tbuckley/cabot-search huggingface dataset:
209. Nuclear Localization Mediated by the Adenoviral-Core Peptide Mu Enhances Phage φC31-Integrase Activity in Mammalian Cells
Authors: Richard P. Harbottle, Laurence Vaysse, Ahad Rahim, Yvonne Kienast, Ourania Passa, Oleg Tolmachov, Charles Coutelle
Journal: Molecular Therapy (2005)

The desired end point of cell targeting and gene delivery in most cases is effective expression of the transported gene. Currently most non-viral vectors utilise DNA molecules, which are maintained only transiently within a cell. The development, therefore, of non-viral gene-transfer technologies that can support stable chromosomal integration and persistent gene expression in vivo is desirable. The potential problem of insertional mutagenesis through non-specific integration mediated by currently used systems (such as the Sleeping Beauty transposon) has lead us to investigate alternative strategies. The Streptomyces phage |[ndash]| derived integrase |[phi]|C31 (|[phi]|C31-Int) catalyses the irreversible integration between two specific sequences, attB and attP. In the human genome 31 potential integration sites have currently been identified and whilst the total number of sites may be higher it is still estimated to be several orders of magnitude lower than those available for other systems. A barrier, which limits the efficiency of this system in mammalian cells, is nuclear entry; |[phi]|C31-Int is of bacteriophage origin and does not have nuclear localising properties. After production in mammalian cells the protein tends to remain localised in the cytoplasm and therefore ineffectual. We hypothesised that it may be possible to increase the activity of |[phi]|C31-Int by fusing it with a nuclear localising sequence (NLS). We have generated a series of nuclear targeted |[phi]|C31-Int proteins by creating fusions between |[phi]|C31-Int and NLS peptides. When fused with the nuclear localising adenoviral core peptide mu the |[phi]|C31-Int protein is effectively translocated to the nucleus wheras the unmodified integrase protein is not. Correspondingly, the efficiency of transgene integration mediated by |[phi]|C31-Int is significantly enhanced in vitro and in vivo following hydrodynamic delivery compared to non-targeted controls.
Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the <scp>J</scp>apanese population
Authors: K. Tomita, M. Sakashita, T. Hirota, S. Tanaka, K. Masuyama, T. Yamada, S. Fujieda, A. Miyatake, N. Hizawa, M. Kubo, Y. Nakamura, M. Tamari
Journal: Allergy (2012)

Abstract Background Allergic rhinitis ( AR ) is a very common disorder peaking in the teenage years that is mediated by hypersensitivity responses to environmental allergens. Although it is well established that the ORMDL 3 locus at chromosome 17q21 is associated with susceptibility to bronchial asthma, the genetic influences of the polymorphisms of the locus in allergic rhinitis are unclear. Objective To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Methods We performed linkage disequilibrium ( LD ) mapping of the locus using the HapMap database and conducted an association study of the locus with a total of 15 tag SNP s in two independent populations. We further evaluated correlations of genotypes with changes in expression of genes at the region in lymphoblastoid cell lines in the Japanese population and assessed the expression levels of the genes in nasal epithelium and various human tissues. Results We found a significant association between a total of five polymorphisms in the 17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246, and rs4794820, and AR (minimum P combined = 0.00074, rs4794820). The expression level of the ORMDL3 transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with P &lt; 0.01 (minimum P = 0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium. Conclusion Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.
Sodium Sulfate Treatment of Hypercalcemia
Authors: Zaven H. Chakmakjian, John E. Bethune
Journal: New England Journal of Medicine (1966)

HYPERCALCEMIA is a clinical finding that is usually controlled by relatively simple procedures but occasionally presents an acute medical emergency. It occurs in a wide variety of disorders such as hyperparathyroidism, carcinoma with or without bony metastasis, multiple myeloma, lymphoma, sarcoidosis, vitamin D intoxication, milk-alkali syndrome, hyperthyroidism, idiopathic hypercalcemia of infancy and, rarely, acute adrenal insuificency.1 , 2 Symptoms vary, depending upon the primary disease producing the hypercalcemia and on the degree of elevation of serum calcium. Hypercalcemia may threaten life, and if the serum calcium concentration is not lowered, the patient may die. This syndrome, which has been called "hypercalcemic crisis," . . .
T-LYMPHOCYTE ALVEOLITIS IN HTLV-I-ASSOCIATED MYELOPATHY
Authors: Mineharu Sugimoto, Hironori Nakashima, Susumu Watanabe, Eiichiro Uyama, Fujiho Tanaka, Masayuki Ando, Shukuro Araki, Shoichiro Kawasaki
Journal: The Lancet (1987)
Barnyard Microbes and Childhood Asthma
Authors: James E. Gern
Journal: New England Journal of Medicine (2011)

It is easy to imagine why children who are raised on farms might grow up healthy: there is plenty of fresh air, exercise, and exposure to sunlight. In fact, studies from Europe, North America, and Australasia provide convincing evidence that allergic diseases and asthma are less likely to develop in children who live on farms than in those who do not.1 Surprisingly, according to the findings of Ege and colleagues in this issue of the Journal, 2 the mechanism responsible for these health effects appears not to be related to clean living but instead to bacteria and fungi from the barnyard. . . .
A Good Pair of Hands
Authors: Bhuvana Chandra
Journal: Annals of Internal Medicine (1999)

On Being a Doctor6 April 1999A Good Pair of HandsBhuvana Chandra, MDBhuvana Chandra, MDNorthridge, CA 91326 (Chandra)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-7-199904060-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail He greeted me as he always did, hands folded weakly together in the gesture of respect that is ubiquitous in India. Namaste: “I bow to the Divine in you.” He could barely lift his head from the thin pillow, and his emaciated arms trembled uncontrollably from the effort of opposing his palms as I approached bed 6, row 2, in a second-floor ward of the Government General Hospital in Madras. Embarrassment heated my face at the reverence that lit up his tired eyes and rekindled, for the tiniest moment, the fading sparks of what had once been the natural élan ... Author, Article, and Disclosure InformationAffiliations: Northridge, CA 91326 (Chandra)Corresponding Author: Bhuvana Chandra, MD, Box 7694, Northridge, CA 91326. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 April 1999Volume 130, Issue 7Page: 610-611KeywordsAbscessesBloodBreadChartsHand strengthHemorrhageStarvationSurgeryTyphoidVeins Issue Published: 6 April 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
A Review of the Melancholy of Anatomy
Authors: Benjamin Spector
Journal: New England Journal of Medicine (1960)

ANY depressed state calls for an occasional diagnostic review, since even the most chronic diseases are not static and patients may be helped by timely revisions of their therapeutic regimens. The slightly whimsical but unfortunately realistic "melancholy of anatomy" was discussed editorially in the April 17, 1958, issue of the Journal. At that time the three following points were made: dissection is indispensable as the pathway to a useful knowledge of anatomy, or, in a more accurate sense, bioanatomy; the supply of anatomic material has become seriously curtailed; and the right of the individual to dispose of his remains . . .
The incidence of gastroschisis: Research urgently needs resources
Authors: Pierpaolo Mastroiacovo, Alessandra Lisi, Eduardo E Castilla
Journal: BMJ (2006)

EDITOR—Kilby says that gastroschisis shows an increasing temporal trend in the number of affected babies born in the United Kingdom,1 a trend that has also been observed in other parts of the world.2

We evaluated the data of 25 registries of members of the International Clearinghouse for Birth Defects …
The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection.
Authors: L. S. Young, I. S. Bevan, M. A. Johnson, P. I. Blomfield, T. Bromidge, N. J. Maitland, C. B. Woodman
Journal: BMJ (1989)

The polymerase chain reaction is an in vitro method for primer directed enzymatic amplification of specific target DNA sequences. The technique was used to detect human papillomavirus types 11 and 16 simultaneously in cellular DNA recovered from cervical smears in 38 women referred for colposcopy to evaluate cytological abnormality and 10 women with no history of cytological abnormality. The polymerase chain reaction was shown to be both specific and sensitive in detecting human papillomavirus DNA such that a single human papillomavirus molecule was detected in 10(5) cells. Of the 38 women with cytological abnormality, all were positive for human papillomavirus on testing with the polymerase chain reaction; 36 were infected with human papillomavirus type 16 and 22 dually infected with human papillomavirus types 11 and 16. Seven of the 10 women with no cytological abnormality were also infected with human papillomavirus type 11 or 16. The use of the polymerase chain reaction will facilitate epidemiological investigation of the aetiological role of human papillomavirus in cervical neoplasia. This preliminary analysis suggests that the prevalence of human papillomavirus infection is greater than previously reported.
Cutaneous infection with Mycobacterium abscessus
Authors: D.A. FITZGERALD, A.G. SMITH, A. LEES, L. YEE, N. COOPER, S.C. HARRIS, J.A. GIBSON
Journal: British Journal of Dermatology (2006)

Journal Article Cutaneous infection with Mycobacterium abscessus Get access D.A. FITZGERALD, D.A. FITZGERALD Departments of Dermatology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Dr D.A.Fitzgerald, Department of Dermatology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.G. SMITH, A.G. SMITH Departments of Dermatology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. LEES, A. LEES Departments of Microbiology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar L. YEE, L. YEE Departments of Microbiology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar N. COOPER, N. COOPER Departments of Histopathology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.C. HARRIS, S.C. HARRIS Departments of Histopathology, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.A. GIBSON J.A. GIBSON Departments of Medicine, Staffordshire General Infirmary, Foregate Street, Stafford ST16 2PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 5, 1 May 1995, Pages 800–804, https://doi.org/10.1111/j.1365-2133.1995.tb00730.x Published: 01 May 1995 Article history Accepted: 17 August 1994 Published: 01 May 1995
Jane Marushka Critchley
Authors: Mair Critchley, Edmund Critchley
Journal: BMJ (2005)

Pioneer of cervical screeningBetty Macgregor was the cytologist who made northeast Scotland the United Kingdom's first centre for systematic cervical screening.It was because of her published results that screening was taken up throughout the UK.She published important papers on many aspects of screening, including cervical cytology, the epidemiology of cervical cancer, improving the prognosis, cost effectiveness, cervical abnormalities in various subgroups of women, and the problems of false negative results.Her booklet Taking Uterine Cervical Smears (1982), published by the British Society of Clinical Cytology, sold 25 000 copies.Betty McPherson was born in Glasgow in 1920.When she was 7 her mother died from tuberculosis.Betty studied medicine at Glasgow University during the second world war, qualifying in 1943.She met Alastair Macgregor there, and they married a year later.She did her house jobs at Glasgow Royal Infirmary and Western General Hospital.During the next few years she raised their four children and worked part time in child welfare clinics.In 1958
Magnetic Vascular Port in Minimally Invasive Direct Coronary Artery Bypass Grafting
Authors: Uwe Klima, Horace MacVaugh, Eric Bagaev, Michael Maringka, S. Kirschner, J. Beilner, Axel Haverich
Journal: Circulation (2004)

Background— Minimally invasive direct coronary artery bypass grafting (MIDCAB) is a well-established operative procedure. However, it is technically demanding and is therefore somewhat underused. We evaluated the clinical and angiographic outcome of patients undergoing a MIDCAB procedure with the Ventrica Magnetic Vascular Port (MVP®) system. Methods and Results— A Ventrica MVP® system was used in 10 of 11 selected MIDCAB patients. The system consists of 6 magnetic clips, with 3 clips forming a set. One magnetic clip set is positioned at the arteriotomy of the target artery and of the bypass graft using a preloaded delivery system. These ports then form an anastomosis by magnetic coupling. The mean age of the 10 patients (6 male) was 60.3±11.0 years. Three patients had an angiogram at the time of discharge and 8 returned for a 6-month angiogram. The total procedure time was 128.2±12.2 minutes. The mean anastomotic time was 199 seconds. The mean ischemic time during the anastomosis was 146±146 seconds. There were no in-hospital complications and no device-related adverse events. All 3 predischarge and all 8 6-month angiograms showed patent anastomoses. Conclusions— The magnetic vascular port facilitates the MIDCAB procedure significantly and reduces the ischemic time during the anastomosis. This minimally invasive procedure has the potential to be an alternative to percutaneous transluminal coronary angioplasty and stenting in proximal left anterior descending (LAD) stenosis. It may expand the acceptance of hybrid procedures in which a left internal mammary artery (LIMA)-to-LAD graft optimally supplies the anterior wall and the septum while the circumflex and right coronary artery may be treated interventionally.
Inhibition of Calcineurin and Sarcolemmal Ca <sup>2+</sup> Influx Protects Cardiac Morphology and Ventricular Function in K <sub>v</sub> 4.2N Transgenic Mice
Authors: Rajan Sah, Gavin Y. Oudit, The-Tin T. Nguyen, Hae W. Lim, Alan D. Wickenden, Gregory J. Wilson, Jeffery D. Molkentin, Peter H. Backx
Journal: Circulation (2002)

Background — Cardiac-targeted expression of truncated K v 4.2 subunit (K v 4.2N) reduces transient outward current ( I to ) density, prolongs action potentials (APs), and enhances contractility in 3- to 4-week-old transgenic mice. By 13 to 15 weeks of age, these mice develop severely impaired cardiac function and signs of heart failure. In this study, we examined whether augmented contractility in K v 4.2N mice results from elevations in intracellular calcium ([Ca 2+ ] i ) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of K v 4.2N mice. Methods and Results — At 3 to 4 weeks of age, L-type Ca 2+ influx and peak [Ca 2+ ] i were significantly elevated in K v 4.2N myocytes compared with control because of AP prolongation. Cardiac calcineurin activity was also significantly elevated in K v 4.2N mice by 5 weeks of age relative to controls and increased progressively as heart disease developed. This was associated with activation of protein kinase C (PKC)-α and PKC-θ but not PKC-ε, as well as increases in β-myosin heavy chain (β-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented increases in heart weight to body weight ratios, interstitial fibrosis, impaired contractility, PKC activation, and changes in the expression patterns of β-MHC and SERCA2a. Conclusions — Our results demonstrate that AP prolongation caused by I to reduction results in enhanced Ca 2+ cycling and hypercontractility in mice and suggests that elevations in [Ca 2+ ] i via I Ca,L and activation of calcineurin play a central role in disease development after I to reduction using the K v 4.2N construct.
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease E-dition: Pathophysiology, Diagnosis, Management, vols 1 &amp; 2
Authors: Frank L. Iber
Journal: JAMA (2007)

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
Translating the Chronic Care Model Into the Community: Results From a Randomized Controlled Trial of a Multifaceted Diabetes Care Intervention
Authors: Gretchen A. Piatt, Janice C. Zgibor, Maria M. Brooks
Journal: Diabetes Care (2006)

We read Belalcazar and Swank’s response (1) to our article with great interest. They have valid concerns regarding potentially biased estimates of treatment effects in small translational research studies where circumstances and environments are not as easily controlled as they are in efficacy-based research (2).

Our study (3) was a pilot, randomized, controlled trial of a multifaceted diabetes care intervention. Eleven primary care practices and their patients ( n = 762), all from the same underserved community, were block randomized to one of three study groups before the …
639. In Vivo Imaging of Lymph Node Metastasis with Telomerase-Specific Replication-Competent Adenovirus Containing Green Fluorescent Protein Gene
Authors: Toru Kojima, Hiroyuki Kishimoto, Yuichi Watanabe, Shunsuke Kagawa, Fuminori Teraishi, Masayoshi Hioki, Yoshihiro Ikeda, Ryo Sakai, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara
Journal: Molecular Therapy (2006)

Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, ultrasonography, and magnetic resonance imaging are noninvasive and are well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here we describe a new approach to visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401, Telomelysin- GFP) and a charged-coupled device (CCD) imaging system. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. OBP-401 contains the replication cassette, in which the hTERT promoter element drives expression of E1A and E1B genes linked with an IRES, and the GFP gene driven by the cytomegalovirus promoter for monitoring viral replication. Quantitative real time PCR analysis targeting the viral E1A sequence in vitro showed that OBP-401 replicated 5|[ndash]|6 logs by 3 days after infection in human cancer cell lines and coordinately induced GFP expression under fluorescence microscopy; OBP-401 replication, however, was attenuated up to 2 logs in normal human lung fibroblasts without GFP expression. We also found that established subcutaneous tumors could be visualized after intratumoral injection of OBP-401. Three weeks after treatment, tumors expressed strong green signals under a three-chip color cooled charged-coupled device camera. Tumor sections diffusely expressed GFP, suggesting in vivo viral replication and spread throughout the tumors. Finally, we examined whether OBP-401 might be useful for detection of lymph node metastasis in an orthotopic rectal cancer model. OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice. Five days after injection, para-aortic lymph node metastasis could be visualized at laparotomy. Histological examination confirmed that GFP-positive lymph nodes contained microscopic metastasis. Our results indicate that intratumoral injection of OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in tumor-specific GFP expression. These observations suggest that intratumoral injection of OBP-401 might be a useful diagnostic method that provides a foundation for future clinical application.
Primary Acquired Sideroblastic Anaemia: Response to Treatment with Pyridoxal-5-Phosphate
Authors: D. Y. Mason, P. M. Emerson
Journal: BMJ (1973)

A 72-year-old woman with primary sideroblastic anaemia showed no response to treatment with pyridoxine. When she was given pyridoxal-5-phosphate there was a prompt reticulocyte response and sustained symptomatic improvement with satisfactory control of the anaemia.
Food Insufficiency Is Associated with High-Risk Sexual Behavior among Women in Botswana and Swaziland
Authors: Sheri D Weiser, Karen Leiter, David R Bangsberg, Lisa M Butler, Fiona Percy-de Korte, Zakhe Hlanze, Nthabiseng Phaladze, Vincent Iacopino, Michele Heisler
Journal: PLoS Medicine (2007)

Both food insufficiency and HIV infection are major public health problems in sub-Saharan Africa, yet the impact of food insufficiency on HIV risk behavior has not been systematically investigated. We tested the hypothesis that food insufficiency is associated with HIV transmission behavior.