tbuckley/cabot-search huggingface dataset:
Auto-Antigenic Protein-DNA Complexes Stimulate Plasmacytoid Dendritic Cells to Promote Atherosclerosis
Authors: Yvonne Döring, Helga D. Manthey, Maik Drechsler, Dirk Lievens, Remco T.A. Megens, Oliver Soehnlein, Martin Busch, Marco Manca, Rory R. Koenen, Jaroslav Pelisek, Mat J. Daemen, Esther Lutgens, Martin Zenke, Christoph J. Binder, Christian Weber, Alma Zernecke
Journal: Circulation (2012)

Inflammation has been closely linked to auto-immunogenic processes in atherosclerosis. Plasmacytoid dendritic cells (pDCs) are specialized to produce type-I interferons in response to pathogenic single-stranded nucleic acids, but can also sense self-DNA released from dying cells or in neutrophil extracellular traps complexed to the antimicrobial peptide Cramp/LL37 in autoimmune disease. However, the exact role of pDCs in atherosclerosis remains elusive.Here we demonstrate that pDCs can be detected in murine and human atherosclerotic lesions. Exposure to oxidatively modified low-density lipoprotein enhanced the capacity of pDCs to phagocytose and prime antigen-specific T cell responses. Plasmacytoid DCs can be stimulated to produce interferon-α by Cramp/DNA complexes, and we further identified increased expression of Cramp and formation of neutrophil extracellular traps in atherosclerotic arteries. Whereas Cramp/DNA complexes aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice, pDC depletion and Cramp-deficiency in bone marrow reduced atherosclerosis and anti-double-stranded DNA antibody titers. Moreover, the specific activation of pDCs and interferon-α treatment promoted plaque growth, associated with enhanced anti-double-stranded-DNA antibody titers. Accordingly, anti-double-stranded DNA antibodies were elevated in patients with symptomatic versus asymptomatic carotid artery stenosis.Self-DNA (eg, released from dying cells or in neutrophil extracellular traps) and an increased expression of the antimicrobial peptide Cramp/LL37 in atherosclerotic lesions may thus stimulate a pDC-driven pathway of autoimmune activation and the generation of anti-double-stranded-DNA antibodies, critically aggravating atherosclerosis lesion formation. These key factors may thus represent novel therapeutic targets.
Effect of Anesthetics on Brain Gamma-Aminobutyric and Glutamic Acid Levels
Authors: Hideo Tsuji, Reuben C. Balagot, Max S. Sadove
Journal: JAMA (1963)

GAMMA-AMINOBUTYRIC ACID was found, by Roberts et al,<sup>1</sup>Awapara et al,<sup>2</sup>and proved by Udenfriend,<sup>3</sup>to be present in considerable amounts in the mammalian brain. The significance of this discovery escaped notice until Florey<sup>4</sup>found that an extract from the mammalian central nervous system inhibited the spontaneous activity of the stretch receptor neuron of the crayfish. He also demonstrated the ability of this extract to block the effect of acetylcholine on this receptor neuron. He called this material "Factor I." Bazemore et al<sup>5</sup>subsequently identified "Factor I" as being primarily composed of gamma-aminobutyric acid. Interest in this substance really perked up, however, with the report of Hayashi et al<sup>6</sup>that gamma-amino-hydroxybutyric acid inhibited, in dogs, convulsions induced by electrical or chemical stimulation; Killam and Bain's<sup>7</sup>findings that semicarbazide induced convulsions in rats are associated with a decrease in brain gamma-aminobutyric acid concentration. Glutamic
Suicidal attempt with propranolol.
Authors: W Wermut, M Wojcicki
Journal: BMJ (1973)

treatment is indicated when retrograde ven- ous pressure is not very marked.With both types of therapy the patient should be am- bulatory since this is the best way to prevent complications.If each patient is indivi- dualized and treated according to specific in- dications, excellent results will be obtained both from injection therapy and from sur- gery.-Weare, etc.,
Effects of gonadectomy and hormonal replacement on rat hearts.
Authors: J Scheuer, A Malhotra, T F Schaible, J Capasso
Journal: Circulation Research (1987)

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 5195: Progressive overpopulation of colonic stem cells during tumorigenesis is linked to delayed licensing of cells for DNA synthesis in the process of crypt cell maturation
Authors: Bruce M. Boman, Tao Zhang, Zenobia Cofer, Juan Palazzo, Jeremy Z. Fields
Journal: Cancer Research (2011)

Abstract Since cancer stem cell (SC) overpopulation drives tumor growth, it is critical to identify mechanisms underlying SC overpopulation. Our hypothesis that SC overpopulation underlies development of colorectal cancer (CRC), which was based on our kinetic studies (Cancer Res 61: 3304-13, 2008), has since been supported by our biologic studies showing that ALDH1 is a specific marker for human colonic SC and can track SC overpopulation during tumor development (Cancer Res 69:3382-9, 2009). We then asked: What cellular mechanisms that normally control SC population size in colonic crypts become dysregulated during colon tumorigenesis? Accordingly, we measured the orderly, sequential phenotypic transitions in human crypts that colonocyte subpopulations undergo during their maturatio– a process involving both proliferation and differentiation. Quantitative immunohistochemical mapping of crypt cell subpopulations was done using markers for SC (ALDH1), proliferating cells (DNA-synthesis-licensing proteins: CDT1/geminin/MCM2), cell-cycle arrest (P21), and apoptosis (M30/TUNEL). Staining indices were used to evaluate changes in maturation during the step-wise progression to colon cancer. The rate of crypt cell maturation was measured using clearance of BrdU from pre-labeled wildtype (C57BL/6) and premalignant (ApcMin/+) mouse intestine. In normal human colon, the proportion of cells expressing licensing proteins was low at crypt bottom (where SC reside), high in the lower crypt where proliferating cells reside, and nil in the upper crypt (where differentiated/apoptotic cells reside). In FAP and adenomatous human crypts, SC and proliferating cell populations expanded towards the crypt top while differentiated/apoptotic subpopulations in the upper crypt contracted. ApcMin/+ mouse crypts had slower BrdU clearance than controls. Colonocytes become licensed for DNA synthesis in the transition from SC to proliferating cells; licensing is delayed in premalignant crypts. Moreover, all transitions between cell phenotypes occur more slowly in premalignant human colonic crypts, indicating that crypt cell maturation becomes progressively delayed during colon tumorigenesis. Since crypt cell maturation regulates colonic SC population size, as maturation becomes progressively delayed, crypt SC overpopulation will develop, leading to dysplasia and colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5195. doi:10.1158/1538-7445.AM2011-5195
Lichen sclerosus et atrophicus of the scalp
Authors: IAIN STEWART FOULDS
Journal: British Journal of Dermatology (1980)

A patient is described who developed pruritic lesions of the scalp with increasing hair loss and plaque formation over a period of 15 years, in association with patches if white atrophic skin on her trunk and vulva in the last 5 years. Biopsies of the scalp and trunk lesions both showed lichen sclerosus et atrophicus. This would appear to be the first recorded case of lichen sclerosus et atrophicus of the scalp in the English literature.
Multiple Lineages of the Non-LTR Retrotransposon Rex1 with Varying Success in Invading Fish Genomes
Authors: Jean-Nicolas Volff, Cornelia Körting, Manfred Schartl
Journal: Molecular Biology and Evolution (2000)

Rex1, together with the related Babar elements, represents a new family of non-long-terminal-repeat (non-LTR) retrotransposons from fish, which might be related to the CR1 clade of LINE elements. Rex1/Babar retrotransposons encode a reverse transcriptase and an apurinic/apyrimidinic endonuclease, which is very frequently removed by incomplete reverse transcription. Different Rex1 elements show a conserved terminal 3′ untranslated region followed by oligonucleotide tandem repeats of variable size and sequence. Phylogenetic analysis revealed that Rex1 retrotransposons were frequently active during fish evolution. They formed multiple ancient lineages, which underwent several independent and recent bursts of retrotransposition and invaded fish genomes with varying success (from <5 to 500 copies per haploid genome). At least three of these ancient Rex1 lineages were detected within the genome of poeciliids. One lineage is absent from some poeciliids but underwent successive rounds of retrotransposition in others, thereby increasing its copy number from <10 to about 200. At least three ancient Rex1 lineages were also detected in the genome project fish Fugu rubripes. Rex1 distribution within one of its major lineages is discontinuous: Rex1 was found in all Acanthopterygii (common ancestor in the main teleost lineage approximately 90 MYA) and in both European and Japanese eels (divergence from the main teleost lineage about 180 MYA) but not in trout, pike, carp, and zebrafish (divergence 100–120 MYA). This might either result from frequent loss or rapid divergence of Rex1 elements specifically in some fish lineages or represent one of the very rare examples of horizontal transfer of non-LTR retrotransposons. This analysis highlights the dynamics and complexity of retrotransposon evolution and the variability of the impact of retrotransposons on vertebrate genomes.
Abstract 4975: Dynamic <i>in vivo</i> interactions of the eleven-nineteen lysine-rich leukemia protein (ELL) in the mammalian nucleus
Authors: Clay Wakano, Temesgen D. Fufa, Timothy J. Stasevich, Taara A. Avery, James G. McNally, Kevin Gardner
Journal: Cancer Research (2010)

Abstract The eleven-nineteen lysine-rich leukemia protein (ELL) is an elongation factor that increases the processivity of RNA polymerase II during transcription. ELL forms a fusion protein with the histone-methyltransferase mixed lineage leukemia protein (MLL) via a chromosomal translocation t(11;19)(q23;p13.1), often associated with acute myeloid leukemia (AML) in both adults and children. This chromosomal translocation alters both proteins, eliminating the carboxyl-terminal methyltransferase domain of MLL and the amino-terminal elongation inhibitory domain of ELL. The biological and regulatory role of normal ELL and ELL in the MLL-ELL fusion protein during transcription is not understood. Transcription is a multi-step process that can be separated into a series of events which involve proteins that form transient and stable complexes with the DNA template at various times during the transcription process. Using the Fluorescence Recovery After Photobleaching (FRAP) approach allows for the dissection of these events in transcription. Transcription in living cells has been examined by photobleaching fluorescently tagged RNA polymerase II, revealing its binding kinetics and quantifying the residency times associated with the different phases of transcription, with shorter residency times correlating with recruitment and initiation and longer residency times with elongation. We have used FRAP to examine the dynamic kinetics of ELL and pol II and other transcriptional elongation factors, including P-TEFb during active transcription in living cells in the presence or absence of specific inhibitors of transcription elongation and initiation. Our results suggest that there is a hierarchy of interactions between elongation factors and pol II during the transcription cycle that is orchestrated through specific interactions with ELL and gives general insights into how disruption of ELL function through its fusion to MLL may selectively influence transcriptional elongation events and gene expression in rapidly growing cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4975.
Norepinephrine sensitivity and desensitization of cultured single vascular muscle cells.
Authors: K Hermsmeyer, R Mason
Journal: Circulation Research (1982)

Isolated single vascular muscle cells were used for studies of the inherent norepinephrine sensitivity and the conditions important for detecting highest norepinephrine sensitivity. Rat vascular muscle cell contractions were quantitated from spontaneous contractions during pulse applications of the drugs, with a time course designed to simulate norepinephrine release in situ. Isolated vascular muscle cells showed a sensitivity to norepinephrine two orders of magnitude greater than those found from isolated intact blood vessels. Associated with the high sensitivity, there was a marked reduction in the response to a second application of norepinephrine or phenylephrine. The reduced second response appears to result from desensitization that is more pronounced in cells that have been exposed to only trace concentrations of catecholamines. These data appear to suggest that there might be continuous suppression of transmitter sensitivity that occurs as a result of transmitter exposure, and possibly cell-to-cell associations. Desensitization would at first severely limit the response to norepinephrine by reducing or eliminating the response to prolonged exposure or a second dose. Thereafter, a lessening of the desensitization process on continuous exposure to catecholamines would be the result, in part, of lowered sensitivity and, in part, of a smaller desensitization response. This process would continuously modulate norepinephrine sensitivity, based on the frequency and extent of stimulation, and we have called it the theory of physiological desensitization.
Critical Surgical Illness
Authors: John H. Wulsin
Journal: JAMA (1972)

This is a four-star volume! Thirty monographs, some 20 to 45 pages in length, cover subjects that represent the principal cause of major morbidity and mortality on most surgical services. The editor declares that the book is about treatment, but the reader should be prepared for academic discussions, solidly founded on historical introduction, pathophysiologic background, and structural change. This is no manual of emergency treatment, suitable for the desk in the admitting and intensive-care units. Rather, the book epitomizes, in print, the professor's approach to those problems discussed in death meetings and complication conferences on a teaching surgical service. And so, dear reader, on the night before such conferences settle down with this book and the following day the thoroughness of your discussion will awe your colleagues.  The tone is set in a scholarly opening chapter (Francis Moore of Harvard) on posttraumatic pulmonary insufficiency. The editor, James Hardy of the
Circulating Anticoagulant in Asymptomatic Persons Seropositive for Human Immunodeficiency Virus (HIV)
Authors: JEAN-JACQUES LEFRERE
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 May 1988Circulating Anticoagulant in Asymptomatic Persons Seropositive for Human Immunodeficiency Virus (HIV)JEAN-JACQUES LEFRERE, M.D., DANIELLE GOZIN, Ph.D., JOELLE LERABLEJEAN-JACQUES LEFRERE, M.D.Search for more papers by this author, DANIELLE GOZIN, Ph.D.Search for more papers by this author, JOELLE LERABLESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-5-771_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The prevalence of circulating anticoagulant has been reported to be high in patients with the acquired immunodeficiency syndrome (AIDS) (1, 2). The association of circulating anticoagulant with Pneumocystis carinii pneumonia has been described by some authors (1) but has not been found by others (3). We prospectively studied the prevalence of this anomaly in asymptomatic persons seropositive for the human immunodeficiency virus (HIV).Twenty-three nonhemophiliac, asymptomatic HIV-seropositive persons detected through systematic screening of blood donations were enrolled. Mean duration of the follow-up was 17 months (range, 12 to 18); 13 subjects had three semestrial controls,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Institut National de Transfusion Sanguine 75015 Paris France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAntiphospholipid thrombosis syndromesState-of-the-Art Review: Antiphospholipid Thrombosis SyndromesA rash, circulating anticoagulant, then meningitisThe Antiphospholipid Thrombosis Syndromes: A Common Multidisciplinary Medical ProblemThe Antiphospholipid and Thrombosis (APL-T) Syndromes: Clinical and Laboratory CorrelatesThe antiphospholipid and thrombosis syndromesPostoperative Complications in Patients With Human Immunodeficiency Virus DiseaseAcquired Circulating AnticoagulantsAnticardiolipin antibodies (ACA) are most often not associated with lupus-like anticoagulant (LLAC) in human immunodeficiency virus (HIV) infectionHemostatic Abnormalities in HIV DiseaseRheumatologic Manifestations of Infection with Human Immunodeficiency Virus (HIV)Brian R. Kaye, MDHematologic aspects of human immunodeficiency virus infection: Laboratory and clinical considerations 1 May 1988Volume 108, Issue 5Page: 771-771KeywordsAIDSAnticoagulantsBlood banksHIVPneumocystis carinii pneumonia Issue Published: 1 May 1988 PDF DownloadLoading ...
Drug Therapy in Anaphylaxis
Authors: Carl E. Arbesman, Robert E. Reisman
Journal: JAMA (1962)

To the Editor:—  We read with great interest the letter Anaphylactoid Reaction to Demethylchlortetracycline Hydrochloride in the Aug. 4, 1962, issue ofThe Journal( 181 :454). This, indeed, is a most unusual type of reaction to see with this particular antibiotic. However, it has been commonly seen with reactions to penicillin.  The treatment of anaphylactic reaction from any cause is the use of epinephrine in dosages of 0.3 to 0.5 cc, repeated every 15 or 30 min as necessary. If this alone does not do the job, intravenous aminophylline and intravenous antihistaminics are also very useful. An intravenous drip with levarterenol ( l -norepinephrine) bitartrate to support the shocklike syndrome is often lifesaving.  It is noted that the authors immediately started the use of corticosteroids. There is no clinical or laboratory evidence that corticosteroids will act quickly enough to be effective in anaphylaxis in either man or animal. Corticosteroids do not
OLD FRACTURES OF THE ANKLE
Authors: EMIL S. GEIST
Journal: JAMA (1924)

Ankle fractures may be divided into four classes, characterized by (<i>a</i>) inversion (Fig. 1); (<i>b</i>) eversion (Fig. 2); (<i>c</i>) backward displacement of the astragalus on the tibia (Fig. 3), and (<i>d</i>) linear fractures, fractures without displacement and other unusual types. While it is not my intention to describe at length these various types of fracture, I may say that the inversion type consists usually of a fracture of the internal malleolus and of the fibula, either at the styloid process or somewhat higher up, and that the astragalus is pushed toward the midline so that the foot appears in more or less inversion. The eversion type, commonly known as Pott's fracture, consists of a tearing off of the ligaments attached to the internal malleolus, or of the malleolus itself and of the fibula from 1 to 3 inches above its lower end. It is characterized by eversion. This is the
Central venulitis in pediatric liver allografts
Authors: Alyssa M. Krasinskas, Eduardo D. Ruchelli, Elizabeth B. Rand, Jesse L. Chittams, Emma E. Furth
Journal: Hepatology (2001)

Central venulitis (CV), a distinct histologic lesion described in adult liver transplants, can occur with acute portal tract rejection or in isolation (ICV). Possible etiologies include immunosuppressive drug toxicity, acute cellular rejection, viral hepatitis, ischemic injury, and recurrent disease. This study was designed to characterize ICV and to assess its potential etiology in pediatric liver recipients because this population generally does not develop recurrent disease or viral hepatitis. All posttransplantation liver biopsy specimens that were obtained from children who received liver allografts over a 4–year period were reviewed. ICV was identified in 12 of 127 posttransplantation biopsies and in 7 of 45 allograft recipients. Only 4 liver transplantations were performed for potentially recurrent diseases (primary sclerosing cholangitis). ICV first appeared in posttransplantation biopsy specimens significantly later than did portal rejection alone. The finding of CV was not significantly correlated with elevation of Tacrolimus levels, reason for transplantation, donor/recipient cytomegalovirus (CMV) status or blood type, cold ischemic times, or the incidence of outflow obstruction. The responses of CV to therapy were variable and, although the majority of cases resolved, several episodes persisted or recurred. In conclusion, ICV occurs in 16% of pediatric liver allograft recipients and does not appear to be related to recurrent disease, viral hepatitis, drug toxicity, or graft ischemia. CV may be a variant of acute rejection, but longer follow–up is required to determine the most adequate therapy for this entity.
Injury surveillance in cricket
Authors: John W Orchard
Journal: British Journal of Sports Medicine (2013)

This issue of the BJSM contains three cricket injury surveillance studies, including the first published multicountry surveillance project. Cricket1 narrowly preceded football2 and rugby union3 to the publication of the sport's first consensus statement of injury definitions in 2005. A major distinction between the statements was that the authors of the cricket statement chose to focus on match time-loss injuries only4 rather than ‘all reported’ injuries5 ,6 (which was the perspective chosen by football and rugby union). One of the reasons for cricket statement focusing on the match time-loss injuries was that owing to limited resources being devoted to injury surveillance in cricket, compliance would presumably be easier if there were fewer reporting requirements. Despite this, it has taken 8 years for the first multicountry study7 (and ironically both time-loss and non-time-loss injuries have been reported). During these years, T20 cricket has become far more prominent than it was and consequently many players have multiple contracts with different teams in a given year, so the original definitions probably …