tbuckley/cabot-search huggingface dataset:
Abstract PR12: CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and Polycomb gene repression
Authors: Christopher M. Egan, Ulrika Nyman, Julie Skotte, Gundula Streubel, Siobhán Turner, David J. O'Connell, Vilma Rraklli, Michael J. Dolan, Naomi Chadderton, Hansen Klaus, Farrar Gwyneth Jane, Kristian Helin, Johan Holmberg, Adrian P. Bracken
Journal: Cancer Research (2013)

Abstract The chromatin remodeler CHD5 is expressed in neural tissues and is frequently deleted in aggressive neuroblastoma. Very little is known about the normal function of CHD5, its mechanism of action or how its deletion may contribute to neuroblastoma. Here we report that depletion of CHD5 in the developing murine neocortex blocks neuronal differentiation leading to an accumulation of undifferentiated progenitors. Consistent with this, ChIP-SEQ analysis of CHD5 shows it binds a large cohort of neuronal genes and is required for facilitating their activation during differentiation. However, CHD5 also binds a cohort of Polycomb target genes and is required for the maintenance of H3K27me3 on their promoters and their sustained repression during differentiation. Finally, we show that the chromodomains of CHD5 directly bind H3K27me3 and are essential for the function of CHD5 during neuronal differentiation. These findings provide new insights into the essential role of CHD5 during neurogenesis and show how the inactivation of this candidate tumor suppressor might contribute to the progression of neuroblastoma via a defect in differentiation. This abstract is also presented as Poster A05. Citation Format: Christopher M. Egan, Ulrika Nyman, Julie Skotte, Gundula Streubel, Siobhán Turner, David J. O'Connell, Vilma Rraklli, Michael J. Dolan, Naomi Chadderton, Hansen Klaus, Farrar Gwyneth Jane, Kristian Helin, Johan Holmberg, Adrian P. Bracken. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and Polycomb gene repression. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr PR12.
Plasma Cell Dyscrasias and Cryoglobulins
Authors: Kurt J. Bloch
Journal: JAMA (1982)

<h3>PLASMA CELL DYSCRASIAS</h3> SEVERAL disorders characterized by the uncontrolled monoclonal proliferation of cells synthesizing antibody (immunoglobulin) are generally included in the group of plasma cell dyscrasias. Their morphological and clinical features, taken together with the type of protein produced by the neoplastic cells, permits their grouping into the three following major categories: (1) multiple myeloma, IgG, A, D, and E; (2) Waldenström's macroglobulinemia, IgM; and (3) heavy-chain diseases, gamma, alpha, and mu. A closely related variant, now more frequently encountered due to the widespread use of serum protein electrophoresis, is benign monoclonal gammopathy, a condition in which a serum protein abnormality is noted in the absence of a significant plasma cell neoplasm. As is true of most other neoplasms, the etiology of these tumors remains unknown. <h3>Multiple Myeloma—Clinical Picture</h3> Multiple myeloma, the most common of the plasma cell dyscrasias, is characterized by the infiltration of the marrow by neoplastic plasma
Modulation of the Hyperpolarization-Activated Current (I <sub>f</sub> ) by Adenosine in Rabbit Sinoatrial Myocytes
Authors: Antonio Zaza, Marcella Rocchetti, Dario DiFrancesco
Journal: Circulation (1996)

Background Modulation of sinoatrial pacemaking by adenosine (Ado) in the absence of concomitant adrenergic stimulation (direct modulation) has been attributed to activation of a K + conductance. In the present study, we evaluated the direct effects of Ado on the pacemaking current I f and tested their interaction with those of acetylcholine (ACh). Methods and Results Rabbit sinoatrial myocytes were patch-clamped at 35°C in the presence of 1 mmol/L BaCl 2 and 2 mmol/L MnCl 2 . Ado (1 μmol/L) reversibly reduced I f by 33.1±5.7% of control (n=5; P &lt;.05). Ado (1 μmol/L) reversibly shifted I f midactivation potential by −6.63±1.18 mV (n=4; P &lt;.05). Fully activated I f conductance (0.262±0.037 versus 0.254±0.036 nS/pF; n=6, NS) and reversal potential (−17.35±0.99 versus −18.01±1.42 mV; n=6, NS) were not changed by 10 μmol/L Ado. The Ado receptor antagonist 8-PST (10 μmol/L) reversed the effect of 0.3 μmol/L Ado by 64.9±4.2% (n=6; P &lt;.05). Ado maximally shifted the I f activation curve by −5.85 mV, with a half-maximal concentration of 0.0796 μmol/L (n=93). The shifts in I f activation induced by Ado (0.3 μmol/L) and ACh (1 μmol/L) separately were −4.89±0.05 and −8.84±0.51 mV, respectively; concomitant Ado and ACh superfusion shifted activation by −9.7±0.45 mV (NS versus ACh alone; n=9). Threshold Ado concentrations dose-dependently reduced the rate of spontaneous pacemaker activity (eg, −18.8±3.4% at Ado 0.03 μmol/L). Conclusions Submicromolar Ado directly inhibits I f and slows pacemaking in sinoatrial myocytes; the mode of I f inhibition is similar to that previously described for ACh. Thus, Ado may exert local modulation of sinus rate through signaling pathways similar to those used by ACh.
Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: The lipid research clinics coronary primary prevention trial
Authors: Lars-Göran Ekelund, Chirayath M. Suchindran, Robert P. McMahon, Gerardo Heiss, Arthur S. Leon, Donald W. Romhilt, Carl L. Rubenstein, Jeffrey L. Probstfield, Joseph F. Ruwitch
Journal: Journal of the American College of Cardiology (1989)
Role of S-adenosyl-L-methionine in liver health and injury
Authors: José M. Mato, Shelly C. Lu
Journal: Hepatology (2007)

S-Adenosylmethionine (SAMe) has rapidly moved from being a methyl donor to a key metabolite that regulates hepatocyte growth, death, and differentiation. Biosynthesis of SAMe occurs in all mammalian cells as the first step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase (MAT). Decreased hepatic SAMe biosynthesis is a consequence of all forms of chronic liver injury. In an animal model of chronic liver SAMe deficiency, the liver is predisposed to further injury and develops spontaneous steatohepatitis and hepatocellular carcinoma. However, impaired SAMe metabolism, which occurs in patients with mutations of glycine N-methyltransferase (GNMT), can also lead to liver injury. This suggest that hepatic SAMe level needs to be maintained within a certain range, and deficiency or excess can both lead to abnormality. SAMe treatment in experimental animal models of liver injury shows hepatoprotective properties. Meta-analyses also show it is effective in patients with cholestatic liver diseases. Recent data show that exogenous SAMe can regulate hepatocyte growth and death, independent of its role as a methyl donor. This raises the question of its mechanism of action when used pharmacologically. Indeed, many of its actions can be recapitulated by methylthioadenosine (MTA), a by-product of SAMe that is not a methyl donor. A better understanding of why liver injury occurs when SAMe homeostasis is perturbed and mechanisms of action of pharmacologic doses of SAMe are essential in defining which patients will benefit from its use. (HEPATOLOGY 2007;45:1306–1312.)
Are steroids required for induction therapy and relapses in lupus nephritis?
Authors: Carlos Abud-Mendoza, Roberto González-Amaro
Journal: Annals of the Rheumatic Diseases (2013)

‘A finger in the wound’, is an expression by Condon et al 1 used in their very interesting paper treating severe lupus nephritis with rituximab and mycophenolate, additionally to intravenous methyl-prednisolone, but not long-term oral steroids, achieving a good clinical response in most patients.

Rheumatologists and nephrologists have the notion that glucocorticoids are the cornerstone for the treatment of autoimmune diseases, particularly lupus nephritis, where steroids …
Pregnancy in Women with Chronic Renal Disease
Authors: Susan Hou
Journal: New England Journal of Medicine (1985)

PREGNANCY in women with chronic renal disease is accompanied by an increase in such complications as hypertension and proteinuria and by increases in prematurity and fetal loss. Although fertility is decreased in women with advanced renal insufficiency, pregnancy sometimes occurs. Moreover, transplantation restores fertility to many women with end-stage renal disease. This article attempts to define some of the risks associated with pregnancy in women with renal disease and to offer guidelines for their care.HypertensionThe problem that poses the greatest danger to the mother's life is severe hypertension, with its risk of central nervous system bleeding. Hypertension is . . .
Hemolytic Anemia Caused By Penicillin
Authors: Eva Selirio
Journal: JAMA (1968)

<h3>To the Editor:—</h3> In the article "Hemolytic Anemia Caused by Penicillin" by Nesmith and Davis (<b>203</b>:27), 1968), the authors reach the conclusion that since the cephalothin-treated autologous erythrocyte<sup>51</sup>Cr half-life was shortened in their patient with antipenicillin antibodies these antibodies caused hemolysis of both penicillin and cephalothin-treated erythrocytes. The interpretation of the results of their survival data are open to question since they do not provide data on the survival of cephalothintreated erythrocytes in normal individuals without antibodies. In a recent report, Molthan et al<sup>1</sup>noted that exposure of washed packed red blood cells to 50 mg/ml of cephalothin at 37 C for three hours produced a reduction of 54% in the hematocrit reading in vitro due to hemolysis. Nesmith and Davis incubated whole blood with cephalothin at a concentration of 25 mg/ml for 90 minutes, including the 30-minute incubation period with<sup>51</sup>Cr. It appears likely that
Phosphoproteomic Profiling of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-Dependent Activation of Human Eosinophils
Authors: T.W. Young, K. Pazdrak, S. Stafford, A. Brasier, J. Wiktorowicz, H. Spratt, A. Kurosky
Journal: Journal of Allergy and Clinical Immunology (2006)
Urticaria-like neutrophilic dermatosis in association with IgA gammopathy: a new entity
Authors: M.M. Levender, D.N. Silvers, M.E. Grossman
Journal: British Journal of Dermatology (2013)

Journal Article Urticaria‐like neutrophilic dermatosis in association with IgA gammopathy: a new entity Get access M.M. Levender, M.M. Levender Department of Dermatology 161 Fort Washington Avenue New York NY 10032 U.S.A Search for other works by this author on: Oxford Academic Google Scholar D.N. Silvers, D.N. Silvers Department of Dermatology 161 Fort Washington Avenue New York NY 10032 U.S.ADepartment of Pathology, Columbia University 161 Fort Washington Avenue New York NY 10032 U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.E. Grossman M.E. Grossman Department of Dermatology 161 Fort Washington Avenue New York NY 10032 U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 5, 1 May 2014, Pages 1189–1191, https://doi.org/10.1111/bjd.12771 Published: 01 May 2014
ENHANCED SENSITIVITY FOR THE ASSESSMENT OF REGIONAL MYOCARDIAL WALL MOTION USING QUANTITATIVE GATED BLOOD POOL SPECT IMAGING
Authors: M. W. Groch, R. C. Marshall, W. D. Erwin, D. J. Schippers, E. L. Lands
Journal: Clinical Nuclear Medicine (1992)

Groch, M. W.; Marshall, R. C.; Erwin, W. D.; Schippers, D. J.; Lands, E. L. Author Information
Health Week in Rural Practice
Authors: P. A. Graham
Journal: BMJ (1967)

We are surprised that in the majority of their cases the common bile duct was sufficiently dilated to allow a 2-cm.transverse incision (producing about a 1.5-cm.stoma after two-layered anastomosis) and also surprised that with a stoma that size they had no cases of cholangitis.On preliminary review, our experience is that a 2.5-cm.stoma is advisable, as recommended by Capper,' and this can be obtained in most cases only by a longitudinal incision in the common bile duct and a transverse (or, preferably, longitudinal) incision in the duodenum.The importance of the larger stoma seems to be to allow free return of duodenal contents from the common bile duct rather than to prevent stenosis, but we are investigating these points further.-Weare, etc.,
NFAT2 and STAT3 control type 2 cytokines in CD5 B cells
Authors: Y Renaudineau, S Garaud, J-O Pers, P Youinou
Journal: Annals of the Rheumatic Diseases (2010)

Purpose Autoimmunity and infl ammation are controlled in part by regulatory B cells expressing interleukin 10 (IL-10).Since, one of the characteristic of CD5 B cells lies in their capacity to produce IL-10, the aim of the subject was to characterise the transcription factors (TF) involved.Method To address this question stably transfected CD5 B cells expressing the cell surface isoform, CD5-E1A, or the intracellular isoform, CD5-E1B, were generated and compared to normal B cells (CD5 blood B cells, CD5 cord blood B cells and CD5 from B chronic lymphocytic leukaemia), T cells and CD5 transfected HepG2 cells.Results Based on the observation that NFAT2 is constitutively present in the nucleus of CD5 B cells and that STAT3 is phosphorylated in its S727, we have tested the implication of these two TFs on the expression of IL-10.First, using specifi c inhibitors-like cyclosporine A (NFATs inhibitor) and AG490 (Jak-2/STATs inhibitor) that abrogate IL-10 expression in CD5 B cells.Second, using a chromatin immunoprecipitation assay to reveal that both TFs bind the IL-10 enhancer in CD5 B cells.Interestingly, NFAT2/STAT3 activation is not restricted to IL-10 since we observed that IL-5 and IL-13 promoters recruits NFAT2/STAT3 and express both transcripts in CD5 B cells.Finally, such effect is restricted to CD5 B cells because it was not observed in T cells and CD5-transfected HepG2 cells.Conclusion Results indicate that constitutive calcineurine/ NFAT2 and Jak2/STAT3 pathways contribute to cytokine type 2 expression in CD5 B cells.This observation provides new directions to polarise the immune system.on August 21,
Recurrent wheezing after respiratory syncytial virus or non‐respiratory syncytial virus bronchiolitis in infancy: a 3‐year follow‐up
Authors: H. Valkonen, M. Waris, A. Ruohola, O. Ruuskanen, T. Heikkinen
Journal: Allergy (2009)

Recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non-RSV bronchiolitis.We identified retrospectively all children <2 years of age who were admitted to Turku University Hospital because of bronchiolitis in the months of August-December during 1988-2001. The primary outcome was recurrent wheezing that required long-term asthma medication. Data on asthma medications of the individual children were derived from the Social Insurance Institution of Finland.Within the first year after hospitalization, 36 of 217 (16.6%) children with non-RSV bronchiolitis developed recurrent wheezing, compared with five of 199 (2.5%) children with RSV bronchiolitis [relative risk (RR) 6.6; 95% confidence interval (CI) 2.6-16.5]. The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years (RR 2.9; 95% CI 1.7-5.1) and 3 years (RR 3.4; 95% CI 2.0-5.7) after hospitalization. The increased risk of recurrent wheezing in children with non-RSV-associated bronchiolitis was observed both in boys and girls at all time points of the 3-year follow-up, and it was not explained by the age difference between the RSV and non-RSV groups or any confounding seasonal factors.Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis.
Contributions of Neuro-anatomy and Neuropathology to Psychiatry
Authors: D. Leigh
Journal: BMJ (1955)

Functional uterine bleeding is defined as bleeding from the cavity of the uterus for which no cause can be found by general or local clinical examination, or by curettage of the cavity.Post-menopausal bleeding is considered to be of a different character.The diagnosis is made after full physical examination, both general and local, with study of the vaginal smears by the Papanicolaou method, and confirmed by curettage and microscopy of the endometrium.The cases are initially divided into age groups.Treatment is considered under four headings- symptomatic, surgical, radiotherapeutic, and hormonaland the indications briefly discussed.The importance of conservative measures in adolescents and in women under the age of 40 is emphasized.It is claimed that the vaginal smear is a valuable method of assessing ovarian function and of diagnosing variations from the normal, thereby providing a rational basis for hormonal therapy.Such therapy should be controlled by a planned series of smears.
Characterization of a Bispecific FLT3 X CD3 Antibody in an Improved, Recombinant Format for the Treatment of Leukemia
Authors: Michael Durben, Dominik Schmiedel, Martin Hofmann, Fabian Vogt, Tina Nübling, Elwira Pyz, Hans-Jörg Bühring, Hans-Georg Rammensee, Helmut R Salih, Ludger Große-Hovest, Gundram Jung
Journal: Molecular Therapy (2015)

FLT3 is a receptor-tyrosine-kinase that is expressed on leukemic cells of the myeloid and lymphoid lineage rather specifically. We here report on the construction and selection of bispecific FLT3 X CD3 antibodies in a new recombinant format, termed Fabsc, that resembles the normal antibody structure more closely than the well-established bispecific single chain (bssc)-format. Our preferred antibody, which emerged from an initial selection procedure utilizing different FLT3- and CD3-antibodies, contains the FLT3-antibody 4G8 and the CD3-antibody UCHT1. The 4G8 X UCHT1 Fabsc-antibody was found to be superior to a bssc-antibody with identical specificities with respect to (i) affinity to the target antigen FLT3, (ii) production yield by transfected cells, and (iii) the diminished formation of aggregates. T-cell activation in the presence and absence of cultured leukemic cells and killing of these cells was comparable for both molecules. In addition, the 4G8 X UCHT1 Fabsc-antibody was found to induce T-cell activation and efficient killing of leukemic blasts in primary peripheral blood mononuclear cell (PBMC) cultures of acute myeloid leukemia (AML) patients. In these experiments, the bispecific molecule was clearly superior to an Fc-optimized monospecific FLT3-antibody described previously, indicating that within PBMC of AML patients the recruitment of T cells is more effective than that of natural killer cells.
Expression and differential regulation of natriuretic peptides in mouse macrophages.
Authors: A M Vollmar, R Schulz
Journal: Journal of Clinical Investigation (1995)

The coexpression of the natriuretic peptides ANP, BNP and CNP as well as their differential regulation in mouse macrophages was demonstrated by quantitative PCR, HPLC analysis, and specific radioimmunoassays. Exposure of peritoneal- and bone marrow-derived macrophages to various immunomodulators revealed that bacterial LPS strikingly increases (up to 300-fold) the mRNA coding for CNP as does zymosan (up to 15-fold). In this respect, neither the phorbol ester PMA nor the glucocorticoid dexamethasone had any effect. Examination of macrophages for ANP mRNA showed a similar response to LPS and zymosan, though only a three- to sixfold increase, confirming previous data. In contrast, the concentration of mRNA coding for brain natriuretic peptide in these cells was reduced by dexamethasone (up to twofold) as well as LPS (two- to fivefold). No change was observed upon challenge with zymosan or PMA. The findings at the mRNA level are complemented by their corresponding peptide products. Incubation of macrophages with LPS resulted in a two- and fivefold elevation of intracellular ANP and CNP immunoreactivity, respectively. The amount of peptides released from cells under these conditions was found increased for ANP (threefold) and CNP (10-fold). No changes were observed for both intra- and extracellular brain natriuretic peptide. The coexpression of natriuretic peptides in macrophages as well as their different regulations by immunomodulators suggest discrete functions of these peptides within the immune system.
Search for the Uremic Toxin
Authors: Morrell M. Avram, Donald A. Feinfeld, Aibar H. Huatuco
Journal: New England Journal of Medicine (1978)

In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.
DIETARY FATS AND THE DIURNAL SERUM TRIGLYCERIDE LEVELS IN MAN
Authors: Peter T. Kuo, John C. Carson
Journal: Journal of Clinical Investigation (1959)

A large number of studies have been made in the attempt to correlate serum cholesterol concentrations in man and in animals with varying amounts and with different kinds of dietary fat.However, only a few observations limited to the effect of diet upon the fasting human serum triglyceride concentration have been reported (1)(2)(3)(4).This may be due, at least in part, to the high lability of this serum lipid fraction.The works of Cunningham and Peters (5), Man and Gildea (6), Elkes, Frazer and Stewart (7), Brun (8), Turner and Steiner (9) and Havel (10, 11) clearly demonstrated that variations in both the fat and carbohydrate contents of each meal consistently produced rapid and marked changes in the triglyceride concentration in the human se- rum, while at the same time, they caused little or no change in the serum cholesterol concentration.Hence, in order to obtain a complete picture of the serum triglyceride level of a given subject, determination of its diurnal variations as well as the fasting level is desirable.The present investigation is designed to study and compare the 24 hour serum triglyceride curves of the same individual after he is stabilized se- quentially on an isocaloric: a) full diet which contains 100 to 140 Gm. of animal fats per day, b) rice and fruit diet, and c) corn oil formula diet in which corn oil constitutes 50 to 70 per cent of the total daily caloric intake of the individual. MATERIAL AND METHODClinical data of patientts studied.Ten cooperative am- bulatory subjects, seven males and three females, with various serum lipid concentrations were selected for the
228 Budd-chiari syndrome (BCS) and heparin induced thrombocytopenia (HIT)
Authors: A. Plessier, Y. Consigny, P.E. Rautou, R. Boucari, A. Bezeaud, L. Boudaoud, J.J. Kiladjian, C. Brumpt, V. Saada, B. Condat, D.C. Valla, M.H. Denninger
Journal: Journal of Hepatology (2006)