tbuckley/cabot-search huggingface dataset:
Presence of a Latent Mitochondrial Targeting Signal in Gene on Mitochondrial Genome
Authors: M. Ueda, M. Fujimoto, S.-i. Arimura, N. Tsutsumi, K.-i. Kadowaki
Journal: Molecular Biology and Evolution (2008)

Organelles, such as mitochondria and chloroplasts, are derived from endosymbionts. Gene transfer events from organelles to the nucleus have occurred over evolutionary time. In the case that a transferred gene in the nucleus needs to go back to the original organelle, it must obtain targeting information for sorting its protein to that organelle. Here, we reveal that the genes for the ribosomal proteins L2 and S4 in the Arabidopsis thaliana mitochondrial (mt) genome contain information for protein targeting into the mitochondria. Similarly, the genes for the ribosomal proteins L2 and S19 in the Oryza sativa mt genome contain information for protein targeting into mitochondria. These results suggest that targeting information already existed in each gene in the plant mt genome before the transfer event to the nucleus occurred. We provide new insights into the timing of the appearance of targeting signals in evolution.
Muscle Function Recovery in Golden Retriever Muscular Dystrophy After AAV1-U7 Exon Skipping
Authors: Adeline Vulin, Inès Barthélémy, Aurélie Goyenvalle, Jean-Laurent Thibaud, Cyriaque Beley, Graziella Griffith, Rachid Benchaouir, Maëva le Hir, Yves Unterfinger, Stéphanie Lorain, Patrick Dreyfus, Thomas Voit, Pierre Carlier, Stéphane Blot, Luis Garcia
Journal: Molecular Therapy (2012)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting from lesions of the gene encoding dystrophin. These usually consist of large genomic deletions, the extents of which are not correlated with the severity of the phenotype. Out-of-frame deletions give rise to dystrophin deficiency and severe DMD phenotypes, while internal deletions that produce in-frame mRNAs encoding truncated proteins can lead to a milder myopathy known as Becker muscular dystrophy (BMD). Widespread restoration of dystrophin expression via adeno-associated virus (AAV)-mediated exon skipping has been successfully demonstrated in the mdx mouse model and in cardiac muscle after percutaneous transendocardial delivery in the golden retriever muscular dystrophy dog (GRMD) model. Here, a set of optimized U7snRNAs carrying antisense sequences designed to rescue dystrophin were delivered into GRMD skeletal muscles by AAV1 gene transfer using intramuscular injection or forelimb perfusion. We show sustained correction of the dystrophic phenotype in extended muscle areas and partial recovery of muscle strength. Muscle architecture was improved and fibers displayed the hallmarks of mature and functional units. A 5-year follow-up ruled out immune rejection drawbacks but showed a progressive decline in the number of corrected muscle fibers, likely due to the persistence of a mild dystrophic process such as occurs in BMD phenotypes. Although AAV-mediated exon skipping was shown safe and efficient to rescue a truncated dystrophin, it appears that recurrent treatments would be required to maintain therapeutic benefit ahead of the progression of the disease.
Patients Leaving Emergency Departments Without Being Seen by a Physician
Authors: Barron H. Lerner
Journal: JAMA (1992)

<h3>To the Editor.</h3> —I read with great interest your two recent articles<sup>1,2</sup>on patients leaving the emergency department prior to receiving care. While the articles dealt thoroughly with the emergency department's complex role in treating patients who lack other health care providers, they make little mention of emergency department use by patients who already have physicians either inside or outside the institution. In my experience at one urban teaching hospital, I found that many such patients, without any acute problems, often came to the emergency department for what amounted to routine evaluation of chronic ailments. In some cases they had been unable to contact their regular health care provider; at other times, they hadn't tried. Needless to say, the emergency department staff wasted much time reviewing often complex medical histories and trying to contact these patients' regular physicians. In most instances, the emergency physician would simply refer them back
Nonaggressive Evaluation in Coronary Artery Disease.
Authors: Samuel Zoneraich
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Nonaggressive Evaluation in Coronary Artery Disease.Samuel Zoneraich, M.D., Olga Zoneraich, M.D.Samuel Zoneraich, M.D.Search for more papers by this author, Olga Zoneraich, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-782_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn easy and harmless method of improving diagnostic precision and evaluating cardiac function and prognosis was used in a prospective cardiographic investigation of 200 hospitalized patients with coronary artery disease. Ninety patients had had one previous episode of myocardial infarction and only angina pectoris on admission. Twenty-eight had had one or two myocardial infarctions in the past and suffered a new infarction. Forty-eight suffered their first myocardial infarction on admission, and 34 complained of repeated bouts of angina pectoris.Simultaneous use of four cardiographic techniques: phonocardiography, apexcardiography, kinetocardiography, and carotid pulse yield meaningful results, even in situations where clinical examination... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Queens, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySeismocardiography is not a new termAuscultation and Phonoarteriography for Detecting Vascular Murmurs in Thyrotoxicosis and Brain DiseasesComputerized system for noninvasive techniques 1 May 1970Volume 72, Issue 5Page: 782-782KeywordsAnginaHeart diseasesHeart rateInfarctionMyocardial infarctionStable coronary artery disease Issue Published: 1 May 1970 PDF downloadLoading ...
Patient-Centered Medical Homes Offer a Model for Better, Cheaper Health Care
Authors: Mike Mitka
Journal: JAMA (2012)

nated from wild nonhuman primate and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat, and rat. Pathogen screening identified retroviruses (4 SFV strains), herpesviruses (cytomegalovirus and lymphocryptovirus), or both in 12 nonhuman primate tissue samples. “Because most emerging infectious diseases of humans are originating in animals, it is of concern that even in this small number of samples from a limited number of animal species, it was possible to identify retroviruses and herpesviruses of potential concern for human populations,” said Gerald Keusch, MD, who was not involved with the research. Keusch, a professor of medicine and international health at Boston University, cochaired the 2009 surveillance and response report with Pappaioanou. None of the samples contained SIV or STLV, which have adapted to humans and spread as HIV and human T-lymphotropic virus (which is capable of causing leukemia, lymphoma, and neurologic disease), respectively; however, SIV and STLV are often present in specimens at bushmeat markets and in hunted nonhuman primates. None of the rodent samples carried viruses: all were negative for leptospira, anthrax, herpesviruses, filoviruses, paramyxoviruses, coronaviruses, flaviviruses, and orthopoxviruses. Broader surveillance is needed to expand the study’s findings, which only begin to paint a picture of the potential risks of imported wildlife products and do not address live wildlife. “We need more and smarter surveillance of the wildlife trade, more control over what is being transported across national boundaries, more and stricter law enforcement measures to stop individuals involved in the business, and better and more meaningful ways to inform the public about the inherent dangers in a believable manner,” said Keusch. “In terms of global spread of infectious diseases, wildlife may be the mosquitoes of the 21st century: effective, elusive, and damned hard to stop.”
Experiments in Plant Hybridisation
Authors: C. A. Clarke
Journal: BMJ (1965)

So long as we insist on judging students by their success in passing examinations it is the bounden duty of teachers, despite the exhortations of the highbrows, to direct their teaching toward this end.The English plan of medical instruction, with its emphasis on " clerking and dressing," on casual ward rounds, and on routine duties in wards and out- patient departments, may have other virtues but certainly fails to give systematic teaching.
Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Androgen-Independent Prostate Cancer
Authors: Michael Stanbrough, Glenn J. Bubley, Kenneth Ross, Todd R. Golub, Mark A. Rubin, Trevor M. Penning, Phillip G. Febbo, Steven P. Balk
Journal: Cancer Research (2006)

Abstract Androgen receptor (AR) plays a central role in prostate cancer, and most patients respond to androgen deprivation therapies, but they invariably relapse with a more aggressive prostate cancer that has been termed hormone refractory or androgen independent. To identify proteins that mediate this tumor progression, gene expression in 33 androgen-independent prostate cancer bone marrow metastases versus 22 laser capture–microdissected primary prostate cancers was compared using Affymetrix oligonucleotide microarrays. Multiple genes associated with aggressive behavior were increased in the androgen-independent metastatic tumors (MMP9, CKS2, LRRC15, WNT5A, EZH2, E2F3, SDC1, SKP2, and BIRC5), whereas a candidate tumor suppressor gene (KLF6) was decreased. Consistent with castrate androgen levels, androgen-regulated genes were reduced 2- to 3-fold in the androgen-independent tumors. Nonetheless, they were still major transcripts in these tumors, indicating that there was partial reactivation of AR transcriptional activity. This was associated with increased expression of AR (5.8-fold) and multiple genes mediating androgen metabolism (HSD3B2, AKR1C3, SRD5A1, AKR1C2, AKR1C1, and UGT2B15). The increase in aldo-keto reductase family 1, member C3 (AKR1C3), the prostatic enzyme that reduces adrenal androstenedione to testosterone, was confirmed by real-time reverse transcription-PCR and immunohistochemistry. These results indicate that enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets. (Cancer Res 2006; 66(5): 2815-25)
Morris Fishbein Fellowship in Medical Journalism
Authors: Marjorie Fishbein Clavey
Journal: JAMA (1977)

<h3>To the Editor.—</h3> My father would have been really delighted with the "Morris Fishbein Fellowship in Medical Journalism." I extend my thanks to the House of Delegates for their wonderful memorial to my Daddy! As some readers may know, on Dec 23, just 87 days after Daddy died, my mother died, too. She was so much a part of everything Daddy did that I wish it were possible to have a fellowship for doctors' wives on how to spend 62 years together happily.
Mechanism of selective epicardial activation delay during acute myocardial ischemia in dogs.
Authors: A Arenal, C Villemaire, S Nattel
Journal: Circulation (1993)

BACKGROUND Previous studies have shown that acute myocardial ischemia in the dog results in much greater activation delays in epicardial than endocardial tissue. These results have been interpreted to indicate enhanced sensitivity of epicardial conduction properties to acute ischemia. This study was designed to test the hypothesis that the ischemic epicardial activation delay during supraventricular rhythms is due to slow conduction across the ischemic myocardial wall prior to epicardial activation and not to enhanced epicardial conduction slowing per se. METHODS AND RESULTS Changes in epicardial and endocardial activation were measured with transmural decapolar needle electrodes during successive 5-minute left anterior descending coronary artery (LAD) occlusions separated by 30-minute reperfusion periods. Occlusions were performed during left atrial pacing, right ventricular pacing with a stimulating electrode located along the longitudinal axis of epicardial fiber orientation in the ischemic zone, or left ventricular pacing in nonischemic tissue located on a line transverse to fiber orientation in the ischemic zone. During both atrial and left ventricular pacing, activation in the ischemic zone began in the endocardium. Epicardial activation resulted from transmural conduction and was markedly delayed compared with endocardial activation during acute myocardial ischemia. During right ventricular stimulation, the ischemic zone epicardium was activated via longitudinal epicardial conduction, and its activation was only slightly delayed by acute ischemia. Epicardial activation mapping was used to assess ischemia-induced changes in longitudinal epicardial conduction velocity and to compare them with changes in transmural velocity during atrial or left ventricular pacing. Longitudinal conduction in the ischemic epicardium was slowed by 13 +/- 4% (mean +/- SE) relative to preischemic control values in contrast to transmural conduction, which was slowed 50 +/- 4% by LAD occlusion during atrial pacing and 49 +/- 5% during left ventricular pacing (both P &lt; .001 versus longitudinal epicardial conduction). Transmural activation studies showed that the midmyocardium is the site of most of the ischemic activation delay during transmural propagation. CONCLUSIONS Epicardial activation is more delayed than endocardial by acute ischemia during supraventricular rhythms in dogs because of slowed conduction across the myocardial wall, not because of enhanced sensitivity of epicardial conduction to depression by acute ischemia.
Jejunal Biopsy in Malabsorptive Disorders of the Adult
Authors: R. H. Girdwood, I. W. Delamore, A. W. Williams
Journal: BMJ (1961)

MEDICA BJOscURNAL3 9 of weakness.Dexamethasone, on the other hand, appeared to favour weight gain and in some cases development of acute Cushingoid changes.Similar observations have been made by others (Falliers and Bukantz, 1959; Friedlaender and Friedlaender, 1959; Neustadt, 1959; Stresemann, 1959).Occasionally patients appeared to respond more favourably to one particular steroid than to others.Though most of the patients in this series were thought to have responded satisfactorily to steroids while under observation as in-patients or to repeated short courses in out-patients, the failure rate of long- term treatment is high (28%).This may in part be due to the cautious selection of patients who, with one exception, were severely incapacitated and who were regarded as having a poor expectation of life.Arnoldsson (1958) reported the persistence of moderate- lo-severe asthma in 20.1% of 144 cases treated with steroids, and Phear et al. (1960) reported poor results in 12% and moderate improvement in 10% of 50 cases.Though reasons for failure, including infection of the respiratory tract, organic disease of the lungs, severe emotional stress, or psychopathic personality, may often be detected, in some cases no satisfactory explanation can be found.Investigation of respiratory function showed that even those who had done best were seldom restored completely to normal.Lowell et al. (1953) have made similar observations.In assessing the effect of treatment it is important to remember that relief of symptoms does not necessarily imply restoration of normal respiratory activity.Although serious side-effects are few it is still too early to assess the final effects of steroid therapy when continued for many years. SummaryShort courses of steroids given in tapered doses over eight days are often effective in controlling exacerbations of asthma, though relapses are common.Long-term steroid therapy may in some cases be maintained with continued benefit for a number of years.If such treatment is terminated after six months or more the patient shows a tendency to relapse severely and sometimes fatally.Particularly careful supervision is therefore required during the ensuing months.The newer range of modified steroids, though more potent on a weight-for-weight basis, have little advantage over prednisolone.We acknowledge with thanks the advice of Mr.
BLASTOMYCOSIS IN AN INFANT.
Authors: J. B. KESSLER
Journal: JAMA (1907)

This is a peculiar disease, from a geographic standpoint. Its home so far seems to be confined to America, and only in a few localities, largely in the Mississippi valley, if we also include the city of Chicago. The forms on the Pacific coast seem to differ from those found in other localities in the United States and are named protozoic and coccidioidal. In cases of protozoan infection the organism develops by endogenous spore formation and not by budding, while in blastomycosis the only way of development in the tissue is by budding. The cultures also differ somewhat from those obtained in blastomycosis. The first case reported from Boston was in the latter part of 1906. There were no recognized cases in England up to 1903; a doubtful one was reported from Madrid the same year. I have seen three cases in the past eight years, one of them somewhat
THE ABSORPTION OF DRUGS
Authors: CARY EGGLESTON
Journal: JAMA (1923)

Most of the drugs employed as therapeutic agents depend on their entrance into the blood stream, either in sufficient concentration or in sufficient total quantity, for the development of their therapeutic actions. Adequate knowledge of their absorption is therefore of fundamental importance to the development of a rational drug therapy. Modern textbooks on pharmacology, however, while discussing in detail the actions of each of the more important drugs, generally pass over the problems of their absorption with only a word or two, if, indeed, they mention them at all. Books and articles on therapeutics are usually even worse offenders. In fact, there seems to be a more or less general assumption that if a drug is soluble in water it will be absorbed in a satisfactory manner when introduced into the alimentary canal or injected into the subcutaneous or intramuscular tissues. A few seem to take the opposite stand, namely,
Drug users' views on general practitioners
Authors: R. Ireland, I. Mcleod
Journal: BMJ (1995)

Unreliability ofreports of hypoglycaemia by diabetic patientsHundreds ofcase reports suggest a problem with human insulin EDrroR,-Simon Heller and colleagues' study of the unreliability of diabetic patients' reports of hypoglycaemia' was conducted after my suggestion to John Ward, one of the authors, that both patients' and their partners' views about loss of awareness with human insulin were important.I am therefore surprised that I was not given an acknowledgement.The study confirms my belief that patients' and their carers' views are important.The authors' suggestion that the validity of previous studies looking into loss of awareness of hypoglycaemia with human insulin is questionable is an understatement.Most scientific studies into loss of hypoglycaemic awareness with human insulin have not included partners as a core factor in the research.2-4Now that the validity of previous studies looking at problems experienced with human insulin have been questioned we must rely on the hundreds of case reports about human insulin from patients and their carers.These suggest that many patients have problems when using human insulin.The patients and their carers confirm an improvement when the patients change to animal insulin.
Arterial blood gas tensions during upper gastrointestinal endoscopy.
Authors: P J Whorwell, C L Smith, K J Foster
Journal: Gut (1976)

Arterial blood gas tensions were measured before and during upper gastrointestinal endoscopy, with (group I) and without (group 2) sedation with intravenous diazepam. There was a highly significant fall in the PaO2, which occurred in both groups and was therefore not attributable to diazepam. Measurement of FEV, and FVC before endoscopy had no predictive value for those patients whose PaO2 fell the most.
Immunopharmacology
Authors: Mark Ballow
Journal: JAMA (1997)

Immunopharmacology has changed dramatically over the past 25 years. Although a variety of traditional nonspecific immunosuppressive drug therapies are available for the treatment of autoimmune disease and organ transplantation rejection, with advances in cell biology and monoclonal antibody technology, a highly specific antibody can be engineered to cell surface determinants on immune cells or tumors or to neutralize inflammatory and immune mediators from an immune response. Many of these modalities are still in early phases of study for the treatment of autoimmune disease. In addition to therapies that suppress immune responses, advances in molecular biology have led to new agents and methods to enhance immune responses and correct immune deficits, such as growth factor replacement and cytokine therapies. Finally, gene therapy is a method for the long-term treatment of disorders in which a defective gene leads to disease.
Minimal Prevalence of Authorship Misrepresentation among Internal Medicine Residency Applicants: Do Previous Estimates of Misrepresentation Represent Insufficient Case Finding?
Authors: Randy S. Hebert, Cheri G. Smith, Scott M. Wright
Journal: Annals of Internal Medicine (2003)

Background: High rates of authorship misrepresentation have been documented among medical trainees. Objective: To assess misrepresentation among internal medicine residency applicants while comparing searches used by previous authors (searches 1 and 2) to a more comprehensive strategy (search 3). Design: Review of 497 residency applications. Setting: Two university-based internal medicine residency programs. Measurements: Search 1 was limited to MEDLINE. Search 2 added Current Contents, Science Citation Index, and BIOSIS and included searching journals by hand. Search 3 added seven other databases and contacts to librarians, editors, and coauthors. Results: 224 applicants reported 634 articles; 630 (99%) were verified. The number of applicants with misrepresented citations varied depending on the search used (56 applicants [25%] in search 1 vs. 34 applicants [15%] in search 2 vs. 4 applicants [1.8%] in search 3). Conclusions: Using a comprehensive search, we found substantially less misrepresentation than had been reported. Previous studies probably overestimated the magnitude of the problem.
INTENSIVE ATORVASTATIN TREATMENT REDUCES CARDIOVASCULAR EVENTS (CVE) IN THOSE WITH DYSLIPIDEMIA, CORONARY HEART DISEASE (CHD) AND WITH MILD OR MORE ADVANCED CHRONIC KIDNEY DISEASE (CKD): AN ANALYSIS OF THE TNT, IDEAL AND ALLIANCE TRIALS
Authors: Daniel J. Wilson, James Shepherd, Terje Pedersen, Michael Koren, Andrei Breazna
Journal: Journal of the American College of Cardiology (2011)