tbuckley/cabot-search huggingface dataset:
854. Feasibility of AAV-Mediated Gene Therapy Examined Using a New Murine Model (D409V/null) of Gaucher Disease
Authors: John Marshall, Kerry McEachern, Jennifer B. Nietupski, Julie A. Cavanagh Kyros, Donna Armentano, Gregory A. Grabowski, Seng H. Cheng
Journal: Molecular Therapy (2004)

Gaucher disease is the most common of the more than 40 currently described lysosomal storage diseases. It is caused by mutations in the gene encoding the lysosomal hydrolase, glucocerebrosidase (GC). The loss or deficiency of this enzyme results in the accumulation of the substrate, glucosylceramide (GL-1), in tissue macrophages primarily of the liver and spleen. A mouse model of the disease (D409V/null) was recently generated. Characterization of this murine model indicated that it displayed several of the biochemical and phenotypic abnormalities shown associated with the human disease. The D409V/null mice exhibited approximately only 5% of normal levels of the enzyme in the visceral tissues and consequently, elevated levels of GL-1 in the liver, spleen, lung and also the bone marrow of these animals. Associated with the abnormal storage of GL-1 in the tissues were the appearance of characteristically enlarged macrophages (Gaucher cells) similar to those observed in Gaucher patients, particularly in the liver, spleen and lung of the mice. To evaluate the potential of gene therapy for treating this disease, an AAV 2/2 and 2/8-pseudotyped vector encoding the human GC were constructed. Since secretion of GC from transduced cells occurs only in cells highly overexpressing the enzyme, efforts were made to optimize its expression. A codon optimized and CpG-reduced synthetic cDNA for human GC was placed under the transcriptional control of an 1-antitrypsin promoter to which was appended two copies of the 1-microglobulin enhancer (DC172). Studies showed that expression from the DC172 promoter was hepatic-restricted and was significantly higher than that attained with either a CMV or the previously described DC190 promoter (human serum albumin promoter linked to two copies of the human prothrombin enhancer). Intravenous administration of 31011 particles of either AAV2/2-DC172-shGC or AAV2/8-DC172-shGC into 4 weeks old D409V/null mice resulted in hepatic transduction and subsequent secretion of supraphysiological levels of GC into the systemic circulation. Expression of GC in animals administered AAV2/8-DC172-hGC were 50 to 100-fold higher than from the corresponding AAV2/2 vector and remained undiminished at 4 months. In contrast to the untreated mice, which displayed characteristic Gaucher cells in the lungs, liver and spleen, treated animals (at 2 months post-treatment) were devoid of these cells and harbored normal tissue levels of GL-1. The absence of elevated GL-1 levels in the tissues of treated animals confirmed that the hepatically-produced enzyme was in a form that was conducive to recapture by the affected cells and that importantly, the levels attained were sufficient to prevent the development of disease manifestations. These data support the continued development of AAV vectors for gene therapy of Gaucher disease.
New Radiographic and Isotopic Procedures in Neurological Diagnosis
Authors: Giovanni Di Chiro
Journal: JAMA (1964)

RECENTLY, new special procedures in neurological diagnosis have been developed at the National Institute of Neurological Diseases and Blindness. These are radiographic (axial transverse encephalography) and isotopic (encephalography using radio-iodinated anti-fibrinogen, and ventriculography and cisternography using radio-iodinated serum albumin) methods. <h3>Axial Transverse Encephalography</h3> In the technique of fractional encephalography with tomography,<sup>1</sup>two well-established radiographic methods are combined, fractional pneumoencephalography and tomography. In fractional pneumoencephalography, intrathecally injected air is followed with serial radiograms as it moves along, "fraction by fraction," through the cerebrospinal fluid pathways. Tomography is a radiographic technique in which the patient or the x-ray tube and film are subjected to various types of movement during the exposure. This results in a photographic blurring of the structures in all but a single layer of the body part under examination. This chosen layer, always in the plane in focus, thus appears sharp and distinct. In the technique of fractional
Characterization of recombinant Mercurialis annua major allergen Mer a 1 (profilin)☆1☆2☆3☆4☆5☆6☆7☆8
Authors: Angel Vallverdú, Juan A. Asturias, M.Carmen Arilla, Nuria Gómez-Bayón, Alberto Martínez, Jorge Martínez, Ricardo Palacios
Journal: Journal of Allergy and Clinical Immunology (1998)
Governance and Professionalism in Medicine
Authors: Harvey Marcovitch
Journal: JAMA (2015)

In Great Britain during the 20th century, undergraduate education was provided by medical schools, continuing professional development was the responsibility of universities linked to their nearest National Health Service (NHS) hospitals, and specialist training and accreditation was in the hands of the Royal Colleges. The latter had the authority to veto training posts in hospitals if they were considered inadequate and moderated every appointment committee for NHS consultant (ie, staff) posts. Professionalism was assumed and governance scarcely existent, with individual physicians holding themselves to account, loosely regulated by a statutory body run by the powerful General Medical Council (GMC). The GMC was established in 1858. In just 20 years, all has changed. Some of the impetus has come from within medicine as understanding risk management and accepting patient autonomy gained ground; however, much has been imposed, precipitated by a series of agonizing public inquiries arising from scandalous health and social care failures.
Self management in asthma care
Authors: B. Thoonen
Journal: BMJ (2000)

Papers p 1507 

Equipping people with asthma with the tools they need to manage their condition is as important as writing the correct prescription,” according to the United Kingdom's National Asthma campaign. Guided self management has an established place in asthma guidelines and recommendations.1-2 Yet the reality of everyday asthma care is quite different from that which the guidelines suggest, as shown by Jones et al in this issue (p 1507).3 Even among general practitioners in an academic setting, asthma remains underdiagnosed and poorly treated,4 despite increased awareness of the condition. Professionals perceive asthma as a lifelong problem, but patients discontinue treatment after a few years or do not consult health professionals at all.5

General practitioners and nurses have an important role in implementing self care programmes. However, Jones et al report that patient self management …
Abciximab in the Treatment of ST-Segment Elevation Myocardial Infarction—Reply
Authors: Giuseppe De Luca, Harry Suryapranata
Journal: JAMA (2005)

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
Arteriosclerosis in Diabetes
Authors: Elliott P. Joslin
Journal: Annals of Internal Medicine (1930)

Article1 July 1930Arteriosclerosis in DiabetesELLIOTT P. JOSLIN, M.D.ELLIOTT P. JOSLIN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-1-54 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEvery other diabetic now dies of arteriosclerosis and the percentage of such cases has been rapidly rising. In the Naunyn Era it was 15 per cent, in the Allen Era 26 per cent, in the first half of the Banting Era it was 41 per cent, but for the last 4 years in 781 fatal cases in my own series it has grown to 50 per cent. In diabetes the percentage mortality from arteriosclerosis is one-third greater than for the population as a whole, if we take Massachusetts for a criterion, because in this state it is responsible for 37...References1 JOSLIN EP: Arteriosclerosis and Diabetes. Annals of Clin Med., 1927, 5, 1061. Google Scholar2 ANDERSON K.: Diabetes Mellitus and Arteriosclerosis. Minn. Med., 1929, 12, 484. Google Scholar3 HUNT HM: Cholesterol in Blood of Diabetics, etc. N. E. Jour. Med., 1929, 201, 659. CrossrefGoogle Scholar4 WHITEHUNT PH: N. E. Jour. Med., 1930, 202, 607. CrossrefGoogle Scholar5 MORRISONBOGAN LBIK: Calcification of Vessels of Diabetics. J. A. M. A. 1929, 92, 1424. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston*Read at the Minneapolis Meeting of the American College of Physicians, February 11, 1930. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAtherosclerosis and Diabetic NephropathyDiabetic Kidney DiseaseDiabetic kidney diseaseThe mechanism of arrhythmias during insulin-induced hypoglycemiaAn Autopsy Study of Cerebrovascular Accident in Diabetes MellitusAction of hypoglycemia on coronary insufficiency and mechanism of ECG alterationsKrankheiten der GefäßeHormonal Aspects of Coronary Artery DiseaseKrankheiten des MyokardsKrankheiten des MyokardsCholesterol content of the coronary arteries and blood in acute coronary artery thrombosisDie experimentelle Arterioskleroseforschung und ihre Ergebnisse für Pathogenese und KlinikErbbiologie und Erbpathologie des Kreislaufapparates 1 July 1930Volume 4, Issue 1Page: 54-66KeywordsMortality ePublished: 1 December 2008 Issue Published: 1 July 1930 PDF downloadLoading ...
Abstract P365: Turning in the Mortality Trends from Coronary Heart Disease in Japan: Age-Specific Analysis of the Regional Difference in Japan from 1969 to 2007
Authors: Akira Okayama, Nagako Okuda, Hirotsugu Ueshima
Journal: Circulation (2014)

Objective: To examine the recent mortality trends of coronary heart disease (CHD), we compared the age specific CHD mortality trends in Japan and in urban and in the rest of Japan, respectively using Vital Statistics. Methods and Results: We compared CHD mortality rates in all Japan, the urban population (20 million) and in the rest of Japan (100 million) from 1969 to 2007 for 30 to 69 years of age. In 1969 [[Unable to Display Character: &amp;#8209;]] 1970, the age[[Unable to Display Character: &amp;#8209;]]adjusted CHD mortality rate was 57.7 per 100,000 for men and 25.9 for women in Japan, and was the same as those of the urban population (59.2 for men and 26.8 for women) and the rest of Japan (57.3 for men and 25.9 for women). The CHD mortality rate in the rest of Japan decreased to 28.4 for men and 7.6 for women in 2006-2007. Although CHD mortality rate in the urban population also decreased to 39.9 for men and 10.1 for women in 2006 - 2007, the decline was much smaller. Trends in age-specific CHD mortality rates was compared between Period I (1969 - 1978), Period II (1981- 1994) and period III (1996 - 2007). Among men in Japan and in the rest of Japan, the decline in the mortality rate for the 30 to 49[[Unable to Display Character: &amp;#8209;]]year[[Unable to Display Character: &amp;#8209;]]old[[Unable to Display Character: &amp;#8209;]]age group was initially observed in Period I and II, and has turned to increase significantly (p&lt;0.001) in the Period III while continuous declining trends in 50-59 and 60-69 year old-age-group. Trends in urban population went ahead, changes in the declining trends was observed both the Period II and III among 30-49 year-old-age group and period III among 50-59 year-old-age group while continuous decline was observed among 60-69 year-old-age group. Similar trends were observed among women. These trends coincide with the increase in the fat intake mainly among younger generation. Conclusions: Observed increase in CHD mortality of men in Japan among younger generation proceeded by those in the urban population may predict the future increase in CHD mortality in Japan.
Mechanism of Initiation of Atrial Flutter in Humans: Site of Unidirectional Block and Direction of Rotation 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
Authors: Jeffrey E. Olgin, Jonathan M. Kalman, Leslie A. Saxon, Randall J. Lee, FACC Michael D. Lesh
Journal: Journal of the American College of Cardiology (1997)
Factors Influencing Glycemic Control in Young People With Type 1 Diabetes in Scotland
Authors: V. Alexander, A. Blair, M. Blair, I. Campbell, A. Collier, J. Croll, A. Connacher, I. Craigie, G. Farmer, M. Fisher, S. Gallacher, S. Gray, S. Greene, A. Harrower, A. Jaapp, R. Jung, C. Kelnar, J. Lawrence, G. Leese, P. Leslie, M. Louden, A. MacCuish, D. Matthews, S. MacRury, M. McGregor, J. McKnight, H. McLaren, B. McSporran, Andrew Morris, L. Murchison, R. Newton, K. Noyes, E. O'Brien, A. Patrick, C. Patterson, D. Pearson, N. Peden, P. Rae, S. Reith, K. Robertson, D. Rooney, I. Ruthven, C. Shepherd, J. Schulga, P. Smail, M. Small, J. Steel, R. Thompson, J. Walker, N. Waugh
Journal: Diabetes Care (2001)

To evaluate differences in HbA1c concentrations between centers and to assess the factors associated with glycemic control in young people with type 1 diabetes in Scotland.Data on 1,755 patients (94% of those registered) were collected from 18 centers providing care to children <15 years of age. At every clinic visit, a duplicate HbA1c sample was measured in a reference laboratory, and clinical information was collected prospectively.Average HbA1c concentration was 9.1% (range 5.0-15.0). The following significant associations with HbA1c level were identified: age, insulin regimen, BMI, season, social circumstances, and family history. HbA1c concentrations were significantly worse in older children (age 10-15 years 9.5% vs. other ages 8.8%, P < 0.001), those using two injections per day (2/day 9.1% vs. 3/day 8.8%, P < 0.01), children without both parents at home (9.4 vs. 9.0%, P < 0.001), a sibling with diabetes (9.7% vs. no family history 9.1%, P < 0.001). HbA1c concentration ranged from 8.1 to 10.2% between centers, after adjustment for factors associated with poor HbA1c (P < 0.001).The overall glycemic control of diabetic young people in Scotland is equivalent to a Diabetes Control and Complications Trial HbA1c concentration of 8.7%, placing the majority at a high risk of the complications of diabetes in adulthood. Although factors were significantly associated with poor HbA1c adjustment for these did not explain the differences between centers. We suggest that factors not analyzed in DIABAUD2 (e.g., deployment of resources, organization of the clinical structure, strategies of care, and clinic philosophy) are the determinants of HbA1c. We speculate that the style of utilization of optimum resources is the key to achieving good glycemic control.
Abstract 16452: Determinants of Vt Occurrence in Patients With Nonischemic and Dilated Cardiomyopathy: Insights From the Study of Explanted Human Hearts
Authors: Lucas Valtuille, Nirmal Parajuli, Konrad S Famulski, Philip F Halloran, Sergi Consolato, Gavin Y Oudit
Journal: Circulation (2014)

Introduction: The molecular and cellular determinants of ventricular tachycardia (VT) in patients with non-ischemic dilated cardiomyopathy (NIDCM) remain poorly defined. Hypothesis: Patients with idiopathic NIDCM and significant VT display different tissue and electrical remodeling when compared to other NIDCM patients with end stage heart failure but no history of ventricular arrhythmias. Methods: History of clinically-significant VT was defined as symptomatic VT, cardiac arrest with documented VT/ventricular fibrillation or appropriate defibrillator shocks. A total of 21 explanted hearts were analyzed (VT=10, no VT=11) in a double-blind, case control study design. The molecular, cellular and histological features of adverse myocardial remodeling were assessed. Results: The two groups were closely matched in sex (male= 80% vs 72%), LVEF (20.8% vs 20.6%, p=0.6), LVAD use (4/10 vs 6/11, p=0.66), and optimal medical therapy. Explanted hearts from patients with VT showed greater hypertrophic changes based on...
ANTACIDS: THEIR EFFECT BY TITRATION AND WITHIN THE HUMAN STOMACH
Authors: Herbert C. Breuhaus, James B. Eyerly
Journal: Annals of Internal Medicine (1941)

Article1 June 1941ANTACIDS: THEIR EFFECT BY TITRATION AND WITHIN THE HUMAN STOMACHHERBERT C. BREUHAUS, M.D., JAMES B. EYERLY, M.D.HERBERT C. BREUHAUS, M.D.Search for more papers by this author, JAMES B. EYERLY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-12-2285 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOf the various forms of treatment used in peptic ulcer, acid neutralization therapy has held the most prominent position for over one hundred years. In the quest for a better antacid many substances have been tried but no ideal agent has been found. Many virtues have been attributed to these compounds but as far as is known their chief value lies in their acid reducing property. We have, therefore, made analyses of some of the more commonly used substances on a basis in which their neutralizing capacity by titration can be compared with their antacid property within the human stomach....References1. HOLLANDER F: The composition of pure gastric juice, Am. Jr. Digest. Dis. and Nutr., 1934, i, 319-329. CrossrefGoogle Scholar2. HOLLANDER F: The composition of gastric juice as a function of its acidity, Jr. Biol. Chem., 1934, civ, 33-42. CrossrefGoogle Scholar3. HOLLANDER F: What constitutes effective neutralization of gastric contents, Am. Jr. Digest. Dis., 1939, vi, 127. Google Scholar4. EYERLYBREUHAUS JBHC: A method of measuring acidity and protein digestion within the human stomach, Am. Jr. Digest. Dis., 1939, vi, 187-191. CrossrefGoogle Scholar5. EYERLY JB: The comparative pH values within the stomach, pylorus and duodenum in antacid therapy. (To be published.) Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication August 20, 1940.From the Gastro-Intestinal Departments of Presbyterian Hospital and Rush Medical College. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySynergy between polymer crystallinity and nanoparticles size for payloads releaseProlonged achlorhydria in duodenal ulcer from intramuscular administration of anticholinergic drugsA Study of AntacidsPeptic Ulcer in Man Part 5. A new Antacid, SCMC, made to meet requirements of Antacid Therapy. Clinical EvaluationMedical Applications of Adsorption and Ion Exchange MaterialsNocturnal Gastric Secretion in Normal and Duodenal Ulcer Patients on Various Forms of Therapy 1 June 1941Volume 14, Issue 12Page: 2285-2291KeywordsGastroenterology and hepatologyPeptic ulcersStomach ePublished: 1 December 2008 Issue Published: 1 June 1941 PDF downloadLoading ...
Abstract P1-07-26: Global analysis of the transcriptome in matched primary and metastatic tumours defines ER specific gene alterations
Authors: Damir Vareslija, Ailis Fagan, Jean McBryan, Patrick Buckley, Michael Farrell, Arnold DK Hill, Leonie Young
Journal: Cancer Research (2015)

Abstract The incidence of brain metastasis (BM) among women with metastatic breast cancer (MBC) is currently on the rise, and it is estimated that between 10-30% of patients diagnosed with breast cancer may also develop BM (Weil 2005). BM is considered a late complication in the clinical setting and is an infrequent occurrence even in mice studies that readily metastasise to other organs (Valiente 2014). While pre-menopausal status and negative estrogen receptor (ER) status are seen as main risk factors (Gil-Gil 2013), it is now recognised that BM is emerging as an increasing clinical problem across the various MBC subtypes. BM patients have very poor overall survival and as a result it is crucial to identify the factors that promote the survival and adaptation of breast cancer cells to allow them to colonise distant sites such as the brain. The ability to predict the BM potential could be of great clinical importance and in this study we decided to investigate the mechanisms underlying BM across the various MBC subtypes. To our surprise, in a cohort of breast cancer patients we found a comparable number of ER positive and ER negative BM. We established that ER positive patients (n=10) had a substantially longer disease latency period (median disease free survival (DFS) 36 months, range 8-85 months) in comparison to ER negative patients (n=8, HER2 positive, n=2, triple negative, n=6), (median DFS 24 months, range 9-60 months). To understand and elucidate the gene alterations required for successful colonisation of the brain we undertook RNAseq of sequential primary and brain metastatic tumours from ER positive (n=4) and ER negative (n=3) breast cancer patients. Significant elevations in gene expression were observed in the brain metastatic tumours in comparison to the matched primary. Though a large degree of patient heterogeneity was observed, common ER-specific metastatic pathways were identified. This study highlights the requirement of unique gene sets for the colonisation to the brain and that functional characterisation of the differentially expressed genes will enable the identification of novel molecular targets for prevention and treatment of breast cancer BM. Citation Format: Damir Vareslija, Ailis Fagan, Jean McBryan, Patrick Buckley, Michael Farrell, Arnold DK Hill, Leonie Young. Global analysis of the transcriptome in matched primary and metastatic tumours defines ER specific gene alterations [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-26.
Follow up at a nurse-led heart failure clinic after hospitalization, effects on morbidity, mortality and self-care behavior. Results from a randomized study
Authors: Anna Strömberg, Jan Mårtensson, Bengt Fridlund, Jan Erik Karlsson, Lars Åke Levin, Ulf Dahlström
Journal: Circulation (2002)

Follow up at a nurse-led heart failure clinic after hospitalization, effects on morbidity, mortality and self-care behavior. Results from a randomized study