tbuckley/cabot-search huggingface dataset:
Myocardial protection from ischemia/reperfusion injury by targeted deletion of matrix metalloproteinase-9
Authors: A. M. Romanic, S. M. Harrison, W. Bao, C. L. Burns-Kurtis, S. Pickering, J. Gu, E. Grau, J. Mao, G. M. Sathe, E. H. Ohlstein, T.-L. Yue
Journal: Cardiovascular Research (2002)

Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mouse.Standard homologous recombination in embryonic stem cells was used to generate a mouse lacking MMP-9. The left anterior descending coronary artery was occluded for 30 min followed by 24 h reperfusion, and the ischemic and infarct sizes were determined. Targeted deletion of MMP-9 protected the heart from no-flow ischemia-reperfusion-induced myocardial injury. The myocardial infarct size was reduced by 17.5% in MMP-9 heterozygotes (+/-) (P<0.01) and 35.4% in MMP-9 knockout (-/-) mice (P<0.01) versus the wild-type (+/+) mice, respectively. Analysis of MMP activity in myocardial extracts by zymography demonstrated that ischemia-reperfusion-induced expression of proMMP-9 and active MMP-9 was reduced by 77.8% (P<0.01) and 69.1% (P<0.001), respectively, in (+/-) mice compared to (+/+) mice, and was absent in (-/-) animals. The expression of TIMP-1, an endogenous inhibitor of MMP-9, was elevated 4.7-fold (P<0.05) and 21.4-fold (P<0.05) in the (+/-) and (-/-) mice, respectively, compared to (+/+) mice. Immunohistochemical analysis revealed that neutrophils were the primary cellular source of MMP-9, and less neutrophils were detected in the ischemic region of the heart following ischemia-reperfusion in (-/-) mice compared to (+/+) mice. Measurement of myeloperoxidase activity, a marker enzyme of neutrophils, demonstrated a 44% reduction in neutrophils infiltrated into the ischemic myocardium in the (-/-) mice compared to the (+/+) mice (P<0.05).These results suggest that MMP-9 plays an important role in ischemia-reperfusion-induced myocardial infarction and MMP-9 could be a target for prevention or treatment of acute ischemic myocardial injury.
MRI Visible Drug Eluting Magnetic Microspheres for Transcatheter Intra-Arterial Delivery to Liver Tumors
Authors: Dong-Hyun Kim, Jeane Chen, Reed A. Omary, Andrew C. Larson
Journal: Theranostics (2015)

Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy.These alginate microspheres were synthesized using a highly efficient microfluidic gelation process.The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile.The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies.A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion.This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.
Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy
Authors: B.Y.S. Chuah, T. Putti, M. Salto-Tellez, A. Charlton, P. Iau, S.A. Buhari, C.I. Wong, S.H. Tan, A.L.A. Wong, C.W. Chan, B.C. Goh, S.-C. Lee
Journal: Annals of Oncology (2011)
Birt-Hogg-Dubé syndrome: diagnosis and management
Authors: Fred H Menko, Maurice AM van Steensel, Sophie Giraud, Lennart Friis-Hansen, Stéphane Richard, Silvana Ungari, Magnus Nordenskjöld, Thomas vO Hansen, John Solly, Eamonn R Maher
Journal: The Lancet Oncology (2009)
Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries☆
Authors: H NYSTROM, P LINDBLOM, A WICKMAN, I ANDERSSON, J NORLIN, J FALDT, P LINDAHL, O SKOTT, M BJARNEGARD, S FITZGERALD
Journal: Cardiovascular Research (2006)

Objective: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function.
Liver toxicity: the Achilles' heel of endothelin receptor antagonist therapy?
Authors: M. M. Hoeper
Journal: European Respiratory Journal (2009)

The medical community has been alerted by case reports of serious liver injury associated with sitaxentan, an endothelin receptor antagonist (ERA) used for the treatment of pulmonary arterial hypertension (PAH). The first of these case reports was published in the June issue of the European Respiratory Journal and described a patient with PAH who was initially treated with bosentan, another ERA 1. This treatment was stopped after 6 months because of an increase in liver aminotransferases. The liver enzymes quickly returned to normal upon withdrawal of bosentan and, a few months later, sitaxentan therapy was started. Four months after this, liver aminotransferases started to increase again and the drug was discontinued, but the liver enzymes continued to rise to almost 1,000 U·L−1 and the patient developed mild hyperbilirubinemia. Under the assumption of a drug-related idiosyncratic reaction, corticosteroid therapy was initiated resulting in prompt and sustained normalisation of liver enzymes.

In the present issue of the European Respiratory Journal , Lavelle et al . 2 from Dublin, Ireland report on two perturbing cases of severe liver toxicity that developed 3 and 4 months, respectively, after sitaxentan therapy had been initiated. These patients showed severe liver dysfunction, with markedly elevated bilirubin levels >300 μmol·L−1 and elevated prothrombin times. In both patients, liver biopsies showed extensive hepatocellular damage and infiltrates of eosinophils and lymphocytes. As in the first case, liver function deteriorated for several weeks after discontinuation of sitaxentan. Corticosteroid therapy was not attempted. One of these patients recovered slowly, the …
Cerivastatin Activates Endothelial Calcium–Activated Potassium Channels and Thereby Modulates Endothelial Nitric Oxide Production and Cell Proliferation
Authors: Christoph Rüdiger Wolfram Kuhlmann, Christine Gast, Fang Li, Matthias Schäfer, Harald Tillmanns, Bernd Waldecker, Johannes Wiecha
Journal: Journal of the American Society of Nephrology (2004)

Statins are known to counteract the process of arteriosclerosis by exerting direct pleiotropic effects on vascular endothelium. The aim of this study was to investigate a possible effect of cerivastatin on endothelial Ca(2+)-activated K+ channels (BK(Ca)) and to assess their contribution to cerivastatin-mediated changes of endothelial nitric oxide (NO) production and proliferation. Membrane potential was measured using bis-1,3-dibutylbarbituric acid-trimethine oxonol-fluorescence imaging. Patch-clamp recordings of BK(Ca) were performed on cultured human umbilical vein endothelial cells. NO production was measured using 4,5-diaminofluorescein-fluorescence imaging and a [(3)H]cGMP RIA. Proliferation was analyzed by means of cell counts and [(3)H]thymidine incorporation (TI). Cerivastatin (0.001 to 0.05 micromol/L) caused a significant membrane hyperpolarization (n = 30; P < 0.05). This effect was abolished using the BK(Ca) inhibitor iberiotoxin (IBX; 100 nmol/L). The addition of mevalonate (500 micromol/L) blocked the BK(Ca) activation induced by cerivastatin (n = 19; P < 0.05). Endothelial cGMP level was increased by acetylcholine (ACh; 1 micromol/L). The combination of ACh and cerivastatin additionally increased cGMP levels, with a maximum at 0.03 micromol/L cerivastatin (84%; n = 10, P < 0.01). ACh-induced increase of cGMP-level was significantly reduced by IBX (n = 10, P < 0.01) as it was with all combined administrations of ACh and cerivastatin. 4,5-Diaminofluorescein-fluorescence measurements revealed a significant increase of NO levels by cerivastatin, which was abolished by IBX (n = 30; P < 0.05). Cell counts and TI demonstrated significant inhibition of human umbilical vein endothelial cell proliferation with a maximum at 0.03 micro mol/L (cell count, -32.2%; TI, -70%; n = 12; P < 0.01). These data show that cerivastatin activates endothelial BK(Ca), which plays an important role in the signaling of cerivastatin-mediated endothelial NO production and proliferation.
Elimination of Endemic Measles, Rubella, and Congenital Rubella Syndrome From the Western Hemisphere
Authors: Mark J. Papania, Gregory S. Wallace, Paul A. Rota, Joseph P. Icenogle, Amy Parker Fiebelkorn, Gregory L. Armstrong, Susan E. Reef, Susan B. Redd, Emily S. Abernathy, Albert E. Barskey, Lijuan Hao, Huong Q. McLean, Jennifer S. Rota, William J. Bellini, Jane F. Seward
Journal: JAMA Pediatrics (2013)

To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained.To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011.Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys.Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels.Since 2001, US reported measles incidence has remained below 1 case per 1,000,000 population. Since 2004, rubella incidence has been below 1 case per 10,000,000 population, and CRS incidence has been below 1 case per 5,000,000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella.The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.
Transparency rules lead to large fall in positive trial results, analysis finds:
Authors: Susan Mayor
Journal: BMJ (2015)

Fewer large clinical trials are reporting positive findings since the introduction of measures designed to improve transparency, shows a study that analysed results from trials funded by the US National Heart, Lung, and Blood Institute (NHLBI).

The study, published in PLoS One ,1 analysed 55 large randomised controlled trials carried out from 1970 to 2012 evaluating drugs or dietary supplements for treating or preventing cardiovascular disease. Trials were included if they had direct costs of over $500 000 (£322 000; €458 000) a year and were carried out in human adults with a primary outcome …
Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme
Authors: Kristina L. Bondurant, Mark D. Crew, Alessandro D. Santin, Timothy J. O'Brien, Martin J. Cannon
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The serine protease stratum corneum chymotryptic enzyme (SCCE) is overexpressed by ovarian tumor cells, but is not expressed by normal tissues, suggesting that SCCE may be an attractive target for immunotherapy. In this study, we tested the hypothesis that dendritic cells loaded with SCCE peptides will induce ovarian tumor antigen–specific CD8+ CTL responses and antigen-specific CD4+ helper T cell responses. Experimental Design: Computer algorithms were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR-binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide-loaded dendritic cells were tested against targets expressing endogenous SCCE, including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL epitope and multiple candidate CD4+ T helper cell epitopes. Results: CD8+ CTL specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE-expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE-expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139 induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110-139-loaded dendritic cells processed and presented the 123-131 epitope, the dominant CD8+ CTL response was directed against alternative epitopes within SCCE 110-139. Conclusions: The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.
Calmodulin Is Essential for Cardiac <i>I</i> <sub>KS</sub> Channel Gating and Assembly
Authors: Liora Shamgar, Lijuan Ma, Nicole Schmitt, Yoni Haitin, Asher Peretz, Reuven Wiener, Joel Hirsch, Olaf Pongs, Bernard Attali
Journal: Circulation Research (2006)

The slow I KS K + channel plays a major role in repolarizing the cardiac action potential and consists of the assembly of KCNQ1 and KCNE1 subunits. Mutations in either KCNQ1 or KCNE1 genes produce the long-QT syndrome, a life-threatening ventricular arrhythmia. Here, we show that long-QT mutations located in the KCNQ1 C terminus impair calmodulin (CaM) binding, which affects both channel gating and assembly. The mutations produce a voltage-dependent macroscopic inactivation and dramatically alter channel assembly. KCNE1 forms a ternary complex with wild-type KCNQ1 and Ca 2+ -CaM that prevents inactivation, facilitates channel assembly, and mediates a Ca 2+ -sensitive increase of I KS- current, with a considerable Ca 2+ -dependent left-shift of the voltage-dependence of activation. Coexpression of KCNQ1 or I KS channels with a Ca 2+ -insensitive CaM mutant markedly suppresses the currents and produces a right shift in the voltage-dependence of channel activation. KCNE1 association to KCNQ1 long-QT mutants significantly improves mutant channel expression and prevents macroscopic inactivation. However, the marked right shift in channel activation and the subsequent decrease in current amplitude cannot restore normal levels of I KS channel activity. Our data indicate that in healthy individuals, CaM binding to KCNQ1 is essential for correct channel folding and assembly and for conferring Ca 2+ -sensitive I KS -current stimulation, which increases the cardiac repolarization reserve and hence prevents the risk of ventricular arrhythmias.
The innate immune response in reperfused myocardium
Authors: L. Timmers, G. Pasterkamp, V. C. de Hoog, F. Arslan, Y. Appelman, D. P. V. de Kleijn
Journal: Cardiovascular Research (2012)

One of the major therapeutic challenges in the arena of interventional cardiology is to design strategies aimed at reducing myocardial tissue damage after myocardial infarction. In response to tissue injury, an innate immune response is initiated that orchestrates homeostatic responses and is a prerequisite for subsequent wound healing. An exaggerated inflammatory reaction, however, countervenes these beneficial effects and contributes to maladaptive tissue damage. Herein, we discuss the pathways involving the innate immune system that have been investigated in the setting of myocardial ischaemia and reperfusion injury. Endogenous 'danger' signals [danger-associated molecular patterns (DAMPs)] are expressed following tissue injury and alert the innate immune system. Toll-like receptors and the complement system are activated, resulting in an inflammatory reaction involving inflammatory cell influx and the production and release of inflammatory cytokines. A potential involvement of cell-derived microparticles in the modulation of the innate immune response following myocardial injury will also be discussed. Our future challenge lies within the counteraction of maladaptive inflammatory cascades, without interfering in the benign wound healing response, and in translating these anti-inflammatory strategies into clinical practice.
Pharmacologic agents targeting autophagy
Authors: Helin Vakifahmetoglu-Norberg, Hong-guang Xia, Junying Yuan
Journal: Journal of Clinical Investigation (2015)

Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies.
DNMT3L Is a Novel Marker and Is Essential for the Growth of Human Embryonal Carcinoma
Authors: Kahori Minami, Tokuhiro Chano, Takahiro Kawakami, Hiroshi Ushida, Ryoji Kushima, Hidetoshi Okabe, Yusaku Okada, Keisei Okamoto
Journal: Clinical Cancer Research (2010)

Testicular germ cell tumors (TGCT) have a unique epigenetic profile distinct from that of other types of cancer. Elucidation of these properties has a potential to identify novel markers for TGCTs.We conducted comprehensive analysis of DNA methyltransferase (DNMT) gene expression in TGCTs. Based on the expression profiles of DNMT genes in TGCTs, we generated a rabbit polyclonal anti-human DNMT3L antibody. We then studied the role of DNMT3L in TGCTs by the treatment of two embryonal carcinoma (EC) cell lines with a small interfering RNA system. Finally, we evaluated the immunohistochemical detection of DNMT3L in TGCT tissues. We also compared the patterns of DNMT3L immunohistochemistry with those of CD30 and SOX2.Among the DNMT genes, we found that mRNA for DNMT3L was specifically expressed in TGCTs, but neither in normal testicular tissues nor in cancer cells of somatic tissue origin. DNMT3L protein was strongly expressed in two EC cell lines, but not in the cell lines of somatic tissue origin. Transfection of small interfering RNA for DNMT3L significantly reduced DNMT3L expression and resulted in growth suppression and apoptosis in EC cells. Immunohistochemical analysis showed that DNMT3L protein was present only in EC cells, but not in the other types of TGCT components and cancer cells of somatic tissue origin. DNMT3L staining was more prominent and specific than CD30 or SOX2 staining for detecting EC cells.DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma.
Asymptomatic, isolated elevations of serum aminotransferase activity: The disorders and their diagnosis
Authors: I. M. Murray-Lyon
Journal: Hepatology (1987)

The accidental finding of raised levels of serum aminotransferase levels may lead to extensive investigations of the liver in apparently healthy people. To identify diagnostic groups and their need for investigations, we have evaluated the results of all investigative procedures carried out in 149 asymptomatic patients with persistently raised serum levels of aminotransferases. Fatty liver was found in 64%. These patients often had a high body weight. A high alcohol intake and diabetes mellitus were also noted. Chronic active or persistent hepatitis was found in 20% of the patients. Six per cent had cirrhosis, 4% had alpha 1 -antitrypsin deficiency, and 3.5% had hemochromatosis. Apart from ferritin, alpha 1 -antitrypsin, and markers for hepatitis B, blood tests were of little value for distinguishing among different diagnostic groups. This was the case also for the imaging procedures, and neither liver scintigraphy nor ultrasonography was a reliable source of diagnostic information. The results of our study indicate that diagnosis in this group of patients cannot be made without liver biopsy.
Relationship Between Posttraumatic Stress Disorder Characteristics of Holocaust Survivors and Their Adult Offspring
Authors: R Yehuda, J Schmeidler, E L Giller, L J Siever, K Binder-Brynes
Journal: American Journal of Psychiatry (1998)

There is controversy regarding the long-lasting effects of the Holocaust on the adult children of Holocaust survivors. In the present study the authors examined the relationship between posttraumatic stress disorder (PTSD) characteristics of Holocaust survivors and their adult children to determine whether differences in symptom severity or diagnostic status of parents would be associated with similar characteristics in their adult children.Holocaust survivors (N = 22) and their offspring (N = 22) were interviewed with several instruments to assess lifetime trauma history, effect of trauma on one's life, level of intrusive and avoidance symptoms in response to reminders of the Holocaust, current and lifetime PTSD, and current and lifetime axis I psychiatric disorder other than PTSD.There were significant relationships between parents and children regarding the effect of trauma on one's life and level of intrusive, but not avoidance, symptoms in response to reminders of the Holocaust. Offspring with traumatic events were more likely to develop PTSD if their parents had PTSD.Symptoms in offspring may be related to presence and severity of symptoms in the parent. Furthermore, PTSD in the parent may be a risk factor for PTSD in offspring.
Why Do We Need Another Antiemetic? Just Ask.
Authors: Mark G. Kris
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.968 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14559888 Why Do We Need Another Antiemetic? Just Ask. Mark G. KrisxMark G. KrisSearch for articles by this author Show More Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer and Weill Medical College of Cornell University, New York, NY https://doi.org/10.1200/JCO.2003.07.968 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria. Diabetes Care 2012;35:80–86
Authors: J Rosenbauer, A Dost, B Karges, A Hungele, A Stahl, C Bächle, EM Gerstl, C Kastendieck, SE Hofer, RW Holl
Journal: Diabetes Care (2012)

In the print version of the article listed above, there is an error in Fig. 1.The vertical whiskers in Fig. 1F representing 95% CIs were not correctly drawn.The corrected Fig.