tbuckley/cabot-search huggingface dataset:
406. rAAV-Mediated Expression of Wnt10b cDNA Prevents the Development of Obesity in DIO Rats
Authors: George Aslanidi, Glenn Philipsberg, Vadim Kroutov, Kenneth Lamb, Erik Kohlbrenner, Martha Campbell-Thompson, Glenn Walter, Philip J. Scarpace, Sergei Zolotukhin
Journal: Molecular Therapy (2006)

Wnt10b is a new recently described member of secreted type glyco-proteins family Wnt. It is classified as the canonical Wnt to activate the β-catenin-TCF pathway and regulates diverse developmental processes. The purpose of this study was to investigate long-term metabolic effects of the Wnt10b in diet-induced obese (DIO) rat model. Sustained expression was achieved by delivering mouse Wnt10b cDNAs via a viral vector. To this end, we have generated recombinant adeno-associated virus (rAAV) vector of serotype 1 encoding Wnt10b cDNAs by using baculovirus expression system. Vector was first tested on immortalized fibroblast cell line (3T3- L1) that differentiate to adipocytes recapitulating metabolic and endocrine functions of adipocytes in vivo. Cells were infected by rAAV1-Wnt10b or rAAV1-GFP (negative control) and than induced to differentiate by using the respective hormone cocktail. We have shown that rAAV-mediated Wnt10b completely blocked differentiation of 3T3-L1 fibroblasts to adipocyte in vitro. The long-term effect of rAAV-mediated Wnt10b on adipogenesis in vivo was tested upon peripheral injection in diet-induced obese (DIO) female rats fed high fat (60%) diet. We have shown that a single im injection of 1x1012 physical particles of rAAV1-Wnt10b resulted in sustained (up to 120 days) statistically significant (p=0.0000007) reduction in body weight (BW) accumulation with attendant reduction in hyperinsulinemia (p=0.0006) and triglycerides plasma level (p=0.0000009). This insulin-enhancing effect was substantiated by IP Glucose Tolerance Test (IP GTT), and was concomitant with the decreases levels of intramyocellular lipids (IMCLs) in the skeletal muscles shown by H-MRS. Distribution of white fat and reduction of visceral white fat pad was measured by MRI. Hormonal profiles were monitored using Enzyme-Linked Immunosorbent Assays (ELISA). The molecular mechanism of weight-reducing effect of transgene Wnt10b expression was found to be a Wnt10b downstream signal transduction inhibiting the expression of major adipogenic transcription factors, C/EBP-alpha and PPAR-gamma, as well as the adipocyte gene FABP-4. The study demonstrated a strong therapeutic effect of rAAV-mediated ectopic expression of Wnt10b on BW and insulin sensitivity. S.Z. is an inventor on patents related to recombinant AAV technology and owns equity in a gene therapy company (AGTC) that is commercializing AAV for gene therapy applications.
Skin Microbiology: Relevance to Clinical Infection
Authors: E. Dorinda Shelley
Journal: JAMA (1982)

This book reviews the enormous progress made in the field of skin bacteriology since 1965, largely stimulated by the important role of disabling skin infections in the Vietnam War and by the Food and Drug Administration review of over-the-counter (OTC) antimicrobial products. Concern at FDA over hexachlorophene toxicity in 1972 led to formation of the OTC Antimicrobial I Panel, which reviewed antimicrobial ingredients designed for daily use in hand washing, surgical scrubs, and first aid products. Panel recommendations led to major changes in effectiveness and toxicity testing, with emphasis on controlled clinical trials (randomized and double-blind with adequate numbers of patients) and specific new procedures such as the glove juice test, detailed in the text. Surprisingly, the book does not mention the OTC Antimicrobial II Panel (1974 to 1980), which continued the review of ingredients in OTC topical antibiotic, antifungal, and acne preparations. However, many of the issues faced by
Clinical Crossroads: Alcoholism and HIV Infection
Authors: Jonathan M. Zenilman, Anne M. Rompalo, Rosemary Jadack
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The Clinical Crossroads article entitled "A Man With Alcoholism and HIV Infection"<sup>1</sup>highlights several important public health issues. The case history described a patient with multiple episodes of high-risk sexual behavior, including anonymous unprotected sex and multiple previous sexually transmitted diseases. Despite having knowledge of human immunodeficiency virus (HIV) transmission modes, the patient describes unprotected sex with a partner whom he suspected of having Kaposi's sarcoma at the time. The patient also discusses how his alcoholism affected his ability to take appropriate precautions and reports that after his HIV diagnosis, he had repeated episodes of unprotected sexual activity associated with alcohol use. In the discussion, Dr U. and Dr Hyman only peripherally address the public health implications of this case, ie, the potential to transmit HIV to others. We raise three major concerns and submit that each of these present profound ethical dilemmas in which public
Treatment of Basal Cell Epithelioma by Laser Radiation
Authors: Leon Goldman, Robert G. Wilson
Journal: JAMA (1964)

TREATMENT of a relatively large basal cell epithelioma is not a remarkable feat. As far as we are aware, its cure by laser radiation has not yet been reported. The biomedical applications of the laser have included studies of the effect on malignancy in animals and man. These have been of investigative nature and in man no cures have been observed.<sup>1-7</sup> <h3>Report of a Case</h3> The patient was a 61-year-old Caucasian male who was admitted to the Dermatology Service of the Cincinnati General Hospital with multiple basal cell malignancies, some superficial, many nodular, some ulcerative and locally invasive up to 6 cm in diameter; they involved the scalp, nose, trunk, and arms. According to the patient, some had shown partial scarring but no lesions had cleared. Multiple biopsies revealed invasive basal cell malignancies. There was no evidence of cysts of the jaw or keratotic changes of the hands suggestive
A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms
Authors: Jeremy Hall, Heather C Whalley, Dominic E Job, Ben J Baig, Andrew M McIntosh, Kathryn L Evans, Pippa A Thomson, David J Porteous, David G Cunningham-Owens, Eve C Johnstone, Stephen M Lawrie
Journal: Nature Neuroscience (2006)
Abstract 1220: Investigation of the biological properties of human breast cancer in a nude rat model
Authors: Reza Bayat Mokhtari, Joris Tchouala Nofiele, Syed S. Islam, Herman Yeger, Hai-Ling Margaret Cheng
Journal: Cancer Research (2014)

Abstract Developing imaging technology for cancer diagnosis and treatment monitoring is best performed on larger pre-clinical animal models recapitulating tumor growth and metastasis more similar to that found in humans. Such models are amenable to morphological and functional imaging techniques at spatial resolutions appropriate for animal imaging and, translatable to human imaging. In comparison to mouse xenografts, rat models offer the advantages of clinical imaging capabilities, development of xenograft and metastatic models, in orthotopic sites. Human breast cancer cell lines MDA-MB-231 and MCF-7 show a variable take rate in mice, ∼ 68% incurring considerable cost and time. Having a more reproducible method is needed for breast cancer studies. Here we present evidence for development of a novel method in the immune-compromised nude rats. Spheroids grown under stem cell conditions were derived from human breast adenocarcinoma estrogen dependent (MCF-7, ZR-75-1) and independent (MDA-MB-231) lines, and xenografted in both subcutaneous and orthotopic (fat pad) sites in the nude rat. To verify that rat tumors could be studied in detail at spatial resolutions achievable on a clinical 3 Tesla scanner, high-resolution magnetic resonance imaging was performed to identify vascular, viable, and necrotic tumor regions. The breast cancer phenotype and was confirmed by immunohistochemistry for ER and HER2. Tumors were characterized with proliferation marker Ki67, vascularization by CD34 and VEGF, and presence of hypoxic regions by HIF1α. Our results indicated that spheroids from all three lines readily generated tumors independent of exogenous estrogen. MRI is an effective and sensitive method for investigating the biological behavior and vascularization of breast cancer. These findings offer a potential novel method for pre-clinical study and investigation of human breast cancer. Citation Format: Reza Bayat Mokhtari, Joris Tchouala Nofiele, Syed S. Islam, Herman Yeger, Hai-Ling Margaret Cheng. Investigation of the biological properties of human breast cancer in a nude rat model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1220. doi:10.1158/1538-7445.AM2014-1220
CFA with preserved lung volumes
Authors: N. STRICKLAND, J M B HUGHES;, M J DOHERTY, P M A CALVERLEY
Journal: Thorax (1998)

Doherty et al 1 seem confident of their ability to distinguish emphysematous spaces from large cystic spaces of honeycomb lung on the basis of a wall thickness on HRCT scanning of greater or less than 1 mm. In cryptogenic fibrosing alveolitis (CFA) we think this is difficult unless an assessment of function (with V/Q scanning or expiratory CT scans) is made at the same time.2 The situation is complicated by the ability of fibrosis in mixed emphysematous-fibrotic areas to support the airways and mitigate the expected gas trapping.

“Emphysematous” changes were …
Rapid Evolution and Gene-Specific Patterns of Selection for Three Genes of Spermatogenesis in Drosophila
Authors: Alberto Civetta, Sujeetha A. Rajakumar, Barb Brouwers, John P. Bacik
Journal: Molecular Biology and Evolution (2005)

Hybrid males resulting from crosses between closely related species of Drosophila are sterile. The F1 hybrid sterility phenotype is mainly due to defects occurring during late stages of development that relate to sperm individualization, and so genes controlling sperm development may have been subjected to selective diversification between species. It is also possible that genes of spermatogenesis experience selective constraints given their role in a developmental pathway. We analyzed the molecular evolution of three genes playing a role during the sperm developmental pathway in Drosophila at an early (bam), a mid (aly), and a late (dj) stage. The complete coding region of these genes was sequenced in different strains of Drosophila melanogaster and Drosophila simulans. All three genes showed rapid divergence between species, with larger numbers of nonsynonymous to synonymous differences between species than polymorphisms. Although this could be interpreted as evidence for positive selection at all three genes, formal tests of selection do not support such a conclusion. Departures from neutrality were detected only for dj and bam but not aly. The role played by selection is unique and determined by gene-specific characteristics rather than site of expression. In dj, the departure was due to a high proportion of neutral synonymous polymorphisms in D. simulans, and there was evidence of purifying selection maintaining a high lysine amino acid protein content that is characteristic of other DNA-binding proteins. The earliest spermatogenesis gene surveyed, which plays a role in both male and female gametogenesis, was bam, and its significant departure from neutrality was due to an excess of nonsynonymous substitutions between species. Bam is degraded at the end of mitosis, and rapid evolutionary changes among species might be a characteristic shared with other degradable transient proteins. However, the large number of nonsynonymous changes between D. melanogaster and D. simulans and a phylogenetic comparative analysis among species confirms evidence of positive selection driving the evolution of Bam and suggests an yet unknown germ cell line developmental adaptive change between these two species.
Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin–restricted miRNA antagonists of miR-27
Authors: Jennifer A. Young, Ka Ka Ting, Jia Li, Thorleif Moller, Louise Dunn, Ying Lu, Angelina J. Lay, Joshua Moses, Leonel Prado-Lourenço, Levon M. Khachigian, Martin Ng, Philip A. Gregory, Gregory J. Goodall, Anna Tsykin, Ilana Lichtenstein, Christopher N. Hahn, Nham Tran, Nicholas Shackel, James G. Kench, Geoffrey McCaughan, Mathew A. Vadas, Jennifer R. Gamble
Journal: Blood (2013)
ACSM's Essentials of Sports Medicine.
Authors: K. BOYD
Journal: Annals of the Rheumatic Diseases (1997)

ACSM’s Essentials of Sports Medicine. Edited by R E Sallis and F Massimino. (Pp 646; £50.00.) St Louis: Mosby, 1997. ISBN0-8151-0157-0.

To many, sports medicine is the treatment of injury in our Olympic and World Champions. Whereas in the United Kingdom this specialty is only starting to emerge in its own right, in other parts of the world, none more so than in the USA, it has been well established for over 25 years and encompasses much more than the care of elite athletes. It recognises the importance of physical activity for health, the benefits of exercise in the prevention and treatment of disease, and the management and rehabilitation of athletes of all abilities. The physician practising sports medicine …
UN delays decision on human cloning
Authors: Susan Mayor
Journal: BMJ (2004)

The United Nations has delayed plans to agree a convention on the cloning of human embryos and announced last week that a working group will be set up to develop a declaration—a much weaker device that would not impose a comprehensive ban on reproductive cloning—to be voted on in three months' time.

The recommendation comes after a meeting in October of the UN's sixth committee, which agrees legal issues, to consider two proposals on human cloning. The first proposal from Costa Rica, also supported by the United States, recommended a complete ban on both reproductive and therapeutic cloning. A second proposal from Belgium suggested a ban on reproductive cloning—which all 191 UN members oppose—but allowing member countries to …
Age Cutoffs for Bioprosthetic vs Mechanical Aortic Valve Replacement
Authors: Stuart J. Head, Ruben L. Osnabrugge, A. Pieter Kappetein
Journal: JAMA (2015)

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
Guanethidine and glucose tolerance in diabetics.
Authors: K. K. Gupta
Journal: BMJ (1968)

the present case is that the retinal changes are considerably larger and more clearly defined than those which have been observed in what one might usefully term "eclipse epidemics" of this condition.'It is pre- sumed that both the greater reduction of vision and the.more marked appearances in this particular case could well be due to the very prolonged gazing at the sun which his delusions appear to have prompted.This case fully underlines the dangers of sun-gazing and watching either when special solar phenomena are pending or for any other reason.I should like once again to reiterate the advice of Flynn' that for the lay public the simplest and safest way of inspecting the sun's disc is by use of the pinhole projection method.-Iam, etc., M.
Better communication is key to recruiting patients to trials
Authors: C. Shannon
Journal: BMJ (2003)

Recruiting enough patients to participate in a trial is one of the biggest challenges in clinical research, and typically just 40% of those approached agree to take part. Effective communication techniques may be the answer, investigators suggested at last week's annual conference of the National Institute for Clinical Excellence (NICE).

The prostate testing for cancer and treatment (PROTECT) trial, which is comparing surgery, radiotherapy, and monitoring for prostate cancer treatments, is one example of successful recruitment on a large scale. “When we started the study there was a lot of concern that this was a trial that couldn't be done,” said Professor Jenny …
Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T‐cell infiltrate and TH<sub>1</sub>‐type cytokine expression in the peri‐implantar tissue
Authors: P. Thomas, B. Summer, C. A. Sander, B. Przybilla, M. Thomas, T. Naumann
Journal: Allergy (2000)

Background: We report on a 37‐year‐old man without history of previous allergic disease who developed an aseptic intolerance reaction to a chromium‐cobalt alloy, with local discomfort, loosening, and absence of fracture healing. Both in vivo and in vitro allergoimmunologic diagnostic tests were performed. Methods: Patch testing was done with a European standard series. Specific serum IgE was measured by CAP‐FEIA. In addition to immunohistology (APAAP method), peri‐implantar tissue was further analyzed by PCR to determine T‐cell‐receptor‐γ rearrangement and thus the potential clonal (antigen‐driven) T‐cell repertoire. The actual tissue mRNA expression for IL‐4, IL‐6, and IFN‐γ was visualized by RT‐PCR. Results: Skin testing gave a delayed‐type reaction to dichromate. Specific serum IgE to natural rubber latex and grass pollen was found – but without clinical symptoms. Immunohistology revealed a monocytic and dense T‐cell infiltrate. The latter, instead of being random, showed an oligoclonal T‐cell receptor rearrangement. In addition, there was TH 1 ‐type mediator expression (IL‐6 and IFN‐γ, but not IL‐4). Conclusions: Skin test, examination of peri‐implantar tissue, and the prompt healing after replacement of the osteosynthesis material suggest an allergic reaction. PCR analysis of peri‐implantar tissue can further help to identify and understand allergy‐mediated implant intolerance reactions.
Michael William Leitrim Clements
Authors: D. Rapley
Journal: BMJ (2001)

Pioneer of cardiovascular gene therapy dies from a heart attack aged 53Jeffrey Isner opened up an entirely new field of revascularisation research using angiogenesis techniques to stimulate new blood vessel growth and bypass clogged vessels.At the time of Isner's death, his work was still considered visionary, yet investigational.Proof of principle had been demonstrated, but randomised trials were just getting under way.In 1994, Isner used a gene transfer technique to grow new blood vessels that could bypass damaged vessels in a patient with critical limb ischaemia and leg pain at rest.The technique delivered the protein vascular endothelial growth factor, or VEGF, through a balloon into the wall of the artery close to the blockage.The gene transfer technique was subsequently made "more straightforward, using intramuscular injection," according to Douglas Losordo, a coinvestigator with Isner at St Elizabeth's Hospital in Boston.By 1998, Isner's team performed the first procedures in the heart, injecting VEGF directly into the cardiac muscle through the chest wall.In 1999, Isner pioneered a catheter based approach.At the American Heart Association scientific sessions on 13 November 2001, two weeks after Isner's death, co-investigators reported his most recent research results.American Heart Association president David Faxon said that although a phase I trial of 19 patients using myocardial VEGF-2 gene transfer with a catheter showed "significant improvement in angina, exercise tolerance, imaging, and increased profusion, only safety-not efficacy-was
Rest of World Ready to Follow This Hemisphere's Approach to Eliminating Polio in Near Future
Authors: Teri Randall
Journal: JAMA (1991)

HEALTH officials in the Americas may have just diagnosed the last new case of poliomyelitis in the Western hemisphere, or may do so very soon. That is the word from the Pan American Health Organization (PAHO), after almost 6 years of an intensive vaccination program. The effort is part of the World Health Organization's (WHO's) commitment to eradicate polio from the globe by the year 2000—mankind's second attempt to rid the planet of a disease after successful eradication of smallpox. "We believe that we may be diagnosing the last cases [in the Americas] in the next few months," says PAHO official Ciro de Quadros, MD, MPH, director of the Regional Expanded Program on Immunization for the Americas. "Possibly, the last case has already been diagnosed." <h3>WHO Adopts Model Strategy</h3> De Quadros, who spearheaded the smallpox vaccination program in his native Brazil two decades ago, says that the experience gained in
Clinical and laboratory study of postvagotomy diarrhoea
Authors: G. G. Browning, K. A. Buchan, C. Mackay
Journal: Gut (1974)

Thirty-two patients with diarrhoea, on average four years following truncal vagotomy and drainage, were studied. A comparison was made with 24 patients without postvagotomy diarrhoea. The incidence of bacterial colonization of the upper small intestine was no different in the two groups, though patients with a gastroenterostomy had a significantly higher incidence than those with a pyloroplasty. There was a higher incidence of `anaerobic colonization9 in patients with diarrhoea, but statistical significance was not reached. Colonization was associated with significantly lower levels of gastric acid secretion. Though 13 patients with diarrhoea had an abnormal faecal fat excretion, no correlation could be found between this and the severity of the diarrhoea or bacterial colonization, either with an anaerobic or a coliform type flora. In patients with diarrhoea, no small intestinal mucosal abnormality was detected, the mean haematological and serum biochemistry values were within normal limits, and the body weight was similar to that before operation. Two patients with diarrhoea had abnormal haematological values five years following vagotomy and gastroenterostomy in association with `anaerobic colonization9 of the upper small intestine. As the incidence of haematological abnormalities after gastric surgery increases with time, colonized patients might merit particularly close clinical observation.
Glucagon Secretion in Acute and Chronic Pancreatitis
Authors: MARK DONOWITZ
Journal: Annals of Internal Medicine (1975)

Plasma pancreatic glucagon concentrations were determined in the basal state and after the infusion of alanine in 10 patients with acute pancreatitis (5 in an initial episode of pancreatitis), in 10 patients with chronic pancreatic insufficiency, and in 21 healthy controls. In acute pancreatitis, basal glucagon levels were nine times normal but were higher during the initial attack than with a history of previous attacks. The glucagon response to alanine was also increased threefold to fourfold in initial attacks. In contrast, after recovery from the initial attack of acute pancreatitis, during acute episodes of pancreatitis in patients with a history of previous attacks, and in patients with pancreatic insufficiency, alanine failed to elicit a consistent rise in plasma glucagon. The data suggest that hyperglucagonemia may contribute to the hyperglycemia of acute pancreatitis, particularly during the initial episode. Loss of alpha cell responsiveness to alanine provides a sensitive index of previous pancreatitis.