tbuckley/cabot-search huggingface dataset:
Genetic Vaccine for Respiratory Syncytial Virus Provides Protection Without Disease Potentiation
Authors: Teresa R Johnson, David Rangel, Barney S Graham, Douglas E Brough, Jason G Gall
Journal: Molecular Therapy (2013)

Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥ 24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.
Gene expression profile of highly purified bone marrow mast cells in systemic mastocytosis
Authors: Cristina Teodosio, Andrés C. García-Montero, María Jara-Acevedo, Laura Sánchez-Muñoz, Carlos E. Pedreira, Ivan Álvarez-Twose, Sergio Matarraz, José M. Morgado, Paloma Bárcena, Almudena Matito, Andrea Mayado, Maria Luz Sanchez, María Diez-Campelo, Luis Escribano, Alberto Orfao
Journal: Journal of Allergy and Clinical Immunology (2013)
Air Pollution and Atherosclerosis: New Evidence to Support Air Quality Policies
Authors: Nino Künzli
Journal: PLoS Medicine (2013)

Increasing attention is being paid to the subject of air pollution, with the bulk of previous work being done in animal models suggesting that exposure to air pollution causes atherosclerosis—stiffening and calcification of the arteries—in rabbits and mice [1,2]. The new findings of Sara Adar and colleagues, published in this week’s PLOS Medicine [3], take us a step forward in clarifying the broader implications of air pollution by offering further evidence in humans that ambient particulate matter (PM) contributes to the development of cardiovascular disease (CVD). CVDs are now the world’s leading causes of death [4]. The most important underlying pathology resulting in CVD is atherosclerosis, known to be a life-long process with a long and silent pre-clinical phase. It has been known since the last century that ambient air pollution can trigger acute cardiovascular morbidities [5], and a comparative risk assessment of established triggers of myocardial infarctions concluded that a rather substantial fraction of these acute and life-threatening events can be attributed to current levels of air pollution [6]. However, it is of importance to understand the causes of atherosclerosis, given that its prevention or deceleration could drastically delay and reduce the burden of CVDs. The hypothesis that ambient air pollution could play a role in these chronic processes was first addressed and confirmed in rabbits and mice [1,2]. Adar et al. have now provided important humanbased results based upon the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA). It is only the second longitudinal study about the impact of air pollution on the progression of atherosclerosis and is the first one based on a general population sample free of CVD at study onset. The authors here share their early findings of MESA, which examined associations of common carotid artery intima-medial thickness (IMT), a surrogate of atherosclerosis, with long-term PM2.5 concentrations among over 5,300 people over an average of two-and-a-half years. They report that higher long-term PM2.5 concentrations are associated with increased IMT progression and that greater reductions in PM2.5 are related to slower IMT progression. MESA replicates findings observed in the first longitudinal study, which was based on data from five clinical trials conducted in volunteers from Los Angeles [7]. Both research teams used IMT as a marker of atherosclerosis [8]. With only two longitudinal studies, it is worth discussing three important issues that need to be addressed in the future, namely the contributing role of noise, the link between cross-sectional and longitudinal findings, and the identification of susceptibility factors.
The most distressing symptom
Authors: T. R. Harrison
Journal: JAMA (1966)

During the period, more remote than one likes to admit, when I was a medical student and then a house officer, the name of Frank Billings was heard many times. The young internists of my generation knew of his work and were conscious of his stature. It is fitting that we meet to honor him in the community he honored by his labors and, indeed, by his presence.  The almost incredible advance in the  and treatment of internal disorders that has occurred within our own life span is to be largely ascribed to the development of objective and precise methods for the study of disease in the living patient. The result has been a strong concern in our hospitals and medical schools with those procedures that prove a diagnosis and thus substitute solid facts for those ephemeral opinions that were often no more than informed—or uninformed— guesses. A perhaps
Pathologists Are Doctors
Authors: Tsuyoshi Inoshita
Journal: Annals of Internal Medicine (1993)

Letters1 April 1993Pathologists Are DoctorsTsuyoshi Inoshita, MDTsuyoshi Inoshita, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-7-199304010-00037 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I deeply regret if I offended anyone by my essay. It was not meant to compare specialties in any objective or scientific manner but rather to describe my experiences along a convoluted career path. Any apparently negative description of pathology was only intended to depict me as a misfit in that specialty because of my personal shortcomings and was definitely not intended to denigrate it or its important function.I understand that modern medicine is a team effort. As a newly minted clinician, I have a productive, cordial, and intellectually stimulating relationships with my pathologist colleagues. I am ... Author, Article, and Disclosure InformationAuthors: Tsuyoshi Inoshita, MDAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1993Volume 118, Issue 7Page: 575KeywordsEmotionsPathologists ePublished: 15 August 2000 Issue Published: 1 April 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Home Uterine Activity Monitoring for Preterm Labor
Authors: Harold C. Sox
Journal: JAMA (1993)

PRETERM birth is a leading cause of perinatal morbidity and mortality in the United States. Preterm neonates are thought to account for at least half of the mortality and morbidity among newborns without congenital anomalies.<sup>1</sup>These conditions represent a leading cause of years of potential life lost before the age of 65 years. Preterm births generate large societal costs by requiring neonatal intensive care and long-term treatment for complications. Both primary and secondary preventive measures have been proposed for the prevention of prematurity. Primary prevention includes efforts to reduce risk factors for prematurity, such as cessation of tobacco, alcohol, and other drug use, and programs to improve nutrition, socioeconomic conditions, and prenatal care. Secondary prevention involves the early detection and treatment of preterm labor. It has been suggested that the risk of preterm birth can be reduced significantly by the prompt initiation of treatment, which includes rest, hydration, and
Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies
Authors: ALAN L. SCHOCKET, J. CLARK HUFF, RONALD I. CARR, DAVID A. NORRIS
Journal: British Journal of Dermatology (1982)

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuclear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I125 Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. there was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.
Predicting longitudinal trajectory of bone mineral density in paediatric systemic lupus erythematosus patients
Authors: Lily Siok Hoon Lim, Susanne M Benseler, Pascal N Tyrrell, Elizabeth Harvey, Diane Herbert, Martin Charron, Earl D Silverman
Journal: Annals of the Rheumatic Diseases (2012)

(1) To identify the average lumbar spine (LS) bone mineral density (BMD) trajectory in paediatric systemic lupus erythematosus (pSLE) patients, and (2) to identify predictors of BMD trajectory.68 consecutive newly diagnosed pSLE patients prospectively followed in our lupus cohort with three annual dual energy x-ray absorptiometry (DEXA) examinations were studied. Low LS BMD was defined as z-score ≤-2.0. Baseline and longitudinal clinical features including disease activity, treatment and bone physiology markers were collected. Hierarchical linear modelling was used to model trajectory of LS BMD and identify predictors.Women constituted 84% of the cohort and median age at diagnosis was 13.1 years. The mean LS BMD z-scores decreased over time (-0.42 at first, -1.02 at second and -1.11 at third DEXA). Initially 9% of patients had a low BMD, which increased to 19% by 3 years after diagnosis. 35% of patients deteriorated in BMD category from the first to third DEXA. LS BMD (adjusted by height-for-age z-score) followed a general deteriorating trajectory of -0.06 z-score/year from diagnosis. Increased rate of deterioration of BMD trajectory was predicted by pubertal status at diagnosis, increased interval cumulative steroid exposure and decreased weight z-scores.The LS BMD of pSLE patients followed a general deteriorating trend over time and could be predicted by a combination of pubertal status at diagnosis, interval cumulative doses of steroids and weight z-scores. Interval cumulative steroid dose represents an important target that clinicians may modify to ameliorate deteriorating BMD trajectory over time.
Abstract 5084: Overcoming the resistance to anti-angiogenic therapy: Itraconazole blocks blood vessel maturation and synergizes with anti-VEGF therapy.
Authors: Chenglai Fu, Stephanie Gerber, Richmond Castillo, Anita van der Zwan, Sushant Kachhap, Hans Hammers
Journal: Cancer Research (2013)

Abstract Background: Anti-angiogenic drugs, such as sunitinib, have been used as a first line therapy for renal cell carcinoma and some other cancers. However, the development of resistance to angiogenesis inhibitors targeting the VEGF pathway is common and impedes the efficacy of cancer treatments. Previously, we found it that blood vessel maturation is a common feature of tumors resistant to sunitinib. Thus, we hypothesized that novel approaches of inhibiting pericyte coverage of the tumor vasculature could be a successful approach to sensitize resistant tumors to sunitinib. Approach: An in vitro angiogenesis model was developed for screening the pericyte recruitment inhibitors. Itraconazole, an anti-fungal drug, was found to block the association of pericyte with newly-formed blood vessel endothelial cells. A sunitinib resistance animal model of Myc-Cap prostate cancer xenograft was used for studying the in vivo effect of treatment. Animals were dosed with itraconazole, sunitinib or the combination when tumors were well established. Result: through the in vitro angiogenesis model, the association of pericyte with endothelial cells was significantly reduced by itraconazole treatment. Its mechanism of action involved inhibition of focal adhesion kinase activity, a protein that plays a central role in cell spreading, differentiation, migration and cell death. Moreover, itraconazole treatment showed reduced pericyte coverage of tumor vasculature in vivo, and synergized with sunitinib treatments. Conclusion: These findings indicated that itraconazole is effective in inhibiting the pericyte coverage of the tumor vasculature and broaden the efficacy of sunitinib. Our results support further preclinical and clinical evaluation of itraconazole combination therapies in cancer treatment. Citation Format: Chenglai Fu, Stephanie Gerber, Richmond Castillo, Anita van der Zwan, Sushant Kachhap, Hans Hammers. Overcoming the resistance to anti-angiogenic therapy: Itraconazole blocks blood vessel maturation and synergizes with anti-VEGF therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5084. doi:10.1158/1538-7445.AM2013-5084
S33 Validation of the GLI-2012 Multi-Ethnic Spirometry Reference Equations in London School Children
Authors: S Lum, R Bonner, J Kirkby, S Sonnappa, J Stocks
Journal: Thorax (2012)

The Global Lung Function Initiative (GLI) recently published the first global all-age (3–95 years) multi-ethnic reference equations for spirometry (Quanjer 2012 ERJ). <h3>Aim</h3> To assess the agreement of the GLI reference range to contemporary lung function data from children living in Britain to verify its appropriateness for clinical use in this population. <h3>Methods</h3> Anthropometry and spirometry were undertaken within a mobile laboratory in primary school children recruited to the Size and Lung function In Children study during one school year (2011–2012). Spirometry Z-scores were calculated using the GLI-2012 reference range, using the ‘Black equation’ for South Asian children, for whom a specific equation has yet to be developed. <h3>Results</h3> Spirometry data from 728 (47% boys; 35% White; 28% Black; 26% South Asian; 11% other/mixed race) healthy children aged 5–11 years from eight London schools were eligible for inclusion. Mean (SD) age of 8 (1.6) years was similar across the 4 ethnic groups. After adjustment for age and sex, Black children were significantly heavier and taller compared to other groups, while South Asians were significantly lighter. When compared with White children, after adjusting for age, sex and standing height, FEV1 was significantly lower by a mean(95%CI) of 14% (11%; 16%) in Black; 11% (9%; 14%) in South Asian and 4% (1%; 8%) in the “other”/mixed race children. Similar patterns were seen for FVC but FEV1/FVC was similar across all groups. When expressed according to ethnic-specific reference equations the mean (SD) for FVC, FEV1 and FEV1/FVC for the White, Black and other groups approximated 0(1) suggesting that the GLI equations are appropriate for use in this population (Figure). Mean (95%CI) FVC and FEV1 were however 3% (–0.1%; 6.1%, p=0.07) higher in South Asian than Black children. <h3>Conclusions</h3> This study shows that the GLI-2012 equations are appropriate for use in children across a wide range of ethnicities. Of the currently available equations, the ‘Black equation’ provides the best fit for South Asian children, although it results in slight over-estimation of lung function, emphasising the need to develop specific coefficients for this group.
STRUCTURE AND DEVELOPMENT OF VIRUSES AS OBSERVED IN THE ELECTRON MICROSCOPE
Authors: Richard A. Rifkind, Gabriel C. Godman, Calderon Howe, Councilman Morgan, Harry M. Rose
Journal: The Journal of Experimental Medicine (1961)

Sequential stages in the development and release of ECHO 9 virus have been illustrated and described. It is suggested that viral particles differentiate and become oriented in columns upon a fine filamentous lattice at cytoplasmic template sites which are distinct from the endoplasmic reticulum. Subsequently, virus is dispersed in the peripheral cytoplasm and gains egress from the cell through rents in the plasma membrane. Complete cellular disruption with viral release may supervene. The virus consists of a 13 to 15 mmicro dense core and a poorly defined outer membrane, 22 to 24 mmicro in diameter. Incomplete forms, lacking the core, are observed in the cytoplasm but have not been seen in the extracellular space.
Quantification of Stromal Thinning, Epithelial Thickness, and Corneal Haze after Photorefractive Keratectomy Using In Vivo Confocal Microscopy
Authors: Torben Møller-Pedersen, Mitchell Vogel, Hong Fang Li, W. Matthew Petroll, H. Dwight Cavanagh, James V. Jester
Journal: Ophthalmology (1997)
Inadvertent self administration of superglue: a consumer hazard.
Authors: S J Morgan, N J Astbury
Journal: BMJ (1984)

Une observation rare: instillation dans un œil de «superglue» (colle de cyanoacrylate) par erreur, a la place d'un collyre dont la bouteille a le meme aspect. Reaction douloureuse et constitution immediate d'une adherence des paupieres; traitement improvise par infiltration d'onguent oculaire de chloramphenicol puis decoupage secondaire de l'enveloppe de colle. La grande erosion corneenne et conjonctivale presente ensuite une cicatrisation sans probleme
Actions of ristocetin on platelets
Authors: J. Koutts, Lyne Stott B. Sc, B. G. Firkin
Journal: American Journal of Hematology (1976)

Abstract The absence of ristocetin‐induced platelet aggregation appears to correlate with the platelet defect in von Willebrand's disease, suggesting that this reaction mimics a physiological process. The effect of ristocetin on plasma and on the residual levels of the von Willebrand factor (vWF), Factor VIII procoagulant activity, and Factor VIII‐related protein in plasma after aggregation of platelet rich plasma by this agent has been studied in order to further elucidate the mechanism and requirements of this reaction. Ristocetin‐induced platelet aggregation causes a consumption of vWF, Factor VIII procoagulant activity, and Factor VIII antigen from the supernatant plasma which is proportional to the number of platelets aggregated. Such a consumption of these factors does not appear to occur after aggregation by other agents. Factor VIII procoagulant activity does not appear necessary for ristocetin‐induced platelet aggregation, yet is utilized in this process. These findings support the hypothesis that the molecule associated with Factor VIII procoagulant activity is carried by the molecule necessary for ristocetin‐induced platelet aggregation.
Cytokine production by bronchoalveolar lavage cells in chronic beryllium disease.
Authors: S S Tinkle, P W Schwitters, L S Newman
Journal: Environmental Health Perspectives (1996)

Chronic beryllium disease (CBD) begins as a sensitizing cell-mediated immune response to beryllium antigen that progresses to granulomatous lung disease. Previous studies demonstrated the involvement of proinflammatory cytokines in the disease process, but the pattern and regulation of cytokine release is unknown. Using bronchoalveolar lavage (BAL) cells from CBD patients in short-term tissue culture, we evaluated cytokine protein levels by enzyme-linked immunosorbent assay and T-lymphocyte proliferation by tritiated thymidine incorporation. We observed the beryllium-stimulated release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) but not interleukin-4 (IL-4). Beryllium-stimulated IFN-gamma release was sustained to 168 hr in culture, whereas IL-2 concentrations returned to baseline after 24 hr. Neutralization of IL-2 decreased beryllium-stimulated T-lymphocyte proliferation, but the level of proliferation remained elevated in comparison to unstimulated BAL cells. These data suggest that T helper 1 (Th1) lymphocytes participate in the beryllium disease process; that IFN-gamma levels remain elevated after IL-2 levels return to baseline; and that IL-2 participates directly in beryllium-stimulated T-cell proliferation, but other T-lymphocyte mitogenic cytokines may be involved.
Appearance of a ventricular 5-HT receptor-mediated inotropic response to serotonin in heart failure
Authors: E QVIGSTAD, T BRATTELID, I SJAASTAD, K ANDRESSEN, K KROBERT, J BIRKELAND, O SEJERSTED, A KAUMANN, T SKOMEDAL, J OSNES
Journal: Cardiovascular Research (2004)

Current pharmacological treatment of congestive heart failure (CHF) addresses changes in neurohumoral stimulation or cardiac responsiveness to such stimulation. Yet, undiscovered neurohumoral changes, adaptive or maladaptive, may occur in CHF and suggest novel pharmacological treatment. Serotonin [5-hydroxytryptamine (5-HT)] enhances contractility and causes arrhythmias through 5-HT(4) receptors in human atrium and ventricle but not through rat ventricular 5-HT(4) receptors.We investigated whether CHF could induce ventricular responsiveness to serotonin.Postinfarction CHF was induced in male Wistar rats by coronary artery ligation. Contractility was measured in left ventricular papillary muscles 6 weeks after infarction. Messenger RNA was quantified by RT-PCR and cAMP by RIA.Serotonin caused positive inotropic (-logEC(50)=7.5) and lusitropic effects in CHF but not Sham papillary muscles. The inotropic effect of 10 muM serotonin in CHF (31.3+/-2.2%) was of similar size as the effect of 10 muM isoproterenol (34.0+/-1.7%). The effects of serotonin were antagonised by GR113808 (0.5-5 nM), consistent with mediation through 5-HT(4) receptors. This was further supported by positive inotropic effects of the 5-HT(4)-selective partial agonist RS67506. Carbachol blunted the serotonin responses and serotonin increased ventricular and cardiomyocyte cAMP, consistent with coupling to G(s) and adenylyl cyclase. Quantitative RT-PCR revealed fourfold increased 5-HT(4(b)) mRNA expression in CHF vs. Sham ventricles.Functional ventricular 5-HT(4) receptors are induced by myocardial infarction and CHF of the rat heart. We propose that they are a model for ventricular 5-HT(4) receptors of human failing heart and may play a pathophysiological role in heart failure.
Transient Remission After Acute Respiratory Infection in Patients with Idiopathic Thrombocytopenic Purpura
Authors: YOSHIYUKl KURATA
Journal: Annals of Internal Medicine (1982)

We describe five patients with chronic idiopathic thrombocytopenic purpura who had transient remission after acute respiratory infection. The level of platelet-associated IgG, measured in three of these patients, was increased before infection but was normal when the platelet count was elevated. The level of circulating immune complexes did not show any significant change. We conclude that the elevation of platelet count after acute respiratory infection was due to the decreased production of platelet autoantibody.
THE Character and Treatment of Frost-bite
Authors: H. E. Munroe
Journal: BMJ (1915)

tDEC. 25, I915 the artery sutured laterally with fine silk sutures.A graft taken from tlle (Fia.3) internal saphenous vein was sutured to the opposite side of the stutured artery (Fig. 4).The operation lasted two hours.On removing the clamps the circulation was perfect, and there was no haemorrlhaae fromii the line of suture.The wound was closed without drainage and the stitches were removed on' the tenth day.'Tlhe patient made an uninterrupted recovery.I ex- tamined him five months after the operation; he was then doing light duty, and the circulation in the limb was normal.