tbuckley/cabot-search huggingface dataset:
Abstract 2297: 15-Deoxy-Δ12,14-prostaglandin J2 upregulates the expression of 15-hydroxyprostaglandin dehydrogenase through DNA methyltrasferase 1 inactivation
Authors: Hye-Ok Jang, Ha-Na Lee, Areumnuri Kim, Do-Hee Kim, Young-Joon Surh, Hye-Kyung Na
Journal: Cancer Research (2014)

Abstract 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the conversion of prostaglandin E2 to a biologically inactive keto metabolite. The down regulation of 15-PGDH is ubiquitously observed in various human malignancies including breast cancer. Hypermethylation of CpG islands present in the gene promoter region is considered to silence the expression of 15-PGDH. However, the molecular mechanisms underlying regulation of 15-PGDH remain largely unknown. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ, has been reported to have anti-inflammatory and anti-carcinogenic activities. In the present study, we have found that 15-PGJ2 upregulates expression and catalytic activity of 15-PGDH in human breast cancer (MDA-MB-231) cells. 15d-PGJ2 decreased the level of CpG methylation in the 15-PGDH promoter in MDA-MB-231 cells as determined by the bisulfite genome sequencing and methyl specific PCR. 15d-PGJ2 inhibited catalytic activity of methyltransferase 1 (DNMT1) but did not influence expression of either mRNA or protein of DNMT1. siRNA knockdown of DNMT1 induced expression of 15-PGDH. Biotinylated 15d-PGJ2 directly interacted with DNMT1 and reduced its catalytic activity. Chromatin-immunoprecipitation analysis revealed that 15d-PGJ2 significantly attenuated DNMT1 binding to the site for AP-1 transcription factor present in the 15-PGDH promoter regions. We also observed that 15-PGJ2 induced expression of c-Fos, but not c-Jun in the nuclear extract of MDA-MD-231 cells. Moreover, 15d-PGJ2 increased the c-Fos binding to the 15-PGDH promoter regions. A non-electrophilic analogue 9,10-dihydro-15d-PGJ2 failed to suppress the methylation of CpG islands present in 15-PGDH promoter and did not affect DNMT1 activity and 15-PGDH expression. This finding suggests that the α,β-unsaturated carbonyl group is essential for 15d-PGJ2-mediated inactivation of DNMT1 and expression of 15-PGDH. In conclusion, 15d-PGJ2 plays as a hypomethylating agent through direct interaction with DNMT1 and thereby suppresses DNMT1-mediated hypermethylation of 15-PGDH promoter, leading to upregulation of 15-PGDH expression. Citation Format: Hye-Ok Jang, Ha-Na Lee, Areumnuri Kim, Do-Hee Kim, Young-Joon Surh, Hye-Kyung Na. 15-Deoxy-Δ12,14-prostaglandin J2 upregulates the expression of 15-hydroxyprostaglandin dehydrogenase through DNA methyltrasferase 1 inactivation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2297. doi:10.1158/1538-7445.AM2014-2297
The Pathogenesis of Congenital Cardiovascular Anomalies
Authors: Benjamin T. Jackson
Journal: New England Journal of Medicine (1968)

Environmental FactorsViral AgentsIn 1941 Gregg31 reported the relation between rubella and congenital malformations. Maternal infection with rubella in the first trimester has now become widely known as the cause of congenital cardiovascular as well as other anomalies. Figures on congenital anomalies in offspring of mothers suffering from rubella in the first trimester have ranged from 12 to 90 per cent. Such variations are fairly easy to understand in the light of some of the difficulties inherent in the epidemiologic investigation of this problem. In retrospective studies there is a tendency for cases of maternal rubella not associated with . . .
Release of alpha 2-plasmin inhibitor from plasma fibrin clots by activated coagulation factor XIII. Its effect on fibrinolysis.
Authors: J Mimuro, S Kimura, N Aoki
Journal: Journal of Clinical Investigation (1986)

When blood coagulation takes place in the presence of calcium ions, alpha 2-plasmin inhibitor (alpha 2PI) is cross-linked to fibrin by activated coagulation Factor XIII (XIIIa) and thereby contributes to the resistance of fibrin to fibrinolysis. It was previously shown that the cross-linking reaction is a reversible one, since the alpha 2PI-fibrinogen cross-linked complex could be dissociated. In the present study we have shown that the alpha 2PI-fibrin cross-linking reaction is also a reversible reaction and alpha 2PI which had been cross-linked to fibrin can be released from fibrin by disrupting the equilibrium, resulting in a decrease of its resistance to fibrinolysis. When the fibrin clot formed from normal plasma in the presence of calcium ions was suspended in alpha 2PI-deficient plasma of buffered saline, alpha 2PI was gradually released from fibrin on incubation. When alpha 2PI was present in the suspending milieu, the release was decreased inversely to the concentrations of alpha 2PI in the suspending milieu. The release was accelerated by supplementing XIIIa or the presence of a high concentration of the NH2-terminal 12-residue peptide of alpha 2PI (N-peptide) which is cross-linked to fibrin in exchange for the release of alpha 2PI. When the release of alpha 2PI from fibrin was accelerated by XIIIa or N-peptide, the fibrin became less resistant to the fibrinolytic process, resulting in an acceleration of fibrinolysis which was proportional to the degree of the release of alpha 2PI. These results suggest the possibility that alpha 2PI could be released from fibrin in vivo by disrupting the equilibrium of the alpha 2PI-fibrin cross-linking reaction, and that the release would result in accelerated thrombolysis.
A NOTE ON THE TREATMENT OF COUGH IN ADVANCED PULMONARY TUBERCULOSIS
Authors: J. Douglas Blackwood
Journal: JAMA (1913)

As the cough in pulmonary tuberculosis is often a very distressing symptom, especially during the night hours, any remedy that will give relief to the sufferer is of value. An intelligent patient of mine, who was suffering with advanced pulmonary tuberculosis, first called my attention to the fact that when he took acetylsalicylic acid (aspirin) in the evening, his cough was much relieved and as a result he passed a more comfortable night. I made use of this observation in several other cases of advanced pulmonary tuberculosis, asking the patients to let me know if they received any benefit from the treatment and in every case reports were favorable. I now frequently advise patients with advanced pulmonary tuberculosis to take acetylsalicylic acid 5 or 10 grains about 8 p. m. when they are troubled with an excessive cough at night. The smaller dose is often sufficient to control the cough
Lipid Research Clinics Program
Authors: Jerome L. Sullivan
Journal: JAMA (1984)

To the Editor.—  A possible confounding factor not addressed by the Lipid Research Clinics study1is the effect of cholestyramine on iron absorption. Cholestyramine can inhibit the absorption of iron by binding both inorganic and heme iron in the gut.2,3Middle-aged American men typically accumulate a surplus of stored iron.4Daily use of cholestyramine for a period of several years may have slowed the acquisition of new iron stores or even caused a net loss. The lack of change in serum iron and hematocrit values and the small changes in iron-binding capacity reported for the cholestyramine group do not rule out significant reductions in the levels of stored iron.  The relevance of changes in iron stores to a study on the prevention of CHD is suggested by a recent hypothesis on iron and the sex difference in CHD.5,6This hypothesis holds that menstruating women may be protected
Activation of Mammalian Target of Rapamycin Signaling Pathway Contributes to Tumor Cell Survival in Anaplastic Lymphoma Kinase–Positive Anaplastic Large Cell Lymphoma
Authors: Francisco Vega, L. Jeffrey Medeiros, Vasiliki Leventaki, Coralyn Atwell, Jeong Hee Cho-Vega, Ling Tian, Francois-Xavier Claret, George Z. Rassidakis
Journal: Cancer Research (2006)

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) resulting in aberrant expression of chimeric nucleophosmin-ALK. Previously, nucleophosmin-ALK has been shown to activate phosphatidylinositol 3-kinase (PI3K) and its downstream effector, the serine/threonine kinase AKT. In this study, we hypothesized that the mammalian target of rapamycin (mTOR) pathway, which functions downstream of AKT, mediates the oncogenic effects of activated PI3K/AKT in ALK+ ALCL. Here, we provide evidence that mTOR signaling phosphoproteins, including mTOR, eukaryotic initiation factor 4E-binding protein-1, p70S6K, and ribosomal protein S6, are highly phosphorylated in ALK+ ALCL cell lines and tumors. We also show that AKT activation contributes to mTOR phosphorylation, at least in part, as forced expression of constitutively active AKT by myristoylated AKT adenovirus results in increased phosphorylation of mTOR and its downstream effectors. Conversely, inhibition of AKT expression or activity results in decreased mTOR phosphorylation. In addition, pharmacologic inhibition of PI3K/AKT down-regulates the activation of the mTOR signaling pathway. We also show that inhibition of mTOR with rapamycin, as well as silencing mTOR gene product expression using mTOR-specific small interfering RNA, decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis in ALK+ ALCL cells. Cell cycle arrest was associated with modulation of G(1)-S-phase regulators, including the cyclin-dependent kinase inhibitors p21(waf1) and p27(kip1). Apoptosis following inhibition of mTOR expression or function was associated with down-regulation of antiapoptotic proteins, including c-FLIP, MCL-1, and BCL-2. These findings suggest that the mTOR pathway contributes to nucleophosmin-ALK/PI3K/AKT-mediated tumorigenesis and that inhibition of mTOR represents a potential therapeutic strategy in ALK+ ALCL.
Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis
Authors: Syed Khizer Hasan, Ashley N. Mays, Tiziana Ottone, Antonio Ledda, Giorgio La Nasa, Chiara Cattaneo, Erika Borlenghi, Lorella Melillo, Enrico Montefusco, José Cervera, Christopher Stephen, Gnanam Satchi, Anne Lennard, Marta Libura, Jo Ann W. Byl, Neil Osheroff, Sergio Amadori, Carolyn A. Felix, Maria Teresa Voso, Wolfgang R. Sperr, Jordi Esteve, Miguel A. Sanz, David Grimwade, Francesco Lo-Coco
Journal: Blood (2008)
Analysis of the Effect of Flow Rate on the Doppler Continuity Equation for Stenotic Orifice Area Calculations
Authors: Curt G. DeGroff, Robin Shandas, Lilliam Valdes-Cruz
Journal: Circulation (1998)

Background —Flow-rate dependencies of the Doppler continuity equation are addressed in this study. Methods and Results —By use of computational fluid dynamic (CFD) software with turbulence modeling, three-dimensional axisymmetric models of round stenotic orifices were created. Flow simulations were run for various orifice area sizes (0.785, 1.13, 1.76, and 3.14 cm 2 ) and flow rates (0.37 to 25.0 L/min). Reynolds numbers ranged from 100 to 8000. Once adequate convergence was obtained with each simulation, the location of the vena contracta was determined. For each run, maximum and average velocities across the cross section of the vena contracta were tabulated and vena contracta cross-sectional area (effective orifice area) determined. The difference between the maximum velocity and the average velocity at the vena contracta was smallest at high-flow states, with more of a difference at low-flow states. At lower-flow states, the velocity vector profile at the vena contracta was parabolic, whereas at high-flow states, the profile became more flattened. Also, the effective orifice area (vena contracta cross-sectional area) varied with flow rate. At moderate-flow states, the effective orifice area reached a minimum and expanded at low- and high-flow states, remaining relatively constant at high-flow states. Conclusions —We have shown that significant differences exist between the maximum velocity and the average velocity at the vena contracta at low flow rates. A likely explanation for this is that viscous effects cause lower velocities at the edges of the vena contracta at low flow rates, resulting in a parabolic profile. At higher-flow states, inertial forces overcome viscous drag, causing a flatter profile. Effective orifice area itself varies with flow rate as well, with the smallest areas seen at moderate-flow states. These flow-dependent factors lead to flow rate–dependent errors in the Doppler continuity equation. Our results have strong relevance to clinical measurements of stenotic valve areas by use of the Doppler continuity equation under varying cardiac output conditions.
Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials
Authors: Wolfram Klapper, Monika Szczepanowski, Birgit Burkhardt, Hilmar Berger, Maciej Rosolowski, Stefan Bentink, Carsten Schwaenen, Swen Wessendorf, Rainer Spang, Peter Möller, Martin Leo Hansmann, Heinz-Wolfram Bernd, German Ott, Michael Hummel, Harald Stein, Markus Loeffler, Lorenz Trümper, Martin Zimmermann, Alfred Reiter, Reiner Siebert
Journal: Blood (2008)
Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias
Authors: M L Tursky, D Beck, J A I Thoms, Y Huang, A Kumari, A Unnikrishnan, K Knezevic, K Evans, L A Richards, E Lee, J Morris, L Goldberg, S Izraeli, J W H Wong, J Olivier, R B Lock, K L MacKenzie, J E Pimanda
Journal: Leukemia (2014)
A GROUP THERAPY PROJECT WITH PARENTS OF BEHAVIOR PROBLEM CHILDREN IN PUBLIC SCHOOLS
Authors: A. D. BUCHMUELLER, MARGARET C.-L. GILDEA
Journal: American Journal of Psychiatry (1949)

Two groups of mothers of behavior problem children have been meeting for group therapy in public schools. The method of group therapy used approximates those described by Slavson and Amster(11, 4). The J group is composed of 8 members of whom 6 are very regular in attending the weekly sessions. The mothers represent 13 children. The H group has fluctuated more in composition. There have been 12 mothers representing 12 children, but their attendance has been much less regular than the J group. On the basis of carefully collected data from home and school, of the 13 children whose mothers are in the J group, 9 have shown measurable improvement. Four are apparently unchanged. Of the 12 youngsters whose mothers have attended the H group 9 are significantly better in behavior and adjustment, 3 are unchanged. In both groups the parents of the children who are unchanged have been irregular in attendance, with the exception of one J group mother who has attended regularly but who in spite of increased insight has been unable to effect much change in her 2 children's behavior. The authors are cognizant of the fact that other shifting elements in the situations surrounding these children may be partly responsible for the improvement seen in each case. Nevertheless the marked improvement shown in home behavior as well as in school in this brief experimental period points to the effectiveness of this method of approach to the problems of the preadolescent child.
Increased Prevalence of Carotid Atherosclerosis in Hepatitis B Virus Carriers
Authors: Nobukazu Ishizaka, Yuko Ishizaka, Eiko Takahashi, Ei-ichi Toda, Hideki Hashimoto, Minoru Ohno, Ryozo Nagai, Minoru Yamakado
Journal: Circulation (2002)

Recent experimental and epidemiological findings suggest that some infectious agents play a role in the development and promotion of atherosclerosis. We have investigated the possible association between hepatitis B virus surface antigen (HBsAg) positivity and carotid arteriosclerosis.In this cross-sectional cohort study, we analyzed data from subjects undergoing general health-screening tests, including both high-resolution B-mode carotid ultrasound and assessment of HBsAg status, between 1994 and 2001 at our institute. Of the 4686 study subjects (3137 men and 1549 women; age 22 to 88 years), 1294 (28%) had carotid artery plaque and 40 (0.9%) were positive for HBsAg, indicating they were hepatitis B virus carriers. No HBsAg-positive subjects were positive either for antibodies against the hepatitis C virus (HCV) or for HCV core proteins. Univariate analysis revealed HBsAg positivity was associated with carotid plaque with an odds ratio of 1.58 (95% CI, 1.14 to 2.19, P<0.05). When other confounding risk factors for atherosclerosis were included as covariates in the statistical analysis, HBsAg positivity was still positively associated with carotid plaque with an odds ratio of 1.57 (95% CI, 1.10 to 2.24, P<0.05).These findings suggest a possible role of chronic hepatitis B infection in the pathogenesis of carotid arteriosclerosis.
Characterization of the renal CD4+ T-cell response in experimental autoimmune glomerulonephritis
Authors: Helmut Hopfer, Julia Holzer, Stefanie Hünemörder, Hans-Joachim Paust, Marlies Sachs, Catherine Meyer-Schwesinger, Jan-Eric Turner, Ulf Panzer, Hans-Willi Mittrücker
Journal: Kidney International (2012)
Trp64Arg polymorphism in<i>ADRB3</i>gene is associated with elite endurance performance: Table 1
Authors: Catalina Santiago, Jonatan R Ruiz, Amaya Buxens, Marta Artieda, David Arteta, Marta González-Freire, Gabriel Rodríguez-Romo, Signe Altmäe, José I Lao, Félix Gómez-Gallego, Alejandro Lucia
Journal: British Journal of Sports Medicine (2009)

In this study, allele and genotype frequencies of the ADRB1 Arg389Gly (rs1801253), ADRB2 Gly16Arg (rs1042713) and Gln27Glu (rs1042714), and ADRB3 Trp64Arg (rs4994) variations were compared in the following three groups of Spanish (Caucasian) men: (1) world-class endurance athletes (E; runners and cyclists, n=100), (2) elite power athletes (P; sprinters, jumpers and throwers, n=53) and (3) non-athletic controls (C; n=100). No significant differences were observed in genotype and allele distributions among the study groups except for the ADRB3 Trp64Arg polymorphism in E versus C (27% vs 8% of carriers of the Arg allele in E and C, p&lt;0.001; frequency of the minor Arg (C) allele of 14% vs 4% in E and C, p=0.001). Heterozygosity for the ADRB3 Trp64Arg polymorphism seems to be associated with elite endurance performance, while other variants of the β-adrenergic receptors' genes do not seem to significantly influence top-level sports performance, at least in athletes of Spanish origin.
THE ACTION OF THE TURKISH BATH IN DISEASE.Read in the Section of Medicine and Physiology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: CHAS. H. SHEPARD
Journal: JAMA (1891)

One year ago, I had the honor of presenting before this Association certain data regarding the treatment of rheumatism by the Turkish bath. Several gentlemen controverted the position taken in that paper, and now it will be my endeavor to give some facts substantiating what was then laid before you, under the title of THE ACTION OF THE TURKISH BATH IN DISEASE. The Turkish bath is simply a convenient manner of applying heat to the body, and is readily adapted to any diseased condition. It is not exhausting, as many suppose, nor is its salutary influence measured by its power to produce abundant sweating. One of the most remarkable properties of the bath is its ability to allay the sense of fatigue. There is an invigoration arising from the contact of the vitalized skin with the dry heat of the bath, which gives an increased power of drinking in oxygen,
324 Regulation of suppressor of cytokine signaling 3 mrna stability by TNF-α involves activation of the MKK6/P38MAPK cascade
Authors: C. Ehlting, E. Schaper, E.D. Brenndörfer, R.J. Matthes, P.C. Heinriche, D. H↑ssinger, J.G. Bode
Journal: Journal of Hepatology (2006)
Complement and immunoglobulin deposits in the skin of patients with atopic dermatitis
Authors: JOHANNES RING, THOMAS SENTER, ROGER C. CORNELL, CARLOS M. ARROYAVE, ENG M. TAN
Journal: British Journal of Dermatology (1978)

The immunofluorescent patterns of uninvolved and involved skin biopsies from eight patients with atopic dermatitis were studied, using direct immunofluorescence techniques to identify deposits of the immunoglobulins G, A and M as well as the complement factors CIq, C3, C4, C5, factor B and properdin. Immunoglobulin deposits (mainly IgG) were found in five patients, complement deposits in three patients in the basement membrane zone. In three patients the immunofluorescence was positive for C3, in two patients for CIq, C4 and C5. Regarding the factors of the alternative pathway of the complement system, two patients showed deposits of properdin, one of factor B. The changes were not confined to the eczematous lesions, but were found in uninvolved skin too. The most prominent changes were observed in patients with severe disease.
Chronic fatigue syndrome or myalgic encephalomyelitis
Authors: Peter White, Maurice Murphy, Jill Moss, George Armstrong, Sir Peter Spencer
Journal: BMJ (2007)

NICE guidelines pave the way forward for patients and doctors

The uncertainty inherent in making a diagnosis of chronic fatigue syndrome (CFS) is reflected by the variety of names (such as myalgic encephalomyelitis; ME) it has been given. The names reflect the hope that such labels can impose some certainty where little exists. Many doctors are reluctant to make a diagnosis of CFS, with half not even believing it exists.1 The consequences of this uncertainty and reluctance have been that patients hear mixed messages and often receive poor, if any, care.2 It is therefore a welcome relief that the National Institute for Health and Clinical Excellence (NICE) has just published clinical guidelines on the diagnosis and management of this disease.3 In this week's BMJ , Baker and Shaw summarise the guidelines.4

How has the development of these guidelines come about? Eleven years ago, three UK royal colleges agreed that CFS/ME existed as an independent diagnosis and that treatments were possible.5 Unfortunately, this had little effect on the provision of services. …