tbuckley/cabot-search huggingface dataset:
721. Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy: From Cell Culture to Clinical Trial
Authors: Jignya Ashar, Terence Partridge, Qi L. Lu
Journal: Molecular Therapy (2006)

Duchenne muscular dystrophy (DMD) results from non-sense or frame-shifting mutations in the dystrophin gene. The majority of these mutations can be corrected by removal of one extra exon to create shortened, but in-frame transcripts and produce at least partially functional proteins. Earlier studies showed that antisense oligonucleotide (AON)-mediated splicing alteration can achieve specific skipping of targeted exon, providing the potential for the treatment of DMD. This promise was firmly established when we demonstrated that AON can specifically remove the mouse dystrophin exon 23 containing a nonsense point mutation and restore the functional levels of dystrophin protein in muscle via intramuscular administration. More recently, we further demonstrated that systemic delivery of AON can effectively restore dystrophin expression in body-wide muscles. These data have prompted much of the current enthusiasm for clinical trials with AONs. We also demonstrated that modifications of AON chemistry are critical for achieving therapeutical effect by antisense therapy. Morpholinos is one of the most effective chemistry for inducing functional levels of dystrophin in bodywide skeletal muscles with improved force generation. We have been examining several chemistries with various delivery systems using mdx mouse as an in vivo model system to search for more effective chemistry and clinically applicable delivery approaches to achieve long-term restoration of dystrophin expression. Individual human dystrophin exon has been selected for systematic screening of AON sequences to maximize the potential of antisense effect as a preparation for clinical trials. We are also developing animal models to select AON sequences for targeting individual human dystrophin exon and to examine the therapeutic capacity of exon skipping in vivo. In conclusion, our results have provides realistic hope for the treatment of a majority of DMD patients.
Abstract 2046: The hepatic miR-200/Zeb module is perturbed in the male Fischer rat following short term treatment with a carcinogenic dose of Phenobarbital
Authors: Costas Koufaris, Jayne Wright, Richard A. Currie, Nigel J. Gooderham
Journal: Cancer Research (2010)

Abstract Few studies have so far examined the role of microRNAs (miRNAs) in directing the adaptive or adverse responses of the liver following chemical carcinogen exposure. Nevertheless, significant evidence supports the importance of miRNAs in normal liver functioning and their dysregulation in diseased states. In this study we chose to look at the effect of Phenobarbital, a prototype rodent non-genotoxic hepatocarcinogen, on liver miRNAs of the male Fischer rat. The animals were exposed to either a carcinogenic (1000 ppm) or two non-carcinogenic (50 and 500 ppm) dietary doses of Phenobarbital for up to 90 days. Microarrays and quantitative Real-time PCR were then used to profile liver miRNA expression. Unsupervised hierarchical clustering separated the samples according to dose after 14 days, that is the carcinogenic dose of Phenobarbital resulted in a distinct miRNA profile. A number of miRNAs showed statistically significant changes in expression uniquely to the carcinogenic dose at 14 days. Prominent was miR-200b, which was specifically upregulated by the carcinogenic dose of Phenobarbital atfter 14 days, but not before then. Real-time PCR confirmed this upregulation of miR-200b and that it was maintained after 90 days exposure to Phenobarbital. Mir-200b is a member of the miR-200 family of miRNAs, which form part of a negative feedback loop with two protein targets: Zeb1 and Zeb2. Western blots confirmed that both proteins are downregulated specifically by the carcinogenic dose of Phenobarbital. This study demonstrates that carcinogenic doses of Phenobarbital cause distinct effects on miRNA expression compared to non-carcinogenic doses, specifically an alteration in the miR-200/Zeb module was observed. Importantly, others have reported perturbation of this module in the liver of rats following carcinogenic treatments with acetoaminofluorine and choline-deficient L-amino Acid Defined diet. Collectively these data suggest that the miR-200/Zeb module could be an important element in the response of the liver to chemical carcinogen exposure. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2046.
Progress in Medical Information Management
Authors: Roger A. Côté
Journal: JAMA (1980)

THE LAST 50 years have witnessed an explosion in the scientific advances available to the medical practitioner in his evaluation and treatment of the patient. The arrival of computer technology has helped to augment the physician's recall of myriad pieces of information to help him evaluate the data for diagnosis and treatment. Inherent in this process is the need for medicine to develop a standardized language for the classification of disease into general groups, as well as detailed schemas for the naming of signs, symptoms, diseases, and procedures. To be useful, the system needs to be completely integrated. We review the historical development of classifications for statistical purposes and the conceptual evolution of nomenclatures and discuss the new nomenclature-classification system called the Systematized Nomenclature of Medicine (SNOMED) . 1 Present and future requirements of the management of medical information will be presented, including SNOMED applications.  PART I  STATISTICAL MANAGEMENT: CLASSIFICATION VS
FDG PET/CT in Eosinophilic Esophagitis
Authors: Aisheng Dong, Yang Wang, Changjing Zuo
Journal: Clinical Nuclear Medicine (2013)

A 37-year-old man presented with left upper abdominal pain for 13 months. Laboratory examinations showed elevated peripheral eosinophils. Chest CT showed thickened wall of the entire esophagus. FDG PET/CT was performed showing diffuse FDG uptake in the thickened esophageal wall. Esophageal endoscopy showed pale and edematous mucosa. Histologic examination of the esophageal biopsy specimens revealed marked eosinophil infiltration of the mucosa. The clinical and pathologic findings were consistent with eosinophilic esophagitis (EoE). This case indicates EoE should be included in the differential diagnosis of abnormal FDG accumulation in the esophageal wall along with malignant and nonmalignant conditions.
Realities Not Myths
Authors: Richard M. Glass
Journal: JAMA (1985)

The Journalperformed a valuable service by publishing the full report of the American Medical Association Committee on Medicolegal Problems regarding the insanity defense,<sup>1</sup>along with the COMMENTARIES describing recommendations by the American Bar Association (ABA)<sup>2</sup>and the American Psychiatric Association (APA)<sup>3</sup>for reform of the insanity defense. Readers were provided with clear expositions of the AMA position favoring the substitution of a<i>mens rea</i>approach for the special defense of insanity and of the ABA and APA positions favoring a tightened insanity defense based on inability to appreciate the wrongfulness of one's conduct at the time of the offense. The real issues were addressed in those articles. Unfortunately, this is certainly not the case in Dr Borelli's COMMENTARY, "Abolition Not Reform."<sup>4</sup>The opinions expressed in that article do not actually deal with the difficult problems embodied in the insanity defense. Furthermore, those opinions present an
Klippel-Trenaunay-Weber Syndrome with Recurrent Pulmonary Embolism
Authors: NICHOLAS MIKULA, SHIV M. GUPTA, MATTHEW MILLER, SAMUEL FELDER
Journal: Clinical Nuclear Medicine (1991)

A man with Klippel-Trenaunay-Weber syndrome had worsening pulmonary hypertension secondary to recurrent multiple pulmonary embolism despite anticoagulation. Pulmonary thromboendarterectomy was done. However, the patient expired 10 days after surgery due to another bout of pulmonary embolism from his right arm or right chest wall.
Serial [I-123] B-CIT SPECT imaging in Parkinson's disease as a marker of disease progression
Authors: Rajesh Krishnamurthy, Kenneth Marek, Paul Hoffer, Robert Innis, John P. Seibyl
Journal: Clinical Nuclear Medicine (1997)

Krishnamurthy, Rajesh MD; Marek, Kenneth MD; Hoffer, Paul MD; Innis, Robert MD, PhD; Seibyl, John P. MD Author Information
Sex Habits: A Vital Factor in Well-Being
Authors: A. Buschke, F. Jacobsohn, Eden Paul, Cedar Paul, Gerard L. Moench
Journal: JAMA (1934)

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
AB0710 Igg4-related disease managed with mycophenolate: a single-centre experience
Authors: M. Andres, P. Vela, A. Begazo, E. Pascual
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IgG4-related diseases are rare fibroinflammatory processes rich in IgG4-positive plasma cells, which may involve any organ, leading to persistent infiltration, dysfunction and stenotic complications. Many aspects of this disorder (such as etiopathogenesis or optimal management scheme) are still to be elucidated. The low incidence of this condition hampers large control studies, so case series might be helpful in this context. <h3>Objectives</h3> To describe our experience dealing with IgG4-related disease in a single Spanish centre with special interest in connective tissue diseases <h3>Methods</h3> We underwent an audit of IgG4-related disease cases currently followed in our Department. Histopathological-proven disease based on currently accepted criteria [1] was required. Demographic, clinical, pathological, radiological, management and outcome features were recorded. <h3>Results</h3> We identified 3 patients with IgG4-related disease, two females and a male, whose ages were between 44 and 58 years. Clinical presentations were as retroperitoneal fibrosis, orbital pseudotumor and inflammatory abdominal aortic aneurism. The follow up in our department was 30, 3 and 1 month, respectively. No other systemic autoimmune disease was identified, but both females had autoantibody-negative thyroid disorders. Serum IgG4 levels were normal in all cases (median 83.7 mg/dL, normal &lt;140). <sup>18</sup>FDG-PET did identify a distant involvement previously undetected in the patient with retroperitoneal fibrosis, becoming negative after treatment. All patients required surgery at the onset: the patient with retroperitoneal fibrosis underwent ureterolysis plus external iliac artery bypass, the patient with orbital pseudotumor a resection due to malign exophtalmos, and the patient with inflammatory aortic aneurism resection plus aortoiliac bypass. After surgery, all patients received prednisone plus mycophenolate mofetil 2gr/day, associating with control of the inflammatory process in terms of clinical, imaging (<sup>18</sup>FDG-PET) and serum inflammatory markers. <h3>Conclusions</h3> IgG4-related disease is a recently characterised disorder, probably underdiagnosed, and with many aspects still to be clarified. In our small case series, prednisone plus mycophenolate seemed a promising management scheme for these patients. <h3>References</h3> Deshpande V. Mod Pathol. 2012; 25:1181-92. <h3>Acknowledgements</h3> To Dr Miguel Trigueros, pathologist, and our colleagues from Vascular Surgery department. <h3>Disclosure of Interest</h3> None Declared
Iron and coronary heart disease. Iron linked to immune activation.
Authors: G Weiss, G Reibnegger, C Murr, H Wachter, D Fuchs
Journal: BMJ (1993)

and greatly inhibit atherogenesis.Interactions in vivo between iron and low density lipoprotein are not well defined.The apparent lack of increased atherosclerosis in haemochromatosis may simply mean that modification of low density lipoprotein catalysed by iron is maximal or nearly maximal at a low level ofexcess iron.
3,4-Diaminopyridine in the Treatment of Lambert–Eaton Myasthenic Syndrome
Authors: Kathleen M. McEvoy, Anthony J. Windebank, Jasper R. Daube, Phillip A. Low
Journal: New England Journal of Medicine (1989)

Lambert-Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscle-action potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and dose-related. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert-Eaton myasthenic syndrome.
Colorectal Cancer Screening
Authors: Judith M. E. Walsh, Jonathan P. Terdiman
Journal: JAMA (2003)

Screening for colorectal cancer reduces mortality in individuals aged 50 years or older. A number of screening tests, including fecal occult blood tests, sigmoidoscopy, double-contrast barium enema, and colonoscopy, are recommended by professional organizations for colorectal cancer screening, yet the rates of colorectal cancer screening remain low. Questions regarding the quality of evidence for each screening test, whether screening for individuals at higher risk should be modified, the availability of the tests, and cost-effectiveness are addressed. Many potential barriers to colorectal cancer screening exist for the patient and the physician. Strategies to increase compliance for colorectal cancer screening are proposed.
Perinatal Determinants Among Children Who Later Develop IDDM
Authors: Troels Bock, Charlotte R Pedersen, Aage Vølund, Camilla S Pallesen, Karsten Buschard
Journal: Diabetes Care (1994)

The aim of this study was to investigate whether children who develop insulin-dependent diabetes mellitus (IDDM) differ in some aspects from a matched control group at the time of birth.We studied all children who were born in Denmark during the period 1973-1977 and admitted to a Danish hospital with a diagnosis of IDDM during 1978-1989. The study was conducted by combining two nationwide registries, The National Patient Registry and The Birth Registry.The criteria were fulfilled by 837 children. Data regarding the age of the parents, the number of previous pregnancies of the mother, the month of birth, and the birth weight and length of the children who developed IDDM were compared with the data of an age- and sex-matched control group of 837 children without IDDM. We did not detect any significant differences between the two groups with respect to the parameters studied.No differences in perinatal determinants could be demonstrated among Danish children who develop IDDM compared with children without diabetes.
Vaccination and rheumatoid arthritis
Authors: J Sibilia
Journal: Annals of the Rheumatic Diseases (2002)

Induction of rheumatoid arthritis by vaccination against hepatitis B—myth or reality?

Recently, medical and public interest in the safety of vaccination, particularly against hepatitis B, has been heightened by reports in medical journals and in the media of possible adverse effects, especially of suspected vaccination-induced autoimmune disorders. Although these suspected effects most commonly belong to the neurological area, a number of authors have published cases of rheumatic disease, notably rheumatoid arthritis (RA), following hepatitis B vaccination.1–10 This editorial does not aim to review the relationship between vaccination and autoimmune disorders, which has already been discussed in several recent and interesting papers,11–13 but to centre the discussion on the possible connection between hepatitis B vaccination and RA.

The rheumatic disorders described following hepatitis B vaccination are heterogeneous but can be divided into three groups. Firstly, transient conditions such as vasculitis, post-vaccinal arthritis or erythema nodosum might be due to the deposition of immune complexes containing viral antigen and anti-hepatitis B antibodies, as seen in some hepatitis B infections, or to hypersensitivity to components of the vaccine like thimesoral or yeast proteins.14,15 Recently, the VAERS (Vaccination Adverse Events Reporting System) database (from July 1990 to August 1999) reported that hepatitis B vaccination was associated with a number of potentially serious arthritic adverse reactions, particularly in the adult female population (female/male ratio = 4.45/1).16 Secondly, it was recently suggested that macrophagic myofasciitis might be induced by intramuscular injection of vaccines containing aluminium hydroxide such as hepatitis B vaccine.17 Thirdly, there are reports of the onset of chronic autoimmune disease and, in particular, of RA.

Several hypotheses can be put forward for the occurrence …
Some American driving licences double as organ donor cards
Authors: C. A Pierach
Journal: BMJ (1999)

Editor—Davidson’s idea of credit cards doubling as organ donor cards1 is good but not new: for years “Organ donor=yes” has been stated on the back of my driving licence in Minnesota. American driving licences are small plastic cards just like credit cards. The system works, yet it is most regrettable that not more people give the affirmative yes to the question of organ donation when they are asked every few years at renewal of their licences.
Longevity of men capable of prolonged vigorous physical exercise: a 32 year follow up of 2259 participants in the Dutch eleven cities ice skating tour.
Authors: J L van Saase, W M Noteboom, J P Vandenbroucke
Journal: BMJ (1990)

OBJECTIVE--To compare the long term survival of a group of athletes taking prolonged vigorous physical exercise to that of the general population. DESIGN--Follow up of a cohort of participants in the Dutch eleven cities ice skating tour (a race and recreational tour) over a distance of 200 kilometers. SETTING--Data on participation from the organising committee and data on mortality from all municipalities in The Netherlands. SUBJECTS--2259 Male athletes. MAIN OUTCOME MEASURES--Comparison of all cause mortality in male participants in the tour with that in the general population of The Netherlands. RESULTS--The standardised mortality ratio for all participants during 32 years of follow up was 0.76 (95% confidence interval 0.68 to 0.85), and 0.90 (0.48 to 1.44) for participants in the race, and 0.72 (0.60 to 0.86) for participants in the recreational tour who finished within the time limit. CONCLUSIONS--The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.
Non-malignant asbestos pleural disease.
Authors: G Hillerdal
Journal: Thorax (1981)

During a 10-year period (1970-79) all patients in Uppsala County found to have pleural changes related to asbestos exposure were followed. The lesions could be divided into four types: parietal pleural plaques, exudative pleurisy, thickening of the visceral pleura, and progressive pleural fibrosis. There were 891 cases. The most common type was parietal plaques, which was seen in 827 patients, some of whom later developed other changes. In 22 types exudation was proven radiologically, and in 84 more cases obliteration of the costo-phrenic angle was seen. The exudations almost all had a benign course, despite sometimes fairly large and bloody effusions. They were practically all symptom-free, being a surprise finding on chest radiography. Thickening of the visceral pleura can only be seen radiologically in the fissures and occurred in a few cases in addition to other changes. In a small group of more heavily exposed individuals, a progressive pleural fibrosis developed, sometimes after an initial effusion.
Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of β-catenin in the liver
Authors: Christine Ovejero, Catherine Cavard, Axel Périanin, Theodorus Hakvoort, Jacqueline Vermeulen, Cécile Godard, Monique Fabre, Philippe Chafey, Kazuo Suzuki, Béatrice Romagnolo, Satoshi Yamagoe, Christine Perret
Journal: Hepatology (2004)

To clarify molecular mechanisms underlying liver carcinogenesis induced by aberrant activation of Wnt pathway, we isolated the target genes of β-catenin from mice exhibiting constitutive activated β-catenin in the liver. Adenovirus-mediated expression of oncogenic β-catenin was used to isolate early targets of β-catenin in the liver. Suppression subtractive hybridization was used to identify the leukocyte cell-derived chemotaxin 2 (LECT2) gene as a direct target of β-catenin. Northern blot and immunohistochemical analyses demonstrated that LECT2 expression is specifically induced in different mouse models that express activated β-catenin in the liver. LECT2 expression was not activated in livers in which hepatocyte proliferation was induced by a β-catenin-independent signal. We characterized by mutagenesis the LEF/TCF site, which is crucial for LECT2 activation by β-catenin. We further characterized the chemotactic property of LECT2 for human neutrophils. Finally, we have shown an up-regulation of LECT2 in human liver tumors that expressed aberrant activation of β-catenin signaling; these tumors constituted a subset of hepatocellular carcinomas (HCC) and most of the hepatoblastomas that were studied. In conclusion , our results show that LECT2, which encodes a protein with chemotactic properties for human neutrophils, is a direct target gene of Wnt/β-catenin signaling in the liver. Since HCC develops mainly in patients with chronic hepatitis or cirrhosis induced by viral or inflammatory factors, understanding the role of LECT2 in liver carcinogenesis is of interest and may lead to new therapeutic perspectives. (Hepatology 2004;40:167-176.)