tbuckley/cabot-search huggingface dataset:
Transcription of granzyme A and B genes is differentially regulated during lymphoid ontogeny.
Authors: K Ebnet, C N Levelt, T T Tran, K Eichmann, M M Simon
Journal: The Journal of Experimental Medicine (1995)

During development, thymocytes express a number of genes typical for activated peripheral T lymphocytes, including granzymes. We have now analyzed by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and cytochemistry fetal liver cells and thymocytes at various developmental stages for the expression of granzyme A-G genes. At days 13-17 of gestation, only granzyme B but none of the other granzymes is expressed in fetal liver. In the most immature, Pgp-1+IL2R alpha-, thymocyte subpopulation mRNAs for granzymes A-C but not for granzymes D-G are detectable. Upon further differentiation via Pgp-1-IL-2R alpha + into more mature Pgp-1-IL-2R alpha- thymocytes the level of expression of granzymes A, B, and C gradually declines reaching its lowest level at the CD4+ 8+ double positive stage. In fetal thymic lobes depleted of lymphoid cells by treatment with deoxyguanosine, no transcripts for granzymes A, B, and C were found indicating that the PCR signals are derived exclusively from early precursor T/natural killer (NK) lineage cells rather than from residual stromal elements. In mature CD4+CD8- and CD4-CD8+ thymocytes, granzyme B mRNA is found at similar levels in both subsets whereas granzyme A mRNA is expressed selectively in the CD4-CD8+ subset. Enzymatic activity of granzyme A was only seen in a fraction of CD4-CD8+ thymocytes negative for heat stable antigen (HSA) but not in the more immature HSA+ fraction of CD4-CD8+ thymocytes. The data suggest that (a) granzyme B is a pro-thymocyte marker for all T/NK lineage cells; (b) granzyme A transcripts are associated with thymocytes with the potential to develop into the CD8+ lineage; and (c) granzyme A enzymatic activity is only expressed in the most mature CD4-CD8+ stage, suggesting that granzyme proteins are not involved in early stages of thymocyte development.
Nucleus-to-Nucleus Gene Transfer and Protein Retargeting into a Remnant Cytoplasm of Cryptophytes and Diatoms
Authors: S. B. Gould, M. S. Sommer, P. G. Kroth, G. H. Gile, P. J. Keeling, U.-G. Maier
Journal: Molecular Biology and Evolution (2006)

The complex plastid of the cryptophyte Guillardia theta and of the diatom Phaeodactylum tricornutum can both be traced back to an engulfed eukaryotic red alga. The eukaryotic origin of these plastids is most obvious in cryptophytes, where the organelle still possesses a remnant nucleus, the nucleomorph. The nucleomorph itself is embedded in the periplastid compartment (PPC), the remnant of the former red algal cytosol. In the cryptophyte and diatom, the complex plastid is surrounded by 4 membranes, the outer one being continuous with the host rough endoplasmatic reticulum. In a recent report, we have shown that a nuclear encoded PPC protein of G. theta expressed in P. tricornutum leads to a localization, recently described as being a "bloblike structure," which can be obtained by mutation of plastid protein-targeting sequences of the diatom itself. Here we present further nucleus-encoded PPC proteins from G. theta, such as the eukaryotic translation elongation factor-1alpha, evidence for their nucleus-to-nucleus gene transfer, and retargeting of the proteins. We also investigated the first nuclear encoded PPC-targeted protein of P. tricornutum (Hsp70) and analyzed it for in vivo localization together with the identified G. theta PPC proteins. This revealed that all localize to the bloblike structures, which we suggest is the highly reduced PPC of P. tricornutum. Furthermore, the described cryptophyte PPC proteins possibly allow the elucidation of the processes by which proteins are involved in different levels of host control over its eukaryotic organelle.
Notch Signaling in Development and Cancer
Authors: Victoria Bolós, Joaquín Grego-Bessa, José Luis de la Pompa
Journal: Endocrine Reviews (2007)

Notch is an evolutionarily conserved local cell signaling mechanism that participates in a variety of cellular processes: cell fate specification, differentiation, proliferation, apoptosis, adhesion, epithelial-mesenchymal transition, migration, and angiogenesis. These processes can be subverted in Notch-mediated pathological situations. In the first part of this review, we will discuss the role of Notch in vertebrate central nervous system development, somitogenesis, cardiovascular and endocrine development, with attention to the mechanisms by which Notch regulates cell fate specification and patterning in these tissues. In the second part, we will review the molecular aspects of Notch-mediated neoplasias, where Notch can act as an oncogene or as a tumor suppressor. From all these studies, it becomes evident that the outcome of Notch signaling is strictly context-dependent and differences in the strength, timing, cell type, and context of the signal may affect the final outcome. It is essential to understand how Notch integrates inputs from other signaling pathways and how specificity is achieved, because this knowledge may be relevant for future therapeutic applications.
Eradication of factor viii inhibitors in patients with mild and moderate hemophilia A
Authors: Christine L. Kempton, Geoff Allen, Jeffrey Hord, Rebecca Kruse‐Jarres, Rajiv K. Pruthi, Christopher Walsh, Guy Young, J. Michael Soucie
Journal: American Journal of Hematology (2012)

In hemophilia A, up to 25% of new antifactor VIII (FVIII) inhibitory antibodies (inhibitors) occur in patients with mild or moderate disease. Once the inhibitor develops, options for management include observation, immune modulation, and immune tolerance induction (ITI). Currently, there is little data to guide a clinician's management decisions. In a case series, eight of the 26 subjects with mild or moderate hemophilia complicated by an inhibitor underwent ITI; two were successful, two were unsuccessful, and four were partially successful. In a systematic review of the literature, 12 of the 16 patients with mild or moderate hemophilia responded to rituximab for treatment to eradicate the inhibitor. To increase our understanding of treatment options for inhibitor eradication in patients with mild or moderate hemophilia A complicated by an inhibitor, a secondary analysis of clinical and treatment characteristics in a cohort of 36 patients with mild or moderate hemophilia A and inhibitor was undertaken. In multivariate analyses, rituximab alone (n = 6) and other immune-modulating treatments alone (n = 2) were significantly associated with an increased likelihood of inhibitor clearance [hazard ratio (HR) = 4.4 (95% CI = 1.06–20.03) and 10.21 (95% CI = 1.17–78.28), respectively], whereas ITI alone (n = 9) was not [HR = 1.35 (95% CI = 0.44–4.07)].
IMPACT OF TIMING TO CORONARY ARTERY BYPASS GRAFTING FOR PATIENTS WITH SIGNIFICANT LEFT MAIN STENOSIS
Authors: John M. Fallon, Joseph P. DeSimone, Bruce J. Leavitt, Robert A. Clough, Elaine M. Olmstead, Donato Sisto, Robert S. Kramer, Benjamin M. Westbrook, Richard A. Boss, Carmine Frumiento, Cathy S. Ross, David J. Malenka, Anthony W. DiScipio
Journal: Journal of the American College of Cardiology (2015)
Prematurity — A Window of Opportunity?
Authors: Mark A. Sperling
Journal: New England Journal of Medicine (2004)

Infants born with evidence of restricted fetal growth — those who are small for gestational age — appear to be at increased risk for metabolic disorders (type 2 diabetes mellitus and dyslipidemia), cardiovascular disease (hypertension and coronary heart disease), and even psychiatric disorders later in life.1,2 Proposed initially by Dr. David Barker and colleagues on the basis of careful epidemiologic studies, these observations have been replicated with variable strength in humans, have been duplicated in some animal models, have spawned an extensive literature, and have provided theories for the developmental origins of some of the most important common chronic . . .
Quantitative assessment of regional left ventricular function by densitometric analysis of digital-subtraction ventriculograms: correlation with myocardial systolic shortening in dogs.
Authors: F Chappuis, T Widmann, B Guth, P Nicod, K L Peterson
Journal: Circulation (1988)

Conventional wall motion analysis of contrast ventriculograms assesses only that part of the wall that is tangential to the x-ray beam. To assess regional left ventricular function in three dimensions, a new computerized method based on densitometric analysis of digital subtraction left ventriculograms was developed and validated in nine open-chest dogs instrumented with a circumflex coronary artery occluder and sonomicrometers in the anterior and posterior walls. Each dog underwent digital subtraction ventriculography at baseline and at five levels (I to V) of dysfunction of the inferior wall induced by progressive stenoses of the circumflex coronary artery. The ventriculogram was divided into six segments around the end-diastolic center of gravity. Time-volume curves were obtained by densitometry in the normal anterior and ischemic inferior segments containing the sonomicrometers. From these curves, regional ejection fraction (R-EF), regional peak ejection rate (R-PER), and regional phase (R-PH) and amplitude (R-AMP) of the first Fourier harmonic were derived. From baseline to level V of dysfunction, myocardial systolic shortening determined by sonomicrometry decreased by 124 +/- 34% of control (mean +/- SD; p less than .001) in the ischemic wall, while it increased by 12 +/- 19% (NS) in the normal wall. At the same time, R-EF, R-PER, and R-AMP decreased in the ischemic segment by 65 +/- 12%, 46 +/- 30%, and 45 +/- 15% of control, respectively (all p less than .01), while they remained unchanged or increased in the normal segment. R-PH was delayed by 14 +/- 5% (p less than .01) in the ischemic segment, but remained unchanged in the normal segment, reflecting the asynchrony of regional left ventricular contraction during ischemia. Densitometric indexes of regional function correlated well with sonomicrometric systolic shortening both in normal and ischemic segments, with r values of .84 for R-EF, .80 for R-AMP, .64 for R-PER, and .55 for R-PH (all p less than .0001). Thus, densitometric analysis of digital subtraction left ventriculograms allows three-dimensional assessment of the extent, velocity, and synchrony of regional left ventricular contraction. Densitometric indexes of regional contraction correlate well with direct measurements of myocardial systolic shortening and are useful in quantitating regional left ventricular dysfunction.
APIXABAN IS EFFICACIOUS AND SAFE IN PATIENTS WITH ATRIAL FIBRILLATION USING CONCOMITANT AMIODARONE: AN ANALYSIS FROM THE ARISTOTLE TRIAL
Authors: Greg C. Flaker, Stefan Hohnloser, Daniel Wojdyla, Elaine Hylek, David Garcia, Renee Sullivan, Renato Lopes, Sana M. Al-Khatib, Christopher Granger
Journal: Journal of the American College of Cardiology (2013)
Schilddrüsenerkrankungen: Pathophysiologie, Diagnostik, Therapie
Authors: William H. Wehrmacher
Journal: JAMA (1974)

In the author's experience, the thyroid disorders cost more sick days among workers in East Germany than diabetes and occupy a substantial part of their endocrinologists' professional time. Dr. Meng has brought out this new book as part of a new series designed to bring a specialist's help mainly to the general practitioner, although without, as he says, any attempt to produce "a monograph or textbook." The book can be divided into three parts: the first considers the historical development of concepts about the thyroid gland, its function and relationship to extrathyroidal factors, and diagnostic measures; the second takes up the ordinary disorders of the thyroid sequentially—nontoxic goiter, hyperthyroidism, acquired hypothyroidism, endocrine ophthalmopathy and pretibial myxedema, congenital hypothyroidism, thyroid tumors, and thyroiditis; the last discusses C-cells and calcitonin, characteristic measurements and treatment with radioactive substances, and treatment with drugs and hormones. Although it is as yet little used in this
Importance of dendrimer size in the hapten density in a conjugate for in vitro testing to determine IgE antibody in patients allergic to betalactams
Authors: C. Mayorga, M.J. Torres, E. Perez-Inestrosa, F. Sanchez-Sancho, M.I. Montañez, J.L. Rodriguez-Bada, A.G. Romano, R. Suau, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2003)
Cytotoxicity of thermosensitive polymers poly(N-isopropylacrylamide), poly(N-vinylcaprolactam) and amphiphilically modified poly(N-vinylcaprolactam)
Authors: Henna Vihola, Antti Laukkanen, Lauri Valtola, Heikki Tenhu, Jouni Hirvonen
Journal: Biomaterials (2004)
1023-96 A randomized double-blind placebo-controlled phase 2 study on the efficacy and safety of fasudil in patients with stable angina
Authors: Ralph M Vicari, Bernard Chaitman, Deborah Keefe, William B Smith, Steven G Chrysant, Melvin J Tonkon, Neville Bittar, Robert J Weiss, Udho Thadani
Journal: Journal of the American College of Cardiology (2004)
Chloroquine-Resistant Falciparum Malaria From Africa
Authors: B. H. Kean
Journal: JAMA (1979)

FALCIPARUM malaria resistant to prophylactic and therapeutic doses of chloroquine phosphate is widespread in Southeast Asia, especially in Vietnam, and occurs in South America, especially in Colombia and Brazil. This development is truly calamitous, since what was almost an ideal drug is becoming of limited value. All malariologists have dreaded the day when chloroquine-resistant malaria from Africa would be described.<sup>1</sup>Alas, evidence presented in two case reports would indicate that the day is here. <h3>Report of a Case</h3> A 49-year-old zoologist who had traveled extensively throughout the world, including Africa, was in generally good health and gave no history of previous malaria. On Feb 25, 1978, he left the United States, taking a group of civilians on a tour of the Kenya highlands. He remained there 17 days and returned to New York on March 17. Two weeks before departure, he began taking chloroquine phosphate (Aralen Phosphate), prophylaxis 500
BMJ tablet app
Authors: D. Payne, F. Godlee
Journal: BMJ (2012)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following BMJ tablet app Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Physicians and the Pharmaceutical Industry
Authors: Marvin Goldstein
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 September 1990Physicians and the Pharmaceutical IndustryMarvin Goldstein, MDMarvin Goldstein, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-5-407 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: I appreciate the efforts of the American College of Physicians Ethics Committee in developing the position paper (1) on physicians and the pharmaceutical industry. I think, however, that they have missed an area of concern; that is, the professors who sell their names as editorial consultants or as authors of "rehash" articles for the "throwaway" journals, as well as those who make themselves available as the "select" lecturers for specific pharmaceutical companies.In point of fact, if the current professors had set a better example for their students in the first place, both in the hospitals and...Reference1. . Physicians and the pharmaceutical industry. Ann Intern Med. 1990;112:624-6. LinkGoogle Scholar1. . Physicians and the pharmaceutical industry. Ann Intern Med. 1990;112:624-6. LinkGoogle Scholar1. . Physicians and the pharmaceutical industry. Ann Intern Med. 1990;112:624-6. LinkGoogle Scholar1. Noble R The pizza parade. Ann Intern Med. 1990;112:237. LinkGoogle Scholar1. . Physicians and the pharmaceutical industry. Ann Intern Med. 1990;112:624-6. LinkGoogle Scholar2. Gove P ed. Webster's Third New International Dictionary of the English Language. Springfield, Massachusetts: Merriam-Webster Inc.; 1981:1241. Google Scholar3. Chren M, Landefeld S, and Murray T. Doctors, drug companies, and gifts. JAMA. 1989;262:3448-51. CrossrefMedlineGoogle Scholar1. . Physicians and the pharmaceutical industry. Ann Intern Med. 1990;112:624-6. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Marvin Goldstein, MDAffiliations: Poughkeepsie Medical Group Poughkeepsie, NY 12603 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEthical Relationships between Drug Companies and the Medical ProfessionConflict of interest and informed consent in industry‐sponsored clinical trials 1 September 1990Volume 113, Issue 5Page: 407-408 ePublished: 1 December 2008 Issue Published: 1 September 1990 PDF downloadLoading ...
High Frequency of Submicroscopic Hemizygous Deletion Is a Major Mechanism of Loss of Expression of<i>PTEN</i>in Uveal Melanoma
Authors: Mohamed H. Abdel-Rahman, Ying Yang, Xiao-Ping Zhou, Elson L. Craig, Frederick H. Davidorf, Charis Eng
Journal: Journal of Clinical Oncology (2005)

Although cytogenetic aberrations at 10q have been reported in up to 27% of uveal melanomas, the role of PTEN in the pathogenesis of uveal melanoma is largely unknown. Our aim was to determine the frequency and clinical significance of PTEN alterations in uveal melanomas.We examined PTEN expression using immunohistochemistry in 75 sporadic uveal melanomas, with an average follow-up of 89 months. Molecular cytogenetic alterations were studied using comparative genomic hybridization (CGH). Genotyping was carried out using an intragenic PTEN marker and two flanking markers. Mutational analysis of PTEN was also carried out.Of the 75 tumors, 12 (16%) showed no PTEN immunostaining, 32 (42.7%) showed weak to moderate staining and the remaining 31 (38.2%) showed staining similar to the normal internal controls. Using CGH, only two (15.4%) of 13 samples showed any loss of 10q. However, in the 38 tumors with informative genotyping, we found that 29 (76.3%) had loss of heterozygosity (LOH) of at least one PTEN marker, and 15 (39.5%) showed LOH of at least two markers. Mutations in the coding region of PTEN were identified in four (11.4%) of 35 tumors. Further, loss of cytoplasmic PTEN expression by immunohistochemistry was associated with shortened disease-free survival (P = .029).This is the first demonstration that PTEN is a tumor suppressor involved in uveal melanoma pathogenesis and may be associated with clinical outcome. Our data also suggest that submicroscopic deletion, but not large deletions, is the major mechanism of loss of PTEN expression in uveal melanomas.
Role and regulation of phosphatidylinositol 3-kinase β in platelet integrin α2β1 signaling
Authors: Alessandra Consonni, Lina Cipolla, Gianni Guidetti, Ilaria Canobbio, Elisa Ciraolo, Emilio Hirsch, Marco Falasca, Mitsuhiko Okigaki, Cesare Balduini, Mauro Torti
Journal: Blood (2011)
Hospitals must use London's appeal to tackle workforce shortages
Authors: D. Singh
Journal: BMJ (2003)

The NHS in London must exploit the capital's reputation as a dynamic, culturally diverse city, as well as being a leader in healthcare training, if it is to tackle shortages in its workforce, says a report published this week by the King's Fund.

High staff turnover, the heavy use of temporary staff, and a high level of recruitment from overseas are all characteristics of the capital's healthcare workforce. It urges the NHS in London not to fight or prevent these trends but to think creatively about how best to manage …
Size and Extent of the Problem
Authors: Joseph F. Sadusk
Journal: JAMA (1966)

An accurate and specific description of the size L and extent of nonnarcotic addiction is a most difficult matter since the drugs are obtained through illicit traffic which cannot be controlled under the present law. Complete data are simply not available for documentation and analysis. Indeed, adequate reports on this topic are not available from other countries either. A complete evaluation of the problem would require data such as the following: (1) The quantity of each sedative and stimulant produced. (2) The channels of distribution for each product with quantitative data that accounts for all of the product produced. (3) The incidence of habituation and addiction to these drugs in the general population. (4) The number of persons annually admitted to hospitals because of acute or chronic intoxication from these drugs. (5) The annual number of arrests for the offering of these drugs for sale under circumstances that do not
Clarifying Confusion: The Confusion Assessment Method
Authors: Sharon K. Inouye
Journal: Annals of Internal Medicine (1990)

Objective: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk settings. Design: Prospective validation study. Setting: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). Patients: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. Measurements and Main Results: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). Conclusions: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium.
Does PEEP impair the hepatic outflow in patients following liver transplantation?
Authors: Fuat H. Saner, Goran Pavlaković, Yanli Gu, Nils R. Fruhauf, Andreas Paul, Arnold Radtke, Silvio Nadalin, Massimo Malagó, Christoph E. Broelsch
Journal: Intensive Care Medicine (2006)
Jefferson on the Metric System
Authors: Harold E. Root
Journal: JAMA (1971)

To the Editor.—  The EDITORIAL on metric measurements ( 218 :731, 1971) would have placed us 200 years ago in the year in 1771, a few years before the American Revolution, which would have eliminated the possibility of John Quincy Adams being Secretary of State. He became Secretary of State in 1817 in the cabinet of James Monroe.  Actually, Thomas Jefferson, as Secretary of State in the cabinet of George Washington, spent much of his first months in office toiling over a report on weights and measures which was considered in its day a philosophical masterpiece, and would have placed the United States on the metric system. Congress, alas, declined to adopt it. 1