tbuckley/cabot-search huggingface dataset:
Human pediatric and adult ventricular cardiomyocytes in culture: assessment of phenotypic changes with passaging
Authors: R Li
Journal: Cardiovascular Research (1996)

Objectives: The purpose of this study was to assess morphologically and biochemically the phenotypic changes which occur in vitro with passaging of human pediatric and adult ventricular cardiomyocytes. Methods: Human ventricular cardiomyocytes from 3 children (1 to 2 years of age) and an adult patient (65 years of age) undergoing open heart surgery and an adult heart transplant patient (55 years of age) were isolated, cultured, purified, and passaged. Growth curves and 3H-thymidine uptake studies were performed. Characterization of the cells was done by light microscopy, transmission electron microscopy, immunofluorescent staining for myoglobin, CK-MB, and cardiac-specific troponin I isoform, human ventricular myosin heavy chain (HVMHC) and light chain 1 (HVMLC1), Northern blot analysis of HVMHC, and CK-MB activity and mass measurements. Passage 3 cardiomyocyte and pediatric myocardial phospholipids were analysed by gas chromatography. Results: Pediatric cells were smaller (P < 0.01) and divided faster (P < 0.001, ANOCOVA) than adult cells. The cardiomyocytes showed phenotypic changes in primary culture with essentially complete loss of sarcomeres by 10 days and a gradual loss of myofilaments with passaging. The cells were identified as cardiomyocytes by immunohistochemistry for myoglobin, CK-MB, cardiac-specific troponin I isoform, HVMHC and HVMLC1, and by Northern blot analysis for the 3′-end of HVMHC mRNA. The composition of phospholipid fatty acids in the cultured pediatric cells was similar to that found in the pediatric myocardium. CK-MB activity and mass could be measured in the cardiomyocytes. The adult cardiomyocytes were more difficult to maintain than the pediatric cells which could be cultured for as long as 6 months. Conclusions: Primary cultures of human pediatric and adult partially differentiated ventricular cardiomyocytes can be passaged. Although rapid disorganization of the myofibrils occurs, the non-contractile cells can be identified as cardiomyocytes by morphological appearance, immunofluorescent staining, Northern blot analysis for HVMHC, and CK-MB activity.
Integral diagnosis and classification of adult mastocytosis: A prospective study of 151 cases
Authors: L. Escribano, R. Núñez, A. García-Montero, A. Prados, M. García-Cosío, L. Sánchez-Muñoz, M. Cuevas, C. Bellas, A. López, M. Angulo, A. Orfao
Journal: Journal of Allergy and Clinical Immunology (2005)
ACE inhibition promotes upregulation of endothelial progenitor cells and neoangiogenesis in cardiac pressure overload
Authors: Patrick Müller, Andrey Kazakov, Philippe Jagoda, Alexander Semenov, Michael Böhm, Ulrich Laufs
Journal: Cardiovascular Research (2009)

Inhibition of the angiotensin-converting enzyme (ACE) prevents maladaptive cardiac remodelling. Endothelial progenitor cells (EPC) from the bone marrow contribute to endothelial repair and neovascularization, effects that are potentially important during cardiac remodelling. We hypothesized that ACE inhibitors may exert beneficial effects during pressure-induced myocardial hypertrophy by regulating progenitor cell function. In C57/Bl6 mice, development of cardiac hypertrophy induced by transaortic constriction (TAC) for 5 weeks was reduced by ramipril, 5 mg/kg p.o., independent of blood pressure lowering. Ramipril prevented TAC-induced apoptosis of cardiac myocytes and endothelial cells. On day 1 after TAC, upregulation of Sca-1pos/KDRpos EPC was observed, which was further increased by ramipril. EPC were persistently elevated in the TAC mice receiving vehicle treatment but not in the ramipril group after 5 weeks. These effects were independent of hypoxia-inducible factor-1α mRNA and protein expression. The ACE inhibitor but not TAC improved the migratory capacity of DiLDLpos EPC. Increased cardiac afterload induced upregulation of extracardiac neoangiogenesis. This effect was enhanced by ACE inhibition. Ramipril but not TAC markedly increased cardiac capillary density determined by the ratio of CD31pos cells to cardiomyocytes. Bone marrow transplantation studies revealed that TAC increased the percentage of bone marrow-derived GFPpos endothelial cells in the myocardium, and ramipril made this effect more pronounced. ACE inhibition prevents pressure-induced maladaptive cardiac hypertrophy and increases intra- and extracardiac neoangiogenesis associated with the upregulation of EPC and amelioration of EPC migration. The regulation of progenitor cells from the bone marrow identifies a novel effect of ACE inhibitors during cardiac remodelling.
Retinoid X receptor gamma signaling accelerates CNS remyelination
Authors: Jeffrey K Huang, Andrew A Jarjour, Brahim Nait Oumesmar, Christophe Kerninon, Anna Williams, Wojciech Krezel, Hiroyuki Kagechika, Julien Bauer, Chao Zhao, Anne Baron-Van Evercooren, Pierre Chambon, Charles ffrench-Constant, Robin J M Franklin
Journal: Nature Neuroscience (2010)
Demonstration of impaired T cell regulation of Epstein-Barr virus stimulated B lymphocytes in rheumatoid arthritis with HLA identical, disease discordant sibling pairs.
Authors: M C Fawcett, D J Walker, I D Griffiths
Journal: Annals of the Rheumatic Diseases (1988)

Lymphocytes from patients with rheumatoid arthritis (RA) show an abnormal response after stimulation with Epstein-Barr virus (EBV), a potent B cell mitogen. In vitro IgM production from EBV stimulated lymphocytes was measured over a 21 day period. In keeping with previous studies, RA lymphocytes showed increasing IgM production between 14 and 21 days, whereas IgM production decreased during this period in normal lymphocytes (p less than 0.001). Experiments on 12 HLA identical, RA discordant sibling pairs were also undertaken. B enriched and T enriched lymphocyte populations were obtained and recombined in both an autologous and homologous manner. The abnormality in IgM production in patients with RA was shown to reside in the RA T cell population (p less than 0.005), and RA B cells combined with normal T cells behaved similarly to autologous cultures of normal B and T cells. The study shows that impaired immunoregulation of EBV stimulated B cells in RA is secondary to a functional defect in RA T cells, but no difference in the concentration of T suppressor/cytotoxic cells could be found between the disease discordant siblings. The abnormality in immunoregulation appears to be secondary to RA, rather than a product of genes encoded within the major histocompatibility complex (MHC) region, as defined by HLA-DR, A, B, and C typing.
Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance
Authors: Maura Agostini, Erik Schoenmakers, Catherine Mitchell, Istvan Szatmari, David Savage, Aaron Smith, Odelia Rajanayagam, Robert Semple, Jian'an Luan, Louise Bath, Anthony Zalin, Mourad Labib, Sudhesh Kumar, Helen Simpson, Dirk Blom, David Marais, John Schwabe, Inês Barroso, Richard Trembath, Nicholas Wareham, Laszlo Nagy, Mark Gurnell, Stephen O'Rahilly, Krishna Chatterjee
Journal: Cell Metabolism (2006)

PPARγ is essential for adipogenesis and metabolic homeostasis. We describe mutations in the DNA and ligand binding domains of human PPARγ in lipodystrophic, severe insulin resistance. These receptor mutants lack DNA binding and transcriptional activity but can translocate to the nucleus, interact with PPARγ coactivators and inhibit coexpressed wild-type receptor. Expression of PPARγ target genes is markedly attenuated in mutation-containing versus receptor haploinsufficent primary cells, indicating that such dominant-negative inhibition operates in vivo. Our observations suggest that these mutants restrict wild-type PPARγ action via a non-DNA binding, transcriptional interference mechanism, which may involve sequestration of functionally limiting coactivators.
Effect of an NK<sub>1</sub>/NK<sub>2</sub> Receptor Antagonist on Airway Responses and Inflammation to Allergen in Asthma
Authors: Johan D. Boot, Sanne de Haas, Svetlana Tarasevych, Christine Roy, Lin Wang, Dilip Amin, Judith Cohen, Peter J. Sterk, Barry Miller, Anne Paccaly, Jacobus Burggraaf, Adam F. Cohen, Zuzana Diamant
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The tachykinins substance P and neurokinin A (NKA) are implicated in the pathophysiology of asthma.We tested the safety, tolerability, and pharmacologic and biological efficacy of a tachykinin NK(1)/NK(2) receptor antagonist, AVE5883, in patients with asthma in two double-blind, placebo-controlled crossover studies.The pharmacologic efficacy of a single inhaled dose (4.8 mg) of AVE5883 was tested against inhaled NKA in 20 patients with asthma. Subsequently, we studied the biological efficacy of the pharmacologically effective dose on inhaled allergen in a multiple-dose trial (4.8 mg three times per day, 9 d) in 12 patients with asthma with dual responses to inhaled house dust mite. On Day 8, an allergen challenge was conducted, and airway response was measured by FEV(1) until 9 hours postallergen. Exhaled NO, provocative concentration of methacholine bromide causing a 20% fall in FEV(1), and induced sputum were performed on Days 1, 7, and 9.AVE5883 had a bad taste, and transient bronchospasm occurred in some subjects. A single inhaled dose shifted the dose response to NKA by 1.2 doubling doses. Pretreatment with multiple doses of AVE5883 enhanced the allergen-induced early and late airway responses. There were no significant differences in the allergen-induced changes in exhaled NO, provocative concentration of methacholine bromide causing a 20% fall in FEV(1), and sputum cell differentials between placebo and AVE5883.Despite its demonstrated pharmacologic activity against inhaled NKA, multiple doses of AVE5883 increased the allergen-induced airway responses without affecting markers of airway hyperresponsiveness and airway inflammation. Our data question the prominent role of neurogenic inflammation in asthma and, consequently, the therapeutic potential of dual tachykinin antagonists.
Effects of Antineoplastic Drugs on Plateau-Phase Cultures of Mammalian Cells. II. Bleomycin and Hydroxyurea2
Authors: F. Mauro, B. Falpo, G. Briganti, R. Elli, G. Zupi
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Effects of Antineoplastic Drugs on Plateau-Phase Cultures of Mammalian Cells. II. Bleomycin and Hydroxyurea Get access F. Mauro, F. Mauro 3Laboratorio di Radiobiologia Animale, C. S. N. Casaccia, Comitato Nazionale Energia Nucleare, Rome, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Falpo, B. Falpo 3Laboratorio di Radiobiologia Animale, C. S. N. Casaccia, Comitato Nazionale Energia Nucleare, Rome, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Briganti, G. Briganti 3Laboratorio di Radiobiologia Animale, C. S. N. Casaccia, Comitato Nazionale Energia Nucleare, Rome, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Elli, R. Elli 4Istituto di Biologia Generale, Facolta di Medicina, Università di Roma, Rome. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Zupi G. Zupi 5Istituto Regina Elena per 10 Studio e la Cura dei Tumori, Viale Regina Elena, Rome. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 715–722, https://doi.org/10.1093/jnci/52.3.715 Published: 01 March 1974 Article history Received: 13 July 1973 Accepted: 11 October 1973 Published: 01 March 1974
Clinical patterns of lichen planopilaris in patients with vulval lichen planus
Authors: A. Chew, C.M. Stefanato, I. Savarese, S.M. Neill, D.A. Fenton, F.M. Lewis
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Lichen planus (LP) is a common inflammatory dermatosis that can affect the skin, scalp or nails, as well as mucosal surfaces, including oral, genital and oesophageal sites and the lacrimal duct. On the scalp, lichen planopilaris (LPP) may precede lesions of classic LP on the body in > 50% of cases,1 2 and clinically it may present with patchy or diffuse hair loss, or in the patterned variant of frontal fibrosing alopecia (FFA).1 In the vulva, three forms of LP are recognized – classic, erosive and hypertrophic. The most common type of vulval LP is erosive LP, which can lead to significant scarring with alteration of the normal vulval architecture. In the vulvovaginal–gingival syndrome subtype of erosive LP, vaginal stenosis can lead to functional and psychosexual sequelae.3 The aims of our study were to determine the frequency of patients with vulval LP and concomitant scalp LPP, and to establish the patterns of scalp LPP in these patients. A secondary aim was to identify the frequency of oral LP in this cohort.
Combination of Multiple Genetic Risk Factors Is Synergistically Associated With Carotid Atherosclerosis in Japanese Subjects With Type 2 Diabetes
Authors: Yoshimitsu Yamasaki, Naoto Katakami, Ken’ya Sakamoto, Hideaki Kaneto, Munehide Matsuhisa, Hiroshi Sato, Masatsugu Hori, Masakazu Haneda, Atsunori Kashiwagi, Yasushi Tanaka, Ryuzo Kawamori, Shin-ichi Kuno
Journal: Diabetes Care (2006)

Several genetic risk factors, such as single nucleotide polymorphisms (SNPs), in candidate genes have been reported to be responsible for intima-media thickness (IMT), which is one of the surrogate end points of cardiovascular events. However, the synergistic effects of SNPs have not been evaluated in detail.We measured the average IMT of the common and internal carotid artery in Japanese type 2 diabetic patients (n = 690) (>50 years old) using ultrasonography. We also determined their genotypes regarding 106 SNPs in candidate genes responsible for cardiovascular diseases. Among the 106 SNPs, we selected 40 common (frequency of minor allele >/=10%) SNPs. We compared the average IMT of subjects with and without any pairs of four genotypes selected from the 40 common SNPs.The combination of methylen-tetrahydrofolate reductase 677 TT genotype and lymphotoxin-alpha (LTA) 252 GG genotype and that of ACE DD genotype and LTA 252 GG genotype were evaluated as responsible for a statistically significant (P = 2.7 x 10(-9) and 3.5 x 10(-6), respectively) increase in average IMT (mean [+/-SD] 1.54 +/- 0.60 and 1.43 +/- 0.58 mm, respectively) compared with those of the subjects without these combinations (1.04 +/- 0.34 and 1.04 +/- 0.34 mm, respectively). No single genotype was shown to be responsible for the statistically significant difference in average IMT after Bonferroni's multiple comparison procedure.The present analysis demonstrates an approach to evaluate combinations of multiple genetic risk factors that are synergistically associated with carotid atherosclerosis.
Effect of smoking on MAP kinase-induced modulation of IL‐8 in human alveolar macrophages
Authors: A. Koch, M. Giembycz, R.G. Stirling, S. Lim, I. Adcock, K. Waßermann, E. Erdmann, K.F. Chung
Journal: European Respiratory Journal (2004)

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking. The smoking-induced regulation of interleukin (IL)‐8 by extracellular signal-regulated kinase (ERK)‐1 and ‐2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor‐κB (NF‐κB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers. IL‐8 production was dependent on phosphorylation of ERK‐1 and ‐2 and p38 MAPK, as examined by PD 098059 (10 µM), an inhibitor of the upstream activator of MAPK kinase (MKK)‐1, and SB 203580 (10 µM), an inhibitor of p38 MAPK. IL‐8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK‐2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK‐2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK‐1 and ‐2. Lipopolysaccharide-induced IL‐8 production was dependent on activation of NF‐κB, as examined by SN 50 (100 µM), an inhibitor of NF‐κB translocation, and the specific NF‐κB inhibitor kinase‐2 inhibitor, AS 602868 (10 µM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF‐κB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay. It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor‐κB activation to increase lipopolysaccharide-induced interleukin‐8 production in alveolar macrophages.
Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation
Authors: Marc Seifert, Ralf Küppers
Journal: The Journal of Experimental Medicine (2009)

The origin of IgM+CD27+ B lymphocytes with mutated IgV genes, which account for ∼20% of human peripheral blood (PB) B cells, is controversially discussed. A generation in a primary diversification pathway, in T cell–independent immune responses, or in T cell–dependent germinal center (GC) reactions has been proposed. We show here that IgM+IgD+CD27+ and IgM+IgD−/lowCD27+ B cell subsets carry, like class-switched memory B cells, mutations in the Bcl6 gene as a genetic trait of a GC experience. Moreover, the identification of PB IgM+IgD+CD27+ B cells clonally related to GC-derived IgG+ memory B cells with shared and distinct IgV gene mutations demonstrates the GC origin also of the former subset. These findings provide genetic evidence for a GC derivation of somatically mutated IgM+ B cells and indicate that adult humans harbor a large population of IgM+IgD+ post-GC memory B cells. Furthermore, the analysis revealed that a highly diverse and often very large population of memory B cells is generated from a given GC B cell clone, and that (preferentially IgM) memory B cells are generated already early in the GC reaction. This provides novel insights into the dynamics of GC reactions and the generation of a memory B cell repertoire.
Neutrophil Function: From Mechanisms to Disease
Authors: Borko Amulic, Christel Cazalet, Garret L. Hayes, Kathleen D. Metzler, Arturo Zychlinsky
Journal: Annual Review of Immunology (2012)

Neutrophils are the most abundant white blood cells in circulation, and patients with congenital neutrophil deficiencies suffer from severe infections that are often fatal, underscoring the importance of these cells in immune defense. In spite of neutrophils' relevance in immunity, research on these cells has been hampered by their experimentally intractable nature. Here, we present a survey of basic neutrophil biology, with an emphasis on examples that highlight the function of neutrophils not only as professional killers, but also as instructors of the immune system in the context of infection and inflammatory disease. We focus on emerging issues in the field of neutrophil biology, address questions in this area that remain unanswered, and critically examine the experimental basis for common assumptions found in neutrophil literature.
Task-Specific Hypoactivation in Prefrontal and Temporoparietal Brain Regions During Motor Inhibition and Task Switching in Medication-Naive Children and Adolescents With Attention Deficit Hyperactivity Disorder
Authors: Anna B. Smith, Eric Taylor, Mick Brammer, Brian Toone, Katya Rubia
Journal: American Journal of Psychiatry (2006)

Objective: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. Method: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). Results: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. Conclusion: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.
Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour
Authors: Kiyoshi Miyagawa, Jill Kent, Adrian Moore, Jean-Paul Charlieu, Melissa H. Little, Kathleen A. Williamson, Anna Kelsey, Keith W. Brown, Shabbir Hassam, Jakob Briner, Yasuhide Hayashi, Hisamaru Hirai, Yoshio Yazaki, Veronica van Heyningen, Nicholas D. Hastie
Journal: Nature Genetics (1998)
The Oxford Dictionary of Medical Quotations
Authors: R. Fox
Journal: Journal of the Royal Society of Medicine (2003)

According to the publisher's blurb, The Oxford Dictionary of Medical Quotations is the 'perfect Christmas present for the doctor who has everything'. It reached me just as the December JRSM went to bed, and I am adding a few hasty sentences as a service to such doctors. But first a word on conflict of interest: Peter McDonald, surgeon and writer, is Honorary Editor at the RSM and I value my happy working relationship with him; only yesterday we met for lunch, when we reached accord on many things other than the proper control of foxes.

In compiling the Dictionary his purpose was to offer a collection of medically related quotations, culled from eclectic reading, that might add spice to an article or lecture. 'Whether readers are looking for a suitable quotation on surgery, science, kidneys, or kindness', he declares in the preface, 'they should find much here to satisfy.' I agree: this is indeed a spicy collection, though not every wise saying is witty or every witty one wise; I spent a happy hour with it on the train home. The quotations, mainly from the English-speaking world, with a bias to the surgical, occupy just over a hundred pages, the other half of the book consisting of an index by subject.

In truth, this is not a dictionary but a miscellany—a 'work in progress' with acknowledged imperfections. It reflects Peter McDonald's enthusiasms. None the worse for that (the index includes foxglove but not fox), but do not look here for a systematic and comprehensive collection. Even for doctors who do not yet have everything it would make an agreeable present.