Epidemiology of diphtheria in South Dakota.

Science.gov (United States)

Golaz, A; Lance-Parker, S; Welty, T; Schaefer, L; Volmer, L; LaFromboise, C; Dixon, J; Haase, T; Kim, C; Popovic, T; Bisgard, K; Strebel, P; Wharton, M

2000-07-01

Respiratory diphtheria was one of the most common causes of death among children in the pre-vaccine era. Since the introduction of diphtheria toxoid vaccine in 1920s, and its widespread use by the late 1940s, diphtheria became increasingly rare in the United States. However, through the 1970s diphtheria remained endemic in some states, with reported incidence rates > 1.0 per million population in six states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington). Starting in 1980, less than five cases have been reported each year in the United States. The majority of culture-confirmed cases have been associated with importation from other countries. Toxigenic Corynebacterium diphtheriae, the organism causing diphtheria, was thought to have become rare or even have disappeared from previously endemic areas such as South Dakota. However, during four months in 1996, 11 persons (one index case, six patients and four household contacts) in an American Indian community in South Dakota were found to be infected by C. diphtheriae; six of these isolates were toxigenic. The findings in this report indicate that despite 20 years without reported respiratory diphtheria cases, toxigenic C. diphtheriae is still present in South Dakota. The continuous circulation of toxigenic strains of C. diphtheriae emphasizes the need for health care providers throughout South Dakota to promote timely vaccination against diphtheria among persons of all ages and ethnic groups, to be aware of the clinical signs and symptoms of diphtheria so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease.

Genetic relationships of Corynebacterium diphtheriae strains isolated from a diphtheria case and carriers by restriction fragment length polymorphism of rRNA genes Relação genética de cepas de Corynebacterium diphtheriae isoladas de caso e seus contatos por RLFP de rRNA gene

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Claudio Tavares Sacchi

1995-08-01

Full Text Available In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells. The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain, that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.No presente estudo, nós reportamos os resultados de uma análise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma criança de 9 anos com difteria e seus 5 contatos. Análise quantitativa por RFLP de rRNA foi usada para determinar a relação destas 7 cepas de C. diphtheriae fornecendo dados de interesse epidemiológico. Nós também testamos estas cepas para toxicidade in vitro usando método de difusão de Elek e in vivo usando método de cultura celular com células VERO. Os resultados de hibridização revelaram que as 5 cepas de C. diphtheriae isoladas dos contatos e uma isolada do caso (cepa isolada

[Cutaneous diphtheria after a minor injury in Sri Lanka].

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Berg, L; Mechlin, A; Schultz, E S

2016-02-01

Cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in Germany. Following travel in Sri Lanka, a 60-year-old German presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. Corynebacterium diphtheriae was isolated from a swab of the lesion. There were no clinical signs of toxic diphtheria. The patient was treated with penicillin G and erythromycin, followed by a slow healing of the lesion. The isolated strain could be identified as toxigenic C. diphtheriae mitis. Due to increased travel activity, dermatologists should have uncommon infections like cutaneous diphtheria in mind.

Diphtheria: forgotten, but not gone.

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Adler, N R; Mahony, A; Friedman, N D

2013-02-01

Diphtheria is an acute, highly infectious, vaccine-preventable and previously endemic disease whose etiologic agent is Corynebacterium diphtheriae. Diphtheria may manifest as an upper respiratory tract infection, a cutaneous infection or as an asymptomatic carrier state. The most common sites of infection are the pharynx and the tonsils, with common clinical manifestations that include sore throat, malaise, cervical lymphadenopathy and low-grade fever. Absorption and dissemination of C. diphtheriae from the respiratory tract can cause disseminated infection and may lead to cardiac or neurological toxicity. The cornerstone of treatment for diphtheria is diphtheria antitoxin. Early treatment is critical as the degree of protection is inversely proportional to the duration of the illness before its administration. Routine childhood vaccination virtually eliminated diphtheria in most industrialised countries. However, in the pre-vaccination era, diphtheria was the most common infectious cause of death in Australia. A case of diphtheria in Brisbane in April 2011 and two recent positive cultures in regional Victoria underscore the need for heightened awareness of C. diphtheriae as an important pathogen. In order to prevent the re-emergence of diphtheria in Australia, public health measures are required to increase immunity in early school leavers and the adult population, and to ensure that travellers to endemic regions are fully immunised. Health policy-makers and clinicians alike should not underestimate the importance of primary vaccination and booster vaccination against diphtheria among healthy adults and travellers. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

An isolated outbreak of diphtheria in South Africa, 2015.

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Mahomed, S; Archary, M; Mutevedzi, P; Mahabeer, Y; Govender, P; Ntshoe, G; Kuhn, W; Thomas, J; Olowolagba, A; Blumberg, L; McCarthy, K; Mlisana, K; DU Plessis, M; VON Gottberg, A; Moodley, P

2017-07-01

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

Respiratory diphtheria in an asylum seeker from Afghanistan arriving to Finland via Sweden, December 2015.

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Sane, Jussi; Sorvari, Tiina; Widerström, Micael; Kauma, Heikki; Kaukoniemi, Ulla; Tarkka, Eveliina; Puumalainen, Taneli; Kuusi, Markku; Salminen, Mika; Lyytikäinen, Outi

2016-01-01

In December 2015, an asylum seeker originating from Afghanistan was diagnosed with respiratory diphtheria in Finland. He arrived in Finland from Sweden where he had already been clinically suspected and tested for diphtheria. Corynebacterium diphtheriae was confirmed in Sweden and shown to be genotypically and phenotypically toxigenic. The event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheria antitoxin availability.

A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

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Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2015-12-01

The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. © 2015 John Wiley & Sons Ltd.

Diphtheria in the postepidemic period, Europe, 2000-2009.

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Wagner, Karen S; White, Joanne M; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S; Neal, Shona; Efstratiou, Androulla

2012-02-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.

Epidemiology of Diphtheria in India, 1996-2016: Implications for Prevention and Control.

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Murhekar, Manoj

2017-08-01

Diphtheria is an acute disease caused by exotoxin-producing Corynebacterium diphtheriae . Globally, diphtheria has been showing a declining trend due to effective childhood vaccination programs. A substantial proportion of global burden of diphtheria is contributed by India. Hospital-based surveillance studies as well as diphtheria outbreaks published in last 20 years (1996-2016) indicate that diphtheria cases are frequent among school-going children and adolescents. In some Indian states, Muslim children are affected more. As per the national level health surveys, coverage of three doses of diphtheria vaccine was 80% during 2015-2016. Information about coverage of diphtheria boosters is not routinely collected through these surveys, but is expected to be low. Few studies also indicate low diphtheria immunity among school-going children and adults. The strategies for prevention of diphtheria need to focus on improving coverage of primary and booster doses of diphtheria vaccines administered as a part of Universal Immunization Program as well as introducing diphtheria vaccine for school-going children.

Diphtheria in the Postepidemic Period, Europe, 2000–2009

Science.gov (United States)

White, Joanne M.; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S.; Neal, Shona; Efstratiou, Androulla

2012-01-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections. PMID:22304732

A case of pharyngeal diphtheria in Germany, June 2015.

Science.gov (United States)

Berger, A; Meinel, D M; Schaffer, A; Ziegler, R; Pitteroff, J; Konrad, R; Sing, Andreas

2016-10-01

In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics. A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection. No secondary cases were found and the patient completely recovered.

A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly

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Kang, Hae Joo; Paterson, Neil G. [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Kim, Chae Un [Cornell University, Ithaca, NY 14853 (United States); Middleditch, Martin [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Chang, Chungyu; Ton-That, Hung [University of Texas–Houston Medical School, Houston, TX 77030 (United States); Baker, Edward N., E-mail: ted.baker@auckland.ac.nz [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand)

2014-05-01

Two crystal structures of the major pilin SpaD from C. diphtheriae have been determined at 1.87 and 2.5 Å resolution. The N-terminal domain is found to contain an isopeptide bond that forms slowly over time in the recombinant protein. Given its structural context, this provides insight into the relationship between internal isopeptide-bond formation and pilus assembly. The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specific sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys–Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys–Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.

Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

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Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

2015-05-01

Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Diphtheria - 'The strangling angel' of children.

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Byard, Roger W

2013-02-01

Diphtheria, an acute infectious condition caused by Corynebacterium diphtheriae, was once a major killer of children. Although the mortality rates dropped dramatically in the mid-twentieth century, due to a combination of improved standards of living and immunization programs, outbreaks are still occurring. Two children, aged four and five years respectively, are reported to demonstrate characteristic features of lethal cases. Death in case 1 was due to an extensive upper airway pseudomembrane causing acute respiratory failure. The diagnosis of diphtheria was only made at postmortem. Death in case 2 was due to acute cardiac failure with heart block complicating diphtheria. Other mechanisms in fatal cases involve disseminated intravascular coagulation, renal and endocrine failure. Declining levels of immunity among adults has resulted in a change in the epidemiological pattern of the disease with an older age of victims in recent outbreaks. As a result of population shifts and failure to immunize children it is likely that forensic pathologists may see more cases of diphtheria in the future. Due to the rarity of cases in Western communities and atypical presentations, the diagnosis may only be established at autopsy. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Identification of a human monoclonal antibody to replace equine diphtheria antitoxin for treatment of diphtheria intoxication.

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Sevigny, Leila M; Booth, Brian J; Rowley, Kirk J; Leav, Brett A; Cheslock, Peter S; Garrity, Kerry A; Sloan, Susan E; Thomas, William; Babcock, Gregory J; Wang, Yang

2013-11-01

Diphtheria antitoxin (DAT) has been the cornerstone of the treatment of Corynebacterium diphtheriae infection for more than 100 years. Although the global incidence of diphtheria has declined steadily over the last quarter of the 20th century, the disease remains endemic in many parts of the world, and significant outbreaks still occur. DAT is an equine polyclonal antibody that is not commercially available in the United States and is in short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we obtained human monoclonal antibodies (hMAbs) directly from antibody-secreting cells in the circulation of immunized human volunteers. We isolated a panel of diverse hMAbs that recognized diphtheria toxoid, as well as a variety of recombinant protein fragments of diphtheria toxin. Forty-five unique hMAbs were tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays with a 50% effective concentration of 0.65 ng/ml for the lead candidate hMAb, 315C4. In addition, 25 μg of 315C4 completely protected guinea pigs from intoxication in an in vivo lethality model, yielding an estimated relative potency of 64 IU/mg. In comparison, 1.6 IU of DAT was necessary for full protection from morbidity and mortality in this model. We further established that our lead candidate hMAb binds to the receptor-binding domain of diphtheria toxin and physically blocks the toxin from binding to the putative receptor, heparin-binding epidermal growth factor-like growth factor. The discovery of a specific and potent human neutralizing antibody against diphtheria toxin holds promise as a potential therapeutic.

Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections

Directory of Open Access Journals (Sweden)

Luciene de Fátima Costa Torres

2013-05-01

Full Text Available Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp, 16S rRNA (C. ulcerans and C. pseudotuberculosis, pld (C. pseudotuberculosis, dtxR (C. diphtheriae and tox [diphtheria toxin (DT ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

Diphtheria outbreak in Maranhão, Brazil: microbiological, clinical and epidemiological aspects.

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Santos, L S; Sant'anna, L O; Ramos, J N; Ladeira, E M; Stavracakis-Peixoto, R; Borges, L L G; Santos, C S; Napoleão, F; Camello, T C F; Pereira, G A; Hirata, R; Vieira, V V; Cosme, L M S S; Sabbadini, P S; Mattos-Guaraldi, A L

2015-03-01

We describe microbiological, clinical and epidemiological aspects of a diphtheria outbreak that occurred in Maranhão, Brazil. The majority of the 27 confirmed cases occurred in partially (n = 16) or completely (n = 10) immunized children (n = 26). Clinical signs and characteristic symptoms of diphtheria such as cervical lymphadenopathy and pseudomembrane formation were absent in 48% and 7% of the cases, respectively. Complications such as paralysis of lower limbs were observed. Three cases resulted in death, two of them in completely immunized children. Microbiological analysis identified the isolates as Corynebacterium diphtheriae biovar intermedius with a predominant PFGE type. Most of them were toxigenic and some showed a decrease in penicillin G susceptibility. In conclusion, diphtheria remains endemic in Brazil. Health professionals need to be aware of the possibility of atypical cases of C. diphtheriae infection, including pharyngitis without pseudomembrane formation.

[Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports].

Science.gov (United States)

Jenssen, Christian; Schwede, Ilona; Neumann, Volker; Pietsch, Cristine; Handrick, Werner

2017-10-01

History and clinical findings  We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis  A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases. Treatment and course  In all three patients, successful handling of the skin and soft tissue infections was possible by combining local treatment with antibiotics. Diphtheria antitoxin was not administered in any case. Conclusion  Based on a review of the recent literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of skin and soft tissue infections due to Corynebacterium ulcerans are discussed. Corynebacterium ulcerans should be considered as a potential cause of severe skin and soft tissue infections. Occupational or domestic animal contacts should be evaluated. © Georg Thieme Verlag KG Stuttgart · New York.

Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii.

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Luong, Truc Thanh; Tirgar, Reyhaneh; Reardon-Robinson, Melissa E; Joachimiak, Andrzej; Osipiuk, Jerzy; Ton-That, Hung

2018-05-01

The actinobacterium Corynebacterium matruchotii has been implicated in nucleation of oral microbial consortia leading to biofilm formation. Due to the lack of genetic tools, little is known about basic cellular processes, including protein secretion and folding, in this organism. We report here a survey of the C. matruchotii genome, which encodes a large number of exported proteins containing paired cysteine residues, and identified an oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA (MdbA Cd ). Crystallization studies uncovered that the 1.2-Å resolution structure of C. matruchotii MdbA (MdbA Cm ) possesses two conserved features found in actinobacterial MdbA enzymes, a thioredoxin-like fold and an extended α-helical domain. By reconstituting the disulfide bond-forming machine in vitro , we demonstrated that MdbA Cm catalyzes disulfide bond formation within the actinobacterial pilin FimA. A new gene deletion method supported that mdbA is essential in C. matruchotii Remarkably, heterologous expression of MdbA Cm in the C. diphtheriae Δ mdbA mutant rescued its known defects in cell growth and morphology, toxin production, and pilus assembly, and this thiol-disulfide oxidoreductase activity required the catalytic motif CXXC. Altogether, the results suggest that MdbA Cm is a major thiol-disulfide oxidoreductase, which likely mediates posttranslocational protein folding in C. matruchotii by a mechanism that is conserved in Actinobacteria IMPORTANCE The actinobacterium Corynebacterium matruchotii has been implicated in the development of oral biofilms or dental plaque; however, little is known about the basic cellular processes in this organism. We report here a high-resolution structure of a C. matruchotii oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA. By biochemical analysis, we demonstrated that C. matruchotii MdbA catalyzes disulfide

Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii.

Science.gov (United States)

Johnstone, Kate J; Robson, Jennifer; Cherian, Sarah G; Wan Sai Cheong, Jenny; Kerr, Kris; Bligh, Judith F

2017-06-01

Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting parous reproductive-aged women. Once considered idiopathic, there is growing evidence of an association with corynebacteria infection, especially in the setting of a distinct histological pattern termed cystic neutrophilic granulomatous mastitis (CNGM). We describe 15 cases with histological features either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent microbiological evidence of Corynebacterium species. The organism was detected by culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine needle aspiration. In seven cases, Gram-positive organisms were seen within vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium kroppenstedtii subsequently identified. These cases provide further evidence in support of this association and in doing so highlight the importance of recognising these histological clues as well as the limitations of Gram stain and microbiological culture in detecting this previously under-recognised disease process. Copyright © 2017 Royal College of Pathologists of Australasia. All rights reserved.

Immunochromatographic Strip Test for Rapid Detection of Diphtheria Toxin: Description and Multicenter Evaluation in Areas of Low and High Prevalence of Diphtheria

Science.gov (United States)

Engler, K. H.; Efstratiou, A.; Norn, D.; Kozlov, R. S.; Selga, I.; Glushkevich, T. G.; Tam, M.; Melnikov, V. G.; Mazurova, I. K.; Kim, V. E.; Tseneva, G. Y.; Titov, L. P.; George, R. C.

2002-01-01

An immunochromatographic strip (ICS) test was developed for the detection of diphtheria toxin by using an equine polyclonal antibody as the capture antibody and colloidal gold-labeled monoclonal antibodies specific for fragment A of the diphtheria toxin molecule as the detection antibody. The ICS test has been fully optimized for the detection of toxin from bacterial cultures; the limit of detection was approximately 0.5 ng of diphtheria toxin per ml within 10 min. In a comparative study with 915 pure clinical isolates of Corynebacterium spp., the results of the ICS test were in complete agreement with those of the conventional Elek test. The ICS test was also evaluated for its ability to detect toxigenicity from clinical specimens (throat swabs) in two field studies conducted within areas of the former USSR where diphtheria is epidemic. Eight hundred fifty throat swabs were examined by conventional culture and by use of directly inoculated broth cultures for the ICS test. The results showed 99% concordance (848 of 850 specimens), and the sensitivity and specificity of the ICS test were 98% (95% confidence interval, 91 to 99%) and 99% (95% confidence interval, 99 to 100%), respectively. PMID:11773096

Diphtheria in a 7-year-old child in north-eastern Nigeria - management in a resource-poor setting.

Science.gov (United States)

Goni, Baba Waru; Gofama, Mustapha M; Lawan, Gana M; Haruna, Yusuph; Bukar, Bakki; Musa, Kida I

2014-01-01

We report a case of a 7-year-old unimmunized child who presented with a 2 week history of nasal quality speech, hoarseness of the voice, regurgitation of feeds, and unstable gait. He had a previous history of fever, severe sore throat and bloody nasal discharge. A throat swab was negative for Corynebacterium diphtheria; however, he had received antibiotics at a primary care clinic prior to presentation. A clinical diagnosis of diphtheria with neurologic complication was made and the child was started on oral erythromycin, nasogastric tube feeding and daily physiotherapy, following which he improved. We did not prescribe diphtheria anti-toxin because of its unavailability.

International External Quality Assurance for Laboratory Diagnosis of Diphtheria ▿

Science.gov (United States)

Neal, S. E.; Efstratiou, A.

2009-01-01

The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Many laboratories reported problems obtaining Elek reagents or media. Only six centers produced acceptable results for all six specimens. Overall, 21% of identification and 13% of toxigenicity reports were unacceptable. Many centers could not isolate the target organism, and most found difficulties with the specimens that contained Corynebacterium striatum as a commensal contaminant. Nineteen centers generated either false-positive or negative toxigenic results, which may have caused inappropriate medical management. The discrepancies in this diphtheria diagnostics EQA alarmingly reflect the urgent need to improve laboratory performance in diphtheria diagnostics in Europe, standardize feasible and robust microbiological methods, and build awareness among public health authorities. Therefore, DIPNET recommends that regular workshops and EQA distributions for diphtheria diagnostics should be supported and maintained. PMID:19828749

Corynebacterium species causing breast abscesses among patients attending a tertiary care hospital in Chennai, South India.

Science.gov (United States)

Poojary, Indira; Kurian, Ann; V A, Jayalekshmi; Devapriya J, Debora; M A, Thirunarayan

2017-07-01

Corynebacterium species other than Corynebacterium diphtheriae were mostly considered contaminants in the past, but there are reports of their association with wide variety of human infections lately. In this study, we look into Corynebacterium species isolated from breast abscess patients and assess their antimicrobial susceptibility pattern and treatment outcomes. Pus samples from suspected breast abscess cases were examined from October 2014 to September 2015. Growth of Gram-positive bacilli morphologically resembling Corynebacterium species were identified by matrix-assisted laser desorption/ionization- time of flight mass spectrometry identifications generated by the Vitek MS system (bioMérieux, France) (MALDI-TOF Vitek MS system) and antimicrobial susceptibility was done. Corynebacterium species were isolated from 10 female breast abscess patients with median age of 36 years (range 25-59 years). Out of the 10 isolates four isolates were identified as C. kroppenstedtii; one isolate as C. striatum and five isolates were identified as C. amycolatum/C.xerosis. Out of four isolates of C .kroppenstedtii, two isolates were resistant to cotrimoxazole and one C. striatum isolate was resistant to penicillin, ampicillin, cotrimoxazole and clindamycin. Of the five isolates identified as C amycolatum/C xerosis, all were sensitive to vancomycin and linezolid but resistant to clindamycin. All the patients were treated with incision, drainage and antibiotics based on the sensitivity pattern; eight were cured and two patients did not come for follow-up. Corynebacterium species should be considered one of the causative agents of breast abscess and a varied susceptibility profile amongst the different species makes susceptibility testing important. Identification by MALDI-TOF Vitek MS system may not differentiate between C. amycolatum and C. xerosis.

Conservación por congelación de Bordetella pertussis y Corynebacterium diphtheriae, empleados en la producción de vacunas para uso humano

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Yilian Plasencia,

2000-11-01

Full Text Available En el presente estudio se evaluó el método de congelación a –70ºC para la preservación de Bordetella pertussis y Corynebacterium diphtheriae. Para verificar el sustento de los cultivos se realizó un adecuado control de calidad, que incluyó comprobación de pureza, viabilidad y estabilidad de las propiedades de interés. En este trabajo se probaron diferentes formulaciones. Se seleccionó la que arrojó los mejores resultados y se realizó un estudio de mantenimiento de las características evaluadas durante el tiempo. Para medir determinados parámetros se realizaron procesos a escala industrial, empleándose para esto un biorreactor Chemap de 35 L. Se tomaron como referencia los valores obtenidos por las cepas conservadas por liofilización. De esta forma se buscaron alternativas y soluciones a problemas presentados en su conservación. Los resultados obtenidos sugieren la posible inclusión en el Programa de Mantenimiento establecido.

Resurgence of diphtheria in rural areas of North Karnataka, India.

Science.gov (United States)

Parande, Mahantesh V; Roy, Subarna; Mantur, B G; Parande, Aisha M; Shinde, Rupali S

2017-01-01

A diphtheria outbreak was identified from Vijayapura (formerly Bijapur) district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP) in North Karnataka since then. A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Throat swabs from 432 suspected cases of diphtheria during 2012-2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB) was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Thirty-eight (8.79%) out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26%) were between 1 and 5 years of age, 14 (36.84%) were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched 'Mission Indradhanush' programme in strengthening Universal Immunisation Programme (UIP).

Toxigenic cutaneous diphtheria in a returned traveller.

Science.gov (United States)

Abdul Rahim, Nur R; Koehler, Ann P; Shaw, Doug D; Graham, Caitlin R

2014-12-31

Diphtheria is rarely reported in Australia. A case of cutaneous diphtheria was reported to the South Australian Department for Health and Ageing in April 2013 in an Australian-born 18-year-old female following travel in India. The case presented with a skin ulcer on her toe. Toxigenic Corynebacterium diphtheriae was isolated from a swab of the lesion. The case was treated with antibiotics. The public health response included infection control advice, assessing the case and household contacts for organism carriage and providing antimicrobial chemoprophylaxis to contacts. Although cutaneous diphtheria is not included as part of the Australian communicable disease surveillance case definition, this may be an oversight as international evidence demonstrates that it is a source of organism transmission and can potentially result in outbreaks among susceptible populations. This formed the rationale for the public health response to this particular case. The protocol for the public health management of diphtheria in South Australia has since been revised to include cutaneous lesions caused by the toxigenic strain of the organism as part of the surveillance case definition. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent

Differential diagnosis diphtheria adults

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Yu. I. Liashenko

2010-01-01

Full Text Available A total of 1,824 human cases of diphtheria, treated at the Clinical Infectious Diseases Hospital SP Botkin (St. Petersburg during 1993, as well as 19 deaths in 1994. It is known that early diagnosis of infectious diseases, especially diphtheria, contributes to the favorable outcome of the disease. The diagnosis of diphtheria at the prehospital stage is always difficult. Presented in detail the differential diagnosis of the disease, clinically similar to diphtheria: Lacunal angina, angina Simanovsky, infectious mononucleosis, angina Ludwig’s angina Dugue, syphilis, non-infectious with clinical «masks» of diphtheria and other. Diphtheria epidemic of 1993–1994 in Russia and, in particular, in St. Petersburg, showed that the late admission of patients with diphtheria infection in hospitals, usually associated with irregular differential diagnosis of this dangerous disease.

SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

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Oliinyk O. S.

2014-02-01

Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

Science.gov (United States)

Smith, Heidi L; Cheslock, Peter; Leney, Mark; Barton, Bruce; Molrine, Deborah C

2016-08-17

Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

Corynebacterium propinquum associated with acute, nongonococcal urethritis.

Science.gov (United States)

Abdolrasouli, Alireza; Roushan, Azita

2013-10-01

Corynebacterium propinquum is usually considered part of the normal human oropharyngeal flora and is rarely responsible for clinical infection. We report here what seems to be the first case of acute purulent urethral discharge in a young Iranian man with urethritis acquired after orogenital contact. Attention should be devoted to less common nondiphtheriae Corynebacterium species for differential diagnosis.

Determinants of Clinical Diphtheria After Sub National Diphtheria Immunization Days In 2012 At Bangkalan

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Feranita Utama

2014-01-01

Full Text Available ABSTRACT The government had held sub-national diphtheria immunization days in 2012 to combat an outbreak of diphtheria in East Java province. However, there werestill regencies or cities which had high incidence and Bangkalanregencywas the highest. The research aimed to analyze the determinants of diphtheria in Bangkalan after SNIDs. This research was case control study with 31 subjects as case and 124 as control spread in 25 case villages and 25 control villages. Bivariate analysis used chi-square and simple logistic regression. Multivariate analysis used logistic regression. Bivariate analysisresult showed that individual and household variables that had associate with incidence of diphtheria in the Bangkalan after SNIDs of diphtheria vaccine in 2012 were DPT immunization status, the status of SNIDs, age, and mother's education level. In this study, there were not associate between village variables with diphtheria in the Bangkalan after SNIDs. Multivariate analysis result showed that had associate with incidence of diphtheria in Bangkalan after SNIDs were no DPT immunization (p=0,012; OR=4,765, incomplete DPT immunization (p=0,001; OR=6,276, 3-7 years of age (p=0,014; OR=15,137, 7-15 years of age (p=0,001;OR=41,984, and no immunization in SNIDs (p=0,020; OR=3,553. Conclusion, the dominantfactors that affected diphtheriainBangkalanwere status of DPTimmunization, ageand the SNIDs of diphtheria. Recommendation, DPTimmunizationshould becomplete, boosterimmunization should be needed, monitoring theimplementation ofsubPIN should be strict, especially inschool, and thecoverage ofDPT3andsubPIN should be increased and its report should be improved. Keywords: diphtheria, sub-nationaldiphtheriaimmunization days, DPT                              immunization

Resurgence of diphtheria in rural areas of North Karnataka, India

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Mahantesh V Parande

2017-01-01

Full Text Available Background: A diphtheria outbreak was identified from Vijayapura (formerly Bijapur district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP in North Karnataka since then. Objectives: A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Materials and Methods: Throat swabs from 432 suspected cases of diphtheria during 2012–2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Results: Thirty-eight (8.79% out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26% were between 1 and 5 years of age, 14 (36.84% were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. Conclusion and Discussion: Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched 'Mission Indradhanush' programme in strengthening Universal Immunisation Programme

A case of respiratory toxigenic diphtheria: contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015.

Science.gov (United States)

Jané, Mireia; Vidal, Maria José; Camps, Neus; Campins, Magda; Martínez, Ana; Balcells, Joan; Martin-Gomez, Maria Teresa; Bassets, Gloria; Herrera-León, Silvia; Foguet, Anton; Maresma, Mar; Follia, Nuria; Uriona, Sonia; Pumarola, Tomàs

2018-03-01

In May 2015, following a 30-year diphtheria-free interval in Catalonia, an unvaccinated 6-year-old child was diagnosed with diphtheria caused by toxigenic Corynebacterium diphtheriae . After a difficult search for equine-derived diphtheria antitoxin (DAT), the child received the DAT 4 days later but died at the end of June. Two hundred and seventeen contacts were identified in relation to the index case, and their vaccination statuses were analysed, updated and completed. Of these, 140 contacts underwent physical examination and throat swabs were taken from them for analysis. Results were positive for toxigenic C. diphtheriae in 10 contacts; nine were asymptomatic vaccinated children who had been in contact with the index case and one was a parent of one of the nine children. Active surveillance of the 217 contacts was initiated by healthcare workers from hospitals and primary healthcare centres, together with public health epidemiological support. Lack of availability of DAT was an issue in our case. Such lack could be circumvented by the implementation of an international fast-track procedure to obtain it in a timely manner. Maintaining primary vaccination coverage for children and increasing booster-dose immunisation against diphtheria in the adult population is of key importance.

Guidelines for the Management of Suspected Microbial Keratitis in ...

African Journals Online (AJOL)

Siegal_D

Suppurative Corneal ulcer occurs following invasion of the cornea by pathogenic bacteria capable of penetrating intact epithelium such as corynebacterium Diphtheriae,. Neisseria Gonorrhoeae and H. influenzae. Non surgical trauma is the commonest factor predisposing the cornea to infection with less virulent organisms ...

Public health action following an outbreak of toxigenic cutaneous diphtheria in an Auckland refugee resettlement centre.

Science.gov (United States)

Reynolds, Gary E; Saunders, Helen; Matson, Angela; O'Kane, Fiona; Roberts, Sally A; Singh, Salvin K; Voss, Lesley M; Kiedrzynski, Tomasz

2016-12-24

Global forced displacement has climbed to unprecedented levels due largely to regional conflict. Degraded public health services leave displaced people vulnerable to multiple environmental and infectious hazards including vaccine preventable disease. While diphtheria is rarely notified in New Zealand, a 2 person outbreak of cutaneous diphtheria occurred in refugees from Afghanistan in February 2015 at the refugee resettlement centre in Auckland. Both cases had uncertain immunisation status. The index case presented with a scalp lesion during routine health screen and toxigenic Corynebacterium diphtheriae was isolated. A secondary case of cutaneous diphtheria and an asymptomatic carrier were identified from skin and throat swabs. The 2 cases and 1 carrier were placed in consented restriction until antibiotic treatment and 2 clearance swabs were available. A total of 164 contacts were identified from within the same hostel accommodation as well as staff working in the refugee centre. All high risk contacts (n=101) were swabbed (throat, nasopharynx and open skin lesions) to assess C. diphtheriae carriage status. Chemoprophylaxis was administered (1 dose of intramuscular benzathine penicillin or 10 days of oral erythromycin) and diphtheria toxoid-containing vaccine offered regardless of immunisation status. Suspected cases were restricted on daily monitoring until swab clearance. A group of 49 low risk contacts were also offered vaccination. Results suggest a significant public health effort was required for a disease rarely seen in New Zealand. In light of increased worldwide forced displacement, similar outbreaks could occur and require a rigorous public health framework for management.

NCBI nr-aa BLAST: CBRC-CREM-01-1346 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-CREM-01-1346 ref|NP_939160.1| Na(+)/H(+) antiporter homolog [Corynebacterium diphtheria...e NCTC 13129] emb|CAE49312.1| Na(+)/H(+) antiporter homolog [Corynebacterium diphtheriae] NP_939160.1 2e-34 34% ...

NCBI nr-aa BLAST: CBRC-AGAM-01-0038 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-AGAM-01-0038 ref|NP_938793.1| Putative cytochrome C biogenesis protein [Corynebacterium diphtheria...e NCTC 13129] emb|CAE48916.1| Putative cytochrome C biogenesis protein [Corynebacterium diphtheriae] NP_938793.1 1.6 24% ...

NCBI nr-aa BLAST: CBRC-PTRO-20-0007 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-PTRO-20-0007 ref|NP_938605.1| immunity-specific protein Beta241 [Corynebacterium diphtheria...e NCTC 13129] emb|CAE48718.1| immunity-specific protein Beta241 [Corynebacterium diphtheriae] NP_938605.1 1e-04 24% ...

In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine.

Science.gov (United States)

Carlin, Gunnar; Viitanen, Eila

2005-05-25

We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid.

Diphtheria Complications

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... Search Form Controls Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

Toxigenic Corynebacterium ulcerans isolated from a free-roaming red fox (Vulpes vulpes).

Science.gov (United States)

Sting, Reinhard; Ketterer-Pintur, Sandra; Contzen, Matthias; Mauder, Norman; Süss-Dombrowski, Christine

2015-01-01

Corynebacterium (C.) ulcerans could be isolated from the spleen of a red fox (Vulpes vulpes) that had been found dead in the state of Baden-Württemberg, Germany. Pathohistological examination suggested that the fox had died of distemper, as was confirmed by PCR. The isolate was identified biochemically, by MALDI-TOF MS, FT-IR and by partial 16S rRNA, rpoB and tox gene sequencing. Using the Elek test the C. ulcerans isolate demonstrated diphtheria toxin production. FT-IR and sequencing data obtained from the C. ulcerans isolate from the red fox showed higher similarity to isolates from humans than to those from wild game.

Diphtheria: It is still prevalent!!!

Science.gov (United States)

Jain, Avani; Samdani, Sunil; Meena, Vinod; Sharma, Man Prakash

2016-07-01

Diphtheria is a respiratory infectious disease of childhood. It is a fatal disease and may cause complications if not recognized early and treated properly. Despite availability of effective vaccination it continues to be reported from many parts of the world particularly developing countries. To assess the demographic and clinical characteristics of diphtheria patients, and the predictors of outcomes of respiratory diphtheria. A prospective analysis of 180 patients with a clinical diagnosis of respiratory diphtheria admitted from 2011 to 2014 at a tertiary referral hospital. They were evaluated with respect to demographic details, immunization status, clinical features, complications and outcomes. Most common age group affected was children less than 5 years of age (87 cases, 48.33%). The peak incidence of diphtheria was seen in the months of September and October (111 cases, 62%). Majority of the patients were unimmunized (54%), followed by partially immunized (21%). The most common complication was respiratory in 80 cases (44%), followed by cardiac complications in 54 cases (30%), and renal (16%) and neurological complications (10%). Cardiac complications were associated with the highest mortality rate (63%). The presence of bull neck and pseudomembrane score >2 was associated with a high mortality. Diphtheria is still a preventable public health problem in many developing countries. Improved vaccination coverage, including booster dosage, coupled with early detection and effective treatment, may all reduce incidence and mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diphtheria

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Diphtheria is a serious bacterial infection. You can catch it from a person who has the infection ... as a toy, that has bacteria on it. Diphtheria usually affects the nose and throat. Symptoms include ...

Diphtheria Disease Villain

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... we can shield ourselves with vaccines, fewer than 5 people get diphtheria each year. Diphtheria is a stubborn ... always foiled by the vaccine against it. Ninety-five percent of people with up-to-date diphtheria vaccine are protected. ...

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia.

Science.gov (United States)

Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

2016-12-01

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. This article is copyright of The Authors, 2016.

Cardiac complications in diphtheria and predictors of outcomes.

Science.gov (United States)

Samdani, Sunil; Jain, Avani; Meena, Vinod; Meena, C B

2018-01-01

To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. Single centre prospective analysis of cardiac complications in diphtheria patients. In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses. Copyright © 2017. Published by Elsevier B.V.

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

Energy Technology Data Exchange (ETDEWEB)

D' Aquino,J.; Tetenbaum-Novatt, J.; White, A.; Berkovitch, F.; Ringe, D.

2005-01-01

The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10{sup -7}, binding site 2 (primary) is a low-affinity binding site with a binding constant of 6.3 x 10{sup -4}. These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A, C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.

Diphtheria Diagnosis and Treatment

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... Search The CDC Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

Tetanus, Diphtheria (Td) Vaccine

Science.gov (United States)

Decavac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They ... United States today, but people who do become infected often have severe ...

Influence of a reducing agent used to prepare radiopharmaceuticals labeled with technetium-99m on the adhesive properties of Corynebacterium diphtheriae strains

International Nuclear Information System (INIS)

Souza, S.M.; Bernardo-Filho, M.; Hirata, R. Jr.; Moreira, L.O.; Mattos-Guaraldi, A.L.

2002-01-01

Aim: In this work we investigated the influence of stannous chloride (SnCl 2 ) used in nuclear medicine as a reducing agent to prepare radiopharmaceuticals labeled with technetium-99m, on the survival and adhesive properties of two toxigenic C. diphtheriae of the sucrose fermenting (241strain) and non fermenting (CDC-E8392 strain) biotypes. Materials and Methods: Bacterial strains were submitted to survival and filamentation induction assays using different concentrations of SnCl 2 . The influence of SnCl 2 on the adhesive properties of C.diphtheriae were evaluated by bacterial autoaggregation, haemagglutination, adherence to glass surface and lectin-binding assays. Results: Differences in survival fractions suggested differences in susceptibility of microorganisms to bactericidal effect of stannous chloride. A percentage of 0.4% bacterial cells of no.241 strain and 0.04% of CDC-E8392 strain survived after 220 μl ml -1 SnCl 2 treatment. Results of both polystyrene and spontaneous autoaggregation tests showed an increase in the hydrophobic surface properties of C. diphtheriae strains. SnCl 2 induced spontaneous bacterial autoaggregation of sucrose fermenting 241 strain. SnCl 2 enhanced adherence to glass and totally inhibited the haemagglutinating activity of the non-sucrose fermenting strain CDC-E8392 strain (original titer=32). Decrease in haemagglutinatination was dependent on the concentration of SnCl 2 used. Lectin-binding assays demonstrated increase in the expression of cell surface receptors to lectin with affinity for molecules containing mannose residues after treatment with SnCl 2 . The presence of SnCl 2 induced differences in the expression of bacterial surface carbohydrates possibly related with differences in degrees of haemagglutination and adherence to glass of diphtheria bacilli. Conclusion: The presence of SnCl 2 may influence on the adhesive properties of bacterial pathogens. The occurrence of cell filamentation suggests a potential genotoxicity

Travelers' Health: Diphtheria

Science.gov (United States)

... membrane tissue. Diphtheria is a nationally notifiable disease. TREATMENT Patients with respiratory diphtheria require hospitalization to monitor ... Jan 20;81(3):24–32. Chapter 3 - Dengue Chapter 3 - Ebola Virus Disease & Marburg Virus Disease ...

Resurgence of Diphtheria in North Kerala, India, 2016: Laboratory Supported Case-Based Surveillance Outcomes

Directory of Open Access Journals (Sweden)

Lucky Sangal

2017-08-01

Full Text Available IntroductionAs part of national program, laboratory supported vaccine preventable diseases surveillance was initiated in Kerala in 2015. Mechanisms have been strengthened for case investigation, reporting, and data management. Specimens collected and sent to state and reference laboratories for confirmation and molecular surveillance. The major objective of this study is to understand the epidemiological information generated through surveillance system and its utilization for action.MethodsSurveillance data captured from reporting register, case investigation forms, and laboratory reports was analyzed. Cases were allotted unique ID and no personal identifying information was used for analysis. Throat swabs were collected from investigated cases as part of surveillance system. All Corynebacterium diphtheriae isolates were confirmed with standard biochemical tests, ELEK’s test, and real-time PCR. Isolates were characterized using whole genome-based multi locus sequence typing method. Case investigation forms and laboratory results were recorded electronically. Public health response by government was also reviewed.ResultsA total of 533 cases were identified in 11 districts of Kerala in 2016, of which 92% occurred in 3 districts of north Kerala; Malappuram, Kozhikode, and Kannur. Almost 79% cases occurred in >10 years age group. In <18 years age group, 62% were male while in ≥18 years, 69% were females. In <10 years age group, 31% children had received three doses of diphtheria vaccine, whereas in ≥10 years, 3% cases had received all doses. Fifteen toxigenic C. diphtheriae isolates represented 6 novel sequence types (STs (ST-405, ST-408, ST-466, ST-468, ST-469, and ST-470. Other STs observed are ST-50, ST-295, and ST-377.ConclusionDiphtheria being an emerging pathogen, establishing quality surveillance for providing real-time information on disease occurrence and mortality is imperative. The epidemiological data thus generated was

Sequence of ligand binding and structure change in the diphtheria toxin repressor upon activation by divalent transition metals.

Science.gov (United States)

Rangachari, Vijayaraghavan; Marin, Vedrana; Bienkiewicz, Ewa A; Semavina, Maria; Guerrero, Luis; Love, John F; Murphy, John R; Logan, Timothy M

2005-04-19

The diphtheria toxin repressor (DtxR) is an Fe(II)-activated transcriptional regulator of iron homeostatic and virulence genes in Corynebacterium diphtheriae. DtxR is a two-domain protein that contains two structurally and functionally distinct metal binding sites. Here, we investigate the molecular steps associated with activation by Ni(II)Cl(2) and Cd(II)Cl(2). Equilibrium binding energetics for Ni(II) were obtained from isothermal titration calorimetry, indicating apparent metal dissociation constants of 0.2 and 1.7 microM for two independent sites. The binding isotherms for Ni(II) and Cd(II) exhibited a characteristic exothermic-endothermic pattern that was used to infer the metal binding sequence by comparing the wild-type isotherm with those of several binding site mutants. These data were complemented by measuring the distance between specific backbone amide nitrogens and the first equivalent of metal through heteronuclear NMR relaxation measurements. Previous studies indicated that metal binding affects a disordered to ordered transition in the metal binding domain. The coupling between metal binding and structure change was investigated using near-UV circular dichroism spectroscopy. Together, the data show that the first equivalent of metal is bound by the primary metal binding site. This binding orients the DNA binding helices and begins to fold the N-terminal domain. Subsequent binding at the ancillary site completes the folding of this domain and formation of the dimer interface. This model is used to explain the behavior of several mutants.

Solution 1H NMR investigation of the active site molecular and electronic structures of substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from Corynebacterium diphtheriae.

Science.gov (United States)

Li, Yiming; Syvitski, Ray T; Chu, Grace C; Ikeda-Saito, Masao; Mar, Gerd N La

2003-02-28

The molecular structure and dynamic properties of the active site environment of HmuO, a heme oxygenase (HO) from the pathogenic bacterium Corynebacterium diphtheriae, have been investigated by (1)H NMR spectroscopy using the human HO (hHO) complex as a homology model. It is demonstrated that not only the spatial contacts among residues and between residues and heme, but the magnetic axes that can be related to the direction and magnitude of the steric tilt of the FeCN unit are strongly conserved in the two HO complexes. The results indicate that very similar contributions of steric blockage of several meso positions and steric tilt of the attacking ligand are operative. A distal H-bond network that involves numerous very strong H-bonds and immobilized water molecules is identified in HmuO that is analogous to that previously identified in hHO (Li, Y., Syvitski, R. T., Auclair, K., Wilks, A., Ortiz de Montellano, P. R., and La Mar, G. N. (2002) J. Biol. Chem. 277, 33018-33031). The NMR results are completely consistent with the very recent crystal structure of the HmuO.substrate complex. The H-bond network/ordered water molecules are proposed to orient the distal water molecule near the catalytically key Asp(136) (Asp(140) in hHO) that stabilizes the hydroperoxy intermediate. The dynamic stability of this H-bond network in HmuO is significantly greater than in hHO and may account for the slower catalytic rate in bacterial HO compared with mammalian HO.

Corynebacterium pilbarense sp. nov., a non-lipophilic corynebacterium isolated from a human ankle aspirate.

Science.gov (United States)

Aravena-Roman, M; Spröer, C; Sträubler, B; Inglis, T; Yassin, A F

2010-07-01

A non-lipophilic coryneform bacterium isolated from an anaerobic Bactec bottle inoculated with an ankle aspirate from a male patient was characterized by phenotypic and molecular taxonomic methods. Chemotaxonomic investigations revealed the presence of short-chain mycolic acids in the cell wall of the bacterium, a feature consistent with members of the genus Corynebacterium. Comparative 16S rRNA gene sequence analysis demonstrated that the isolate displayed 92.0-99.0 % gene sequence similarity with members of the genus Corynebacterium, with Corynebacterium ureicelerivorans as the most closely related phylogenetic species (99.0 % gene sequence similarity). However, the isolate could be genomically separated from C. ureicelerivorans on the basis of DNA-DNA hybridization studies (39.5 % relatedness). Furthermore, the isolate could also be differentiated from C. ureicelerivorans and other species of the genus Corynebacterium on the basis of biochemical properties. Based on both phenotypic and phylogenetic evidence, it is proposed that this isolate be classified as representing a novel species, Corynebacterium pilbarense sp. nov. (type strain IMMIB WACC 658(T)=DSM 45350(T)=CCUG 57942(T)).

Baseline immunity to diphtheria and immunologic response after booster vaccination with reduced diphtheria and tetanus toxoid vaccine in Thai health care workers.

Science.gov (United States)

Wiboonchutikul, Surasak; Manosuthi, Weerawat; Sangsajja, Chariya; Thientong, Varaporn; Likanonsakul, Sirirat; Srisopha, Somkid; Termvises, Patamavadee; Rujitip, Jitlada; Loiusirirotchanakul, Suda; Puthavathana, Pilaipan

2014-07-01

A prospective study to evaluate immune status against diphtheria and immunologic response after tetanus-diphtheria (Td) booster vaccination was conducted in 250 Thai health care workers (HCWs). A protective antibody was found in 89.2% of the HCWs (95% confidence interval [CI], 83.3%-91.5%) before receipt of the Td booster vaccination, compared with 97.2% (95% CI, 95.1%-99.3%) after receipt of the first dose of booster (P diphtheria increased from 0.39 IU/mL (95% CI, 0.35-0.44 IU/mL) before the Td booster vaccination to 1.20 IU/mL (95% CI, 1.12-1.29 IU/mL) after the vaccination (P diphtheria, which still circulates in Thailand. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

A Case-control Study of Diphtheria in the High Incidence City of Hyderabad, India.

Science.gov (United States)

Allam, Ramesh Reddy; Uthappa, Chengappa Kechamada; Duerst, Rebecca; Sorley, Evan; Udaragudi, Prasada Rao; Kampa, Shankar; Dworkin, Mark S

2016-03-01

India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. We performed a 1:1 case-control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls : There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58-8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18-13.45) remained significantly associated with diphtheria on multivariate analysis. To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered.

Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

Science.gov (United States)

Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

Radioimmunodiffusion technique for determining diphtheria antitoxin

International Nuclear Information System (INIS)

Maniar, A.C.

1977-01-01

A radioimmunodiffusion technique for detecting low levels of diphtheria antitoxin was developed. Diphtheria toxoid was labelled with 125 I to facilitate detection of lines of precipitation by the use of X-ray film, the lower limit of detection being 0.001 unit per millilitre of diphtheria antitoxin. (author)

Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

Science.gov (United States)

Nanthavong, Naphavanh; Black, Antony P; Nouanthong, Phonethipsavanh; Souvannaso, Chanthasone; Vilivong, Keooudomphone; Muller, Claude P; Goossens, Sylvie; Quet, Fabrice; Buisson, Yves

2015-01-01

During late 2012 and early 2013 several outbreaks of diphtheria were notified in the North of the Lao People's Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12-59 months. Serum samples, socio-demographic data, nutritional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4-28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74-85, 4], p = 0.01) and the lack of advice on vaccination given at birth (OR: 9.8 [95% CI: 1.5-63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008-0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical deficiencies in the methods of storage and distribution of vaccines as well as unreliability of vaccination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against

Two cases of cutaneous diphtheria associated with occupational pig contact in Germany.

Science.gov (United States)

Berger, A; Boschert, V; Konrad, R; Schmidt-Wieland, T; Hörmansdorfer, S; Eddicks, M; Sing, A

2013-12-01

In 2010, two independent cases of cutaneous diphtheria caused by toxigenic C. ulcerans were identified in Germany. Both patients had intense occupational contact with pigs. Diagnostic work-up comprising biochemical differentiation, rpoB sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis, real-time tox PCR and Elek test as well as public health measures including an intensified source tracing involving 83 asymptomatic pigs of an associated pig farm are presented. © 2012 Blackwell Verlag GmbH.

Diphtheria outbreak in Thailand, 2012; seroprevalence of diphtheria antibodies among Thai adults and its implications for immunization programs.

Science.gov (United States)

Wanlapakorn, Nasamon; Yoocharoen, Pornsak; Tharmaphornpilas, Piyanit; Theamboonlers, Apiradee; Poovorawan, Yong

2014-09-01

An age distribution shift in diphtheria cases during a 2012 outbreak in northeastern of Thailand suggests adults are increasingly at risk for infection in Thailand. Data regarding immunity against diphtheria among the adult Thai population is limited. We review a 2012 diphtheria outbreak in Thailand and conducted a nationwide seroepidemiological survey to determine the prevalence of diphtheria antibodies among Thai adults in order to inform immunization programs. A total of 41 confirmed cases, 6 probable cases and 101 carriers of diphtheria were reported from northeastern and upper southern Thailand. The diphtheria outbreak in northeastern Thailand occurred among adults aged > or =15 years; sporadic cases occurred among children from upper southern Thailand. We conducted a seroepidemiological survey of 890 Thai adults from 4 age groups (20-29, 30-39, 40-49 and 50-59 years) in 7 different geographical areas of Thailand (Chiang Mai, Ratchaburi, Chon Buri, Nakhon Si Thammarat, Phitsanulok, Khon Kaen and Songkhla). Diptheria toxin antibody levels were measured with a commercially available ELISA test. The seroprotection rate ranged from 83% to 99%, with the highest in eastern Thailand (Chon Buri, 99%) and the lowest in northern Thailand (Chiang Mai, 83%). Diphtheria antibodies declined with increasing age. We recommend one doseof diphtheria-tetanus toxoid (dT) vaccine once after 20 years of age in order to boost the antibody and revaccinations every 10 years to prevent future outbreaks.

Insight of Genus Corynebacterium: Ascertaining the Role of Pathogenic and Non-pathogenic Species.

Science.gov (United States)

Oliveira, Alberto; Oliveira, Leticia C; Aburjaile, Flavia; Benevides, Leandro; Tiwari, Sandeep; Jamal, Syed B; Silva, Arthur; Figueiredo, Henrique C P; Ghosh, Preetam; Portela, Ricardo W; De Carvalho Azevedo, Vasco A; Wattam, Alice R

2017-01-01

This review gathers recent information about genomic and transcriptomic studies in the Corynebacterium genus, exploring, for example, prediction of pathogenicity islands and stress response in different pathogenic and non-pathogenic species. In addition, is described several phylogeny studies to Corynebacterium , exploring since the identification of species until biological speciation in one species belonging to the genus Corynebacterium . Important concepts associated with virulence highlighting the role of Pld protein and Tox gene. The adhesion, characteristic of virulence factor, was described using the sortase mechanism that is associated to anchorage to the cell wall. In addition, survival inside the host cell and some diseases, were too addressed for pathogenic corynebacteria, while important biochemical pathways and biotechnological applications retain the focus of this review for non-pathogenic corynebacteria. Concluding, this review broadly explores characteristics in genus Corynebacterium showing to have strong relevance inside the medical, veterinary, and biotechnology field.

Neurologic manifestations of diphtheria and pertussis.

Science.gov (United States)

Sanghi, Viraj

2014-01-01

Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality?

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Fisker, Ane B

2016-01-01

BACKGROUND: Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review...

Diphtheria in the Dominican Republic: reduction of cases following a large outbreak.

Science.gov (United States)

Garib, Zacarías; Danovaro-Holliday, M Carolina; Tavarez, Yira; Leal, Irene; Pedreira, Cristina

2015-10-01

To describe the most recent outbreak of diphtheria in the Dominican Republic and the disease's occurrence and vaccination coverage in 2004-2013. Clinical data of diphtheria cases that occurred in 2004 and that met the study's case definition were reviewed along with socioeconomic and epidemiological information from the cases' families. Univariate and multivariate analyses were performed to assess risk factors for fatal diphtheria. Routine surveillance and vaccination coverage data are presented. From January 2004-April 2005, a total of 145 diphtheria cases were reported; 80 (66%) of the 122 cases reported in 2004 met the case definition; 26 were fatal (case-fatality rate: 32.5%). Incidence was highest in the group 1-4 years of age at 5.3 per 100 000; 62.5% were male. Of the 80 cases, 61 (76%) where hospitalized in Hospital A, 17 in Hospital B, and 2 in two other hospitals. Earlier onset (first half of 2004), birth order, and tracheotomy were associated with fatal diphtheria (P diphtheria incidence was 4.91 cases/1 million people in 2000-2003, climbed to 8.8 cases per million in 2004-2005, and dropped to 0.38 in 2006-2014; no diphtheria cases have been reported since 2011. DTP3 vaccination coverage ranged from 72%-81% in 2000-2004 and from 81%-89% in 2005-2013. The 2004-2005 diphtheria outbreak in the Dominican Republic resulted in important and avoidable morbidity and mortality. Annual cases declined and no cases have been reported in recent years. Maintaining high vaccination coverage and diligent surveillance are crucial to preventing diphtheria outbreaks and controlling the disease.

Corynebacterium species isolated from patients with mastitis.

Science.gov (United States)

Paviour, Sue; Musaad, Sahar; Roberts, Sally; Taylor, Graeme; Taylor, Susan; Shore, Keith; Lang, Selwyn; Holland, David

2002-12-01

Corynebacteria were isolated from breast tissue, pus, or deep wound swabs of 24 women; the most common species isolated was the newly described Corynebacterium kroppenstedtii, followed by Corynebacterium amycolatum and Corynebacterium tuberculostearicum. Gram-positive bacilli were seen in samples sent for culture or in histological specimens for 12 women, and 9 of the 12 women from whom adequate histological specimens were obtained had conditions that met the criteria for granulomatous lobular mastitis, a chronic inflammatory disease of unknown etiology.

Diphtheria in the Dominican Republic: reduction of cases following a large outbreak

Directory of Open Access Journals (Sweden)

Zacarías Garib

Full Text Available OBJECTIVE: To describe the most recent outbreak of diphtheria in the Dominican Republic and the disease's occurrence and vaccination coverage in 2004-2013. METHODS: Clinical data of diphtheria cases that occurred in 2004 and that met the study's case definition were reviewed along with socioeconomic and epidemiological information from the cases' families. Univariate and multivariate analyses were performed to assess risk factors for fatal diphtheria. Routine surveillance and vaccination coverage data are presented. RESULTS: From January 2004-April 2005, a total of 145 diphtheria cases were reported; 80 (66% of the 122 cases reported in 2004 met the case definition; 26 were fatal (case-fatality rate: 32.5%. Incidence was highest in the group 1-4 years of age at 5.3 per 100 000; 62.5% were male. Of the 80 cases, 61 (76% where hospitalized in Hospital A, 17 in Hospital B, and 2 in two other hospitals. Earlier onset (first half of 2004, birth order, and tracheotomy were associated with fatal diphtheria (P < 0.05; cases in Hospital A were also more likely to be fatal (P = 0.066. The average annual diphtheria incidence was 4.91 cases/1 million people in 2000-2003, climbed to 8.8 cases per million in 2004-2005, and dropped to 0.38 in 2006-2014; no diphtheria cases have been reported since 2011. DTP3 vaccination coverage ranged from 72%-81% in 2000-2004 and from 81%-89% in 2005-2013. CONCLUSIONS: The 2004-2005 diphtheria outbreak in the Dominican Republic resulted in important and avoidable morbidity and mortality. Annual cases declined and no cases have been reported in recent years. Maintaining high vaccination coverage and diligent surveillance are crucial to preventing diphtheria outbreaks and controlling the disease.

Stealth and mimicry by deadly bacterial toxins

DEFF Research Database (Denmark)

Yates, S.P.; Jørgensen, Rene; Andersen, Gregers Rom

2006-01-01

Diphtheria toxin and exotoxin A are well-characterized members of the ADP-ribosyltransferase toxin family that serve as virulence factors in the pathogenic bacteria, Corynebacterium diphtheriae and Pseudomonas aeruginosa.  New high-resolution structural data of the Michaelis complex...

STUDY OF CARDIAC INVOLVEMENT IN DIPHTHERIA

Directory of Open Access Journals (Sweden)

Bala Raju Gundam

2016-07-01

Full Text Available BACKGROUND Diphtheria still endemic in many developing countries and is responsible for high case fatality. Myocardial involvement is a serious complication of diphtheria and diphtheria myocarditis frequently complicated by arrhythmias causes sudden death if not managed properly. So, early and adequate administration of Anti-Diphtheritic Serum (ADS and frequent monitoring particularly 24 hrs. ECG monitoring is helpful to detect any serious cardiac arrhythmias. METHODS A prospective study on patients who were culture positive diagnosed on the basis of WHO definition were treated and analysed in respect to homographic details, immunisation strategy, and clinical features with particular attention to myocarditis. RESULTS In the study, common age group affected by diphtheria was 5 to 10 years. Incidence of myocarditis more in same age group. Out of 64 patients with myocarditis, 23 patients died. CONCLUSION Incidence of diphtheria has increased in the recent years. Commonly effected age group is 5 to 10 years and most of them are presented with asymptomatic myocarditis. Symptomatic diphtheritic myocarditis has high mortality rate even with aggressive management. Patient who presented with either LBBB alone are with combination of other conduction of abnormalities has high mortality rate.

Mathematical modeling of diphtheria transmission in Thailand.

Science.gov (United States)

Sornbundit, Kan; Triampo, Wannapong; Modchang, Charin

2017-08-01

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diphtheria outbreak with high mortality in northeastern Nigeria.

Science.gov (United States)

Besa, N C; Coldiron, M E; Bakri, A; Raji, A; Nsuami, M J; Rousseau, C; Hurtado, N; Porten, K

2014-04-01

SUMMARY A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64.3%) of whom were children aged diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

Science.gov (United States)

Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

Science.gov (United States)

Haywood, Matthew James; Vijendren, Ananth; Acharya, Vikas; Mulla, Rohinton; Panesar, Miss Jaan

2017-03-06

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans , with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery. 2017 BMJ Publishing Group Ltd.

Features of Diphtheria in Children

Directory of Open Access Journals (Sweden)

O.K. Koloskova

2014-09-01

Full Text Available The lecture describes the etiology, epidemiology, classification and clinical features of diphtheria in children, taking into account various sites, covers the issues of diagnosis. Treatment for diphtheria in children is carried as per the order of Ministry of Healthcare of Ukraine № 354 dated July 9, 2004 in accordance with the form and severity of the disease.

The changing epidemiology of diphtheria in Jordan*

OpenAIRE

Khuri-Bulos, N.; Hamzah, Y.; Sammerrai, S. M.; Shehabi, A.; Hamed, R.; Arnaout, M. A.; Turk, J.; Qubain, H.

1988-01-01

Outbreaks of diphtheria used to occur regularly in Jordan, the last such outbreak being in 1977-78. Since that time, a massive immunization programme targeted at pre-school-age children has been markedly successful. Hence, when an outbreak of diphtheria occurred in 1982-83, it was unexpected. Of the 35 patients who were treated at the Jordan University Hospital, two died and the remaining 33 recovered uneventfully. Contrary to our findings in previous diphtheria epidemics in Jordan, this outb...

[First confirmed case of laryngeal diphtheria in Djibouti].

Science.gov (United States)

Koeck, J L; Merle, C; Bimet, F; Kiredjian, M; Goullin, B; Teyssou, R

2000-01-01

The first bacteriologically confirmed case of laryngeal diphtheria in Djibouti was reported in 1998. It involved a three-year-old native-born infant who had been vaccinated during the first year of life with three doses of a combined vaccine against diphtheria, tetanus, poliomyelitis, and pertussis. A rapid clinical improvement was observed under erythromycin treatment. Other cases of laryngeal diphtheria have been observed. It is important to reverse decreasing vaccinal coverage in Djibouti and to warn incoming travelers of the need to be adequate immunized against diphtheria. Enhanced epidemiologic surveillance of this disease is also needed.

Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations

NARCIS (Netherlands)

Bissumbhar, B.; Rakhmanova, A.G.; Berbers, G.; Iakolev, A.; Nosikova, E.; Melnick, O.; Ovtcharenko, E.; Rümke, H. C.; Ruitenberg, E.J.

2004-01-01

Aims: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer ≥3.0 IU/ml was used. In addition,

Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus

DEFF Research Database (Denmark)

Aaby, Peter; Jensen, Henrik; Samb, Badara

2003-01-01

Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...

The changing epidemiology of diphtheria in Jordan*

Science.gov (United States)

Khuri-Bulos, N.; Hamzah, Y.; Sammerrai, S. M.; Shehabi, A.; Hamed, R.; Arnaout, M. A.; Turk, J.; Qubain, H.

1988-01-01

Outbreaks of diphtheria used to occur regularly in Jordan, the last such outbreak being in 1977-78. Since that time, a massive immunization programme targeted at pre-school-age children has been markedly successful. Hence, when an outbreak of diphtheria occurred in 1982-83, it was unexpected. Of the 35 patients who were treated at the Jordan University Hospital, two died and the remaining 33 recovered uneventfully. Contrary to our findings in previous diphtheria epidemics in Jordan, this outbreak largely involved adolescents and young adults. PMID:3260143

Postbooster Antibodies from Humans as Source of Diphtheria Antitoxin.

Science.gov (United States)

Bermejo-Martin, Jesús F; Avila-Alonso, Ana; González-Rivera, Milagros; Tamayo, Eduardo; Eiros, Jose María; Almansa, Raquel

2016-07-01

Diphtheria antitoxin for therapeutic use is in limited supply. A potential source might be affinity-purified antibodies originally derived from plasma of adults who received a booster dose of a vaccine containing diphtheria toxoid. These antibodies might be useful for treating even severe cases of diphtheria.

Difteria pelo Corynebacterium ulcerans: uma zoonose emergente no Brasil e no mundo

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Alexandre Alves de Souza de Oliveira Dias

2011-12-01

Full Text Available O artigo revisa a literatura sobre a emergência de infecções humanas causadas por Corynebacterium ulcerans em diversos países, incluindo o Brasil. Foi realizada análise de artigos publicados entre 1926 e 2011 nas bases Medline/PubMed e SciELO, bem como artigos e informes do Ministério da Saúde. Apresenta-se um esquema de triagem, rápido, econômico e de fácil execução, capaz de permitir a realização do diagnóstico presuntivo de C. ulcerans e C. diphtheriae na maioria dos laboratórios brasileiros públicos e privados. A circulação de C. ulcerans em vários países, aliada aos recentes casos de isolamento do patógeno no Rio de Janeiro, é um alerta a clínicos, veterinários e microbiologistas sobre a ocorrência de difteria zoonótica e a circulação do C. ulcerans em regiões urbanas e rurais do território nacional e/ou da América Latina.

Sudden death of a child due to respiratory diphtheria.

Science.gov (United States)

Swain, Rajanikanta; Behera, Chittaranjan; Arava, Sudheer Kumar; Kundu, Naveen

2016-06-01

A four-year-old girl presented to the emergency department with respiratory distress. Death occurred despite attempted resuscitation. The illness was not clinically diagnosed. Her father revealed that she had a fever and sore throat for the last four days and was not immunised for diphtheria. Characteristic gross and microscopic pathology of respiratory diphtheria and microbiological findings were observed. The cause of death was acute respiratory failure consequent upon upper airway obstruction from diphtheria. Forensic pathologists should remember that the diphtheria cases can cause sudden death especially in developing countries. © The Author(s) 2016.

Corynebacterium tapiri sp. nov. and Corynebacterium nasicanis sp. nov., isolated from a tapir and a dog, respectively.

Science.gov (United States)

Baumgardt, Sandra; Loncaric, Igor; Kämpfer, Peter; Busse, Hans-Jürgen

2015-11-01

Two Gram-stain-positive bacterial isolates, strain 2385/12T and strain 2673/12T were isolated from a tapir and a dog's nose, respectively. The two strains were rod to coccoid-shaped, catalase-positive and oxidase-negative. The highest 16S rRNA gene sequence similarity identified Corynebacterium singulare CCUG 37330T (96.3% similarity) as the nearest relative of strain 2385/12T and suggested the isolate represented a novel species. Corynebacterium humireducens DSM 45392T (98.7% 16S rRNA gene sequence similarity) was identified as the nearest relative of strain 2673/12T. Results from DNA-DNA hybridization with the type strain of C. humireducens demonstrated that strain 2673/12T also represented a novel species. Strain 2385/12T showed a quinone system consisting predominantly of menaquinones MK-8(H2) and MK-9(H2) whereas strain 2673/12T contained only MK-8(H2) as predominant quinone. The polar lipid profiles of the two strains showed the major compounds phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid. Phosphatidylinositol was identified as another major lipid in 2673/12T whereas it was only found in moderate amounts in strain 2385/12T. Furthermore, moderate to minor amounts of phosphatidylinositol-mannoside, β-gentiobiosyl diacylglycerol and variable counts of several unidentified lipids were detected in the two strains. Both strains contained corynemycolic acids. The polyamine patterns were characterized by the major compound putrescine in strain 2385/12T and spermidine in strain 2673/12T. In the fatty acid profiles, predominantly C18:1ω9c and C16:0 were detected. The two strains are distinguishable from each other and the nearest related established species of the genus Corynebacterium phylogenetically and phenotypically. In conclusion, two novel species of the genus Corynebacterium are proposed, namely Corynebacterium tapiri sp. nov. (type strain, 2385/12T = CCUG 65456T = LMG 28165T) and Corynebacterium nasicanis sp. nov. (type

ORF Alignment: NC_002935 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available ... [Corynebacterium diphtheriae] ... Length = 91 ... Query: 15 ... ILTPAQERVAQAIARLGPEISLTDISRMVGGH...PNASRQHIKTLENSGYISATQKRGAAGR 74 ... ILTPAQERVAQAIARLGPEISLTDISRMVGGHPNASRQ...HIKTLENSGYISATQKRGAAGR Sbjct: 1 ... ILTPAQERVAQAIARLGPEISLTDISRMVGGHPNASRQHIKTLENSGYISATQKRGAAGR 60 ...

Quantitative estimation of diphtheria and tetanus toxoids. 4. Toxoids as international reference materials defining Lf-units for diphtheria and tetanus toxoids.

Science.gov (United States)

Lyng, J

1990-01-01

The Lf-unit, which is used in the control of diphtheria and tetanus toxoid production and in some countries also to follow immunization of horses for production of antitoxins, has hitherto been defined by means of antitoxin preparations. A diphtheria toxoid and a tetanus toxoid preparation, both freeze-dried, were examined in an international collaborative study for their suitability to serve as reference reagents in the flocculation tests and for defining the Lf-units. It was shown that flocculation tests using the reference toxoids are very reproducible and reliable and the WHO Expert Committee on Biological Standardization established: the toxoid called DIFT as the International Reference Reagent of Diphtheria Toxoid for Flocculation Test with a defined content of 900 Lf-units of diphtheria toxoid per ampoule; and the toxoid called TEFT as the International Reference Reagent of Tetanus Toxoid for Flocculation Test with a defined content of 1000 Lf-units of diphtheria toxoid per ampoule.

Diphtheria outbreak in Lao People's Democratic Republic, 2012-2013.

Science.gov (United States)

Sein, Carolyn; Tiwari, Tejpratap; Macneil, Adam; Wannemuehler, Kathleen; Soulaphy, Chanthavy; Souliphone, Phouthone; Reyburn, Rita; Ramirez Gonzalez, Alejandro; Watkins, Margaret; Goodson, James L

2016-08-05

Diphtheria is a vaccine-preventable disease. When vaccination coverage and population immunity are low, outbreaks can occur. We investigated a diphtheria outbreak in Lao People's Democratic Republic that occurred during 2012-2013 and highlighted challenges in immunization services delivery to children in the country. We reviewed diphtheria surveillance data from April 1, 2012-May 31, 2013. A diphtheria case was defined as a respiratory illness consisting of pharyngitis, tonsillitis, or laryngitis, and an adherent tonsillar or nasopharyngeal pseudomembrane. To identify potential risk factors for diphtheria, we conducted a retrospective case-control study with two aged-matched neighborhood controls per case-patient in Houaphan Province, using bivariate analysis to calculate matched odds ratio (mOR) with 95% confidence intervals (CI). Reasons for non-vaccination among unvaccinated persons were assessed. Sixty-two clinical cases of diphtheria and 12 diphtheria-related deaths were reported in seven of 17 provinces. Among case-patients, 43 (69%) were diphtheria case-patients from Houaphan province and 79 matched-controls were enrolled. Five (12%) case-patients and 20 (25%) controls had received DTP3 (mOR=0.4, CI=0.1-1.7). No diphtheria toxoid-containing vaccine was received by 20 (48%) case-patients and 38 (46%) controls. Among case-patients and controls with no DTP dose, 43% of case-patients and 40% of controls lacked access to routine immunization services. Suboptimal DTP3 coverage likely caused the outbreak. To prevent continued outbreaks, access to routine immunization services should be strengthened, outreach visits need to be increased, and missed opportunities need to be minimized. In the short term, to rapidly increase population immunity, three rounds of DTP immunization campaign should be completed, targeting children aged 0-14years in affected provinces. Copyright © 2016 Elsevier Ltd. All rights reserved.

METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

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Isayenko Ye. Yu

2016-12-01

Full Text Available Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount

ORF Alignment: NC_002935 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available in ... [Corynebacterium diphtheriae] ... Length = 134 ... Query: 4 ... RQVEYKGVHFFPPEDDACLVFSWSERRR...ILPIWVDVEEGIRLSERSEHGAPRRPLAHDVL 63 ... RQVEYKGVHFFPPEDDACLVFSWSERRRILPIWV...DVEEGIRLSERSEHGAPRRPLAHDVL Sbjct: 1 ... RQVEYKGVHFFPPEDDACLVFSWSERRRILPIWVDVEEGIRLSERSEHGAPRRPLAHDVL 60 ... Query

ORF Alignment: NC_002935 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available tein ... [Corynebacterium diphtheriae] ... Length = 153 ... Query: 139 PAIPDDGPEIIVMTHPLDNVSEIDDV...HAEFLDQPDDDWLELYHFRGKALPRHALELLRTT 198 ... PAIPDDGPEIIVMTHPLDNVSEIDDVHAEFL...DQPDDDWLELYHFRGKALPRHALELLRTT Sbjct: 1 ... PAIPDDGPEIIVMTHPLDNVSEIDDVHAEFLDQPDDDWLELYHFRGKALPRHALELLRTT 60 ... Qu

Draft Genome Sequence of Corynebacterium kefirresidentii SB, Isolated from Kefir.

Science.gov (United States)

Blasche, Sonja; Kim, Yongkyu; Patil, Kiran R

2017-09-14

The genus Corynebacterium includes Gram-positive species with a high G+C content. We report here a novel species, Corynebacterium kefirresidentii SB, isolated from kefir grains collected in Germany. Its draft genome sequence was remarkably dissimilar (average nucleotide identity, 76.54%) to those of other Corynebacterium spp., confirming that this is a unique novel species. Copyright © 2017 Blasche et al.

CLINICAL FEATURES OF CHILDREN WITH DIPHTHERIA ON SOETOMO HOSPITAL

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Dwiyanti Puspitasari

2017-04-01

Full Text Available Introduction: Diphtheria is an important disease in children that could lead to fatal disease. East Java Province was declared to have Diphtheria outbreak in 2011 with increasing morbidity and mortality, including on Soetomo Hospital. Our paper aimed to describe the profi le of diphtheria cases in children admitted at dr Sutomo Hospital. Method: This descriptive study reviewed all medical records of diphtheritic patients admitted to Dr. Soetomo Hospital, January 2004–December 2010, of concerns were clinical presentations, age, sex, immunizations status, complications, and outcomes. Result: From 148 diphtheria cases, 22.3% were bacteriologically proven; 53.4% were male with sex ratio 1.1:1. The age proportion of ≤ 5 years old, 5- ≤ 10 years old, and > 10 years old were 61.5%, 31.8%, and 6.7%. Fever occurred in 99% cases, sore throat, stridor and bullneck occurred respectively in 62.2%, 39.9%, and 29.7% cases. There were 56.8% severe and 41.9% moderate diphtheria. Subjects were immunized in 84%, but none of them have adequate immunization. Myocarditis, being one of the commonest complications occurred in 11.4% cases and tracheostomy was the second (4.0%. All of the death cases (7.9% were unvaccinated and in severe form. Discussion: The mostly prevalent clinical manifestations in diphtheria children were fever and sore throat. Half of the cases came with severe diphtheria and most cases were inadequately vaccinated. Death occurred in the unvaccinated and severe form.

Recall Responses to Tetanus and Diphtheria Vaccination Are Frequently Insufficient in Elderly Persons

Science.gov (United States)

Weinberger, Birgit; Schirmer, Michael; Matteucci Gothe, Raffaella; Siebert, Uwe; Fuchs, Dietmar; Grubeck-Loebenstein, Beatrix

2013-01-01

Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological “non-responder type.” Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite

THE ACCELERATED METHOD FOR IDENTIFICATION OF PATHOGENIC CORYNEBACTERIUM

Directory of Open Access Journals (Sweden)

S. A. Gabrielyan

2013-01-01

Full Text Available Abstract. The detection of cystinase activity is one of most important tests in the laboratory diagnosis of diphtheria, giving the opportunity to differentiate potential toxigenic species from other coryneform bacteria. The original recipe of Pizu media for detection of cystinase activity, proposed in 1939–1940, was modified several times (1982, 1989 for different reasons. In the last modification the Pizu media was prepared by using the AGV media as a nutritional base. We suggest a modification of Pizu media using Mueller-Hinton agar as nutritional basis. The Mueller-Hinton agar has a number of advantages: higher nutritional value, standardization, transparency and availability. A positive result is defined within 2–4 hours after inoculation of enough quantity of material (pure culture or C. diphtheriaе in association with other microorganisms as a brown halo surrounding black colonies. The brown halo does not appear in the upper part of the media (0,5–1 cm. The modified media was checked with 21 strains of C. diphtheriaе (tox+, nine strains of coryneform bacteria, control strains NCTC 10648, NCTC 10356, NCTC 3984. The modified Pizu media is registered in the RA mental property agency as an invention (no. 1877 A2, 15.12.2006.

Corynebacterium minutissimum vascular graft infection: case report and review of 281 cases of prosthetic device-related Corynebacterium infection.

Science.gov (United States)

Reece, Rebecca M; Cunha, Cheston B; Rich, Josiah D

2014-09-01

Corynebacterium spp. have proven their pathogenic potential in causing infections, particularly in the setting of immunosuppression and prosthetic devices. We conducted a PubMed literature review of all cases of Corynebacterium prosthetic device infections published in the English language through December 2013. The majority of cases involved peritoneal dialysis and central venous catheters, but prosthetic joints and central nervous system shunts/drains were also involved. The management of these cases in terms of retention or removal of the device was not uniform; however, the overall mortality remained the same among both groups. All of these prosthetic device infections pose potential problems in management when the device cannot be removed safely for the patient, especially with the lack of data on the pathogenicity of Corynebacterium species. However with better identification of species and sensitivities, successful treatment is possible even with retention of the device.

Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis

Science.gov (United States)

Hammarlund, Erika; Thomas, Archana; Poore, Elizabeth A.; Amanna, Ian J.; Rynko, Abby E.; Mori, Motomi; Chen, Zunqiu; Slifka, Mark K.

2016-01-01

Background. Many adult immunization schedules recommend that tetanus and diphtheria vaccination be performed every 10 years. In light of current epidemiological trends of disease incidence and rates of vaccine-associated adverse events, the 10-year revaccination schedule has come into question. Methods. We performed cross-sectional analysis of serum antibody titers in 546 adult subjects stratified by age or sex. All serological results were converted to international units after calibration with international serum standards. Results. Approximately 97% of the population was seropositive to tetanus and diphtheria as defined by a protective serum antibody titer of ≥0.01 IU/mL. Mean antibody titers were 3.6 and 0.35 IU/mL against tetanus and diphtheria, respectively. Antibody responses to tetanus declined with an estimated half-life of 14 years (95% confidence interval, 11–17 years), whereas antibody responses to diphtheria were more long-lived and declined with an estimated half-life of 27 years (18–51 years). Mathematical models combining antibody magnitude and duration predict that 95% of the population will remain protected against tetanus and diphtheria for ≥30 years without requiring further booster vaccination. Conclusions. These studies demonstrate that durable levels of protective antitoxin immunity exist in the majority of vaccinated individuals. Together, this suggests that it may no longer be necessary to administer booster vaccinations every 10 years and that the current adult vaccination schedule for tetanus and diphtheria should be revisited. PMID:27060790

Anti-diphtheria immunity in Nigerian mothers and their newborns.

Science.gov (United States)

Cummings, Henry; Sadoh, Ayebo Evawere; Oviawe, Osawaru; Sadoh, Wilson Ehidiamen

2014-05-30

Immunity to diphtheria has been noted to wane with age such that previous studies have shown that a significant proportion of females with characteristics comparable to those of Nigerian women of reproductive age have inadequate levels of immunity to diphtheria. Thus, it is envisaged that Nigerian newborns may inherit inadequate levels of immunity to diphtheria from their mothers. Cord blood and peripheral maternal blood samples were collected from 231 mother-infant pairs at delivery. Anti-diphtheria antibody titres were assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Recruited babies were those born at term with normal birth weight. As much as 29.9% of both mothers and their babies had no protection (antibody titrediphtheria. Ninety (39.0% CI 33%,45%) mothers and 107 (46.3% CI 40%,52%) babies were inadequately protected (antibody titrediphtheria. The difference in the geometric mean antibody titres of mothers and babies was statistically significant (pdiphtheria. Vaccination of parturient women with booster doses of diphtheria toxoid vaccine is recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Local reactions after diphtheria-tetanus-acellular pertussis vaccines in mice; changes in histopathology at the injection site].

Science.gov (United States)

Nagaoka, Chiharu; Katsuta, Tomohiro; Honjo, Ayako; Tateyama, Satoshi; Tokutake, Tadaomi; Arimoto, Yutaka; Nakajima, Natsuki; Goshima, Toshiro; Kato, Tatsuo

2006-03-01

Diphtheria-tetanus-acellular pertussis vaccine (DTaP) developed in Japan is now widely used worldwide. DTaP is safer than the diphtheria-tetanus-whole-cell pertussis vaccine (DTwP) and has fewer severe side effects, but local reactions such as redness, swelling, and induration are still reported. The pathophysiological mechanism of these reactions is controversial. To clarify the cause of local reactions, we conducted studies using the mouse model. After administering either one or two abdominal subcutaneous DTaP inoculations, we observed changes in histopathology at the injection site at 24h, 48h, and 7 days. The control group, inoculated with physiologic saline, showed no significant changes either pathologically or with the naked eye. All mice after DTaP vaccination showed indurations at the injection site. Pathologically, we watched leukocyte invasion into or around the site, especially neutrophils and eosinophils. After the first vaccination, the extent of the invasion was strong 24h and 7 days later. At 24h following the second vaccination, a dramatic leukocyte invasion seen persisted at 7days. At 7 days after the first vaccination, peripheral fibrosis had begun, and when a second vaccination was administered, it began even earlier at the second site. These histopathological changes show that local reactions are caused by both inflammatory and allergic responses. Because this mouse study resulted in the same pattern of reactions observed in humans, this method will be useful for studies focusing on local reactions.

Tetanus, Diphtheria, and Pertussis Vaccines: MedlinePlus Health Topic

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... Know (Centers for Disease Control and Prevention) - PDF Topic Image MedlinePlus Email Updates Get Tetanus, Diphtheria, and ... updates by email What's this? GO Related Health Topics Childhood Immunization Diphtheria Immunization Tetanus Whooping Cough National ...

Staphylococcus aureus shifts towards commensalism in response to Corynebacterium species

Directory of Open Access Journals (Sweden)

Matthew M Ramsey

2016-08-01

Full Text Available Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence towards a commensal state when exposed to commensal Corynebacterium species.

Immunity to tetanus and diphtheria in the UK in 2009.

Science.gov (United States)

Wagner, Karen S; White, Joanne M; Andrews, Nick J; Borrow, Ray; Stanford, Elaine; Newton, Emma; Pebody, Richard G

2012-11-19

This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (pdiphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, pdiphtheria in 2009 were 29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule. Copyright © 2012 Elsevier Ltd. All rights reserved.

diphtheriae in a child Corynebacterium

African Journals Online (AJOL)

isolated from blood cultures in suspected cases of. lE. Hpwever, his .... dextrin -, maltose +, sucrose -, catalase +,glucose +, mannitol-, trehalose -, nitrate ... by Abbott.9 Whether in acquired or congenital heart disease, the bacteraemia of lE is ...

Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

NARCIS (Netherlands)

Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

2007-01-01

OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.

Science.gov (United States)

Zasada, Aleksandra A; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

2013-11-19

Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

[THE EFFECTIVENESS OF VACCINATION AGAINST DIPHTHERIA IN THE VORONEZH REGION].

Science.gov (United States)

Mamchik, N P; Gabbasova, N V; Sitnik, T N; Borisova, L S

2015-01-01

The purpose of the study was the assessment of the effectiveness of vaccination against diphtheria in the Voronezh region over the epidemic period of 1993-1997 and epidemiological welfare during 2010-2014. of the study: data of the official statistical reporting--forms number 1, 6, the serum level of antitoxic antibodies to diphtheria in 19319 healthy individuals were analyzed with the aid of epidemiological (descriptive and evaluative), immunological and statistical methods. During the epidemic rise of diphtheria (1993-1997) 75% of cases were amounted to the adult population of the Voronezh region, half of them--were not immunized against diphtheria. In 1993 there was begun mass vaccination of adult population, immunization coverage by 1998 reached 95%. According to seromonitoring data the share of seronegatives to diphtheria among cases examined during the period of 1995-2000 accountedfrom 11.9 to 24.9%. During the period of sporadic morbidity (1998-2007 years) among patients the 80% of cases have been vaccinated with an interval from the last inoculation of 3-5 years, which casts doubt on the effectiveness of vaccines. Since 2008 the incidence of diphtheria in the Voronezh region was not recorded. Against the background of 98% coverage of vaccination of the total population, the share of seronegatives for the last 5 years have decreased by 2.5 times and in 2014 reached the required performance. Documented inoculation indices fail to reflect the level of the actual protection against infection. In the conditions of the absence of the morbidity only serological monitoring is an objective criterion of the protectability of the population from infection.

Seroprevalence study of anti diphtheria antibodies in two age-groups of Romanian adults.

Science.gov (United States)

Dragomirescu, Cristiana Cerasella; Coldea, Ileana-Luminiţa; Ilie, Anamaria; Stănescu, Aurora; Ungureanu, Vasilica; Popa, Mircea Ioan

2014-01-01

Diphtheria represents a serious infectious disease with high epidemic potential. It is a vaccine preventable disease (a minimum vaccine coverage of 95% for children of 1 year and 90% in adults could prevent the disease). Diphtheria vaccination is included in the National Immunization Program (NIP). Complete vaccination for children consists in DTaP (diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine) vaccine administration from the age of 2 months until 4 years and dT vaccine (tetanus toxoid and a reduced dose of diphtheria toxoid) at 14 years old. The aim of this paper was to highlight the protection against diphtheria of an age segment of the Romanian adult population (20 to 39 years old) using a seroprevalence study. The Romanian subjects were selected from two age groups: 20-29 years (n = 219) and 30-39 years (n = 229), representative for all counties of Romania. The commercial kit Anti-Diphtheria Toxoid ELISA (IgG) (EUROIMMUN) was used to detect the antibodies of IgG class against diphtheria toxoid in the sera obtained from our subjects. We detected a 56.6% rate of positive sera (> 0.1 IU/ml--protection level) for the 20-29 age group and 31.7% positivity for the 30-39 age group. These data show a low protection level against diphtheria of the Romanian adult population, which decreases with age. The serologic data on preventable vaccine diseases are useful in order to evaluate the success of the immunization programs.

Mutant with diphtheria toxin receptor and acidification function but defective in entry of toxin

International Nuclear Information System (INIS)

Kohno, Kenji; Hayes, H.; Mekada, Eisuke; Uchida, Tsuyoshi

1987-01-01

A mutant of Chinese hamster ovary cells, GE1, that is highly resistant to diphtheria toxin was isolated. The mutant contains 50% ADP-ribosylatable elongation factor 2, but its protein synthesis was not inhibited by the toxin even at concentrations above 100 μg/ml. 125 I-labeled diphtheria toxin was associated with GE1 cells as well as with the parent cells but did not block protein synthesis of GE1 cells even when the cells were exposed to low pH in the presence or absence of NH 4 Cl. The infections of GE1 cells and the parent cells by vesicular stomatitis virus were similar. GE1 cells were cross-resistant to Pseudomonas aeruginosa exotoxin A and so were about 1,000 times more resistant to this toxin than the parent cells. Hybrids of GE1 cells and the parent cells or mutant cells lacking a functional receptor were more sensitive to diphtheria toxin than GE1 cells. These results suggest that entry of diphtheria toxin into cells requires a cellular factor(s) in addition to those involved in receptor function and acidification of endosomes and that GE1 cells do not express this cellular factor. This character is recessive in GE1 cells

Diphtheria and the Vaccine (Shot) to Prevent It: Information for Parents

Science.gov (United States)

... PARENTS | DISEASES and the VACCINES THAT PREVENT THEM | Diphtheria and the Vaccine (Shot) to Prevent It Last ... April 2017 The best way to protect against diphtheria is by getting the diphther ia-tet anus- ...

Tdap Vaccine (Tetanus, Diphtheria and Pertussis): What You Need to Know

Science.gov (United States)

... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

INTERACTION OF RECOMBINANT DIPHTHERIA TOXOIDS WITH CELLULAR RECEPTORS in vitro

Directory of Open Access Journals (Sweden)

K. Yu. Manoilov

2016-06-01

Full Text Available The aim of the research was to compare in vitro characteristics of reception of the natural diphtheria toxin — DT and its nontoxic recombinant analogs — toxoids. For assessing ligand-receptor interaction the method of immunoenzyme analysis and ELISA was used, where the bonding layer recombinant analogues of diphtheria toxin cell receptor HB-EGF from sensitive and resistant to the toxin of the organisms were served. According to the results of ELISA the natural diphtheria toxin, in contrast to recombinant toxoids — CRM197, and B subunit, interacted with mouse HB-EGF with a very low affinity. While human HB-EGF with an equally high affinity connected as toxoids as native diphtheria toxin. Therefore, the analyzed recombinant analogs of toxin obtained in E. coli cells did not reproduce in full measure the receptor specificity of the natural toxin, which should be considered in the case of using these proteins as biotech products.

J-GLOBAL MeSH Dictionary: Corynebacterium pseudotuberculosis [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term Corynebacterium pseudotuberculosis... 名詞 一般 * * * * Corynebacterium pseudotuberculosis ... MeSH D016925 200906025325177003 C LS07 UNKNOWN_2 Corynebacterium pseudotuberculosis

Level of Immunological Protection against Diphtheria in the Population of Dnipropetrovsk Region

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G.O. Revenko

2016-11-01

Full Text Available Background. Diphtheria — an infectious disease, the spread of which is limited by population post-vaccination immunity. In the system of epidemiological surveillance of diphtheria, for objective assessment and prediction of epidemic situation in low intensity of epidemic process of this infection, the serological control of immunity is crucial. The objective: prognosis of epidemic situation in terms of the risk of diphtheria outbreaks in Ukraine by the detection of population post-vaccination immunity against diphtheria in Dnipropetrovsk region and evaluation of the effectiveness of widespread vaccination. Materials and methods. 483 people aged 0 to 78 years were examined in total in 2015 (children — 234, adults — 249 persons. Evaluation of specific immunity against diphtheria was carried on with the following criteria: those with levels of antibodies 0.015–0.06 IU/mL should be considered as relatively protected; 0.1–0.5 IU/ml — with average level of protection; > 1.0 IU/ml — with high level of protection. Protective antibody titer should be considered the concentration of not less than 0.1 IU/ml. Results. It was established that the level of protective immunity against diphtheria was 69.5 %. Reliable level of immunological protection of children was 70.9 %, among adults — 68.3 %. None age group had sufficient threshold level of antitoxic immunity required to stop the transmission of diphtheria pathogen. Percentage of protected persons decreased with increasing age of people (both in children and adults. This situation may create conditions for outbreaks of diphtheria in Dnipropetrovsk region. Conclusions. The presented results indicate the importance of maintaining protective antibody levels through widespread immunization of children, as well as booster vaccination among adolescents and adults that will exclude the category of susceptible layer of the population.

Structural perturbation of diphtheria toxoid upon adsorption to aluminium hydroxide adjuvant

NARCIS (Netherlands)

Regnier, M.; Metz, B.; Tilstra, W.; Hendriksen, C.; Jiskoot, W.; Norde, W.; Kersten, G.

2012-01-01

Aluminium-containing adjuvants are often used to enhance the potency of vaccines. In the present work we studied whether adsorption of diphtheria toxoid to colloidal aluminium hydroxide induces conformational changes of the antigen. Diphtheria toxoid has a high affinity for the aluminium hydroxide

Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

Science.gov (United States)

Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

2014-06-30

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

Science.gov (United States)

2011-05-13

... Factor-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. [[Page... veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid conjugate by subcutaneous... provides for the veterinary prescription use of IMPROVEST (gonadotropin releasing factor-diphtheria toxoid...

Anticancer peptides from bacteria

OpenAIRE

Tomasz M. Karpiński; Anna K. Szkaradkiewicz

2013-01-01

Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data ...

The life and death of translation elongation factor 2

DEFF Research Database (Denmark)

Jørgensen, Rene; Merrill, A.R.; Andersen, Gregers Rom

2006-01-01

The eukaryotic elongation factor 2 (eEF2) occupies an essential role in protein synthesis where it catalyses the translocation of the two tRNAs and the mRNA after peptidyl transfer on the 80S ribosome. Recent crystal structures of eEF2 and the cryo-EM reconstruction of its 80S complex now provide...... diphthamide residue, which is ADP-ribosylated by diphtheria toxin from Corynebacterium diphtheriae and exotoxin A from Pseudomonas aeruginosa....

DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

Science.gov (United States)

... STATEMENT DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are ... www. immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by ...

Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

Science.gov (United States)

... is taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): ... vis-statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: ...

External quality assessments for microbiologic diagnosis of diphtheria in Europe.

Science.gov (United States)

Both, Leonard; Neal, Shona; De Zoysa, Aruni; Mann, Ginder; Czumbel, Ida; Efstratiou, Androulla

2014-12-01

The European Diphtheria Surveillance Network (EDSN) ensures the reliable epidemiological and microbiologic assessment of disease prevalence in the European Union. Here, we describe a survey of current diagnostic techniques for diphtheria surveillance conducted across the European Union and report the results from three external quality assessment (EQA) schemes performed between 2010 and 2014. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children

Science.gov (United States)

Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-01-01

Abstract Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children. Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule. Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection. Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies. The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The

Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Directory of Open Access Journals (Sweden)

G.P. Silva

2013-02-01

Full Text Available Serogroup B Neisseria meningitidis (MenB is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization. Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine, its use should be restricted to outbreaks of meningococcal disease.

A cross-reacting material CRM197 conjugate vaccine induces diphtheria toxin neutralizing antibody response in children and adolescents infected or not with HIV.

Science.gov (United States)

Silva, Giselle P; Santos, Rafaela S; Pereira-Manfro, Wânia F; Ferreira, Bianca; Barreto, Daniella M; Frota, Ana Cristina C; Hofer, Cristina B; Milagres, Lucimar G

2017-07-05

Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM 197 ) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0.01IU/ml of antibody) and only 8 (19%) showed complete protection (≥0.1IU/ml). About half of the HC (56%) had complete protection before immunization and 6 subjects (12%) had no protection against diphtheria. After one and two vaccine injections, 96% of HC and 64% of HI vaccinees, respectively, showed full protection against diphtheria. These data indicate that CRM 197 was able to induce primary and/or booster response in both groups of individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin

International Nuclear Information System (INIS)

Rolf, J.M.; Gaudin, H.M.; Tirrell, S.M.; MacDonald, A.B.; Eidels, L.

1989-01-01

An anti-idiotypic serum prepared against the combining site (idiotype) of specific anti-diphtheria toxoid antibodies was characterized with respect to its interaction with highly diphtheria toxin-sensitive Vero cells. Although the anti-idiotypic serum protected Vero cells against the cytotoxic action of diphtheria toxin, it did not prevent the binding of 125 I-labeled diphtheria toxin to the cells but did inhibit the internalization and degradation of 125 I-labeled toxin. This anti-idiotypic serum immunoprecipitated a cell-surface protein from radiolabeled Vero cells with an apparent Mr of approximately 15,000. These results are consistent with the hypothesis that the anti-idiotypic serum contains antibodies that carry an internal image of an internalization site on the toxin and that a cell-surface protein involved in toxin internalization possesses a complementary site recognized by both the toxin and the anti-idiotypic antibodies

Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

International Nuclear Information System (INIS)

Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

2005-01-01

Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

Diphtheria toxin-induced channels in Vero cells selective for monovalent cations

International Nuclear Information System (INIS)

Sandvig, K.; Olsnes, S.

1988-01-01

Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of 45 Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+, K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed

[Diphtheria in the military forces: lessons and current status of prophylaxis, prospects of epidemiological control process].

Science.gov (United States)

Belov, A B; Ogarkov, P I

2014-01-01

We analyzed the epidemiological situation of diphtheria in the world and in Russia and experience of mass vaccination of military personnel and civil population with diphtheria toxoid for the last 50 years. Early diagnosis of diphtheria in military personnel has a prognostic value. Authors described the peculiarities of epidemiological process of diphtheria in military personnel in 80-90 years of 20th century and organizational aspects of mass vaccination with diphtheria toxoid. Authors analyzed current problems of epidemiology and prophylaxis of diphtheria in military personnel and civil population and possible developments. According to long-term prognosis authors mentioned the increase of morbidity and came to conclusion that it is necessary enhance the epidemiological surveillance. Authors presented prospect ways of improvement of vaccination and rational approaches to immunization of military personnel under positive long-term epidemiological situation.

Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin

Energy Technology Data Exchange (ETDEWEB)

Rolf, J.M.; Gaudin, H.M.; Tirrell, S.M.; MacDonald, A.B.; Eidels, L.

1989-03-01

An anti-idiotypic serum prepared against the combining site (idiotype) of specific anti-diphtheria toxoid antibodies was characterized with respect to its interaction with highly diphtheria toxin-sensitive Vero cells. Although the anti-idiotypic serum protected Vero cells against the cytotoxic action of diphtheria toxin, it did not prevent the binding of /sup 125/I-labeled diphtheria toxin to the cells but did inhibit the internalization and degradation of /sup 125/I-labeled toxin. This anti-idiotypic serum immunoprecipitated a cell-surface protein from radiolabeled Vero cells with an apparent Mr of approximately 15,000. These results are consistent with the hypothesis that the anti-idiotypic serum contains antibodies that carry an internal image of an internalization site on the toxin and that a cell-surface protein involved in toxin internalization possesses a complementary site recognized by both the toxin and the anti-idiotypic antibodies.

Determination of the therapeutic potential of human umbilical cord ...

African Journals Online (AJOL)

This research was conducted to evaluate the therapeutic potential of human umbilical cord blood, by determining their effect on bacterial pathogens which included: Streptobacillus sp, Corynebacterium diphtheriae, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. Cord blood samples were obtained ...

Seroepidemiology of diphtheria and tetanus among children and young adults in Tajikistan: nationwide population-based survey, 2010.

Science.gov (United States)

Khetsuriani, Nino; Zakikhany, Katherina; Jabirov, Shamsiddin; Saparova, Nargis; Ursu, Pavel; Wannemuehler, Kathleen; Wassilak, Steve; Efstratiou, Androulla; Martin, Rebecca

2013-10-01

Tajikistan had a major diphtheria outbreak (≈ 10,000 cases) in the 1990 s, which was controlled after nationwide immunization campaigns with diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases have been reported. However, in coverage surveys conducted in 2000 and 2005, diphtheria-tetanus-pertussis vaccine coverage was lower than administratively reported estimates raising concerns about potential immunity gaps. To further assess population immunity to diphtheria in Tajikistan, diphtheria antibody testing was included in a large-scale nationwide serosurvey for vaccine-preventable diseases conducted in connection with a poliomyelitis outbreak in 2010. In addition, the serosurvey provided an opportunity to assess population immunity to tetanus. Residents of all regions of Tajikistan aged 1-24 years were included in the serosurvey implemented during September-October 2010. Participants were selected through stratified cluster sampling. Specimens were tested for diphtheria antibodies using a Vero cell neutralization assay and for tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations ≥ 0.1 IU/mL were considered seropositive. Overall, 51.4% (95% CI, 47.1%-55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%-82.5%) were seropositive for tetanus. The lowest percentages of seropositivity for both diseases were observed among persons aged 10-19 years: diphtheria seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3% (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%). Population immunity for diphtheria in Tajikistan is low, particularly among 10-19 year-olds. Population immunity to tetanus is generally higher than for diphtheria, but is suboptimal among 10-19 year-olds. These findings highlight the need to improve routine immunization service delivery, and support a

Tetanus and diphtheria immunity in refugees in Europe in 2015.

Science.gov (United States)

Jablonka, Alexandra; Behrens, Georg M N; Stange, Marcus; Dopfer, Christian; Grote, Ulrike; Hansen, Gesine; Schmidt, Reinhold Ernst; Happle, Christine

2017-04-01

Current political crises in the Middle East and economic discrepancies led millions of people to leave their home countries and to flee to Western Europe. This development raises unexpected challenges for receiving health care systems. Although pan-European initiatives strive for updated and optimized vaccination strategies, little data on immunity against vaccine-preventable diseases in the current refugee population exist. We quantified serum IgG against tetanus and diphtheria (TD) in n = 678 refugees currently seeking shelter in six German refugee centers. Reflecting current migration statistics in Europe, the median age within the cohort was 26 years, with only 23.9 % of female subjects. Insufficient IgG levels without long-term protection against tetanus were found in 56.3 % of all refugees. 76.1 % of refugees had no long-term protection against diphtheria. 47.7 % of subjects needed immediate vaccination against tetanus, and 47.7 % against diphtheria. For both diseases, an age-dependent decline in protective immunity occurred. We observed a considerably low rate of tetanus-protected refugees, and the frequency of diphtheria-immune refugees was far from sufficient to provide herd immunity. These findings strongly support recent intentions to implement and enforce stringent guidelines for refugee vaccination in the current crisis.

Access to diphtheria antitoxin for therapy and diagnostics.

Science.gov (United States)

Both, L; White, J; Mandal, S; Efstratiou, A

2014-06-19

The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore--besides efforts to improve the current supply of DAT--accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.

Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

Directory of Open Access Journals (Sweden)

Saliou Pierre

2005-11-01

Full Text Available Abstract Background Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi, stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP vaccines. Methods In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+ every two weeks for seven months or no chemoprophylaxis (CH-. After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05. The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05 and 77% and 91% for tetanus toxoid (P > 0.05. In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05. While analysis for pertussis showed a 43% (CH+ and 67% (CH- response (P Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

ORIGINAL ARTICLE DIPHTHERIA MORTALITY IN NIGERIA: THE ...

African Journals Online (AJOL)

Dr Oboro VO

AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY MAY 2011 ... RESULTS: Nine cases of diphtheria were seen and three mortalities were recorded giving a mortality rate ... tissue edema and airway obstruction by the.

Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

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Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

2018-02-01

The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

Identification of membrane-associated proteins with pathogenic potential expressed by Corynebacterium pseudotuberculosis grown in animal serum.

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Raynal, José Tadeu; Bastos, Bruno Lopes; Vilas-Boas, Priscilla Carolinne Bagano; Sousa, Thiago de Jesus; Costa-Silva, Marcos; de Sá, Maria da Conceição Aquino; Portela, Ricardo Wagner; Moura-Costa, Lília Ferreira; Azevedo, Vasco; Meyer, Roberto

2018-01-25

Previous works defining antigens that might be used as vaccine targets against Corynebacterium pseudotuberculosis, which is the causative agent of sheep and goat caseous lymphadenitis, have focused on secreted proteins produced in a chemically defined culture media. Considering that such antigens might not reflect the repertoire of proteins expressed during infection conditions, this experiment aimed to investigate the membrane-associated proteins with pathogenic potential expressed by C. pseudotuberculosis grown directly in animal serum. Its membrane-associated proteins have been extracted using an organic solvent enrichment methodology, followed by LC-MS/MS and bioinformatics analysis for protein identification and classification. The results revealed 22 membrane-associated proteins characterized as potentially pathogenic. An interaction network analysis indicated that the four potentially pathogenic proteins ciuA, fagA, OppA4 and OppCD were biologically connected within two distinct network pathways, which were both associated with the ABC Transporters KEGG pathway. These results suggest that C. pseudotuberculosis pathogenesis might be associated with the transport and uptake of nutrients; other seven identified potentially pathogenic membrane proteins also suggest that pathogenesis might involve events of bacterial resistance and adhesion. The proteins herein reported potentially reflect part of the protein repertoire expressed during real infection conditions and might be tested as vaccine antigens.

Binding of Diphtheria Toxin to Phospholipids in Liposomes

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Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

1980-04-01

Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

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Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

2015-07-31

Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anticancer peptides from bacteria

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Tomasz M. Karpiński

2013-08-01

Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

Immunity to Diphtheria and Tetanus in Army Personnel and Adult Civilians in Mashhad, Iran.

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Hosseini Shokouh, Seyyed Javad; Mohammadi, Babak; Rajabi, Jalil; Mohammadian Roshan, Ghasem

2017-03-24

This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18-34 years had at least basic protection against diphtheria (antitoxin level ≥0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols.

A Spontaneous Joint Infection with Corynebacterium striatum▿

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Scholle, David

2006-01-01

Corynebacterium striatum is a ubiquitous saprophyte with the potential to cause bacteremia in immunocompromised patients. Until now, spontaneous infection of a natural joint has not been reported. When phenotyping failed, gene sequencing was used to identify the species. The isolate demonstrated high-level resistance to most antibiotics.

Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study.

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Li, Xiaomei; Chen, Meng; Zhang, Tiegang; Li, Juan; Zeng, Yang; Lu, Li

2015-01-01

The aim of this study was to assess the level of humoral immunity against diphtheria and pertussis by measuring IgG to diphtheria toxoid (DT) and pertussis toxin (PT) in general population of Beijing. A total of 2147 subjects aged 0-74 y were selected with a random sample of resident population in Beijing. The information of socio-demographic characteristics, vaccination history, disease history of diphtheria and pertussis were collected for each subject by questionnaire. Serum samples were tested for IgG antibodies to DT and PT by using commercial ELISA kits. The overall positivity rate of anti-DT IgG was 66.28% with the mean concentration of 2.169 IU/ml. Age stratified data showed that the highest positivity rate of 97.63% was observed in 1-4 y and the rates decreased with age. The positivity rates were only around 50% or below since 25 y old. The positivity rate of anti-PT IgG was 12.34% with the mean concentration of 15.163 IU/ml. The highest level of positivity rate (22.23%) and antibody level (23.101 IU/ml) was seen in diphtheria was observed at 1 y and 6 y respectively, which was consistent with the current immunization schedule. But there was no significant increase of immunity to pertussis observed after booster immunization at 18-24 months, but the proportions of undetectable were lowest in diphtheria and all the age groups showed a low immunity to pertussis indicating the potential risk of transmission and outbreaks of the 2 diseases in Beijing.

Sigma factors and promoters in Corynebacterium glutamicum

Czech Academy of Sciences Publication Activity Database

Pátek, Miroslav; Nešvera, Jan

2011-01-01

Roč. 154, 2-3 (2011), s. 101-113 ISSN 0168-1656 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * Sigma factors * Promoters Subject RIV: EE - Microbiology, Virology Impact factor: 3.045, year: 2011

Seroprevalence of antibody against diphtheria among the population in Khon Kaen province, Thailand.

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Bansiddhi, Hataichanok; Vuthitanachot, Viboonsuk; Vuthitanachot, Chanpim; Prachayangprecha, Slinporn; Theamboonlers, Apiradee; Poovorawan, Yong

2015-03-01

To assess diphtheria immunity in the northeastern region of Thailand, a seroepidemiological survey was undertaken in 2011 from 516 healthy individuals (age range 2-87 years) in Khon Kaen province. Diphtheria antitoxin levels were measured by enzyme-linked immunosorbent assay and titers of ≥0.1 IU/mL were considered to be protective antitoxin levels. Among the studied population, 94.8% have fully protective levels. The younger population (age range 2-19 years) has higher diphtheria immunity with seroprotection rates of 96.8% to 97.9%, compared with the adult population. The proportion of protective diphtheria antitoxin levels declines to 88.3% to 91.9% in the middle-aged group (20-50 years), and appeared to be higher again in the older age-group (50-70 years). To avoid epidemic spreading, promoting immunization booster programs will be helpful, especially among the adult population (20-50 years). Finally, this study may serve as a valuable guide in deciding exactly which age-groups should be targeted by such an effort. © 2012 APJPH.

Enacting cultural boundaries in French and German diphtheria serum research.

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Klöppel, Ulrike

2008-06-01

The experimental development of a therapeutic serum against diphtheria between 1891 and 1894 was characterized by a scientific competition that pitted Emil Behring from the Institute for Infectious Diseases in Berlin against Emile Roux and Elie Metschnikoff from the Pasteur Institute in Paris. In general, their competition can be regarded as an extension of the fundamental differences that separated the research schools of Robert Koch and Louis Pasteur. However, to characterize the competition for a diphtheria-serum as "national rivalry" fails to account adequately for the mutual adoption of experimental practices by the Berlin and Parisian protagonists, whose contributions to the development of a therapeutic serum were intertwined in complex ways. Nor can it be characterized as "cooperation," given their fierce public disputes over scientific concepts and the fact that these disputes also shaped the peculiarities of the experimental procedures in Berlin and Paris. A close analysis reveals a complex picture of the dynamic interaction between the conceptual and experimental activities of Behring, Roux, and Metschnikoff- interaction that defined as well as bridged the "French" and "Prussian" experimental systems of diphtheria-serum research.

Corynebacterium macginleyi isolated from a corneal ulcer

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Kathryn Ruoff

2010-02-01

Full Text Available We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT. To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

Comparison of antimicrobial susceptibilities of Corynebacterium species by broth microdilution and disk diffusion methods.

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Weiss, K; Laverdière, M; Rivest, R

1996-01-01

Corynebacterium species are increasingly being implicated in foreign-body infections and in immunocompromised-host infections. However, there are no specific recommendations on the method or the criteria to use in order to determine the in vitro activities of the antibiotics commonly used to treat Corynebacterium infections. The first aim of our study was to compare the susceptibilities of various species of Corynebacterium to vancomycin, erythromycin, and penicillin by using a broth microdilution method and a disk diffusion method. Second, the activity of penicillin against our isolates was assessed by using the interpretative criteria recommended by the National Committee for Clinical Laboratory Standards for the determination of the susceptibility of streptococci and Listeria monocytogenes to penicillin. Overall, 100% of the isolates were susceptible to vancomycin, while considerable variations in the activities of erythromycin and penicillin were noted for the different species tested, including the non-Corynebacterium jeikeium species. A good correlation in the susceptibilities of vancomycin and erythromycin between the disk diffusion and the microdilution methods was observed. However, a 5% rate of major or very major errors was detected with the Listeria criteria, while a high rate of minor errors (18%) was noted when the streptococcus criteria were used. Our findings indicate considerable variations in the activities of erythromycin and penicillin against the various species of Corynebacterium. Because of the absence of definite recommendations, important discrepancies were observed between the methods and the interpretations of the penicillin activity. PMID:8849254

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children: A cross-sectional study.

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Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-12-01

Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in

Assessment of Serologic Immunity to Diphtheria-Tetanus-Pertussis After Treatment of Korean Pediatric Hematology and Oncology Patients

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Kwon, Hyo Jin; Lee, Jae-Wook; Chung, Nak-Gyun; Cho, Bin; Kim, Hack-Ki

2012-01-01

The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination. PMID:22219618

Interdigital foot infections: Corynebacterium minutissimum and agents of superficial mycoses

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Fatma Mutlu Sariguzel

2014-09-01

Full Text Available Interdigital foot infections are mostly caused initially by dermatophytes, yeasts and less frequently by bacteria. Erythrasma caused by Corynebacterium minutissimum can be confused with superficial mycoses. The aim of the study was to determine the prevalence of the etiologic agents of superficial mycoses and the frequency of Corynebacterium minutissimum in interdigital foot infections. All the samples obtained from the 121 patients with interdigital foot infections were examined directly with the use of 20% potassium hydroxide mounts and Gram stain under the microscope and cultured on Sabouraud's dextrose agar plates. In identification of superficial mycoses, the rate was found to be 14% with the cultural method and 14% with direct microscopic examination. Using a combination of direct microscopic examination and culture, a 33.8% ratio was achieved. In the culture of these samples, the most isolated factor was Trichophyton rubrum (33.7%. In 24 of the patients (19.8% Corynebacterium minutissimum was detected by Gram staining, in 6 of these patients Trichophyton rubrum was found, Trichophyton mentagrophytes was found in 2 and Trichosporon spp. was found in 1. The examination of interdigital foot lesions in the laboratory, the coexistence of erythrasma with dermatophytes and yeast should be considered.

A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

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Rohde, K A; Cunningham, K C; Henriquez, K M; Nielsen, A R; Worzella, S L; Hayney, M S

2014-12-01

Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

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Tanriover, Mine Durusu; Soyler, Canan; Ascioglu, Sibel; Cankurtaran, Mustafa; Unal, Serhat

2014-07-01

Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital. Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values. A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis. We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of "lifelong vaccination" should be implemented and every encounter with the patient should be regarded as a chance for catch-up. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Native valve endocarditis due to Corynebacterium group JK.

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Moffie, B G; Veenendaal, R A; Thompson, J

1990-12-01

We report a case of a 32-yr-old woman on chronic intermittent haemodialysis, who developed endocarditis due to a Corynebacterium group JK, involving both the native aortic and mitral valves. Despite a four-week treatment with vancomycin, an aortic root abscess developed. The diagnosis was confirmed on autopsy.

Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

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Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

2011-01-01

This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

Re-emergence of diphtheria and pertussis: implications for Nigeria.

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Sadoh, A E; Oladokun, R E

2012-11-26

In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

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Baseman, Joel B.; Pappenheimer, A. M.; Gill, D. M.; Harper, Annabel A.

1970-01-01

The blood clearance and distribution in the tissues of 125I after intravenous injection of small doses (1.5–5 MLD or 0.08–0.25 µg) of 125I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected 125I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal. PMID:5511567

Corynebacterium species: an uncommon agent of peritoneal dialysis-related peritonitis and a challenging treatment

OpenAIRE

Ferreira, Joel; Teixeira e Costa, Fernando; Ramos, Aura

2015-01-01

Introduction: Corynebacterium is a component of normal skin flora and it is responsible for an increasing incidence of nosocomial infections in the last decades. Peritonitis and exit-site infections caused by this microorganism are uncommon but have a significant clinical impact due to their high relapsing rate. The ideal therapeutic approach in these situations is not yet clearly defined. Methods: Retrospective analysis of Corynebacterium spp peritonitis in a peritoneal dialysis unit between...

Fatal case of bacteremia caused by an atypical strain of Corynebacterium mucifaciens

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Vlademir Vicente Cantarelli

Full Text Available Corynebacterium species have often been considered normal skin flora or contaminants; however, in recent years they have been increasingly implicated in serious infections. Moreover, many new species have been discovered and old species renamed, especially after molecular biology techniques were introduced. Corynebacterium mucifaciens is mainly isolated from blood and from other normally-sterile body fluids; it forms slightly yellow, mucoid colonies on blood agar. We report a fatal case of bacteremia due to an atypical strain of C. mucifaciens. This strain had atypical colony morphology; analysis of the 16S rRNA gene was used to define the species.

Isolamento de Corynebacterium aquaticum em leite bubalino

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Andréa Alice da Fonseca Oliveira

2005-08-01

Full Text Available Estudou-se 548 quartos mamários de búfalas, realizando-se exame clínico, CMT para detecção de mastite e coleta de amostras para isolamento bacteriano. Houve crescimento em duas amostras de Corynebacterium aquaticum caracterizadas bioquimicamente. Relata-se a participação do agente como colonizador do úbere e possível causador de mastites em bubalinos.

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

International Nuclear Information System (INIS)

Rocchi, P.; Ferreri, A.M.; Capucci, A.; Prodi, G.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (less than 8 x 10(-6)). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTr) mutants up to 1000-fold. The maximum recovery of DTr mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

International Nuclear Information System (INIS)

Rocchi, P.; Ferreri, A.M.; Capucci, A.; Prodi, G.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency ( -6 ). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTsup(r)) mutants up to 1000-fold. The maximum recovery of DTsup(r) mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages. (author)

Diphtheria, tetanus, poliomyelitis, yellow fever and hepatitis B seroprevalence among HIV1-infected migrants. Results from the ANRS VIHVO vaccine sub-study.

Science.gov (United States)

Mullaert, Jimmy; Abgrall, Sophie; Lele, Nathalie; Batteux, Frederic; Slama, Lilia Ben; Meritet, Jean-Francois; Lebon, Pierre; Bouchaud, Olivier; Grabar, Sophie; Launay, Odile

2015-09-11

Few data are available on the seroprotection status of HIV1-infected patients with respect to vaccine-preventable diseases. To describe, in a population of HIV1-infected migrants on stable, effective ART therapy, the seroprevalence of diphtheria, poliomyelitis, tetanus, yellow fever antibodies and serostatus for hepatitis B, and to identify factors associated with seroprotection. Vaccine responses against diphtheria, tetanus, poliomyelitis and yellow fever were also studied. Sub-Saharan African patients participating in the ANRS-VIHVO cohort were enrolled prior to travel to their countries of origin. Serologic analyses were performed in a central laboratory before and after the trip. Univariate and multivariate logistic regression was used to identify factors associated with initial seroprotection. 250 patients (99 men and 151 women) were included in the seroprevalence study. Median age was 45 years (IQR 39-52), median CD4 cell count was 440/μL (IQR 336-571), and 237 patients (95%) had undetectable HIV1 viral load. The initial seroprevalence rates were 69.0% (95%CI 63.2-74.7) for diphtheria, 70.7% (95%CI 65.0-76.3) for tetanus, and 85.9% (95%CI 81.6-90.2) for yellow fever. Only 64.4% (95%CI 58.5-70.3) of patients had protective antibody titers against all three poliomyelitis vaccine strains before travel. No serological markers of hepatitis B were found in 18.6% of patients (95%CI 13.7-23.3). Patient declaration of prior vaccination was the only factor consistently associated with initial seroprotection. We found a low prevalence of seroprotection against diphtheria, poliomyelitis, tetanus and hepatitis B. HIV infected migrants living in France and traveling to their native countries need to have their vaccine schedule completed. Copyright © 2015 Elsevier Ltd. All rights reserved.

A microbiological and clinical review on Corynebacterium kroppenstedtii

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Andreas Tauch

2016-07-01

Full Text Available The genus Corynebacterium represents a taxon of Gram-positive bacteria with a high G + C content in the genomic DNA. Corynebacterium kroppenstedtii is an unusual member of this taxon as it lacks the characteristic mycolic acids in the cell envelope. Genome sequence analysis of the C. kroppenstedtii type strain has revealed a lipophilic (lipid-requiring lifestyle and a remarkable repertoire of carbohydrate uptake and utilization systems. Clinical isolates of C. kroppenstedtii have been obtained almost exclusively from female patients and mainly from breast abscesses and cases of granulomatous mastitis. However, the role of C. kroppenstedtii in breast pathologies remains unclear. This review provides a comprehensive overview of the taxonomy, microbiology, and microbiological identification of C. kroppenstedtii, including polyphasic phenotypic approaches, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the use of 16S rRNA gene sequencing. A clinical review presents reported cases, various antimicrobial treatments, antibiotic susceptibility assays, and antibiotic resistance genes detected during genome sequencing. C. kroppenstedtii must be considered a potential opportunistic human pathogen and should be identified accurately in clinical laboratories.

Lichen planus following tetanus-diphtheria-acellular pertussis vaccination: A case report and review of the literature.

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Rosengard, Heather C; Wheat, Chikoti M; Tilson, Matthew P; Cuda, Jonathan D

2018-01-01

Lichen planus is an inflammatory dermatosis with a prevalence of approximately 1%. Recent meta-analyses show that patients with hepatitis C virus have a 2.5- to 4.5-fold increased risk of developing lichen planus. Lichen planus has also followed vaccinations and has specifically been attributed to the hepatitis B vaccine, the influenza vaccine, and the tetanus-diphtheria-acellular pertussis vaccine. We describe a case of lichen planus in a hepatitis C virus-infected African American male occurring in temporal association with the administration of the tetanus-diphtheria-acellular pertussis vaccine. The patient's presentation was clinically consistent with lichen planus and confirmed by biopsy. It is likely that many cases of vaccine-induced lichen planus have gone unpublished or unrecognized. In areas with high prevalence of hepatitis C virus infection, we may expect to see more cases of vaccine-induced lichen planus especially in light of the updated Centers for Disease Control and Prevention tetanus-diphtheria-acellular pertussis vaccination recommendations. This case serves to educate healthcare providers about vaccine-induced lichen planus and, in particular, the need to counsel hepatitis C virus-infected patients about a potential risk of developing lichen planus following vaccination. We also reflect on current theories suggesting the T-cell-mediated pathogenesis of lichen planus and the role that hepatitis C virus and toxoid or protein vaccines may play in initiating the disease.

Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

Science.gov (United States)

... Safe Videos for Educators Search English Español Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth / For ... child outweigh the potential risks. Caring for Your Child After DTaP Immunization Your child may have a ...

Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh

DEFF Research Database (Denmark)

Zeitlyn, S; Rahman, A K; Nielsen, B H

1992-01-01

OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose...... of the vaccine and followed up six weeks later to ascertain compliance with having second dose. Factors associated with non-compliance were evaluated. SETTING: Dhaka treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 136 unimmunised children aged 6 weeks to 23...... of immunisation, and she was given clear instructions to bring the child back after four weeks for the second dose. MAIN OUTCOME MEASURE: Rate of non-compliance with advice to return child for second vaccination. RESULTS: 46 of 113 children (41%) received the second dose of the vaccine. Factors most closely...

Td Vaccine (Tetanus and Diphtheria): What You Need to Know

Science.gov (United States)

VACCINE INFORMATION STATEMENT Td Vaccine (Tetanus and Diphtheria) What You Need to Know Many Vaccine Information Statements are available in Spanish and other languages. See www. immunize. org/ vis Hojas de ...

Genetics and Genomics of the Genus Amycolatopsis

OpenAIRE

Kumari, Rashmi; Singh, Priya; Lal, Rup

2016-01-01

Actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (Mycobacterium tuberculosis, M. leprae, Corynebacterium diphtheriae, Nocardia farcinica), plant pathogens (Streptomyces scabies, Leifsonia xyli) along with organisms that produces antibiotic (Streptomycetes, Amycolatopsis, Salinospora). Interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal propert...

An unusual case of chronic nonhealing periorbital ulceration due to a new species of Corynebacterium sp. strain UCL557

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Bipasa Chakraborty

2016-01-01

Full Text Available Nondiphtherial Corynebacterium (diphtheroids has been related to blood and wound infections but are an uncommon cause for soft tissue infection. We report a case of periorbital soft tissue infection with ulceration caused by multidrug-resistant Corynebacterium spp. in a 9-year-old girl who is apparently immunocompetant. Computed tomography scan showed soft tissue involvement of right periorbital region with no bony destructions or focal calcifications. Vision remained unaffected. Patient was treated by debridement and skin grafting, but condition did not improve. Pus collected from the periorbital ulcerated area was cultured in blood agar and Corynebacterium spp. was isolated from the pure culture, which was identified as a new species Corynebacterium sp. strain UCL557 using 16S rDNA- based molecular technique based on nucleotide homology and phylogenetic analysis. Antibiogram showed multiresistance pattern with sensitivity to ceftriaxone-sulbactum vancomycin and linezolid. After initiation of treatment with vancomycin infusion and oral linezolid, the patient responded well and lesion started to heal. To the best of our knowledge, this is the first ever case report of periorbital ulceration by new species of Corynebacterium sp. strain UCL557.

Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.

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Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B

2013-07-01

Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

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Francisco A. B. Speranza

2012-09-01

Full Text Available We assessed the IgG levels anti-diphtheria (D-Ab and T cell counts (CD4+ and CD8+ in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART. Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml than HAART-patients (geometric mean of 0.39 IU/ml. The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.

Science.gov (United States)

Csuka, Dorottya; Czirják, László; Hóbor, Renáta; Illes, Zsolt; Bánáti, Miklós; Rajczy, Katalin; Tordai, Attila; Füst, George

2013-07-01

Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population. Copyright © 2013 Elsevier Ltd. All rights reserved.

SURVEI TITER ANTI BODI ANAK SEKOLAH USIA 6--17 TAHUN DI DAERAH KLB DIFTERI DAN NON KLB DI INDONESIA

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Noer Endah Pracoyo

2014-02-01

Full Text Available AbstractDiphtheriae  is an  reemerging infectious disease  widespread in the world. Bacterial infection of Corynebacterium diphtheria usually not invasive, but the bacteria can produce toxins that cause pathological effects on the heart muscle and other organs, and a 10-17% death-risk was occurred.  Diphtheriae can be prevented by immunization.  Immunizations are given to infants at the age of 0-11 months and procead to booster for pupils at Elementary School. The imunization program at school is a routinely cunducted. Such program held annualy on certain month that called as “BIAS pupils immunization month” . To examine antibody  titer of diphtheriae, research for sero  survey titer antibody titer of diphtheriae was conducted on pupils between 6 and 17 years old at outbreak areas and non outbreak area.The research started in May 2010 and finished in Desember 2010. The aim of the research was to measure the antibody titer in area of outbreak and non outbreak of school children. Design was case control study. Sera of the respondens were axamined by Elisa for detecting antibody titers against diphtheriae. The study awarded ethical clearence from Research Ethics Committee of the National Institute of Health Research and Developmnent. Number of sample cases were 225 samples and 225 control. Analysis of the data by using the soft ware (SPSS 16.00. The result of this research were respondens who lived in the outbreak area with risk of dipthteriae infection of 2,3 times than respondens who lived in the non outbreak area. The immunization of diphthteriae more important for antibody titers.Keywords: Antibody titer diphtheriae, outbreak areaAbstrakDifteria adalah  penyakit infeksi Reemerging tersebar luas di dunia. Infeksi kuman Corynebacterium diphtheria  biasanya tidak invasif, tetapi kuman dapat memproduksi toksin yang dapat menimbulkan efek patologis pada otot jantung dan organ lain, dan berisiko terjadi kematian (10-17%. Difteri dapat

Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

Science.gov (United States)

Hagemann, Jürgen Benjamin; Essig, Andreas; Herrmann, Manuel; Liebold, Andreas; Quader, Mohamed Abo

2015-12-01

Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment. Copyright © 2015 Elsevier GmbH. All rights reserved.

Urethritis due to corynebacterium striatum: An emerging germ.

Science.gov (United States)

Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

2015-01-01

Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

Fatal diphtheria myocarditis in a 3-year-old girl-related to late availability and administration of antitoxin?

NARCIS (Netherlands)

Van Damme, Karlijn; Peeters, Natasja; Jorens, Philippe G; Boiy, Tine; Deplancke, Marjan; Audiens, Hilde; Wojciechowski, Marek; De Dooy, Jozef; Te Wierik, Margreet; Vlieghe, Erika

2017-01-01

Sporadic cases of diphtheria are very rare throughout Europe. A 3-year-old incompletely vaccinated girl was admitted with pharyngotonsillitis caused by diphtheria. On day 9 of her illness, renal and cardiac failure with a third-degree AV-block occurred. Unfortunately, she died within 36 h of

Corynebacterium jeikeium jk0268 constitutes for the 40 amino acid long PorACj, which forms a homooligomeric and anion-selective cell wall channel.

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Narges Abdali

Full Text Available Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.

Snippets from the past: the evolution of Wade Hampton Frost's epidemiology as viewed from the American Journal of Hygiene/Epidemiology.

Science.gov (United States)

Morabia, Alfredo

2013-10-01

Wade Hampton Frost, who was a Professor of Epidemiology at Johns Hopkins University from 1919 to 1938, spurred the development of epidemiologic methods. His 6 publications in the American Journal of Hygiene, which later became the American Journal of Epidemiology, comprise a 1928 Cutter lecture on a theory of epidemics, a survey-based study of tonsillectomy and immunity to Corynebacterium diphtheriae (1931), 2 papers from a longitudinal study of the incidence of minor respiratory diseases (1933 and 1935), an attack rate ratio analysis of the decline of diphtheria in Baltimore (1936), and a 1936 lecture on the age, time, and cohort analysis of tuberculosis mortality. These 6 American Journal of Hygiene /American Journal of Epidemiology papers attest that Frost's personal evolution mirrored that of the emerging "early" epidemiology: The scope of epidemiology extended beyond the study of epidemics of acute infectious diseases, and rigorous comparative study designs and their associated quantitative methods came to light.

Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a Distinctive Histopathologic Entity Not Always Demonstrably Attributable to Corynebacterium Infection.

Science.gov (United States)

D'Alfonso, Timothy M; Moo, Tracy-Ann; Arleo, Elizabeth K; Cheng, Esther; Antonio, Lilian B; Hoda, Syed A

2015-10-01

Granulomatous lobular mastitis (GLM) is an uncommon condition that typically occurs in parous, reproductive-aged women and can simulate malignancy on the basis of clinical and imaging features. A distinctive histologic pattern termed cystic neutrophilic granulomatous mastitis (CNGM) is seen in some cases of GLM and has been associated with Corynebacterium infection. We sought to further characterize the clinical, imaging, and histopathologic features of CNGM by studying 12 cases and attempted to establish the relationship of this disease with Corynebacterium infection. Patients were women ranging in age from 25 to 49 years (median: 34 y), and all presented with a palpable mass that was painful in half of the cases. In 2 of 9 cases, imaging was highly suspicious for malignancy (BI-RADS 5). CNGM was characterized by lobulocentric granulomas with mixed inflammation and clear vacuoles lined by neutrophils within granulomas. Gram-positive bacilli were identified in 5/12 cases. In 4 patients, the disease process worsened after the diagnostic core biopsy, with the development of a draining sinus in 2 cases. No growth of bacteria was seen in any microbial cultures. No bacterial DNA was identified by 16S rDNA polymerase chain reaction for 1 case that showed gram-positive bacilli on histology. Patients were treated with variable combinations of surgery, antibiotics, and steroids. The time to significant resolution of symptoms ranged from 2 weeks to 6 months. Similar to other forms of GLM, CNGM can mimic malignancy clinically and on imaging. When encountered in a needle core biopsy sample, recognition of the characteristic histologic pattern and its possible association with Corynebacterium infection can help guide treatment.

Experimental transmission of Corynebacterium pseudotuberculosis in horses by house flies

Science.gov (United States)

The route of infection of pigeon fever remains undetermined. The purpose of this study was to investigate house flies (Musca domestica L.) as vectors of Corynebacterium pseudotuberculosis in horses. Eight ponies were used in a randomized, controlled, blinded experimental study. Ten wounds were creat...

Immunity against diphtheria and tetanus in human immunodeficiency virus-infected Danish men born 1950-59

DEFF Research Database (Denmark)

Kurtzhals, J A; Kjeldsen, K; Heron, I

1992-01-01

To evaluate the possible need for vaccination against diphtheria and tetanus of patients infected with the human immunodeficiency virus (HIV), antibodies were measured in blood samples from 78 Danish HIV-infected men, born 1950-59, who could be expected to have received primary vaccination before...... they contracted the HIV infection. No patients (95% confidence interval: 0-4) had tetanus antibodies below the protective level, whereas 24 of the 78 patients (16-33) were unprotected against diphtheria. In the background population of the same age group and sex, 5% and 10% have been found unprotected against...... tetanus and diphtheria, respectively. No relationship between disease stages and antibody levels could be found. Neither was there any difference between patients with normal and reduced numbers of CD4+ lymphocytes. From 25 patients two blood samples were taken at an interval of at least one year. Anti...

Over-expression of NAD kinase in Corynebacterium crenatum and ...

African Journals Online (AJOL)

in Corynebacterium crenatum SYPA5-5 and to study its impact in presence of high (HOS) ... Results: In HOS condition, NAD+ kinase activity increased by 116 %, while ... (NADPH), an important co-enzyme during ... Polymerase, TaKaRa) using C. crenatum .... were washed with cold 100 mM PBS (pH 7.5) ..... Catalase and.

Physiological roles of sigma factor SigD in Corynebacterium glutamicum

Czech Academy of Sciences Publication Activity Database

Taniguchi, H.; Busche, T.; Patschkowski, T.; Niehaus, K.; Pátek, Miroslav; Kalinowski, J.; Wendisch, V.F.

2017-01-01

Roč. 17, č. 158 (2017), s. 158 ISSN 1471-2180 R&D Projects: GA ČR(CZ) GA17-06991S Institutional support: RVO:61388971 Keywords : Corynebacterium glutamicum * Sigma factor * SigD Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.644, year: 2016

Collaborative study for establishment of the European Pharmacopoeia BRP batch 1 for diphtheria toxin.

Science.gov (United States)

Sesardic, D; Prior, C; Daas, A; Buchheit, K H

2003-07-01

A stable liquid candidate Biological Reference Preparation (BRP) for diphtheria toxin was prepared in peptone buffer (nominal content of diphtheria toxin: 1 Lf/ml, 0.4 micro g/ml), filled in ampoules (filling volume: 1 ml) and characterised in a collaborative study. The toxin is to be used in the test "Absence of toxin and irreversibility of toxoid" as described in the current European Pharmacopoeia (Ph. Eur.) monograph Diphtheria Vaccine (Adsorbed) (2002:0443). Eleven laboratories assessed the specific activity of the preparation by in vivo and in vitro assays. The material is assumed to have satisfactory stability with a calculated predicted loss of activity of LD( 50)/ml (lethal challenge) and >75 000 Lr/Lf (intradermal challenge). The candidate BRP was successfully used in nine laboratories and confirmed suitable for use in the Vero cell test for "Absence of toxin and irreversibility of toxoid" as described in the Ph. Eur. monograph 2002:0443; i.e., concentrations of 5 x 10( -5) Lf/ml and below caused cytotoxic effects in the Vero cell test. Due to its liquid nature, the stability of the material will be monitored at regular intervals and preparation of a stable freeze-dried formulation will be considered for long-term use. Additional studies will be performed to confirm suitability of this BRP for other applications. The candidate BRP was adopted as the Ph. Eur. reference material for Diphtheria Toxin Batch 1 by the Ph. Eur. Commission at its session in March 2003.

Tools for genetic manipulations in Corynebacterium glutamicum and their applications

Czech Academy of Sciences Publication Activity Database

Nešvera, Jan; Pátek, Miroslav

2011-01-01

Roč. 90, č. 5 (2011), s. 1641-1654 ISSN 0175-7598 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * Plasmid vectors * Promoters Subject RIV: EE - Microbiology, Virology Impact factor: 3.425, year: 2011

Tips and tricks for the assembly of a Corynebacterium pseudotuberculosis genome using a semiconductor sequencer

DEFF Research Database (Denmark)

Ramos, Rommel Thiago Jucá; Carneiro, Adriana Ribeiro; Soares, Siomar de Castro

2013-01-01

that enable reference-based assembly, such as the one used in the present study, Corynebacterium pseudotuberculosis biovar equi, which causes high economic losses in the US equine industry. The quality treatment strategy incorporated into the assembly pipeline enabled a 16-fold greater use of the sequencing...... was validated by comparative genomics with other species of the genus Corynebacterium. The present study presents a modus operandi that enables a greater and better use of data obtained from semiconductor sequencing for obtaining the complete genome from a prokaryotic microorganism, C. pseudotuberculosis, which...

A RecET-assisted CRISPR-Cas9 genome editing in Corynebacterium glutamicum.

Science.gov (United States)

Wang, Bo; Hu, Qitiao; Zhang, Yu; Shi, Ruilin; Chai, Xin; Liu, Zhe; Shang, Xiuling; Zhang, Yun; Wen, Tingyi

2018-04-23

Extensive modification of genome is an efficient manner to regulate the metabolic network for producing target metabolites or non-native products using Corynebacterium glutamicum as a cell factory. Genome editing approaches by means of homologous recombination and counter-selection markers are laborious and time consuming due to multiple round manipulations and low editing efficiencies. The current two-plasmid-based CRISPR-Cas9 editing methods generate false positives due to the potential instability of Cas9 on the plasmid, and require a high transformation efficiency for co-occurrence of two plasmids transformation. Here, we developed a RecET-assisted CRISPR-Cas9 genome editing method using a chromosome-borne Cas9-RecET and a single plasmid harboring sgRNA and repair templates. The inducible expression of chromosomal RecET promoted the frequencies of homologous recombination, and increased the efficiency for gene deletion. Due to the high transformation efficiency of a single plasmid, this method enabled 10- and 20-kb region deletion, 2.5-, 5.7- and 7.5-kb expression cassette insertion and precise site-specific mutation, suggesting a versatility of this method. Deletion of argR and farR regulators as well as site-directed mutation of argB and pgi genes generated the mutant capable of accumulating L-arginine, indicating the stability of chromosome-borne Cas9 for iterative genome editing. Using this method, the model-predicted target genes were modified to redirect metabolic flux towards 1,2-propanediol biosynthetic pathway. The final engineered strain produced 6.75 ± 0.46 g/L of 1,2-propanediol that is the highest titer reported in C. glutamicum. Furthermore, this method is available for Corynebacterium pekinense 1.563, suggesting its universal applicability in other Corynebacterium species. The RecET-assisted CRISPR-Cas9 genome editing method will facilitate engineering of metabolic networks for the synthesis of interested bio-based products from renewable

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Roth, Adam Anders Edvin

2012-01-01

Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

Directory of Open Access Journals (Sweden)

M.H. Sonobe

2007-01-01

Full Text Available A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test. In this study, the serum titers (values between 1.0 and 19.5 IU measured by a modified TOBI test (Modi-TOBI test and toxin neutralization assays were correlated (P < 0.0001. Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001 and for diphtheria (r² = 0.93, P < 0.0001 between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Dynamic changes of horse serum T-globulin immunization with snake venoms, tetanus and diphtheria toxoids.

Science.gov (United States)

Lee, H F; Lee, J D; Lee, Y C

1979-12-01

In course of immunizing horses with snake venoms, tetanus and diphtheria toxoids, a new serum component, T-globulin, was formed and migrated between the beta- and gamma-globulins. The T-globulin content was parallel with the antibody titre after the middle course of immunization. There were many components in snake antivenin and T-globulin was composed of most of those components. The components of diphtheria T-globulin were the same as those of crude antitoxin and tetanus T-globulin except one precipitin.

Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study.

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Swart, E M; van Gageldonk, P G M; de Melker, H E; van der Klis, F R; Berbers, G A M; Mollema, L

2016-01-01

To evaluate the National Immunisation Programme (NIP) a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC) areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier. In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS) and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml) was used as minimum protective level. In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (pdiphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11) of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations) without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups. The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community after introduction in the Netherlands has not disappeared, despite national long-term high vaccination coverage.

Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication

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Leonie Schnell

2016-07-01

Full Text Available 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-dimethylphenylsemicarbazone (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. Here, we demonstrate that EGA also protects human cells from diphtheria toxin by inhibiting the pH-dependent translocation of DTA across cell membranes. The results suggest that EGA might serve for treatment and/or prevention of the severe disease diphtheria.

Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

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Ang, L W; James, L; Goh, K T

2016-03-01

In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P < 0.0005). It may be of value to consider additional vaccination efforts to protect older adults at higher risk for exposure against diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental transmission of Corynebacterium pseudotuberculosis biovar equi in horses by house flies

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The route of Corynebacterium pseudotuberculosis infection in horses remains undetermined, but transmission by insects is suspected. Scientists from CMAVE and Auburn University investigated house flies (Musca domestica L.) as possible vectors. Three ponies were directly inoculated with C. pseudotuber...

Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.

Science.gov (United States)

Park, Cheol Keun; Jung, Woo Hee; Koo, Ja Seung

2016-08-01

Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.

Autoradiographic assay of mutants resistant to diphtheria toxin in mammalian cells in vitro

International Nuclear Information System (INIS)

Ronen, A.; Gingerich, J.D.; Duncan, A.M.V.; Heddle, J.A.

1984-01-01

Diptheria toxin kills mammalian cells by ribosylating elongation factor 2, a protein factor necessary for protein synthesis. The frequency of cells able to form colonies in the presence of the toxin can be used as an assay for mutation to diphtheria toxin resistance. Resistance to diphtheria toxin can also be detected autoradiographically in cells exposed to [ 3 H]leucine after treatment with the toxin. In cultures of Chinese hamster ovary cells, the frequency of such resistant cells is increased by exposure of the cells to γ-rays, ultraviolet light, ethylnitrosourea, mitomycin c, ethidium bromide, and 5-bromo-2'-deoxyuridine in a dose- and time-dependent manner. The resistant cells form discrete microcolonies if they are allowed to divide several times before intoxication which indicates that they are genuine mutants. The assay is potentially adaptable to any cell population that can be intoxicated with diphtheria toxin and labeled with [ 3 H]leucine, whether or not the cells can form colonies. It may be useful, therefore, for measuring mutation rates in slowly growing or nondividing cell populations such as breast, brain, and liver, as well as in cells that do divide but cannot be readily cloned, such as the colonic epithelium. 23 references, 6 figures

Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department

Science.gov (United States)

Zibners, Lara

2017-02-01

Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted.

An RNAi-Enhanced Logic Circuit for Cancer Specific Detection and Destruction

Science.gov (United States)

2013-02-01

monomeric protein secreted by Corynebacterium diphtheriae, and pro-apoptotic members of Bcl-2 family: mBax (Mus musculus), hBax ( Homo sapiens ), and its...Gata3 mStaple. Intron- feature sequences – donor site, branch point, poly- pyrimidine tract, and acceptor site – were selected based on previously...sequences found in literature our intron features were chosen according SplicePort [4], an online analyzer that detects the likelihood of splicing to

Functional characterization of a vanillin dehydrogenase in Corynebacterium glutamicum

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Ding, Wei; Si, Meiru; Zhang, Weipeng; Zhang, Yaoling; Chen, Can; Zhang, Lei; Lu, Zhiqiang; Chen, Shaolin; Shen, Xihui

2015-01-01

Vanillin dehydrogenase (VDH) is a crucial enzyme involved in the degradation of lignin-derived aromatic compounds. Herein, the VDH from Corynebacterium glutamicum was characterized. The relative molecular mass (Mr) determined by SDS-PAGE was ~51kDa, whereas the apparent native Mr values revealed by gel filtration chromatography were 49.5, 92.3, 159.0 and 199.2kDa, indicating the presence of dimeric, trimeric and tetrameric forms. Moreover, the enzyme showed its highest level of activity toward vanillin at pH 7.0 and 30C, and interestingly, it could utilize NAD+ and NADP+ as coenzymes with similar efficiency and showed no obvious difference toward NAD+ and NADP+. In addition to vanillin, this enzyme exhibited catalytic activity toward a broad range of substrates, including p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, o-phthaldialdehyde, cinnamaldehyde, syringaldehyde and benzaldehyde. Conserved catalytic residues or putative cofactor interactive sites were identified based on sequence alignment and comparison with previous studies, and the function of selected residues were verified by site-directed mutagenesis analysis. Finally, the vdh deletion mutant partially lost its ability to grow on vanillin, indicating the presence of alternative VDH(s) in Corynebacterium glutamicum. Taken together, this study contributes to understanding the VDH diversity from bacteria and the aromatic metabolism pathways in C. glutamicum. PMID:25622822

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine.

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Tomovici, A; Barreto, L; Zickler, P; Meekison, W; Noya, F; Voloshen, T; Lavigne, P

2012-03-30

Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates

DEFF Research Database (Denmark)

Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P.

2016-01-01

Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses...... prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post......-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after...

Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

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Silvana Vargas Superti

2009-04-01

Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

Complete genome sequence of Corynebacterium pseudotuberculosis Cp31, isolated from an Egyptian buffalo

DEFF Research Database (Denmark)

Silva, Artur; Ramos, Rommel Thiago Jucá; Ribeiro Carneiro, Adriana

2012-01-01

Corynebacterium pseudotuberculosis is of major veterinary importance because it affects many animal species, causing economically significant livestock diseases and losses. Therefore, the genomic sequencing of various lines of this organism, isolated from different hosts, will aid in the developm...

Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

Science.gov (United States)

Pourakbari, Babak; Moradi, Behnaz; Mirzaee, Farin; Mahmoudi, Shima; Teymuri, Mostafa; Mamishi, Setareh

2013-01-01

Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

An unusual etiological agent of implantable cardioverter device endocarditis: Corynebacterium mucifaciens

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Adnan Kaya

2016-03-01

Full Text Available Cardiac pacing devices and implantable cardioverter defibrillator (ICD are becoming the mainstay of therapy in cardiology and infective endocarditis (IE and pocket infection; however, these devices require careful monitoring. Here, we describe a case of a 68-year-old female with an ICD presenting with a previously unknown etiological agent of IE, Corynebacterium mucifaciens.

Brain and lung cryptococcoma and concurrent corynebacterium pseudotuberculosis infection in a goat: a case report

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MCR Luvizotto

2009-01-01

Full Text Available A four-year-old male goat with a history of neurological disorder was euthanized. It presented uncommon nodules in the brain and lungs associated with multiple abscesses, predominantly in the spleen and liver. Histological examination of brain and lung sections revealed yeast forms confirmed to be Cryptococcus gattii after a combination of isolation and polymerase chain reaction (PCR procedures. Moreover, Corynebacterium pseudotuberculosis infection was diagnosed by PCR of samples from the lung, spleen and liver. The present report highlights the rare concurrent infection of C. gatti and C. pseudotuberculosis in an adult goat from São Paulo state, Brazil, and indicates the necessity of surveillance in the treatment of goats with atypical pulmonary infections associated with neurological disorders.

Assignment of sigma factors of RNA polymerase to promoters in Corynebacterium glutamicum

Czech Academy of Sciences Publication Activity Database

Dostálová, Hana; Holátko, Jiří; Busche, T.; Rucká, Lenka; Rapoport, Andrey; Halada, Petr; Nešvera, Jan; Kalinowski, J.; Pátek, Miroslav

2017-01-01

Roč. 7, JUN 23 (2017), s. 1-13, č. článku 133. ISSN 2191-0855 R&D Projects: GA ČR(CZ) GA17-06991S Institutional support: RVO:61388971 Keywords : Corynebacterium glutamicum * Promoter * Sigma factor Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.825, year: 2016

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

Science.gov (United States)

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department [digest].

Science.gov (United States)

Zibners, Lara; Chaudhari, Pradip

2017-02-22

Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

Risk factors for invasive reptile-associated salmonellosis in children.

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Meyer Sauteur, Patrick M; Relly, Christa; Hug, Martina; Wittenbrink, Max M; Berger, Christoph

2013-06-01

Reptile-associated salmonellosis (RAS) in children has been reported primarily due to direct contact with turtles, but recently also due to indirect contact with more exotic reptiles, causing disease in infants. To evaluate risk factors for RAS, we reviewed the RAS cases published in the literature since 1965. A case was defined as a child ≤18 years of age with an epidemiological link by identification of Salmonella enterica in cultures from both the affected child and the exposed reptile. We identified a total of 177 otherwise healthy children (median age 1.0 years, range 2 days to 17.0 years). RAS manifested mainly with gastrointestinal disease, but 15% presented with invasive RAS, including septicemia, meningitis, and bone and joint infection. The children with invasive RAS were significantly younger than children with noninvasive disease (median age 0.17 and 2.0 years, preptiles other than turtles, including iguanas, bearded dragons, snakes, chameleons, and geckos. Children exposed to those latter reptiles usually kept indoors were younger than children exposed to turtles mostly kept outdoors (preptiles, other than turtles, kept indoors is associated with RAS at younger age and more invasive disease. This finding is helpful for recognizing or even preventing invasive RAS in young infants that are at highest risk.

Function of Corynebacterium glutamicum promoters in Eschrichia coli, Streptomyces lividans, and Baccillus subtilis

Czech Academy of Sciences Publication Activity Database

Pátek, Miroslav; Muth, G.; Wohlleben, W.

2003-01-01

Roč. 104, - (2003), s. 325-334 ISSN 0168-1656 R&D Projects: GA AV ČR IPP1050128; GA ČR GA525/01/0916 Institutional research plan: CEZ:AV0Z5020903 Keywords : corynebacterium glutamicum * escherichia coli * promoters Subject RIV: EE - Microbiology, Virology Impact factor: 2.543, year: 2003

Tumor-associated macrophages: Oblivious confederates in invasive mammary carcinoma

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Imtiaz Ahmed

2017-01-01

Full Text Available Background: The infiltrating margins of carcinomas are associated with presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Amongst the inflammatory cells, Tumor Associated Macrophages (TAMs play a key role in the tumorigenesis. This study elucidates the density of TAMs in invasive mammary carcinomas and attempts to establish aa association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Materials and Methods: 90 diagnosed archival cases of invasive mammary carcinomas at a tertiary care centre were included. Density of TAMs was assessed by using CD68 which is a pan-macrophage marker by immunohistochemistry on the archival tissue blocks. The density TAMs (CD68 positive cells was dichotomised into high (>50 CD68 positive cells/ HPF and low (<5050 CD68 positive cells/ HPF and compared with the above mentioned pathological variables using appropriate statistical tests. Results: The density of TAMs was significantly higher around the infiltrating edge of the carcinoma in comparison to the adjoining normal terminal duct lobular units. The density of TAMs was more in the infiltrating edge of the tumor than within the tumor nodule/nests. A higher TAM density showed a significant association in tumors having large tumor size, higher histological grade, nodal metastasis, absence of ER and PR expression and Her2Neu overexpression (p value <0.05. Conclusion: TAMs play an important role in tumor progression in invasive mammary carcinomas. This is as a result of the multiple roles enacted by TAMs in the various stages of tumor development starting from tumor growth, invasion, angiogenesis and metastases. Targeted therapy against TAMs has great potential in the being important components of future treatment strategies against breast carcinomas.

Resurgence of diphtheria in rural areas of North Karnataka, India

OpenAIRE

Mahantesh V Parande; Subarna Roy; B G Mantur; Aisha M Parande; Rupali S Shinde

2017-01-01

Background: A diphtheria outbreak was identified from Vijayapura (formerly Bijapur) district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP) in North Karnataka since then. Objectives: A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Materials and Methods: Throat swabs from 432 suspected cases of dipht...

Seroprevalence and Determinants of Immunity to Diphtheria for Children Living in Two Districts of Contrasting Incidence During an Outbreak in East Java, Indonesia.

Science.gov (United States)

Hughes, Gareth J; Mikhail, Amy F W; Husada, Dominicus; Irawan, Eveline; Kafatos, George; Bracebridge, Samantha; Pebody, Richard; Efstratiou, Androulla

2015-11-01

In 2012, an ongoing outbreak of diphtheria in Indonesia was focused in the province of East Java. There was a need to assess vaccine coverage and immunity gaps in children. We conducted a cross-sectional seroprevalence and vaccine coverage survey of children 1-15 years of age in 2 districts of East Java: one of high incidence (on the island of Madura) and one of low incidence (on the mainland). From each district, we sampled 150 children (10 children per year of age). Sera and throat swabs were taken to determine immunity and carriage status. Immunity was defined as ≥0.1 international unit/mL of antibody to diphtheria toxin. A total of 297 children were selected to participate in the study. Coverage of three doses of combined vaccine for diphtheria, tetanus and pertussis was significantly lower (P Java. Immunity in high incidence districts is likely because of natural immunity acquired through exposure to toxigenic C. diphtheriae. Booster vaccines are essential for achieving protective levels of immunity.

Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study.

Science.gov (United States)

Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

2014-06-21

Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist

Characterization of Staphylococcus and Corynebacterium clusters in the human axillary region.

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Chris Callewaert

Full Text Available The skin microbial community is regarded as essential for human health and well-being, but likewise plays an important role in the formation of body odor in, for instance, the axillae. Few molecular-based research was done on the axillary microbiome. This study typified the axillary microbiome of a group of 53 healthy subjects. A profound view was obtained of the interpersonal, intrapersonal and temporal diversity of the human axillary microbiota. Denaturing gradient gel electrophoresis (DGGE and next generation sequencing on 16S rRNA gene region were combined and used as extent to each other. Two important clusters were characterized, where Staphylococcus and Corynebacterium species were the abundant species. Females predominantly clustered within the Staphylococcus cluster (87%, n = 17, whereas males clustered more in the Corynebacterium cluster (39%, n = 36. The axillary microbiota was unique to each individual. Left-right asymmetry occurred in about half of the human population. For the first time, an elaborate study was performed on the dynamics of the axillary microbiome. A relatively stable axillary microbiome was noticed, although a few subjects evolved towards another stable community. The deodorant usage had a proportional linear influence on the species diversity of the axillary microbiome.

Dot immunoassay for the simultaneous determination of postvaccination immunity against pertussis, diphtheria, and tetanus.

Science.gov (United States)

Khramtsov, Pavel; Bochkova, Maria; Timganova, Valeria; Zamorina, Svetlana; Rayev, Mikhail

2017-06-01

A dot immunoassay for simultaneous semiquantitative detection of IgG against tetanus toxoid (Ttx) and diphtheria toxoid (Dtx) and qualitative detection of anti-Bordetella pertussis IgGs in human blood serum using carbon nanoparticles functionalized with streptococcal protein G was developed. Inactivated B. pertussis cells in suspension form were used as an antigen in the immunoassay. Pertussis, tetanus, and diphtheria antigens were separately spotted onto nitrocellulose strips, and then the immunostrips were successively incubated with blood sera and a suspension of carbon nanoparticles. The immunostrips were then scanned with a flatbed scanner, and the images obtained were processed with ImageJ. One hundred fifty-five venous blood serum samples from children vaccinated with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine were tested in comparison with a conventional ELISA and agglutination test. The total time required for analysis of 32 serum samples was less than 3 h. Comparison between the results of the dot immunoassay and the corresponding ELISA/agglutination test revealed a high level of agreement (Cohen's kappa between 0.765 and 0.813). The lower limit of quantification was 0.06 IU/ml for anti-Ttx and anti-Dtx. The intra-assay coefficients of variation were less than 15% for anti-Ttx and anti-Dtx and less than 10% for anti-pertussis. The diagnostic sensitivity of detection of the antibody protection level was 93.5% for anti-Ttx [95% confidence interval (CI) 83.5-97.9%], 92.4% for anti-Dtx (95% CI 80.9297.5%), and 90.2% for anti-pertussis (95% CI 75.9-96.8%). The diagnostic specificity was 90.9% for anti-Ttx (95% CI 57.1-99.5%), 85% for anti-Dtx (95% CI 61.1-96.0%), and 89.3% for anti-pertussis (95%CI 80.8-94.5%). The dot immunoassay developed does not require expensive reading equipment, and allows detection of antibodies against three antigens in a single analysis. The immunostrips can be stored for a long time without changes in the

Plant Invasions Associated with Change in Root-Zone Microbial Community Structure and Diversity.

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Richard R Rodrigues

Full Text Available The importance of plant-microbe associations for the invasion of plant species have not been often tested under field conditions. The research sought to determine patterns of change in microbial communities associated with the establishment of invasive plants with different taxonomic and phenetic traits. Three independent locations in Virginia, USA were selected. One site was invaded by a grass (Microstegium vimineum, another by a shrub (Rhamnus davurica, and the third by a tree (Ailanthus altissima. The native vegetation from these sites was used as reference. 16S rRNA and ITS regions were sequenced to study root-zone bacterial and fungal communities, respectively, in invaded and non-invaded samples and analyzed using Quantitative Insights Into Microbial Ecology (QIIME. Though root-zone microbial community structure initially differed across locations, plant invasion shifted communities in similar ways. Indicator species analysis revealed that Operational Taxonomic Units (OTUs closely related to Proteobacteria, Acidobacteria, Actinobacteria, and Ascomycota increased in abundance due to plant invasions. The Hyphomonadaceae family in the Rhodobacterales order and ammonia-oxidizing Nitrospirae phylum showed greater relative abundance in the invaded root-zone soils. Hyphomicrobiaceae, another bacterial family within the phyla Proteobacteria increased as a result of plant invasion, but the effect associated most strongly with root-zones of M. vimineum and R. davurica. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt showed bacteria responsible for nitrogen cycling in soil increased in relative abundance in association with plant invasion. In agreement with phylogenetic and functional analyses, greater turnover of ammonium and nitrate was associated with plant invasion. Overall, bacterial and fungal communities changed congruently across plant invaders, and support the hypothesis that

Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002-20121.

Science.gov (United States)

Strollo, Sara; Lionakis, Michail S; Adjemian, Jennifer; Steiner, Claudia A; Prevots, D Rebecca

2016-01-01

Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis-associated hospitalizations in the United States. We extracted data for 33 states for 2002-2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005-2012 for men (annual change -3.9%) and women (annual change -4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease.

INVASIVESNET towards an International Association for Open Knowledge on Invasive Alien Species

Science.gov (United States)

Lucy, Frances; Roy, Helen; Simpson, Annie; Carlton, James T.; Hanson, John Mark; Magellan, Kit; Campbell, Marnie L.; Costello, Mark J.; Pagad, Shyama; Hewitt, Chad L; McDonald, Justin; Cassey, Phillip; Thomaz, Sidinei M; Katsanevakis, Stelios; Zenetos, Argyro; Tricarico, Elena; Boggero, Angela; Groom, Quentin J.; Adriaens, Tim; Vanderhoeven, Sonia; Torchin, Mark E.; Hufbauer, Ruth A.; Fuller, Pam; Carman, Mary R; Conn, David Bruce; Vitule, Jean R. S.; Canning-Clode, João; Galil, Bella S; Ojaveer, Henn; Bailey, Sarah A; Therriault, Thomas W; Claudi, Renata; Gazda, Anna; Dick, Jaimie T A; Caffrey, Joe; Witt, Arne; Kenis, Marc; Lehtiniemi, Maiju; Helmisaari, Harry; Panov, Vadim E

2016-01-01

In a world where invasive alien species (IAS) are recognised as one of the major threats to biodiversity, leading scientists from five continents have come together to propose the concept of developing an international association for open knowledge and open data on IAS—termed “INVASIVESNET”. This new association will facilitate greater understanding and improved management of invasive alien species (IAS) and biological invasions globally, by developing a sustainable network of networks for effective knowledge exchange. In addition to their inclusion in the CBD Strategic Plan for Biodiversity, the increasing ecological, social, cultural and economic impacts associated with IAS have driven the development of multiple legal instruments and policies. This increases the need for greater co-ordination, co-operation, and information exchange among scientists, management, the community of practice and the public.

Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms

DEFF Research Database (Denmark)

Lopez-Perez, Mary; Villasis, Elizabeth; Machado, Ricardo L D

2012-01-01

Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC) invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins, which are polymorphic and not fully...... characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1) and five...... pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant...

Characterization and antimicrobial susceptibility of one antibiotic-sensitive and one multidrug-resistant Corynebacterium kroppenstedtii strain isolated from patients with granulomatous mastitis

Directory of Open Access Journals (Sweden)

I. Fernández-Natal

2016-11-01

Full Text Available Human infections associated with Corynebacterium kroppenstedtii are rarely reported, and this organism is usually described as antibiotic sensitive. Almost all published cases of C. kroppenstedtii infections have been associated with breast pathology in women and have been described in New Zealand, France, Canada, India and Japan. Here we describe the microbiologic characteristics of two strains isolated from two women diagnosed of granulomatous mastitis in Spain. One C. kroppenstedtii isolate was antibiotic sensitive while the other was multidrug resistant. Biochemical identification was possible using a wide battery of methods including API Coryne V2.0, API Strep, API NH, API NE, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene amplification and sequencing. Antimicrobial susceptibility to 28 antibiotics as determined by Etest showed one isolate being sensitive to benzylpenicillin, ciprofloxacin, moxifloxacin, gentamicin, vancomycin, clindamycin, tetracycline, linezolid and rifampin. The second isolate showed resistance to ciprofloxacin, moxifloxacin, clindamycin, tetracycline and rifampin. The multidrug-resistant isolate contained the erm(X, tet(W, cmx, aphA1-IAB, strAB and sul1 resistance genes known from the R plasmid pJA144188 of Corynebacterium resistens. These genes were absent in the genome of the antibiotic-sensitive isolate. This report confirms the tropism of this microorganism for women's breasts and presents the first description of a multidrug-resistant C. kroppenstedtii strain.

Plasmid Vectors for Testing In Vivo Promoter Activities in Corynebacterium glutamicum and Rhodococcus erythropolis

Czech Academy of Sciences Publication Activity Database

Knoppová, Monika; Phensaijai, M.; Veselý, Martin; Zemanová, Martina; Nešvera, Jan; Pátek, Miroslav

2007-01-01

Roč. 55, - (2007), s. 234-239 ISSN 0343-8651 R&D Projects: GA ČR GA526/04/0542; GA ČR GA204/06/0330 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium * rhodoccoccus * promoter-probe vectors Subject RIV: EE - Microbiology , Virology Impact factor: 1.167, year: 2007

Channels Formed by Botulinum, Tetanus, and Diphtheria Toxins in Planar Lipid Bilayers: Relevance to Translocation of Proteins across Membranes

Science.gov (United States)

Hoch, David H.; Romero-Mira, Miryam; Ehrlich, Barbara E.; Finkelstein, Alan; Dasgupta, Bibhuti R.; Simpson, Lance L.

1985-03-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as ``tunnel proteins'' for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.

Bone erosion and subacromial bursitis caused by diphtheria-tetanus-poliomyelitis vaccine.

Science.gov (United States)

Salmon, J H; Geoffroy, M; Eschard, J P; Ohl, X

2015-11-17

Revaxis(®) is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare. We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolic engineering of the L-valine biosynthesis pathway in Corynebacterium glutamicum using promoter activity modulation

Czech Academy of Sciences Publication Activity Database

Holátko, Jiří; Elišáková, Veronika; Prouza, Marek; Sobotka, Miroslav; Nešvera, Jan; Pátek, Miroslav

2009-01-01

Roč. 139, č. 3 (2009), s. 203-210 ISSN 0168-1656 R&D Projects: GA ČR GA204/06/0330 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * valine production * promoters Subject RIV: EE - Microbiology, Virology Impact factor: 2.881, year: 2009

Corynebacterium renale as a cause of reactions to the complement fixation test for Johne's disease

NARCIS (Netherlands)

Gilmour, N.J.L.; Goudswaard, J.

Complement fixation (C.F.) tests and fluorescent antibody (F.A.) tests were carried out on sera from rabbits inoculated with Corynebacterium renale and Mycobacterium johnei, and on sera from cattle with C. renale pyelonephritis and with Johne's disease. Cross-reactions were a feature of the C.F.

Flux through the tetrahydrodipicolinate succinylase pathway is dispensable for L-lysine production in Corynebacterium glutamicum.

Science.gov (United States)

Shaw-Reid, C A; McCormick, M M; Sinskey, A J; Stephanopoulos, G

1999-03-01

The N-succinyl-LL-diaminopimelate desuccinylase gene (dapE) in the four-step succinylase branch of the L-lysine biosynthetic pathway of Corynebacterium glutamicum was disrupted via marker-exchange mutagenesis to create a mutant strain that uses only the one-step meso-diaminopimelate dehydrogenase branch to overproduce lysine. This mutant strain grew and utilized glucose from minimal medium at the same rate as the parental strain. In addition, the dapE- strain produced lysine at the same rate as its parent strain. Transformation of the parental and dapE- strains with the amplified meso-diaminopimelate dehydrogenase gene (ddh) on a plasmid did not affect lysine production in either strain, despite an eightfold amplification of the activity of the enzyme. These results indicate that the four-step succinylase pathway is dispensable for lysine overproduction in shake-flask culture. In addition, the one-step meso-diaminopimelate dehydrogenase pathway does not limit lysine flux in Corynebacterium under these conditions.

Factors associated with airway colonisation and invasion due to ...

African Journals Online (AJOL)

Factors associated with airway colonisation and invasion due to Klebsiella spp. ... for nosocomial infections which occurred more conunonly with antibiotic-resistant organisms. ... acute community-acquired chest infections, and nosocomial chest infections. Primary acute conununity-acquired pneumonia was unconunon.

Improved L-ornithine production in Corynebacterium crenatum by introducing an artificial linear transacetylation pathway.

Science.gov (United States)

Shu, Qunfeng; Xu, Meijuan; Li, Jing; Yang, Taowei; Zhang, Xian; Xu, Zhenghong; Rao, Zhiming

2018-05-04

L-Ornithine is a non-protein amino acid with extensive applications in the food and pharmaceutical industries. In this study, we performed metabolic pathway engineering of an L-arginine hyper-producing strain of Corynebacterium crenatum for L-ornithine production. First, we amplified the L-ornithine biosynthetic pathway flux by blocking the competing branch of the pathway. To enhance L-ornithine synthesis, we performed site-directed mutagenesis of the ornithine-binding sites to solve the problem of L-ornithine feedback inhibition for ornithine acetyltransferase. Alternatively, the genes argA from Escherichia coli and argE from Serratia marcescens, encoding the enzymes N-acetyl glutamate synthase and N-acetyl-L-ornithine deacetylase, respectively, were introduced into Corynebacterium crenatum to mimic the linear pathway of L-ornithine biosynthesis. Fermentation of the resulting strain in a 5-L bioreactor allowed a dramatically increased production of L-ornithine, 40.4 g/L, with an overall productivity of 0.673 g/L/h over 60 h. This demonstrates that an increased level of transacetylation is beneficial for L-ornithine biosynthesis.

Housing is positively associated with invasive exotic plant species richness in New England, USA.

Science.gov (United States)

Gavier-Pizarro, Gregorio I; Radeloff, Volker C; Stewart, Susan I; Huebner, Cynthia D; Keuler, Nicholas S

2010-10-01

Understanding the factors related to invasive exotic species distributions at broad spatial scales has important theoretical and management implications, because biological invasions are detrimental to many ecosystem functions and processes. Housing development facilitates invasions by disturbing land cover, introducing nonnative landscaping plants, and facilitating dispersal of propagules along roads. To evaluate relationships between housing and the distribution of invasive exotic plants, we asked (1) how strongly is housing associated with the spatial distribution of invasive exotic plants compared to other anthropogenic and environmental factors; (2) what type of housing pattern is related to the richness of invasive exotic plants; and (3) do invasive plants represent ecological traits associated with specific housing patterns? Using two types of regression analysis (best subset analysis and hierarchical partitioning analysis), we found that invasive exotic plant richness was equally or more strongly related to housing variables than to other human (e.g., mean income and roads) and environmental (e.g., topography and forest cover) variables at the county level across New England. Richness of invasive exotic plants was positively related to area of wildland-urban interface (WUI), low-density residential areas, change in number of housing units between 1940 and 2000, mean income, plant productivity (NDVI), and altitudinal range and rainfall; it was negatively related to forest area and connectivity. Plant life history traits were not strongly related to housing patterns. We expect the number of invasive exotic plants to increase as a result of future housing growth and suggest that housing development be considered a primary factor in plans to manage and monitor invasive exotic plant species.

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

DEFF Research Database (Denmark)

Gyhrs, A; Pedersen, B K; Bygbjerg, I

1991-01-01

(1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

A Novel Corynebacterium glutamicum l-Glutamate Exporter.

Science.gov (United States)

Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

2018-03-15

Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to

Tetanus and diphtheria immunity among term and preterm infant-mother pairs in Turkey, a country where maternal and neonatal tetanus have recently been eliminated.

Science.gov (United States)

Erener-Ercan, Tugba; Aslan, Mustafa; Vural, Mehmet; Erginoz, Ethem; Kocazeybek, Bekir; Ercan, Gokmen; Turkgeldi, Lale Wetherilt; Perk, Yildiz

2015-03-01

The aim of our study was to investigate the anti-tetanus and anti-diphtheria antibody titres and the placental transfer of these antibodies in a group of vaccinated and unvaccinated mothers and their term or preterm offsprings. Anti-tetanus and anti-diphtheria toxoid IgG antibodies were measured quantitatively by ELISA in 91 infant-mother pairs. Protective concentrations of anti-tetanus and anti-diphtheria were found in 58.3 and 50% of mothers in the unvaccinated group and 94.5 and 85.5% of the mothers in the vaccinated group. Protective concentrations were found in 63.9 and 50% of cord samples, respectively, in the unvaccinated group and in 96.4 and 85.5% of cord samples, respectively, in the vaccinated group (p = 0.0001). There were no differences in the maternal and cord geometric mean concentrations (GMCs) of anti-toxoid antibodies between those who received two doses or one dose of Td. The GMCs of maternal and cord anti-tetanus and anti-diphtheria were statistically similar between preterm and term groups. Placental transfer ratios (TR) for anti-tetanus and anti-diphtheria were 175 and 150%, respectively, in the preterm group and 213 and 178%, respectively, in the term group. There was a strong correlation between maternal and cord anti-toxoid antibody levels. Maternal vaccination was the only predictor of having protective concentrations of anti-toxoid antibodies in cord blood. Vaccinating pregnant women with at least one dose of Td would confer protection for both the term and preterm infant-mother pairs. Therefore, health personnel caring for pregnant women have the responsibility to emphasize the importance of Td vaccination to avoid missed immunization opportunities.

Evaluation of Immunogenicity of Yersinia enterocolitica O:8 Oligopolysaccaride-DiphtheriaeToxoide Conjugate in Mice

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SM Rezavian

2015-06-01

Full Text Available Background & objectives: Yersiniosis is created by Yersinia enterocolitica O:8 and causes problems in the world especialy in cold and mild countries. The purpose of this study is to evaluate the immunogenicity of Yersinia enterocolitica O:8 oligopolysaccaride (OPS conjugate to diphtheria toxoid (DT as a vaccine candidate.   Methods : After cultivation of bacteria, the LPS were isolated by modified hot phenol method. Then dialysis and concentration were done and the OPS were extracted by acetic acid 2%. To conjugate with diphtheria toxoid, ADH was used as a spacer molecule and EDAC as a linker. Conjugate was purified by gel filtration. Then 4 groups of female BALB/c mice were selected (15 mice in each group. Injection was performed intraperitoneally in three doses with two weeks interval. Then serum samples were collected and antibody response against OPS was measured by indirect ELISA method for detection of total IgG, IgA, IgM, IgG1, IgG2a, IgG2b and IgG3.   Results: After second and third doses, OPS-DT recieved group showed significant increase in all types of antibodies titer in anti-OPS in comparison to group that recived nonconjugated OPS. The increase in titer of antibodies was as: OPS-DT>OPS>DT. A remarkable increase was shown in total IgG and IgM titers (with total amount of 3204 and 670, respectively. In IgG1 subclass the amount was 920 and in other subclasses of IgG (IgG3, IgG2a and IgG2b the amounts were 910, 110, and 99, respectively.   Conclusion: The results shows that OPS of Yersinia enterocolitica O:8 increases the anti-OPS antibodies in the form of conjugate with diphtheria toxoid and could be considered as an appropriate vaccine candidate.

Optimization of lysine metabolism in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Rytter, Jakob Vang

,000,000 tons. The aim of this project is to optimize the yield of lysine in C. glutamicum using metabolic engineering strategies. According to a genome scale model of C. glutamicum, theoretically there is much room for increasing the lysine yield (Kjeldsen and Nielsen 2009). Lysine synthesis requires NADPH......Commercial pig and poultry production use the essential amino acid lysine as a feed additive with the purpose of optimizing the feed utilization. Lysine is produced by a fermentation process involving either Corynebacterium glutamicum or Escherichia coli. The global annual production is around 1...... the project intends to eliminate. PGI catalyzes the conversion of alpha-D-glucose-6-phosphate to fructose-6-phosphate just downstream of the branch in the glycolysis, but it also catalyzes the reverse reaction. It is unknown whether up- or down-regulation of the pgi is required to increase the flux through...

[A large-scale epidemic of diphtheria in Moscow in recent years: patterns of development].

Science.gov (United States)

Chistiakova, G G; Filatov, N N; Korzhenkova, M P; Solodovnikov, Iu P; Lytkina, I N; Maksimova, N M; Markina, S S

2001-01-01

Data on the dynamics of diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered. Mainly these groups determined tense epidemiological situation in diphtheria in Moscow.

Immobilazation of aerobic microorganisms on glassy sintered material, illustrated by the example of the production of L leucine using Corynebacterium glutamicum. Immobilisierung von aeroben Mikroorganismen an Glassintermaterial am Beispiel der L-Leucin-Produktion mit Corynebacterium glutamicum

Energy Technology Data Exchange (ETDEWEB)

Buechs, J.

1988-12-01

The aim of this study was to develop the carrier fixation of aerobic microorganisms on open-pore sintered glass material. The fermentative production of L-leucine from {alpha} cetonic isocaproic acid with Corynebacterium glutamicum was chosen as an example of a microbial process with a high demand of oxygen. (orig.).

Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination : Preparation, characterization and evaluation in guinea pigs

NARCIS (Netherlands)

Amidi, Maryam; Pellikaan, Hubert C.; Hirschberg, Hoang; de Boerd, Anne H.; Crommelin, Daan J. A.; Hennink, Wim E.; Kersten, Gideon; Jiskoot, Wim

2007-01-01

this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a

Synthetic promoter libraries for Corynebacterium glutamicum

DEFF Research Database (Denmark)

Rytter, Jakob Vang; Helmark, Søren; Chen, Jun

2014-01-01

The ability to modulate gene expression is an important genetic tool in systems biology and biotechnology. Here, we demonstrate that a previously published easy and fast PCR-based method for modulating gene expression in lactic acid bacteria is also applicable to Corynebacterium glutamicum. We co...... promoter library (SPL) technology is convenient for modulating gene expression in C. glutamicum and should have many future applications, within basic research as well as for optimizing industrial production organisms....... constructed constitutive promoter libraries based on various combinations of a previously reported C. glutamicum -10 consensus sequence (gngnTA(c/t)aaTgg) and the Escherichia coli -35 consensus, either with or without an AT-rich region upstream. A promoter library based on consensus sequences frequently found...... in low-GC Gram-positive microorganisms was also included. The strongest promoters were found in the library with a -35 region and a C. glutamicum -10 consensus, and this library also represents the largest activity span. Using the alternative -10 consensus TATAAT, which can be found in many other...

Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002–20121

Science.gov (United States)

Strollo, Sara; Lionakis, Michail S.; Adjemian, Jennifer; Steiner, Claudia A.

2017-01-01

Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis–associated hospitalizations in the United States. We extracted data for 33 states for 2002–2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005–2012 for men (annual change –3.9%) and women (annual change –4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease. PMID:27983497

Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms.

Directory of Open Access Journals (Sweden)

Mary Lopez-Perez

Full Text Available Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL and the Reticulocyte Binding-Like (PfRh proteins, which are polymorphic and not fully characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1 and five members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5 families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr. Moreover, the invasion pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN variant. The ebl and Pfrh expression levels in a field isolate displaying the NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the major players in this invasion pathway. Notably, our studies demonstrate the uniqueness of the Peruvian P. falciparum field isolates in terms of their invasion profiles and ligand polymorphisms, and present a unique opportunity for studying the ability of P. falciparum parasites to expand their invasion repertoire after being reintroduced to human populations. The present study is directly relevant to asexual blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to

Accessibility Changes within Diphtheria Toxin T Domain upon Membrane Penetration Probed by Hydrogen Exchange and Mass Spectrometry

Czech Academy of Sciences Publication Activity Database

Man, Petr; Montagner, C.; Vitrac, H.; Kavan, Daniel; Pichard, S.; Gillet, D.; Forest, E.; Forge, V.

2011-01-01

Roč. 414, č. 1 (2011), s. 123-134 ISSN 0022-2836 Institutional research plan: CEZ:AV0Z50200510 Keywords : diphtheria toxin * translocation domain * protein/membrane interactions Subject RIV: CE - Biochemistry Impact factor: 4.001, year: 2011

Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

NARCIS (Netherlands)

Melker, de H.

1999-01-01

In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.

In a

Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.

Science.gov (United States)

Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

2017-01-02

An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel

Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq

Science.gov (United States)

Al-Bayati, Firas A.; Al-Mola, Hassan F.

2008-01-01

Antimicrobial activity of organic and aqueous extracts from fruits, leaves and roots of Tribulus terrestris L., an Iraqi medicinal plant used as urinary anti-infective in folk medicine, was examined against 11 species of pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Corynebacterium diphtheriae, Escherichia coli, Proteus vulgaris, Serratia marcescens, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans using microdilution method in 96 multiwell microtiter plates. All the extracts from the different parts of the plant showed antimicrobial activity against most tested microorganisms. The most active extract against both Gram-negative and Gram-positive bacteria was ethanol extract from the fruits with a minimal inhibitory concentration (MIC) value of 0.15 mg/ml against B. subtilis, B. cereus, P. vulgaris and C. diphtheriae. In addition, the same extract from the same plant part demonstrated the strongest antifungal activity against C. albicans with an MIC value of 0.15 mg/ml. PMID:18257138

Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates.

Science.gov (United States)

Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P; Nielsen, Flemming; Grandjean, Philippe; Budtz-Jørgensen, Esben; Heilmann, Carsten

2016-01-01

Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results suggested that cellular mechanisms right after antigen exposure should be investigated more closely to identify possible mechanisms of immunosuppression from PFAS.

Identification of clinically relevant Corynebacterium strains by Api Coryne, MALDI-TOF-mass spectrometry and molecular approaches.

Science.gov (United States)

Alibi, S; Ferjani, A; Gaillot, O; Marzouk, M; Courcol, R; Boukadida, J

2015-09-01

We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 97 Corynebacterium clinical in comparison to identification strains by Api Coryne and MALDI-TOF-MS using 16S rRNA gene and hypervariable region of rpoB genes sequencing as a reference method. C. striatum was the predominant species isolated followed by C. amycolatum. There was an agreement between Api Coryne strips and MALDI-TOF-MS identification in 88.65% of cases. MALDI-TOF-MS was unable to differentiate C. aurimucosum from C. minutissimum and C. minutissimum from C. singulare but reliably identify 92 of 97 (94.84%) strains. Two strains remained incompletely identified to the species level by MALDI-TOF-MS and molecular approaches. They belonged to Cellulomonas and Pseudoclavibacter genus. In conclusion, MALDI-TOF-MS is a rapid and reliable method for the identification of Corynebacterium species. However, some limits have been noted and have to be resolved by the application of molecular methods. Copyright © 2015. Published by Elsevier SAS.

Effect of diphtheria toxin T-domain on endosomal pH

Directory of Open Access Journals (Sweden)

A. J. Labyntsev

2015-08-01

Full Text Available A key step in the mode of cytotoxic action of diphtheria toxin (DT is the transfer of its catalytic domain (Cd from endosomes into the cytosol. The main activity in this process is performed by the transport domain (Td, but the molecular mechanism of its action remains unknown. We have previously shown that Td can have some influence on the endosomal transport of DT. The aim of this work was to study the effect of diphtheria toxin on the toxin compartmentalization in the intracellular transporting pathway and endosomal pH. We used recombinant fragments of DT, which differed only by the presence of Td in their structure, fused with fluorescent proteins. It was shown that the toxin fragment with Td moved slower by the pathway early-late endosomes-lysosomes, and had a slightly different pattern of colocalization with endosomal markers than DT fragment without Td. In addition, endosomes containing DT fragments with Td had a constant pH of about 6.5 from the 10th to 50th minute of observation, for the same time endosomes containing DT fragments without Td demons­trated a decrease in pH from 6.3 to 5.5. These results indicate that Td inhibits acidification of endosomal medium. One of possible explanations for this may be the effect of the ion channel formed by the T-domain on the process of the endosomal acidification. This property of Td may not only inhibit maturation of endosomes but also inhibit activation of endosomal pH-dependent proteases, and this promotes successful transport of Cd into the cell cytosol.

Complete Sucrose Metabolism Requires Fructose Phosphotransferase Activity in Corynebacterium glutamicum To Ensure Phosphorylation of Liberated Fructose

OpenAIRE

Dominguez, H.; Lindley, N. D.

1996-01-01

Sucrose uptake by Corynebacterium glutamicum involves a phosphoenolpyruvate-dependent sucrose phosphotransferase (PTS), but in the absence of fructokinase, further metabolism of the liberated fructose requires efflux of the fructose and reassimilation via the fructose PTS. Mutant strains lacking detectable fructose-transporting PTS activity accumulated fructose extracellularly but consumed sucrose at rates comparable to those of the wild-type strain.

‘Corynebacterium fournierii,’ a new bacterial species isolated from the vaginal sample of a patient with bacterial vaginosis

Directory of Open Access Journals (Sweden)

K. Diop

2017-07-01

Full Text Available Here we describe briefly ‘Corynebacterium fournierii’ strain Marseille P2948 (= CSUR P2948 = DSM103271, a new bacterium that was isolated from the vaginal sample of a 21-year-old woman with bacterial vaginosis.

A meta-analysis of trait differences between invasive and non-invasive plant species

OpenAIRE

van Kleunen, Mark; Weber, Ewald; Fischer, Markus

2010-01-01

A major aim in ecology is identifying determinants of invasiveness. We performed a meta-analysis of 117 field or experimental-garden studies that measured pair-wise trait differences of a total of 125 invasive and 196 non-invasive plant species in the invasive range of the invasive species. We tested whether invasiveness is associated with performance-related traits (physiology, leaf-area allocation, shoot allocation, growth rate, size and fitness), and whether such associations depend on typ...

Desulfurization of dibenzothiophene by Corynebacterium sp. strain SY1

International Nuclear Information System (INIS)

Omori, Toshio; Monna, L.; Saiki, Yuko; Kodama, Tohru

1992-01-01

Strain SY1, identified as a Corynebacterium sp., was isolated on the basis of the ability to utilize dibenzothiophene (DBT) as a sole source of sulfur. Strain SY1 could utilize a wide range of organic and inorganic sulfur compounds, such as DBT sulfone, dimethyl sulfide, dimethyl sulfoxide, dimethyl sulfone, CS 2 , FeS 2 , and even elemental sulfur. Strain SY1 metabolized DBT to dibenzothiophene-5-oxide, DBT sulfone, and 2-hydroxybiphenyl, which was subsequently nitrated to produce at least two different hydroxynitrobiphenyls during cultivation. These metabolites were separated by silica gel column chromatography and identified by nuclear magnetic resonance, UV, and mass spectral techniques. Resting cells of SY1 desulfurized toluenesulfonic acid and released sulfite anion. On the basis of these results, a new DBT degradation pathway is proposed

Genome sequence of Corynebacterium pseudotuberculosis biovar equi strain 258 and prediction of antigenic targets to improve biotechnological vaccine production

DEFF Research Database (Denmark)

Soares, Siomar C; Trost, Eva; Ramos, Rommel T J

2013-01-01

Corynebacterium pseudotuberculosis is the causative agent of several veterinary diseases in a broad range of economically important hosts, which can vary from caseous lymphadenitis in sheep and goats (biovar ovis) to ulcerative lymphangitis in cattle and horses (biovar equi). Existing vaccines ag...

Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.

Science.gov (United States)

Vlug, Eva J; van de Ven, Robert A H; Vermeulen, Jeroen F; Bult, Peter; van Diest, Paul J; Derksen, Patrick W B

2013-10-01

Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

The effects of ascorbic acid on diphtheria toxin and intoxicated hela cells

International Nuclear Information System (INIS)

Clark, C.E.; Smith, T.J.

1976-01-01

Ascorbic acid (vitamin C) prevented diphtheria toxin from inhibiting the incorporation of [U- 14 C]-alanine into trichloroacetic acid precipitable material in HeLa cells. Ascorbic acid did not exhibit an effect on the adenosine diphosphate-ribosylation of amino acyl transferase 2 nor did it separate fragment A from fragment B in ''nicked'' toxin. A non-specific reducing agent, para-methylaminophenol sulfate, exhibited an effect of HeLa cells very similar to the results of ascorbic acid. Citric acid, a tricarboxylic acid, had no effect on HeLa cells. (auth.)

Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

Directory of Open Access Journals (Sweden)

Ahmed Al-Jazzar

2016-12-01

Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

Corynebacterium glutamicum for Sustainable Bioproduction: From Metabolic Physiology to Systems Metabolic Engineering.

Science.gov (United States)

Becker, Judith; Gießelmann, Gideon; Hoffmann, Sarah Lisa; Wittmann, Christoph

Since its discovery 60 years ago, Corynebacterium glutamicum has evolved into a workhorse for industrial biotechnology. Traditionally well known for its remarkable capacity to produce amino acids, this Gram-positive soil bacterium, has become a flexible, efficient production platform for various bulk and fine chemicals, materials, and biofuels. The central turnstile of all these achievements is our excellent understanding of its metabolism and physiology. This knowledge base, together with innovative systems metabolic engineering concepts, which integrate systems and synthetic biology into strain engineering, has upgraded C. glutamicum into one of the most successful industrial microorganisms in the world.

First report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus).

Science.gov (United States)

Oliveira, Manuela; Barroco, Cynthia; Mottola, Carla; Santos, Raquel; Lemsaddek, Abdelhak; Tavares, Luis; Semedo-Lemsaddek, Teresa

2014-09-21

Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis, a common disease in small ruminant populations throughout the world and responsible for a significant economic impact for producers. To our knowledge, this is the first characterization of C. pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus). In this study, phenotypic and genotypic identification methods allocated the swine isolates in C. pseudotuberculosis biovar ovis. The vast majority of the isolates were able to produce phospholipase D and were susceptible to most of the antimicrobial compounds tested. Macrorestriction patterns obtained by Pulsed Field Gel Electrophoresis (PFGE) grouped the C. pseudotuberculosis in two clusters with a high similarity index, which reveals their clonal relatedness. Furthermore, swine isolates were compared with C. pseudotuberculosis from caprines and PFGE patterns also showed high similarity, suggesting the prevalence of dominant clones and a potential cross-dissemination between these two animal hosts. This work represents the first report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig and alerts for the importance of the establishment of suitable control and sanitary management practices to control the infection and avoid further dissemination of this important pathogen to other animal hosts.

Immunity to tetanus and diphtheria in rural Africa

DEFF Research Database (Denmark)

Kurtzhals, J A; Kjeldsen, K; Hey, A S

1997-01-01

To assess the effect of the Expanded Program on Immunization (EPI) in rural Africa, blood samples were collected in two Kenyan sublocations. Serum antibodies against tetanus toxoid were measured in 155 individuals 1-70 years of age. Titers greater than the protective level of 0.01 IU/ml were found...... in 47% of the population. Protection was significantly higher in children born after the launching of the EPI (68%) and in women who had been at childbearing age since then (69%). Significantly lower protection was demonstrated in other age and sex-groups. The level of protection in children was equal...... in the two populations, whereas protection in fertile women was significantly lower in the population living a long distance from a health center. Diphtheria anti-toxin was measured in the samples from one sublocation, and 70 of 84 individuals (83%) had antibody levels greater than the protective level...

The WHO Review of the Possible Nonspecific Effects of Diphtheria-Tetanus-Pertussis Vaccine

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Benn, Christine S

2016-01-01

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...

Rational Design of a Corynebacterium glutamicum Pantothenate Production Strain and Ins Characterization by Metabolic Flux Analysis and Genome-Wide Transcriptional Profiling

Czech Academy of Sciences Publication Activity Database

Hüser, A.T.; Chassagnole, Ch.; Lindley, N.D.; Merkamm, M.; Guyonvarch, A.; Elišáková, Veronika; Pátek, Miroslav; Kalinowski, J.; Brune, I.; Pühler, A.; Tauch, A.

2005-01-01

Roč. 71, č. 6 (2005), s. 3255-3268 ISSN 0099-2240 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * metabolic flux Subject RIV: EE - Microbiology, Virology Impact factor: 3.818, year: 2005

Pyruvate:Quinone Oxidoreductase in Corynebacterium glutamicum: Molecular Analysis of the pqo Gene, Significance of the Enzyme, and Phylogenetic Aspects

Czech Academy of Sciences Publication Activity Database

Schreiner, M. E.; Riedel, Ch.; Holátko, Jiří; Pátek, Miroslav; Eikmanns, B. J.

2006-01-01

Roč. 188, č. 4 (2006), s. 1341-1350 ISSN 0021-9193 R&D Projects: GA ČR GA525/04/0548 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * pqo * molecular analysis Subject RIV: EE - Microbiology, Virology Impact factor: 3.993, year: 2006

Mural endocarditis caused by Corynebacterium mustelae in a dog with a VSD.

Science.gov (United States)

Winter, Randolph L; Gordon, Sonya G; Zhang, Shuping; Hariu, Crystal D; Miller, Matthew W

2014-01-01

A 6 yr old female spayed large Munsterlander was evaluated following a 3 wk history of lethargy, inappetence, intermittent fever, and a recent change to the timing of her previously diagnosed heart murmur. Physical examination revealed marked dehydration, lethargy, and a grade 5/6 to-and-fro heart murmur that was auscultated best at the right sternal border. The dog was febrile, and echocardiography revealed a large, mobile, vegetative lesion in the right ventricular outflow tract associated with a ventricular septal defect (VSD). Mild aortic insufficiency was present. Corynebacterium mustelae (C. mustelae) was isolated from a pooled blood culture. Treatment of infective endocarditis (IE) was initiated along with supportive care, and the patient was discharged 9 days later. The dog remained without clinical signs 132 days after discharge. VSD is rarely mentioned as a predisposing factor for development of IE in veterinary literature; however, this report highlights that dogs with a VSD may be at risk for IE. To the authors' knowledge, this is the first documented case of a canine infection with C. mustelae. Infection with C. mustelae in this case represents a novel agent for IE in the dog.

Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid

Science.gov (United States)

de Groot, Anne Marit; Platteel, Anouk C. M.; Kuijt, Nico; van Kooten, Peter J. S.; Vos, Pieter Jan; Sijts, Alice J. A. M.; van der Maaden, Koen

2017-01-01

The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin’s physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro. It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID) immunization with subunit vaccines, which opens possibilities for future ID vaccination designs. PMID:29375544

Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid.

Science.gov (United States)

de Groot, Anne Marit; Platteel, Anouk C M; Kuijt, Nico; van Kooten, Peter J S; Vos, Pieter Jan; Sijts, Alice J A M; van der Maaden, Koen

2017-01-01

The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin's physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro . It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID) immunization with subunit vaccines, which opens possibilities for future ID vaccination designs.

Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid

Directory of Open Access Journals (Sweden)

Anne Marit de Groot

2017-12-01

Full Text Available The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin’s physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs, representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT and tetanus toxoid (TT intradermally. First, the piercing ability of the ceramic (alumina npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro. It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID immunization with subunit vaccines, which opens possibilities for future ID vaccination designs.

Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine

DEFF Research Database (Denmark)

Orntoft, Nikolaj W; Thorsen, Kasper; Benn, Christine S

2013-01-01

identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using......Background. Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. Methods. To investigate possible changes in gene expression after DTP vaccination, we...... expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. Results. We found very few transcripts to alter...

The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community

DEFF Research Database (Denmark)

Mogensen, Søren Wengel; Andersen, Andreas; Rodrigues, Amabelia

2017-01-01

Background We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s. Methods The child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV...

The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains

DEFF Research Database (Denmark)

Soares, Siomar C; Silva, Artur; Trost, Eva

2013-01-01

, Corynebacterium pseudotuberculosis infections pose a rising worldwide economic problem in ruminants. The complete genome sequences of 15 C. pseudotuberculosis strains isolated from different hosts and countries were comparatively analyzed using a pan-genomic strategy. Phylogenomic, pan-genomic, core genomic...

Safety and immunogenicity of tetanus-diphtheria-acellular pertussis vaccine administered to children 10 or 11 years of age.

Science.gov (United States)

Marshall, Gary S; Pool, Vitali; Greenberg, David P; Johnson, David R; Sheng, Xiaohua; Decker, Michael D

2014-11-01

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

BIOCHEMICAL AND PHYLOGENETIC STUDIES OF CreD OF Corynebacterium glutamicum

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Muhammad Tausif Chaudhry

2015-06-01

Full Text Available CreD characterized as Mg2+-dependent phosphohydrolase with conserved HD domain was involved in 4-cresol metabolism in Corynebacterium glutamicum. Native molecular mass of 54 kDa suggested that the biological unit is a dimer. No deoxynucleotide triphosphate triphosphohydrolase (dNTPase activity was detected for CreD. The apparent Km and Vmax values for 4-nitrophenyl phosphate were 0.35 mM and 16.23 M min-1 mg-1, respectively, while calculated values for kcat and kcat/Km were 0.4 s-1 and 1.14103 M-1 s-1, respectively. Among thiol group inhibitors, iodoacetic acid significantly inhibited phosphohydrolase activity. Sequence identity and phylogenetic analysis suggested universal existence of CreD homologues. Involvement of HD-domain hydrolase in aromatic degradation has not been reported before.

Production of L-valine from metabolically engineered Corynebacterium glutamicum.

Science.gov (United States)

Wang, Xiaoyuan; Zhang, Hailing; Quinn, Peter J

2018-05-01

L-Valine is one of the three branched-chain amino acids (valine, leucine, and isoleucine) essential for animal health and important in metabolism; therefore, it is widely added in the products of food, medicine, and feed. L-Valine is predominantly produced through microbial fermentation, and the production efficiency largely depends on the quality of microorganisms. In recent years, continuing efforts have been made in revealing the mechanisms and regulation of L-valine biosynthesis in Corynebacterium glutamicum, the most utilitarian bacterium for amino acid production. Metabolic engineering based on the metabolic biosynthesis and regulation of L-valine provides an effective alternative to the traditional breeding for strain development. Industrially competitive L-valine-producing C. glutamicum strains have been constructed by genetically defined metabolic engineering. This article reviews the global metabolic and regulatory networks responsible for L-valine biosynthesis, the molecular mechanisms of regulation, and the strategies employed in C. glutamicum strain engineering.

Characterization of ultraviolet light-induced diphtheria toxin-resistant mutations in normal and Xeroderma pigmentosum human fibroblasts

International Nuclear Information System (INIS)

Glover, T.W.

1979-01-01

Quantitative mutagenesis studies in human cells have been severely limited by the lack of reliable genetic markers. Experiments were therefore performed to develop and characterize a better quantitative mutation assay for human cells. The uv-induction of diphtheria toxin resistant (DT/sup r/) mutations in normal and excision repair defective xeroderma pigmentosum (XP) fibroblasts has been quantitatively characterized. A concentration of diphtheria toxin to use in the selection of resistant mutants was determined whereby DT/sup r/ cells are cross-resistant to Pseudomonas aeurginosa exotoxin A, indicating mutants have altered elongation factor-2 (EF-2) which is not susceptible to ADP-ribosylation by either toxin. Results of this study indicate that XP fibroblasts have higher uv-induced mutation frequencies per unit uv-dose but similar frequencies per unit survival compared to normal cells as measured using a new genetic marker for quantitative mutagenesis. Furthermore, these results support a prediction of the mutation theory of cancer, namely, that cells from individuals with certain human syndromes that predispose the individual to cancer will have higher induced mutation frequencies than cells from non-susceptible individuals. This newly characterized genetic marker should be useful in quantitative mutagenesis studies in human cells

Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates.

Science.gov (United States)

Bröker, Michael

2016-03-03

When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed.

Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

DEFF Research Database (Denmark)

Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang

2011-01-01

BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1...

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

Science.gov (United States)

Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

2018-04-01

We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

Preventing the preventable through effective surveillance: the case of diphtheria in a rural district of Maharashtra, India.

Science.gov (United States)

Phalkey, Revati K; Bhosale, Rajesh V; Joshi, Abhijeet P; Wakchoure, Sushil S; Tambe, Muralidhar P; Awate, Pradip; Marx, Michael

2013-04-08

Epidemic diphtheria is still poorly understood and continues to challenge both developing and developed countries. In the backdrop of poor immunization coverage, non-existent adult boosters, weak case based surveillance and persistence of multiple foci, there is a heightened risk of re-emergence of the disease in epidemic forms in India. Investigating each outbreak to understand the epidemiology of the disease and its current status in the country is therefore necessary. Dhule a predominantly tribal and rural district in Northern Maharashtra has consistently recorded low vaccination coverages alongside sporaidic cases of diphtheria over the last years. This study reports the findings of an onsite survey conducted to assess a recent outbreak of diphtheria in Dhule district and the response mounted to it. Secondary data regarding outbreak detection and response were obtained from the district surveillance office. Clinical data were extracted from hospital records of eleven lab confirmed cases including one death case. Frequency distributions were calculated for each identified clinical and non- clinical variable using Microsoft™ Excel® 2010. Our findings suggest a shift in the median age of disease to adolescents (10-15 years) without gender differences. Two cases (18%) reported disease despite immunization. Clinical symptoms included cough (82%), fever (73%), and throat congestion (64%). About 64% and 36% of the 11 confirmed cases presented with a well defined pseudomembrane and a tonsillar patch respectively. Drug resistance was observed in all three culture positive cases. One death occurred despite the administration of Anti-Diphtheric Serum in a partially immunized case (CFR 9%). Genotyping and toxigenicity of strain was not possible due to specimen contamination during transport as testing facilities were unavailable in the district. The outbreak raises several concerns regarding the epidemiology of diphtheria in Dhule. The reason for shift in the median

Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

Science.gov (United States)

Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

2016-03-03

The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children Vietnamese children aged <2 years.

PcaO Positively Regulates pcaHG of the β-Ketoadipate Pathway in Corynebacterium glutamicum▿

OpenAIRE

Zhao, Ke-Xin; Huang, Yan; Chen, Xi; Wang, Nan-Xi; Liu, Shuang-Jiang

2010-01-01

We identified a new regulator, PcaO, which is involved in regulation of the protocatechuate (PCA) branch of the β-ketoadipate pathway in Corynebacterium glutamicum. PcaO is an atypical large ATP-binding LuxR family (LAL)-type regulator and does not have a Walker A motif. A mutant of C. glutamicum in which pcaO was disrupted (RES167ΔpcaO) was unable to grow on PCA, and growth on PCA was restored by complementation with pcaO. Both an enzymatic assay of PCA 3,4-dioxygenase activity (encoded by p...

IMMUNOGENICITY AND SAFETY OF QUINVAXEM® (DIPHTHERIA, TETANUS, WHOLE-CELL PERTUSSIS, HEPATITIS B AND HAEMOPHILUS INFLUENZAE TYPE B VACCINE) GIVEN TO VIETNAMESE INFANTS AT 2 TO 4 MONTHS OF AGE.

Science.gov (United States)

Huu, Tran Ngoc; Phuong, Nguyen Thi Minh; Toan, Nguyen Trong; Thang, Ho Vinh

2015-07-01

Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem® vaccine in children. A total of 131 infants received the Quinvaxem® vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP ≥ 0.15 µg/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP ≥ 0.15 µg/ml). The Quinvaxem® vaccine was well tolerated and has a low rate of adverse events. Quinvaxem® given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam.

Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

NARCIS (Netherlands)

Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

1993-01-01

This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual

Accessibility changes within diphtheria toxin T domain when in the functional molten globule state, as determined using hydrogen/deuterium exchange measurements

Czech Academy of Sciences Publication Activity Database

Man, Petr; Montagner, C.; Vitrac, H.; Kavan, Daniel; Pichard, S.; Gillet, D.; Forest, E.; Forge, V.

2010-01-01

Roč. 277, č. 3 (2010), s. 653-662 ISSN 1742-464X Institutional research plan: CEZ:AV0Z50200510 Keywords : diphtheria toxin * hydrogen/deuterium exchanges * mass spectrometry Subject RIV: CE - Biochemistry Impact factor: 3.129, year: 2010

The effect of vitamin A supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model

DEFF Research Database (Denmark)

Jørgensen, Mathias Jul; Hein-Kristensen, Line; Hempel, Casper

2011-01-01

infectious diseases when given with the diphtheria-tetanus-pertussis (DTP) vaccine. The immunological effects of combining the 2 treatments are unknown. Methods: We studied the effect of treating C57BL/6 mice with VAS and DTP, 1 week prior to infection with Plasmodium berghei ANKA. The progression of disease...

Qualification guideline of the German X-ray association (DRG) und the German association for interventional radiology and minimal invasive therapy (DeGIR) for the performance of interventional-radiological minimal invasive procedures on arteries and veins

International Nuclear Information System (INIS)

Buecker, A.; Gross-Fengels, W.; Haage, P.; Huppert, P.; Landwehr, P.; Loose, R.; Reimer, P.; Tacke, J.; Vorwerk, D.; Fischer, J.

2012-01-01

The topics covered in the qualification guideline of the German X-ray association (DRG) und the German association for interventional radiology and minimal invasive therapy (DeGIR) for the performance of interventional-radiological minimal invasive procedures on arteries and veins are the following: Practical qualification: aorta iliac vessels and vessels in the upper and lower extremities, kidney and visceral arteries, head and neck arteries, dialysis shunts, veins and pulmonary arteries, aorta aneurysms and peripheral artery aneurysms. Knowledge acquisition concerning radiation protection: legal fundamentals, education and training, knowledge actualization and quality control, definition of the user and the procedure, competence preservation.

Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

Science.gov (United States)

Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

2015-01-01

Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

Science.gov (United States)

Chen, Can; Pan, Junfeng; Yang, Xiaobing; Guo, Chenghao; Ding, Wei; Si, Meiru; Zhang, Yi; Shen, Xihui; Wang, Yao

2016-01-01

Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

Directory of Open Access Journals (Sweden)

André Bandiera de Oliveira Santos

Full Text Available Abstract Introduction Perineural invasion is a unique route for tumor dissemination. In basal cell carcinomas, the incidence is low, but increases in advanced cases. Its importance is recognized but not fully understood. Objective To compare head and neck basal cell carcinomas with and without perineural invasion. Methods A retrospective medical chart review of multidisciplinary surgeries for basal cell carcinomas that required a head and neck surgery specialist in a tertiary referral center was performed. Clinical-demographics and histopathological features were analyzed. Results Of 354 cases, perineural invasion was present in 23.1%. Larger tumors and morpheaform subtype were statistically related to perineural invasion. Nodular and superficial subtypes were less frequent in positive cases. No significant difference was found in gender, age, ulceration, location, and mixed histology. Conclusion In this series of selected patients with basal cell carcinomas submitted to major resections, perineural invasion was clearly related to morpheaform subtype and to larger tumors. Other classically associated features, such as location in high-risk mask zone of the face, male gender and mixed histology, were not so strongly linked to perineural invasion.

Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

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Anne Le Flèche-Matéos

2012-01-01

Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

APLICACION DE TECNICAS DE INGENIERIA METABOLICA AL MEJORAMIENTO DE LA PRODUCCION DE TREHALOSA POR CORYNEBACTERIUM GLUTAMICUM.

OpenAIRE

PADILLA IGLESIAS, LEANDRO MAURICIO

2004-01-01

La Trehalosa es un disacárido con tremendas aplicaciones en la industria biotecnológica y alimenticia. Este compuesto se encuentra en muchos organismos, a causa de su capacidad de proteger las células contra el calor y la deshidratación. Un ejemplo, es la bacteria Gram-positiva Corynebacterium glutamicum, la cual sintetiza trehalosa a través de dos rutas principales, TreYZ y OtsBA, usando ADP-glucosa (especulativamente) y UDP-glucosa, respectivamente, como dadores de unidades de ...

Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013.

Science.gov (United States)

O'Halloran, Alissa C; Lu, Peng-Jun; Williams, Walter W; Ding, Helen; Meyer, Sarah A

2016-07-01

The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Radio frequency energy for non-invasive and minimally invasive skin tightening.

Science.gov (United States)

Mulholland, R Stephen

2011-07-01

This article reviews the non-invasive and minimally invasive options for skin tightening, focusing on peer-reviewed articles and presentations and those technologies with the most proven or promising RF non-excisional skin-tightening results for excisional surgeons. RF has been the mainstay of non-invasive skin tightening and has emerged as the "cutting edge" technology in the minimally invasive skin-tightening field. Because these RF skin-tightening technologies are capital equipment purchases with a significant cost associated, this article also discusses some business issues and models that have proven to work in the plastic surgeon's office for non-invasive and minimally invasive skin-tightening technologies. Copyright © 2011 Elsevier Inc. All rights reserved.

Determination of the Presence of crpgenes in Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus delbrueckii and Corynebacterium veraSuş

OpenAIRE

BELDÜZ, Ali Osman; DEMİRBAĞ, Zihni; DÜLGER, Sabriye

2014-01-01

Polymerase chain reaction (PCR) was employed to detect the presence of cyclic AMP receptor protein (CPR) in a number of diverse organisms. In PCR, two primers specific to the crp gene of Escherichia coli were used. Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus delbrueckii and Corynebacterium veraSuş all showed the same size of PCR frağments (708 bp) and same restriction frağment length polymorphizm (RFLP).

A new polymorphism in the GRP78 is not associated with HBV invasion

Science.gov (United States)

Zhu, Xiao; Wang, Yi; Tao, Tao; Li, Dong-Pei; Lan, Fei-Fei; Zhu, Wei; Xie, Dan; Kung, Hsiang-Fu

2009-01-01

AIM: To examine the association between -86 bp (T > A) in the glucose-regulated protein 78 gene (GRP78) and hepatitis B virus (HBV) invasion. METHODS: DNA was genotyped for the single-nucleotide polymorphism by polymerase chain reaction followed by sequencing in a sample of 382 unrelated HBV carriers and a total of 350 sex- and age-matched healthy controls. Serological markers for HBV infection were determined by enzyme-linked immunosorbent assay kits or clinical chemistry testing. RESULTS: The distributions of allelotype and genotype in cases were not significantly different from those in controls. In addition, our findings suggested that neither alanine aminotransferase/hepatitis B e antigen nor HBV-DNA were associated with the allele/genotype variation in HBV infected individuals. CONCLUSION: -86 bp T > A polymorphism in GRP78 gene is not related to the clinical risk and acute exacerbation of HBV invasion. PMID:19842229

Genomic comparison of invasive and rare non-invasive strains reveals Porphyromonas gingivalis genetic polymorphisms

Directory of Open Access Journals (Sweden)

Svetlana Dolgilevich

2011-03-01

Full Text Available Porphyromonas gingivalis strains are shown to invade human cells in vitro with different invasion efficiencies, varying by up to three orders of magnitude.We tested the hypothesis that invasion-associated interstrain genomic polymorphisms are present in P. gingivalis and that putative invasion-associated genes can contribute to P. gingivalis invasion.Using an invasive (W83 and the only available non-invasive P. gingivalis strain (AJW4 and whole genome microarrays followed by two separate software tools, we carried out comparative genomic hybridization (CGH analysis.We identified 68 annotated and 51 hypothetical open reading frames (ORFs that are polymorphic between these strains. Among these are surface proteins, lipoproteins, capsular polysaccharide biosynthesis enzymes, regulatory and immunoreactive proteins, integrases, and transposases often with abnormal GC content and clustered on the chromosome. Amplification of selected ORFs was used to validate the approach and the selection. Eleven clinical strains were investigated for the presence of selected ORFs. The putative invasion-associated ORFs were present in 10 of the isolates. The invasion ability of three isogenic mutants, carrying deletions in PG0185, PG0186, and PG0982 was tested. The PG0185 (ragA and PG0186 (ragB mutants had 5.1×103-fold and 3.6×103-fold decreased in vitro invasion ability, respectively.The annotation of divergent ORFs suggests deficiency in multiple genes as a basis for P. gingivalis non-invasive phenotype. Access the supplementary material to this article: Supplement, table (see Supplementary files under Reading Tools online.

Surgical Site Infection by Corynebacterium macginleyi in a Patient with Neurofibromatosis Type 1

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Bruno Cacopardo

2013-01-01

Full Text Available Corynebacterium (C. macginleyi is a gram positive, lipophilic rod, usually considered a colonizer of skin and mucosal surfaces. Several reports have associated C. macginleyi with ocular infections, such as conjunctivitis and endophthalmitis. However, even if rare, extraocular infections from C. macginleyi may occur, especially among immunocompromised patients and patients with indwelling medical devices. We report herein the first case of surgical site infection by C. macginleyi after orthopaedic surgery for the correction of kyphoscoliosis in a patient with neurofibromatosis type 1. Our patient developed a nodular granulomatous lesion of about two centimetres along the surgical scar, at the level of C4-C5, with purulent discharge and formation of a fistulous tract. Cervical magnetic resonance imaging showed the presence of a two-centimetre fluid pocket in the subcutaneous tissue. Several swabs were collected from the borders of the lesion as well as from the exudate, with isolation of C. macginleyi. The isolate was susceptible to beta-lactams, cotrimoxazole, linezolid, and glycopeptides but resistant to quinolones, third-generation cephalosporins, and erythromycin. Two 30-day courses of antibiotic therapy with amoxicillin/clavulanate (1 g three times/day and cotrimoxazole (800/160 mg twice a day were administered, obtaining a complete healing of the lesion.

Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

Directory of Open Access Journals (Sweden)

Can Chen

Full Text Available Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Transcriptional Analysis of the groES-groEL1, groEL2, and dnaK genes in Corynebacterium glutamicum: Characterization of Heat Shock-Induced Promoters

Czech Academy of Sciences Publication Activity Database

Barreiro, C.; González-Lavado, E.; Pátek, Miroslav; Martin, J. F.

2004-01-01

Roč. 186, č. 14 (2004), s. 4813-4817 ISSN 0021-9193 R&D Projects: GA AV ČR KSK5052113 Keywords : corynebacterium glutamicum * mrna Subject RIV: EE - Microbiology, Virology Impact factor: 4.146, year: 2004

Nitrogen fixation rates associated with the invasive macroalgae Sargassum horneri around Catalina Island, CA

Science.gov (United States)

DeLiberto, A.

2016-02-01

Nitrogen fixation is an important process which allows organisms access to biologically unavailable dinitrogen gas. Bacteria, known as diazotrophs use the enzyme nitrogenase to convert N2 to NH3. These bacteria, including certain species of heterotrophic bacteria and cyanobacteria, can be symbiotically associated with marine macroalgae, facilitating nutrient cycling in oligotrophic regions. As many species within the genera Sargassum are associated with nitrogen fixation, this study hypothesized that nitrogenase activity would be associated with the benthic invasive Sargassum horneri on Catalina Island. In the past decade, Sargassum horneri, an invasive from Japan, has spread throughout the waters around Catalina Island. Using the acetylene reduction procedure using flame ionization detection, initial nitrogenase activity of S. horneri sampled from Indian Rock was observed. Nitrogen fixation rates increased with decomposition, particularly in dark/anaerobic treatments, suggesting the presence of heterotrophic bacteria. In addition, acetate additions greatly increase nitrogen fixation rates, once again indicating heterotrophic nitrogen fixing bacteria.

Bioconversion of sugar cane molasses into glutamic acid by gamma irradiated corynebacterium glutamicum

International Nuclear Information System (INIS)

El-Batal, A.I.

1996-01-01

Corynebacterium glutamicum (ATCC 13058) was used for glutamic acid production from sugar cane molasses which contain sufficient. The addition of 5 units ml 4 of penicillin G was superior in glutamic acid production (11.5 g L 4 ). Tweens and their saturated fatty acids were effective on the accumulation of glutamic acid in the culture medium and the maximum yield (16.6 g L 4 ) was the addition of 5 mg ml 4 Tween 40. Gamma irradiation prior to Tween-40 treatment of bacterial cells resulted in an obvious increase in glutamic acid production and it was maximum (23.72 g L 4 ) at 0.1 k Gy exposure dose of inocula. 5 tabs

Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

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Murphy, John R.

2011-01-01

Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study

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Naleway Allison

2009-10-01

Full Text Available Abstract Background Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td vaccine and the risk of local reactions may increase with number of prior Td vaccinations. Methods To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004. Results Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2. Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics. Conclusion Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.

Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

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Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

2018-01-02

Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Surface-associated plasminogen binding of Cryptococcus neoformans promotes extracellular matrix invasion.

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Jamal Stie

2009-06-01

Full Text Available The fungal pathogen Cryptococcus neoformans is a leading cause of illness and death in persons with predisposing factors, including: malignancies, solid organ transplants, and corticosteroid use. C. neoformans is ubiquitous in the environment and enters into the lungs via inhalation, where it can disseminate through the bloodstream and penetrate the central nervous system (CNS, resulting in a difficult to treat and often-fatal infection of the brain, called meningoencephalitis. Plasminogen is a highly abundant protein found in the plasma component of blood and is necessary for the degradation of fibrin, collagen, and other structural components of tissues. This fibrinolytic system is utilized by cancer cells during metastasis and several pathogenic species of bacteria have been found to manipulate the host plasminogen system to facilitate invasion of tissues during infection by modifying the activation of this process through the binding of plasminogen at their surface.The invasion of the brain and the central nervous system by penetration of the protective blood-brain barrier is a prerequisite to the establishment of meningoencephalitis by the opportunistic fungal pathogen C. neoformans. In this study, we examined the ability of C. neoformans to subvert the host plasminogen system to facilitate tissue barrier invasion. Through a combination of biochemical, cell biology, and proteomic approaches, we have shown that C. neoformans utilizes the host plasminogen system to cross tissue barriers, providing support for the hypothesis that plasminogen-binding may contribute to the invasion of the blood-brain barrier by penetration of the brain endothelial cells and underlying matrix. In addition, we have identified the cell wall-associated proteins that serve as plasminogen receptors and characterized both the plasminogen-binding and plasmin-activation potential for this significant human pathogen.The results of this study provide evidence for the

Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

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Abu-lail Rasha

2010-07-01

Full Text Available Abstract Introduction Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences. Case presentation A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events. Conclusion On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.

 Invasibility of three major non-native invasive shrubs and associated factors in Upper Midwest U.S. forest lands

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W. Keith Moser; Zhaofei Fan; Mark H. Hansen; Michael K. Crosby; Shirley X. Fan

2016-01-01

We used non-native invasive plant data from the US Forest Service’s Forest Inventory and Analysis (FIA) program, spatial statistical methods, and the space (cover class)-for-time approach to quantify the invasion potential and success ("invasibility") of three major invasive shrubs (multiflora rose, non-native bush honeysuckles, and common buckthorn...

Dual production of poly(3-hydroxybutyrate) and glutamate using variable biotin concentrations in Corynebacterium glutamicum.

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Jo, Sung-Jin; Leong, Chean Ring; Matsumoto, Ken'ichiro; Taguchi, Seiichi

2009-04-01

We previously synthesized poly(3-hydroxybutyrate) [P(3HB)] in recombinant Corynebacterium glutamicum, a prominent producer of amino acids. In this study, a two-step cultivation was established for the dual production of glutamate and P(3HB) due to the differences in the optimal concentration of biotin. Glutamate was extracellularly produced first under the biotin-limited condition of 0.3 microg/L. Production was then shifted to P(3HB) by addition of biotin to a total concentration of 9 microg/L. The final products obtained were 18 g/L glutamate and 36 wt% of P(3HB).

Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

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Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

2016-06-01

Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

Association of secondhand smoke exposure with pediatric invasive bacterial disease and bacterial carriage: a systematic review and meta-analysis.

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Chien-Chang Lee

2010-12-01

Full Text Available A number of epidemiologic studies have observed an association between secondhand smoke (SHS exposure and pediatric invasive bacterial disease (IBD but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis, Haemophilus influenzae type B (Hib, and Streptococcus pneumoniae (S. pneumoniae.Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52-2.69 for invasive meningococcal disease, 1.21 (95% CI 0.69-2.14 for invasive pneumococcal disease, and 1.22 (95% CI 0.93-1.62 for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19-2.36 for N. meningitidis, 1.66 (95% CI 1.33-2.07 for S. pneumoniae, and 0.96 (95% CI 0.48-1.95 for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72-6.13.When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be associated with invasive meningococcal disease. The

Secondary invasions of noxious weeds associated with control of invasive Tamarix are frequent, idiosyncratic and persistent

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González, Eduardo; Sher, Anna A.; Anderson, Robert M.; Bay, Robin F.; Bean, Daniel W.; Bissonnete, Gabriel J.; Cooper, David J.; Dohrenwend, Kara; Eichhorst, Kim D.; El Waer, Hisham; Kennard, Deborah K.; Harms-Weissinger, Rebecca; Henry, Annie L.; Makarick, Lori J.; Ostoja, Steven M.; Reynolds, Lindsay V.; Robinson, W. Wright; Shafroth, Patrick B.; Tabacchi, Erich

2017-01-01

Control of invasive species within ecosystems may induce secondary invasions of non-target invaders replacing the first alien. We used four plant species listed as noxious by local authorities in riparian systems to discern whether 1) the severity of these secondary invasions was related to the control method applied to the first alien; and 2) which species that were secondary invaders persisted over time. In a collaborative study by 16 research institutions, we monitored plant species composition following control of non-native Tamarix trees along southwestern U.S. rivers using defoliation by an introduced biocontrol beetle, and three physical removal methods: mechanical using saws, heavy machinery, and burning in 244 treated and 79 untreated sites across six U.S. states. Physical removal favored secondary invasions immediately after Tamarix removal (0–3 yrs.), while in the biocontrol treatment, secondary invasions manifested later (> 5 yrs.). Within this general trend, the response of weeds to control was idiosyncratic; dependent on treatment type and invader. Two annual tumbleweeds that only reproduce by seed (Bassia scoparia and Salsola tragus) peaked immediately after physical Tamarix removal and persisted over time, even after herbicide application. Acroptilon repens, a perennial forb that vigorously reproduces by rhizomes, and Bromus tectorum, a very frequent annual grass before removal that only reproduces by seed, were most successful at biocontrol sites, and progressively spread as the canopy layer opened. These results demonstrate that strategies to control Tamarix affect secondary invasions differently among species and that time since disturbance is an important, generally overlooked, factor affecting response.

Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

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Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

2007-01-01

Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

The invasion risk of species associated with Japanese Tsunami Marine Debris in Pacific North America and Hawaii.

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Therriault, Thomas W; Nelson, Jocelyn C; Carlton, James T; Liggan, Lauran; Otani, Michio; Kawai, Hiroshi; Scriven, Danielle; Ruiz, Gregory M; Clarke Murray, Cathryn

2018-01-25

Marine debris from the Great Tsunami of 2011 represents a unique transport vector for Japanese species to reach Pacific North America and Hawaii. Here we characterize the invasion risk of invertebrate species associated with tsunami debris using a screening-level risk assessment tool - the Canadian Marine Invasive Screening Tool (CMIST). Higher-risk invertebrate invaders were identified for each of five different ecoregions. Some of these are well-known global invaders, such as the mussel Mytilus galloprovincialis and the ascidian Didemnum vexillum which already have invasion histories in some of the assessed ecoregions, while others like the sea star Asterias amurensis and the shore crab Hemigrapsus sanguineus have yet to invade large portions of the assessed ecoregions but also are recognized global invaders. In general, the probability of invasion was lower for the Gulf of Alaska and Hawaii, in part due to lower climate matches and the availability of other invasion vectors. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion

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Petter Michaela

2008-07-01

Full Text Available Abstract Background Plasmodium falciparum STEVOR proteins, encoded by the multicopy stevor gene family have no known biological functions. Their expression and unique locations in different parasite life cycle stages evoke multiple functionalities. Their abundance and hypervariability support a role in antigenic variation. Methods Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant antigens of this gene family and to follow changes in STEVOR expression in parasite populations panned on CSA or CD36 receptors. Immunofluorescence assays and immunoelectron microscopy were performed to study the subcellular localization of STEVOR proteins in different parasite stages. The capacity of the antibody to inhibit merozoite invasion of erythrocytes was assessed to determine whether STEVOR variants were involved in the invasion process. Results Antigenic variation of STEVORs at the protein level was observed in blood stage parasites. STEVOR variants were found to be present on the merozoite surface and in rhoptries. An insight into a participation in erythrocyte invasion was gained through an immunofluorescence analysis of a sequence of thin slides representing progressive steps in erythrocyte invasion. An interesting feature of the staining pattern was what appeared to be the release of STEVORs around the invading merozoites. Because the anti-STEVOR antibody did not inhibit invasion, the role of STEVORs in this process remains unknown. Conclusion The localization of STEVOR proteins to the merozoite surface and the rhoptries together with its prevalence as a released component in the invading merozoite suggest a role of these antigens in adhesion and/or immune evasion in the erythrocyte invasion process. These observations would also justify STEVORs for undergoing antigenic variation. Even though a role in erythrocyte invasion remains speculative, an association of members of the STEVOR protein family with

AVALIAÇÃO DE FONTES DE CARBONO PARA A PRODUÇÃO DE INIBIDOR DE CRESCIMENTO DE Aspergillus fumigatus USP2 por Corynebacterium sp.

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Gabrielle Fernanda Zimmer

2013-07-01

Full Text Available O aumento significativo na incidência de infecções fúngicas invasivas e a resistência natural de agentes etiológicos a antifúngicos existentes têm motivado a constante pesquisa por novos agentes antifúngicos nos ultimos anos. Neste sentido, foi selcionada uma cepa de Corynebacterium sp. com potencial antagonista frente à Aspergilus fumigatus USP2. A cepa foi cultivada em fase submersa e em fase sólida, avaliando-se a variação das fontes de glicose, sacarose e glicerol em presença de peptona, bem como o meio sintético Czapek. Os caldos de cultivo submerso foram utilizados para o ensaio de antagonismo microbiano com o fungo Aspergillus fumigatus USP2. Os resultados apontam que o cultivo em fase sólida utilizando glicose como fonte de carbono apresenta maior potencial inibitório da cepa de Corynebacterium sp. sobre o fungo Aspergillus fumigatus USP2.

Aggregative adherent strains of Corynebacterium pseudodiphtheriticum enter and survive within HEp-2 epithelial cells

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Monica Cristina de Souza

2012-06-01

Full Text Available Corynebacterium pseudodiphtheriticum is a well-known human pathogen that mainly causes respiratory disease and is associated with high mortality in compromised hosts. Little is known about the virulence factors and pathogenesis of C. pseudodiphtheriticum. In this study, cultured human epithelial (HEp-2 cells were used to analyse the adherence pattern, internalisation and intracellular survival of the ATCC 10700 type strain and two additional clinical isolates. These microorganisms exhibited an aggregative adherence-like pattern to HEp-2 cells characterised by clumps of bacteria with a "stacked-brick" appearance. The differences in the ability of these microorganisms to invade and survive within HEp-2 cells and replicate in the extracellular environment up to 24 h post infection were evaluated. The fluorescent actin staining test demonstrated that actin polymerisation is involved in the internalisation of the C. pseudodiphtheriticum strains. The depolymerisation of microfilaments by cytochalasin E significantly reduced the internalisation of C. pseudodiphtheriticum by HEp-2 cells. Bacterial internalisation and cytoskeletal rearrangement seemed to be partially triggered by the activation of tyrosine kinase activity. Although C. pseudodiphtheriticum strains did not demonstrate an ability to replicate intracellularly, HEp-2 cells were unable to fully clear the pathogen within 24 h. These characteristics may explain how some C. pseudodiphtheriticum strains cause severe infection in human patients.

The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

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Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

2016-08-17

Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. Copyright © 2016 GSK group of companies. Published by Elsevier Ltd.. All rights reserved.

Incidence and Predictors of Invasive Candidiasis Associated with Candidemia in Children

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Festekjian, Ara; Neely, Michael

2009-01-01

Background Risk factors for invasive candidiasis in children with candidemia are poorly defined. Methods We performed a retrospective cohort study of all children with candidemia at our tertiary children’s hospital from 2000 to 2006. Invasive candidiasis was diagnosed by review of the medical record and standardized EORTC/MSG criteria. A variety of risk factors for invasive candidiasis were explored. Results Of 194 episodes of candidemia in the microbiology laboratory database, 180 clinical records were available. Evaluation for invasive candidiasis consisted of 174 (97%) echocardiograms; 167 (93%) dilated ophthalmologic examinations, 136 (76%) chest CT scans, and 108 (60%) abdominal ultrasounds (complete, hepatosplenic or renal). Of the 180, 15 (8%) patients were identified with invasive candidiasis (4 proven, 1 probable, 10 possible). Prematurity candidiasis. Conclusions Invasive candidiasis, especially proven or probable, in the setting of candidemia was not common in our hospital, but premature infants and immunocompromised children were at significantly higher risk. Based on our findings, extensive imaging and examination by an ophthalmologist was particularly low-yield for invasive candidiasis in immunocompetent children beyond infancy. PMID:19821906

In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein

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Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques

2016-01-01

BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation...... of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were...... not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous. CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing...

Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum

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Nadja A. Henke

2018-04-01

Full Text Available Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, C. glutamicum has been engineered for the production of a number of value-added compounds including terpenoids. Both C40 and C50 carotenoids, including the industrially relevant astaxanthin, and short-chain terpenes such as the sesquiterpene valencene can be produced with this organism. In this study, systematic metabolic engineering enabled construction of a patchoulol producing C. glutamicum strain by applying the following strategies: (i construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of ispA from Escherichia coli; (ii prevention of carotenoid-like byproduct formation; (iii overproduction of limiting enzymes from the 2-c-methyl-d-erythritol 4-phosphate (MEP-pathway to increase precursor supply; and (iv heterologous expression of the plant patchoulol synthase gene PcPS from Pogostemon cablin. Additionally, a proof of principle liter-scale fermentation with a two-phase organic overlay-culture medium system for terpenoid capture was performed. To the best of our knowledge, the patchoulol titers demonstrated here are the highest reported to date with up to 60 mg L−1 and volumetric productivities of up to 18 mg L−1 d−1.

Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas

International Nuclear Information System (INIS)

Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.; Winter, Jordan; Hruban, Ralph H.; Guler, Mehmet; Schulick, Richard D.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.; Herman, Joseph M.

2010-01-01

Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.

Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9.

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Justin V Joseph

Full Text Available Glioblastoma (GBM is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs, have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.

CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum.

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Cho, Jae Sung; Choi, Kyeong Rok; Prabowo, Cindy Pricilia Surya; Shin, Jae Ho; Yang, Dongsoo; Jang, Jaedong; Lee, Sang Yup

2017-07-01

Genome engineering of Corynebacterium glutamicum, an important industrial microorganism for amino acids production, currently relies on random mutagenesis and inefficient double crossover events. Here we report a rapid genome engineering strategy to scarlessly knock out one or more genes in C. glutamicum in sequential and iterative manner. Recombinase RecT is used to incorporate synthetic single-stranded oligodeoxyribonucleotides into the genome and CRISPR/Cas9 to counter-select negative mutants. We completed the system by engineering the respective plasmids harboring CRISPR/Cas9 and RecT for efficient curing such that multiple gene targets can be done iteratively and final strains will be free of plasmids. To demonstrate the system, seven different mutants were constructed within two weeks to study the combinatorial deletion effects of three different genes on the production of γ-aminobutyric acid, an industrially relevant chemical of much interest. This genome engineering strategy will expedite metabolic engineering of C. glutamicum. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines.

Science.gov (United States)

Gyhrs, A; Pedersen, B K; Bygbjerg, I; Henrichsen, J; Heron, I; Petersen, I; Skinhoj, P

1991-11-01

In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.

Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database

International Nuclear Information System (INIS)

Huang, Baojun; Sun, Zhe; Wang, Zhenning; Lu, Chong; Xing, Chengzhong; Zhao, Bo; Xu, Huimian

2013-01-01

Peritoneal dissemination is the most common type of recurrence in advanced gastric cancer. The main mechanism is thought to be via the exfoliation of free cancer cells (FCCs) from tumor in the gastric serosa. The frequency of recurrence thus increases once the tumor cells penetrate the serosa. However, this type of recurrence also occurs in patients without serosal invasion, though the mechanisms responsible for have not been fully established. We therefore investigated the factors associated with peritoneal dissemination in patients with non-serosa-invasive gastric cancer. A total of 685 patients with non-serosa-invasive gastric cancer who underwent curative resection with retrieval of more than 15 nodes were selected. The associations between clinicopathological features and peritoneal dissemination were analyzed. Among them, the tumor infiltrating growth pattern (INF) were classified into α, β and γ according to the Japanese Classification of Gastric Carcinoma (JCGC). The overall incidence of peritoneal metastasis was 20% (137/685). Age, Borrmann type, differentiation, INF, nodal status and free cancer cells (FCCs) were correlated with peritoneal dissemination using univariate analysis. However, only INF, Borrmann type and TNM node stage were identified as independent correlated factors with peritoneal metastasis by multivariate analysis when FCCs were excluded, and these were also prognostic factors. Peritoneal dissemination was more common in patients with INFγ, Borrmann III/IV and N3 stage. Among patients without FCCs, nodal involvement or vessel invasion, only INF remained an independent associated factor according to multivariate analysis. Tumor infiltrating growth pattern (INF), together with Borrmann type and TNM node stage, are important factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer

RESULTS OF THE IMMUNIZATION ACCORDING TO THE NATIONAL CALENDAR ASSOCIATED WITH VACCINATION AGAINST INFLUENZA IN CHILDREN WITH SOMATIC DISORDERS AND IMMUNODEFICIENCY

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S. M. Kharit

2014-01-01

Full Text Available Aim: to study safety and immunological efficacy of vaccination against influenza in separate and associated immunization according to the National Calendar. Patients and methods: 100 children with various disorders as well as children with HIV subjected to revaccination against diphtheria, tetanus, measles, parotiditis and rubella, were included into the study. Children were divided into 5 groups of 20 persons each: groups of separate or associated vaccination. In order to assess safety of vaccination children were observed for 30 days after vaccination. In order to analyze immunologic efficacy participants were taken serum tests before and on the 30th day after vaccination. Results: the study demonstrated high safety of the vaccine against influenza. Mild and moderate topical and general reactions were observed in isolated instances and did not differ in comparison groups. Simultaneous vaccination against influenza with immunization against diphtheria, parotiditis and rubella did not influence synthesis of antibodies, while synthesis of antibodies against measles was decreased; immunization against diphtheria and measles when associated with vaccination against influenza depressed synthesis of antibodies against A/H3N2 influenza. Conclusions: vaccine against influenza has low reactivity, high safety and can be used in association with immunization according to the National calendar in independence to somatic disorders of patients. 

In Silico Genome-Scale Reconstruction and Validation of the Corynebacterium glutamicum Metabolic Network

DEFF Research Database (Denmark)

Kjeldsen, Kjeld Raunkjær; Nielsen, J.

2009-01-01

A genome-scale metabolic model of the Gram-positive bacteria Corynebacterium glutamicum ATCC 13032 was constructed comprising 446 reactions and 411 metabolite, based on the annotated genome and available biochemical information. The network was analyzed using constraint based methods. The model...... was extensively validated against published flux data, and flux distribution values were found to correlate well between simulations and experiments. The split pathway of the lysine synthesis pathway of C. glutamicum was investigated, and it was found that the direct dehydrogenase variant gave a higher lysine...... yield than the alternative succinyl pathway at high lysine production rates. The NADPH demand of the network was not found to be critical for lysine production until lysine yields exceeded 55% (mmol lysine (mmol glucose)(-1)). The model was validated during growth on the organic acids acetate...

Influence of Corynebacterium parvum on the phagocytosis of 198Au colloids in rats

International Nuclear Information System (INIS)

Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S.

1982-01-01

The kinetics of the phagocytosis of gelatin-protected 198 Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the 198 Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell. (author) [es

Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109.

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Abdali, Narges; Younas, Farhan; Mafakheri, Samaneh; Pothula, Karunakar R; Kleinekathöfer, Ulrich; Tauch, Andreas; Benz, Roland

2018-05-09

Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes. In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum ΔporAΔporH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene

Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections.

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Khodr, Zeina G; Bukowinski, Anna T; Gumbs, Gia R; Conlin, Ava Marie S

2017-10-09

To protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at risk was 17% lower if vaccination was received between 27 and 36weeks of pregnancy (RR, 0.83; 95% CI, 0.74-0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74-0.98). Maternal Tdap vaccination between 27 and 36weeks of pregnancy was consistently protective against infant ARI in the first 2months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

International Nuclear Information System (INIS)

Tomkins, D.J.; Wei, L.; Laurie, K.E.

1985-01-01

It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dip/sup r/) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis ( 3 H-thymidine, autoradiography) or protein synthesis ( 35 S-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test

Safety of a tetanus-diphtheria-acellular pertussis vaccine when used off-label in an elderly population.

Science.gov (United States)

Tseng, Hung Fu; Sy, Lina S; Qian, Lei; Marcy, S Michael; Jackson, Lisa A; Glanz, Jason; Nordin, Jim; Baxter, Roger; Naleway, Allison; Donahue, James; Weintraub, Eric; Jacobsen, Steven J

2013-02-01

Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

Pharmacists’ Attitudes and Practices Regarding Tetanus, Diphtheria and Pertussis (Tdap Vaccination in Pregnancy and Surrounding Newborns

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Christine A Echtenkamp

2018-04-01

Full Text Available Background: Bordetella pertussis or whooping cough is a serious and vaccine-preventable illness. Despite widespread vaccination in the pediatric population, pertussis still infects approximately 100,000 infants each year in the United States. The purpose of this study was to determine gaps in pharmacists’ understanding, attitudes, practices, and barriers surrounding the tetanus, diphtheria, and pertussis (Tdap vaccination recommendation for patients who are pregnant or planning to come in close contact with infants. Methods: This study was a descriptive, exploratory electronic survey. The survey assessed three major areas; the role of the pharmacist in Tdap vaccination, perceived barriers to vaccination, and understanding the recommendations. Results: A total of 225 pharmacists responded to the survey. Pharmacists who responded to this survey agreed that pharmacists should have a role vaccinating the public and individuals expecting to come into contact with a newborn, (88.5% and 86.9% respectively, but fewer agreed that pharmacists should have a role vaccinating pregnant women against tetanus, diphtheria, and pertussis (77%, p < 0.001. Based on the responses to case scenarios, only 22.5% and 30.6% of respondents understood the recommendations. Numerous barriers to vaccinating pregnant women were identified. Conclusion: While most pharmacists surveyed felt they should have a role in vaccinating pregnant women and those expecting to come in contact with a newborn, there are barriers to implementing this practice. Future efforts should focus on further evaluating identified gaps and developing programs for pharmacists that emphasize the significance of vaccinating these patients to reduce the burden of pertussis in infants.

Association Between Allergies and Psychiatric Disorders in Patients Undergoing Invasive Procedures.

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Aberle, Dwight; Wu, Stephanie E; Oklu, Rahmi; Erinjeri, Joseph; Deipolyi, Amy R

Associations between allergies and psychiatric disorders have been reported in the context of depression and suicide; psychiatric disorders may affect pain perception. To investigate the relationship of allergies with psychiatric disorders and pain perception in the context of invasive procedures, specifically during tunneled hemodialysis catheter placement. We identified 89 patients (51 men, 38 women), mean age 66 years (range: 23-96), who underwent tunneled hemodialysis catheter placement (1/2014-2/2015), recording numeric rating scale pain scores, medications, psychiatric history, allergies, and smoking status. Of 89 patients, 47 patients had no allergies, and 42 had ≥1 allergy. Patients with allergies were more likely to have a pre-existing psychiatric disorder compared to those without allergies, odds ratio 2.6 (95% CI: 1.0-6.8). Having allergies did not affect procedural sedation or postprocedural pain scores. Multiple logistic regression with age, sex, smoking, presence of allergies, psychiatric history, inpatient/outpatient status, procedure time, and procedural sedation administration as inputs and postprocedural pain as the outcome showed that the only independent predictor was receiving procedural sedation (P = 0.005). Findings corroborate anecdotal reports of allergies as a marker for psychiatric history. However, having allergies was not associated with increased pain or need for more sedation. Further studies could prospectively assess whether allergies and psychiatric disorders affect patient/doctor perceptions beyond pain during invasive procedures. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Association of code status discussion with invasive procedures among advanced-stage cancer and noncancer patients

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Sasaki A

2017-07-01

Full Text Available Akinori Sasaki,1 Eiji Hiraoka,1 Yosuke Homma,2 Osamu Takahashi,3 Yasuhiro Norisue,4 Koji Kawai,5 Shigeki Fujitani4 1Department of Internal Medicine, 2Department of Emergency Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City, Chiba, 3Department of Internal Medicine, St. Luke’s International Hospital, Chuo-ku, Tokyo, 4Department of Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City, Chiba, 5Department of Gastroenterology, Ito Municipal Hospital, Ito City, Shizuoka, Japan Background: Code status discussion is associated with a decrease in invasive procedures among terminally ill cancer patients. We investigated the association between code status discussion on admission and incidence of invasive procedures, cardiopulmonary resuscitation (CPR, and opioid use among inpatients with advanced stages of cancer and noncancer diseases. Methods: We performed a retrospective cohort study in a single center, Ito Municipal Hospital, Japan. Participants were patients who were admitted to the Department of Internal Medicine between October 1, 2013 and August 30, 2015, with advanced-stage cancer and noncancer. We collected demographic data and inquired the presence or absence of code status discussion within 24 hours of admission and whether invasive procedures, including central venous catheter placement, intubation with mechanical ventilation, and CPR for cardiac arrest, and opioid treatment were performed. We investigated the factors associated with CPR events by using multivariate logistic regression analysis. Results: Among the total 232 patients, code status was discussed with 115 patients on admission, of which 114 (99.1% patients had do-not-resuscitate (DNR orders. The code status was not discussed with the remaining 117 patients on admission, of which 69 (59% patients had subsequent code status discussion with resultant DNR orders. Code status discussion on admission decreased the incidence of central venous

Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease.

Science.gov (United States)

Bröker, Michael; Cooper, Brian; Detora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo(®)) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.

Functional analysis of sequences adjacent to dapE of Corynebacterium glutamicum reveals the presence of aroP, which encodes the aromatic amino acid transporter.

Science.gov (United States)

Wehrmann, A; Morakkabati, S; Krämer, R; Sahm, H; Eggeling, L

1995-10-01

An initially nonclonable DNA locus close to a gene of L-lysine biosynthesis in Corynebacterium glutamicum was analyzed in detail. Its stepwise cloning and its functional identification by monitoring the amino acid uptakes of defined mutants, together with mechanistic studies, identified the corresponding structure as aroP, the general aromatic amino acid uptake system.

Biological invasions, ecological resilience and adaptive governance.

Science.gov (United States)

Chaffin, Brian C; Garmestani, Ahjond S; Angeler, David G; Herrmann, Dustin L; Stow, Craig A; Nyström, Magnus; Sendzimir, Jan; Hopton, Matthew E; Kolasa, Jurek; Allen, Craig R

2016-12-01

In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services. Copyright © 2016. Published by Elsevier Ltd.

Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

OpenAIRE

Hoch, D H; Romero-Mira, M; Ehrlich, B E; Finkelstein, A; DasGupta, B R; Simpson, L L

1985-01-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as "tunnel proteins" for translocation of active peptide fragments. These f...

Coryneform bacteria associated with canine otitis externa

DEFF Research Database (Denmark)

Aalbæk, Bent; Bemis, David A.; Schjærff, Mette

2010-01-01

This study aims to investigate the occurrence of coryneform bacteria in canine otitis externa. A combined case series and case-control study was carried out to improve the current knowledge on frequency and clinical significance of coryneform bacteria in samples from canine otitis externa. A total...... of 16 cases of otitis externa with involvement of coryneform bacteria were recorded at two referral veterinary hospitals in Denmark and the US, respectively. Coryneform bacteria were identified by partial 16S rRNA gene sequencing. Corynebacterium auriscanis was the most common coryneform species (10...... cases). Small colony variants of this species were also observed. Other coryneform isolates were identified as Corynebacterium amycolatum (3 cases), Corynebacterium freneyi (2 cases) and an Arcanobacterium-like species (1 case). The coryneform bacteria were in all cases isolated together with other...

Operation Pied Piper: a geographical reappraisal of the impact of wartime evacuation on scarlet fever and diphtheria rates in England and Wales, 1939-1945.

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Smallman-Raynor, M R; Cliff, A D

2015-10-01

This paper examines the geographical impact of the British Government's wartime evacuation scheme on notified rates of two common acute childhood diseases (scarlet fever and diphtheria) in the 1470 local government districts of England and Wales, 1939-1945. Drawing on the notifications of communicable diseases collated by the General Register Office (GRO), we establish pre-war (baseline) disease rates for the 1470 districts. For the war years, techniques of binary logistic regression analysis are used to assess the associations between (a) above-baseline ('raised') disease rates in evacuation, neutral and reception districts and (b) the major phases of the evacuation scheme. The analysis demonstrates that the evacuation was temporally associated with distinct national and regional effects on notified levels of disease activity. These effects were most pronounced in the early years of the dispersal (1939-1941) and corresponded with initial levels of evacuation-related population change at the regional and district scales.

The two-component signal transduction system CopRS of Corynebacterium glutamicum is required for adaptation to copper-excess stress

OpenAIRE

Schelder, S.; Zaade, D.; Litsanov, B.; Bott, M.; Brocker, M.

2011-01-01

Copper is an essential cofactor for many enzymes but at high concentrations it is toxic for the cell. Copper ion concentrations ≥50 µM inhibited growth of Corynebacterium glutamicum. The transcriptional response to 20 µM Cu(2+) was studied using DNA microarrays and revealed 20 genes that showed a ≥ 3-fold increased mRNA level, including cg3281-cg3289. Several genes in this genomic region code for proteins presumably involved in the adaption to copper-induced stress, e. g. a multicopper oxidas...

Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

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Zhen Li

2017-10-01

Full Text Available Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6, metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production.

Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

Science.gov (United States)

Li, Zhen; Liu, Jian-Zhong

2017-01-01

Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6), metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production. PMID:29089930

Detoxification of furfural in Corynebacterium glutamicum under aerobic and anaerobic conditions.

Science.gov (United States)

Tsuge, Yota; Hori, Yoshimi; Kudou, Motonori; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

2014-10-01

The toxic fermentation inhibitors in lignocellulosic hydrolysates raise serious problems for the microbial production of fuels and chemicals. Furfural is considered to be one of the most toxic compounds among these inhibitors. Here, we describe the detoxification of furfural in Corynebacterium glutamicum ATCC13032 under both aerobic and anaerobic conditions. Under aerobic culture conditions, furfuryl alcohol and 2-furoic acid were produced as detoxification products of furfural. The ratio of the products varied depending on the initial furfural concentration. Neither furfuryl alcohol nor 2-furoic acid showed any toxic effect on cell growth, and both compounds were determined to be the end products of furfural degradation. Interestingly, unlike under aerobic conditions, most of the furfural was converted to furfuryl alcohol under anaerobic conditions, without affecting the glucose consumption rate. Both the NADH/NAD(+) and NADPH/NADP(+) ratio decreased in the accordance with furfural concentration under both aerobic and anaerobic conditions. These results indicate the presence of a single or multiple endogenous enzymes with broad and high affinity for furfural and co-factors in C. glutamicum ATCC13032.

Influence of Corynebacterium parvum on the phagocytosis of /sup 198/Au colloids in rats

Energy Technology Data Exchange (ETDEWEB)

Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S. (Buenos Aires Univ. Nacional (Argentina). Facultad de Farmacia y Bioquimica)

1982-07-01

The kinetics of the phagocytosis of gelatin-protected /sup 198/Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the /sup 198/Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell.

The Trojan Horse of the microbiological arms race: phage-encoded toxins as a defence against eukaryotic predators.

Science.gov (United States)

Arnold, Jason W; Koudelka, Gerald B

2014-02-01

Phage-encoded Shiga toxin (Stx) acts as a bacterial defence against the eukaryotic predator Tetrahymena. To function as an effective bacterial anti-predator defence, Stx must kill a broad spectrum of predators. Consistent with that assertion, we show here that bacterially encoded Stx efficiently kills the bacteriovore Acanthamoeba castellanii in co-culture. We also show that, in addition to Stx, the phage-encoded exotoxin, diphtheria toxin (Dtx) expressed by Corynebacterium diphtheriae also can function as part of an anti-predator strategy; it kills Acanthamoeba in co-culture. Interestingly, only exotoxins produced by bacteria internalized by the Acanthamoeba predator are cytolethal; the presence of purified Dtx or Stx in culture medium has no effect on predator viability. This finding is consistent with our results indicating that intoxication of Acanthamoeba by these exotoxins does not require a receptor. Thus bacteria, in the disguise of a food source, function as a 'Trojan Horse', carrying genes encoding an exotoxin into target organisms. This 'Trojan Horse' mechanism of exotoxin delivery into predator cells allows intoxication of predators that lack a cell surface receptor for the particular toxin, allowing bacteria-bearing exotoxins to kill a broader spectrum of predators, increasing the fitness of the otherwise 'defenceless' prey bacteria. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Soil nutritional status and biogeography influence rhizosphere microbial communities associated with the invasive tree Acacia dealbata.

Science.gov (United States)

Kamutando, Casper N; Vikram, Surendra; Kamgan-Nkuekam, Gilbert; Makhalanyane, Thulani P; Greve, Michelle; Roux, Johannes J Le; Richardson, David M; Cowan, Don; Valverde, Angel

2017-07-26

Invasiveness and the impacts of introduced plants are known to be mediated by plant-microbe interactions. Yet, the microbial communities associated with invasive plants are generally poorly understood. Here we report on the first comprehensive investigation of the bacterial and fungal communities inhabiting the rhizosphere and the surrounding bulk soil of a widespread invasive tree, Acacia dealbata. Amplicon sequencing data indicated that rhizospheric microbial communities differed significantly in structure and composition from those of the bulk soil. Two bacterial (Alphaproteobacteria and Gammaproteobacteria) and two fungal (Pezizomycetes and Agaricomycetes) classes were enriched in the rhizosphere compared with bulk soils. Changes in nutritional status, possibly induced by A. dealbata, primarily shaped rhizosphere soil communities. Despite a high degree of geographic variability in the diversity and composition of microbial communities, invasive A. dealbata populations shared a core of bacterial and fungal taxa, some of which are known to be involved in N and P cycling, while others are regarded as plant pathogens. Shotgun metagenomic analysis also showed that several functional genes related to plant growth promotion were overrepresented in the rhizospheres of A. dealbata. Overall, results suggest that rhizosphere microbes may contribute to the widespread success of this invader in novel environments.

Diphtheria toxin can simultaneously bind to its receptor and adenylyl-(3',5')-uridine 3'-monophosphate

International Nuclear Information System (INIS)

Barbieri, J.T.; Collins, C.M.; Collier, R.J.

1986-01-01

Diphtheria toxin (DT) that was bound to receptors on BS-C-1 cells was able to bind approximately 1 molar equiv of adenylyl-(3',5')-uridine 3'-monophosphate (ApUp). In contrast, receptor-bound CRM197, a mutant form of toxin with greatly diminished affinity for dinucleotides, did not bind ApUp. Affinity of the dinucleotide for receptor-bound toxin differed from that for free toxin by less than an order of magnitude. These results indicate that the receptor site and the ApUp site on the toxin do not significantly overlap. BS-C-1 cells were incubated with or without 125 I-DT or CRM 197. They were then incubated with [ 32 P]ApUp, and assayed

Development and evaluation of chitosan microspheres for tetanus, diphtheria and divalent vaccines: a comparative study of subcutaneous and intranasal administration in mice.

Science.gov (United States)

Hashem, Fahima M; Fahmy, Sahar A; El-Sayed, Aly M; Al-Sawahli, Majid M

2013-01-01

There is a need to use the new technologies to induce immunity with minimum number of vaccination sessions to ensure compliance with reducing cost. To develop single shot vaccines of tetanus, diphtheria and divalent toxoids microsphere's formulations and to induce their immune response after intranasal and subcutaneous administration in mice. The microspheres were prepared using different concentrations of chitosan. Microsphere's morphology, particle size analysis, encapsulation efficiency and antigen integrity were performed and the best formulations were selected for in vitro and in vivo testing in mice. The developed microspheres have a yield percent of 70.3-91.5%. In vitro release of antigens indicated that tetanus release was increased up to 75 and 81% post T5 and TD5 formulations respectively, whereas diphtheria cumulative release increased up to 74 and 69% post D3 and TD5, respectively. Antibody levels produced were lower than that obtained from alum adsorbed vaccine but higher than the minimum level required to induce immunogenicity (>0.01 IU/mL). The subcutaneous route of administration was superior over the intranasal route in producing higher antibody levels. Chitosan microspheres were developed successfully and prove that chitosan represents a good candidate for vaccines delivery.

Quinone-dependent D-lactate dehydrogenase Dld (Cg1027 is essential for growth of Corynebacterium glutamicum on D-lactate

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Oikawa Tadao

2010-12-01

Full Text Available Abstract Background Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032. Results Here, the gene cg1027 was shown to encode the quinone-dependent D-lactate dehydrogenase (Dld by enzymatic analysis of the protein purified from recombinant E. coli. The absorption spectrum of purified Dld indicated the presence of FAD as bound cofactor. Inactivation of dld resulted in the loss of the ability to grow with D-lactate, which could be restored by plasmid-borne expression of dld. Heterologous expression of dld from C. glutamicum ATCC 13032 in C. efficiens enabled this species to grow with D-lactate as sole carbon source. Homologs of dld of C. glutamicum ATCC 13032 are not encoded in the sequenced genomes of other corynebacteria and mycobacteria. However, the dld locus of C. glutamicum ATCC 13032 shares 2367 bp of 2372 bp identical nucleotides with the dld locus of Propionibacterium freudenreichii subsp. shermanii, a bacterium used in Swiss-type cheese making. Both loci are flanked by insertion sequences of the same family suggesting a possible event of horizontal gene transfer. Conclusions Cg1067 encodes quinone-dependent D-lactate dehydrogenase Dld of Corynebacterium glutamicum. Dld is essential for growth with D-lactate as sole carbon source. The genomic region of dld likely has been acquired by horizontal gene transfer.

Crystallization and preliminary X-ray diffraction studies of FAD synthetase from Corynebacterium ammoniagenes

International Nuclear Information System (INIS)

Herguedas, Beatriz; Martínez-Júlvez, Marta; Frago, Susana; Medina, Milagros; Hermoso, Juan A.

2009-01-01

Native and selenomethionine-labelled FAD synthetase from C. ammoniagenes have been crystallized by the hanging-drop vapour-diffusion method. A MAD data set for SeMet-labelled FAD synthetase was collected to 2.42 Å resolution, while data sets were collected to 1.95 Å resolution for the native crystals. FAD synthetase from Corynebacterium ammoniagenes (CaFADS), a prokaryotic bifunctional enzyme that catalyses the phosphorylation of riboflavin as well as the adenylylation of FMN, has been crystallized using the hanging-drop vapour-diffusion method at 277 K. Diffraction-quality cubic crystals of native and selenomethionine-labelled (SeMet-CaFADS) protein belonged to the cubic space group P2 1 3, with unit-cell parameters a = b = c = 133.47 Å and a = b = c = 133.40 Å, respectively. Data sets for native and SeMet-containing crystals were collected to 1.95 and 2.42 Å resolution, respectively

Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

Science.gov (United States)

Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

2017-01-01

ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322

Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau

DEFF Research Database (Denmark)

Andersen, Annemette; Bjerregaard-Andersen, Morten; Rodrigues, Amabelia

2017-01-01

study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR......Background: In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls. Methods: In an observational......-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP...

Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

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Jonathan A Ewald

Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients

DEFF Research Database (Denmark)

Kronborg, Gitte; Weis, Nina; Madsen, Hans O

2002-01-01

for pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae....... The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role......Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor...

Arbuscular and Ectomycorrhizal Fungi Associated with the Invasive Brazilian Pepper Tree (Schinus terebinthifolius) and Two Native Plants in South Florida

Science.gov (United States)

Dawkins, Karim; Esiobu, Nwadiuto

2017-01-01

The potential role of soil fungi in the invasion of the Brazilian pepper tree (Schinus terebinthifolius—BP) in Florida is not known; although the low biotic resistance of Florida soils is often invoked to explain the prevalence of many invasive species. To gain an initial insight into BP's mycorrhizal associations, this study examined the rhizobiome of BP and two native plants (Hamelia patens and Bidens alba) across six locations. Arbuscular mycorrhizal fungi (AMF) associated with the roots of the target plants and bulk soil was characterized by spore morphotyping. Sequence analysis of metagenomic DNA from lateral roots/rhizosphere of BP (n = 52) and a native shrub H. patens (n = 37) on the same parcel yielded other fungal associates. Overall, the total population of AMF associated with BP was about two folds greater than that of the two native plants (p = 0.0001) growing on the same site. The dominant AMF under Schinus were members of the common Glomus and Rhizophagus spp. By contrast, the most prevalent AMF in the bulk soil and rhizosphere of the two Florida native plants, Acaulospora spp (29%) was sharply diminished (9%) under BP rhizosphere. Analysis of the ITS2 sequences also showed that Schinus rhizosphere had a high relative abundance of ectomycorrhizal fungi (76.5%) compared to the native H. patens (2.6%), with the species Lactifluus hygrophoroides (Basidiomycota) being the most prevalent at 61.5% (p < 0.05). Unlike the native plants where pathogenic fungi like Phyllosticta sp., Phoma sp., and Neofusicoccum andium were present (8.1% for H. patens), only one potentially pathogenic fungal taxon was detected (3.9%) under BP. The striking disparity in the relative abundance of AMF and other fungal types between BP and the native species is quite significant. Fungal symbionts could aide plant invasion via resource-use efficiency and other poorly defined mechanisms of protection from pathogens in their invaded range. This report exposes a potentially

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

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Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

An Evolutionary Modelling Approach To Understanding The Factors Behind Plant Invasiveness And Community Susceptibility To Invasion

DEFF Research Database (Denmark)

Warren, John; Topping, Christopher John; James, Penri

2011-01-01

Ecologists have had limited success in understanding which introduced species may become invasive. An evolutionary model is used to investigate which traits are associated with invasiveness. Translocation experiments were simulated in which species were moved into similar but evolutionary younger...

Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum.

Science.gov (United States)

Liu, Jiao; Wang, Yu; Lu, Yujiao; Zheng, Ping; Sun, Jibin; Ma, Yanhe

2017-11-16

Corynebacterium glutamicum is an important industrial workhorse and advanced genetic engineering tools are urgently demanded. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) have revolutionized the field of genome engineering. The CRISPR/Cas9 system that utilizes NGG as protospacer adjacent motif (PAM) and has good targeting specificity can be developed into a powerful tool for efficient and precise genome editing of C. glutamicum. Herein, we developed a versatile CRISPR/Cas9 genome editing toolbox for C. glutamicum. Cas9 and gRNA expression cassettes were reconstituted to combat Cas9 toxicity and facilitate effective termination of gRNA transcription. Co-transformation of Cas9 and gRNA expression plasmids was exploited to overcome high-frequency mutation of cas9, allowing not only highly efficient gene deletion and insertion with plasmid-borne editing templates (efficiencies up to 60.0 and 62.5%, respectively) but also simple and time-saving operation. Furthermore, CRISPR/Cas9-mediated ssDNA recombineering was developed to precisely introduce small modifications and single-nucleotide changes into the genome of C. glutamicum with efficiencies over 80.0%. Notably, double-locus editing was also achieved in C. glutamicum. This toolbox works well in several C. glutamicum strains including the widely-used strains ATCC 13032 and ATCC 13869. In this study, we developed a CRISPR/Cas9 toolbox that could facilitate markerless gene deletion, gene insertion, precise base editing, and double-locus editing in C. glutamicum. The CRISPR/Cas9 toolbox holds promise for accelerating the engineering of C. glutamicum and advancing its application in the production of biochemicals and biofuels.

Distance to invasive heart centre, performance of acute coronary angiography, and angioplasty and associated outcome in out-of-hospital cardiac arrest: a nationwide study.

Science.gov (United States)

Tranberg, Tinne; Lippert, Freddy K; Christensen, Erika F; Stengaard, Carsten; Hjort, Jakob; Lassen, Jens Flensted; Petersen, Frants; Jensen, Jan Skov; Bäck, Caroline; Jensen, Lisette Okkels; Ravkilde, Jan; Bøtker, Hans Erik; Terkelsen, Christian Juhl

2017-06-01

To evaluate whether the distance from the site of event to an invasive heart centre, acute coronary angiography (CAG)/percutaneous coronary intervention (PCI) and hospital-level of care (invasive heart centre vs. local hospital) is associated with survival in out-of-hospital cardiac arrest (OHCA) patients. Nationwide historical follow-up study of 41 186 unselected OHCA patients, in whom resuscitation was attempted between 2001 and 2013, identified through the Danish Cardiac Arrest Registry. We observed an increase in the proportion of patients receiving bystander CPR (18% in 2001, 60% in 2013, P acute CAG/PCI (5% in 2001, 27% in 2013, P acute CAG/PCI annually in each region was defined as the CAG/PCI index. The following variables were associated with lower mortality in multivariable analyses: direct admission to invasive heart centre (HR 0.91, 95% CI: 0.89-0.93), CAG/PCI index (HR 0.33, 95% CI: 0.25-0.45), population density above 2000 per square kilometre (HR 0.94, 95% CI: 0.89-0.98), bystander CPR (HR 0.97, 95% CI: 0.95-0.99) and witnessed OHCA (HR 0.87, 95% CI: 0.85-0.89), whereas distance to the nearest invasive centre was not associated with survival. Admission to an invasive heart centre and regional performance of acute CAG/PCI were associated with improved survival in OHCA patients, whereas distance to the invasive centre was not. These results support a centralized strategy for immediate post-resuscitation care in OHCA patients. © The Author 2017. Published on behalf of the European Society of Cardiology.

Active migration is associated with specific and consistent changes to gut microbiota in Calidris shorebirds.

Science.gov (United States)

Risely, Alice; Waite, David W; Ujvari, Beata; Hoye, Bethany J; Klaassen, Marcel

2018-03-01

Gut microbes are increasingly recognised for their role in regulating an animal's metabolism and immunity. However, identifying repeatable associations between host physiological processes and their gut microbiota has proved challenging, in part because microbial communities often respond stochastically to host physiological stress (e.g. fasting, forced exercise or infection). Migratory birds provide a valuable system in which to test host-microbe interactions under physiological extremes because these hosts are adapted to predictable metabolic and immunological challenges as they undergo seasonal migrations, including temporary gut atrophy during long-distance flights. These physiological challenges may either temporarily disrupt gut microbial ecosystems, or, alternatively, promote predictable host-microbe associations during migration. To determine the relationship between migration and gut microbiota, we compared gut microbiota composition between migrating and non-migrating ("resident") conspecific shorebirds sharing a flock. We performed this across two sandpiper species, Calidris ferruginea and Calidris ruficollis, in north-western Australia, and an additional C. ruficollis population 3,000 km away in southern Australia. We found that migrants consistently had higher abundances of the bacterial genus Corynebacterium (average 28% abundance) compared to conspecific residents (average gut community variation when excluding Corynebacterium. Our findings suggest a consistent relationship between Corynebacterium and Calidris shorebirds during migration, with further research required to identify causal mechanisms behind the association, and to elucidate functionality to the host. However, outside this specific association, migrating shorebirds broadly maintained gut community structure, which may allow them to quickly recover gut function after a migratory flight. This study provides a rare example of a repeatable and specific response of the gut microbiota to a

Unconventional gas development facilitates plant invasions.

Science.gov (United States)

Barlow, Kathryn M; Mortensen, David A; Drohan, Patrick J; Averill, Kristine M

2017-11-01

Vegetation removal and soil disturbance from natural resource development, combined with invasive plant propagule pressure, can increase vulnerability to plant invasions. Unconventional oil and gas development produces surface disturbance by way of well pad, road, and pipeline construction, and increased traffic. Little is known about the resulting impacts on plant community assembly, including the spread of invasive plants. Our work was conducted in Pennsylvania forests that overlay the Marcellus and Utica shale formations to determine if invasive plants have spread to edge habitat created by unconventional gas development and to investigate factors associated with their presence. A piecewise structural equation model was used to determine the direct and indirect factors associated with invasive plant establishment on well pads. The model included the following measured or calculated variables: current propagule pressure on local access roads, the spatial extent of the pre-development road network (potential source of invasive propagules), the number of wells per pad (indicator of traffic density), and pad age. Sixty-one percent of the 127 well pads surveyed had at least one invasive plant species present. Invasive plant presence on well pads was positively correlated with local propagule pressure on access roads and indirectly with road density pre-development, the number of wells, and age of the well pad. The vast reserves of unconventional oil and gas are in the early stages of development in the US. Continued development of this underground resource must be paired with careful monitoring and management of surface ecological impacts, including the spread of invasive plants. Prioritizing invasive plant monitoring in unconventional oil and gas development areas with existing roads and multi-well pads could improve early detection and control of invasive plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

Science.gov (United States)

Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

2005-08-01

The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

Science.gov (United States)

Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo®) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need. PMID:21904459

Specific IgE and IgG4 immune responses to tetanus and diphtheria toxoid in atopic and nonatopic children during the first two years of life

NARCIS (Netherlands)

Dannemann, A.; van Ree, R.; Kulig, M.; Bergmann, R. L.; Bauer, P.; Forster, J.; Guggenmoos-Holzmann, I.; Aalberse, R. C.; Wahn, U.

1996-01-01

BACKGROUND: In order to investigate, whether atopic and nonatopic children show differences in their specific IgE and IgG4 immune responses to tetanus (T) and diphtheria (D) antigens, we studied 538 children who had been followed from birth on and from whom records had been kept of all

Microparasites and Placental Invasiveness in Eutherian Mammals.

Directory of Open Access Journals (Sweden)

Isabella Capellini

Full Text Available Placental invasiveness-the number of maternal tissue layers separating fetal tissues from maternal blood-is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness.

Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes.

Science.gov (United States)

Ma, B; Li, H; Zhang, C; Yang, K; Qiao, B; Zhang, Z; Xu, Y

2013-10-01

To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Belgian Serosurveillance/Seroprevalence Study of Diphtheria, Tetanus and Pertussis Using a Luminex xMAP Technology-Based Pentaplex

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Raissa Nadège Caboré

2016-05-01

Full Text Available Serosurveillance and seroprevalence studies are an essential tool to monitor vaccine-preventable diseases. We have developed a magnetic bead-based pentaplex immunoassay (MIA for the simultaneous detection of IgG antibodies against diphtheria toxin (DT, tetanus toxin (TT, pertussis toxin (PT, filamentous hemagglutinin (FHA and pertactin (Prn. The in-house pentaplex MIA showed a good correlation with commercial ELISAs with correlation coefficients between 0.89 for PT and 0.98 for TT. Intra- and inter-assay variability was <10%. A total of 670 anonymized serum samples collected in 2012 in Belgian adults (ages 20–29.9 years were analyzed. Geometric mean concentrations (GMC were 0.2 (0.13–0.29 IU/mL for DT, 0.63 (0.45–0.82 IU/mL for TT, 3.9 (2.6–5.8 IU/mL for PT, 16.3 (11.7–22.7 IU/mL for FHA and 15.4 (10.1–23.6 IU/mL for Prn. Antibody concentrations were below the protective level of 0.1 IU/mL in 26.4% of the sera for DT and in 8.6% of the sera for TT. Anti-PT IgG concentrations indicative of recent pertussis infection (>125 IU/mL were detected in 1.2% of the subjects. High anti-PT antibodies were not correlated with high antibodies against any of the four other vaccine antigens. This pentaplex MIA will be used for a new large-scale Belgian serosurveillance/seroprevalence study of diphtheria, tetanus and pertussis.

Stress in biological invasions: Introduced invasive grey squirrels increase physiological stress in native Eurasian red squirrels.

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Santicchia, Francesca; Dantzer, Ben; van Kesteren, Freya; Palme, Rupert; Martinoli, Adriano; Ferrari, Nicola; Wauters, Lucas Armand

2018-05-23

Invasive alien species can cause extinction of native species through processes including predation, interspecific competition for resources or disease-mediated competition. Increases in stress hormones in vertebrates may be associated with these processes and contribute to the decline in survival or reproduction of the native species. Eurasian red squirrels (Sciurus vulgaris) have gone extinct across much of the British Isles and parts of Northern Italy following the introduction of North American invasive grey squirrels (Sciurus carolinensis). We extracted glucocorticoid metabolites from faecal samples to measure whether the presence of the invasive species causes an increase in physiological stress in individuals of the native species. We show that native red squirrels in seven sites where they co-occurred with invasive grey squirrels had glucocorticoid concentrations that were three times higher than those in five sites without the invasive species. Moreover, in a longitudinal study, stress hormones in native red squirrels increased after colonisation by grey squirrels. When we experimentally reduced the abundance of the invasive grey squirrels, the concentration of faecal glucocorticoid metabolites in co-occurring red squirrels decreased significantly between pre- and postremoval periods. Hence, we found that the invasive species acts as a stressor which significantly increases the concentrations of glucocorticoids in the native species. Given that sustained elevations in glucocorticoids could reduce body growth and reproductive rate, our results are consistent with previous studies where the co-occurrence of the invasive grey squirrel was associated with smaller size and lower reproductive output in red squirrels. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

ALDH1A3: A Marker of Mesenchymal Phenotype in Gliomas Associated with Cell Invasion.

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Wenlong Zhang

Full Text Available Aldehyde dehydrogenases (ALDH is a family of enzymes including 19 members. For now, ALDH activity had been wildly used as a marker of cancer stem cells (CSCs. But biological functions of relevant isoforms and their clinical applications are still controversial. Here, we investigate the clinical significance and potential function of ALDH1A3 in gliomas. By whole-genome transcriptome microarray and mRNA sequencing analysis, we compared the expression of ALDH1A3 in high- and low- grade gliomas as well as different molecular subtypes. Microarray analysis was performed to identify the correlated genes of ALDH1A3. We further used Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathways analysis to explore the biological function of ALDH1A3. Finally, by mRNA knockdown we revealed the relationship between ALDH1A3 and the ability of tumor invasion. ALDH1A3 overexpression was significantly associated with high grade as well as the higher mortality of gliomas in survival analysis. ALDH1A3 was characteristically highly expressed in Mesenchymal (Mes subtype gliomas. Moreover, we found that ALDH1A3 was most relevant to extracellular matrix organization and cell adhesion biological process, and the ability of tumor invasion was suppressed after ALDH1A3 knockdown in vitro. In conclusion, ALDH1A3 can serve as a novel marker of Mes phenotype in gliomas with potential clinical prognostic value. The expression of ALDH1A3 is associated with tumor cell invasion.

Overexpression of CD97 confers an invasive phenotype in glioblastoma cells and is associated with decreased survival of glioblastoma patients.

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Michael Safaee

Full Text Available Mechanisms of invasion in glioblastoma (GBM relate to differential expression of proteins conferring increased motility and penetration of the extracellular matrix. CD97 is a member of the epidermal growth factor seven-span transmembrane family of adhesion G-protein coupled receptors. These proteins facilitate mobility of leukocytes into tissue. In this study we show that CD97 is expressed in glioma, has functional effects on invasion, and is associated with poor overall survival. Glioma cell lines and low passage primary cultures were analyzed. Functional significance was assessed by transient knockdown using siRNA targeting CD97 or a non-target control sequence. Invasion was assessed 48 hours after siRNA-mediated knockdown using a Matrigel-coated invasion chamber. Migration was quantified using a scratch assay over 12 hours. Proliferation was measured 24 and 48 hours after confirmed protein knockdown. GBM cell lines and primary cultures were found to express CD97. Knockdown of CD97 decreased invasion and migration in GBM cell lines, with no difference in proliferation. Gene-expression based Kaplan-Meier analysis was performed using The Cancer Genome Atlas, demonstrating an inverse relationship between CD97 expression and survival. GBMs expressing high levels of CD97 were associated with decreased survival compared to those with low CD97 (p = 0.007. CD97 promotes invasion and migration in GBM, but has no effect on tumor proliferation. This phenotype may explain the discrepancy in survival between high and low CD97-expressing tumors. This data provides impetus for further studies to determine its viability as a therapeutic target in the treatment of GBM.

Clinical, social and ethical issues associated with non-invasive prenatal testing for aneuploidy.

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Griffin, Blanche; Edwards, Samantha; Chitty, Lyn S; Lewis, Celine

2018-03-01

Non-invasive prenatal testing (NIPT), based on analysis of cell-free foetal DNA, is rapidly becoming a preferred method to screen for chromosomal aneuploidy with the technology now available in over 90 countries. This review provides an up-to-date discussion of the key clinical, social and ethical implications associated with this revolutionary technology. Stakeholders are positive about a test that is highly accurate, safe, can be perfomed early in pregnancy, identifies affected pregnancies that might otherwise have been missed and reduces the need for invasive testing. Nevertheless, professional societies currently recommend it as an advanced screening test due to the low false positive rate (FPR). Despite the practical and psychological benefits, a number of concerns have been raised which warrant attention. These include the potential for routinisation of testing and subsequent impact on informed decision-making, an "easy" blood test inadvertently contributing to women feeling pressured to take the test, fears NIPT will lead to less tolerance and support for those living with Down syndrome and the heightened expectation of having "perfect babies". These issues can be addressed to some extent through clinician education, patient information and establishing national and international consensus in the development of comprehensive and regularly updated guidelines. As the number of conditions we are able to test for non-invasively expands it will be increasingly important to ensure pre-test counselling can be delivered effectively supported by knowledgeable healthcare professionals.

Expression, crystallization and preliminary crystallographic study of GluB from Corynebacterium glutamicum

International Nuclear Information System (INIS)

Liu, Qingbo; Li, Defeng; Hu, Yonglin; Wang, Da-Cheng

2013-01-01

GluB, a substrate-binding protein from C. glutamicum, was expressed, purified and crystallized, followed by X-ray diffraction data collection and preliminary crystallographic analysis. GluB is a substrate-binding protein (SBP) which participates in the uptake of glutamic acid in Corynebacterium glutamicum, a Gram-positive bacterium. It is part of an ATP-binding cassette (ABC) transporter system. Together with the transmembrane proteins GluC and GluD and the cytoplasmic protein GluA, which couples the hydrolysis of ATP to the translocation of glutamate, they form a highly active glutamate-uptake system. As part of efforts to study the amino-acid metabolism, especially the metabolism of glutamic acid by C. glutamicum, a bacterium that is widely used in the industrial production of glutamic acid, the GluB protein was expressed, purified and crystallized, an X-ray diffraction data set was collected to a resolution of 1.9 Å and preliminary crystallographic analysis was performed. The crystal belonged to space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 82.50, c = 72.69 Å

FudC, a protein primarily responsible for furfural detoxification in Corynebacterium glutamicum.

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Tsuge, Yota; Kudou, Motonori; Kawaguchi, Hideo; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

2016-03-01

Lignocellulosic hydrolysates contain compounds that inhibit microbial growth and fermentation, thereby decreasing the productivity of biofuel and biochemical production. In particular, the heterocyclic aldehyde furfural is one of the most toxic compounds found in these hydrolysates. We previously demonstrated that Corynebacterium glutamicum converts furfural into the less toxic compounds furfuryl alcohol and 2-furoic acid. To date, however, the genes involved in these oxidation and reduction reactions have not been identified in the C. glutamicum genome. Here, we show that Cgl0331 (designated FudC) is mainly responsible for the reduction of furfural into furfuryl alcohol in C. glutamicum. Deletion of the gene encoding FudC markedly diminished the in vivo reduction of furfural to furfuryl alcohol. Purified His-tagged FudC protein from Escherichia coli was also shown to convert furfural into furfuryl alcohol in an in vitro reaction utilizing NADPH, but not NADH, as a cofactor. Kinetic measurements demonstrated that FudC has a high affinity for furfural but has a narrow substrate range for other aldehydes compared to the protein responsible for furfural reduction in E. coli.

Metabolic engineering of Corynebacterium glutamicum for fermentative production of chemicals in biorefinery.

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Baritugo, Kei-Anne; Kim, Hee Taek; David, Yokimiko; Choi, Jong-Il; Hong, Soon Ho; Jeong, Ki Jun; Choi, Jong Hyun; Joo, Jeong Chan; Park, Si Jae

2018-05-01

Bio-based production of industrially important chemicals provides an eco-friendly alternative to current petrochemical-based processes. Because of the limited supply of fossil fuel reserves, various technologies utilizing microbial host strains for the sustainable production of platform chemicals from renewable biomass have been developed. Corynebacterium glutamicum is a non-pathogenic industrial microbial species traditionally used for L-glutamate and L-lysine production. It is a promising species for industrial production of bio-based chemicals because of its flexible metabolism that allows the utilization of a broad spectrum of carbon sources and the production of various amino acids. Classical breeding, systems, synthetic biology, and metabolic engineering approaches have been used to improve its applications, ranging from traditional amino-acid production to modern biorefinery systems for production of value-added platform chemicals. This review describes recent advances in the development of genetic engineering tools and techniques for the establishment and optimization of metabolic pathways for bio-based production of major C2-C6 platform chemicals using recombinant C. glutamicum.

Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

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Jeroen F Vermeulen

Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study

DEFF Research Database (Denmark)

Doherty, Jennifer A; Rossing, Mary Anne; Cushing-Haugen, Kara L

2010-01-01

, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat...... through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95......% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190...

Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

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Bolton, Kelly L; Chenevix-Trench, Georgia; Goh, Cindy

2012-01-01

Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear....

Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

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De Oliveira Tiago

2012-04-01

Full Text Available Abstract Background We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC cells. Methods Syndecan-2 (SDC-2 expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. Results SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. Conclusion SDC-2 is a novel (perineural invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.

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Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert

2017-07-01

: Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015. We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA). A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P  vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination. Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the

Mena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM.

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Roussos, Evanthia T; Goswami, Sumanta; Balsamo, Michele; Wang, Yarong; Stobezki, Robert; Adler, Esther; Robinson, Brian D; Jones, Joan G; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

2011-08-01

Mena, an actin regulatory protein, functions at the convergence of motility pathways that drive breast cancer cell invasion and migration in vivo. The tumor microenvironment spontaneously induces both increased expression of the Mena invasive (Mena(INV)) and decreased expression of Mena11a isoforms in invasive and migratory tumor cells. Tumor cells with this Mena expression pattern participate with macrophages in migration and intravasation in mouse mammary tumors in vivo. Consistent with these findings, anatomical sites containing tumor cells with high levels of Mena expression associated with perivascular macrophages were identified in human invasive ductal breast carcinomas and called TMEM. The number of TMEM sites positively correlated with the development of distant metastasis in humans. Here we demonstrate that mouse mammary tumors generated from EGFP-Mena(INV) expressing tumor cells are significantly less cohesive and have discontinuous cell-cell contacts compared to Mena11a xenografts. Using the mouse PyMT model we show that metastatic mammary tumors express 8.7 fold more total Mena and 7.5 fold more Mena(INV) mRNA than early non-metastatic ones. Furthermore, Mena(INV) expression in fine needle aspiration biopsy (FNA) samples of human invasive ductal carcinomas correlate with TMEM score while Mena11a does not. These results suggest that Mena(INV) is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that Mena(INV) expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.

Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

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Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

2014-10-01

Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

Complete genome sequence and lifestyle of black-pigmented Corynebacterium aurimucosum ATCC 700975 (formerly C. nigricans CN-1 isolated from a vaginal swab of a woman with spontaneous abortion

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Gartemann Karl-Heinz

2010-02-01

Full Text Available Abstract Background Corynebacterium aurimucosum is a slightly yellowish, non-lipophilic, facultative anaerobic member of the genus Corynebacterium and predominantly isolated from human clinical specimens. Unusual black-pigmented variants of C. aurimucosum (originally named as C. nigricans continue to be recovered from the female urogenital tract and they are associated with complications during pregnancy. C. aurimucosum ATCC 700975 (C. nigricans CN-1 was originally isolated from a vaginal swab of a 34-year-old woman who experienced a spontaneous abortion during month six of pregnancy. For a better understanding of the physiology and lifestyle of this potential urogenital pathogen, the complete genome sequence of C. aurimucosum ATCC 700975 was determined. Results Sequencing and assembly of the C. aurimucosum ATCC 700975 genome yielded a circular chromosome of 2,790,189 bp in size and the 29,037-bp plasmid pET44827. Specific gene sets associated with the central metabolism of C. aurimucosum apparently provide enhanced metabolic flexibility and adaptability in aerobic, anaerobic and low-pH environments, including gene clusters for the uptake and degradation of aromatic amines, L-histidine and L-tartrate as well as a gene region for the formation of selenocysteine and its incorporation into formate dehydrogenase. Plasmid pET44827 codes for a non-ribosomal peptide synthetase that plays the pivotal role in the synthesis of the characteristic black pigment of C. aurimucosum ATCC 700975. Conclusions The data obtained by the genome project suggest that C. aurimucosum could be both a resident of the human gut and possibly a pathogen in the female genital tract causing complications during pregnancy. Since hitherto all black-pigmented C. aurimucosum strains have been recovered from female genital source, biosynthesis of the pigment is apparently required for colonization by protecting the bacterial cells against the high hydrogen peroxide concentration in

The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

International Nuclear Information System (INIS)

Jolly, Shruti; Kestin, Larry L.; Goldstein, Neal S.; Vicini, Frank A.

2006-01-01

Purpose: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. Methods and Materials: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. Results: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p = 0.04). On multivariate analysis, positive margin (p < 0.01), positive/no reexcision (p = 0.04), and presence of LCIS (p = 0.02) remained independently associated with IBTR; positive margin (p < 0.01) and LCIS (p = 0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p < 0.01). Conclusion: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT

Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

Czech Academy of Sciences Publication Activity Database

Busche, T.; Šilar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, J.

2012-01-01

Roč. 13, č. 445 (2012), s. 445-464 ISSN 1471-2164 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * ECF sigma factor * Anti-sigma factor Subject RIV: EE - Microbiology, Virology Impact factor: 4.397, year: 2012

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial.

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Aaby, Peter; Ravn, Henrik; Roth, Adam; Rodrigues, Amabelia; Lisse, Ida Maria; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Rasmussen, Julie; Biering-Sørensen, Sofie; Whittle, Hilton; Benn, Christine Stabell

2012-08-01

Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

Risk Factors Associated with Invasive Cervical Carcinoma among ...

African Journals Online (AJOL)

BACKGROUND: Cervical cancer is a more serious public health problem than other cancers in women in Sub-Saharan Africa in general and in Ethiopia in particular. Thus, this study assessed risk factors related to invasive cervical carcinomas in southwestern Ethiopia. METHODS: Unmatched case control study was ...

Metabolic Engineering of Corynebacterium glutamicum for Methanol Metabolism

Science.gov (United States)

Witthoff, Sabrina; Schmitz, Katja; Niedenführ, Sebastian; Nöh, Katharina; Noack, Stephan

2015-01-01

Methanol is already an important carbon feedstock in the chemical industry, but it has found only limited application in biotechnological production processes. This can be mostly attributed to the inability of most microbial platform organisms to utilize methanol as a carbon and energy source. With the aim to turn methanol into a suitable feedstock for microbial production processes, we engineered the industrially important but nonmethylotrophic bacterium Corynebacterium glutamicum toward the utilization of methanol as an auxiliary carbon source in a sugar-based medium. Initial oxidation of methanol to formaldehyde was achieved by heterologous expression of a methanol dehydrogenase from Bacillus methanolicus, whereas assimilation of formaldehyde was realized by implementing the two key enzymes of the ribulose monophosphate pathway of Bacillus subtilis: 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase. The recombinant C. glutamicum strain showed an average methanol consumption rate of 1.7 ± 0.3 mM/h (mean ± standard deviation) in a glucose-methanol medium, and the culture grew to a higher cell density than in medium without methanol. In addition, [13C]methanol-labeling experiments revealed labeling fractions of 3 to 10% in the m + 1 mass isotopomers of various intracellular metabolites. In the background of a C. glutamicum Δald ΔadhE mutant being strongly impaired in its ability to oxidize formaldehyde to CO2, the m + 1 labeling of these intermediates was increased (8 to 25%), pointing toward higher formaldehyde assimilation capabilities of this strain. The engineered C. glutamicum strains represent a promising starting point for the development of sugar-based biotechnological production processes using methanol as an auxiliary substrate. PMID:25595770

Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

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Hellevik Turid

2012-04-01

Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

Metabolic evolution and a comparative omics analysis of Corynebacterium glutamicum for putrescine production.

Science.gov (United States)

Li, Zhen; Shen, Yu-Ping; Jiang, Xuan-Long; Feng, Li-Shen; Liu, Jian-Zhong

2018-02-01

Putrescine is widely used in the industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Because the highest titer of putrescine is much lower than that of its precursor L-ornithine reported in microorganisms to date, further work is needed to increase putrescine production in Corynebacterium glutamicum. We first compared 7 ornithine decarboxylase genes and found that the Enterobacter cloacae ornithine decarboxylase gene speC1 was most suitable for putrescine production in C. glutamicum. Increasing NADPH availability and blocking putrescine oxidation and acetylation were chosen as targets for metabolic engineering. The putrescine producer C. glutamicum PUT4 was first constructed by deleting puo, butA and snaA genes, and replacing the fabG gene with E. cloacae speC1. After adaptive evolution with C. glutamicum PUT4, the evolved strain C. glutamicum PUT-ALE, which produced an 96% higher amount of putrescine compared to the parent strain, was obtained. The whole genome resequencing indicates that the SNPs located in the odhA coding region may be associated with putrescine production. The comparative proteomic analysis reveals that the pentose phosphate and anaplerotic pathway, the glyoxylate cycle, and the ornithine biosynthetic pathway were upregulated in the evolved strain C. glutamicum PUT-ALE. The aspartate family, aromatic, and branched chain amino acid and fatty acid biosynthetic pathways were also observed to be downregulated in C. glutamicum PUT-ALE. Reducing OdhA activity by replacing the odhA native start codon GTG with TTG and overexpression of cgmA or pyc458 further improved putrescine production. Repressing the carB, ilvH, ilvB and aroE expression via CRISPRi also increased putrescine production by 5, 9, 16 and 19%, respectively.

Diphtheria Toxin-Induced Cell Death Triggers Wnt-Dependent Hair Cell Regeneration in Neonatal Mice.

Science.gov (United States)

Hu, Lingxiang; Lu, Jingrong; Chiang, Hao; Wu, Hao; Edge, Albert S B; Shi, Fuxin

2016-09-07

Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablated in vivo by the aminoglycoside antibiotic neomycin. A variety of Wnts (Wnt1, Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt7b, Wnt9a, Wnt9b, and Wnt11) and Wnt pathway component Krm2 were upregulated after DT damage. Nuclear β-catenin was upregulated in HCs and supporting cells of the DT-damaged cochlea. Pharmacological inhibition of Wnt decreased spontaneous regeneration, confirming a role of Wnt signaling in HC regeneration. Inhibition of Notch signaling further potentiated supporting cell proliferation and HC differentiation that occurred spontaneously. The absence of new HCs in the neomycin ears was correlated to less robust Wnt pathway activation, but the ears subjected to neomycin treatment nonetheless showed increased cell division and HC differentiation after subsequent forced upregulation of β-catenin. These studies suggest, first, that Wnt signaling plays a key role in regeneration, and, second, that the outcome of a regenerative response to damage in the newborn cochlea is determined by reaching a threshold level of Wnt signaling rather than its complete absence or presence. Sensory HCs of the inner ear do not regenerate in the adult, and their loss is a major cause of deafness. We found that HCs regenerated spontaneously in the newborn mouse after diphtheria toxin (DT)-induced, but not neomycin-induced, HC death. Regeneration depended on activation of Wnt signaling, and regeneration in DT-treated ears correlated to a higher level of Wnt activation than occurred in nonregenerating neomycin-treated ears. This is significant because insufficient

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo® in the context of treatment and prevention of invasive disease

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Bröker M

2011-07-01

Full Text Available Michael Bröker, Brian Cooper, Lisa M DeTora, Jeffrey J StoddardGlobal Medical Affairs, Novartis Vaccines and Diagnostics, Marburg, Germany, and Cambridge, MA, USAAbstract: Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo® was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.Keywords: invasive meningococcal disease, quadrivalent meningococcal conjugate vaccine, Neisseria meningitidis

Lactate production as representative of the fermentation potential of Corynebacterium glutamicum 2262 in a one-step process.

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Khuat, Hoang Bao Truc; Kaboré, Abdoul Karim; Olmos, Eric; Fick, Michel; Boudrant, Joseph; Goergen, Jean-Louis; Delaunay, Stéphane; Guedon, Emmanuel

2014-01-01

The fermentative properties of thermo-sensitive strain Corynebacterium glutamicum 2262 were investigated in processes coupling aerobic cell growth and the anaerobic fermentation phase. In particular, the influence of two modes of fermentation on the production of lactate, the fermentation product model, was studied. In both processes, lactate was produced in significant amount, 27 g/L in batch culture, and up to 55.8 g/L in fed-batch culture, but the specific production rate in the fed-batch culture was four times lower than that in the batch culture. Compared to other investigated fermentation processes, our strategy resulted in the highest yield of lactic acid from biomass. Lactate production by C. glutamicum 2262 thus revealed the capability of the strain to produce various fermentation products from pyruvate.

Osmolality, temperature, and membrane lipid composition modulate the activity of betaine transporter BetP in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Ozcan, Nuran; Ejsing, Christer S.; Shevchenko, Andrej

2007-01-01

The gram-positive soil bacterium Corynebacterium glutamicum, a major amino acid-producing microorganism in biotechnology, is equipped with several osmoregulated uptake systems for compatible solutes, which is relevant for the physiological response to osmotic stress. The most significant carrier......P activity. We further correlated the change in BetP regulation properties in cells grown at different temperatures to changes in the lipid composition of the plasma membrane. For this purpose, the glycerophospholipidome of C. glutamicum grown at different temperatures was analyzed by mass spectrometry using...... quantitative multiple precursor ion scanning. The molecular composition of glycerophospholipids was strongly affected by the growth temperature. The modulating influence of membrane lipid composition on BetP function was further corroborated by studying the influence of artificial modulation of membrane...

Comparison of two biochemical methods for identifying Corynebacterium pseudotuberculosis isolated from sheep and goats.

Science.gov (United States)

Huerta, Belén; Gómez-Gascón, Lidia; Vela, Ana I; Fernández-Garayzábal, José F; Casamayor, Almudena; Tarradas, Carmen; Maldonado, Alfonso

2013-06-01

The biochemical pattern of Cowan and Steel (BPCS) was compared with a commercial biochemical strip for the identification of Corynebacterium pseudotuberculosis isolated from small ruminants. On 16S rRNA gene sequencing, 40/78 coryneform isolates from the lymph nodes of sheep and goats with lesions resembling caseous lymphadenitis were identified as C. pseudotuberculosis. The sensitivities of the BPCS and the commercial biochemical strip relative to 16S rRNA sequencing were 80% and 85%, and their specificities were 92.1% and 94.7%, respectively; the level of agreement between the BPCS and the commercial biochemical strip was high (κ=0.82). Likelihood ratios for positive and negative results were 10.0 and 0.22 for the BPCS, and 16.0 and 0.16 for the commercial biochemical strip, respectively. These results indicate that the BPCS and the commercial biochemical strip are both useful for identifying C. pseudotuberculosis in veterinary microbiology laboratories. Copyright © 2012 Elsevier Ltd. All rights reserved.

ADJUVANT PROPERTIES OF NANOPARTICLES IMMOBILIZED RECOMBINANT DIPHTHERIA TOXOID FRAGMENT

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T. O. Chudina

2017-08-01

Full Text Available The aim of the research was to compare the characteristics of nanoparticles with different chemical structure and size (colloidal gold Gold 1 and Gold 2, calcium phosphate CaP and poly(lactideco-glykolid PLGA 1 and 2 to find the most efficient carriers of antigen — recombinant diphtheria toxoid for per os immunization. According to the MTT test, all studied particles show no significant cytotoxic impact on the studied cells in vitro, with the exception of CaP nanoparticles, which in high concentrations have cytotoxic effect on the U937 cells, and Gold nanoparticles 1 and 2, that are able to inhibit growth of the L929 cells. The most effective phagocytosis by macrophage-like cells J774 is observed for PLGA nanoparticles 1 and 2 with the immobilized antigen, while Gold nanoparticles 1 and 2 with antigen can interact with the surface of these cells without being phagocytated by them. In BALB/c mice immunized per os with antigen immobilized on PLGA 1 and 2 as well as Gold 2 carriers, the concentration of specific IgA antibodies in blood significantly increases after the second immunization, compared with controls. In the group of mice treated with PLGA 2 conjugated antigen, the concentration of specific IgG in blood after the third immunization also increases. These results show the promise of nanoparticles PLGA 1 and 2 as adjuvant for immunization per os.

An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae

DEFF Research Database (Denmark)

Jamal, Syed Babar; Hassan, Syed Shah; Tiwari, Sandeep

2017-01-01

proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983) were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries...

Bacterial Invasion of the Inner Ear in Association With Pneumococcal Meningitis

DEFF Research Database (Denmark)

Møller, Martin Nue; Brandt, Christian; Østergaard, Christian

2014-01-01

OBJECTIVE: To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. STUDY DESIGN: A well-established adult rat model of Streptococcus pneumoniae meningitis was used. METHODS: Thirty rats were inoculated intrathecally with S. pneumoniae...... scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial...... spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. CONCLUSION: From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral...

Earthworm invasion in North America: Food resource competition affects native millipede survival and invasive earthworm reproduction

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Bruce Snyder; Mac Callaham; Christopher Lowe; Paul Hendrix

2013-01-01

The invasive non-native earthworm Amynthas agrestis (Goto and Hatai, 1899) has recently been documented invading forests of the Appalachian Mountains in the southeastern United States. This epigeic earthworm decreases the depth of organic soil horizons, and this may play a role in the decrease of millipede richness and abundance associated with A. agrestis invasion. To...

A first step in understanding an invasive weed through its genes: an EST analysis of invasive Centaurea maculosa.

Science.gov (United States)

Broz, Amanda K; Broeckling, Corey D; He, Ji; Dai, Xinbin; Zhao, Patrick X; Vivanco, Jorge M

2007-05-24

The economic and biological implications of plant invasion are overwhelming; however, the processes by which plants become successful invaders are not well understood. Limited genetic resources are available for most invasive and weedy species, making it difficult to study molecular and genetic aspects that may be associated with invasion. As an initial step towards understanding the molecular mechanisms by which plants become invasive, we have generated a normalized Expressed Sequence Tag (EST) library comprising seven invasive populations of Centaurea maculosa, an invasive aster in North America. Seventy-seven percent of the 4423 unique transcripts showed significant similarity to existing proteins in the NCBI database and could be grouped based on gene ontology assignments. The C. maculosa EST library represents an initial step towards looking at gene-specific expression in this species, and will pave the way for creation of other resources such as microarray chips that can help provide a view of global gene expression in invasive C. maculosa and its native counterparts. To our knowledge, this is the first published set of ESTs derived from an invasive weed that will be targeted to study invasive behavior. Understanding the genetic basis of evolution for increased invasiveness in exotic plants is critical to understanding the mechanisms through which exotic invasions occur.

Metabolic engineering of Corynebacterium glutamicum aimed at alternative carbon sources and new products

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Volker Fritz Wendisch

2012-10-01

Full Text Available Corynebacterium glutamicum is well known as the amino acid-producing workhorse of fermentation industry, being used for multi-million-ton scale production of glutamate and lysine for more than 60 years. However, it is only recently that extensive research has focused on engineering it beyond the scope of amino acids. Meanwhile, a variety of corynebacterial strains allows access to alternative carbon sources and/or allows production of a wide range of industrially relevant compounds. Some of these efforts set new standards in terms of titers and productivities achieved whereas others represent a proof-of-principle. These achievements manifest the position of C. glutamicum as an important industrial microorganism with capabilities far beyond the traditional amino acid production. In this review we focus on the state of the art of metabolic engineering of C. glutamicum for utilization of alternative carbon sources, (e.g. coming from wastes and unprocessed sources, and construction of C. glutamicum strains for production of new products such as diamines, organic acids and alcohols.

Positive feedback between mycorrhizal fungi and plants influences plant invasion success and resistance to invasion.

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Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

2010-08-24

Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.

Positive feedback between mycorrhizal fungi and plants influences plant invasion success and resistance to invasion.

Directory of Open Access Journals (Sweden)

Qian Zhang

2010-08-01

Full Text Available Negative or positive feedback between arbuscular mycorrhizal fungi (AMF and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb. Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.

Plant invasions: Merging the concepts of species invasiveness and community invasibility

Czech Academy of Sciences Publication Activity Database

Richardson, D. M.; Pyšek, Petr

2006-01-01

Roč. 30, č. 3 (2006), s. 409-431 ISSN 0309-1333 Institutional research plan: CEZ:AV0Z60050516 Keywords : plant invasions * species invasiveness * community invasibility Subject RIV: EF - Botanics Impact factor: 1.278, year: 2006

Sensitivity of cancer cells to truncated diphtheria toxin.

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Yi Zhang

2010-05-01

Full Text Available Diphtheria toxin (DT has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines.In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC tumor growth, respectively.Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50 ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice.DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.

Invasion of vascular cells in vitro by Porphyromonas endodontalis.

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Dorn, B R; Harris, L J; Wujick, C T; Vertucci, F J; Progulske-Fox, A

2002-04-01

The objective of this study was to determine whether laboratory strains and clinical isolates of microorganisms associated with root canal infections can invade primary cultures of cardiovascular cells. Quantitative levels of bacterial invasion of human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC) were measured using a standard antibiotic protection assay. Transmission electron microscopy was used to confirm and visualize internalization within the vascular cells. Of the laboratory and clinical strains tested, only P. endodontalis ATCC 35406 was invasive in an antibiotic protection assay using HCAEC and CASMC. Invasion of P. endodontalis ATCC 35406 was confirmed by transmission electron microscopy. Certain microorganisms associated with endodontic infections are invasive. If bacterial invasion of the vasculature contributes to the pathogenesis of cardiovascular disease, then microorganisms in the pulp chamber represent potential pathogens.

Activity of disinfectants and biofilm production of Corynebacterium pseudotuberculosis

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Maria da C.A. Sá

2013-11-01

Full Text Available To verify the occurrence of caseous lymphadenitis in sheep and goats on farms of Pernambuco, Brazil, and in animals slaughtered in two Brazilian cities (Petrolina/PE and Juazeiro/BA, and to characterize the susceptibility profile of Corynebacterium pseudotuberculosis to disinfectants and antimicrobials, and its relationship with biofilm production were the objectives of this study. 398 samples were tested for sensitivity to antimicrobial drugs, disinfectants, and biofilm production. Among the 108 samples collected on the properties, 75% were positive for C. pseudotuberculosis. Slaughterhouse samples indicated an occurrence of caseous lymphadenitis in 15.66% and 6.31% for animals slaughtered in Petrolina and Juazeiro respectively. With respect to antimicrobials, the sensitivity obtained was 100% for florfenicol and tetracycline; 99.25% for enrofloxacin, ciprofloxacin and lincomycin; 98.99% for cephalothin; 98.74% for norfloxacin and sulfazotrim; 97.74% for gentamicin; 94.22% for ampicillin; 91.71% for amoxicillin; 91.21% for penicillin G; 89.19% for neomycin and 0% for novobiocin. In analyzes with disinfectants, the efficiency for chlorhexidine was 100%, 97.20% for quaternary ammonium, 87.40% for chlorine and 84.40% for iodine. 75% of the isolates were weak or non-biofilm producers. For the consolidated biofilm, found that iodine decreased biofilm formation in 13 isolates and quaternary ammonia in 11 isolates. The reduction of the biofilm formation was observed for iodine and quaternary ammonium in consolidated biofilm formation in 33% and 28% of the isolates, respectively. The results of this study highlight the importance of establishing measures to prevent and control the disease.

An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

DEFF Research Database (Denmark)

Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

2015-01-01

.8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs. CONCLUSION: Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally...

Gene expression analysis of early stage endometrial cancersreveals unique transcripts associated with grade and histologybut not depth of invasion

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John eRisinger

2013-06-01

Full Text Available Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least 4-fold (univariate t-test, p <0.001 between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

Extravillous trophoblast invasion in placenta accreta is associated with differential local expression of angiogenic and growth factors: a cross-sectional study.

Science.gov (United States)

Duzyj, C M; Buhimschi, I A; Laky, C A; Cozzini, G; Zhao, G; Wehrum, M; Buhimschi, C S

2018-02-22

Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over-invasion in placenta accreta is associated with aberrant invasion-site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme. Cross-sectional series. Yale-New Haven Hospital. Women with histologically confirmed normal and abnormal placentation. Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor β (TGFβ) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (VEGF) mediators hypoxia-inducible factor-1α (HIF1α) and endostatin, were assessed using immunoassay. Differences in median H-score by immunostaining and in mean serum level by immunoassay. By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase-14. Absent decidual HIF1α and endostatin were observed in areas of VEGF upregulation. TGFβ1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age. Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling. Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds. Placenta accreta histology shows dysregulation of angiogenic and growth factors. © 2018 Royal College of Obstetricians and Gynaecologists.

E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis.

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Liu, Jiang-Bo; Feng, Chen-Yi; Deng, Miao; Ge, Dong-Feng; Liu, De-Chun; Mi, Jian-Qiang; Feng, Xiao-Shan

2017-08-01

This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.

Evaluation of immunogenicity and safety of the new tetanus-reduced diphtheria (Td) vaccines (GC1107) in healthy Korean adolescents: a phase II, double-blind, randomized, multicenter clinical trial.

Science.gov (United States)

Rhim, Jung-Woo; Lee, Kyung-Yil; Kim, Sang-Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Kim, Hwang Min; Choi, Young-Youn; Ma, Sang-Hyuk; Kim, Dong-Ho; Ahn, Dong Ho; Kang, Jin-Han

2013-04-01

This phase II clinical trial was conducted to compare the immunogenicity and safety of a newly developed tetanus-reduced diphtheria (Td) vaccine (GC1107-T5.0 and GC1107-T7.5) and control vaccine. This study was also performed to select the proper dose of tetanus toxoid in the new Td vaccines. Healthy adolescents aged between 11 and 12 yr participated in this study. A total of 130 subjects (44 GC1107-T5.0, 42 GC1107-T7.5 and 44 control vaccine) completed a single dose of vaccination. Blood samples were collected from the subjects before and 4 weeks after the vaccination. In this study, all subjects (100%) in both GC1107-T5.0 and GC1107-T7.5 groups showed seroprotective antibody levels (≥ 0.1 U/mL) against diphtheria or tetanus toxoids. After the vaccination, the geometric mean titer (GMT) against diphtheria was significantly higher in Group GC1107-T5.0 (6.53) and GC1107-T7.5 (6.11) than in the control group (3.96). The GMT against tetanus was 18.6 in Group GC1107-T5.0, 19.94 in GC1107-T7.5 and 19.01 in the control group after the vaccination. In this study, the rates of local adverse reactions were 67.3% and 59.1% in GC1107-T5.0 and GC1107-7.5, respectively. No significant differences in the number of adverse reactions, prevalence and degree of severity of the solicited and unsolicited adverse reactions were observed among the three groups. Thus, both newly developed Td vaccines appear to be safe and show good immunogenicity. GC1107-T5.0, which contains relatively small amounts of tetanus toxoid, has been selected for a phase III clinical trial.

Anti-vascular endothelial growth factor therapy-induced glioma invasion is associated with accumulation of Tie2-expressing monocytes

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Hossain, Mohammad B.; Conrad, Charles A.; Aldape, Kenneth D.; Fuller, Gregory N.; Marini, Frank C.; Alonso, Marta M.; Idoate, Miguel Angel; Gilbert, Mark R.; Fueyo, Juan; Gomez-Manzano, Candelaria

2014-01-01

The addition of anti-angiogenic therapy to the few treatments available to patients with malignant gliomas was based on the fact that these tumors are highly vascularized and on encouraging results from preclinical and clinical studies. However, tumors that initially respond to this therapy invariably recur with the acquisition of a highly aggressive and invasive phenotype. Although several myeloid populations have been associated to this pattern of recurrence, a specific targetable population has not been yet identified. Here, we present evidence for the accumulation of Tie2-expressing monocytes/macrophages (TEMs) at the tumor/normal brain interface of mice treated with anti-VEGF therapies in regions with heightened tumoral invasion. Furthermore, we describe the presence of TEMs in malignant glioma surgical specimens that recurred after bevacizumab treatment. Our studies showed that TEMs enhanced the invasive properties of glioma cells and secreted high levels of gelatinase enzymatic proteins. Accordingly, Tie2+MMP9+ monocytic cells were consistently detected in the invasive tumor edge upon anti-VEGF therapies. Our results suggest the presence of a specific myeloid/monocytic subpopulation that plays a pivotal role in the mechanism of escape of malignant gliomas from anti-VEGF therapies and therefore constitutes a new cellular target for combination therapies in patients selected for anti-angiogenesis treatment. PMID:24809734

MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK.

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Iseki, Yasuhito; Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Hirakawa, Kosei; Ohira, Masaichi

2018-04-01

miR-96 is reported to inhibit reversion cysteine-rich Kazal motif (RECK), which is associated with tumor invasion, in solid cancer types (e.g. breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of this study is to clarify whether miR-96 is similarly associated with tumor invasion in colorectal cancer. We performed western blotting to investigate the expression of RECK when miR-96 mimics or inhibitors were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was assessed by a reverse transcription polymerase chain reaction. An invasion assay was used to evaluate tumor invasion. The expression of RECK was inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96 mimics were shown to promote tumor invasion. miR-96 may be associated with tumor invasion through inhibition of RECK expression in colorectal cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Molecular cloning and expression of Corynebacterium glutamicum genes for amino acid synthesis in Escherichia coli cells

International Nuclear Information System (INIS)

Beskrovnaya, O.Yu.; Fonshtein, M.Yu.; Kolibaba, L.G.; Yankovskii, N.K.; Debabov, V.G.

1989-01-01

Molecular cloning of Corynebacterium glutamicum genes for threonine and lysine synthesis has been done in Escherichia coli cells. The clonal library of EcoRI fragments of chromosomal DNA of C. glutamicum was constructed on the plasmid vector λpSL5. The genes for threonine and lysine synthesis were identified by complementation of E. coli mutations in thrB and lysA genes, respectively. Recombinant plasmids, isolated from independent ThrB + clone have a common 4.1-kb long EcoRI DNA fragment. Hybrid plasmids isolated from LysA + transductants of E. coli have common 2.2 and 3.3 kb long EcoRI fragments of C. glutamicum DNA. The hybrid plasmids consistently transduced the markers thrB + and lysA + . The Southern hybridization analysis showed that the cloned DNA fragments hybridized with the fragments of identical length in C. glutamicum chromosomes

A first step in understanding an invasive weed through its genes: an EST analysis of invasive Centaurea maculosa

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He Ji

2007-05-01

Full Text Available Abstract Background The economic and biological implications of plant invasion are overwhelming; however, the processes by which plants become successful invaders are not well understood. Limited genetic resources are available for most invasive and weedy species, making it difficult to study molecular and genetic aspects that may be associated with invasion. Results As an initial step towards understanding the molecular mechanisms by which plants become invasive, we have generated a normalized Expressed Sequence Tag (EST library comprising seven invasive populations of Centaurea maculosa, an invasive aster in North America. Seventy-seven percent of the 4423 unique transcripts showed significant similarity to existing proteins in the NCBI database and could be grouped based on gene ontology assignments. Conclusion The C. maculosa EST library represents an initial step towards looking at gene-specific expression in this species, and will pave the way for creation of other resources such as microarray chips that can help provide a view of global gene expression in invasive C. maculosa and its native counterparts. To our knowledge, this is the first published set of ESTs derived from an invasive weed that will be targeted to study invasive behavior. Understanding the genetic basis of evolution for increased invasiveness in exotic plants is critical to understanding the mechanisms through which exotic invasions occur.

Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum.

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Wen, Jingbai; Xiao, Yanqiu; Liu, Ting; Gao, Qiuqiang; Bao, Jie

2018-01-01

Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock. We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum . Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment. The high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients

Ultraviolet light induction of diphtheria toxin-resistant mutations in normal and DNA repair-deficient human and Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Trosko, J.E.; Schultz, R.S.; Chang, C.C.; Glover, T.

1980-01-01

The role on unrepaired DNA lesions in the production of mutations is suspected of contributing to the initiation phase of carcinogenesis. Since the molecular basis of mutagenesis is not understood in eukaryotic cells, development of new genetic markers for quantitative in vitro measurement of mutations for mammalian cells is needed. Furthermore, mammalian cells, genetically deficient for various DNA repair enzymes, will be needed to study the role of unrepaired DNA lesions in mutagenesis. The results in this report relate to preliminary attempts to characterize the diphtheria toxin resistance marker as a useful quantitative genetic marker in human cells and to isolate and characterize various DNA repair-deficient Chinese hamster cells

Implantation of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers

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Viacheslav, Ilyin; Kiryukhina, Nataliya

Nasal carriage of Staphylococcus aureus is a well-documented risk factor of infection and inflammation of the skin, soft tissues and bacteremia. It is also known that most often etiology of these disorders is associated with autoinfection. The present-day methods of opportunistic pathogens eradication from the nasal cavity are based principally on the use of antiseptic and antibacterial agents. For instance, a local antibiotic mupirocin in the form of nasal ointment is considered to be the gold standard for the treatment of S. aureus carriage. The literature describes investigations showing how mupirocin can strengthen antibiotic resistance in S. aureus strains, including those with methicillin resistance (MRSA). It is also common knowledge that recolonization of the nasal mucous membrane takes place within several months after mupirocin treatment. This circumstance dictates the necessity to look for alternative ways of preventing the S. aureus carriage and methods of elimination. One of the methods of nasal S. aureus elimination is implantation of nonpathogenic microorganisms which will extrude opportunistic pathogens without impinging the symbiotic microbiota. Effectiveness of saline suspension of Corynebacterium pseudodiphtheriticum containing spray was assessed in a several chamber experiments with simulation of some spaceflight factors (dry immersion, isolation). Various schemes of application of preparations were applied. In all cases of corynebacteria application the strong inhibiting effect against S. aureus was detected. This fact opens a prospect of using nonpathogenic corynebacteria as a nasal probiotic. Administration of the nasal corynebacteria spray possibly prevented cross-infection by MRSA and appearance of staphylococcal infection. Further pre-clinical and clinical study of this bacterial therapy method is under development.

A review of the influence of root-associating fungi and root exudates on the success of invasive plants

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Cindy Bongard

2012-08-01

Full Text Available Plant-fungal interactions are essential for understanding the distribution and abundance of plants species. Recently, arbuscular mycorrhizal fungal (AMF partners of non-indigenous invasive plants have been hypothesized to be a critical factor influencing the invasion processes. AMF are known to improve nutrient and moisture uptake, as well as disrupt parasitic and pathogenic microbes in the host plant. Such benefits may enable invaders to establish significant and persistent populations in environments previously dominated by natives. Coupling these findings with studies on invader pathogen-disrupting root exudates is not well documented in the literature describing plant invasion strategies. The interaction effects of altered AMF associations and the impact of invader root exudates would be more relevant than understanding the AMF dynamics or the phytochemistry of successful invaders in isolation, particularly given that AMF and root exudates can have a similar role in pathogen control but function quite differently. One means to achieve this goal is to assess these strategies concurrently by characterizing both the general (mostly pathogens or commensals and AM-specific fungal colonization patterns found in field collected root samples of successful invaders, native plants growing within dense patches of invaders, and native plants growing separately from invaders. In this review I examine the emerging evidence of the ways in which AMF-plant interactions and the production of defensive root exudates provide pathways to invasive plant establishment and expansion, and conclude that interaction studies must be pursued to achieve a more comprehensive understanding of successful plant invasion.

First report of the intracellular fish parasite Sphaerothecum destruens associated with the invasive topmouth gudgeon (Pseudorasbora parva in France

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Charrier Amélie

2016-01-01

Full Text Available Sphaerothecum destruens has emerged as a serious parasite of fish. Its life cycle, as well as its association with Asian cyprinids, allows it to infect a wide range of hosts. The topmouth gudgeon (Pseudorasbora parva, an invasive species that has rapidly colonized Europe, has been shown to be a healthy carrier of the parasite. However, in France, the presence of S. destruens and its possible association with P. parva have not yet been demonstrated. Here, we screened topmouth gudgeon DNA for S. destruens using PCR amplification of an 18S rRNA gene fragment of the parasite. Sequencing and phylogenetic analysis confirmed the presence of S. destruens in the invasive fish species. Our results suggest that P. parva can be a potent vector of the parasite, and has the potential to become a major ecological and economic threat to the French fish population.

Invasive fungal infections in Colombian patients with systemic lupus erythematosus.

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Santamaría-Alza, Y; Sánchez-Bautista, J; Fajardo-Rivero, J F; Figueroa, C L

2018-06-01

Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality and hospital readmission compared with patients with systemic lupus erythematosus without invasive fungal infection.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

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Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

Phenology of exotic invasive weeds associated with downy brome

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The exotic and highly invasive annual grass downy brome (Bromus tectorum) has invaded millions of hectares of rangelands throughout the Intermountain West. Downy brome increases the chance, rate, season and spread of wildfires, resulting in the destruction of native plant communities and the wildli...

Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

Science.gov (United States)

Boyle, Michelle J; Reiling, Linda; Feng, Gaoqian; Langer, Christine; Osier, Faith H; Aspeling-Jones, Harvey; Cheng, Yik Sheng; Stubbs, Janine; Tetteh, Kevin K A; Conway, David J; McCarthy, James S; Muller, Ivo; Marsh, Kevin; Anders, Robin F; Beeson, James G

2015-03-17

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Does responsiveness to arbuscular mycorrhizas depend on plant invasive status?

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1. Some posit invasive alien plants are less dependent on mycorrhizal associations than native plants, and thus weak mycorrhizal responsiveness may be a general mechanism of plant invasion. 2. Here, we tested whether mycorrhizal responsiveness varies by plant invasive status while controlling for ph...

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

Energy Technology Data Exchange (ETDEWEB)

Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B. [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Revetta, Frank [Department of Pathology, Vanderbilt University, Nashville, TN (United States); Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Department of Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States)

2015-01-01

The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. - Highlights: • Chemical inhibition of TGFβ signaling advances collective invasion

Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

DEFF Research Database (Denmark)

Song, H.; Koessler, T.; Ahmed, S.

2008-01-01

allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

Antibacterial activity of essential oils extracted from Satureja hortensis against selected clinical pathogens

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Görmez, Arzu; Yanmiş, Derya; Bozari, Sedat; Gürkök, Sumeyra

2017-04-01

The antibiotic resistance of pathogenic microorganisms has become a worldwide concern to public health. To overcome the current resistance problem, new antimicrobial agents are extremely needed. The aim of the present study was to evaluate the antibacterial activity of Satureja hortensis essential oils against seven clinical pathogens. Chemical compositions of hydro distillated essential oils from S. hortensis were analyzed by GS-MS. The antibacterial activity was investigated against Corynebacterium diphtheria, Salmonella typhimurium, Serratia plymuthica Yersinia enterocolitica, Y. frederiksenii, Y. pseudotuberculosis and Vibrio cholerae by the use of disc diffusion method and broth micro dilution method. The minimum inhibitory concentration (MIC) values of essential oils were found as low as 7.81 µg/mL. Notably, essential oils of S. hortensis exhibited remarkable antimicrobial activities against the tested clinical pathogens. The results indicate that these essential oils can be used in treatment of different infectious diseases.

5-Nitroimidazole Derivatives and their Antimicrobial Activity

International Nuclear Information System (INIS)

Khan, K.M.; Salar, U.; Yousuf, S.; Naz, F.

2016-01-01

5-Nitroimidazole derivatives 2-8 were synthesized from secnidazole. The syntheses were accomplished in two steps which start from the oxidation of secnidazole to the secnidazolone 1. Secnidazolone 1 was converted into its hydrazone derivative 2-8 by treating with different substituted acid hydrazide. Compounds 2-8 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, compounds 3 and 4 showed the significant activity against Staphylococcus epidermidis, however, compound 2 showed good inhibitions against Corynebacterium diphtheria when compared with the standard. Compound 3 showed good inhibitory potential against tested Gram-negative bacterial strains i.e. Enterobacter aerogene, Escherichia coli, Salmonella typhi, Salmonella paratyphi A, Shigella flexeneri and Vibrio choleriae. All synthetic derivatives were also tested against eight fungal stains, however, they were weekly active against Aspergillus flavus and Candida albican. The synthesized compounds were characterized by different spectroscopy techniques. (author)

Heterologous expression of the Halothiobacillus neapolitanus carboxysomal gene cluster in Corynebacterium glutamicum.

Science.gov (United States)

Baumgart, Meike; Huber, Isabel; Abdollahzadeh, Iman; Gensch, Thomas; Frunzke, Julia

2017-09-20

Compartmentalization represents a ubiquitous principle used by living organisms to optimize metabolic flux and to avoid detrimental interactions within the cytoplasm. Proteinaceous bacterial microcompartments (BMCs) have therefore created strong interest for the encapsulation of heterologous pathways in microbial model organisms. However, attempts were so far mostly restricted to Escherichia coli. Here, we introduced the carboxysomal gene cluster of Halothiobacillus neapolitanus into the biotechnological platform species Corynebacterium gluta-micum. Transmission electron microscopy, fluorescence microscopy and single molecule localization microscopy suggested the formation of BMC-like structures in cells expressing the complete carboxysome operon or only the shell proteins. Purified carboxysomes consisted of the expected protein components as verified by mass spectrometry. Enzymatic assays revealed the functional production of RuBisCO in C. glutamicum both in the presence and absence of carboxysomal shell proteins. Furthermore, we could show that eYFP is targeted to the carboxysomes by fusion to the large RuBisCO subunit. Overall, this study represents the first transfer of an α-carboxysomal gene cluster into a Gram-positive model species supporting the modularity and orthogonality of these microcompartments, but also identified important challenges which need to be addressed on the way towards biotechnological application. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering biotin prototrophic Corynebacterium glutamicum strains for amino acid, diamine and carotenoid production.

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Peters-Wendisch, P; Götker, S; Heider, S A E; Komati Reddy, G; Nguyen, A Q; Stansen, K C; Wendisch, V F

2014-12-20

The Gram-positive Corynebacterium glutamicum is auxotrophic for biotin. Besides the biotin uptake system BioYMN and the transcriptional regulator BioQ, this bacterium possesses functional enzymes for the last three reactions of biotin synthesis starting from pimeloyl-CoA. Heterologous expression of bioF from the Gram-negative Escherichia coli enabled biotin synthesis from pimelic acid added to the medium, but expression of bioF together with bioC and bioH from E. coli did not entail biotin prototrophy. Heterologous expression of bioWAFDBI from Bacillus subtilis encoding another biotin synthesis pathway in C. glutamicum allowed for growth in biotin-depleted media. Stable growth of the recombinant was observed without biotin addition for eight transfers to biotin-depleted medium while the empty vector control stopped growth after the first transfer. Expression of bioWAFDBI from B. subtilis in C. glutamicum strains overproducing the amino acids l-lysine and l-arginine, the diamine putrescine, and the carotenoid lycopene, respectively, enabled formation of these products under biotin-depleted conditions. Thus, biotin-prototrophic growth and production by recombinant C. glutamicum were achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

Cellular Entry of the Diphtheria Toxin Does Not Require the Formation of the Open-Channel State by Its Translocation Domain

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Alexey S. Ladokhin

2017-09-01

Full Text Available Cellular entry of diphtheria toxin is a multistage process involving receptor targeting, endocytosis, and translocation of the catalytic domain across the endosomal membrane into the cytosol. The latter is ensured by the translocation (T domain of the toxin, capable of undergoing conformational refolding and membrane insertion in response to the acidification of the endosomal environment. While numerous now classical studies have demonstrated the formation of an ion-conducting conformation—the Open-Channel State (OCS—as the final step of the refolding pathway, it remains unclear whether this channel constitutes an in vivo translocation pathway or is a byproduct of the translocation. To address this question, we measure functional activity of known OCS-blocking mutants with H-to-Q replacements of C-terminal histidines of the T-domain. We also test the ability of these mutants to translocate their own N-terminus across lipid bilayers of model vesicles. The results of both experiments indicate that translocation activity does not correlate with previously published OCS activity. Finally, we determined the topology of TH5 helix in membrane-inserted T-domain using W281 fluorescence and its depth-dependent quenching by brominated lipids. Our results indicate that while TH5 becomes a transbilayer helix in a wild-type protein, it fails to insert in the case of the OCS-blocking mutant H322Q. We conclude that the formation of the OCS is not necessary for the functional translocation by the T-domain, at least in the histidine-replacement mutants, suggesting that the OCS is unlikely to constitute a translocation pathway for the cellular entry of diphtheria toxin in vivo.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

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Reinaldo de Menezes Martins

2008-11-01

Full Text Available A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK, which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (>0.15 µg/mL with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Urinary collecting system invasion is associated with poor survival in patients with clear-cell renal cell carcinoma.

Science.gov (United States)

Bailey, George C; Boorjian, Stephen A; Ziegelmann, Matthew J; Westerman, Mary E; Lohse, Christine M; Leibovich, Bradley C; Cheville, John C; Thompson, R Houston

2017-04-01

To evaluate the prognostic significance of urinary collecting system invasion (UCSI) in a large series of patients with clear-cell renal cell carcinoma (RCC). Patients with clear-cell RCC treated with nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained registry. One urological pathologist re-reviewed all slides. Cancer-specific survival was estimated using the Kaplan-Meier method, and associations of UCSI with death from RCC were evaluated using Cox models. Of the 859 patients with clear-cell RCC, 58 (6.8%) had UCSI. At last follow-up, 310 patients had died from RCC at a median of 1.8 years after surgery. The median follow-up for patients alive at last follow-up was 8.2 years. The estimated cancer-specific survival at 10 years after surgery for patients with UCSI was 17%, compared with 60% for patients without UCSI (P system invasion is associated with poor prognosis among patients with clear-cell RCC. If validated, consideration should be given to including UCSI in future staging systems. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Five potential consequences of climate change for invasive species.

Science.gov (United States)

Hellmann, Jessica J; Byers, James E; Bierwagen, Britta G; Dukes, Jeffrey S

2008-06-01

Scientific and societal unknowns make it difficult to predict how global environmental changes such as climate change and biological invasions will affect ecological systems. In the long term, these changes may have interacting effects and compound the uncertainty associated with each individual driver. Nonetheless, invasive species are likely to respond in ways that should be qualitatively predictable, and some of these responses will be distinct from those of native counterparts. We used the stages of invasion known as the "invasion pathway" to identify 5 nonexclusive consequences of climate change for invasive species: (1) altered transport and introduction mechanisms, (2) establishment of new invasive species, (3) altered impact of existing invasive species, (4) altered distribution of existing invasive species, and (5) altered effectiveness of control strategies. We then used these consequences to identify testable hypotheses about the responses of invasive species to climate change and provide suggestions for invasive-species management plans. The 5 consequences also emphasize the need for enhanced environmental monitoring and expanded coordination among entities involved in invasive-species management.

Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

Science.gov (United States)

Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

2016-01-01

CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

Engineered coryneform bacteria as a bio-tool for arsenic remediation.

Science.gov (United States)

Villadangos, Almudena F; Ordóñez, Efrén; Pedre, Brandán; Messens, Joris; Gil, Jose A; Mateos, Luis M

2014-12-01

Despite current remediation efforts, arsenic contamination in water sources is still a major health problem, highlighting the need for new approaches. In this work, strains of the nonpathogenic and highly arsenic-resistant bacterium Corynebacterium glutamicum were used as inexpensive tools to accumulate inorganic arsenic, either as arsenate (As(V)) or arsenite (As(III)) species. The assays made use of "resting cells" from these strains, which were assessed under well-established conditions and compared with C. glutamicum background controls. The two mutant As(V)-accumulating strains were those used in a previously published study: (i) ArsC1/C2, in which the gene/s encoding the mycothiol-dependent arsenate reductases is/are disrupted, and (ii) MshA/C mutants unable to produce mycothiol, the low molecular weight thiol essential for arsenate reduction. The As(III)-accumulating strains were either those lacking the arsenite permease activities (Acr3-1 and Acr3-2) needed in As(III) release or recombinant strains overexpressing the aquaglyceroporin genes (glpF) from Corynebacterium diphtheriae or Streptomyces coelicolor, to improve As(III) uptake. Both genetically modified strains accumulated 30-fold more As(V) and 15-fold more As(III) than the controls. The arsenic resistance of the modified strains was inversely proportional to their metal accumulation ability. Our results provide the basis for investigations into the use of these modified C. glutamicum strains as a new bio-tool in arsenic remediation efforts.

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

International Nuclear Information System (INIS)

Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

2001-01-01

We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

E-commerce trade in invasive plants.

Science.gov (United States)

Humair, Franziska; Humair, Luc; Kuhn, Fabian; Kueffer, Christoph

2015-12-01

Biological invasions are a major concern in conservation, especially because global transport of species is still increasing rapidly. Conservationists hope to anticipate and thus prevent future invasions by identifying and regulating potentially invasive species through species risk assessments and international trade regulations. Among many introduction pathways of non-native species, horticulture is a particularly important driver of plant invasions. In recent decades, the horticultural industry expanded globally and changed structurally through the emergence of new distribution channels, including internet trade (e-commerce). Using an automated search algorithm, we surveyed, on a daily basis, e-commerce trade on 10 major online auction sites (including eBay) of approximately three-fifths of the world's spermatophyte flora. Many recognized invasive plant species (>500 species) (i.e., species associated with ecological or socio-economic problems) were traded daily worldwide on the internet. A markedly higher proportion of invasive than non-invasive species were available online. Typically, for a particular plant family, 30-80% of recognized invasive species were detected on an auction site, but only a few percentages of all species in the plant family were detected on a site. Families that were more traded had a higher proportion of invasive species than families that were less traded. For woody species, there was a significant positive relationship between the number of regions where a species was sold and the number of regions where it was invasive. Our results indicate that biosecurity is not effectively regulating online plant trade. In the future, automated monitoring of e-commerce may help prevent the spread of invasive species, provide information on emerging trade connectivity across national borders, and be used in horizon scanning exercises for early detection of new species and their geographic source areas in international trade. © 2015 Society for

Liver injury in invasive aspergillus. Echographic findings

International Nuclear Information System (INIS)

Otero Fernandez, R.; Garcia Revillo, J.; Paez Moreno, J.; Zurera Tendero, L.J.

1994-01-01

Aspergillus is the second most common mycoses in immuno compromised patients. The invasive form is associated with a mortality of approximately 100%. We present a case of invasive aspergillus in a heart transplant recipient in whom ultrasound disclosed the presence of liver injury which was later confirmed by necropsy. We review the available literature. (Author) 15 refs

A comparative study on phyllosphere nitrogen fixation by newly isolated Corynebacterium sp. & Flavobacterium sp. and their potentialities as biofertilizer.

Science.gov (United States)

Giri, S; Pati, B R

2004-01-01

A number of nitrogen fixing bacteria has been isolated from forest phyllosphere on the basis of nitrogenase activity. Among them two best isolates are selected and identified as Corynebacterium sp. AN1 & Flavobacterium sp. TK2 able to reduce 88 and 132 n mol of acetylene (10(8)cells(-1)h(-1)) respectively. They were grown in large amount and sprayed on the phyllosphere of maize plants as a substitute for nitrogenous fertilizer. Marked improvements in growth and total nitrogen content of the plant have been observed by the application of these nitrogen-fixing bacteria. An average 30-37% increase in yield was obtained, which is nearer to chemical fertilizer treatment. Comparatively better effect was obtained by application of Flavobacterium sp.

The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

International Nuclear Information System (INIS)

Chen, Wen-Liang; Kuo, Kuang-Tai; Chou, Teh-Ying; Chen, Chien-Lung; Wang, Chih-Hao; Wei, Yau-Huei; Wang, Liang-Shun

2012-01-01

Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0

Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Taizhou Polytechnic College, Taizhou (China); Zhang, Ling; Shao, Yueting; Liang, Zuowen; Shao, Chen; Wang, Bo; Guo, Baofeng; Li, Na; Zhao, Xuejian [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Li, Yang, E-mail: lyang@jlu.edu.cn [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Xu, Deqi [Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

2011-12-16

Highlights: Black-Right-Pointing-Pointer Neu3 is as one of the sialidases and regulates cell surface functions. Black-Right-Pointing-Pointer A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. Black-Right-Pointing-Pointer The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. Black-Right-Pointing-Pointer Targeting Neu3 may have utility for gene-based therapy of human cancer metastasis. -- Abstract: Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed

Rapid detection of Corynebacterium pseudotuberculosis in clinical samples from sheep.

Science.gov (United States)

Kumar, Jyoti; Tripathi, Bhupendra Nath; Kumar, Rajiv; Sonawane, Ganesh Gangaram; Dixit, Shivendra Kumar

2013-08-01

Corynebacterium pseudotuberculosis, a Gram-positive bacterium is the causative agent of caseous lymphadenitis (CLA), a chronic disease of sheep, goats and other warm blooded animals. In the present study, a total of 1,080 sheep reared under semi-intensive system on organized farms situated in the semi arid tropical region of Rajasthan, India, was clinically examined. Pus samples from superficial lymph nodes of 25 (2.31%) adult sheep showing clinical lesions similar to CLA were collected for laboratory analyses. On the basis of morphological, cultural and biochemical characteristics 12 (48%) bacterial isolates from pus identified it as C. pseudotuberculosis. A polymerase chain reaction (PCR) assay targeting Putative oligopeptide/dipeptide ABC transporter, nicotinamide adenine dinucleotide phosphate (NADP) oxidoreductase coenzyme F420-dependent and proline iminopeptidase (PIP) genes of C. pseudotuberculosis was developed that showed 14 pus samples as positive. All C. pseudotuberculosis isolates were also found positive for these genes in the PCR. The specificity of the PCR products was confirmed by sequencing of the amplified products that showed 98-100% homology with published sequences available in the NCBI database. The present study shows the incidence of CLA as 2.31%, 1.1% and 1.29% based on clinical, bacterial culture and direct pus PCR assay, respectively. The PCR assay was rapid, specific and as significant as bacterial culture in detecting bacteria directly in the clinical pus samples. The PCR assay developed in the study can be applied for the diagnosis and control of CLA. Furthermore, the assay can also be applied to detect C. pseudotuberculosis in various clinical samples.

Isoprenoid Pyrophosphate-Dependent Transcriptional Regulation of Carotenogenesis in Corynebacterium glutamicum

Directory of Open Access Journals (Sweden)

Petra Peters-Wendisch

2017-04-01

Full Text Available Corynebacterium glutamicum is a natural producer of the C50 carotenoid decaprenoxanthin. The crtEcg0722crtBIYEb operon comprises most of its genes for terpenoid biosynthesis. The MarR-type regulator encoded upstream and in divergent orientation of the carotenoid biosynthesis operon has not yet been characterized. This regulator, named CrtR in this study, is encoded in many actinobacterial genomes co-occurring with terpenoid biosynthesis genes. CrtR was shown to repress the crt operon of C. glutamicum since DNA microarray experiments revealed that transcript levels of crt operon genes were increased 10 to 70-fold in its absence. Transcriptional fusions of a promoter-less gfp gene with the crt operon and crtR promoters confirmed that CrtR represses its own gene and the crt operon. Gel mobility shift assays with purified His-tagged CrtR showed that CrtR binds to a region overlapping with the −10 and −35 promoter sequences of the crt operon. Isoprenoid pyrophosphates interfered with binding of CrtR to its target DNA, a so far unknown mechanism for regulation of carotenogenesis. The molecular details of protein-ligand interactions remain to be studied. Decaprenoxanthin synthesis by C. glutamicum wild type was enhanced 10 to 30-fold upon deletion of crtR and was decreased 5 to 6-fold as result of crtR overexpression. Moreover, deletion of crtR was shown as metabolic engineering strategy to improve production of native and non-native carotenoids including lycopene, β-carotene, C.p. 450 and sarcinaxanthin.

Molecular epidemiology of Corynebacterium pseudotuberculosis isolated from horses in California.

Science.gov (United States)

Haas, Dionei J; Dorneles, Elaine M S; Spier, Sharon J; Carroll, Scott P; Edman, Judy; Azevedo, Vasco A; Heinemann, Marcos B; Lage, Andrey P

2017-04-01

Corynebacterium pseudotuberculosis biovar Equi is an important pathogen of horses. It is increasing in frequency in the United States, and is responsible for various clinical forms of infection, including external abscesses, internal abscesses of the abdominal or thoracic cavities, and ulcerative lymphangitis. The host/pathogen factors dictating the form or severity of infection are currently unknown. Our recent investigations have shown that genotyping C. pseudotuberculosis isolates using enterobacterial repetitive intergenic consensus (ERIC)-PCR is useful for understanding the evolutionary genetics of the species as well for molecular epidemiology studies. The aims of the present study were to assess (i) the genetic diversity of C. pseudotuberculosis strains isolated from horses in California, United States and (ii) the epidemiologic relationships among isolates. One hundred and seven C. pseudotuberculosis biovar Equi isolates from ninety-five horses, and two C. pseudotuberculosis biovar Ovis strains, C. pseudotuberculosis ATCC 19410 T type strain and C. pseudotuberculosis 1002 vaccine strain, were fingerprinted using the ERIC 1+2-PCR. C. pseudotuberculosis isolated from horses showed a high genetic diversity, clustering in twenty-seven genotypes with a diversity index of 0.91. Minimal spanning tree showed four major clonal complexes with a pattern of temporal clustering. Strains isolated from the same horse showed identical ERIC 1+2-PCR genotype, with the exception of two strains isolated from the same animal that showed distinct genotypes, suggesting a co-infection. We found no strong genetic signals related to clinical form (including internal versus external infections). However, temporal clustering of genotypes was observed. Copyright © 2016. Published by Elsevier B.V.

Mutagenic Deimmunization of Diphtheria Toxin for Use in Biologic Drug Development

Directory of Open Access Journals (Sweden)

Joerg U. Schmohl

2015-10-01

Full Text Available Background: Targeted toxins require multiple treatments and therefore must be deimmunized. We report a method of protein deimmunization based on the point mutation of highly hydrophilic R, K, D, E, and Q amino acids on the molecular surface of truncated diphtheria-toxin (DT390. Methods: Based on their surface position derived from an X-ray-crystallographic model, residues were chosen for point mutation that were located in prominent positions on the molecular surface and away from the catalytic site. Mice were immunized with a targeted toxin containing either a mutated DT390 containing seven critical point mutations or the non-mutated parental toxin form. Results: Serum analysis revealed a significant 90% reduction in anti-toxin antibodies in mice immunized with the mutant, but not the parental drug form despite multiple immunizations. The experiment was repeated in a second strain of mice with a different MHC-haplotype to address whether point mutation removed T or B cell epitopes. Findings were identical indicating that B cell epitopes were eliminated from DT. The mutant drug form lost only minimal activity in vitro as well as in vivo. Conclusion: These findings indicate that this method may be effective for deimmunizing of other proteins and that discovery of a deimmunized form of DT may lead to the development of more effective targeted toxin.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

Directory of Open Access Journals (Sweden)

Hanane Ennajdaoui

2016-05-01

Full Text Available Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3 expression correlates with malignancy, but its role(s in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP revealed significant overlap of IGF2BP3 and microRNA (miRNA binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

Science.gov (United States)

Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

2016-05-31

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Minimally invasive distal pancreatectomy

NARCIS (Netherlands)

Røsok, Bård I.; de Rooij, Thijs; van Hilst, Jony; Diener, Markus K.; Allen, Peter J.; Vollmer, Charles M.; Kooby, David A.; Shrikhande, Shailesh V.; Asbun, Horacio J.; Barkun, Jeffrey; Besselink, Marc G.; Boggi, Ugo; Conlon, Kevin; Han, Ho Seong; Hansen, Paul; Kendrick, Michael L.; Kooby, David; Montagnini, Andre L.; Palanivelu, Chinnasamy; Wakabayashi, Go; Zeh, Herbert J.

2017-01-01

The first International conference on Minimally Invasive Pancreas Resection was arranged in conjunction with the annual meeting of the International Hepato-Pancreato-Biliary Association (IHPBA), in Sao Paulo, Brazil on April 19th 2016. The presented evidence and outcomes resulting from the session

Ancestral origins and invasion pathways in a globally invasive bird correlate with climate and influences from bird trade.

Science.gov (United States)

Jackson, Hazel; Strubbe, Diederik; Tollington, Simon; Prys-Jones, Robert; Matthysen, Erik; Groombridge, Jim J

2015-08-01

Invasive species present a major threat to global biodiversity. Understanding genetic patterns and evolutionary processes that reinforce successful establishment is paramount for elucidating mechanisms underlying biological invasions. Among birds, the ring-necked parakeet (Psittacula krameri) is one of the most successful invasive species, established in over 35 countries. However, little is known about the evolutionary genetic origins of this species and what population genetic signatures tell us about patterns of invasion. We reveal the ancestral origins of populations across the invasive range and explore the potential influence of climate and propagule pressure from the pet trade on observed genetic patterns. Ring-necked parakeet samples representing the ancestral native range (n = 96) were collected from museum specimens, and modern samples from the invasive range (n = 855) were gathered from across Europe, Mauritius and Seychelles, and sequenced for two mitochondrial DNA markers comprising 868 bp of cytochrome b and control region, and genotyped at 10 microsatellite loci. Invasive populations comprise birds that originate predominantly from Pakistan and northern areas of India. Haplotypes associated with more northerly distribution limits in the ancestral native range were more prevalent in invasive populations in Europe, and the predominance of Asian haplotypes in Europe is consistent with the higher number of Asian birds transported by the pet trade outside the native range. Successful establishment of invasive species is likely to be underpinned by a combination of environmental and anthropogenic influences. © 2015 John Wiley & Sons Ltd.

Macrodinychus mites as parasitoids of invasive ants: an overlooked parasitic association.

Science.gov (United States)

Lachaud, Jean-Paul; Klompen, Hans; Pérez-Lachaud, Gabriela

2016-07-21

Mites are frequent ant symbionts, yet the exact nature of their interactions with their hosts is poorly known. Generally, myrmecophilous mites show adaptations for dispersal through phoresis, but species that lack such an adaptation may have evolved unusual specialized relationships with their hosts. The immature stages of Macrodinychus multispinosus develop as ectoparasitoids of pupae of the invasive ant Paratrechina longicornis. Feeding stages show regressed locomotor appendages. These mites complete their development on a single host, sucking all of its body content and therefore killing it. Locally high proportions of parasitized host pupae suggest that M. multispinosus could serve as a biological control agent. This is the ninth species of Macrodinychus reported as ant parasite, and the third known as parasitoid of invasive ants, confirming a unique habit in the evolution of mite feeding strategies and suggesting that the entire genus might be parasitic on ants. Several mites' characteristics, such as their protective morphology, possible viviparity, lack of a specialized stage for phoretic dispersal, and low host specificity, combined with both the general low aggressiveness of invasive P. longicornis towards other ants and its possible susceptibility to generalist ectoparasites would account for the host shift in native macrodinychid mites.

Evaluation of three methods for DNA fingerprinting of Corynebacterium pseudotuberculosis strains isolated from goats in Poland.

Science.gov (United States)

Stefańska, Ilona; Rzewuska, Magdalena; Binek, Marian

2008-01-01

Phenotypic approaches based on metabolic and biological characteristics of Corynebacterium pseudotuberculosis have been limited due to insufficient discrimination between closely related isolates. In this paper we present performance and convenience of three molecular typing methods: BOX-PCR, random amplification of polymorphic DNA (RAPD) and amplification of DNA fragments surrounding rare restriction site (ADSRRS-fingerprinting) in genome analysis of these bacteria. Among examined 61 strains there were distinguished four, eight and 10 different genotypes by BOX-PCR, RAPD and ADSRRS-fingerprinting, respectively. The value of discrimination index was the lowest for BOX-PCR (D = 0.265), much bigger for RAPD (D = 0.539) and the highest for ADSRRS-fingerprinting (D = 0.604). The good discriminatory ability and reproducibility of RAPD and ADSRRS-fingerprinting indicates that those techniques may be particularly applied for epidemiological studies of C. pseudotuberculosis isolates. We found that ADSRRS-fingerprinting is a rapid method offering good discrimination power, excellent reproducibility and may be applied for epidemiological studies of intraspecific genetic relatedness of C. pseudotuberculosis strains.

Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

NARCIS (Netherlands)

Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

2008-01-01

Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

High-resolution detection of DNA binding sites of the global transcriptional regulator GlxR in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Jungwirth, Britta; Sala, Claudia; Kohl, Thomas A

2013-01-01

of the 6C non-coding RNA gene and to non-canonical DNA binding sites within protein-coding regions. The present study underlines the dynamics within the GlxR regulon by identifying in vivo targets during growth on glucose and contributes to the expansion of knowledge of this important transcriptional......The transcriptional regulator GlxR has been characterized as a global hub within the gene-regulatory network of Corynebacterium glutamicum. Chromatin immunoprecipitation with a specific anti-GlxR antibody and subsequent high-throughput sequencing (ChIP-seq) was applied to C. glutamicum to get new...... mapping of these data on the genome sequence of C. glutamicum, 107 enriched DNA fragments were detected from cells grown with glucose as carbon source. GlxR binding sites were identified in the sequence of 79 enriched DNA fragments, of which 21 sites were not previously reported. Electrophoretic mobility...

New parasitoid-predator associations: female parasitoids do not avoid competition with generalist predators when sharing invasive prey

Science.gov (United States)

Chailleux, Anaïs; Wajnberg, Eric; Zhou, Yuxiang; Amiens-Desneux, Edwige; Desneux, Nicolas

2014-12-01

Optimal habitat selection is essential for species survival in ecosystems, and interspecific competition is a key ecological mechanism for many observed species association patterns. Specialized animal species are commonly affected by resource and interference competition with generalist and/or omnivorous competitors, so avoidance behavior could be expected. We hypothesize that specialist species may exploit broad range cues from such potential resource competitors (i.e., cues possibly common to various generalist and/or omnivorous predators) to avoid costly competition regarding food or reproduction, even in new species associations. We tested this hypothesis by studying short-term interactions between a native larval parasitoid and a native generalist omnivorous predator recently sharing the same invasive host/prey, the leaf miner Tuta absoluta. We observed a strong negative effect of kleptoparasitism (food resource stealing) instead of classical intraguild predation on immature parasitoids. There was no evidence that parasitoid females avoided the omnivorous predator when searching for oviposition sites, although we studied both long- and short-range known detection mechanisms. Therefore, we conclude that broad range cue avoidance may not exist in our biological system, probably because it would lead to too much oviposition site avoidance which would not be an efficient and, thus, beneficial strategy. If confirmed in other parasitoids or specialist predators, our findings may have implications for population dynamics, especially in the current context of increasing invasive species and the resulting creation of many new species associations.

Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

International Nuclear Information System (INIS)

Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

2011-01-01

Highlights: → NDRG1 was knockdown in cervical and ovarian cancer cell lines by shRNA technology. → NDRG1 knockdown resulted in increased cell invasion activities. → Ninety-six common deregulated genes in both cell lines were identified by cDNA microarray. → Eleven common NDRG1-regulated genes might enhance cell invasive activity. → Regulation of invasion by NDRG1 is an indirect and complicated process. -- Abstract: N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.

Ultrasonographic diagnosis and minimally invasive treatment of a patent urachus associated with a patent omphalomesenteric duct in a newborn

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Bertozzi, Mirko; Recchia, Nicola; Di Cara, Giuseppe; Riccioni, Sara; Rinaldi, Victoria Elisa; Esposito, Susanna; Appignani, Antonino

2017-01-01

Abstract Rational: Patent urachus (PU) is due to an incomplete obliteration of the urachus, whereas patent omphalomesenteric duct (POMD) is due to an incomplete obliteration of the vitelline duct. These anomalies are very rarely associated with one another. We describe a case of a newborn with a PU associated with a POMD, who was diagnosed by an abdominal ultrasound (US) and laparoscopy, and managed with a minimally invasive excision. Patient concern: A 28-day-old male neonate was referred to our hospital to investigate a delay in umbilical healing, with blood-mucinous material spillage for 3 weeks prior to the referral. The baby had no symptoms and was in good general health. Diagnosis: After a thorough cleaning of the umbilical stump, a clear granuloma with a suspected fistula was evident under the seat of the ligature of the stump. An abdominal US examination revealed the formation of a full communication, starting below the umbilical stump and developing along the anterior abdominal wall that connected with the bladder dome. The US also revealed a tubular formation containing air, which was compatible with POMD, in the deepest portion of the same umbilical stump. Considering these findings, the rare diagnosis of a PU associated with a POMD duct was suspected. Interventions: The child was then hospitalized for an elective laparoscopy that confirmed the US picture, and a minimally invasive excision was performed. Outcome: The postoperative course was favorable and uneventful. Lessons: Our case underlines the importance of evaluating all persisting umbilical lesions without delay when conventional pharmacological therapies fail. Using a US as the first approach is valuable and should be supported by laparoscopy to confirm the diagnosis; a minimally invasive excision of the remnants appears to be an effective therapeutic approach. PMID:28746173

Demand- and supply-side determinants of diphtheria-pertussis-tetanus nonvaccination and dropout in rural India.

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Ghosh, Arpita; Laxminarayan, Ramanan

2017-02-15

Although 93% of 12- to 23-month-old children in India receive at least one vaccine, typically Bacillus Calmette-Guérin, only 75% complete the recommended three doses of diphtheria-pertussis-tetanus (DPT, also referred to as DTP) vaccine. Determinants can be different for nonvaccination and dropout but have not been examined in earlier studies. We use the three-dose DPT series as a proxy for the full sequence of recommended childhood vaccines and examine the determinants of DPT nonvaccination and dropout between doses 1 and 3. We analyzed data on 75,728 6- to 23-month-old children in villages across India to study demand- and supply-side factors determining nonvaccination with DPT and dropout between DPT doses 1 and 3, using a multilevel approach. Data come from the District Level Household and Facility Survey 3 (2007-08). Individual- and household-level factors were associated with both DPT nonvaccination and dropout between doses 1 and 3. Children whose mothers had no schooling were 2.3 times more likely not to receive any DPT vaccination and 1.5 times more likely to drop out between DPT doses 1 and 3, compared with children whose mothers had 10 or more years of schooling. Although supply-side factors related to availability of public health facilities and immunization-related health workers in villages were not correlated with dropout between DPT doses 1 and 3, children in districts where 46% or more villages had a healthcare subcentre were 1.5 times more likely to receive at least one dose of DPT vaccine compared with children in districts where 30% or fewer villages had subcentres. Nonvaccination with DPT in India is influenced by village- and district-level contextual factors over and above individuals' background characteristics. Dropout between DPT doses 1 and 3 is associated more strongly with demand-side factors than with village- and district-level supply-side factors. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.

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Tolboom, Tanja C A; van der Helm-Van Mil, Annette H M; Nelissen, Rob G H H; Breedveld, Ferdinand C; Toes, René E M; Huizinga, Tom W J

2005-07-01

Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. FLS from patients with RA were more invasive than FLS from patients with OA (P patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P patient characteristic, given the much smaller intraindividual than interindividual FLS variation.

Invasive ductal carcinoma within fibroadenoma: a case report

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2009-01-01

Introduction Fibroadenoma is the most common benign tumor of the female breast with the highest incidence before age 30. Fibroadenoma may be associated with fibrocystic changes, proliferative epithelial changes, and extremely rarely, with non-invasive and invasive cancer. Case presentation We present a rare case of a 39 years old female with invasive ductal carcinoma arising within fibroadenoma. Conclusion There is a low percentage of fibroadenomas harboring carcinoma; however, all breast lumps should be seriously managed; extirpation and histological examination is recommended. PMID:19946485

Associations between antioxidant vitamins and the risk of invasive cervical cancer in Chinese women: A case-control study.

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Guo, Liyuan; Zhu, Hong; Lin, Chengjun; Che, Jianhua; Tian, Xiujuan; Han, Shiyu; Zhao, Honghui; Zhu, Yumei; Mao, Dongwei

2015-09-04

Previous studies on the associations between dietary antioxidant vitamins and the risk of cervical cancer remain inconsistent, and little evidence is available for serum antioxidant vitamins, which provide more accurate measurements of these nutrients. We conducted a case-control study of 458 incident cases with invasive cervical cancer and 742 controls to assess the effects of diet or serum antioxidant vitamins. Higher serum antioxidant vitamins were associated with a lower risk of cervical cancer after adjusting for potential confounders. The odds ratios (ORs) for the highest (vs. lowest) quartile were 0.66 (95% confidence interval [CI] = 0.46-0.93; P = 0.024) for α-carotene, 0.63 (95% CI = 0.45-0.90; P = 0.006) for β-carotene, 0.53 (95% CI = 0.37-0.74; P vitamin E, and 0.48 (95% CI = 0.33-0.69; P vitamin C. Dietary intakes of vitamins E and C were inversely associated with the risk of cervical cancer. Risk of cervical cancer from serum antioxidant vitamins was more evident in passive smokers than non-passive smokers. These findings indicated that antioxidant vitamins (mainly α-carotene, β-carotene, and vitamins E and C) might be beneficial in reducing the risk of invasive cervical cancer in Chinese women, especially in passive smokers.

Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells.

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Wenjing Zhao

Full Text Available The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293 and liver (HL-7702 cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion.