tbuckley/cabot-search huggingface dataset:
TCT-642 Two zotarolimus-eluting stent generations: a meta-analysis of 12 randomized trials versus other limus-eluting stents and an adjusted indirect comparison
Authors: Salvatore Cassese, Gjin Ndrepepa, Lamin King, Tomohisa Tada, Massimiliano Fusaro, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2012)
The Japanese medaka, Oryzias latipes, as a new model organism for studying environmental germ-cell mutagenesis.
Authors: A Shima, A Shimada
Journal: Environmental Health Perspectives (1994)

The effects of genotoxic substances on ecosystems should be assessed using various test systems with multiple genetic end points. The most widely used test system has been the specific-locus test developed by W.L. Russell, using the mouse. We are developing a new, nonmammalian test system using the Japanese medaka, Oryzias latipes. We have examined 625,926 embryos that correspond to 1,586,649 loci. In the medaka test system, four genetic end points are evaluated: dominant lethals, total mutations, viable mutations, and malformations. Because the medaka is an oviparous experimental animal, we were able to determine that approximately 90% of spontaneous as well as gamma-ray-induced total mutants died during development, irrespective of spermatogenesis stages at the time of exposure. Exposure of sperm and spermatids to ethylnitrosourea (ENU) also resulted in embryonic death of approximately 90% of total mutants. In sharp contrast, approximately 90% of total mutants recovered from ENU-exposed spermatogonia became viable mutants. These results indicate that the quantitative relationship between induction of specific-locus mutations and dominant lethals remains the same among spermatogenesis stages for gamma-rays, while it is biased excessively to the induction of specific-locus mutations in ENU-exposed spermatogonia. Thus, the assessment should integrate at least two factors, agent-specific and species-specific effects.
Relationship between plasma benzodiazepine receptor ligand concentrations and severity of hepatic encephalopathy
Authors: Anthony S. Basile, Phil M. Harrison, Robin D. Hughes, Zi-Quang Gu, Lewis Pannell, Angelique McKinney, E. Anthony Jones, Roger Williams
Journal: Hepatology (1994)

Levels of benzodiazepine receptor ligands were measured in plasma samples from 25 patients in various stages of hepatic encephalopathy due to fulminant liver failure who were not exposed to pharmaceutical benzodiazepines immediately before or during hospitalization. Chromatographic analysis of extracted plasma samples revealed one to nine fractions containing material that competitively inhibited [3H]flumazenil binding to benzodiazepine receptors with the pharmacological properties of benzodiazepine receptor agonists. Two of these peaks were positively identified as the 1,4-benzodiazepines diazepam and N-desmethyldiazepam on the basis of chromatographic, ultraviolet and mass spectral evidence. The plasma levels of diazepam and N-desmethyldiazepam were significantly increased above control values in stage 4 hepatic encephalopathy, whereas total benzodiazepine receptor ligand concentrations were increased above control in stages 1 through 4. A significant but weak linear correlation was found between the relative increase in the levels of diazepam, N-desmethyldiazepam and total benzodiazepine receptor ligands and the severity of hepatic encephalopathy. Thus increased concentrations of benzodiazepine receptor ligands appear to contribute to the enhancement of GABAergic neurotransmission in hepatic encephalopathy, particularly in stage 4. These results constitute further support for a role for benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy associated with acute liver failure.
Withholding intravenous drugs did not improve survival to hospital discharge in out-of-hospital cardiac arrest
Authors: Ian G. Stiell
Journal: Annals of Internal Medicine (2010)

ACP Journal Club16 March 2010Withholding intravenous drugs did not improve survival to hospital discharge in out-of-hospital cardiac arrestIan G. Stiell, MD, MScIan G. Stiell, MD, MScUniversity of Ottawa, Ottawa, Ontario, Canada (I.G.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-6-201003160-02008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationOlasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009;302:2222−9. https://pubmed.ncbi.nlm.nih.gov/19934423Clinical Impact RatingsEmergency Med: Cardiology: Reference1 ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005;112(24 Suppl):IV1-203. [PMID: 16314375] Google Scholar Author, Article, and Disclosure InformationAuthors: Ian G. Stiell, MD, MScAffiliations: University of Ottawa, Ottawa, Ontario, Canada (I.G.S.)This article was published at Annals.org on 2 March 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 March 2010Volume 152, Issue 6Page: JC3-8KeywordsAdvanced cardiac life supportAmbulancesCardiopulmonary resuscitationDrug administrationDrugsHeartRandomized trialsResuscitationShockSurvival analysis ePublished: 16 March 2010 Issue Published: 16 March 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Treatment of chronic neutropenia associated with large granular lymphocytosis with cyclosporine a and filgrastim
Authors: Ann Jakubowski, Elliott F. Winton, Alison Gencarelli, Janice Gabrilove
Journal: American Journal of Hematology (1995)

Abstract A patient with neutropenia and life‐threatening infections secondary to T‐γ lymphoproliferative disease, who did not respond to treatment with recombinant human G‐CSF (filgrastim), was treated with filgrastim plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta‐TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be beneficial.
Occurrence of p53 Gene Abnormalities in Gastric Carcinoma Tumors and Cells Lines
Authors: J.-H. Kim, T. Takahashi, I. Chiba, J.-G. Park, M. J. Birrer, J. K. Roh, H. D. Lee, J.-P. Kim, J. D. Minna, A. F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (1991)

We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma.
Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans.
Authors: S Gillis, R Kozak, M Durante, M E Weksler
Journal: Journal of Clinical Investigation (1981)

Human lymphocytes from elderly and young donors were cultured with phytohemagglutinin (PHA) or concanavalin A. Cultures from old donors produced less T cell growth factor (TCGF) and incorporated less tritiated thymidine (3H-Tdr) than did similar cultures from young donors in the presence of either mitogen. Furthermore, the response of lymphocytes from elderly donors to TCGF was impaired. Thus, PHA-activated T cells from aged donors showed no increase tritiated thymidine incorporation when incubated with exogenous human TCGF. In contrast, addition of exogenous human TCGF to PHA-activated peripheral blood leukocytes from younger individuals increased tritiated thymidine incorporation by 30-50%. The impaired response to TCGF was associated with decreased binding of TCGF by PHA-activated cells from old donors. TCGF production or responsiveness was not associated with the presence of "suppressor" activity in elderly T cell preparations. These studies suggest a possible molecular mechanism for the impaired proliferative response of elderly human T cells. These data lend support to the hypothesis that defects in the capacity to either produce or respond to TCGF may be a fundamental cause of immune deficiency.
Infantile hemangioendothelioma of the liver
Authors: Dena M. Selby, Thomas J. Stocker, Myron A. Waclawiw, Charles L. Hitchcock, Kamal G. Ishak
Journal: Hepatology (1994)

Clinical and morphological findings in 91 patients with infantile hemangioendothelioma of the liver are reported. The study comprised 56 girls and 35 boys ranging in age from premature infant to 3 yr; one outlier patient was 18 yr old. Most patients with infantile hemangioendothelioma (87%) were first seen before the age of 6 mo. Congestive heart failure was evident in 15%. Skin hemangiomas were noted in 11%. Anemia, hyperbilirubinemia and increased AST level were present. Solitary lesions were more common than multiple ones (3:2). Immunohistochemical staining of tumor cells for factor VIII was positive in 20 of 21 cases tested; testing for blood group antigen was positive in 8 of 28 cases. Cytokeratin staining verified the presence of bile ducts, some of which appeared to be the result of transformation of injured liver. No pericytes were identified on electron microscopy. The 6-mo survival rate, based on 71 cases, was 70%. Average time of follow-up for the survivors was 7.7 yr. All deaths occurred during the initial presentation/hospitalization of infants, with the exception of two patients who died 3 mo and 7 mo after diagnosis. More recent analytic methods, including immunohistochemical stains and flow cytometric studies, do not contribute to the practical assessment of this tumor. Covariates with significant value in predicting death 6 mo after diagnosis included presence of congestive heart failure, jaundice, multiple tumor nodules and absence of cavernous differentiation.
Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell–mediated hepatitis
Authors: Michael Kremer, Ian Neil Hines, Richard Jameson Milton, Michael Daryl Wheeler
Journal: Hepatology (2006)

Steatohepatitis enhances the severity of liver injury caused by acute inflammation. The purpose of this study was to test the hypothesis that fatty liver due to chronic choline-deficient diet exacerbates concanavalin A (ConA)-induced liver hepatitis, which is predominantly facilitated by T cells. Male C57BL/6 mice were fed either control choline-sufficient diet (CSD) or choline-deficient diet (CDD) for 6 weeks before ConA administration. Mice were sacrificed 3, 9, and 24 hours after ConA injection. Liver injury measured by aspartate aminotransferase (AST), alanine aminotransferase (ALT), pathology, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining was minimal in mice fed either diet before ConA exposure. However, ConA-induced liver injury was significantly greater in CDD-fed mice compared with control-fed mice. Liver cytokines were assessed by quantitative real-time polymerase chain reaction (PCR). The expression of T helper (Th) 1 cytokines tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and interferon gamma (IFN-γ) were dramatically elevated after ConA in CDD-fed mice compared with control-fed mice. CDD also enhanced ConA-induced STAT4 activation, but not STAT6. Notably, regulators of T-cell differentiation were strongly shifted toward a predominant Th1 profile. T-bet, regulator of the Th1 response, was up-regulated in CDD-fed mice, whereas Th2 regulator GATA-3 was significantly suppressed in CDD-fed mice after ConA. Moreover, the expression of suppressor of cytokine signaling (SOCS)-1, SOCS-3, and repressor of GATA-3 (ROG) favored a predominant Th1 cytokine response in CDD-fed mice. In conclusion , these data support the hypothesis that hepatosteatosis caused by CDD is associated with more severe ConA-induced hepatitis due to a predominant shift toward Th1 response.
Increased left ventricular stiffness impairs filling in dogs with pulmonary emphysema in respiratory failure.
Authors: A Gomez, S Mink
Journal: Journal of Clinical Investigation (1986)

In a chronic canine model of pulmonary emphysema, we studied the interaction between left ventricular (LV) mechanics and pulmonary disease during severe hypoxemia. The hypoxemia was similar to that which may occur during a severe exacerbation of chronic obstructive lung disease. In six dogs with papain-induced emphysema and in seven dogs without emphysema, LV mechanics were examined when a hypoxic gas mixture was inspired to reduce PO2 to about 35 mmHg (hypoxic study) and during nonhypoxic conditions (room air study). In both groups, LV diastolic compliance was reduced during the hypoxic study by a similar amount. This finding could not be explained in terms of ventricular interdependence. Our analysis suggested that hypoxia decreased diastolic compliance (i.e., increased LV diastolic stiffness) by impairing LV relaxation. The primary effect of hypoxia was to decrease the extent to which LV relaxation occurred for a given end-diastolic pressure, while the rate of LV relaxation was decreased just slightly. This study indicates that severe hypoxemia because of respiratory failure may impair myocardial relaxation leading to a decrease in LV filling.
Canada's federal and provincial governments reach agreement over healthcare spending
Authors: David Spurgeon
Journal: BMJ (2004)

Canada's Prime Minister Paul Martin, provincial prime ministers, and territorial leaders have reached a new, 10 year agreement on reforming the country's health system that will cost the federal government $C41.2bn (£17.7bn; $31.8bn; €26bn).

The deal promises reductions in patients' waiting times for access to the system; an increase in the number of health professionals; some short term home care and end of life services; increased funding and reforms for northern communities; a national pharmaceuticals strategy whereby patients would be covered for illnesses that had exceptionally high treatment costs; and a new immunisation programme for children.

The initial response from the Canadian Medical Association, nurses, pharmacists, and healthcare associations was positive. The president of the Canadian …
Commentaries on the end of year editorial on the definition of ischaemia in last December's issue
Authors: A. G Kleber
Journal: Cardiovascular Research (1995)

Journal Article Commentaries on the end of year editorial on the definition of ischaemia in last December's issue Get access André G Kléber André G Kléber Department of Physiology, University of Bern, Bern, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Pages 280–281, https://doi.org/10.1016/S0008-6363(95)90000-4 Published: 01 February 1995
John ("Jack") Angell-James
Authors: C. Richmond
Journal: BMJ (2002)

Jack Angell-James was, in his day, the doyen of ear, nose, and throat surgeons. In the 1960s he pioneered two major new operations. One was transethmoidal hypophysectomy, harpooning the pituitary gland through the nose, using a microscope and instruments that he had designed. The operation left patients with a 1 cm incision and saved them from hugely invasive brain surgery. For a while the technique was used for some metastasised hormone dependent breast tumours. Few surgeons were sufficiently …
Targeting B-Cell Receptor Signaling for Anticancer Therapy: The Bruton's Tyrosine Kinase Inhibitor Ibrutinib Induces Impressive Responses in B-Cell Malignancies
Authors: Adrian Wiestner
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2012.44.4281 Journal of Clinical Oncology - published online before print October 8, 2012 PMID: 23045586 Targeting B-Cell Receptor Signaling for Anticancer Therapy: The Bruton's Tyrosine Kinase Inhibitor Ibrutinib Induces Impressive Responses in B-Cell Malignancies Adrian WiestnerxAdrian WiestnerSearch for articles by this author Show More National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD https://doi.org/10.1200/JCO.2012.44.4281 First Page Full Text PDF Figures and Tables Supplements © 2012 by American Society of Clinical Oncology
Reducing the Risk of Multiple Births by Transfer of Two Embryos after in Vitro Fertilization
Authors: Allan Templeton, Joan K. Morris
Journal: New England Journal of Medicine (1998)

In vitro fertilization is associated with a high risk of multiple births, which is a direct consequence of the number of embryos transferred. However, other factors that contribute to the risk are not well defined.Using the data base established by the Human Fertilization and Embryology Authority in the United Kingdom, we studied the factors associated with an increased risk of multiple births in 44,236 cycles in 25,240 women. The factors included the woman's age, the cause and duration of infertility, previous attempts at in vitro fertilization, previous live births, number of eggs fertilized, and number of embryos transferred.Older age, tubal infertility, longer duration of infertility, and a higher number of previous attempts at in vitro fertilization were all associated with a significantly decreased chance of a birth and of multiple births. Previous live birth was associated with an increased chance of a birth but not of multiple births. The higher the number of eggs fertilized, the higher the likelihood of a live birth. When more than four eggs were fertilized, there was no increase in the birth rate for women receiving three transferred embryos as compared with those receiving two, but there was a considerable increase in the rate of multiple births when three were transferred (odds ratio, 1.6; 95 percent confidence interval, 1.5 to 1.8).Among women undergoing in vitro fertilization, the chances of a live birth are related to the number of eggs fertilized, presumably because of the greater selection of embryos for transfer. When more than four eggs are fertilized and available for transfer, the woman's chance of a birth is not diminished by transferring only two embryos. Transferring more embryos increases the risk of multiple births.
Treatment of Herpes Zoster with Liver Extract
Authors: H. S. Gaskell
Journal: BMJ (1949)

Although the eruption of herpes zoster may appear without discomfort, the pain associated with the condition is some- times considerable; and post-herpetic neuralgia may occur with such severity and persistence that, as Osler (1898) recorded, it has been known to drive a patient to commit suicide.The treatments recommended have been legion, including iron, arsenic, strychnine, gelsemium, valerian, and aconite, as well as the customary analgesics; freezing, liniments, diathermy, and the injection of distilled water beneath the skin have also been used.Dickie (1946) relieved herpetic pain in prisoners of war by use of injections of liver extract, which was the only drug available.I have since had the opportunity of observing the effect of liver extract administered empirically to 20 patients with herpes zoster.In all cases the preparation used was "neo-hepatex," administered intramuscularly.Case Histories Case 1.-June 19, 1946.Male aged 76.Herpes of left fore- head, with severe pain.Dosage: 4 ml.The following day there was no pain and the lesion had not extended.A further 2 ml. was given the next day.There was no post-herpetic pain or recurrence.Case 2.-July 20, 1946.Male aged 47.Herpes of forehead.Dosage: 4 ml.first day, followed by 2 ml. on the two ensuing days.Pain ceased after the first injection.Case 3.-Oct.2, 1946.Female aged 71.Herpes involving the twelfth thoracic segment on the left side, with severe pain.Dosage: Two injections of 4 ml., with three days' interval.
Testosterone metabolism to 5?-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes
Authors: E. Makrantonaki, C.C. Zouboulis
Journal: British Journal of Dermatology (2007)

Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator-activated receptor (PPAR) ligands were suggested to be adequate candidates.The influence of testosterone and linoleic acid, a PPAR ligand, as single agents and in combination with of LY191704, a 5alpha-reductase type I inhibitor, was examined on 5alpha-dihydrotestosterone (5alpha-DHT) synthesis and lipid content in human SZ95 sebocytes.Cell proliferation and viability were measured by the 4-methylumbelliferyl heptanoate fluorescence assay and by the Boehringer Lactate Dehydrogenase Assay kit, respectively. 5alpha-DHT enzyme-linked immunosorbent assay was used for the detection of 5alpha-DHT synthesis in cell supernatants after treatment, whereas lipid production was documented by means of the Nile red lipid microassay and fluorescence microscopy.Testosterone promoted 5alpha-DHT synthesis (P < 0.001), whereas linoleic acid increased sebaceous lipids (P < 0.001). The combination of testosterone and linoleic acid exhibited a synergistic effect on the synthesis of 5alpha-DHT (P < 0.01 vs. testosterone) and sebaceous lipids (P < 0.01 vs. linoleic acid). Furthermore, LY191704 reduced 5alpha-DHT and sebaceous lipid levels (P < 0.01 and P < 0.001 in comparison with testosterone/linoleic acid, respectively). Cell proliferation and viability remained unchanged under treatment with all compounds tested.These data suggest a catalytic effect of PPAR ligands on cellular testosterone activation by 5alpha-reduction and the importance of the latter for the regulation of sebaceous lipids.