tbuckley/cabot-search huggingface dataset:
An Assay of Goldenrod as a Cause of Hay Fever
Authors: WARREN T. VAUGHAN
Journal: Annals of Internal Medicine (1932)

Article1 December 1932An Assay of Goldenrod as a Cause of Hay FeverWARREN T. VAUGHAN, M.D., F.A.C.P., RUTH W. CROCKETTWARREN T. VAUGHAN, M.D., F.A.C.P.Search for more papers by this author, RUTH W. CROCKETTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-6-6-789 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGoldenrod, apparently our most popular aspirant for the title of "national flower" has in years past been reputed to be the principal cause of autumnal hay fever and asthma. Our modern concept of the etiology of pollen asthma has demonstrated that wind borne pollens are of far greater importance in this malady than are the pollens of those plants which are cross fertilized by insects. Indeed, the importance of wind distribution has been so emphasized, that prominent students of allergy have stated that goldenrod and other insect pollinated plants are of very little importance in the causation of pollen allergy....References1 SCHEPPEGRELL W: Hay fever and asthma, 1922, Lea & Febiger, Philadelphia. Google Scholar2 DURHAM OC: Personal communication. Google Scholar3 BLACKDURHAM JHOC: Elm pollen as a complicating factor in hay fever, Jr. Allergy, 1930, i, 501-505. CrossrefGoogle Scholar4 HEALTH NEWS: H-23, Apr. 25, 1931, U. S. P. H. S. Google Scholar5 TALMAN CF: Air a vast carrier of living matter, New York Times, Sci. Sect., 1931, Nov. 1. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WARREN T. VAUGHAN, M.D., F.A.C.P.; RUTH W. CROCKETTAffiliations: Richmond, VirginiaReceived for publication, April 1, 1932. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOn the CoverEvidence of group specific and species specific sensitization to pollen 1 December 1932Volume 6, Issue 6Page: 789-794KeywordsAllergy and immunologyAsthmaEtiologyFeversPollen ePublished: 1 December 2008 Issue Published: 1 December 1932 PDF downloadLoading ...
Immune activation in the small intestine in patients with rheumatoid arthritis
Authors: R Nissinen
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To determine whether inflammation in the gut associated immune system is activated in rheumatoid arthritis (RA). The expression of chemokine receptor- (CCR4, CCR5) and cytokine- (interleukin (IL)2, IL10, interferon γ (IFNγ), tumour necrosis factor α (TNFα), and transforming growth factor β (TGFβ)) specific mRNA in intestinal biopsy samples from patients with RA was examined. <b>Methods:</b> Duodenal biopsy samples from 13 patients with RA and 15 control subjects were studied. The mRNA expression of CCR4, CCR5, IL2, IL10, IFNγ, TNFα, and TGFβ in intestinal biopsy samples was demonstrated by real time quantitative reverse transcriptase-polymerase chain reaction. <b>Results:</b> The mRNA expression of CCR4, CCR5, and IL10 in intestinal biopsy samples was increased in patients with RA in comparison with control subjects (p = 0.001, p = 0.046, p = 0.019). No difference in the expression levels of IL2, IFNγ, TNFα, or TGFβ was seen between patients with RA and controls. <b>Conclusions:</b> The increased intestinal mRNA expression of IL10, CCR5, and CCR4 suggests that gut associated immune cells are activated in patients with RA.
Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency
Authors: Tatsuyoshi Kawamura, Youichi Ogawa, Yuumi Nakamura, Satoshi Nakamizo, Yoshihiro Ohta, Hajime Nakano, Kenji Kabashima, Ichiro Katayama, Schuichi Koizumi, Tatsuhiko Kodama, Atsuhito Nakao, Shinji Shimada
Journal: Journal of Clinical Investigation (2012)

Zinc deficiency can be an inherited disorder, in which case it is known as acrodermatitis enteropathica (AE), or an acquired disorder caused by low dietary intake of zinc. Even though zinc deficiency diminishes cellular and humoral immunity, patients develop immunostimulating skin inflammation. Here, we have demonstrated that despite diminished allergic contact dermatitis in mice fed a zinc-deficient (ZD) diet, irritant contact dermatitis (ICD) in these mice was more severe and prolonged than that in controls. Further, histological examination of ICD lesions in ZD mice revealed subcorneal vacuolization and epidermal pallor, histological features of AE. Consistent with the fact that ATP release from chemically injured keratinocytes serves as a causative mediator of ICD, we found that the severe ICD response in ZD mice was attenuated by local injection of soluble nucleoside triphosphate diphosphohydrolase. In addition, skin tissue from ZD mice with ICD showed increased levels of ATP, as did cultured wild-type keratinocytes treated with chemical irritants and the zinc-chelating reagent TPEN. Interestingly, numbers of epidermal Langerhans cells (LCs), which play a protective role against ATP-mediated inflammatory signals, were decreased in ZD mice as well as samples from ZD patients. These findings suggest that upon exposure to irritants, aberrant ATP release from keratinocytes and impaired LC-dependent hydrolysis of nucleotides may be important in the pathogenesis of AE.
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors
Authors: Thibault Voron, Orianne Colussi, Elie Marcheteau, Simon Pernot, Mevyn Nizard, Anne-Laure Pointet, Sabrina Latreche, Sonia Bergaya, Nadine Benhamouda, Corinne Tanchot, Christian Stockmann, Pierre Combe, Anne Berger, Franck Zinzindohoue, Hideo Yagita, Eric Tartour, Julien Taieb, Magali Terme
Journal: The Journal of Experimental Medicine (2015)

Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8+ T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A–VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.
Recognition of influenza A matrix protein by HLA-A2-restricted cytotoxic T lymphocytes. Use of analogues to orientate the matrix peptide in the HLA-A2 binding site.
Authors: F Gotch, A McMichael, J Rothbard
Journal: The Journal of Experimental Medicine (1988)

CTL specific for the influenza A virus matrix peptide 57-68 and restricted by HLA-A2 were studied. Their ability to recognize a set of analogue peptides, each of which differed from the natural peptide by a single amino acid, was analyzed. This revealed a core of five amino acids, 61-65, where one or more changes completely abrogated recognition. The glycine at position 61 was the only residue where no substitution was tolerated. Analogue peptides that did not induce CTL-mediated lysis were tested as competitors with the natural peptide; those with substitutions at positions 60, 64, and 65 inhibited, identifying residues that interact with the TCR. Another approach was to test a set of four CTL clones on all of the analogues. Marked differences in recognition by individual CTL clones were observed for several substituted peptides. The data indicate that most of the analogues bind to HLA-A2 with possible differences in fine positioning of the peptide. An alpha helical orientation for the peptide is discussed.
MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin's disease.
Authors: P Klimo, J M Connors
Journal: Journal of Clinical Oncology (1985)

Seventy patients with advanced Hodgkin's disease, 54 with new disease, and 16 in first relapse after initial radiotherapy, have been treated with a seven-drug, 8-month program: MOPP (nitrogen mustard, vincristine, procarbazine, prednisone)/ABV (Adriamycin [Adria Laboratories of Canada, Mississauga, Ontario], bleomycin, vinblastine) hybrid. A single involved field of radiotherapy was given to selected partial responders after 6 months of chemotherapy. Forty-six of the 52 (88%) evaluable new-disease patients and 14 of the 16 (87%) evaluable patients with relapsing disease reached a complete response. The actuarial overall survival at 49 months for the patients with new disease was 90% (median follow-up from diagnosis was 27 months). For the patients with relapsing disease, the actuarial survival at 54 months was 79% (median follow-up from diagnosis was 27 months). The actuarial relapse-free survival at 41 months for complete responders was 93% for patients with new disease (median follow-up after treatment was 20 months) and 80% for those with relapsing disease (median follow-up after treatment was 27 months). Toxicity was moderate, with two treatment-related deaths and eight episodes of serious infection. These results compare favorably with the best results reported in the literature. Furthermore, they were achieved with a moderate level of toxicity, high drug delivery rates, and a relatively short duration of treatment. The efficacy and toxicity data of the MOPP/ABV hybrid program will now be evaluated in a prospectively randomized multicenter study.
The strength of genetic interactions scales weakly with mutational effects
Authors: Andrea Velenich, Jeff Gore
Journal: Genome biology (2013)

Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae. We discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics. Although epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes.
CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer
Authors: Kristin V. Tarbell, Mark Lee, Erik Ranheim, Cheng Chi Chao, Maija Sanna, Seon-Kyeong Kim, Peter Dickie, Luc Teyton, Mark Davis, Hugh McDevitt
Journal: The Journal of Experimental Medicine (2002)

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.
319 PATIENTS WITH COMPENSATED CIRRHOSIS HAVE SELECTIVE PARESIS OF FLAGELLIN-INDUCED INNATE IMMUNE RESPONSES DUE TO FAILURES IN ERK SIGNALLING
Authors: W. Alazawi, R. Lahiri, A. Spyrou, E. Giles, Z. Bashir, A. O'Brien, A. Stagg, J. Waters, G.R. Foster
Journal: Journal of Hepatology (2013)
Overexpression of the Na <sup>+</sup> /K <sup>+</sup> ATPase α2 But Not α1 Isoform Attenuates Pathological Cardiac Hypertrophy and Remodeling
Authors: Robert N. Correll, Petra Eder, Adam R. Burr, Sanda Despa, Jennifer Davis, Donald M. Bers, Jeffery D. Molkentin
Journal: Circulation Research (2013)

Rationale: The Na + /K + ATPase (NKA) directly regulates intracellular Na + levels, which in turn indirectly regulates Ca 2+ levels by proximally controlling flux through the Na + /Ca 2+ exchanger (NCX1). Elevated Na + levels have been reported during heart failure, which permits some degree of reverse-mode Ca 2+ entry through NCX1, as well as less efficient Ca 2+ clearance. Objective: To determine whether maintaining lower intracellular Na + levels by NKA overexpression in the heart would enhance forward-mode Ca 2+ clearance and prevent reverse-mode Ca 2+ entry through NCX1 to protect the heart. Methods and Results: Cardiac-specific transgenic mice overexpressing either NKA-α1 or NKA-α2 were generated and subjected to pressure overload hypertrophic stimulation. We found that although increased expression of NKA-α1 had no protective effect, overexpression of NKA-α2 significantly decreased cardiac hypertrophy after pressure overload in mice at 2, 10, and 16 weeks of stimulation. Remarkably, total NKA protein expression and activity were not altered in either of these 2 transgenic models because increased expression of one isoform led to a concomitant decrease in the other endogenous isoform. NKA-α2 overexpression but not NKA-α1 led to significantly faster removal of bulk Ca 2+ from the cytosol in a manner requiring NCX1 activity. Mechanistically, overexpressed NKA-α2 showed greater affinity for Na + compared with NKA-α1, leading to more efficient clearance of this ion. Furthermore, overexpression of NKA-α2 but not NKA-α1 was coupled to a decrease in phospholemman expression and phosphorylation, which would favor greater NKA activity, NCX1 activity, and Ca 2+ removal. Conclusions: Our results suggest that the protective effect produced by increased expression of NKA-α2 on the heart after pressure overload is due to more efficient Ca 2+ clearance because this isoform of NKA preferentially enhances NCX1 activity compared with NKA-α1.
Effects of S-Nitrosation and Cross-Linking of Hemoglobin on Hypoxic Pulmonary Vasoconstriction in Isolated Rat Lungs
Authors: Steven Deem, Joung-Uk Kim, Belur N. Manjula, A. Seetharama Acharya, Mark E. Kerr, Rakesh P. Patel, Mark T. Gladwin, Erik R. Swenson
Journal: Circulation Research (2002)

Free hemoglobin (Hb) and red blood cells augment hypoxic pulmonary vasoconstriction (HPV) by scavenging nitric oxide (NO). S-nitrosation of Hb (SNO-Hb) may confer vasodilatory properties by allowing release of NO during deoxygenation and/or by interaction with small-molecular weight thiols. Likewise, cross-linking of free Hb may limit its vasoconstrictive effect by preventing abluminal movement of the molecule. We compared the effects of free SNO-Hb and Hb intramolecularly cross-linked at the beta-cysteine 93 residue [Bis(maleidophenyl)-polyethylene glycol2000HbA (Bis-Mal-PEGHb)] to those of free oxyHb on pulmonary artery pressure (PAP), HPV, and exhaled NO (eNO) in isolated, perfused rat lungs. Ventilation of lungs with anoxic gas for 5 minutes reduced perfusate PO2 to 11+/-1.0 Torr. Addition of SNO-Hb or Bis-Mal-PEGHb (100 micromol/L) to buffer perfusate increased normoxic PAP and augmented HPV in similar magnitude as free oxyHb, but had no effect on eNO. Addition of the allosteric modulator inositol hexaphosphate to increase Hb P50 and the thiol glutathione (GSH) to allow removal of NO from Hb via transnitrosation to the perfusate did not reduce augmentation of HPV by SNO-Hb or increase eNO. GSH resulted in an approximately 50% reduction in perfusate [S-nitrosothiol], in association with an increase in perfusate [metHb]. Free SNO-Hb is a net NO scavenger and pulmonary vasoconstrictor in this model, although thiol-mediated release of NO from SNO-Hb does occur. However, release of NO from SNO-Hb was not influenced by deoxygenation-mediated allosteric changes in Hb across a broad range of oxyHb saturation. Cross-linking of Hb does not limit its pulmonary vasoconstrictor effects.
Healthcare use and prescription patterns associated with adult asthma in Korea: analysis of the NHI claims database
Authors: S. Kim, J. Kim, K. Kim, Y. Kim, Y. Park, S. Baek, S. Y. Park, S.-Y. Yoon, H.-S. Kwon, Y. S. Cho, T.-B. Kim, H.-B. Moon
Journal: Allergy (2013)

Background National Health Insurance (NHI) claim records could provide valuable data for epidemiological studies of asthma in Korea. The aim of this study is to estimate the prevalence of adult asthma and to investigate asthma-related healthcare use and prescription patterns in Korea over 5 years. Methods National Health Insurance claim records from January 1, 2006 to December 31, 2010 were analyzed in a retrospective, population-based study. Outcome measures included asthma prevalence, healthcare use, and prescription patterns over time, by type of hospital, and by medical specialty. Additionally, we assessed differences in healthcare use between newly diagnosed and previously diagnosed patients in 2009. Results Over 5 years, the prevalence of asthma among Korean adults increased from 4944 to 5707 cases per 100 000 population (from 3760 to 4445 in men and from 6108 to 6951 in women). Asthma-related outpatient visits decreased from 4.82 ± 8.02 to 3.44 ± 5.50. Approximately 3% of all patients were hospitalized and 2.4% received asthma-related emergency treatment each year. Pulmonary function tests were performed in 10–11% of patients an average of 1.3 times per year. Newly diagnosed patients experienced fewer asthma-related hospitalizations (1.78% vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously diagnosed group. Prescriptions of inhaled corticosteroids-based inhalers were maintained with about 20% of average of all types of hospitals. Conclusions The prevalence of asthma in Korea has increased over a recent 5-year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.
Baseline Characteristics of Participants in the Randomized National Lung Screening Trial
Authors: D. R. Aberle, A. M. Adams, C. D. Berg, J. D. Clapp, K. L. Clingan, I. F. Gareen, D. A. Lynch, P. M. Marcus, P. F. Pinsky
Journal: JNCI Journal of the National Cancer Institute (2010)

The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population. Eligible participants were aged 55–74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys. The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher. The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers.