Justin Rossi, Andre Machado, Michael S. Okun
Journal: JAMA Neurology (2014)

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 Neurology 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 Neurology journal
EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial
Authors: Andrew S C Rice, Robert H Dworkin, Tom D McCarthy, Praveen Anand, Chas Bountra, Philip I McCloud, Julie Hill, Gary Cutter, Geoff Kitson, Nuket Desem, Milton Raff
Journal: The Lancet (2014)
Synthesis, Binding, Release, and Metabolism of Norepinephrine in Normal and Transplanted Dog Hearts
Authors: LINCOLN T. POTTER, THEODORE COOPER, VALLEE L. WILLMAN, DAVID E. WOLFE
Journal: Circulation Research (1965)

The ability of normal and transplanted dog hearts to make, bind, store, and metabolize norepinephrine was studied. Transplanted hearts were used in order to assess the effects of adrenergic denervation. Normal hearts bound large quantities of administered C 14 -dopamine and synthesized considerable quantities of norepinephrine in both the atria and ventricles. Isolated perfused normal hearts steadily removed about 56% of infused dl -H 3 -norepinephrine; a binding mechanism was the major means of inactivation of the amine. Uptake of radioactive norepinephrine was greater in the ventricles than in the atria because they received more of the amine, and the turnover rate of the labeled amine was also highest in the ventricles. Subcellular fractionation of the bound amine demonstrated that it was localized in particles of microsomal size; radioautographic studies demonstrated the presence of H 3 -norepinephrine only in association with nerves. About 57% of the H 3 -norepinephrine released from normal hearts was metabolized, primarily by O-methylation. After autotransplantation, and degeneration of postganglionic sympathetic nerves, the average catecholamine content of the hearts fell to 1.2% of normal, C 14 -dopamine uptake and formation of norepinephrine were reduced to a few per cent of normal, and the uptake and retention of H 3 -norepinephrine was 6.1% of normal under the conditions used. Binding of norepinephrine to unknown sites in the transplanted tissue served temporarily as an important mechanism of inactivation of the amine, but this norepinephrine was very rapidly released and nearly 85% metabolized, again predominantly by O-methylation. The fine structure of the transplanted tissues was barely distinguishable from that of normal hearts by electron microscopy. In vitro assays of catechol-O-methyltransferase and monoamine oxidase showed little change in activity upon adrenergic denervation. These results demonstrate the importance of the adrenergic innervation of the heart for the normal synthesis, storage and inactivation of norepinephrine.
The Relief of Abdominal Pains.
Authors: J. A. Work
Journal: JAMA (1894)

Elkhart, Ind., October 1,1894. <h3>To the Editor:</h3> —In answer to J. Lue Sutherland's case reported in theJournalof September 29, the Doctor asks? Was it a case of subacute peritonitis? It may have<i>become</i>so; for, nearly five weeks intervened from time of first attack of pain until death ensued; giving ample time for inflammation to occur, if the first<i>cause</i>of trouble was not promptly removed. Too often the physician's sympathy is enlisted by the entreaties of the patient for relief of pain, so that the proper means to remove the cause is not employed at once. And this is the suggestion I would make in this class of cases: If pain and distress is in gastric region give an emetic; if in lower abdomen, thoroughly empty the rectum and colon by a warm water enema, and then if there is no relief, give a quick active purgative
Methodological concerns about a recent meta‐analysis of the influence of the I148M variant of patatin‐like phospholipase domain containing 3 on the susceptibility and histological severity of nonalcoholic fatty liver disease
Authors: Liu Liu, Jiang-Hua Shao, Kai Wang, Fu-Zhou Hua
Journal: Hepatology (2011)

We read the meta-analysis by Sookoian and Pirola1 with great interest. Their meta-analysis suggests that patatin-like phospholipase domain containing 3 rs738409 C/G is a strong modifier of the natural history of nonalcoholic fatty liver disease. However, several points should be mentioned here. The perfect searching strategy and the use of more related databases allow researchers to include an extensive number of potentially eligible studies, and this is crucial for a meta-analysis. Although the Medical Literature Analysis and Retrieval System Online (MEDLINE) database is one of the most comprehensive databases for health care information, its coverage is not complete.2 Lemeshow et al.3 and Seminara et al.4 suggested that at least MEDLINE, another electronic database, and hand searching should be used for a thorough search. In this meta-analysis, only the MEDLINE database was searched for eligible studies. In addition, Sookoian and Pirola1 limited the search to publications written in English. Using this approach, they may have neglected some eligible studies, and this may have resulted in selection or publication bias. Moreover, local databases also should have been searched. The Hardy-Weinberg equilibrium should be evaluated in a control group. The deviation from the Hardy-Weinberg equilibrium presents the probability of genotyping errors, selection bias, or other bias.5 However, the Hardy-Weinberg equilibrium test was not performed in this meta-analysis. According to the sources of the controls, a case-control study is usually categorized as a hospital-based case-control (HCC) study (the controls are hospitalized patients) or a population-based case-control study (the controls are healthy people). A meta-analysis based on an HCC study may be biased because HCC controls always have some kind of disease, unhealthy life habit, or risk genotype.6 It is routine in a meta-analysis for a stratified analysis to be performed according to the sources of the controls to confirm the validity of the results rather than bias.6 Similarly, to retain the homogeneity and make the results more reliable, Sookoian and Pirola1 should perform a subgroup analysis for this meta-analysis and thus confirm the validity of the results. Liu Liu M.D.*, Kai Wang M.D.*, Fu-Zhou Hua M.D. [email protected] , Jiang-Hua Shao M.D.*, * Departments of Gastrointestinal Surgery, Nanchang University, Nanchang City, Jiangxi, China, Anesthesiology, Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi, China.
The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: The Multi-Ethnic Study of Atherosclerosis
Authors: Otto A. Sanchez, Daniel A. Duprez, Hossein Bahrami, Lori B. Daniels, Aaron R. Folsom, Joao A. Lima, Alan Maisel, Carmen A. Peralta, David R. Jacobs
Journal: Metabolism (2013)
Preferential venoconstriction by cyclooxygenase inhibition in vivo without attenuation of nitroglycerin venodilation.
Authors: T Münzel, D J Stewart, J Holtz, E Bassenge
Journal: Circulation (1988)

Because prostacyclin is a rather potent venodilator in vivo, we analyzed the effect of cyclooxygenase inhibition on venous tone in 14 anesthetized dogs during ganglionic and beta-adrenergic blockade and atraumatic conditions. Effective vascular stiffness (a reciprocal of effective vascular compliance) as a variable of integrated venous tone was 0.30 +/- 0.01 mm Hg.kg/ml (n = 35) and was augmented up to twofold by diclofenac (1, 3, and 10 mg/kg i.v.), ibuprofen (6 and 60 mg/kg), or indomethacin (5 mg/kg) parallel to augmentations in central venous pressure, while the rise in arterial pressure was less than half of the increase induced by equivenoconstrictor dosages of norepinephrine. After preconstriction by indomethacin or diclofenac, nitroglycerin (1.5 micrograms/kg/min) lowered effective vascular stiffness (by 24 +/- 2% or 23 +/- 5%, respectively), similarly as during preconstriction by norepinephrine (by 24 +/- 4%). Long-term cyclooxygenase inhibition (diclofenac 2 x 1 mg/kg/day for 4 days) did not modify arterial pressure, heart rate, or hematocrit levels in conscious dogs at rest, but it lowered plasma volume to 52.5 +/- 1.9 ml/kg (sham treatment: 59.1 +/- 1.6 ml/kg, p less than 0.05, n = 4). In conclusion, venoconstriction by clinical dosages of cyclooxygenase inhibitors does not interfere with the venodilator action of nitroglycerin and is compensated chronically by adjustments of plasma volume.
How to Use an Article About Genetic Association
Authors: John Attia, John P. A. Ioannidis, Ammarin Thakkinstian, Mark McEvoy, Rodney J. Scott, Cosetta Minelli, John Thompson, Claire Infante-Rivard, Gordon Guyatt
Journal: JAMA (2009)

This is the first in a series of 3 articles serving as an introduction to clinicians wishing to read and critically appraise genetic association studies. We summarize the key concepts in genetics that clinicians must understand to review these studies, including the structure of DNA, transcription and translation, patterns of inheritance, Hardy-Weinberg equilibrium, and linkage disequilibrium. We review the types of DNA variation, including single-nucleotide polymorphisms (SNPs), insertions, and deletions, and how these can affect protein function. We introduce the idea of genetic association for both single-candidate gene and genome-wide association studies, in which thousands of genetic variants are tested for association with disease. We use the APOE polymorphism and its association with dementia as a case study to demonstrate the concepts and introduce the terminology used in this field. The second and third articles will focus on issues of validity and applicability.
AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis
Authors: Megan Griffey, Shannon L. Macauley, Judith M. Ogilvie, Mark S. Sands
Journal: Molecular Therapy (2005)

Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). The earliest clinical sign in INCL is blindness, followed by seizures, cognitive deficits, and early death. Little is known about the progression of the visual deficits in INCL. Here we characterize the progressive retinal dysfunction and examine the efficacy of AAV2-mediated ocular gene therapy in the murine model of INCL. Significant decreases in both mixed rod/cone and pure cone electroretinographic amplitudes were observed at as early as 2 months of age. Intravitreal injection of AAV2-PPT1 increased enzyme levels in the eye to greater than normal levels. The increased PPT1 activity correlated with improvements in the histological abnormalities as well as both mixed rod/cone and pure cone functions. We also demonstrated that palmitoyl protein thioesterase-1 activity was detected in the brain following intravitreal injection. The brain activity is likely due to anterograde axonal transport along the optic tracts. Interestingly, the degree of neurodegeneration throughout the visual pathways of the brain was greatly reduced in AAV-treated INCL mice. Therefore, intravitreal AAV-mediated gene therapy has direct benefits to the eye and to distal sites in the brain along the visual pathways.
Cholesterol- and caveolin-rich membrane domains are essential for phospholipase A-dependent EDHF formation
Authors: A GRAZIANI, V BRICKO, M CARMIGNANI, W GRAIER, K GROSCHNER
Journal: Cardiovascular Research (2004)

Cholesterol-rich membrane domains, which contain the scaffold protein caveolin-1 (Cav-1) (caveolae), represent an important structural element involved in endothelial signal transduction. The present study was designed to investigate the role of these signaling platforms in the generation of endothelial-derived hyperpolarizing factor (EDHF).Caveolae were disrupted by cholesterol depletion with methyl-beta-cyclodextrin (MbetaCD 10 mM). MbetaCD-induced modulation of non-nitric oxide-/non-prostanoid-dependent (EDHF)-mediated vasorelaxation was studied in pig coronary arteries. Effects of MbetaCD on endothelial Ca(2+) signaling and phospholipase A(2) (cPLA(2)) activity were determined using fura-2 imaging and measurement of [(3)H]-arachidonate mobilization in cultured pig aortic endothelial cells (PAEC). Cellular localization of caveolin-1 and phospholipase A(2) was investigated by cell fractionation, and interaction of cPLA(2) with caveolin-1 was tested by immunoprecipitation experiments.MbetaCD inhibited EDHF-mediated relaxations of pig coronary arteries induced by bradykinin (100 nM) or ionomycin (300 nM) but not relaxations induced by the NO donor DEA/NO (1 microM). Exposure of arteries to cholesterol-saturated MbetaCD failed to affect EDHF-mediated relaxations. Cholesterol depletion with MbetaCD did not affect bradykinin or ionomycin-induced Ca(2+) signaling in pig aortic endothelial cells, but was associated with enhanced basal and reduced Ca(2+)-dependent release of arachidonic acid (AA). Cell fractionation experiments indicated targeting of cPLA(2) to low density, caveolin-1 rich membranes and immunoprecipitation experiments demonstrated association of phospholipase A(2) with the scaffold protein of caveolae, caveolin-1. Cholesterol depletion with MbetaCD did not disrupt the interaction between cPLA(2) and caveolin-1 but prevented targeting of cPLA(2) to low density membranes. Exogenous supplementation of arachidonic acid after cholesterol depletion partially restored EHDF responses in pig coronary arteries.The integrity of caveolin-1-containing membrane microdomains is prerequisite for arachidonic acid recruitment and EDHF signaling in porcine arteries.
Higher hospital volume and specialisation
Authors: S. Lyman
Journal: BMJ (2010)

Outcomes are better in hospitals that do more procedures

The association between surgical volume and patient outcomes for total joint replacement and other surgical procedures has been examined extensively.1 2 3 4 5 The reasons why surgeons who perform a higher volume of cases have better outcomes are intuitive. Surgeons who have more experience with a procedure tend to deliver better outcomes—after all, “practice makes perfect,” even beyond the learning curve.

What is less well understood is why a hospital procedural volume-outcome association persists even after adjusting for surgeon volume. Patients operated on by lower volume surgeons in high volume hospitals still have better outcomes than those operated on by similar volume surgeons in lower volume hospitals. This effect is thought to result from improved care processes in higher volume hospitals.

In the linked study (doi:10.1136/bmj.c165), Hagen and colleagues examine one possible explanation for this hospital volume-outcome association.6 They show that hospitals that specialise in orthopaedic surgery have better patient outcomes for total joint …
The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection
Authors: Lynda Anne Szczech, Samir K. Gupta, Ramez Habash, Antonio Guasch, Robert Kalayjian, Richard Appel, Timothy A. Fields, Laura P. Svetkey, Katherine H. Flanagan, Paul E. Klotman, Jonathan A. Winston
Journal: Kidney International (2004)
Heat Thwarts HIV
Authors: M. J. Friedrich
Journal: JAMA (2012)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
SC-25 * INVESTIGATING THE ROLE OF ASCL1 IN REGULATING DIFFERENTIATION OF GLIOBLASTOMA PRECURSOR CELLS
Authors: N. Park, R. Vaner, E. Ling, L. Lee, P. Dirks
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM), the most common and lethal adult primary brain tumour, exhibits cellular heterogeneity and a subpopulation of tumour cells exhibits the neural precursor phenotype and drives tumourigenesis. These findings suggest that tumours may represent aberrant organogenesis with growth caused by unlimited proliferation and failure of differentiation of malignant precursor cells. As GBM-neural stem (GNS) cells have precursor cell properties, promotion of differentiation represents a potential strategy for treatment. A key regulator of neuronal differentiation is ASCL1 during normal development and adult neurogenesis. Microarray analysis of ASCL1 expression in primary GNS cultures (n = 33) revealed two subgroups of GNS cultures as having either high or low expression. Evidence suggests that GNS cells with high expression of ASCL1 exhibit neuronal lineage commitment whereas GNS cells with low expression of ASCL1 do not undergo lineage commitment. This was confirmed using immunocytochemistry, quantitative real-time PCR and Western blot analysis. Furthermore, a dependent relationship was observed between ASCL1 subgroups and GNS subgroups responsive to inhibitors of Notch signaling. Treatment of the responder subgroup with a gamma-secretase inhibitor resulted in an increase in neuronal lineage markers and concomitant decrease in stem cell frequencies, as measured by immunocytochemistry and in vitro limiting dilution assays, respectively. Dominant-negative studies of ASCL1 suggest that ASCL1 is necessary for these effects in vitro and have been validated in vivo. This study aims to determine whether neuronal differentiation by blocking Notch signaling is mediated by ASCL1