tbuckley/cabot-search huggingface dataset:
The Development of Myocardial Fibrosis in Transgenic Mice With Targeted Overexpression of Tumor Necrosis Factor Requires Mast Cell–Fibroblast Interactions
Authors: Weili Zhang, Amanda L. Chancey, Huei-Ping Tzeng, Zhenqing Zhou, Kory J. Lavine, Feng Gao, Natarajan Sivasubramanian, Philip M. Barger, Douglas L. Mann
Journal: Circulation (2011)

Background— Transgenic mice with cardiac-restricted overexpression of tumor necrosis factor (MHCsTNF mice) develop progressive myocardial fibrosis, diastolic dysfunction, and adverse cardiac remodeling. Insofar as tumor necrosis factor (TNF) does not directly stimulate fibroblast collagen synthesis, we asked whether TNF-induced fibrosis was mediated indirectly through interactions between mast cells and cardiac fibroblasts. Methods and Results— Cardiac mast cell number increased 2 to 3 fold ( P &lt;0.001) in MHCsTNF mice compared with littermate controls. Outcrossing MHCsTNF mice with mast cell–deficient (c-kit −/− ) mice showed that the 11-fold increase ( P &lt;0.001) in collagen volume fraction in MHCsTNF/c-kit +/− mice was abrogated in MHCsTNF/c-kit −/− mice, and that the leftward shifted left ventricular pressure–volume curve in the MHCsTNF/c-kit +/− mice was normalized in the MHCsTNF/c-kit −/− hearts. Furthermore, the increase in transforming growth factor β1 and type I transforming growth factor β receptor messenger RNA levels was significantly ( P =0.03, P =0.01, respectively) attenuated in MHCsTNF/c-kit −/− when compared with MHCsTNF/c-kit +/− mice. Coculture of fibroblasts with mast cells resulted in enhanced α-smooth muscle actin expression, increased proliferation and collagen messenger RNA expression, and increased contraction of 3-dimensional collagen gels in MHCsTNF fibroblasts compared with littermate fibroblasts. The effects of mast cells were abrogated by type I transforming growth factor β receptor antagonist NP-40208. Conclusions— These results suggest that increased mast cell density with resultant mast cell–cardiac fibroblast cross-talk is required for the development of myocardial fibrosis in inflammatory cardiomyopathy. Cardiac fibroblasts exposed to sustained inflammatory signaling exhibit an increased repertoire of profibrotic phenotypic responses in response to mast cell mediators.
Early False-Negative Bone Scan in a Spiral Fracture
Authors: GREGORY COCCARO, NANDA Y. KHEDKAR, PATRICK J. PELLER, CHARLES J. MARTINEZ
Journal: Clinical Nuclear Medicine (1994)

Ninety-five percent of bone scans show abnormal results by 24 hours after a fracture, and 100% show abnormal results by 72 hours after a fracture in patients younger than 65 years of age (1). A 21-month-old child fell and suffered a large, spiral fracture of the right femur. After plain film radiographs, bone imaging was performed to evaluate the possibility of child abuse. The bone scan, performed 29 hours after the injury, failed to demonstrate any abnormal Tc-99m MDP uptake at the spiral fracture site. Negative results of bone imaging performed early after trauma may not exclude the possibility of a fracture, particularly spiral fractures. Follow-up bone imaging in a few days may be of value.
PHIMOSIS; A PLEA FOR ITS RELIEF BY EARLY OPERATION.Read in the Section on Diseases of Children, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: J. A. HOFHEIMER
Journal: JAMA (1893)

The subject of this paper is as old as medicine itself; my attention, however, within the past few years has especially been called to various ailments of infancy and childhood, which may have been directly attributed to phimosis. In many of the cases this condition had been overlooked by physicians previously in attendance. In some of the cases attended by the writer from their birth, phimosis had been the last thing considered, but a relief of this malformation would always bring about an amelioration of the various symptoms, and in most cases an absolute cure. In advising an operation for phimosis it is not my object to indorse circumcision as done according to the rites of certain oriental religions; but to perform an operation based strictly on anatomic and physiologic data. The main purpose of the prepuce is to act as a protection to the sensitive glans penis; and to
Response to Letter by Hamilton et al
Authors: Liliana R.V. Castro, Julia Schittl, Rodolphe Fischmeister
Journal: Circulation Research (2011)

come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Abstract 1223: Conditional Knockout of CXCR4 Receptor Reveals its Role in Vascularization and the Differentiation of Endothelial Progenitor Cells (EPCs).
Authors: Sangmo Kwon, Rie Ito, Bungil Choi, Michiru kobori, Yoichiro Iwakura, Takayuki Asahara
Journal: Circulation (2006)
Exchange Transfusion in Haemolytic Disease of the Newborn
Authors: W. Walker, G. A. Neligan
Journal: BMJ (1955)

PART I. TREATMENT In the treatment of haemolytic disease of the newborn we regard it as proved that early exchange transfusion is superior to simple transfusion.The evidence in support of this was obtained in controlled trials carried out in various British centres between October, 1949, and August, 1951 (Mollison and Walker, 1952).The Newcastle-upon-Tyne cases that formed part of these trials provide a comparison between early exchange and late simple transfusion.All infants in this centre were the result of spontaneous delivery.Those with a cord Hb level of 14.8 g.% or less were selected at random for either exchange or simple transfusion.When in- dicated, exchange transfusion of at least 60 ml.per lb.(132 ml. per kg.) body weight was carried out within nine hours of birth.A total of 86 children were included in the trial (Table I).In the group selected for simple transfusion this was given if the Hb level fell to 11 g.% during the first fourteen days of life.Apart from the type of transfusion given, all babies received identical care.TABLE T.-A Controlled Trial of Exchange and Simple Tranisfu- sion in 86 Infants with Haemolytic Disease (National Investi- gation, Newcastle-upon-Tyne Centre, 1949-52) No. of No. with No. of Cases Kernicterus Deaths Simple transfusion .. 42 9 13 Exchange ,, .. 44 0 2 *Cases from the Princess
The importance of adult life-span perspective in explaining variations in political ideology
Authors: Grzegorz Sedek, Malgorzata Kossowska, Klara Rydzewska
Journal: Behavioral and Brain Sciences (2014)

Abstract As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.
Abstract LB-99: Identification and characterization of small molecule thieno[3,2-d]pyrimidine inhibitors of Protein Kinase C iota (PKCι)
Authors: Christelle Soudy, Emma Stanway, Bhavisha Patel, Caroline Barton, Michelle Barnard, Leon Pang, Paul Owen, Andrew Turnbull, Bruce A. Ruggeri, Bruce D. Dorsey, Mark A. Ator, Greg R. Ott, Mark Linch, Philippe Riou, Peter J. Parker, Sven Kjaer, Christian Dillon, Neil Q. McDonald, Jon Roffey
Journal: Cancer Research (2014)

Abstract We describe a novel series of small molecule ATP-competitive inhibitors of the atypical class of Protein Kinase C (PKC). The PKC family of serine/threonine kinases are divided into four structurally and functionally distinct sub-types: classic (PKCα, PKCβ, PKCγ); novel (PKCδ, PKCε, PKCη, PKCθ); atypical (PKCι,PKCζ); and PKNs (PKN1, PKN2, PKN3). The PKCs have been defined as key regulators in a multitude of signal transduction pathways that impinge on diverse cellular processes such as proliferation, differentiation, and survival. The regulation and functions of the atypical PKCs are distinct from the classic and novel PKCs.Both atypical isoforms have been implicated in various models of cancer, and PKCι in particular has been described as a potential oncogene. Its abundance is frequently increased, primarily through PKCι gene amplification, in many epithelial tumours including: subsets of squamous non-small cell lung carcinoma, serous ovarian carcinoma, and squamous esophageal carcinoma. It has been widely demonstrated that deregulation of PKCι signalling leads to unconstrained cell growth, increased migratory and invasive behaviour, and aberrant cellular polarity, which is a hallmark of aggressive cancers. Together, these data make a strong case for the inhibition of PKCι as a novel therapeutic strategy. We have discovered a series of ATP-competitive thieno[3,2-d]pyrimidine- based PKCι inhibitors from a high throughput screen. Using structure-based design we have optimized the series and demonstrated potent and selective inhibition of PKCι in biochemical and cellular models. The biochemical, structural, and cellular characterization of these compounds will be described herein. Citation Format: Christelle Soudy, Emma Stanway, Bhavisha Patel, Caroline Barton, Michelle Barnard, Leon Pang, Paul Owen, Andrew Turnbull, Bruce A. Ruggeri, Bruce D. Dorsey, Mark A. Ator, Greg R. Ott, Mark Linch, Philippe Riou, Peter J. Parker, Sven Kjaer, Christian Dillon, Neil Q. McDonald, Jon Roffey. Identification and characterization of small molecule thieno[3,2-d]pyrimidine inhibitors of Protein Kinase C iota (PKCι). [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 LB-99. doi:10.1158/1538-7445.AM2014-LB-99
Spontaneous in vitro differentiation of antigen-specific lymphocytes from a patient with immunoglobulin M gammopathy.
Authors: J Halper, E A Kabat, E F Osserman, P Tonda, B Pernis
Journal: Journal of Clinical Investigation (1982)

Recently we have identified two monoclonal immunoglobulin M (IgM) proteins that bind Klebsiella polysaccharides. The lymphocytes of one of these patients (M.A.Y.) were available for study. A substantial proportion of the B lymphocytes isolated from this patient's peripheral blood also bound Klebsiella polysaccharides with a pattern of specificity identical to that of the monoclonal IgM, and reacted with an anti-idiotypic antiserum directed against this IgM. Stripping the surface immunoglobulin from these lymphocytes eliminated this reactivity. Although no plasma cells were detected in the freshly isolated peripheral blood lymphocytes of this patient, plasma cells binding Klebsiella polysaccharide appeared after 7 d of in vitro culture. This occurred regardless of whether the cultures were supplemented with autologous plasma, normal human plasma, or fetal calf serum. Pokeweed mitogen neither stimulated nor inhibited the in vitro differentiation of the monoclonal B lymphocytes into plasma cells. This differentiation was, however, abrogated by F(ab')2 fragments of anti-human IgM and by anti-idiotypic antibodies, as well as by the Klebsiella polysaccharide with which the monoclonal IgM reacted.
The Use of Lithium in Affective Disorders: II. Prophylaxis of Depression in Chronic Recurrent Affective Disorder
Authors: RONALD R. FIEVE, STANLEY H. PLATMAN, ROBERT R. PLUTCHIK
Journal: American Journal of Psychiatry (1968)

In a longitudinal outpatient study, the authors found that lithium produced a mild decrease in depth of depression scores among patients who had been on the drug for more than seven months, as compared with patients who had been receiving lithium less than seven months. They assess the factors contributing to reported positive clinical results of maintenance lithium treatment in recurrent affective disorder.
Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
Authors: Soraya Bravo, Felipe Núñez, Fernando Cruzat, Eduardo G Cafferata, Giancarlo V De Ferrari, Martín Montecino, Osvaldo L Podhajcer
Journal: Molecular Therapy (2013)

Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity of other heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκB-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as well as other diseases.
THE SEATTLE POST-INFARCTION MODEL IS HIGHLY PREDICTIVE OF MORTALITY AFTER ACUTE MYOCARDIAL INFARCTION IN PATIENTS FROM INTERMOUNTAIN HEALTHCARE
Authors: Benjamin Davies Horne, Eric Ketchum, Joseph B. Muhlestein, Raymond McCubrey, Tami Bair, Jeffrey L. Anderson, Wayne Levy
Journal: Journal of the American College of Cardiology (2014)
Opposition grows in France to new charges for drugs and ambulance trips
Authors: Brad Spurgeon
Journal: BMJ (2007)

An initiative from the World Health Organization has been launched to make drugs as simply and safely available to children as they are to adults.Speaking last week at the launch in London, WHO's assistant director general, Howard Zucker, said that "there is a gap between the availability of children's medicines and the actual need.That gap is global and must be addressed."The problem is not new."It's a reality we've lived with for many years," Dr Zucker admitted.Most drugs are developed for and tested in adults.Less than a third come in a form appropriate for children.As a result, many children are treated using drugs that are effectively unlicensed.Medical staff may be obliged to estimate the appropriate fraction of an adult dose, and then crush tablets or extract part of the contents of a capsule.One study by WHO has shown that drug errors are three times as common in children as in adults (JAMA 2001;285:2114-20).Unicef claims that of the 10 million under 5s who will have died by the end of this year, specific products for children could have saved two thirds.Hans Hogerzeil, WHO's director of drugs policy and standards, listed areas in which more effort is needed, in which drugs do exist but were of unknown safety and efficacy.Examples include agents for dealing with tuberculosis; HIV; and several neglected conditions, such as schistosomiasis.Development is essential in areas in which adult drugs need to be adapted to make them suitable and safe for children.Illnesses in this category include malaria, neonatal infections that could be treated by antibiotics, and tuberculosis.Finally, said Dr Hogerzeil, improved access is the priority where drugs exist but are prevented from reaching the children who needed them because of cost."Make medicines child size" is at www.who.int/childmedicines/en. WHO launches� campaign to make drugs� s�afer for childrenUK NEWS GMC approves change in the standard of proof, p 1230 World NEWS �d�� �a�� a��o�� dr�g co�panies to pro�ote off��a�e� �ses, p 122� �d�� �a�� a��o�� dr�g co�panies to pro�ote off��a�e� �ses, p 122� , p 122� ��j.co�Go�iath �oves into hea�thcare records Go�iath �oves into hea�thcare records
Aortic Debridement-Long-term Follow-up
Authors: LEE P. ENRIGHT, E. WILLIAM HANCOCK, NORMAN E. SHUMWAY
Journal: Circulation (1971)

The clinical and hemodynamic data available in the five-to eight-year follow-up of 45 patients who underwent aortic debridement for aortic stenosis are presented. Eight patients (18%) remain in follow-up (average duration 6.4 years) with excellent clinical results. Twenty-seven (60%) of these patients have undergone a second operative procedure for correction of aortic stenosis, having achieved an average of 4.3 years of palliation prior to the second operative procedure. Including the operative deaths occurring with the second procedure and the subsequent follow-up of these patients, 29 patients are alive with average follow-up period of 5.7 years. Two of these deaths were not due to cardiovascular disease. Substantial residual aortic gradients were compatible with excellent periods of palliation, provided a reduction of the gradient for the particular patient was achieved. We feel that operative debridement for aortic stenosis, when technically feasible, is a realistic approach to this disease state. Although reoperation may eventually be necessary in the course of the patient's disease, a significant period of palliation with limited morbidity is gained by the patient.
The Physiologic Approach to Hyperuricemia
Authors: Asghar Rastegar, Samuel O. Thier
Journal: New England Journal of Medicine (1972)

HYPERURICEMIA is an easily detected and common chemical abnormality. Since the clinical importance of this abnormality has not been well defined, hyperuricemia presents a confusing problem for the clinician. Despite this uncertainty, a wide variety of potent agents have been developed to treat the abnormality. These agents have differing mechanisms of action to achieve the same end. They also have important side effects and interactions. A rational approach to hyperuricemia will require the physician to be firmly grounded in the biochemistry of uric acid metabolism, the physiology of uric acid excretion and the pharmacology of hypouricemic agents, as well as . . .
Biopsy of Cervical Node
Authors: Marvin P. Fried
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The evaluation of an adult with cervical lymphadenopathy leads to many diagnostic possibilities. This was represented via algorithm by Greenfield and Jordan. One of the major considerations, however, was not given its due importance. Metastatic carcinoma has long been known to be a major cause of cervical lymphadenopathy. One of the fundamental teachings of Martin and Romieu<sup>1</sup>was that asymmetric enlargement of one or more cervical lymph nodes in an adult was cancerous until proved otherwise. Naturally, other possibilities need to be considered, but carcinoma, especially with a primary lesion somewhere in the head and neck, must be close to the top of the diagnostic list and should not be considered as an afterthought. This is compounded by the authors, who direct the algorithm toward nurses and physician assistants who may not have acquired the skills of thoroughly examining the head and neck (nasopharyngoscopy and indirect
Sideroblastic anemias: Variations on imprecision in diagnostic criteria, proposal for an extended classification of sideroblastic anemias
Authors: Sibel Koc, John W. Harris
Journal: American Journal of Hematology (1998)

Sideroblastic anemias are caused by a diversity of hereditary, congenital, or acquired disorders. Criteria used in describing sideroblastic anemias vary widely among standard medical textbooks and even so have been imprecisely applied in the literature. Recent discoveries concerning the basic pathophysiologic mechanisms involving the molecular biology of nuclear and mitochondrial DNA, erythroid ALA synthase (ALAS-2), and iron transport have made the classification of sideroblastic anemias very complex. We recommend a more precise evaluation and documentation of the components that characterize the sideroblastic abnormality and propose an extended classification of the sideroblastic anemias. Am. J. Hematol. 57:1–6, 1998. © 1998 Wiley-Liss, Inc.
Children with asthma and their families benefit from asthma education
Authors: D. Spurgeon
Journal: BMJ (2009)

Education on asthma management delivered to children and their families in small, interactive groups has improved their quality of life and reduced the number of visits to the emergency department and the need for oral corticosteroids, a Canadian study reports ( CMAJ doi:10.1503/cmaj.080947).

The randomised controlled trial looked at 398 children aged 3 to 16 years admitted to the emergency department of the Children’s Hospital of Winnipeg, Manitoba. Children in the control group followed the usual care recommended by their family physician, along with an …
The role of transcription and messenger RNA stability in the regulation of epidermal growth factor receptor gene expression in regenerating mouse liver
Authors: Shinzaburo Noguchi, Yoshito Ohba, Takami Oka
Journal: Hepatology (1992)

The influence of partial hepatectomy on epidermal growth factor receptor gene expression was studied in mouse liver. Epidermal growth factor receptor binding and epidermal growth factor receptor messenger RNA levels in the liver showed a rapid peak 8 hr after partial hepatectomy, whereas the sham operation had no effects on these levels. The peak epidermal growth factor receptor messenger RNA level was approximately threefold higher than preoperative values. The increase in epidermal growth factor receptor messenger RNA levels occurred primarily as a consequence of an increase in the rate of transcription. Partial hepatectomy slightly increased the half-life of epidermal growth factor receptor messenger RNA in the liver from 2.8 to 3.6 hr. Treatment of partially hepatectomized mice with cycloheximide increased hepatic epidermal growth factor receptor messenger RNA levels about fivefold by prolonging the half-life of the messenger RNA to 11.2 hr, although this treatment inhibited the increase in transcription induced by partial hepatectomy. Cycloheximide also increased epidermal growth factor receptor messenger RNA levels in the liver or kidney of sham-operated mice about threefold, primarily through stabilizing epidermal growth factor receptor messenger RNA. In contrast, cycloheximide had no effects on beta-actin messenger RNA levels in the liver and kidney. These results suggest that transcription induced by partial hepatectomy requires protein synthesis and that labile proteins are involved in the regulation of the stability of epidermal growth factor receptor messenger RNA.