tbuckley/cabot-search huggingface dataset:
Genetic Alterations in Mouse Medulloblastomas and Generation of Tumors<i>De novo</i>from Primary Cerebellar Granule Neuron Precursors
Authors: Frederique Zindy, Tamar Uziel, Olivier Ayrault, Christopher Calabrese, Marc Valentine, Jerold E. Rehg, Richard J. Gilbertson, Charles J. Sherr, Martine F. Roussel
Journal: Cancer Research (2007)

Abstract Mice lacking p53 and one or two alleles of the cyclin D–dependent kinase inhibitor p18Ink4c are prone to medulloblastoma development. The tumor frequency is increased by exposing postnatal animals to ionizing radiation at a time when their cerebella are developing. In irradiated mice engineered to express a floxed p53 allele and a Nestin-Cre transgene, tumor development can be restricted to the brain. Analysis of these animals indicated that inactivation of one or both Ink4c alleles did not affect the time of medulloblastoma onset but increased tumor invasiveness. All such tumors exhibited complete loss of function of the Patched 1 (Ptc1) gene encoding the receptor for sonic hedgehog, and many exhibited other recurrent genetic alterations, including trisomy of chromosome 6, amplification of N-Myc, modest increases in copy number of the Ccnd1 gene encoding cyclin D1, and other complex chromosomal rearrangements. In contrast, medulloblastomas arising in Ptc1+/− mice lacking one or both Ink4c alleles retained p53 function and exhibited only limited genomic instability. Nonetheless, complete inactivation of the wild-type Ptc1 allele was a universal event, and trisomy of chromosome 6 was again frequent. The enforced expression of N-Myc or cyclin D1 in primary cerebellar granule neuron precursors isolated from Ink4c−/−, p53−/− mice enabled the cells to initiate medulloblastomas when injected back into the brains of immunocompromised recipient animals. These “engineered” tumors exhibited gene expression profiles indistinguishable from those of medulloblastomas that arose spontaneously. These results underscore the functional interplay between a network of specific genes that recurrently contribute to medulloblastoma formation. [Cancer Res 2007;67(6):2676–84]
Elegies for Angels, Punks, and Raging Queens
Authors: R. Hurley
Journal: BMJ (2010)

Today, a piece of musical theatre about people who have died from AIDS might be considered in poor taste, but this work is joyous and inspiring. In rhyming monologues and song, Elegies for Angels, Punks, and Raging Queens tells the stories of some 30 people who have died from AIDS. It’s glitzy and gauche, with slick choreography, rousing group anthems, sentimental spotlit solos, and key changes a plenty. More than that, though, it reminds us that the HIV epidemic is about millions of individual people with their …
Research in General Internal Medicine
Authors: Paul F. Griner, Edward Huth
Journal: Annals of Internal Medicine (1982)

Editorials1 April 1982Research in General Internal MedicinePAUL F. GRINER, M.D., EDWARD HUTH, M.D.PAUL F. GRINER, M.D.Search for more papers by this author, EDWARD HUTH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-4-518 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis issue carries two articles (1, 2) from faculty of general medicine divisions. These articles were selected from 80 submitted in response to a call from the Society for Research and Education in Primary Care Internal Medicine for articles to be published in a supplement illustrating current research in general internal medicine. Some articles were returned as being more appropriate for a different journal. Many more were rejected either because the question being addressed was not considered substantial or, more commonly, a good question was pursued with an insufficiently rigorous study design. These observations support an impression that both the...References1. ARONSONKOMAROFFPASSERVINBRANCH MATCW. Heterophil antibody in adults with sore throat: frequency and clinical presentation. Ann Intern Med. 1982 96 505-8. LinkGoogle Scholar2. LIPKINLAMB MG. The couvade syndrome: an epidemiologic study. Ann Intern Med. 1982;96:509-11. LinkGoogle Scholar3. TARLOV A. Academic general internal medicine. Ann Intern Med. 1982;96:239-40. LinkGoogle Scholar4. FRIEDMANGERTMANROSENCRANSEISENBERGPOZEN RPAJJ. General internal medicine units in academic medical centers: their emergence and functions. Ann Intern Med. 1982;96:233-8. LinkGoogle Scholar5. MCDERMOTT W. Education and general medical care. Ann Intern Med. 1982;96:512-7. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAn Informatics-based Chronic Disease Practice: Case Study of a 35-year Computer-based Longitudinal Record SystemPreventive Medicine: Notes Toward an Agenda for ChangeFunding for medical care researchGrowing upThe Academic Viability of General Internal Medicine The Views of Department of Medicine ChairmenROBERT H. FRIEDMAN, M.D., JANET T. POZEN, Ph.D.Research and Training Programs in General Internal MedicineWILLIAM M. TIERNEY, M.D. 1 April 1982Volume 96, Issue 4Page: 518-519 Issue Published: 1 April 1982 PDF DownloadLoading ...
Breath measurements as volatile organic compound biomarkers.
Authors: L Wallace, T Buckley, E Pellizzari, S Gordon
Journal: Environmental Health Perspectives (1996)

A brief review of the uses of breath analysis in studies of environmental exposure to volatile organic compounds (VOCs) is provided. The U.S. Environmental Protection Agency's large-scale Total Exposure Assessment Methodology Studies have measured concentrations of 32 target VOCs in the exhaled breath of about 800 residents of various U.S. cities. Since the previous 12-hr integrated personal air exposures to the same chemicals were also measured, the relation between exposure and body burden is illuminated. Another major use of the breath measurements has been to detect unmeasured pathways of exposure; the major impact of active smoking on exposure to benzene and styrene was detected in this way. Following the earlier field studies, a series of chamber studies have provided estimates of several important physiological parameters. Among these are the fraction, f, of the inhaled chemical that is exhaled under steady-state conditions and the residence times. tau i in several body compartments, which may be associated with the blood (or liver), organs, muscle, and fat. Most of the targeted VOCs appear to have similar residence times of a few minutes, 30 min, several hours, and several days in the respective tissue groups. Knowledge of these parameters can be helpful in estimating body burden from exposure or vice versa and in planning environmental studies, particularly in setting times to monitor breath in studies of the variation with time of body burden. Improvements in breath methods have made it possible to study short-term peak exposure situations such as filling a gas tank or taking a shower in contaminated water.
Abstract 822: Change in Regional Strain after Cardiac Resynchronization Therapy
Authors: Chinami Miyazaki, Grace Lin, Margaret M Redfield, Raul E Espinosa, Charles J Bruce, Fletcher A Miller, Jae K Oh
Journal: Circulation (2008)

Background: Cardiac resynchronization therapy (CRT) improves global systolic function in left ventricle. However, the impact of CRT on regional myocardial function is less clear. The aim of this study, therefore, is to evaluate regional changes in myocardial strain after CRT. Methods: Speckle tracking echocardiography (STE) was performed in 91 patients before and 6 month after CRT. Peak longitudinal strain was measured in 18 segments at base, mid and apex in three apical views. Left ventricular end-systolic volume (ESV) was measured by biplane Simpson’s method and reverse remodeling was defined as 10 % reduction in ESV at 6 month after CRT. Results: Peak strain improved in basal and mid segments of medial walls (basal inferoseptal, anteroseptal and inferior segments, p&lt;0.05, mid inferoseptal and inferior segments: p&lt;0.01) in entire group after CRT, with a greater degree of improvement in CRT responders than in nonresponders (Figure ). There was no significant improvement in free wall strain, with significant reduction in basal inferolateral segment after CRT (P=0.047) in entire group. Nonresponders had significant reduction in strain at the mid anterolateral segment (P=0.004) (Figure ). Strain of the apical segments also did not improve. Conclusions: CRT induces reverse remodeling by enhancing regional myocardial function in the septum, but suppresses the function in the free wall. Lack of reverse remodeling after CRT was characterized by the reduced function in lateral segments without improvement in septal function..
Alcohol histories taken from elderly people
Authors: P C Naik, R G Jones
Journal: BMJ (1994)

EDITOR, - We wish to respond to D Thompson's comments on our study.1 Thompson states that we claim that elderly people are more likely than younger people to hide their drinking and that there is no evidence to support this. This information is stated in our introduction and is based on earlier literature.2

Thompson also emphasises that studies have shown that older people drink less than younger ones. But …
Eradication of disseminated leukemia in a syngeneic murine leukemia model using pretargeted anti-CD45 radioimmunotherapy
Authors: John M. Pagel, Nathan Hedin, Lacey Drouet, Brent L. Wood, Anastasia Pantelias, Yukang Lin, Donald K. Hamlin, D. Scott Wilbur, Ajay K. Gopal, Damian Green, Frederick R. Appelbaum, Oliver W. Press
Journal: Blood (2007)
Both, toxin A and toxin B, are important in<i>Clostridium difficile</i>infection.
Authors: Sarah A. Kuehne, Stephen T. Cartman, Nigel P. Minton
Journal: Gut Microbes (2011)

The bacterium Clostridium difficile is the leading cause of healthcare associated diarrhoea in the developed world and thus presents a major financial burden. The main virulence factors of C. difficile are two large toxins, A and B. Over the years there has been some debate over the respective roles and importance of these two toxins. To address this, we recently constructed stable toxin mutants of C. difficile and found that they were virulent if either toxin A or toxin B was functional. This underlined the importance of each toxin and the necessity to consider both when developing countermeasures against Clostridium difficile infection (CDI). In this article we discuss our findings in the context of previous work and outline some of the challenges which face the field as a result.
GP workforce crisis is predicted as earnings fall for seventh year in a row
Authors: G. Iacobucci
Journal: BMJ (2014)

GPs in the United Kingdom have seen their income fall for the seventh successive year in real terms, as rises in practice expenses continue to outstrip increases in earnings.

New figures published by the Health and Social Care Information Centre show that the average income in real terms of contractor GPs (those working under national General Medical Services (GMS) and local Personal Medical Services (PMS) contracts) was £102 000 (€130 000; $170 000) before tax in 2012-13, down from £104 100 in 2011-12 (figure⇓).1 The figures mean that the annual income of contractor GPs has fallen by 22% in real terms since 2005-06, when it stood at £129 994.



The …
Metabolic Basis of Sexual Dimorphism in PKU Mice After Genome-targeted PAH Gene Therapy
Authors: Li Chen, Swan N Thung, Savio LC Woo
Journal: Molecular Therapy (2007)

We have previously reported a transgene delivery system based on phiBT1 bacteriophage integrase that results in targeted insertion of transgenes into mammalian genomes, and its use in the delivery of murine phenylalanine hydroxylase (PAH) complementary DNA (cDNA) into the hepatocytes of male phenylketonuria (PKU) mice, leading to a complete and permanent correction of their hyperphenylalaninemic phenotype. In this study, we report only partial phenotypic correction in female PKU mice, even though hepatic PAH activities in both sexes after gene treatment were similar. Daily injections of tetrahydrobiopterin (BH4), an essential co-factor for phenylalanine hydroxylation, in the gene-treated females led to complete correction of their PKU phenotype. After gonadectomy, serum phenylalanine levels in the gene-treated females were reduced to normal, whereas those in the gene-treated males remained unchanged. The sterile gene-treated PKU mice were subjected to daily sex hormone injections. Whereas the estradiol-treated sterile males developed hyperphenylalaninemia, the dihydrotestosterone-treated sterile females remained normal phenylalaninemic. The results indicate that it is estrogen that suppresses the steady-state levels of BH4 in mouse hepatocytes that became limiting, which is the underlying mechanism for the observed sexual dimorphism in PKU mice after PAH gene treatment. Livers of the PAH gene–corrected PKU mice also appeared normal and without apparent pathologies. We have previously reported a transgene delivery system based on phiBT1 bacteriophage integrase that results in targeted insertion of transgenes into mammalian genomes, and its use in the delivery of murine phenylalanine hydroxylase (PAH) complementary DNA (cDNA) into the hepatocytes of male phenylketonuria (PKU) mice, leading to a complete and permanent correction of their hyperphenylalaninemic phenotype. In this study, we report only partial phenotypic correction in female PKU mice, even though hepatic PAH activities in both sexes after gene treatment were similar. Daily injections of tetrahydrobiopterin (BH4), an essential co-factor for phenylalanine hydroxylation, in the gene-treated females led to complete correction of their PKU phenotype. After gonadectomy, serum phenylalanine levels in the gene-treated females were reduced to normal, whereas those in the gene-treated males remained unchanged. The sterile gene-treated PKU mice were subjected to daily sex hormone injections. Whereas the estradiol-treated sterile males developed hyperphenylalaninemia, the dihydrotestosterone-treated sterile females remained normal phenylalaninemic. The results indicate that it is estrogen that suppresses the steady-state levels of BH4 in mouse hepatocytes that became limiting, which is the underlying mechanism for the observed sexual dimorphism in PKU mice after PAH gene treatment. Livers of the PAH gene–corrected PKU mice also appeared normal and without apparent pathologies.
Non-dermatophytes in onychomycosis of the toenails
Authors: D.H. ELLIS, A.B. WATSON, J.E. MARLEY, T.G. WILLIAMS
Journal: British Journal of Dermatology (1997)

A multicentre trial for the treatment of dermatophyte onychomycosis of the toenails with terbinafine was carried out in Australia and New Zealand. Between eight and 12 nail samples were obtained from each of the 118 patients in the 48-week trial, and each sample was investigated by direct microscopy and culture for dermatophyte and non-dermatophyte fungi. Patients were randomized to treatment with terbinafine at 250 mg/day or placebo for the first 12 weeks of the study, then non-responders were offered a 12-week course of terbinafine from week 28. All patients had a dermatophyte infection. In 42 patients (36%) microscopy and mycological culture identified dermatophytes alone. In the remaining 76 patients (64%), a non-dermatophyte mould or yeast was also isolated at some stage during the trial, but in only three patients did the same non-dermatophyte persist in two or more successive nail specimens. The presence of a fungal contaminant in addition to a dermatophyte had no apparent effect on the efficacy of treatment with terbinafine. We conclude that non-dermatophyte moulds and yeasts are generally found as contaminating organisms in dermatophyte onychomycosis, secondary to the dermatophytes, and that they do not influence the outcome of treatment.
Clinical History, Skin Prick Test and RAST in the Diagnosis of Birch and Timothy Pollinosis
Authors: G. Petersson, S. Djueborg, R. Ingestad
Journal: Allergy (1986)

The diagnostic efficacy of clinical history (CH), skin prick test (SPT) and RAST was estimated in relation to nasal and conjunctival provocation tests (NPT, CPT) in 69 patients with seasonal rhinoconjunctivitis. The extracts used were freeze‐dried, and biologically standardized birch and timothy allergen preparations matched to the extracts on Phadebas RAST® discs. Based on single determinations the sensitivity, specificity and predictive values were calculated. There were highly significant ( P &lt; 0.001) correlations between all parameters: NPT, CPT, CH, SPT and RAST. For birch the combination of SFT and RAST made the PTs superfluous as both sensitivity and specificity then reached 100%. With timothy the sensitivity was 97% and with the addition of CH 100%. However, the specificity was only 79% through combining CH, SPT and RAST. The present study using the same standardized allergen preparation in all tests showed a good correlation between indirect test results and provocation tests.
The Long-term Psychological Effects of Daily Sedative Interruption on Critically Ill Patients
Authors: John P. Kress, Brian Gehlbach, Maureen Lacy, Neil Pliskin, Anne S. Pohlman, Jesse B. Hall
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Critically ill patients often receive sedatives, which may delay liberation from mechanical ventilation and intensive care unit discharge. Daily interruption of sedatives alleviates these problems, but the impact of this practice on long-term psychological outcomes is unknown. We compared psychological outcomes of intensive care unit patients undergoing daily sedative interruption (intervention) with those without this protocol (control). Assessments using (1) the Revised Impact of Event Scale (evaluates signs of posttraumatic stress disorder [PTSD]), (2) the Medical Outcomes Study 36 item short-form health survey, (3) the State-Trait Anxiety Inventory, (4) the Beck Depression Inventory-2, (5) and the Psychosocial Adjustment to Illness score (overall quality of adjustment to current or residual effects of illness) were done by blinded observers. The intervention group had a better total Impact of Events score (11.2 vs. 27.3, p=0.02), a trend toward a lower incidence of PTSD (0% vs. 32%, p=0.06), and a trend toward a better total Psychosocial Adjustment to Illness score (46.8 vs. 54.3, p=0.08). We conclude that daily sedative interruption does not result in adverse psychological outcomes, reduces symptoms of PTSD, and may be associated with reductions in posttraumatic stress disorder.
Cl- secretion induced by bile salts. A study of the mechanism of action based on a cultured colonic epithelial cell line.
Authors: K Dharmsathaphorn, P A Huott, P Vongkovit, G Beuerlein, S J Pandol, H V Ammon
Journal: Journal of Clinical Investigation (1989)

When applied to the basolateral (serosal) side of the T84 colonic epithelial monolayer, taurodeoxycholate caused net Cl- secretion in a dose-dependent manner with a threshold effect observed at 0.2 mM. In contrast, when applied to the apical (luminal) surface, concentrations of taurodeoxycholate below 1 mM had little or no effect. Only when the concentration of taurodeoxycholate present on the apical side was greater than or equal to 1 mM did apical addition results in an electrolyte transport effect. This apical effect on electrolyte transport was associated with an abrupt increase in the permeability of the monolayer. Cyclic AMP and cyclic GMP in the T84 monolayers were not increased by the bile salt, but in the presence of extracellular Ca2+, free cytosolic Ca2+ increased with a graded dose effect and time course that corresponded approximately to the changes in short circuit current (Isc). The results suggest that luminal bile salts at a relatively high concentration (greater than or equal to 1 mM) increase tight junction permeability. Once tight junction permeability increases, luminal bile salts could reach the basolateral membrane of the epithelial cells where they act to increase free cytosolic Ca2+ from extracellular sources. The resulting increases in free cytosolic Ca2+, rather than in cyclic nucleotides, appear to be involved in transcellular Cl- secretion.
Bioterrorism on the Home Front
Authors: H. Clifford Lane, Anthony S. Fauci
Journal: JAMA (2001)

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
Retention of CD34+ CML stem/progenitor cells during imatinib treatment and rapid decline after treatment with second-generation BCR–ABL inhibitors
Authors: Y Minami, A Abe, M Minami, K Kitamura, J Hiraga, S Mizuno, K Ymamoto, M Sawa, Y Inagaki, K Miyamura, T Naoe
Journal: Leukemia (2012)

ABL-tyrosine kinase inhibitor (TKI), imatinib (IM) is suggested to be effective for proliferating leukemic cells, not quiescent chronic myeloid leukemia (CML) stem cells.1, 2, 3 Recent clinical trials suggest that CML treatment can be improved with more potent BCR–ABL inhibition during the second generation of ABL-tyrosine kinase inhibitors (2nd-TKIs) such as dasatinib and nilotinib.4 To comparatively examine the effects of IM and 2nd-TKIs on the BCR–ABL-positive hematopoietic stem cells (HSC) and progenitors, we investigated 47 CML-chronic phase cases using methods previously reported with FACSAria and quantitative real-time-PCR of BCR–ABL among each sorted population: total mononuclear cells, HSC/Thy-1+, HSC/Thy-1−, common myeloid progenitors, granulocyte macrophage progenitors and megakaryocyte erythroid progenitors (detailed in Supplementary Materials and Methods).5, 6 By using this method in the HSC population, more than 30% of cells are supposed to have stem cell potential, probably as long-term culture-initiating cells.7
1041-93 Caspase inhibition reduces calpain-activation and calpain induced troponin-I cleavage, calpain induced cytochrome C release and apoptosis in the postmyocardial infarction remodeling myocardium
Authors: Y Chandrashekhar, Ruth Anway, Somasundaram Porur, Inder Anand
Journal: Journal of the American College of Cardiology (2004)
English NHS to set up new reporting system for errors
Authors: S. Mayor
Journal: BMJ (2000)

The NHS in England is to set up a new, national system for logging all failures, mistakes, and “near misses” in health care and is to move away from the current “blame culture” to one that can learn from adverse events; these changes follow recommendations in a major report published last week.

The report suggests that the health service can learn from industry, particularly aviation, about how to learn from incidents and near misses. It acknowledges that the great majority of NHS care is of a very high clinical standard and serious failures are uncommon.

It points out, however, that up to 850000 adverse healthcare events occur each year in the NHS hospital sector alone. Lack …