tbuckley/cabot-search huggingface dataset:
1065. AAV2 Vector-Delivered Myostatin Propeptide Improves Muscle Healing after Injury
Authors: Jinhong Zhu, Yong Li, Chunping Qiao, Xiao Xiao, Johnny Huard
Journal: Molecular Therapy (2006)

Skeletal muscle injuries are the most common injuries encountered in sports medicine. Muscle injuries can heal spontaneously through regeneration, but fibrosis impedes this process and results in incomplete functional recovery. We have demonstrated that TGF-β1 plays a significant role in both the initiation of fibrosis and the inducement of myofibrotic differentiation by myogenic cells in injured muscle. However, the recent identification of myostatin (MSTN), a member of the TGF-β superfamily, may yield new avenues for therapeutic intervention to improve muscle healing. MSTN is a potent negative regulator of muscle growth, and MSTN-deficient mice show dramatically increased skeletal muscle mass. We have found that the injured skeletal muscle of MSTN knockout (MSTN-/-) mice develops significantly less fibrous scar tissue and significantly larger regenerating myofibers than observed in normal wild-type (WT) control mice. We also found that MSTN stimulates proliferation and myofibrotic differentiation of fibroblasts in vitro. These results suggest that, like TGF-β1, MSTN may play a role in fibrosis. Myostatin propeptide (MPRO) inhibits MSTN's biologic activity by blocking the binding of MSTN to its receptor. In vivo overexpression of MPRO produces mice with increased muscle mass comparable to that observed in MSTN-/- mice. We hypothesized that use of MPRO in injured skeletal muscle would enhance muscle regeneration and inhibit fibrosis. In this study, we used an adeno-associated virus (AAV) vector to deliver the MPRO to myoblasts in vitro and direct injection of the virus to deliver the MPRO to the gastrocnemius muscle (GM) in vivo. In vitro, MPRO effectively neutralized MSTN and stimulated differentiation of C2C12 myoblasts. In contrast to uninfected C2C12 myoblasts, AAV2-MPRO-transduced myoblasts readily fused into larger myotubes containing numerous myonuclei. The addition of AAV2-MPRO led to a significant increase in the cells' fusion index in culture. We then injected the AAV2 vector carrying the MPRO gene into the GMs of adult BL6J mice; we injected the same amount of PBS into littermates as the control. Three weeks after AAV2 vector delivery, we lacerated both GMs of each mouse. Four weeks after vector injection, we observed larger-diameter regenerating myofibers in the GMs overexpressing MPRO than in the nontransduced GMs, although the difference was not significant. Masson's Trichrome histochemistry showed significantly less fibrous scar tissue in the AAV2-transduced GMs than in the control GMs. These findings are consistent with results from our previous studies showing that MSTN deficiency improves muscle healing after injury and show that the direct delivery of AAV2-MPRO into skeletal muscle is an effective and novel approach to improving muscle healing.
Implications of the Principle of Question Propagation for Comparative-Effectiveness and “Data Mining” Research
Authors: Mia Djulbegovic, Benjamin Djulbegovic
Journal: JAMA (2011)

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
High-dose-rate brachytherapy with a custom-surface mold to treat recurrent squamous cell carcinomas of the skin of the forearm
Authors: Marc S. Rudoltz, Ryan S. Perkins, Robert W. Luthmann, Todd D. Fracke, Tina M. Green, N.Fred Eaglstein, Lisa G. Hochman, Scot N. Ackerman
Journal: Journal of the American Academy of Dermatology (1998)
Effects of mycotoxins in health and disease
Authors: D. L. Sudakin
Journal: JAMA (1997)

To the Editor.  —In the Medical News & Perspectives article by Mr Marwick, 1 the threat of a toxic mold hazard associated with flooding in the Midwest underscores a much larger threat posed by mycotoxins. The Centers for Disease Control and Prevention report 2 noted numerous illnesses and deaths attributed the Stachybotrys atra mycotoxins in the United States as a relatively recent phenomenon. We have postulated that exposure to S atra explains the mystery surrounding the 10th plague mentioned in Exodus. 3   Unfortunately, literature on plant pathology and veterinary science is not routinely accessible through medical search engines, and the extent of human and animal mycotoxin pathology is largely unknown to the medical community. Mycotoxins are ubiquitous, extremely potent, biologically active toxins, which in trifling amounts cause numerous diseases in animals and humans. 4 Mycotoxins may be the purloined letter we have been looking for to explain other human disease
A PERIODICAL PAINFUL AFFECTION, BELIEVED TO BE LOCATED IN THE LIVER, ITS CAPSULE, OR BOTH, OR POSSIBLY AN IRRITATION OF THE CAPSULE OF GLISSON.
Authors: R. HARVEY REED
Journal: JAMA (1884)

Read in the Section on Practice of Medicine and Materia Medica of American Medical Association, May, 1884. Although the anatomy of the Capsule of Glisson was carefully pointed out by Dr. Francis Glisson in his work on "The Anatomy of the Liver" as early as the middle of the sixteenth century; and although occasionally ever since, medical writers have hinted at diseases of this tunic, yet after a review of many of their writings, and after comparing them with the condition we have designated as above, we are forced to conclude that it is a separate and distinct disease, readily recognizable from associate diseases of the liver, and meriting a distinct place of its own in the catalogue of hepatic maladies. <h3>DEFINITION.</h3> For the sake of brevity we will only use the term "Irritation of the Capsule of Glisson," to designate this disease which we believe to be a rheumatoid
Endogenous Retinoic Acid Signaling Colocalizes With Advanced Expression of the Adult Smooth Muscle Myosin Heavy Chain Isoform During Development of the Ductus Arteriosus
Authors: Melissa C. Colbert, Margaret L. Kirby, Jeffrey Robbins
Journal: Circulation Research (1996)

Abstract During fetal development, a specialized vessel, the ductus arteriosus, shunts blood from the pulmonary artery to the aorta, thus bypassing the lungs. The ductus differs primarily from the great vessels in that it is a muscular rather than an elastic artery, and the etiology of this differential development remains controversial. We present evidence that retinoic acid (RA) may contribute to the unique muscle phenotype of the ductus arteriosus. Using a transgenic mouse carrying an RA response element– lacZ transgene that expresses β-galactosidase (β-gal) in response to endogenous RA signals during embryonic and fetal development, we observe a strong β-gal signal in the ductus arteriosus. By immunofluorescence, this signal colocalizes with the expression of the adult-specific smooth muscle myosin heavy chain isoform, SM2. The β-gal signal is present throughout fetal development and persists in the neonate until the ductus arteriosus is completely closed. β-Gal–positive cells are first detected by immunofluorescence at 13.5 days postcoitum (dpc) in the mesenchyme surrounding the ductus. By 15.5 dpc, very intense β-gal staining localizes to the ductus arteriosus but is absent or minimal in the pulmonary trunk and aortic arch; by 17.5 dpc, the smooth muscle layers of the tunica media in the ductus arteriosus exhibit positive β-gal staining. Immunostaining with antibodies against smooth muscle myosins shows that, while SM1 is expressed in all embryonic vessels, SM2 is precociously expressed in the ductus arteriosus. Furthermore, SM2 expression can be detected in the ductus as early as 15.5 dpc. In the neonate, the β-gal signal persists in the smooth muscle layer of the ductus and immunostaining colocalizes with SM2 expression. These data suggest that RA may play a role in inducing and maintaining smooth muscle differentiation in the developing ductus arteriosus and may promote precocious expression of the adult vascular phenotype.
TRPC Channel Upregulation in Chronically Hypoxic Pulmonary Arteries
Authors: Philip I. Aaronson
Journal: Circulation Research (2006)

hronic alveolar hypoxia causes structural and functional changes in pulmonary arteries (PAs) leading to increased pulmonary vascular resistance, secondary pulmonary hypertension (SPH), and, as a possible consequence, right heart failure.These changes are likely to result, at least in part, from the altered expression of ion channels in pulmonary arterial smooth muscle cells (PASMCs), and recent reports indicate that an increase in the expression of TRPC (canonical transient receptor potential) channels in these cells may play an important role.What has not been evident, however, is the mechanism by which chronic hypoxia (CH) enhances TRPC channel expression in these cells.In this issue of Circulation Research, Wang and colleagues 1 now elegantly demonstrate that an increased expression of TRPC1 and TRPC6 in PASMCs during CH in mice and rats is mediated by the ubiquitous oxygen-sensitive transcription factor hypoxia-inducible factor 1 (HIF-1).
Treatment of leprosy
Authors: Diana N J Lockwood, Bhushan Kumar
Journal: BMJ (2004)

The evidence base for newer drug combinations and shorter regimens is weak 

Leprosy still poses major therapeutic challenges. We have effective antibiotics to cure the infection, but the immune mediated peripheral nerve damage can continue long after effective antimicrobial treatment has started, and patients continue to be stigmatised. Effective management should therefore include treatment of nerve damage and reactions, prevention of disability, and reduction of stigma. The regimens recommended by the World Health Organization of six or 24 months' multidrug treatment (rifampicin, dapsone, and clofazimine) produce good clinical responses and low rates of relapse. The long term outcome for shorter regimens and other drug combinations, however, is not known. Testing for recent nerve damage and treating it with steroids is essential. Dermatologists already have an important role in treating patients in the large Indian and Brazilian cities, and this is likely to increase as leprosy programmes are integrated into primary care.

The WHO recommended multidrug regimen of rifampicin, clofazimine, and dapsone has been used since 1982. It is highly effective, and more than 11.2 million patients have received it.1 2 Patients receive rifampicin 600 mg monthly, dapsone 100 mg daily, with clofazimine 300 mg monthly and 50 mg daily added in for patients with multibacillary leprosy. The clinical classification uses the number of skin lesions for grouping patients into paucibacillary (five or fewer lesions) and multibacillary (more than five lesions) leprosy.3 Where possible, …
Integrins in invasive growth
Authors: Cord Brakebusch, Daniel Bouvard, Fabio Stanchi, Takao Sakai, Reinhard Fässler
Journal: Journal of Clinical Investigation (2002)

Invasive growthInteractions between tumor cells and the ECM strongly influence tumor development, affecting cell proliferation and survival, as well as the ability to migrate beyond the original location into other tissues to form metastases.Many of these interactions are mediated by integrins, a ubiquitously expressed family of adhesion receptors.Integrins are essential for cell attachment and control cell migration, cell cycle progression, and programmed cell death, responses that they regulate in synergy with other signal transduction pathways.This large group of transmembrane proteins is formed from 18 α and 8 β subunits, which dimerize to yield at least 24 different integrin heterodimers, each with distinct ligand binding and signaling properties.With their extracellular domain, integrins can bind to different ECM molecules, such as collagens and laminins, or to cellular receptors, such as VCAM-1.Their intracellular domains connect directly or indirectly to the actin cytoskeleton, thus linking the cytoskeleton to the ECM.Integrins also serve as bidirectional signaling receptors, inducing changes in protein activities or gene expression in response to ligand binding, while also modulating adhesive affinity on the cell surface in response to changes in cellular physiology.Here, we describe how integrins affect migration, proliferation, and survival of both transformed and normal cells, and we discuss how they modulate invasive growth in vivo.Throughout, we stress that many of these functions are restricted to particular cell types and may be altered upon transformation.
REGENERATION OF THE THYROID GLAND AND THE PREVENTION OF RECURRENT GOITERS
Authors: J. EARL ELSE
Journal: JAMA (1927)

The prevention of recurrent goiter is an important problem in the treatment of thyroid disease. A review of patients seen complaining of recurrent goiter permits the following classification: (1) pseudorecurrences; (2) recurrence of goiter without symptoms, and (3) recurrence of goiter with symptoms. <h3>PSEUDORECURRENCES</h3> Pseudorecurrences are generally the result of (1) diagnostic error; (2) symptoms due to permanent lesions, and (3) insufficient operation. This paper will not deal with that group. <h3>RECURRENCE WITHOUT SYMPTOMS</h3> In the group of recurrences without symptoms are placed those patients who have a definite enlargement of the remaining thyroid without the symptoms of hyperthyroidism and a normal or subnormal basal metabolic rate. The following pathologic processes have been recognized: (1) colloid goiter, which is probably the most common form; (2) diffuse adenomatous goiter, and (3) true adenoma. Patients with a goiter of the true colloid type are relieved by desiccated thyroid. Goiters belonging in the
Nonelectronic vs Electronic Hemoglobin Techniques
Authors: Bernadine Paulshock
Journal: JAMA (1973)

To the Editor.—  The precision and reproducibility of clinical laboratory testing has been greatly increased by the introduction of electronic machinery to substitute for earlier laboratory methods. Nevertheless, not all medicine can be practiced in automated electronic enclaves, and there is still need for inexpensive and easy screening tests for common diseases. Even in medical centers where clinical laboratories boast sophisticated instruments for measuring hemoglobin, blood donors are often still screened for anemia by the copper sulfate technique. The solutions, however, must be meticulously prepared and frequently changed in order to maintain a reasonable degree of reliability.  The increasing emphasis on community health centers in medically and economically underprivileged areas makes the availability of a portable, inexpensive, and reasonably accurate method for detection of anemia very desirable, since anemia is common among the poor who are more often deficient in hemoglobin on a nutritional basis or victims of genetic hemoglobinopathies.
Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology
Authors: Mark Friedberg
Journal: JAMA (1999)

ContextRecent studies have found that when investigators have financial relationships with pharmaceutical or product manufacturers, they are less likely to criticize the safety or efficacy of these agents. The effects of health economics research on pharmaceutical company revenue make drug investigations potentially vulnerable to this bias.ObjectiveTo determine whether there is an association between pharmaceutical industry sponsorship and economic assessment of oncology drugs.DesignMEDLINE and HealthSTAR databases (1988-1998) were searched for original English-language research articles of cost or cost-effectiveness analyses of 6 oncology drugs in 3 new drug categories (hematopoietic colony-stimulating factors, serotonin antagonist antiemetics, and taxanes), yielding 44 eligible articles. Two investigators independently abstracted each article based on specific criteria.Main Outcome MeasureRelationships between funding source and (1) qualitative cost assessment (favorable, neutral, or unfavorable) and (2) qualitative conclusions that overstated quantitative results.ResultsPharmaceutical company–sponsored studies were less likely than nonprofit-sponsored studies to report unfavorable qualitative conclusions (1/20 [5%] vs 9/24 [38%]; P=.04), whereas overstatements of quantitative results were not significantly different in pharmaceutical company–sponsored (6/20 [30%]) vs nonprofit-sponsored (3/24 [13%]) studies (P=.26).ConclusionsAlthough we did not identify bias in individual studies, these findings indicate that pharmaceutical company sponsorship of economic analyses is associated with reduced likelihood of reporting unfavorable results.
PITYRIASIS RUBRA PILARIS IN IDENTICAL TWINS.
Authors: ERIK A. KNUDSEN
Journal: British Journal of Dermatology (1958)

British Journal of DermatologyVolume 70, Issue 1 p. 27-29 PITYRIASIS RUBRA PILARIS IN IDENTICAL TWINS. ERIK A. KNUDSEN, ERIK A. KNUDSEN Department of Dermatology, The Finsen Institute, Copenhagen, Denmark. (Chief: Professor Poul V. Marcussen, M.D.)Search for more papers by this author ERIK A. KNUDSEN, ERIK A. KNUDSEN Department of Dermatology, The Finsen Institute, Copenhagen, Denmark. (Chief: Professor Poul V. Marcussen, M.D.)Search for more papers by this author First published: January 1958 https://doi.org/10.1111/j.1365-2133.1958.tb13788.xCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume70, Issue1January 1958Pages 27-29 RelatedInformation
A framework for structural constraints on feature creation
Authors: Scott A. Huettel, Gregory R. Lockhead
Journal: Behavioral and Brain Sciences (1998)

We address two major limitations of Schyns et al. First, we clarify their concept of “features” by postulating several levels for processing. The composition of the feature set at each level determines the set at the next higher level, following simple structural guidelines. Second, we show that our proposed framework reconciles feature-creation and fixed-feature approaches.
High incidence of left atrial appendage thrombus in end-stage renal disease patients receiving maintenance hemodialysis
Authors: Masato Nishimura, Tetsuya Hashimoto, Hiroyuku Kobayashi, Toyofumi Fukuda, Koji Okino, Noriyuki Yamamoto, Toshihiko Ono
Journal: Journal of the American College of Cardiology (2003)
Abstract A89: Sulfated polysaccharides from marine brown alga alleviate pancreatic cancer metastasis
Authors: Caroline R. Delma, Somasundaram S. Thirugnanasambandan, Guruprasad Srinivasan, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan
Journal: Cancer Research (2013)

Abstract Pancreatic cancer is one of the most deadly cancers with a five year survival rate of less than six percent. The poor prognosis can be attributed to the fact that more than three fourth of the patients have metastasis at the time of diagnosis. In view of the increasing evidence that sulfated polysaccharides attenuate tumor invasion, we attempted to evaluate the anti-metastatic potential of sulfated polysaccharide fractions from a marine brown alga, Turbinaria conoides in pancreatic cancer. Exposure of human pancreatic adenocarcinoma cells (MiaPaCa-2, Panc-1, BxPC-3 and Panc-3.27) to partially purified polysaccharide fractions showed a negative regulation of both the transcriptional activation (QPCR) and cellular expression (immunoblotting) of adhesion molecules, Mucin-16, E-Selectin and metastasis efficiency modifying SPA 1 and Dnmt3b. All encompassed, transcriptional profiling pertaining to tumor invasion and metastasis (QPCR profiling) revealed cell-type unique, yet comprehensive inhibition, including 62, 65, 64 and 51 of 93 transcripts in Mia PaCa-2, Panc-1, BxPC3 and Panc-3.27 cells, respectively. Extracellular matrix metalloproteinases MMP-2 and MMP-9, which play a significant and definite role in the invasion and metastasis of pancreatic cancer were completely muted as evidenced by reduced activity (by gelatin zymography) and secretion (by immunoblotting) in cells exposed to all fractions. Relatively, fraction V showed robust inhibitory potential in this setting. Together, these data suggest that fractions of sulfated polysaccharides, specifically fraction V, may serve as a potential drug deliverable to alleviate pancreatic cancer metastasis. This study prompts us to investigate further the active constituents in the sulfated polysaccharide fraction and their target binding affinity, (here in this case, to MUC16 and/or MMPs) and their mode of signal transduction. These in vitro studies and studies testing its efficacy in an in vivo setting are currently in process in our laboratory. Citation Format: Caroline R. Delma, Somasundaram S. Thirugnanasambandan, Guruprasad Srinivasan, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Sulfated polysaccharides from marine brown alga alleviate pancreatic cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A89.