tbuckley/cabot-search huggingface dataset:
TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice
Authors: Perrine Martin, Clarisse Dubois, Emilie Jacquier, Sarah Dion, Maryline Mancini-Bourgine, Ophélie Godon, Roland Kratzer, Karine Lelu-Santolaria, Alexei Evlachev, Jean-François Meritet, Yasmin Schlesinger, Dominique Villeval, Jean-Marc Strub, Alain Van Dorsselaer, Jean-Baptiste Marchand, Michel Geist, Renée Brandely, Annie Findeli, Houda Boukhebza, Thierry Menguy, Nathalie Silvestre, Marie-Louise Michel, Geneviève Inchauspé
Journal: Gut (2014)

<h3>Objective</h3> To assess a new adenovirus-based immunotherapy as a novel treatment approach to chronic hepatitis B (CHB). <h3>Methods</h3> TG1050 is a non-replicative adenovirus serotype 5 encoding a unique large fusion protein composed of a truncated HBV Core, a modified HBV Polymerase and two HBV Envelope domains. We used a recently described HBV-persistent mouse model based on a recombinant adenovirus-associated virus encoding an over length genome of HBV that induces the chronic production of HBsAg, HBeAg and infectious HBV particles to assess the ability of TG1050 to induce functional T cells in face of a chronic status. <h3>Results</h3> In <i>in vitro</i> studies, TG1050 was shown to express the expected large polyprotein together with a dominant, smaller by-product. Following a single administration in mice, TG1050 induced robust, multispecific and long-lasting HBV-specific T cells detectable up to 1 year post-injection. These cells target all three encoded immunogens and display bifunctionality (ie, capacity to produce both interferon γ and tumour necrosis factor α as well as cytolytic functions). In addition, control of circulating levels of HBV DNA and HBsAg was observed while alanine aminotransferase levels remain in the normal range. <h3>Conclusions</h3> Injection of TG1050 induced both splenic and intrahepatic functional T cells producing cytokines and displaying cytolytic activity in HBV-naïve and HBV-persistent mouse models together with significant reduction of circulating viral parameters. These results warrant clinical evaluation of TG1050 in the treatment of CHB.
Lead Poisoning in an Art Conservator
Authors: Alf Fischbein, Joyce Wallace, Karl E. Anderson, Shigeru Sassa, Steven Kon, Arthur N. Rohl, Attallah Kappas
Journal: JAMA (1982)

A case of lead poisoning in a female art conservator is reported. The patient had experienced excessive lead exposure while restoring an antique Peruvian tapestry from the Chancay period (1000 to 1500 AD) using a powdered pigment (cinnabar), which had been recovered from the same tomb in which the tapestry was found. Over two months, prominent neurological, gastrointestinal, and diffuse muscular symptoms developed. Severe anemia accompanied by basophilic stippling of RBCs led to the diagnosis of lead poisoning, which was confirmed by markedly elevated blood lead levels (up to 130 micrograms/dL) and impairment of heme synthetic enzymes. The severity of the intoxication necessitated chelation therapy. Chemical analysis of the antique powdered pigment showed it to be the source of lead exposure, in that it contained about 1% lead.
Widespread Evolutionary Conservation of Alternatively Spliced Exons in Caenorhabditis
Authors: Manuel Irimia, Jakob L. Rukov, David Penny, Jordi Garcia-Fernandez, Jeppe Vinther, Scott W. Roy
Journal: Molecular Biology and Evolution (2007)

Alternative splicing (AS) contributes to increased transcriptome and proteome diversity in various eukaryotic lineages. Previous studies showed low levels of conservation of alternatively spliced (cassette) exons within mammals and within dipterans. We report a strikingly different pattern in Caenorhabditis nematodes-more than 92% of cassette exons from Caenorhabditis elegans are conserved in Caenorhabditis briggsae and/or Caenorhabditis remanei. High levels of conservation extend to minor-form exons (present in a minority of transcripts) and are particularly pronounced for exons showing complex patterns of splicing. The functionality of the vast majority of cassette exons is underscored by various other features. We suggest that differences in conservation between lineages reflect differences in levels of functionality and further suggest that these differences are due to differences in intron length and the strength of consensus boundaries across lineages. Finally, we demonstrate an inverse relationship between AS and gene duplication, suggesting that the latter may be primarily responsible for the emergence of new functional transcripts in nematodes.
Systemic corticosteroids for subcutaneous panniculitis‐like T‐cell lymphoma
Authors: E. Guenova, S. Schanz, W. Hoetzenecker, J.A. DeSimone, T. Mehra, B. Voykov, M. Urosevic‐Maiwald, M. Berneburg, R. Dummer, L.E. French, K. Kerl, J. Kamarashev, G. Fierlbeck, A. Cozzio
Journal: British Journal of Dermatology (2014)

Background Primary cutaneous γ/δ T-cell lymphoma (PCGD-TCL) is aggressive and has a poor prognosis. In contrast, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) of the α/β T-cell receptor phenotype is known to follow an indolent course and have a more favourable prognosis. In the past, PCGD-TCL and SPTCL were often considered to be a manifestation of the same disease, and aggressive systemic polychemotherapy has commonly been the first-line therapy for both. Given the understanding that SPTCL is a separate and less aggressive entity, clinical data exclusively evaluating the efficacy of conservative treatment in SPTCL are needed. Objectives To assess the overall clinical response to systemic corticosteroids in the treatment of SPTCL. Methods This was a retrospective cross-sectional study based on a patient data repository from two tertiary care university hospitals in Zürich (Switzerland) and Tübingen (Germany). The repository spanned 13 years. Results In four of the five patients (80%) with SPTCL, treatment with systemic corticosteroids induced a complete remission. Conclusions Systemic corticosteroids may be an excellent first-line single-agent therapy for SPTCL.
RANOLAZINE FOR THE TREATMENT OF DIASTOLIC HEART FAILURE IN PATIENTS WITH PRESERVED EJECTION FRACTION: RESULTS FROM THE RALI-DHF STUDY
Authors: Lars Maier, Rolf Wachter, Frank Edelmann, Beth Layug, Ewa Karwatowska-Prokopczuk, Luiz Belardinelli, Gerd Hasenfuss, Claudius Jacobshagen
Journal: Journal of the American College of Cardiology (2012)
Tibial Bone-marrow Transfusions in Infants
Authors: F. W. Gunz, R. F. A. Dean
Journal: BMJ (1945)

Both rectal paraldehyde and avertin in basal anaesthetic doses were first tried to control the spasms, but were unsatisfactory because they were not retained.Pentothal, in doses of 0.25 g. intravenously, was then used as a temporary expedient, but was not very successful.Intramuscular paraldehyde in doses of 3 c.cm. was now tried, and as it proved extremely effective it was continued as required for the control of spasms until Oct. 6.For the first few days a dose of 2 or 3 c.cm. was given twice every 24 hours, and later once.To combat the increasing dehydration, an intravenous drip was started on Sept. 28 and was continued for 48 hours, the needle being kept in the vein by a plaster-of-Paris splint to the forearm.On Sept. 29 the temperature rose to 103°, the pulse to 160, and the respirations to 45.The chest was very bubbly, cyanosis was present, and it was clear that pneumonia would be likely to supervene.Sulphathiazole was therefore given, first by drip and afterwards by mouth, until Oct. 5, to a total of 26 g.The child's condition, which was critical, showed slight improvement on Oct. 2, reflex convulsions became easier to control, and he was able to take fluids by the mouth.His condition then gradually improved, reflex spasms having ceased by Oct. 8 and the tonic rigidity by Oct. 25.He was discharged well on Oct. 30.
IMMEDIATE IMPACT OF A 10-WEEK MIDDLE SCHOOL INTERVENTION TO IMPROVE HEALTH BEHAVIORS AND REDUCE CARDIOVASCULAR RISK FACTORS &amp;ndash; PROJECT HEALTHY SCHOOLS IN MICHIGAN
Authors: Taylor F. Eagle, Roopa Gurm, Cydni Smith, Nicole Corriveau, Jean Du-Russel-Weston, LaVaughn Palma-Davis, Susan Aaronson, Caren Goldberg, Eva Kline-Rogers, Elizabeth Jackson, Kim Eagle
Journal: Journal of the American College of Cardiology (2012)
&lt;emph type="ital"&gt;Study of Hands&lt;/emph&gt;
Authors: Thomas B. Cole
Journal: JAMA (2010)

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
Teaching of Surgery in Medical Schools
Authors: Claude E. Welch
Journal: JAMA (1969)

What does the student want from medical school? What does he get? These questions concern not only every teacher, but every physician who is interested in his profession.  There is no doubt that this is a permissive age. It must be expected that the solid walls of structured curricula will continue to be battered by waves of electivism. In some schools, almost all clinical subjects have become elective; in every curriculum, relaxation of strict requirements is the order of the day.  In any such revision, the teaching of surgery has tended to become particularly vulnerable. If surgery is the mere repetition of mechanical motions, as some educators believe, it would be appropriate to relegate it to postgraduate education or to a trade school. Medicine, meanwhile, remains relatively inviolate. This is true for many reasons, of which the most practical is that a student may be given important responsibility for the
Evaluation of Chest Pain in the Emergency Department
Authors: Mark A. Hlatky
Journal: New England Journal of Medicine (1997)

Each year 5 million patients come to emergency departments with chest pain.1 Some have acute, life-threatening illness, but many others have nothing seriously wrong; some have a history of coronary disease, whereas others have never had a cardiac evaluation. The task of the physician in the emergency department is to sort out the confusing array of patients with chest pain, and to do so rapidly, accurately, and efficiently.Acute myocardial ischemia as a result of coronary atherosclerosis is the key concern in patients with chest pain. Patients with acute coronary syndromes are at considerable risk for death and serious complications, . . .
Hepatitis B virus infection in Singapore.
Authors: R Guan
Journal: Gut (1996)

Although Singapore is in an endemic region for hepatitis B infection, the hepatitis B carriage rate of 5-6% is relatively low. The highest positivity rates for hepatitis B surface antigen (HBsAg) are found in the paediatric age group, with another peak in 40-49 year olds. Studies suggest that, although perinatal transmission is an important route of infection, most children acquire the virus through horizontal transmission between family members. Viral replication continues at a high rate in young carriers and tends to slow down with increasing age. Up to 50% of hepatitis B carriers in Singapore have chronic hepatitis, shown by raised serum ALT values and liver histology, and about 10% are infected with the precore mutant virus. About 20% of carriers have cirrhosis. Among patients with HCC, up to 75% are HBsAg positive, of whom 45% are still viraemic. Mass vaccination against hepatitis B was introduced into Singapore on a voluntary basis in 1983, with compulsory vaccination of babies born to HBeAg positive mothers since 1985. The number of cases of acute hepatitis B has fallen by 60% between 1989 and 1995 although the problems of the longterm complications of chronic hepatitis B still need to be tackled.
Test can predict which patients will benefit from hormonal treatments
Authors: S. Mayor
Journal: BMJ (2003)

A new test that is based on detecting the activity rather than just the quantity of oestrogen receptors in breast cells has shown promising results, indicating that the test may improve the accuracy of predicting which patients will benefit from hormonal treatments for breast cancer.

Hormonal treatments such as tamoxifen and anastrazole have greatly improved survival from breast cancer, because most breast cancers are stimulated by oestrogen. However, about 30% of patients with breast cancer in which oestrogen receptors are present do not respond to tamoxifen.

Also, a substantial proportion of patients who initially respond to tamoxifen develop resistance. The decision to use these …
Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma
Authors: Jean Bousquet, Eva Mantzouranis, Alvaro A. Cruz, Nadia Aït-Khaled, Carlos E. Baena-Cagnani, Eugene R. Bleecker, Chris E. Brightling, Peter Burney, Andrew Bush, William W. Busse, Thomas B. Casale, Moira Chan-Yeung, Rongchang Chen, Badrul Chowdhury, Kian Fan Chung, Ronald Dahl, Jeffrey M. Drazen, Leonardo M. Fabbri, Stephen T. Holgate, Francine Kauffmann, Tari Haahtela, Nikolaï Khaltaev, James P. Kiley, Mohammad R. Masjedi, Yousser Mohammad, Paul O'Byrne, Martyn R. Partridge, Klaus F. Rabe, Alkis Togias, Christiaan van Weel, Sally Wenzel, Nanshan Zhong, Torsten Zuberbier
Journal: Journal of Allergy and Clinical Immunology (2010)
Alterations in T-tubule and dyad structure in heart disease: challenges and opportunities for computational analyses
Authors: Eva Poláková, Eric A. Sobie
Journal: Cardiovascular Research (2013)

Compelling recent experimental results make clear that sub-cellular structures are altered in ventricular myocytes during the development of heart failure, in both human samples and diverse experimental models. These alterations can include, but are not limited to, changes in the clusters of sarcoplasmic reticulum (SR) Ca2+-release channels, ryanodine receptors, and changes in the average distance between the cell membrane and ryanodine receptor clusters. In this review, we discuss the potential consequences of these structural alterations on the triggering of SR Ca2+ release during excitation–contraction coupling. In particular, we describe how mathematical models of local SR Ca2+ release can be used to predict functional changes resulting from diverse modifications that occur in disease states. We review recent studies that have used simulations to understand the consequences of sub-cellular structural changes, and we discuss modifications that will allow for future modelling studies to address unresolved questions. We conclude with a discussion of improvements in both experimental and mathematical modelling techniques that will be required to provide a stronger quantitative understanding of the functional consequences of changes in sub-cellular structure in heart disease.
A New Dietary Approach to Reduce the Risk of Type 2 Diabetes?
Authors: Jerry L. Nadler
Journal: Diabetes Care (2004)

The projections for a continued rapid growth in the incidence of type 2 diabetes indicate the need of developing cost-effective approaches that can be widely employed to prevent or delay this major disorder. There is recent evidence that intensive lifestyle modification can be effective in reducing type 2 diabetes development (1). However, the role of particular micronutrients in the diet that may have a protective effect has not been well studied.

In this issue of Diabetes Care , there are two interesting prospective studies suggesting that an increased intake of magnesium (Mg) in the diet could have a protective role in reducing the risk of type 2 diabetes. Lopez-Ridaura et al. (2) evaluated dietary intake of different nutrients every 2–4 years in 85,060 women in the Nurses Health Study and 42,872 men in the Health Professional’s Follow-up Study. The medical history and lifestyle characteristics were followed for 18 years in the women and 12 years in the men. There was a significant reduction of relative risk of type 2 diabetes development in both men and women in the highest quintiles of Mg intake. These relationships remained significant after adjusting for age, total energy intake, family history of diabetes, physical activity, alcohol intake, or other dietary components analyzed. Adjustment for BMI somewhat attenuated the relationships, but the effect of Mg remained significant. Less than 5% of the cohort was …
Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.
Authors: J H Galla, D N Bonduris, P W Sanders, R G Luke
Journal: Journal of Clinical Investigation (1984)

We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and 125I-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25 +/- 1 to 43 +/- 1 meq/L; P less than 0.01), distally determined SNGFR declined progressively (40.9 +/- 1.7 to 28.3 +/- 1.8 nl/min; P less than 0.01), while in early distal tubule fluid, flow rate (8.6 +/- 0.7 to 3.4 +/- 0.6 nl/min) and Cl concentration (36 +/- 2 to 19 +/- 3 meq/L) decreased and osmolality (110 +/- 5 to 208 +/- 12 mosmol/kg) increased (P less than 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009 +/- 112 to 765 +/- 128 peq/min; P less than 0.01). In early distal tubule fluid, Cl concentration correlated positively and osmolality negatively with distally determined SNGFR (P less than 0.05). Proximally determined SNGFRs did not differ among the four groups. Proximal tubule stop-flow pressure responses to increasing rates of orthograde perfusion of the loop segment from 0 to 40 nl/min did not differ between groups CON and CDA-2. We interpret these data to show that reductions in SNGFR in CDA in the rat can occur by tubuloglomerular feedback (TGF) in the absence of differences in ECF volume or of alterations in TGF sensitivity during metabolic alkalosis. Of the proposed signals for TGF sensed by the macula densa, distal tubule fluid osmolality or some related variable is the signal most compatible with our data.
Screening Tests for Alcohol Use Disorders
Authors: Warren G. Thompson
Journal: Annals of Internal Medicine (1999)

Letters4 May 1999Screening Tests for Alcohol Use DisordersWarren G. Thompson, MDWarren G. Thompson, MDUniversity of Tennessee Graduate School of Medicine; Knoxville, TN 37920 (Thompson)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-9-199905040-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Steinbauer and colleagues (1) demonstrate that the Alcohol Use Disorders Identification Test (AUDIT) is superior to the CAGE questionnaire for most sex and ethnic groups. The authors point out that the CAGE questionnaire has “the advantages of brevity, ease of recall, and ease of scoring.”Piccinelli and colleagues (2) used the AUDIT in an outpatient Italian population and obtained similar sensitivities and specificities. In that study, using the same score (≥ 5) with only five questions (1, 2, 4, 5, and 10) gave nearly the same results as using the whole questionnaire. It would be interesting to ...References1. Steinbauer JR, Cantor SB, Holzer CE, Volk RJ. Ethnic and sex bias in primary care screening tests for alcohol use disorders. Ann Intern Med. 1998;129:353-62. LinkGoogle Scholar2. Piccinelli M, Tessari E, Bortolomasi M, Piasere O, Semenzin M, Garzotto N, et al . Efficacy of the alcohol use disorders identification test as a screening tool for hazardous alcohol intake and related disorders in primary care: a validity study. BMJ. 1997;314:420-4. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Warren G. Thompson, MDAffiliations: University of Tennessee Graduate School of Medicine; Knoxville, TN 37920 (Thompson) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEthnic and Sex Bias in Primary Care Screening Tests for Alcohol Use Disorders Jeffrey R. Steinbauer , Scott B. Cantor , Charles E. Holzer III , and Robert J. Volk Screening Tests for Alcohol Use Disorders Richard Saitz Screening Tests for Alcohol Use Disorders Robert J. Volk , Scott B. Cantor , and Jeffrey R. Steinbauer Metrics 4 May 1999Volume 130, Issue 9Page: 779KeywordsAlcoholismOutpatientsQuestionnairesSpecificity ePublished: 15 August 2000 Issue Published: 4 May 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Adult T‐cell leukemia initially manifesting as facial diplegia
Authors: H. Sawada, M. Matsui, F. Udaka, M. Nishimura, M. Fujita, K. Kameyama
Journal: American Journal of Hematology (1989)

Abstract We report an unusual case of adult T‐cell leukemia (ATL) initially manifesting as facial palsy due to ATL meningitis, which was caused by lymphoid cells in the cerebrospinal fluid (CSF) with a different phenotype from those in the blood. A DNA southern blot analysis of the blood cells confirmed the diagnosis of ATL. The aberrant cells in the CSF contained nuclei with simple indentations and responded well to the initial chemotherapy, while leukemic cells in the blood showed lobulated or convoluted nuclei and were resistant to treatment. Flow cytometry performed before treatment demonstrated that the majority of the cells in the CSF were CD3 + CD4 + CD8‐CD25 +, consistent with ATL, whereas they expressed the CD45R antigen, which the blood ATL cells did not. These differences in the subphenotype, cell morphology, and responsiveness to treatment among the ATL cells in blood and CSF suggest that a single clone or subclone with heterogeneous nature was not generated, before the final development of ATL.
Inappropriate increase in erythropoietin titers during chemotherapy
Authors: Ettore Piroso, Allan J. Erslev, Jaime Caro
Journal: American Journal of Hematology (1989)

Abstract Serial erythropoietin measurements by RIA were performed in six patients with acute leukemia treated by intensive chemotherapy. In all cases erythropoietin titers increased after the onset of treatment, although the hemoglobin concentration remained at stable values. Subsequently the erythropoietin titers gradually returned to baseline levels. In same patients this reduction occurred at the end of chemotherapy, in others coincident with infections and antibiotic therapy. In four patients this decrease occurred at the time of bone marrow recovery. The explanation for this inappropriate increase in erythropoietin titers is not clear but may be related to a direct or indirect effect of a suppressed marrow on sites of erythropoietin production or catabolism.