tbuckley/cabot-search huggingface dataset:
The importance of active ERM proteins stabilization by NHERF1/EBP50 in tumor progression
Authors: Fabiana C. Morales, Yoko Takahashi, Erica L. Kreimann, Maria-Magdalena Georgescu
Journal: Cancer Research (2005)

5477  NHERF1/EBP50 was identified as a regulator factor of the Na+/H+ exchanger isoform 3 (NHE3). EBP50 is a 358-residue adaptor molecule that has two PDZ domains and a C-terminal ezrin-radixin-moesin (ERM)-binding sequence that interacts to the N-terminal domain of the ERM proteins, including merlin, the product of the neurofibromatosis-2 (NF2) tumor suppressor gene. While the loss of expression of merlin was involved in cancer progression, less is known about EBP50’s role on cell growth. In order to understand the regulation of ERM proteins and EBP50 in progression of cancer we used glioblastoma cell lines to identify the pattern of expression of these proteins. Out of 10 glioblastoma cell lines tested, three showed a high expression level of EBP50 and ezrin compared to normal tissue while merlin is downregulated. This finding suggests a correlation in between the expression levels of EBP50 and ERM proteins. To investigate the in vivo role of EBP50 in tumor formation and metastasis we generated mice with targeted disruption of the EBP50 gene. Embryonic stem cells were electroporated with the targeting construct that replaced the first 4 exons of the EBP50 gene with a neomycin cassette flanked by loxP sites. We confirmed that EBP50 was efficiently disrupted in mice by Southern and Western blot analysis. EBP50 is mainly expressed in kidney and intestine of wild type (WT) mice and ezrin is expressed in parallel with EBP50. Purification of kidney and intestine brush border membranes (BBM) from both WT and knockout (KO) mice showed that ezrin and moesin are downregulated in the BBM fraction of KO mice, suggesting a regulation of ERM proteins by EBP50. We also found that EBP50 is necessary for the maintenance of active phosphorylated ERM at the BBM. Immunofluorescense experiments showed that indeed ezrin is downregulated from the apical membrane of polarized epithelial cells of KO mice. Kidney and intestine BBM were fractionated in a Sephadex S-300 gel filtration column in order to identify protein complexes with ERM proteins. Our results showed that EBP50 co-fractionates with ezrin in WT BBM. Electron microscopy analysis of KO intestinal epithelium cells revealed disorganized microvilli and an altered actin-rich terminal web region suggesting a loss of organization of the apical cytoskeleton. In this work we propose a mechanism in which EBP50 is necessary for the recruitment of active ERM proteins to the plasma membrane and we discuss the implications of cell polarity disruption for tumorigenesis.
Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin–dependent neointimal formation
Authors: Catherine A. E. Mason, Jean-Luc Bigras, Stacy B. O'Blenes, Bin Zhou, Brendan McIntyre, Norimasa Nakamura, Yasufumi Kaneda, Marlene Rabinovitch
Journal: Nature Medicine (1999)
GAL4–NF-κB Fusion Protein Augments Transgene Expression from Neuronal Promoters in the Rat Brain
Authors: B.H. Liu, Y. Yang, J.F.R. Paton, F. Li, J. Boulaire, S. Kasparov, S. Wang
Journal: Molecular Therapy (2006)

Targeted gene expression mediated by a mammalian cellular promoter is desirable for gene therapy in the brain, where there are a variety of different neuronal phenotypes, several types of supportive cells, and blood vessels. However, this approach can be hampered by weak activity of some cellular promoters. In view of the potency of the transcription factor NF-kappaB in regulating neuronal gene expression, we have assessed whether it can be used to enhance the strength of neuron-specific promoters. Our approach was to use a neuronal promoter to drive expression of a chimeric transactivator, which consisted of a part of the transcriptional activation domain of the NF-kappaB p65 protein fused to the DNA-binding domain of GAL4 protein from yeast. The second copy of the neuronal promoter was modified by introducing the unique GAL4 binding sequences at its 5' end and used to drive the expression of a transgene. Binding of the chimeric transcriptional activator upstream of the second promoter was expected to potentiate its transcriptional activity. In this study, the approach was applied to the platelet-derived growth factor beta chain and synapsin-1 neuron-specific promoters and tested in vitro and in vivo using plasmid, lentiviral, and baculoviral vectors. We observed up to a 100-fold improvement in reporter gene expression in cultured neurons and 20-fold improvement in the rat brain in vivo. Moreover, the cell-type specificity of the two tested promoters was well preserved and restricted to neurons. Finally, the expression driven by the new lentiviral vectors with the p65-potentiated synapsin-1 promoter showed no signs of decline or cell damage 4 weeks after injection. This approach should be suitable for constructing powerful and stable gene expression systems based on weak cell-specific promoters in neuronal phenotypes.
Abstract P362: Surveillance Of Non-Communicable Diseases By Non-Physician Health Workers In Kerala: the Epidemiology of Non-communicable Diseases in Rural Areas (ENDIRA) study
Authors: Amitava Banerjee, Jacob Joseph, Ajit Thachil, Thankachan V Attacheril, Jaideep Menon
Journal: Circulation (2014)

Introduction: India carries the greatest burden of global non-communicable diseases(NCDs). There are few contemporary, community-based studies of prevalence, particularly in rural settings despite known regional variations. Given the shortage of physicians in rural India, there is an urgent need for large-scale, region-specific studies of NCDs using non-physician health workers. Methods: In central Kerala, India, a population of 113,462 was defined by five panchyats(village councils), consisting of 75 wards in Ernakulam district. The "Epidemiology of Non-communicable Diseases in Rural Areas" (ENDIRA) study was conducted via ASHAs (Accredited Social Health Activists), who are non-physician health workers employed by State Government of Kerala to each cover one ward. Standardised questionnaires were used in household interviews of individuals ≥18 years during 2012 to gather sociodemographic, lifestyle and medical data. Results: ASHAs recruited 84456 adults who were included in the analyses (25.4% below the poverty line). NCDs were relatively common: prevalence of myocardial infarction(MI) 1.4%, stroke 0.3%, respiratory diseases 5.0%, and cancer 1.1%. 84.1% of the population was vegetarian, 15.9% ate meat/fish ≥ 1 day per week, 4.2% had ≥1 alcoholic drink per week and 8.1% smoked regularly. Compared with males, females were older, had lower BMI (p&lt;0.0001), more likely to be hypertensive (p&lt;0.0001), less likely to smoke or drink alcohol, have diabetes or dyslipidaemia (p&lt;0.0001). NCDs were more common in males than females: MI (1.9% vs 0.9%), stroke (0.5% vs 0.3%), cancer (1.2% vs 0.9%) and respiratory diseases (5.9% vs 4.0%); p&lt;0.0001. Age≥65 years, hypertension, diabetes, dyslipidaemia, smoking and male gender were strongly associated with MI and stroke (Table 1). Conclusions: Non-physician health workers (ASHAs) were able to effectively conduct a large-scale prevalence study of NCDs in Kerala, including risk factors. In rural Kerala, traditional risk factors were strongly associated with MI and stroke.
Enlargement and Displacement of the Mediastinum
Authors: R. H. Mcdonald
Journal: Annals of Internal Medicine (1927)

Article1 July 1927Enlargement and Displacement of the MediastinumR. H. MCDONALD, M.D.R. H. MCDONALD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-1-28 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe mediastinum is that portion of the thoracic cavity which is bounded above by the superior thoracic inlet, below by the diaphragm, posteriorly by the anterior surface of the bodies of the thoracic vertebrae, anteriorly by the posterior surface of the sternum and laterally by the mediastinal reflections of the pleura. It is divided, arbitrarily, into anterior, middle, posterior and superior divisions. The superior division lies above the level of the pericardium and of the other three, the middle division contains the pericardium and heart, while the anterior and posterior divisions are respectively the portions anterior and posterior to the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland Clinic Cleveland, Ohio*Clinical discussion given before the American College of Physicians at the Cleveland Clinic, February 22-25, 1927. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1927Volume 1, Issue 1Page: 28-32KeywordsHeartPericardiumSternumVertebrae ePublished: 1 December 2008 Issue Published: 1 July 1927 PDF downloadLoading ...
A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy
Authors: Kang Zhang, Marina Kniazeva, Min Han, Wen Li, Zhengya Yu, Zhenglin Yang, Yang Li, Michael L. Metzker, Rando Allikmets, Donald J. Zack, Laura E. Kakuk, Pamela S. Lagali, Paul W. Wong, Ian M. MacDonald, Paul A. Sieving, David J. Figueroa, Christopher P. Austin, Robert J. Gould, Radha Ayyagari, Konstantin Petrukhin
Journal: Nature Genetics (2001)
Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats
Authors: Onur Cil, Cristina Esteva-Font, Sadik Taskin Tas, Tao Su, Sujin Lee, Marc O. Anderson, Mert Ertunc, Alan S. Verkman
Journal: Kidney International (2015)
Single blind, randomised trial of efficacy and acceptability of oral Picolax versus self administered phosphate enema in bowel preparation for flexible sigmoidoscopy screening Commentary: participants should have been told they were being randomised Commentary: opportunity for patient partnership was lost
Authors: W. S Atkin
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To compare the acceptability and efficacy of two methods of self administered bowel preparation for flexible sigmoidoscopy screening: a single phosphate enema and a single sachet of Picolax. <b>Design:</b> Single blind, randomised trial. <b>Setting:</b> Endoscopy units of two general hospitals. <b>Participants:</b> 1442 men and women aged 55-64 years who had agreed to be screened by flexible sigmoidoscopy. <b>Main outcome measures:</b> Attendance rates, compliance with allocated preparations, adverse effects, quality of bowel preparation, procedure time, and yield of neoplasia. <b>Results:</b> Compliance with the enema was higher than with the Picolax (608 (84%) <i>v</i> 566 (79%); difference 6%, 95% confidence interval 2% to 10%). Almost half of those who refused Picolax used an enema at home. Wind, incontinence, and sleep disturbance were more frequent in the Picolax group than the enema group; bottom soreness was more frequent in the enema group. Around 30% (187) found the diet restriction required by Picolax difficult; 78% (471) found the enema easy to administer. The quality of preparation was better with the enema; the proportion of procedures complete to the descending colon was greater and the mean duration of the procedure was shorter. There was no significant difference in polyp detection rates. <b>Conclusion:</b> A single phosphate enema self administered around one hour before leaving home is a more acceptable and effective method of preparing the distal bowel for flexible sigmoidoscopy than Picolax.
Development of a high-throughput diagnostic assay for lung cancer
Authors: Ying-Horng (Steve) Liu, Kathlynn Brown
Journal: Clinical Cancer Research (2006)

A107   Lung cancer is the largest cancer killer of both men and women. The correct histopathological diagnosis of a tumor is critical in determining the appropriate treatment. However, precise classification of tumors remains a significant biomedical challenge. Furthermore, tumors of similar histology can have different clinical outcomes, stressing the need for more detailed molecular classifications. Our overall goal is to generate a panel of cell-specific molecules that can be used to classify tumor types and utilize these cancer specific reagents in a high throughput diagnostic assay. Using phage display technologies, we have developed methods to isolate peptides that bind to specific tumor cell lines, even in the absence of knowledge of the cell surface receptor profile. By this method, we have identified targeting peptides for 5 lung cancer cell lines and have determined their binding profile to a large panel of lung cancer cell lines. The isolated peptides display remarkable cell-specificities, and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. Furthermore, these peptides can be conjugated to fluorescent nanoparticles (quantum dots, Qdots) in order to rapidly assess cellular binding both quantitatively and qualitatively. This fluorescent-based assay can be multiplexed so that multiple binding events can be examined on a single sample and is amenable to using fresh or fixed cells. At the end of this project we will have developed a novel diagnostic platform that can be expanded to clinical samples.
Cunningham's Text-Book of Anatomy.
Authors: Daniel John Cunningham
Journal: Annals of Internal Medicine (1952)

For the twelfth edition of this classic textbook, the whole text has been reviewed and revised to take into account new developments in the study and teaching of anatomy. Chapters on the central nervous system, digestive system, and respiratory system have been almost entirely rewritten. A completely new feature is the addition of an atlas of anatomical structure using radiographs and tomographs (CT scans).
DIABETES MELLITUS, HYPERTHYROIDISM AND ADDISON'S DISEASE IN ONE PATIENT
Authors: L BRESLAW, J LASHOF, C KLEIN
Journal: Annals of Internal Medicine (1953)

Case Reports1 February 1953DIABETES MELLITUS, HYPERTHYROIDISM AND ADDISON'S DISEASE IN ONE PATIENTLEONARD BRESLAW, M.D., JOYCE LASHOF, M.D., CHARLES KLEIN, M.D.LEONARD BRESLAW, M.D.Search for more papers by this author, JOYCE LASHOF, M.D.Search for more papers by this author, CHARLES KLEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-38-2-338 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA review of the literature reveals no well documented case of the existence of diabetes mellitus, hyperthyroidism and Addison's disease in one patient. Rowntree and Snell1 reported one such case, but some doubt was cast on its validity by Rhind and Wilson.2CASE REPORTThe patient, a Russian-born white woman who was 48 years old at the time of her initial hospital admission, entered the Bronx Hospital for the first time on September 29, 1947, in a stupor, with a history of nausea and vomiting of two days' duration. Past history revealed that the patient had had typhoid fever in...Bibliography1. RowntreeSnell LGAM: Clinical study of Addison's disease, Mayo Clinic Monographs, 1931, W. B. Saunders Co., Philadelphia. Google Scholar2. RhindWilson EGA: Diabetes mellitus in Addison's disease, Lancet 2: 37-38 (July 12) 1941. CrossrefGoogle Scholar3. Williams RH: Textbook of endocrinology, 1950, W. B. Saunders Co., Philadelphia. Google Scholar4. Rossman I: Personal communication to the authors. Google Scholar5. GitmanAntJacobi LMM: Combined hyperthyroidism and adrenal cortical insufficiency: effect of iodine therapy: case report, Ann. Int. Med. 19: 507-514 (Sept.) 1943. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication June 20, 1952.From the Medical Service of Dr. Abner Stern, The Bronx Hospital, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAddison’s DiseaseThyroid disease in diabetics.Die pathologische Morphologie der endokrinen RegulationsstörungenDiabetes Mellitus and Addison's DiseaseDas PankreasADDISON'S DISEASE COMPLICATED BY PREGNANCY AND DIABETES MELLITUS 1 February 1953Volume 38, Issue 2Page: 338-342KeywordsDiabetes mellitusHyperthyroidismMedical servicesNauseaTyphoidVomiting Issue Published: 1 February 1953 PDF downloadLoading ...
501. Aerosols of Compacted DNA Nanoparticles Retain Structural Integrity and Biological Activity
Authors: Rajagopal Ramesh, Isao Ito, Ryo Miyahara, Yuji Saito, Zheng Wu, Abner M. Mhashilkar, Deborah R. Wilson, Cynthia D. Branch, Sunil Chada, Jack A. Roth
Journal: Molecular Therapy (2004)

The melanoma differentiation associated gene-7 (mda-7), also known as interleukin-24 (IL-24), is a novel gene with tumor suppressor, anti-angiogenic and cytokine properties. In vitro adenovirus-mediated gene transfer of the mda-7/IL-24 gene (Ad-mda7) results in ubiquitous growth suppression of human cancer cells with minimal toxicity to normal cells. Intratumoral administration of Ad-mda7 to lung tumor xenografts results in growth suppression via induction of apoptosis and anti-angiogenic mechanisms. Although these results are encouraging, one limitation of this approach is its locoregional clinical application-systemic delivery of adenoviruses for treatment of disseminated cancer is not feasible at the present time. An alternative approach that is suitable for systemic application is liposomal gene delivery. We recently demonstrated that DOTAP:cholesterol (DOTAP:Chol) liposomes effectively deliver tumor suppressor genes to primary and disseminated lung tumors. In the present study, therefore, we evaluated liposome-mediated delivery of the mda-7/IL-24 gene to primary and disseminated lung tumors in vivo. We demonstrate that DOTAP:Chol efficiently delivers the mda-7/IL-24 gene to human lung tumor xenografts resulting in suppression of tumor growth. Growth-inhibitory effects were observed in both primary (P = 0.001) and metastatic lung tumors (P = 0.02). Furthermore, tumor vascularization was reduced in mda-7/IL-24-treated tumors. Finally, growth was also inhibited in murine syngenic tumors treated with DOTAP:Chol-mda-7 complex (P = 0.01). This is the first report demonstrating (1) systemic therapeutic effects of mda-7/IL-24 in lung cancer and (2) anti-tumor effects of mda-7 in syngeneic cancer models. Our findings are important for the development of mda-7/IL-24 treatments for primary and disseminated cancers.
Abstract 37: Lipoprotein Subclasses and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis
Authors: Rachel H Mackey, Samia Mora, Alain G Bertoni, Christina Wassel, Mercedes Carnethon, Christopher T Sibley, David C Goff
Journal: Circulation (2014)

Lipoprotein changes often precede incident type 2 diabetes and may be diabetogenic, but effects of lipid-lowering medications, ethnicity and sex on these associations are unclear. In the Multi-Ethnic Study of Atherosclerosis, among 5636 men and women, ages 45-84, without baseline diabetes or CVD, 694 diabetes cases were identified during mean follow-up of 7.7 years. NMR spectroscopy was used to measure lipoprotein particle concentrations and size, including a calculated lipoprotein-related insulin resistance score (LP-IR), on baseline plasma. Analyses were stratified by baseline lipid-lowering medication (primarily statin) use, as “untreated” (n=4816) or “treated” (n=820), and by glucose &lt;100 vs.100-125 mg/dl (impaired fasting glucose, IFG). Among treated and untreated participants, higher LP-IR, larger mean VLDL particle size, HOMA-IR and (log)insulin were associated with incident diabetes, adjusted for age, ethnicity and sex (HRs per SD &gt;1.5, p&lt;0.05). Associations of LP-IR and VLDL size with incident diabetes remained significant when additionally adjusted for HDL-C, (log) triglycerides, BMI, glucose, family history of diabetes, physical activity and alcohol use and among treated participants with IFG, and were similar by sex and race-ethnicity. In conclusion, lipoprotein particle measures, particularly LP-IR and VLDL size, were robustly associated with incident diabetes among both untreated and treated ethnically diverse adults.
Abstract 16884: Involvement of Hydrogen Sulfide (H2S) in Dexamethasone (DEX) Induced Hypertension in Rat
Authors: Erminia Donnarumma, Emma Mitidieri, Teresa Tramontano, Vincenzo Brancaleone, Mariarosaria Bucci, Roberta d’Emmanuele di Villa Bianca, Raffaella Sorrentino
Journal: Circulation (2014)

Introduction: Glucocorticoid (GC) excess is related to hypertension. The deletion of endothelial GC-receptors abrogates the blood pressure increase, suggesting GC-induced hypertension is endothelium-dependent. In response to shear stress endothelium releases nitric oxide, endothelial derived hyperpolarizing factor (EDHF) and prostacyclin. Recently H2S has been proposed as a candidate for EDHF. H2S is mainly produced by the enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) from L-cysteine. The aim of this study was to investigate the EDHF/H2S signaling in GC-hypertension. Methods: Male Wistar rats were treated with DEX (1.5 mg/kg/sc) or vehicle (VEH) for 8 days. Systolic blood pressure (SBP) was monitored every 2 days. EDHF was evaluated in mesenteric plexus and carotid artery performing a concentration-effect curve of acetylcholine in presence of indomethacin (INDO) and nitro-L-arginine methyl ester (L-NAME). Apamin (APA) plus charibdotoxin (CTX), SKCa and BKCa inhibitors, or propargylglycine (PAG), CSE inhibitor, were used. CBS and CSE levels were analyzed by immunoblot. H2S levels were measured by a colorimetric assay. Results: DEX treatment significantly increased SBP compared to VEH (*p&lt;0.05, **p&lt;0.01, ***p&lt;0.001 at days 2-4, 6, 8 respectively). EDHF-mediated relaxation of mesenteric bed or carotid artery was markedly reduced in DEX group compared to VEH (***p&lt;0.001). APA and CTX as well as PAG abolished EDHF-mediated relaxation in DEX or VEH group (***,°°°p&lt;0.001 respectively). CBS and CSE levels were significantly reduced in mesenteric plexus and carotid artery in DEX group (*p&lt;0.05). The H2S production was markedly reduced in mesenteric plexus and carotid artery (*p&lt;0.05, **p&lt;0.01 respectively) as well as plasmatic H2S levels (*p&lt;0.05) in DEX rats compared to VEH. Conclusions: Our data demonstrate that GC-excess induces an impairment of H2S/EDHF signaling indicating an additional cause of GC-mediated hypertension.
ACUTE ACCIDENTAL SUPERFICIAL X-RAY BURNS..
Authors: R. D. Sweet.
Journal: British Journal of Dermatology (1962)

Journal Article ACUTE ACCIDENTAL SUPERFICIAL X‐RAY BURNS.: An Interim Report of 11 Cases. Get access R. D. Sweet. R. D. Sweet. South Devon and East Cornwall Hospital, Plymouth Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 11, 1 November 1962, Pages 392–402, https://doi.org/10.1111/j.1365-2133.1962.tb13433.x Published: 01 November 1962