tbuckley/cabot-search huggingface dataset:
38. Morpholino Antisense Oligonucleotide Induced Exon Skipping Efficiently Restores Dystrophin Expression in the mdx Mouse
Authors: Dominic J. Wells, Caroline McCulley, Anna Graham, Ke Liu, Kim E. Wells
Journal: Molecular Therapy (2006)

Although antisense oligonucleotides (AO) have been used most commonly to inhibit gene expression, they can also be used to modify splicing of the primary transcript by targeting the exon splicing enhancers or the 3'/5' splice sites. Recent studies have shown that the morpholino chemistry is particularly useful as such AOs are not readily degraded. The mdx mouse is dystrophin deficient due to a premature stop codon in exon 23. Using an AO that targets exon 23, we have examined the longevity of exon skipping by RT-PCR and dystrophin transcript can still be detected 14 weeks after a single intramuscular injection of morpholino AO and dystrophin is clearly present at least 4 months post treatment. This is substantially longer than the expression seen in similar studies using a 2-O-methyl phosphorothioate AO. We have used similar techniques to examine the dose/volume relationship in preparation for clinical trials of this approach in Duchenne muscular dystrophy (DMD). As the diaphragm of the mdx mouse is the muscle that most closely resembles the pathology in DMD, exhibiting substantial fibrosis and fibre loss, we have used the diaphragm to test the effect of increased fibrosis in reducing AO uptake by the muscle fibres by treating mice at different ages. Delivery of AO in mice younger than 2 weeks can largely prevent the development of dystrophic pathology and treatment at later ages reduces the membrane fragility as determined by uptake of Evans Blue dye. These pre-clinical studies demonstrate the effectiveness of the morpholino based AO in inducing long-lived expression of dystrophin and this approach is now being taken forward to a UK clinical trial in DMD by the MDEX Consortium.
RENAL FUNCTION IN METHOTREXATE TREATED PSORIATICS
Authors: Cameron Kennedy, Harvey Baker
Journal: British Journal of Dermatology (1976)

Journal Article RENAL FUNCTION IN METHOTREXATE TREATED PSORIATICS Get access Cameron Kennedy, Cameron Kennedy Department of Dermatology, The London Hospital (Whitechapel), Whitechapel, London, E1 1BB Search for other works by this author on: Oxford Academic Google Scholar Harvey Baker Harvey Baker Department of Dermatology, The London Hospital (Whitechapel), Whitechapel, London, E1 1BB Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 6, 1 June 1976, Pages 702–703, https://doi.org/10.1111/j.1365-2133.1976.tb05172.x Published: 01 June 1976
Uncertainty about Postmenopausal Estrogen
Authors: Lee Goldman, Anna N.A. Tosteson
Journal: New England Journal of Medicine (1991)

Despite the important epidemiologic evidence provided by Dr. Stampfer and his colleagues in this issue of the Journal 1 of the apparently protective effect of postmenopausal estrogen-replacement therapy against coronary events in women, it is disappointing that we in medicine collectively have not made more progress toward resolving the clinical conundrum of postmenopausal estrogen replacement. After all, this is a therapy that may affect the development of the most common cause of death in women (coronary heart disease), one of the two leading causes of death from cancer in women (breast cancer), a major cause of morbidity in women (osteoporosis), and . . .
Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic anti-angiogenic gene therapy for fibrotic pancreatic tumors
Authors: Qixian Chen, Kensuke Osada, Takehiko Ishii, Makoto Oba, Satoshi Uchida, Theofilus A. Tockary, Taisuke Endo, Zhishen Ge, Hiroaki Kinoh, Mitsunobu R. Kano, Keiji Itaka, Kazunori Kataoka
Journal: Biomaterials (2012)
Knowledge Is Power
Authors: Anna Wald
Journal: JAMA Pediatrics (2013)

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
Hepatodiaphragmatic Interposition of Jejunum, Ileum, Cecum and Ascending Colon with Intestinal Obstruction
Authors: David Wyatt Aiken
Journal: New England Journal of Medicine (1958)

INTERPOSITION of intestine between liver and diaphragm was first noted1 not long after roentgen rays came into diagnostic usage. The condition has been extensively described and reviewed,2 3 4 5 6 and theoretical etiologic mechanisms of its occurrence thoroughly discussed.7 In Europe it has been called Chilaiditi's8 syndrome. It is known almost exclusively as a radiologic diagnosis involving colon far more often than small intestine, and is usually an unsuspected, incidental, asymptomatic finding. It occurred in approximately 1 of every 1000 abdominal roentgenograms in one series.9 Discussion of its causative factors, typical clinical and x-ray manifestations and differential diagnosis may be found in a . . .
How Cardiologists Learn About Echocardiography
Authors: PHIL R. MANNING
Journal: Annals of Internal Medicine (1979)

Mandatory continuing medical education, because of the need to validate participation, rewards classroom activities but not self-education. To determine if self-education is still a major study method for practicing physicians, we surveyed 158 cardiologists to learn how they first heard of, and continued their education in, echocardiography, a technique in which 81% of the physician-sample received no training in medical school, residency, or fellowship. Initial and continuing sources of information included professional journals and literature, meetings and conferences, discussion with colleagues, and courses. Professional journals ranked first in use; individual and group learning activities were used about equally by physicians. Recent legislation requiring validation of attendance may cause educators and legislators to ignore the self-learner. This study should remind educators and legislators that variations in learning style must be considered when planning and legislating approaches in continuing medical education.
The <i>LMP7-K</i> Allele of the Immunoproteasome Exhibits Reduced Transcript Stability and Predicts High Risk of Colon Cancer
Authors: Barbara Fellerhoff, Songhai Gu, Barbara Laumbacher, Andreas G. Nerlich, Elisabeth H. Weiss, Jürgen Glas, Reinhard Kopp, Judith P. Johnson, Rudolf Wank
Journal: Cancer Research (2011)

Abstract Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N1 = 112, N2 = 62; controls, N = 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR = 8.10, P = 1.10 × 10−11) and low risk with the LMP7-Q/Q genotype (OR = 0.10, P = 5.97 × 10−13). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-γ stimulation of colon carcinoma cell lines (N = 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t½ ≈ 7 minutes) compared with LMP7-Q (t½ ≈ 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-γ stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (&amp;lt;20%) changes. These results suggest that the presence of LMP7-K can reduce the formation of immunoproteasomes and thus peptide processing, followed by reduced peptide–HLA presentation, a crucial factor in the immune response against cancer. Cancer Res; 71(23); 7145–54. ©2011 AACR.
Statins, the cholesterol controversy, and preventive cardiology
Authors: Daniel Steinberg
Journal: The Lancet (2009)

One of the patients I see at my lipid clinic had his first anginal pains in 1965 when he was just 34 years old and serving in the US Army Air Corps. He had had florid xanthelasthma for many years and his total blood cholesterol at this time was a little over 9·3 mmol/L. The flight surgeon on duty reassured him that there was no necessary connection between blood cholesterol and heart disease. He was returned to active duty under no treatment. 2 years later, he had his first myocardial infarction and began intensive drug and diet treatment.
Observation and Simulation of the Circulation, Acid-Base Balance, and Response to CO <sub>2</sub> in Cheyne-Stokes Respiration
Authors: RAMON L. LANGE, JAMES T. BOTTICELLI, ROBERT P. CARLISLE, THEOFILOS J. TSAGARIS, JAMES D. HORGAN
Journal: Circulation (1968)

Circulatory, chemical, and ventilatory response factors in Cheyne-Stokes respiration (CSR) were studied by experimental procedures and by mathematical analysis. Hemodynamic, ventilatory, and blood gas patterns in 16 patients with heart disease and CSR (group A) and 16 patients with congestive heart failure (CHF) without CSR (group B) were compared. CO 2 and oxygen were administered to group A. The phenomena exhibited by patients with CSR were simulated by a mathematical model. The following conclusions were drawn: (1) Reduced blood flow and respiratory alkalosis were similar in both groups; (2) circulation times, lung to artery, were 29 sec greater than normal in patients with CSR but only 8 sec greater than normal in group B patients; (3) the abnormal CO 2 response in CSR, a reduction in threshold and sensitivity, was similar to that in CHF, suggesting that abnormal respiratory mechanics were responsible; (4) mathematical simulation of CSR was possible by appropriate prolongation of circulation time alone; the CO 2 response (reduction in threshold and sensitivity) had no significant effect on stability; (5) damping of oscillatory ventilation by CO 2 inhalation could be efficiently simulated; (6) CSR with cycle periods less than 50 sec suggests increased neural or chemoreceptor excitability, anemia, or hypoxemia as contributory factors, whereas longer periods suggest primary circulatory factors.
Sir Charles Tupper
Authors: W. Arthur Harland
Journal: New England Journal of Medicine (1959)

CHARLES Tupper, the son of a Baptist minister, was born in Amherst, Nova Scotia, in 1821. The family was poor, and money was borrowed to enable him to complete his medical education at Edinburgh University, where he was granted the diplomas of M.D. and L.R.C.P. After graduating he practiced in his home town for eleven years before entering the political arena. In 1855 he ran against and defeated Joseph Howe, the renowned leader of the Government in the colonial legislative assembly. He became a member of the Government two years later and by 1864 had been appointed premier.Tupper was . . .
Changes in plasma half-life and clearance of 3H-25-hydroxyvitamin D3 in patients with intestinal malabsorption.
Authors: A J Batchelor, G Watson, J E Compston
Journal: Gut (1982)

The plasma disappearance of intravenously administered tracer doses of tritium-labelled 25-hydroxyvitamin D3 (25OHD3) wa studied in six normal subjects and in 15 patients with intestinal malabsorption. The plasma half-life was significantly shorter and the clearance rate significantly greater in the group with malabsorption compared with the controls. One explanation for this increased elimination could be interruption of an enterohepatic circulation of 25OHD occurring in subjects with malabsorption and such a mechanism could account for the loss of endogenous vitamin D in these patients.
Time to assess alternatives to hydroxyethyl starch to use instead of 0.9% saline in fluid replacement
Authors: M. Cruickshanks, G. B. Drummond, S. Paterson-Brown, A. G. M. T. Powell
Journal: BMJ (2013)

Intravenous fluids containing hydroxyethyl starch have been withdrawn from use in acutely unwell patients in the UK following a recommendation by the Medicines and Healthcare Products Regulatory Agency (MHRA).1 This recommendation was based on findings by Haase and colleagues that hydroxyethyl starch compared with crystalloids or albumin was associated with an increased need for renal replacement therapy and blood transfusion …
Response related factors in recombinant interferon alfa-2b treatment of chronic hepatitis C.
Authors: R Perez, R Pravia, A Linares, M Rodriguez, J L Lombrana, A Suarez, S Riestra, C A Navascues, L Rodrigo
Journal: Gut (1993)

In an analysis of the clinical and laboratory variables that can influence the response to interferon alfa-2b treatment, 48 patients with chronic hepatitis C virus infection received interferon 5 million units (MU) subcutaneously three times weekly for eight weeks followed by 3 MU three times weekly for seven months. Response related factors on univariate analysis were found to be age &gt; 40 years, non-parenteral source of infection, pretreatment positive antinuclear antibodies (ANA), cirrhosis, and high serum iron, ferritin, gamma glutamyl transferase, and IgM. An independent predictive value (multivariate analysis) was also found for cirrhosis, ANA, serum iron, and ferritin. A baseline aspartate aminotransferase/alanine aminotransferase ratio of 0.5 and a striking increase during interferon treatment were associated with a complete response.
Paired tumor biopsy analysis and safety data from a pilot study evaluating Tremelimumab - a monoclonal antibody against CTLA-4 - in combination with ablative therapy in patients with hepatocellular carcinoma (HCC)
Authors: Austin Duffy, Sid P Kerkar, David E Kleiner, Susanna Ulahannan, Metin Kurtoglu, Oxana Rusher, Suzanne Fioravanti, Melissa Walker, William D Figg, Kathryn Compton, Aradhana Venkatesan, Nadine Abi-Jaoudeh, Brad Wood, Tim F Greten
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated down regulation of T cell activation. Both transcatheter arterial chemoembolization (TACE) and radiofrequency
THE RÔLE OF RENAL METABOLISM IN HYPERTENSION AND UREMIA
Authors: S. Rodbard, L. N. Katz
Journal: The Journal of Experimental Medicine (1941)

1. The chemical mediator of renal hypertension is rapidly destroyed by the metabolic activity of the normal kidney. The excretory function of the kidney plays little, if any, rôle in eliminating the mediator of hypertension. 2. If specific substances are responsible for the uremic syndrome, they are neither produced nor eliminated to any significant extent by the metabolic activity of the kidneys. The elimination of these postulated uremia-producing substances would have to be primarily dependent upon the excretory activities of the kidney. 3. No evidence was obtained to support the view that a unilateral ureterovenous fistula leads to "nephrotoxic" symptoms.
Association of Left Pleural Effusion with Pericardial Disease
Authors: James M. Weiss, David H. Spodick
Journal: New England Journal of Medicine (1983)

DURING cardiac failure unilateral pleural effusions tend to be right-sided, and bilateral pleural effusions tend to show more fluid on the right.1 We tested our impression that the opposite is true for pericarditis — i.e., that unilateral pleural effusions tend to be left-sided and bilateral effusions larger on the left — by reviewing patients with pericardial disease, who were subdivided to reflect pericardial and cardiac factors that may have been related to production of pleural fluid. Among 35 patients with pericardial disease and pleural effusion, we found that the pleural effusion was predominantly right-sided in only three and solely or . . .
Decrease of elevated N,N-dimethylglycine and N-methylglycine in human immunodeficiency virus infection during short-term highly active antiretroviral therapy
Authors: Markus P. Look, Reiner Riezler, Heiner K. Berthold, Sally P. Stabler, Kirsten Schliefer, Robert H. Allen, Tilman Sauerbruch, J[uuml ]rgen K. Rockstroh
Journal: Metabolism (2001)
Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1
Authors: Edmund R Hollis II, Ken Kadoya, Matthew Hirsch, Richard J Samulski, Mark H Tuszynski
Journal: Molecular Therapy (2008)

Adeno-associated virus (AAV) is frequently used for gene transfer into the central nervous system (CNS). Similar to adenovirus and rabies virus, AAV can be taken up by axons and retrogradely transported, resulting in neuronal gene expression distant from the injection site. We investigated the retrograde transport properties of self-complementary AAV (scAAV) serotypes 1-6 following peripheral injection. Injection of scAAV into either rat extensor carpi muscle or sciatic nerve resulted in detectable retrograde vector transport and reporter gene expression in spinal cord motor neurons (MNs). Serotype 1 resulted in the highest level of retrograde transport, with 4.1 ± 0.3% of cervical MNs projecting to the extensor carpi transduced following intramuscular injection, and 7.5 ± 3.1% of lumbar MNs transduced after sciatic nerve injection. In contrast to scAAV1, retrograde transduction with scAAV2 was undetectable following intramuscular injection, and was detected in only 0.81 ± 0.15% of MNs projecting to the sciatic nerve following intranerve injection. Furthermore, sciatic injection of single-stranded AAV1 required injection of tenfold higher numbers of viral particles for detectable transgene expression compared to scAAV1, and then only 0.91 ± 0.24% of lumbar MNs were transduced. Our data provide the basis for increased retrograde transduction efficiency using peripheral injections of scAAV1 vectors for therapeutic gene delivery to the spinal cord.
Behavioral methods and organic solvents: questions and consequences.
Authors: A Iregren
Journal: Environmental Health Perspectives (1996)

This paper reviews some illustrative examples of studies of human neurobehavioral effects from experimental as well as long-term occupational organic-solvent exposure. My objective is to present a selection of neurobehavioral solvent studies with the educational aim that we may hopefully learn from the early experiences of others. Some of the methodological problems encountered in these studies are discussed, as well as some reasons for the relative success of the work performed by certain Scandinavian research teams.
Cancer of the Lower Large Bowel
Authors: Isaac M. Webber
Journal: New England Journal of Medicine (1949)

THE intent of this survey is to present an investigation of facts pertinent to the care of 100 consecutive patients with cancer involving the lower segments of the large bowel and to offer an appraisal of the therapeutic effort employed in their management.This series includes both service and private patients at the Maine General Hospital, private patients at the Eye and Ear Infirmary and the Mercy Hospital, all of Portland, and one or more patients treated in each of six other institutions in outlying towns. It is obvious, then, that no one of these patients received all the advantages . . .
The Domain of General Internal Medicine: A Perspective from Trainees
Authors: Vineet Arora, Phil Hemstreet
Journal: Annals of Internal Medicine (2004)

Letters5 October 2004The Domain of General Internal Medicine: A Perspective from TraineesVineet Arora, MD, MA and Phil Hemstreet, MDVineet Arora, MD, MAFrom University of Chicago, Chicago, IL 60637, and University of Texas—Houston, Houston, TX 77030.Search for more papers by this author and Phil Hemstreet, MDFrom University of Chicago, Chicago, IL 60637, and University of Texas—Houston, Houston, TX 77030.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-7-200410050-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We applaud Dr. Larson and the Society of General Internal Medicine (SGIM) Task Force on the Domain of Internal Medicine on their report (1), which highlights several key problems with the training of future general internists. However, at a recent meeting of the American College of Physicians (ACP) Council of Associates, our group, composed of trainees in internal medicine, expressed concern over several issues that were not addressed.The addition of a fourth or “mastery” year for general internal medicine training without a substantial discussion of the current financial pressures facing trainees is potentially harmful to future ...Reference1. Larson EB. Health care system chaos should spur innovation: summary of a report of the Society of General Internal Medicine Task Force on the Domain of General Internal Medicine. Ann Intern Med. 2004;140:639-43. [PMID: 15096335] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Vineet Arora, MD, MA; Phil Hemstreet, MDAffiliations: From University of Chicago, Chicago, IL 60637, and University of Texas—Houston, Houston, TX 77030. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHealth Care System Chaos Should Spur Innovation: Summary of a Report of the Society of General Internal Medicine Task Force on the Domain of General Internal Medicine Eric B. Larson , and the Society of General Internal Medicine (SGIM) Task Force on the Domain of General Internal Medicine*The Domain of General Internal Medicine: A Perspective from Trainees Eric B. Larson , for the SGIM Task Force on the Domain of General Internal Medicine Metrics 5 October 2004Volume 141, Issue 7Page: 578KeywordsForecastingHealth careHospital medicineInpatientsOutpatientsSub-specialty care ePublished: 5 October 2004 Issue Published: 5 October 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...