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Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yanping Li, Rong Cheng Li, Qiang Ye, Changgui Li, You Ping Liu, Xiao Ma, Yanan Li, Hong Zhao, Xiaoling Chen, Deepak Assudani, Naveen Karkada, Htay Htay Han, Olivier Van Der Meeren, Narcisa Mesaros
We conducted three phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received three doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 months of age (Group B)...
October 21, 2016: Human Vaccines & Immunotherapeutics
Anagha Loharikar, Laure Dumolard, Susan Chu, Terri Hyde, Tracey Goodman, Carsten Mantel
Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries...
October 21, 2016: MMWR. Morbidity and Mortality Weekly Report
Konstantin Evdokimov, Kong Sayasinh, Phonethipsavanh Nouanthong, Keooudomphone Vilivong, Bounthome Samountry, Darouny Phonekeo, Michel Strobel, Frank Haegeman, Peter Heimann, Claude P Muller, Antony P Black
OBJECTIVES: In Lao People's Democratic Republic (PDR) the high burden of vaccine preventable diseases is thought to be mainly due to low vaccine coverage. Here, we investigated the seroprotective response against diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine in children. METHODS: Serum was collected from 1131 children aged 9 to 50 months and their mothers in a cross-sectional study between December 2013 and July 2014...
October 15, 2016: Clinical Microbiology and Infection
Peter Aaby, Henrik Ravn, Christine S Benn
BACKGROUND: World Health Organization recently reviewed the possible nonspecific effects of diphtheria-tetanus-pertussis (DTP) vaccine. The results were considered inconsistent though most studies suggested deleterious effects. We examined whether inconsistencies in results reflected differences in effect of DTP or differences in the methodology used in different studies. METHODS: If children remain unvaccinated because they are frail or if children (including dead ones) with no information on vaccination status are classified as "unvaccinated," the mortality rate becomes unnaturally high among "unvaccinated" controls...
November 2016: Pediatric Infectious Disease Journal
Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
Peter Aaby, Jens Nielsen, Christine S Benn, Jean-François Trape
BACKGROUND: Diphtheria-tetanus-pertussis (DTP) may be associated with increased female mortality; the effect of co-administration with BCG is not known. METHODS: Between 1989 and 1997, we examined female and male mortality rates in rural Senegal where 7824 infants received the first dose of DTP and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine...
October 13, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
Julian P T Higgins, Karla Soares-Weiser, José A López-López, Artemisia Kakourou, Katherine Chaplin, Hannah Christensen, Natasha K Martin, Jonathan A C Sterne, Arthur L Reingold
OBJECTIVES:  To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN:  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies...
October 13, 2016: BMJ: British Medical Journal
Rama Kandasamy, Merryn Voysey, Fiona McQuaid, Karlijn de Nie, Rebecca Ryan, Olivia Orr, Ulrike Uhlig, Charles Sande, Daniel O'Connor, Andrew J Pollard
OBJECTIVE:  To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. DESIGN:  Systematic review of randomised controlled trials, cohort studies, and case-control studies. DATA SOURCES:  Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included...
October 13, 2016: BMJ: British Medical Journal
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Jeannette Scholl, Dimitris Dionyssiou, Efterpi Demiri, Cornelia Halin, Lothar C Dieterich, Michael Detmar
Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell-related networks, and indeed depletion of CD4(+) cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema...
October 6, 2016: JCI Insight
Bahaa Abu-Raya, Tobias R Kollmann, Arnaud Marchant, Duncan M MacGillivray
Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation...
2016: Frontiers in Immunology
J V Pai-Dhungat
No abstract text is available yet for this article.
February 2016: Journal of the Association of Physicians of India
Leonie Schnell, Ann-Katrin Mittler, Andrea Mattarei, Domenico Azarnia Tehran, Cesare Montecucco, Holger Barth
Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA) from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA) has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT)...
July 15, 2016: Toxins
Ousseny Zerbo, Berwick Chan, Kristin Goddard, Ned Lewis, Karin Bok, Nicola P Klein, Roger Baxter
BACKGROUND/OBJECTIVE: We describe the establishment of a dynamic database linking mothers to newborns with the goal of studying vaccine safety in both pregnant women and their children and provide results of a study utilizing this database as a proof of concept. METHODS: All Kaiser Permanente Northern California (KPNC) live births and their mothers were eligible for inclusion in the pregnancy database. We used the medical record number (MRN), a unique identifier, to retrieve information about events that occurred during the pregnancy and at delivery and linked this same MRN to newborns for post-partum follow up...
October 7, 2016: Vaccine
Michelle S Y Ng, Alice Y W Foong, Mark J A Koh
INTRODUCTION: The development of cutaneous neoplasms at immunization sites following vaccination is uncommon, and only few have been reported in the literature worldwide. We report an unusual case of an ulcerated giant dermatofibroma that developed as a chronic nonhealing plaque in the immunization scar of a young boy after vaccination. CASE REPORT: A 13-month-old Chinese boy presented with an unusual skin reaction on the vaccination site at the right anterolateral thigh following a routine intramuscular injection of '5-in-1' (diphtheria, tetanus, pertussis, polio and Haemophilus influenzae B) vaccine at 4 months of age...
May 2016: Case Reports in Dermatology
Isabel de de la Fuente Garcia, Léna Coïc, Jean-Marie Leclerc, Caroline Laverdière, Céline Rousseau, Philippe Ovetchkine, Bruce Tapiéro
BACKGROUND: The objective of this retrospective study was to assess protection against vaccine preventable diseases (VPDs) in children treated for acute lymphoblastic leukemia (ALL). PROCEDURE: Clinical characteristics and vaccination records were collected. Antibodies against VPDs were measured after completion of chemotherapy and after a booster dose of vaccine. Immunization status of household members was evaluated. RESULTS: Sixty children were included...
October 8, 2016: Pediatric Blood & Cancer
Ranee Seither, Kayla Calhoun, Jenelle Mellerson, Cynthia L Knighton, Erica Street, Vance Dietz, J Michael Underwood
State-mandated vaccination requirements for school entry protect children and communities against vaccine-preventable diseases (1). Each school year, federally funded immunization programs (e.g., states, territories, jurisdictions) collect and report kindergarten vaccination data to CDC. This report describes vaccination coverage estimates in all 50 states and the District of Columbia (DC), and the estimated number of kindergartners with at least one vaccine exemption in 47 states and DC, during the 2015-16 school year...
October 7, 2016: MMWR. Morbidity and Mortality Weekly Report
Holly A Hill, Laurie D Elam-Evans, David Yankey, James A Singleton, Vance Dietz
Sustained high coverage with recommended vaccinations among children has kept many vaccine-preventable diseases at low levels in the United States (1). To assess coverage with vaccinations recommended for children by age 2 years in the United States (2), CDC analyzed data collected by the 2015 National Immunization Survey (NIS) for children aged 19-35 months (born January 2012-May 2014). Overall, coverage did not change during 2014-2015. Coverage in 2015 was highest for ≥3 doses of poliovirus vaccine (93...
October 7, 2016: MMWR. Morbidity and Mortality Weekly Report
Jason C Gardenier, Geoffrey E Hespe, Raghu P Kataru, Ira L Savetsky, Jeremy S Torrisi, Gabriela D García Nores, Joseph J Dayan, David Chang, Jamie Zampell, Inés Martínez-Corral, Sagrario Ortega, Babak J Mehrara
Development of novel treatments for lymphedema has been limited by the fact that the pathophysiology of this disease is poorly understood. It remains unknown, for example, why limb swelling resulting from surgical injury resolves initially, but recurs in some cases months or years later. Finding answers for these basic questions has been hampered by the lack of adequate animal models. In the current study, we used Cre-lox mice that expressed the human diphtheria toxin receptor (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate the lymphatic system of the hind limb...
September 22, 2016: JCI Insight
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