tbuckley/cabot-search huggingface dataset:
Abstract 3395: Role of ErbB3 signaling in tumor cell motility and metastasis
Authors: Tatiana Smirnova, Jeffrey Wyckoff, Jeffrey E. Segall
Journal: Cancer Research (2010)

Abstract The major cause of death for most cancers, including that of the breast, is from metastasis. One of the trends in anticancer therapy research has recently been inhibiting the epidermal growth factor receptor (EGFR, ErbB) family that is part of the subclass I of the receptor tyrosine kinase superfamily. ErbB receptors are involved in activating such key pathways as PI3-kinase and Ras/MAP kinase. Close to 30% of highly invasive human breast cancers show elevated expression/activity of the ErbB2 receptor, a marker for poor prognosis and decreased disease-free survival. The preferred heterodimerization partner of ErbB2 is ErbB3. Previous data from our laboratory has shown that increasing expression of ErbB3 caused a significant increase in intravasation and metastasis without affecting primary tumor growth/formation. The ligand for ErbB3 is Heregulin Beta 1 (HRGβ1) and its binding leads to heterodimerization with other ErbB's, followed by activation of signaling pathways that result in cell chemotaxis and movement. Knowing that ErbB3 is important for metastasis, our goal is to determine which signaling pathway downstream of ErbB3 is responsible for metastasis as well as what cellular property (e.g. motility or chemotaxis) and which step of metastasis is affected (invasion, intravasation, lung seeding). Stably transduced MTLn3 cells (rat mammary adenocarcinoma cell line) overexpressing WT and mutant versions of ErbB3 defective in PI3K, MAPK and Grb7 signaling were used for in vitro and in vivo experiments examining the role of ErbB3 signaling pathways. WT and mutant versions of ErbB3 were compared in their ability to chemotax in vitro. Orthotopic injection of the WT and mutant MTLn3 cell lines into the mammary fatpads of SCID mice has allowed us to examine their in vivo invasion potential by measuring the ability of cells to migrate out of the primary tumor towards a gradient of HRGβ1, intravasation - number of cells able to enter blood stream, and live imaging using multiphoton microscopy which will allow to see tumor cell polarization and movement towards blood vessels. In addition, tail vein injection tested the ability of cells to seed the lungs. While previous data from our laboratory has shown that ErbB3 overexpression significantly enhances metastasis, it is still not known how. Preliminary results from these experiments suggest a key role for tyrosine residues on the ErbB3 receptor that couple to the PI3-kinase pathway in tumor cell motility and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3395.
Site-specific Gene Insertion Mediated by a Cre-loxP-carrying Lentiviral Vector
Authors: Gilles Michel, Yin Yu, Tammy Chang, Jiing-Kuan Yee
Journal: Molecular Therapy (2010)

Retroviral vectors have been used to treat patients with the X-linked severe combined immunodeficiency disease and chronic granulomatous disease. In both cases, success has been undermined by clonal expansion of transduced cells in some patients due to insertional mutagenesis induced by random vector integration. This outcome underscores the importance of designing vectors for site-specific gene insertion to avoid unanticipated gene disruption or gene activation. In the present study, we incorporated the sequence-specific Cre protein into lentiviral virions. We demonstrated that the virion-associated Cre protein remained enzymatically active and was capable of directing site-specific insertion of a gene in the vector into a defined loxP site in the host genome. As there are loxP-like sequences throughout human genome that can be recognized by either wild-type Cre or Cre variants, our study demonstrates a new strategy of designing lentiviral-based vector for gene targeting.
4-Nitroquinoline-1-Oxide Induces the Formation of Cellular Topoisomerase I-DNA Cleavage Complexes
Authors: Ze-Hong Miao, V. Ashutosh Rao, Keli Agama, Smitha Antony, Kurt W. Kohn, Yves Pommier
Journal: Cancer Research (2006)

Abstract RecQ helicase BLM-deficient cells are characteristically hypersensitive to 4-nitroquinoline-1-oxide (4NQO). We recently reported that isogenic BLM-deficient cells (PNSG13) are more sensitive than BLM-complemented cells (PNSF5) to camptothecin, which specifically traps topoisomerase I cleavage complexes (Top1cc). We now report that PNSG13 are also 3.5-fold more sensitive to 4NQO compared with PNSF5 and that 4NQO induces higher levels of Top1cc and reduced histone γ-H2AX in PSNG13 than in PNSF5. Similarly, 4NQO induces more Top1cc in primary fibroblasts from a patient with Bloom syndrome than in normal human fibroblasts. 4NQO also induces Top1cc in colon cancer HCT116 and HT29 cells in a time- and concentration-dependent fashion. Of note, distinct from camptothecin, the Top1cc produced by 4NQO accumulate progressively after 4NQO addition and persist following 4NQO removal. The Top1cc induced by 4NQO are detectable by alkaline elution. To examine the functional relevance of the Top1cc induced by 4NQO, we used two stable topoisomerase I small interfering RNA (siRNA) cell lines derived from HCT116 and MCF7 cells. Both topoisomerase I siRNA cell lines are resistant to 4NQO, indicating that Top1cc contribute to the cellular activity of 4NQO. Collectively, these data show that 4NQO is an effective inducer of cellular Top1cc. Because 4NQO does not directly trap Top1cc in biochemical assays, we propose that active metabolites of 4NQO trap Top1cc by forming DNA adducts. Induction of Top1cc and histone γ-H2AX by 4NQO may contribute to the cellular effects of 4NQO, including its selective activity toward RecQ helicase BLM-deficient cells.(Cancer Res 2006; 66(13): 6540-5)
The Morality of Transplantation-Reply
Authors: Mark Siegler
Journal: JAMA (1991)

<h3>In Reply.</h3> —The circumstances of liver transplantation are unique for the following reasons, which we noted in our article: (1) there is a severe shortage of donor livers and some criteria regarding allocation must be used; (2) alcohol-related liver disease is the cause of end-stage liver disease in the majority of patients; and (3) in contrast to other causes of end-stage liver disease, alcoholism is treatable and alcohol-related end-stage liver disease is preventable. In this context, we suggest that it is fair to hold alcoholics responsible for refusing alcoholism treatment and to assign them a lower priority for liver transplantation. We do not propose, as Surman suggests, extending this policy to other circumstances in which health care resources are only relatively scarce. In our article, we also state that since the enterprise of organ transplantation depends on the public for organ donation and financial support, the public's values and views
Hemostatic predictors of cardiovascular disease: prospective evaluation of the framingham offspring study
Authors: Geoffrey H. Tofler, Joseph Massaro, James E. Muller, Daniel Levy, Murray A. Mittleman, Izabela Lipinska, DaLl Feng, Christopher O'Donnell, Peter W. Wilson, Ralph B. Dágostino
Journal: Journal of the American College of Cardiology (2002)
Regular Exercise Training Prevents Aortic Valve Disease in Low-Density Lipoprotein–Receptor–Deficient Mice
Authors: Yasuharu Matsumoto, Volker Adams, Saskia Jacob, Norman Mangner, Gerhard Schuler, Axel Linke
Journal: Circulation (2010)

Background— Regular exercise training (ET) slows the progression of atherosclerotic lesions, reduces oxidative stress, and increases nitric oxide bioavailability, all of which may be expected to improve degenerative aortic valve disease. Methods and Results— Four-week-old low-density lipoprotein–receptor–deficient mice (n=94) were randomly divided into 4 groups: Group 1 (control group), normal diet plus sedentary activity; group 2 (cholesterol group), cholesterol diet plus sedentary activity; group 3 (regular ET group), cholesterol diet plus regular ET (60 min/day, 5 days/week) for 16 weeks; and group 4 (occasional exercise group), cholesterol diet plus occasional ET (1 day/week) for 16 weeks. At 20 weeks of age, histological analysis was performed. A significant increase in aortic valve thickness was evident in the cholesterol group compared with the control group. Importantly, regular but not occasional ET significantly reduced aortic valve thickness compared with the cholesterol group (control 31.3±3.0 μm, cholesterol 50.1±3.4 μm, regular exercise 30.4±1.2 μm, and occasional exercise 48.9±3.2 μm). Immunohistochemistry revealed that a cholesterol diet disrupted and regular ET preserved endothelial integrity on the aortic valve surface. Furthermore, serum myeloperoxidase, accumulation of macrophages and oxidized low-density lipoprotein, in situ superoxide, activated myofibroblasts/osteoblast phenotypes, and mineralization were increased in the cholesterol group but were decreased by regular ET. Polymerase chain reaction revealed increased messenger RNA expression for α-smooth muscle actin, bone morphogenetic protein-2, runt-related transcription factor-2, and alkaline phosphatase in the cholesterol group, whereas these were diminished by regular ET. Moreover, regular ET significantly increased circulating levels of fetuin-A compared with the cholesterol group. Conclusions— In the low-density lipoprotein–receptor–deficient mouse, regular ET prevents aortic valve sclerosis by numerous mechanisms, including preservation of endothelial integrity, reduction in inflammation and oxidative stress, and inhibition of the osteogenic pathway.
Role of cytomegalovirus and asymmetric dimethylarginine in the derangement of nitric oxide synthase in cardiac allograft recipients
Authors: Bing Y. Wang, Bill Fearon, Ken Y. Lin, Shyam N. Panchal, Shao Z. Gao, Hannah A. Valantine, John P. Cooke
Journal: Journal of the American College of Cardiology (2003)
Bacterial Endocarditis and Mural Thrombi in the Heart
Authors: JACQUES B. WALLACH, MACELLIS GLASS, LESLIE LUKASH, ALFRED A. ANGRIST
Journal: Circulation (1954)

The infrequent occurrence of mural thrombi in the chambers of the heart is noted. The relevant literature is reviewed. The findings in eighty-two cases of bacterial endocarditis superimposed on rheumatic heart disease and in 47 examples of bacterial endocarditis without underlying rheumatic valvulitis are reported. These findings may reflect the infrequency of auricular fibrillation and of severe mitral stenosis in cases of bacterial endocarditis. The results further substantiate the origin of emboli from the valvular vegetations, bacterial or nonbacterial, rather than from the cardiac chambers, and this correlates with the bland character of most of the infarcts.
Epidemiology and Prevention of Adolescent Injury
Authors: Carol W. Runyan
Journal: JAMA (1989)

INJURY, only recently recognized as a public health problem, is a major source of morbidity and mortality among adolescents. Prevention has been hampered by inadequacies in record keeping, research, and conceptualization of the problem.<sup>1</sup>Published reviews have relied primarily on mortality data and given meager attention to intentional injury or methodological concerns.<sup>2-4</sup>This article reviews the epidemiology of injury for youths aged 10 through 19 years, discusses selected interventions, and suggests a research agenda. <h3>GENERAL EPIDEMIOLOGIC PATTERNS Mortality</h3> Injuries are the leading cause of death for persons between the ages of 1 and 44 years. They account for 40% of all years of potential life lost before age 65 years, far exceeding the figures for cancer and heart disease.<sup>1</sup>Among adolescents aged 10 through 14 and 15 through 19 years, injuries are responsible for 57% and 79% of all deaths, respectively, and the death rates have increased in
Abstract 5412: Antitumor properties of ouabain in lipid double emulsion in orthotopic canine osteosarcoma xenografted mouse model
Authors: Jun Wu, Meng-Yin Hsieh, Yan Wang, Eugene Roberts, Derek Vallejo, Abraham Lee, Richard Ermel
Journal: Cancer Research (2014)

Abstract Canine cancers develop in immunocompetent environments and share many similar features observed in human cancers, such as long periods of latency for initiation, progression and development, metastasis, acquired drug resistance and recurrence. Osteosarcoma is a primary bone tumor that occurs in dogs. It is highly aggressive and metastatic in nature, and the therapeutic methods utilized to treat this primary canine tumor are very limited. We have successfully established canine osteosarcoma orthotopic xenograft models with NSG mice (from Jackson Lab) in vivo. Ouabain, known as Na+, K+ ATPase inhibitor, has been used for many years in human clinical applications for the treatment of congestive heart failure. Recently, ouabain has been investigated for potential anticancer properties. However, the therapeutic dose window is very narrow because the side effects of ouabain overdose can be lethal. In an attempt to mitigate such narrow therapeutic margin of safety, ouabain was formulated in lipid double emulsion by using microfluidic synthesis method or membrane emulsification method. Our preliminary results showed enhanced antitumor activities of ouabain in double emulsion or nanoemulsion against canine osteosarcoma cell lines in vitro and in orthotopic xenograft models in vivo. The safety and delivery efficiency of ouabain in vivo was also improved, suggesting a therapeutic application of ouabain double emulsion could be benefit in canine osteosarcoma targeting therapy. Citation Format: Jun Wu, Meng-Yin Hsieh, Yan Wang, Eugene Roberts, Derek Vallejo, Abraham Lee, Richard Ermel. Antitumor properties of ouabain in lipid double emulsion in orthotopic canine osteosarcoma xenografted mouse model. [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 5412. doi:10.1158/1538-7445.AM2014-5412
Use and Prescription of Antibiotics in Primary Health Care Settings in China
Authors: Jin Wang, Pan Wang, Xinghe Wang, Yingdong Zheng, Yonghong Xiao
Journal: JAMA Internal Medicine (2014)

IMPORTANCE Appropriate antibiotic use is a key strategy to control antibacterial resistance.The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care.OBJECTIVE To identify current patterns of antibiotic use and explore the reasons for inappropriate prescription in primary health care settings in China. DESIGN, SETTING, AND PARTICIPANTSA total of 48 primary health care facilities in China were randomly selected from 6 provinces at various levels of economic development.Data for the years 2009 through 2011 from 39 qualifying facilities (23 city and 16 rural primary health care centers) were analyzed retrospectively.The study sample consisted of prescription records for 7311 outpatient visits and 2888 inpatient hospitalizations.MAIN OUTCOMES AND MEASURES General health center information, drug usage, disease diagnoses, and antibiotic use by outpatients and inpatients were surveyed.Cases of inappropriate antibiotic prescription were identified. RESULTSMost staff in the primary health care facilities had less than a college degree, and the medical staff consisted primarily of physician assistants, assistant pharmacists, nurses, and nursing assistants.The median (range) governmental contribution to each facility was 34.0% (3.6%-92.5%) of total revenue.The facilities prescribed a median (range) of 28 (8-111) types of antibiotics, including 34 (10-115) individual agents.Antibiotics were included in 52.9% of the outpatient visit prescription records: of these, only 39.4% were prescribed properly.Of the inpatients, 77.5% received antibiotic therapy: of these, only 24.6% were prescribed properly.Antibiotics were prescribed for 78.0% of colds and 93.5% of cases of acute bronchitis.Of the antibiotic prescriptions, 28.0% contained cephalosporins and 15.7% fluoroquinolones.A total of 55.0% of the antibiotic prescriptions were for antibiotic combination therapy with 2 or more agents.In nonsurgical inpatients in cities, the mean (SD) duration of antibiotic therapy was 10.1 (7.8) days.Of the surgical patients, 98.0% received antibiotics, with 63.8% of these prescriptions for prophylaxis.CONCLUSIONS AND RELEVANCE Antibiotics are frequently prescribed in Chinese primary health care facilities, and a large proportion of these prescriptions are inappropriate.Frequent and inappropriate use of antibiotics in primary health care settings in China is a serious problem that likely contributes to antimicrobial resistance worldwide.
Acute Pulmonary Edema of High Altitude
Authors: Charles S. Houston
Journal: New England Journal of Medicine (1960)

MOUNTAINEERS have from time to time reported cases of rapid death attributed to pneumonia, occurring most often in healthy, active persons engaged in strenuous activity at altitudes from 14,000 feet upward. Most of the reports, by nonmedical authors, have appeared in lay publications. The course of the disease has been too fulminating and has not responded to adequate antibiotics to be typical of pneumonia. Consequently, some physician climbers have suspected another cause such as acute pulmonary edema.In 1959 I had the unusual opportunity of seeing such a case within reach of hospital facilities, and this single case is presented . . .
Incidence of Estrogen Receptor in Benign Nevi and Human Malignant Melanoma
Authors: Prabir K. Chaudhuri, Michael J. Walker, Henry A. Briele, Craig W. Beattie, Tapas K. Das Gupta
Journal: JAMA (1980)

This study was performed as an initial step to evaluate the possible effects of steroid hormones on benign nevi. Cytoplasmic receptors for estrogen were found in nine (41%) of 21 benign nevi from melanoma patients. Ten (37%) of 27 melanoma tumor tissues also had receptor for estrogen. Benign nevi from 17 normal persons had no estrogen receptor activity. The similar incidence of estrogen receptor in benign nevi from melanoma patients and in melanoma tissue itself, compared with the absence of receptor in benign nevi from a normal population, suggest that steroid hormones such as estrogen may represent a molecular alteration associated with a potential pathophysiologic transformation of a benign nevus to its malignant counterpart.
Activation of peripheral blood mononuclear cells in bronchoalveolar lavage fluid from patients with sarcoidosis: visualisation of single cell activation products.
Authors: P Pantelidis, A M Southcott, A D Cambrey, G J Laurent, R M du Bois
Journal: Thorax (1994)

BACKGROUND--Interstitial lung diseases are characterised by the recruitment of mononuclear cells to disease sites where maturation occurs and activation products, including lysozyme (LZM), are released. Analysis of in vitro cell culture supernatants for activation products masks the functional heterogeneity of cell populations. It is therefore necessary to examine the secretion of activation products by single cells to assess whether the activation of newly recruited mononuclear phagocytes at the sites of disease in the lung is uniform and controlled by the local microenvironment. METHODS--The reverse haemolytic plaque assay was used to evaluate, at a single cell level, the ability of bronchoalveolar lavage (BAL) fluid from seven patients with sarcoidosis to activate Ficoll-Hypaque-separated peripheral blood mononuclear cells by comparison with BAL fluid from six normal volunteers and nine patients with systemic sclerosis. Monolayers of peripheral blood mononuclear cells and sheep red blood cells were cultured either alone or in the presence of 20% (v/v) BAL fluid with a polyclonal anti-LZM antibody. LZM/anti-LZM complexes bound to red blood cells surrounding the secreting cells were disclosed following complement lysis of red blood cells and quantification of plaque dimensions using microscopy and image analysis. RESULTS--Bronchoalveolar lavage fluid from all the patients with sarcoidosis increased LZM secretion by peripheral blood mononuclear cells compared with unstimulated mononuclear cells. By contrast, BAL fluid from the other individuals had no effect on LZM secretion. CONCLUSIONS--Single cells activated by BAL fluid can be evaluated by the reverse haemolytic plaque assay. BAL fluid from patients with sarcoidosis, but not from patients with systemic sclerosis or normal individuals, contains components capable of activating mononuclear phagocytes to secrete lysozyme.
Collaborative genomics for human health and cooperation in the Mediterranean region
Authors: Tayfun Özçelik, Moien Kanaan, Karen B Avraham, Drakoulis Yannoukakos, André Mégarbané, Ghazi O Tadmouri, Lefkos Middleton, Giovanni Romeo, Mary-Claire King, Ephrat Levy-Lahad
Journal: Nature Genetics (2010)
Home Visiting Narrative
Authors: Cynthia S. Minkovitz, Kay M. Gonsalves O’Neill, Anne K. Duggan
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence
Authors: Jemma Evans, Natalie J. Hannan, Tracey A. Edgell, Beverley J. Vollenhoven, Peter J. Lutjen, Tiki Osianlis, Lois A. Salamonsen, Luk J.F. Rombauts
Journal: Human Reproduction Update (2014)

BACKGROUNDImprovements in vitrification now make frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer, with reports from observational studies and randomized controlled trials suggesting that: (i) the endometrium in stimulated cycles is not optimally prepared for implantation; (ii) pregnancy rates are increased following FET and (iii) perinatal outcomes are less affected after FET.