tbuckley/cabot-search huggingface dataset:
Oral Propafenone To Convert Recent-Onset Atrial Fibrillation in Patients with and without Underlying Heart Disease
Authors: Giuseppe Boriani
Journal: Annals of Internal Medicine (1997)

Background: The effectiveness of oral propafenone in converting recent-onset atrial fibrillation to sinus rhythm has been established by controlled trials. However, it is not clear whether the effectiveness of propafenone is affected by the presence or absence of underlying heart disease. Objectives: To investigate the safety and effectiveness of oral propafenone and the role of underlying heart disease. Design: Randomized, single-blind, controlled study. Setting: 3 teaching hospitals. Patients: 240 hospitalized patients with recent-onset atrial fibrillation. Intervention: Propafenone (one 600-mg oral dose) or placebo. Measurements: Conversion rates at 3 and 8 hours. Results: Propafenone was more effective than placebo for converting atrial fibrillation to sinus rhythm at 3 hours: Fifty-four of 119 patients (45%) receiving propafenone and 22 of 121 patients (18%) receiving placebo had conversion (P < 0.001). It was also more effective at 8 hours: Ninety-one of 119 patients (76%) receiving propafenone and 45 of 121 patients (37%) receiving placebo had conversion (P < 0.001). Subgroup analysis showed that among patients without heart disease, 78% of those receiving propafenone and 56% of those receiving placebo converted to sinus rhythm within 8 hours (P = 0.02). In those with hypertension, the rate was 70% for those receiving propafenone and 27% for those receiving placebo (P < 0.001); in patients with structural heart disease, the rate was 81% for those receiving propafenone and 17% for those receiving placebo (P < 0.001). Conclusions: Oral loading of propafenone was more effective than placebo for conversion to sinus rhythm within 8 hours and had a favorable safety profile. The rate of spontaneous conversion to sinus rhythm was higher in patients without structural heart disease; this finding has important implications for the assessment of drug effectiveness in recent-onset atrial fibrillation.
Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome
Authors: Christoph P Hofstetter, Niklas A V Holmström, Johan A Lilja, Petra Schweinhardt, Jinxia Hao, Christian Spenger, Zsuzsanna Wiesenfeld-Hallin, Shekar N Kurpad, Jonas Frisén, Lars Olson
Journal: Nature Neuroscience (2005)
Abstract 5586: Phase I study of PARP inhibitor ABT-888 and carboplatin with novel imaging in metastatic breast cancer (MBC) (NCI-8609)
Authors: Bhuvaneswari Ramaswamy, Maryam B. Lustberg, Robert Wesolowski, Rachel M. Layman, Ewa Mrozek, Erin M. Olson, Eleni Andreopoulou, Alejandra Garcia-Villa, Jeff Chalmers, Jeffrey A. Cotrill, Julie Nutter, Jamie Ledin, Larry J. Schaaf, Saeed Bajestani, Weiqiang Zhao, Susan Geyer, Alice Chen, Charles L. Shapiro, Miguel A. Villalona-Calero, Michael Knopp, Michael R. Grever
Journal: Cancer Research (2012)

Abstract Purpose: ABT-888 is an oral inhibitor of PARP 1 and 2 and potentiates activity of platinums in preclinical models. We are conducting a phase I study of ABT-888 on 2 different schedules (7 and 14 day) plus q 3 week carboplatin (C) to identify the recommended phase II dose schedules (RPTD-7and 14 day) for this regimen in patients (pts) with MBC who are: (1) triple negative (TN); or (2) estrogen receptor positive (ER+) with defective Fanconi Anemia (FA) pathway (no FANCD2 foci in tumor). Study design: Eligible pts received C-AUC 5 Q 3weeks (except dose level 1-AUC 6) plus escalating doses of ABT-888 BID on a 7 or 14-day schedule using a 3+3 dose escalation design. Blood samples were collected during cycles 1 and 2 for PAR assay and CTCs isolated to measure gamma H2Ax. We performed 3′-[F-18] Fluoro-3′-deoxythymidine(FLT) PET scans to assess cellular tumor proliferation at baseline, cycle 1 day 7 and 14 and after cycle 3. FDG-PET-CT scans were used to assess response. Results: 22 pts (20-TN, 2-ER+ w/FA defect) with median age of 56.5 yrs (range 31-69) were enrolled on 5 dose levels. Dose level 1 with C at AUC 6 was too toxic with 3 DLTs (Table 1). Further dose escalations were performed with C at AUC-5. Dose reductions in C were made in subsequent cycles for thrombocytopenia, anemia and fatigue. Maximum reduction in thymidine uptake in tumors was seen on day 7 FLT scans. CTCs were isolated using an immunomagnetic negative depletion method on 8 pt samples to date (median-59, range 0-684 CTCs). Gamma H2Ax analysis on sequential samples is ongoing. Four pts have had an unconfirmed partial response (PR) with &amp;gt; 50% tumor shrinkage; 2 of the 4 pts had a defective FA pathway. Conclusions: Thrombocytopenia is the major DLT when ABT-888 is given in combination with C, where lower AUC of C is better tolerated and shows promising activity of this combination. FA deficiency (5/14=27%) seen in this group is consistent with our previous reports. The study is supported U01 CA076576. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5586. doi:1538-7445.AM2012-5586
The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9
Authors: Koichi Tabeta, Kasper Hoebe, Edith M Janssen, Xin Du, Philippe Georgel, Karine Crozat, Suzanne Mudd, Navjiwan Mann, Sosathya Sovath, Jason Goode, Louis Shamel, Anat A Herskovits, Daniel A Portnoy, Michael Cooke, Lisa M Tarantino, Tim Wiltshire, Benjamin E Steinberg, Sergio Grinstein, Bruce Beutler
Journal: Nature Immunology (2006)
Alteration of membrane phospholipid bilayer organization in human erythrocytes during drug-induced endocytosis.
Authors: S L Schrier, D T Chiu, M Yee, K Sizer, B Lubin
Journal: Journal of Clinical Investigation (1983)

Our plan was to evaluate the potentially important role of phospholipids in erythrocyte shape alterations by determining if their orientation was altered during endocytosis. Stomatocytosis and endocytosis were induced in normal intact human erythrocytes by incubation with three agents: primaquine, vinblastine, and chlorpromazine, each of which has its own requirements and time course for producing endocytosis. The organization of the phospholipid bilayer was assessed by measuring the extent of degradation of phophatidylcholine (PC), phophatidylethanolamine (PE), phosphatidylserine (PS), and sphingomyelin (SM) produced by exposure of erythrocytes to a nonpenetrating protease-free phospholipase A2 alone or in combination with a purified sphingomyelinase as well. The induction of stomatocytosis did not change this orientation. However, correlating with the onset of endocytosis but not its extent, there was an increase in PE degradation, which could be detected regularly only by use of phospholipase A2 alone. Use of the combination of phospholipase A2 and sphingomyelinase showed that the extent and course of endocytosis was paralleled by an apparent movement of PC and SM from the outer to the inner half of the lipid bilayer. Since no further PE was hydrolyzed and because no PS was ever degraded, this inward movement of PC and SM did not represent the establishment of complete symmetry in the membrane. By adjusting the experimental design it was possible to implicate the endocytic process, and not insertion of drug in the membrane, as the cause of the alterations in phospholipid organization seen. Our findings indicate that the phospholipid orientation is very closely involved in the endocytosis process and that specific states of phospholipid asymmetry may be related to identifiable membrane events.
All Placebos Are Not Created Equally
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2013)

Karin Meissner, MD; Margrit Fässler, MD; Gerta Rücker, PhD; Jos Kleijnen, PhD; Asbjorn Hróbjartsson, PhD; Antonius Schneider, MD; Gerd Antes, MD; Klaus Linde, MD
THE IMPACT OF LOW LEVEL OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL ON 6-MONTH ANGIOGRAPHIC AND 2-YEAR CLINICAL OUTCOMES IN ACUTE MYOCARDIAL INFARCTION PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Ji Young Park, Seung-Woon Rha, Amro Elnagar, Byoung Geol Choi, Sung il Im, Sunwon Kim, Jin Oh Na, Seongwoo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Hong-Seog Seo, Chang Gyu Park, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2012)
Abstract 3683: Crenolanib, a novel Type I, mutant-specific inhibitor of Class III receptor tyrosine kinases, preferentially binds to phosphorylated kinases
Authors: Chaitanya Muralidhara, Abhijit Ramachandran, Vinay K. Jain
Journal: Cancer Research (2012)

Abstract Introduction: Crenolanib (CP-868,596) is a benzimidazole tyrosine kinase inhibitor (TKI), known to potently inhibit the platelet derived growth factor receptors (PDGFR) alpha and beta, and the Fms-like tyrosine kinase 3 (FLT3). Crenolanib has been evaluated as a single agent (Lewis N, et al, J Clin Oncol 2009), and in combination with docetaxel ± axitinib (Michael M, et al, Br J Cancer 2010), and was found to be well tolerated, with transient elevation of liver enzymes at higher doses. We describe here the characterization of crenolanib as a unique chemotype, mutant-specific Type I TKI. Methods: The relative affinities of tyrosine kinase inhibitors for phosphorylated and non-phosphorylated ABL1 have been previously used to accurately distinguish type I from type II inhibitors (Wodicka LM, et al, Chem Biol 2010). The effect of ABL1 A-loop phosphorylation on crenolanib affinity was investigated in a competition binding assay (Karaman MW, et al, Nat Biotech 2008). The binding constants (Kds) of crenolanib for FLT3 (wild-type and five mutant isoforms) were also determined using the KINOMEscan KdELECT Assay (DiscoveRx, San Diego, CA), and compared with the Kds of 442 TKIs reported (Davis MI, et al, Nat Biotech 2011). The Kds of crenolanib for PDGFRα, PDGFRα, and c-KIT (wild-type and two mutant isoforms) are being determined. Results: The Kd of crenolanib for phosphorylated ABL1 and ABL(T315I) were 7- and 15-fold lower than the Kds for non-phosphorylated ABL1 and ABL(T315I) respectively. Based on this higher affinity for p-ABL1 relative to np-ABL1, crenolanib appears to be a Type I inhibitor. Furthermore, crenolanib has a 10-fold affinity shift between the non-autoinhibited and autoinhibited states of FLT3, which is in the range of affinity shifts reported for other Type I TKIs, in contrast to the 100- to 1000-fold affinity shift reported for Type II TKIs. Crenolanib also has the highest affinity for three constitutively activate isoforms of FLT3 (FLT3-ITD, FLT3-D835Y, FLT3-D835V) compared to 442 kinases reported (Davis MI, et al, Nat Biotech 2011). Crenolanib is a next-generation, mutant-specific TKI, currently in Phase II development in adult and pediatric gliomas, and in PDGFRAD842V-mutant GIST. The unique and specific kinase inhibition profile is hypothesized to translate to greater therapeutic effect, accompanied by fewer adverse events in the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3683. doi:1538-7445.AM2012-3683
BULLOUS PEMPHIGOID OF CHILDHOOD AND COELIAC DISEASE REPORT OF A CASE
Authors: F. O. C. MEENAN, S. F. CAHALANE
Journal: British Journal of Dermatology (1969)

SUMMARY.— The case of a boy aged 3 with bullous pemphigoid, who also had clinical and pathological evidence of coeliac disease, is described. Two brothers had coeliac disease. The association of the 2 conditions is interesting but it is not suggested on the present evidence that there is a causal relationship between them.
Chemical Carcinogenesis and Cancers
Authors: Kurt Stern
Journal: JAMA (1965)

This impressive treatise reflects, to a large extent, the lifetime experience of the senior author and may be considered a companion piece to his earlier monograph<i>Occupational Tumors and Allied Diseases</i>(1942). The present book deals not only with cancers occurring in high-risk occupations, but with the total carcinogenic environment surrounding modern man. The text expounds the physicochemical properties of the important classes of organic and inorganic carcinogens, and critically analyzes their mechanisms, their relationship to mutagens and teratogens, and factors modifying carcinogenesis. In the presentation of methods for bioassay of carcinogens, the insidious effects of small doses acting over prolonged periods of time are documented, and attention is called to the fact that few carcinogens have an effective attack rate of 100%. Discussing the serious difficulties in performance and interpretation of carcinogen assays, the authors propose specific approaches in order to deal effectively with the man-made "pathogenic chemical jungle"
A PLEA FOR MORE THOROUGH EXAMINATION OF DOUBTFUL SPECIMENS OF ECTOPIC PREGNANCY.
Authors: J. WESLEY BOVÉE
Journal: JAMA (1904)

Every abdominal surgeon meets with cases in which, before or during operation, the diagnosis of ectopic pregnancy is made, but in which no fetus or placenta is found. In such, absence of the fetus is attributed to the rapid absorptive action of the peritoneum on the nearly boneless ovum, and the absence of the placenta to interruption of the pregnancy before the development of that structure is commonly understood to begin. It is now known, however, that the trophoblast enters into the formation of that structure early in the developmental stage of segregation or cell division. In observing the work of others, I am sure this diagnosis is adhered to even without microscopic examination, if blood, either loose or encysted, is found in the peritoneal cavity, and a tube or ovary, or both, distended by blood coagulum. In my own experience, several times I have found that microscopic examination
STUDIES ON ANTIBODY FORMATION BY PERITONEAL EXUDATE CELLS IN VITRO
Authors: John M. McKenna, Kingsley M. Stevens
Journal: The Journal of Experimental Medicine (1960)

Cells from peritoneal exudates of rabbits sacrificed 3 days after an intraperitoneal injection of sterile mineral oil were grown in tissue cultures in medium 199 (75 per cent); normal rabbit serum (25 per cent). Antibody produced by the cells was assayed by an hemagglutination technique in which the antigens used were adsorbed to formalinized tanned sheep erythrocytes. These sensitized cells agglutinate in the presence of antibody specific to the adsorbed antigen. It has been demonstrated that: Peritoneal exudate cells produced hemagglutinating antibody to bovine gamma globulin (BGG) in a replicating tissue culture system for approximately 3 weeks when taken from animals given either primary or secondary injections of BGG. The mean hemagglutinating titer was 30 for the primary and 32 for the secondary systems. Since the other cell types did not persist, it is felt that monocytes were responsible for these results. Monocytes taken from normal rabbits and exposed to either BGG or egg albumen (EA) in vitro produced titers of 28 for about 2 weeks. Monocytes taken from rabbits given hyperimmunizing injections of BGG produced titers of 147 for about 1 week. Endotoxin from Salmonella typhosa caused the monocytes to form antibody as if they had been taken from hyperimmunized rabbits. This was true both when the antigen was given in vivo together with the endotoxin as well as when the cells were exposed to antigen in vitro. The titers were 223 and 97, respectively. Neither freshly harvested nor cultured monocytes were phagocytic for carbon particles or bacteria in vitro. Monocytes in tissue culture appeared to assume the morphology of fibroblasts, but did not stain with the characteristics of fibroblasts. The morphologic changes and staining characteristics of monocytes in tissue culture have been described. The implications of these findings have been discussed and an attempt made to integrate them into general biological theory.
Capitalizing on promising research areas
Authors: Charles Marwick
Journal: JAMA (1984)

Of the 11 institutes at the NIH, all except one are targeted to a disease or population. The exception is the National Institute of General Medical Sciences (NIGMS), the fourth largest in terms of budget. The institute's programs are focused on basic, noncategorical research, without which many of the advances that will eventually have an impact on specific diseases cannot take place, observes the present director, Ruth L. Kirschstein, MD.  This is not to say that other institutes at the NIH are not engaged in basic research, of course, she adds, but this institute's research areas do not have a specific, categorical focus.  There's an excellent example to illustrate this, Kirschstein goes on. She notes that one of this year's General Motors Cancer Research Foundation awards went to Barnett Rosenberg, PhD, of Michigan State University, East Lansing, in recognition of his work in the development of the anticancer drug cisplatin.
Innate Signaling Promotes Formation of Regulatory Nitric Oxide–Producing Dendritic Cells Limiting T-Cell Expansion in Experimental Autoimmune Myocarditis
Authors: Gabriela Kania, Stefanie Siegert, Silvia Behnke, Rafael Prados-Rosales, Arturo Casadevall, Thomas F. Lüscher, Sanjiv A. Luther, Manfred Kopf, Urs Eriksson, Przemyslaw Blyszczuk
Journal: Circulation (2013)

Activation of innate pattern-recognition receptors promotes CD4+ T-cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood.Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund's adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund's adjuvant, converted CD11b(hi)CD11c(-) monocytes into tumor necrosis factor-α- and nitric oxide synthase 2-producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2-mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2-dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, nitric oxide synthase 2 production by both radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo.Innate Toll-like receptor 2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T-cell responses in experimental autoimmune myocarditis via nitric oxide. Therefore, activation of innate pattern-recognition receptors is critical not only for disease induction but also for counterregulatory mechanisms, protecting the heart from exaggerated autoimmunity.
Chronic illness and disability are a hidden economic burden in Australia
Authors: J. Parry
Journal: BMJ (2012)

<h3>Introduction</h3> Dietary sodium intake affects the function of several target organs involved with volume homeostasis. We hypothesized that dietary sodium similarly affects the heart as a target organ, specifically myocardial relaxation. <h3>Methods</h3> Thirteen healthy volunteers (age 38.6 ± 4 y) entered a two-week crossover design study (week 1, high sodium diet [HS]&gt;200 mmol Na/day; week 2, low sodium diet [LS],&lt;10 mmol Na/day). At the end of each study week, tissue Doppler imaging of mitral annular velocities (mean early diastolic myocardial relaxation velocity), renal blood flow and aldosterone secretion were measured at baseline and after infusion of angiotensin II (Ang II) (3 ng/kg/min × 45 min). <h3>Results</h3> On HS diet myocardial relaxation velocity (E9) was greater than on LS diet (14.0 ± 1.2 vs.12.6 ± 1.0 cm/s, p = 0.02), despite an increase in systolic blood pressure of 7 mm Hg. In response to Ang II infusion, E9 was significantly reduced on the HS diet when compared to the LS diet (HSΔ -1.4 ± 0.4 vs. LSΔ -0.1 ± 0.3 cm/s, p = 0.02). E9 significantly correlated with endogenous Ang II only on the HS diet. There were no significant changes in estimates of left ventricular filling pressures (E/E9) with either maneuver. Response characteristics paralleled those measured simultaneously in renal blood flow and adrenal secretion of aldosterone. <h3>Conclusions</h3> Dietary sodium intake modulates myocardial relaxation velocity and its responsiveness to Ang II. The relationship between Ang II and myocardial relaxation is dependent on dietary sodium intake and is identical to relationships in other sodium-sensitive target organs. Abnormalities in these mechanisms may play a role in clinical abnormalities of diastolic dysfunction.
Granulocyte/macrophage colony-stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with<i>de novo</i>vascular endothelial growth factor transcription in the ulcer bed
Authors: F. Cianfarani, R. Tommasi, C.M. Failla, M.T. Viviano, G. Annessi, M. Papi, G. Zambruno, T. Odorisio
Journal: British Journal of Dermatology (2005)

Journal Article Granulocyte/macrophage colony‐stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with de novo vascular endothelial growth factor transcription in the ulcer bed Get access F. Cianfarani, F. Cianfarani Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar R. Tommasi, R. Tommasi Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar C.M. Failla, C.M. Failla Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar M.T. Viviano, M.T. Viviano Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar G. Annessi, G. Annessi Histopathology Department, Istituto Dermopatico dell'Immacolata, IDI‐IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Papi, M. Papi Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar G. Zambruno, G. Zambruno Laboratory of Molecular and Cell Biology, VIII Dermatology Division Search for other works by this author on: Oxford Academic Google Scholar T. Odorisio T. Odorisio Laboratory of Molecular and Cell Biology, VIII Dermatology Division Teresa Odorisio. E‐mail: t.odorisio@idi.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 1, 1 January 2006, Pages 34–41, https://doi.org/10.1111/j.1365-2133.2005.06925.x Published: 01 January 2006 Article history Accepted: 30 April 2005 Published: 01 January 2006
US doctors' politics shift left, study shows
Authors: M. McCarthy
Journal: BMJ (2014)

Judging by their political contributions, US doctors seem to be shifting to the left, a new study has found.1 

In the study researchers analyzed contributions from US physicians to Republican and Democratic candidates and to partisan organizations in presidential and congressional elections over 22 years, from the 1991-92 election cycle through to the 2011-12 cycle. They found that the number and percentage of doctors donating to the parties had risen substantially over two decades: 11 801 (2.6%) contributed a total of $20m (£11.9m; €14.7m) in the 1991-92 cycle, whereas 67 852 (9.4%) contributed $143.2m in the 2011-12 cycle. 

The researchers also found that, although substantially more doctors gave to Republicans over the 22 years studied, the percentage that did so had declined since 1996, falling to below 50% in the 2007-08 …