tbuckley/cabot-search huggingface dataset:
Abstract 15892: mRNA Stability Hu Proteins Regulate Human Cardiac Sodium Channel Expression
Authors: Anyu Zhou, Ian Greener, An Xie, Guangbin Shi, Kai-Chien Yang, Hong Liu, Cody Rutledge, Samuel Dudley
Journal: Circulation (2014)

Human heart failure has been associated with reduced cardiac Nav1.5 Na+ channel current and SCN5A mRNA abundance. We hypothesized that reduced mRNA stability would contribute to the reduction of SCN5A mRNA. Hu proteins are known to contribute to mRNA stability The SCN5A mRNA 3’-untranslated region (UTR) contains two sets of putative Hu protein binding site. Over-expression of HuR and HuB in cardiomyocytes derived from primary human fetal ventricle increased wild-type SCN5A mRNA 46.3% (P=0.004) and 60.7% (P=0.008), respectively. Knocking down of HuR or HuB by siRNA decreased SCN5A mRNA by 27.5% (P=0.000) and 20.4% (P=0.02). RNA immunoprecipitation showed HuR associated with SCN5A mRNA. This suggested Hu family proteins might play an important role in upregulation of SCN5A expression by stabilizing SCN5A mRNA. In addition, we found HuR mRNA decreased 38.9% (P=0.034) in peripheral white blood cells of heart failure patients with implanted cardioverter-defibrillator (ICD) and evidence of appropriate event-driven therapy compared to control subjects. The decrease of HuR mRNA correlated with a reduction of wild-type SCN5A mRNA abundance in white blood cells from these patients. Our results demonstrate an additional layer of SCN5A posttranscriptional regulation in addition to alternative splicing that can contribute to sodium channel down-regulation in heart failure. Our results also suggest that circulating HU protein assessment may be useful in arrhythmic risk stratification and that exogenous HU protein overexpression may help reduce arrhythmic risk in heart failure.
End of the Hunt
Authors: M. Therese Southgate
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 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
Abstract 1962: Differential Response to Vascular Stenting in Control Vs Insulin-Treated Diabetic Pigs: Analysis of Carotid, Renal and Coronary Bare Metal Stents (BMS) and Coronary Sirolimus Eluting Stents (SES)
Authors: Michael Jonas, Elazer R Edelman, Aaron B Baker, Anna Spognardi, Adam Groothuis, Philip Seifert, Campbell Rogers
Journal: Circulation (2006)

Background: Diabetes (DM) is consistently associated with increased cardiovascular disease risk and worse outcomes from revascularization including endovascular BMS and SES. We studied the response of coronary and peripheral arteries to SES and BMS in a unique insulin treated DM pig model.  Methods and Results: controlled, chronic (9 wks) hyperglycemia was achieved in pigs after Streptozotocin induction and daily insulin injections. 30 coronary stents (18 BMS, 12 SES) and 22 peripheral stents (12 carotid, 10 renal, all BMS) were deployed in DM and control pigs. SES reduced neointimal proliferation in Controls, but not DM coronaries. DM pigs developed thicker neointima in response to carotid and renal stenting at 28-d (Figure A). Fibrin deposition and intimal neo-vascularization were increased while re-endothelialization blunted in DM. Stenting elicited increased vascular inflammation (CD-45 + tissue macrophages) across stented sites that correlated with neointimal response in DM but not controls (Figure B). DM pig vessels did exhibit altered signaling pathway activation with increased p-ERK (Thr202/Tyr204) and reduced p-Akt (Ser473) immunohistochemically stained cells; most prominently in stented peripheral arteries.  Conclusions: In-stent carotid and renal neointimal proliferation is increased in insulin treated DM while the response to local drug elution in coronary stents is blunted. Chronic controlled hyperglycemia results in mechanistically and quantitatively varied neointimal proliferation that is vascular bed-specific.
Diagnostic comparison between pleural fluid cytology (PFC), cellular block (CB) and pleural biopsy (PB) under visual guidance
Authors: Cristina Fernandez, Karen Czischke, Gerardo Mordojovic, Gabriel Cavada, Maite Oyonarte, Roberto Gonzalez, Andrea Retamal
Journal: European Respiratory Journal (2011)

PFC is the less invasive method for diagnosing pleural neoplasms and the reported sensitivity is 50%.   Methods:  All patients evaluated at our institution who had PFC and CB done between May 2009 to June 2010 and had PB indicated where included in the study. Diagnostic categories were specified for the analysis of PC and CB. The pathologist who read the PFC and CB was blind to the PB final diagnosis. The accuracy of the techniques was compared to PB.  Statistical analysis: Kappa (k) index was used to evaluate the concordance between the different techniques versus the PB and the concordance between PFC and CB. The sensitivity and specificity for malignancy was established for every technique.   Results:  92 patients were included in the study. The PB was positive in 71 (77%) cases. The PFC was positive in 42 (45.6%) and the CB was positive in 35 (38%) of the cases. PB/PFC agreement was 68.5%; k=0.4. PB/CB agreement was 61.5%; k=0.32. PFC/CB agreement was 84.6%; k=0.68. Eleven out of 12 effusions with PFC suspicious of malignancy turned out to be malignant when compared to PB and all the suspicious CB where malignant in the PB. For PFC sensitivity was 64.3%, specificity was 100%, with a positive predicted value (PPV) of 100% and a negative predicted value of (NPV) 45%. For CB sensitivity was 59.2%, specificity was 100% with a PPV of 100% and a NPV of 42%.   Conclusion:  There is good agreement between PFC and CB for the diagnosis of malignancy. CB trends to agree more than PFC with PB in the diagnosis of pleural mesothelioma. The sensitivity and specificity of PFC in the diagnosis of malignancy is similar to what is reported in the literature.
Science commentary: Insulin-like growth factor and cognitive function
Authors: A. Berger
Journal: BMJ (2001)

Insulin-like growth factors (IGFs) are peptides that regulate the growth, metabolism, survival, and differentiation of cells and are regulated by growth hormone. Both IGF-I and IGF-II consist of small peptides that share about 50% homology with proinsulin and are produced chiefly by the liver. IGF-I is an important cell growth regulator, but the role of IGF-II is less clear. IGF-II acts mainly via IGF-I receptors; IGF-II receptors do exist, but their role is believed simply to …
Lesson of the week: Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate
Authors: A J Drake, R J Howells, J P H Shield, A Prendiville, P S Ward, E C Crowne
Journal: BMJ (2002)

Inhaled corticosteroids are central to the successful long term management of asthma and are generally regarded as safe.1 Systemic adverse effects have been described in children but are thought to be rare.2 High dose inhaled corticosteroids are used in the step-up phase of treatment to optimise the control of asthma. Fluticasone propionate may be prescribed at higher doses to relieve respiratory symptoms in the belief that it generates fewer side effects than other inhaled steroids. Some studies have shown that fluticasone is safer than beclomethasone or budesonide, with limited oral absorption and extensive hepatic first pass metabolism leading to a lower systemic bioavailability.3 Others have shown that appreciable amounts of inhaled fluticasone are absorbed from the lung4; fluticasone has also been associated with growth retardation and adrenal suppression in children.5 Reports of adrenal insufficiency in childhood secondary to inhaled steroids have not described hypoglycaemia as a presenting feature.5–7 We report on four children with asthma presenting with acute hypoglycaemia secondary to adrenal suppression caused by inhaled fluticasone propionate.
Immunoediting of tumors results in broad phenotypic changes including loss of immune recognition, altered response to therapy, and reduced differentiation
Authors: Keith L. Knutson, Hailing Lu, Brad Stone, Arianna Smorlesi, Ekram Gad, Mary L. Disis
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5313 

In recent years it has become clearer that the targeting of a single tumor antigen can lead to the generation of antigen-loss variants through immunoselection. It may be important to understand the resulting phenotype of the tumor since subsequent therapy would likely be impacted. In this study we investigated the phenotype of antigen-loss variants tumors that were generated by an immune response targeting a single antigen. A mouse mammary carcinoma line (MMC) was developed from a spontaneous tumor derived from the FVB-based neu-transgenic mouse. This cell line, when injected as a cell suspension into non-tumor bearing neu-transgenic animals forms tumors that grow stoichiometrically and predictably. The tumors are similar to human HER-2/neu-overexpressing tumors in that they are estrogen-receptor negative, doxorubicin-resistant, and resistant to low dose tamoxifen. The tumors that develop following injection retain HER-2/neu, MHC class I and class II, also similar to human breast cancer. When injected into FVB parental mice, which do not carry the transgene, tumors are rejected due to the development of a strong immune response against the foreign antigen, rat neu. However, after a long latency tumors can develop in the FVB parental strains. A cell line (ANV) was generated from a tumor derived from the FVB parental that was injected with MMC. It was observed that the tumor cells were rat neu-negative variants, indicating immunoselection in vivo . Tumors induced, in vivo , using ANV grew equally well in both the neu-transgenic and FVB mice. Unlike MMC, the ANV cells had increased tamoxifen sensitivity and did not respond to anti-neu monoclonal trastuzumab-like antibody treatment. Microscopic inspection of the cell lines revealed a change from an epithelial-like (MMC) to a spindle-like (ANV) morphology. RNA microarray analysis showed that the ANV were less differentiated and had either reduced or lost expression of many mammary gland epithelium-associated gene products such as TGF-beta, IGFBP-5, lactoferrin, and parathyroid hormone-like peptide. These results suggest that, in addition to loss of the antigen that was targeted in the immune response, tumors that arise as a result of immune escape can have a significantly altered phenotype and ultimately a different response to subsequent therapy.
Abstract 13014: Porphyromonas Gingivalis, a Potent Periodontal Pathogen, Induces Cardiac Rupture After Myocardial Infarction in Mice
Authors: Yuka Shiheido, Yasuhiro Maejima, Jun-ichi Suzuki, Norio Aoyama, Naho Kobayashi, Makoto Kaneko, Yuichi Izumi, Mitsuaki Isobe
Journal: Circulation (2014)

Introduction: Accumulating lines of evidence suggest that there is a strong association between periodontal disease and coronary artery diseases. However, the effects of periodontal disease on the pathophysiology of myocardial infarction (MI) remain unknown.

Hypothesis: Periodontal pathogens mediate detrimental effects on the infarcted myocardium.

Methods: C57BL/6J male mice were split into 3 groups. Before and after coronary artery ligation, each group was injected with one of the following bacteria or substance: Porphyromonas gingivalis (P.g.), Aggregatibacter actinomycetemcomitans (A.a.: a periodontal pathogen), or phosphate buffered saline (PBS). In vitro experiments were also conducted using cultured cardiomyocytes (CMs).

Results: Observation of the mice lasted for 14 days after MI. A significant increase of mortality, due to cardiac rupture, was observed on days 4 and 5 after MI in the P.g.-injected mice compared to the A.a.-injected or PBS-injected mice (P.g. [n=19] vs PBS [n=12] 42.1 vs 0%, p < 0.05, A.a. [n=7] vs PBS [n=12] 14.2 vs 0%). The release of H2O2 from the infarcted myocardium significantly increased in the P.g. group compared to the PBS group (P.g. [n=6] vs PBS [n=6]: 31.0 ± 9.1 vs 6.3 ± 3.4 pmol, p < 0.05). In the infarcted myocardium, the protein level of matrix metalloproteinase-9 (MMP-9), a protease which interrupts the healing process of damaged tissues, was significantly accumulated in the P.g. group (3.5 ± 0.9 fold, n=7) compared to the PBS group (n=7). Zymography revealed that MMP-9 activity was significantly higher in the P.g. group (2.9 ± 0.6 fold, n=7) than in the PBS group (n=7). These results suggest that infection with P.g. promotes production of H2O2, an enhancer of the MMP-9 activity, thereby aggravating the stability of the infarcted myocardium. In addition, the level of p18 Bax, an active form of Bax that strongly promotes apoptosis, significantly increased in the P.g. group (1.7 ± 0.1 fold, n=5) compared to the PBS group (n=5). Treatment with gingipain, a cysteine protease uniquely secreted from P.g., on cultured CMs promoted the accumulation of p18 Bax and CMs death.

Conclusions: Infection with P.g. during MI plays a detrimental role in the healing process of the myocardium, which in turn contributes to cardiac rupture.
Abstract 15922: Role of Polo-Like Kinase-1 in Intimal Hyperplasia in Saphenous Vein Graft: Potential Implication in Vein-Graft Disease
Authors: Swastika Sur, Songcang Chen, Jeffrey T Sugimoto, Devendra K Agrawal
Journal: Circulation (2014)

Coronary revascularization by coronary artery bypass grafting (CABG) is the choice of procedure in patients with multi-vessel or left main coronary artery disease. Concerns have been raised on the long term result of CABG using saphenous vein graft (SVG) as its patency significantly declines following surgery, compared to internal mammary artery (IMA), which is almost immune to restenosis. Proliferation of smooth muscle cells (SMCs) is the key event in the pathogenesis of intimal hyperplasia leading to SVG failure. PDGF-BB is a major growth factor released at the site of pulsatile stretch- and shear stress-induced graft injury. Here, we examined, for the first time, the expression of PLK1 and its phosphorylation/activation in isolated human bypass graft conduits. Human SV and IMA vessels were freshly collected, SMCs isolated and cultured up to 5th passage. In cultured SMCs, effect of PDGF-BB was examined on total and phosphorylated PLK1 (pPLK1) by Western blot analysis. Cell proliferation was measured using thymidine incorporation, MTT method and cell count. We found significantly higher expression of pPLK1 and total PLK1 in PDGF-stimulated SV SMCs than IMA. SV SMCs had 5-fold increase in the density of pPLK1 and had 2-fold increase in the density of total PLK1. While in the IMA SMCs, increase in pPLK1 was significantly lower than in SV SMCs. Also, this increase was not sustained. These data suggest a greater and sustained sensitivity of SV SMCs to PDGF-BB induced PLK1 activity than that of IMA. A PLK1 blocker inhibited PDGF-induced proliferation in both IMA and SV SMCs. These data demonstrate differential activity of PDGF-induced PLK1 activation, which was greater in SV SMCs than in IMA. This could explain the development of intimal hyperplasia in SV conduits than the IMA following CABG. Thus, inhibition of PLK1 could be a target in developing better therapeutic approach to prevent vein-graft disease.
Abstract 5553: Monotherapy efficacy of catalytic and allosteric inhibitors of AKT in breast cancer models with AKT1E17K mutations
Authors: Barry R. Davies, Nin Guan, Armelle Logie, Amy Palmer, Vivien Jacobs, Neil James, Emma L. Jenkins
Journal: Cancer Research (2014)

Abstract AKT1E17K mutations occur at low frequency in a variety of solid tumors, including those of the breast and urinary bladder. Although this mutation has been shown to transform rodent cells in culture, it was found to be less oncogenic than PIK3CA mutations in breast epithelial cells. Moreover, the therapeutic potential of AKT inhibitors in human tumors with an endogenous AKT1E17K mutation is not known. Expression of exogenous copies of AKT1E17K in MCF10A breast epithelial cells increased phosphorylation of AKT and its substrates, and induced colony formation in soft agar. These effects were inhibited by the allosteric and catalytic AKT inhibitors MK-2206 and AZD5363, respectively. We identified two breast cancer explant models with AKT1E17K mutation (HBC-x2 and HBCx-31). Dosing of AZD5363 at 150 mg/kg twice daily or MK-2206 at 120 mg/kg 3 times a week significantly inhibited tumor growth in both models, but AZD5363 was significantly more active than MK-2206 at the dosing schedules employed, in both models. Pharmacodynamics were assessed in the HBC-x2 model at 2 h after the final dose. Both compounds significantly inhibited phosphorylation of PRAS40 and S6, caused relocalisation of FOXO3a to the nucleus, and reduced Ki67 staining. The data indicate that breast cancers with AKT1E17K mutations are rational targets for monotherapy treatment with AKT inhibitors. Citation Format: Barry R. Davies, Nin Guan, Armelle Logie, Amy Palmer, Vivien Jacobs, Neil James, Emma L. Jenkins. Monotherapy efficacy of catalytic and allosteric inhibitors of AKT in breast cancer models with AKT1E17K mutations. [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 5553. doi:10.1158/1538-7445.AM2014-5553
PENICILLIN THERAPY AT THE UNIVERSITY OF MINNESOTA HOSPITALS: 1942-1944
Authors: Wesley W. Spink, Wendell H. Hall
Journal: Annals of Internal Medicine (1945)

Article1 April 1945PENICILLIN THERAPY AT THE UNIVERSITY OF MINNESOTA HOSPITALS: 1942-1944WESLEY W. SPINK, M.D., F.A.C.P., WENDELL H. HALL, M.D.WESLEY W. SPINK, M.D., F.A.C.P.Search for more papers by this author, WENDELL H. HALL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-4-510 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOn July 9, 1942, J. E., a seven year old girl, entered the University Hospitals. Two days later, she received penicillin because of a severe staphylococcic bacteremia, with 68 colonies of coagulase-positive staphylococci per cubic centimeter of blood. Pneumonia and an acute osteomyelitis of the left femur were also present. Her general condition improved rapidly. This patient was the first to receive penicillin at the University Hospitals. Since that time, over a period of two years, a total of 200 patients have received penicillin under our supervision. The purpose of this report is not to review the voluminous literature on... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minnesota*Prepared for presentation at the Regional Meeting of the American College of Physicians in Chicago, November 4, 1944.From the Division of Internal Medicine, University of Minnesota Hospitals, Minneapolis.This and other investigations with penicillin have been supported by grants from the Medical Research Fund of the Graduate School, the Charles P. DeLaittre Fund of the Minnesota Medical Foundation and the Committee on Scientific Research of the American Medical Association.The penicillin was provided by the Office of Scientific Research and Development from supplies assigned by the Committee on Medical Research for investigations recommended by the Committee on Chemotherapeutic and other Agents of the National Research Council. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byStaphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and ManagementBacteremia, Sepsis, and Infective Endocarditis Associated with Staphylococcus aureusStaphylococcal Infections: A Historical PerspectiveAlexander fleming: The spectrum of penicillinA NEW EPIDEMIC PHAGE TYPE OF STAPHYLOCOCCUS AUREUSStaphylococcal infectionsTHE CURRENT PROBLEM OF STAPHYLOCOCCAL INFECTIONS*DAVID E. ROGERS, M.D.THE CLINICAL PROBLEM OF ANTIMICROBIAL RESISTANT STAPHYLOCOCCIPEMPHIGUS ACUTUS TREATED WITH ANTIBIOTICSPenicillin in secondary infections of advanced cervical malignancies 1 April 1945Volume 22, Issue 4Page: 510-525KeywordsBacteremiaBloodChemotherapeutic agentsFemurGraduate medical educationHospital medicineOsteomyelitisPenicillinPneumoniaResearch funding ePublished: 1 December 2008 Issue Published: 1 April 1945 PDF downloadLoading ...
Unrecognized Hyperthyroidism Masked as Heart Disease
Authors: SAMUEL A.  LEVINE
Journal: Annals of Internal Medicine (1930)

Article1 July 1930Unrecognized Hyperthyroidism Masked as Heart DiseaseSAMUEL A. LEVINE, M.D.SAMUEL A. LEVINE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-1-67 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe subject of this discussion concerns itself with a group of patients who suffered from one or another form of heart disease not unlike those customarily seen in any general practice but in whom a previously unrecognized element of hyperthyroidism proved to be a most important factor. The great importance of this undetected burden to the circulation will become clear when the therapeutic results obtained are taken up. At the outset it must be understood that the cases which form the subject of this problem are not the "ordinary" cases of exophthalmic goitre or toxic adenoma. They are not the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass.*Read before the American College of Physicians, February 10, 1930, Minneapolis, Minn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byANGINA PECTORIS AND THYROTOXICOSISANGINA IN WOMENDas Elektrokardiogramm bei Überfunktionszuständen der SchilddrüseChronic hyperthyroidismComplete thyroidectomy in advanced heart diseaseStudies in thyroid heart diseaseThyrotoxic circulatory symptoms with low metabolic rate 1 July 1930Volume 4, Issue 1Page: 67-80KeywordsAdenomasCardiovascular therapyHyperthyroidismPrimary care ePublished: 1 December 2008 Issue Published: 1 July 1930 PDF downloadLoading ...
Abstract 10443: Statins Reduce New-Onset Atrial Fibrillation in Patients with First Time Myocardial Infarction and Show Dose and Type Dependent Effect - A National Cohort Study.
Authors: Casper N Bang, Gunnar H Gislason, Anders M Greve, Lars Kober, Christian Torp-Pedersen, Kristian Wachtell
Journal: Circulation (2011)

Objective: Statins have been reported as an upstream therapy to prevent atrial fibrillation (AF) due to pleiotropic effects, but previous studies have reported conflicting results in primarily smal...