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Sample records for edwardsiella tarda pathogenesis

  1. Pathogenesis of and strategies for preventing Edwardsiella tarda infection in fish

    PubMed Central

    2012-01-01

    Edwardsiella tarda is one of the serious fish pathogens, infecting both cultured and wild fish species. Research on edwardsiellosis has revealed that E. tarda has a broad host range and geographic distribution, and contains important virulence factors that enhance bacterial survival and pathogenesis in hosts. Although recent progress in edwardsiellosis research has enabled the development of numerous, highly effective vaccine candidates, these efforts have not been translated into a commercialized vaccine. The present review aims to provide an overview of the identification, pathology, diagnosis and virulence factors of E. tarda in fish, and describe recent strategies for developing vaccines against edwardsiellosis. The hope is that this presentation will be useful not only from the standpoint of understanding the pathogenesis of E. tarda, but also from the perspective of facilitating the development of effective vaccines. PMID:23035843

  2. Hemolysins of Edwardsiella tarda.

    PubMed Central

    Watson, J J; White, F H

    1979-01-01

    Isolates of Edwardsiella tarda from four sources produced nonfilterable hemolsin in trypticase soy broth. The cell-associated hemolysin was partially heat labile, destroyed by formalin and sensitive to treatment with trypsin. These characteristics, and the observation that Ca++ or Mg++ ions enhanced activity, suggest that a proteinaceous, enzymic component may be responsible for the hemolytic activity. PMID:34473

  3. Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

    PubMed Central

    Zhang, Lingzhi; Ni, Chunshan; Xu, Wenting; Dai, Tongcheng; Yang, Dahai; Wang, Qiyao; Zhang, Yuanxing

    2016-01-01

    ABSTRACT Edwardsiella tarda is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that E. tarda replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular E. tarda escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence in vivo. Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis. IMPORTANCE Many pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here, Edwardsiella tarda is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of E. tarda in vivo. Our work provides evidence

  4. Edwardsiella tarda EsaE (Orf19 protein) is required for the secretion of type III substrates, and pathogenesis in fish.

    PubMed

    Zhou, Ying; Liu, Lu Yi; He, Tian Tian; Laghari, Zubair Ahmed; Nie, Pin; Gao, Qian; Xie, Hai Xia

    2016-07-15

    Type III secretion system (T3SS) is a large macromolecular assembly found on the surface of many pathogenic Gram-negative bacteria. Edwardsiella tarda is an important Gram-negative pathogen that employs T3SS to deliver effectors into host cells to facilitate its survival and replication. EseB, EseC, and EseD, when secreted, form a translocon complex EseBCD on host membranes through which effectors are translocated. The orf19 gene (esaE) of E. tarda is located upstream of esaK, and downstream of esaJ, esaI, esaH and esaG in the T3SS gene cluster. When its domains were searched using Delta-Blast, the EsaE protein was found to belong to the T3SS YscJ/PrgK family. In the present study, it is found that EsaE is not secreted into culture supernatant, and the deletion of esaE abolished the secretion of T3SS translocon proteins EseBCD and T3SS effector EseG. Increased steady-state protein level of EseC and EseD was detected in bacterial pellet of ΔesaE strain although a reduced level was observed for the eseC and eseD transcription. EsaE was found to localize on membrane but not in the cytoplasm of E. tarda by fractionation. In blue gourami fish infection model, 87.88% of blue gourami infected with ΔesaE strain survived whereas only 3.03% survived when infected with wild-type strain. Taken together, our study demonstrated that EsaE is probably an apparatus protein of T3SS, which contributes to the pathogenesis of E. tarda in fish. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.

    PubMed

    Li, Mo-Fei; Wang, Chong; Sun, Li

    2015-02-01

    Edwardsiella tarda, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors, ivy and mliC (ivy(Et) and mliC(Et)). We recently studied IvyEt and found it to be implicated in E. tarda virulence. In the present study, we characterized MliC(Et) in comparison with Ivy(Et) in a turbot model. MliC(Et) contains the FWSKG motif and two cysteines (C33 and C98) that are highly conserved in subgroup 1 MliCs but are of unknown functional importance. To examine the essentialness of these conserved structural features, recombinant MliC(Et) (rMliC) and its mutants bearing C33S and W79A (of the FWSKG motif) substitutions were prepared. Subsequent analysis showed that rMliC (i) inhibited lysozyme-induced lysis of a Gram-positive bacterium, (ii) reduced serum-facilitated lysozyme killing of E. tarda, and (iii) when introduced into turbot, promoted bacterial dissemination in fish tissues. The C33S mutation had no influence on the activity of rMliC, while the W79A mutation slightly but significantly enhanced the activity of rMliC. Knockout strains of either mliC(Et) or ivy(Et) were severely attenuated for the ability of tissue invasion, host lethality, serum survival, and intracellular replication. The lost virulence of the mliC transformant (TXΔmliC) was restored by complementation with an introduced mliC(Et) gene. Compared to the Δivy(Et) or ΔmliC(Et) single-knockout strains, the ΔmliC(Et) Δivy(Et) double-knockout strain was significantly impaired in most of the virulence features. Together, these results provide the first evidence that the conserved cysteine is functionally dispensable to a subgroup 1 MliC and that as a virulence factor, MliC(Et) most likely works in a concerted and parallel manner with Ivy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Edwardsiella tarda invasion of fish cell lines and the activation of divergent cell death pathways.

    PubMed

    Wang, Bin; Yu, Tong; Dong, Xue; Zhang, Zenghu; Song, Lin; Xu, Ying; Zhang, Xiao-Hua

    2013-05-03

    Edwardsiella tarda is an important gram-negative intracellular pathogen of fish. However, the invasive features of E. tarda to fish cells and the pathogenesis of host cell death have not been thoroughly investigated. In this study, two fish cell models were used to investigate the interactions between E. tarda and its cellular hosts. E. tarda invaded and replicated in both cell lines. Epithelioma papulosum cyprini (EPC) cells were more sensitive to E. tarda infection than the flounder gill cell line FG-9307, with higher levels of intracellular bacteria in the former. The invasion and intracellular replication of E. tarda in FG-9307 cells were studied at the ultrastructural level, and infected cells with large amounts of replicated bacteria and destroyed organelles were observed. Apoptosis was observed in EPC cells upon infection, characterized by the occurrence of apoptotic bodies, DNA ladder, increased Annexin V binding and the activation of caspase-3, whereas E. tarda infected FG-9307 cells were negative for all of those features. E. tarda infection in FG-9307 cells failed to protect the staurosporine-induced apoptosis. Moreover, both intrinsic and extrinsic pathways were activated in EPC cells upon E. tarda infection. The present study revealed that E. tarda interacts with fish cells in different manners, and divergent pathways were activated in these cellular hosts to mediate cell death. These results provided new information on the interactions between E. tarda and fish cells.

  7. Edwardsiella tarda EscE (Orf13 Protein) Is a Type III Secretion System-Secreted Protein That Is Required for the Injection of Effectors, Secretion of Translocators, and Pathogenesis in Fish.

    PubMed

    Lu, Jin Fang; Wang, Wei Na; Wang, Gai Ling; Zhang, He; Zhou, Ying; Gao, Zhi Peng; Nie, Pin; Xie, Hai Xia

    2015-10-12

    The type III secretion system (T3SS) of Edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. The orf13 gene (escE) of E. tarda is located 84 nucleotides (nt) upstream of esrC in the T3SS gene cluster. We found that EscE is secreted and translocated in a T3SS-dependent manner and that amino acids 2 to 15 in the N terminus were required for a completely functional T3SS in E. tarda. Deletion of escE abolished the secretion of T3SS translocators, as well as the secretion and translocation of T3SS effectors, but did not influence their intracellular protein levels in E. tarda. Complementation of the escE mutant with a secretion-incompetent EscE derivative restored the secretion of translocators and effectors. Interestingly, the effectors that were secreted and translocated were positively correlated with the EscE protein level in E. tarda. The escE mutant was attenuated in the blue gourami fish infection model, as its 50% lethal dose (LD50) increased to 4 times that of the wild type. The survival rate of the escE mutant-strain-infected fish was 69%, which was much higher than that of the fish infected with the wild-type bacteria (6%). Overall, EscE represents a secreted T3SS regulator that controls effector injection and translocator secretion, thus contributing to E. tarda pathogenesis in fish. The homology of EscE within the T3SSs of other bacterial species suggests that the mechanism of secretion and translocation control used by E. tarda may be commonly used by other bacterial pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Comparative analysis of Edwardsiella tarda isolates from fish in the eastern United States suggests the existence of two genetically distinct species, Edwardsiella tarda and Edwardsiella pseudotarda sp. nov

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, is often implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of a collection of E. tarda isolates from 4 different fish species in the eastern United State...

  9. Edwardsiella tarda infections in Florida racoons, Procyon lotor.

    PubMed

    White, F H; Watson, J J; Hoff, G L; Bigler, W J

    1975-12-01

    Edwardsiella tarda was isolated from the large intestine of seven (17%) of 42 racoons from Florida. The rate varied from 12% in South Florida to 25% in North Florida. In addition, 52% of the racoons examined were carrying Salmonella, with numerous serotypes represented.

  10. The macrophage chemotactic activity of Edwardsiella tarda extracellular products

    USDA-ARS?s Scientific Manuscript database

    The chemoattractant capabilities of Edwardsiella tarda extracellular products (ECP) were investigated from two isolates, the virulent FL6-60 parent and less virulent RET-04 mutant. Chemotaxis and chemokinesis were assayed in vitro using blind well chambers with peritoneal macrophages obtained from ...

  11. Discriminatory PCR assays differentiate between Edwardsiella tarda and Edwardsiella tarda-like species and identify the predominant species in catfish aquaculture

    USDA-ARS?s Scientific Manuscript database

    Recently a new taxa of Edwardsiella, phenotypically similar to E. tarda, has been described from fishes of Europe and Asia. Based on extensive genetic and phenotypic characterization, researchers have determined this new strain does not belong to any established taxa within the genus Edwardsiella a...

  12. Real-time PCR assays for detection and quactification of Edwardsiella tarda, Edwardsiella piscicida, Edwardsiella piscicida-like sp. in catfish tissues and pond water

    USDA-ARS?s Scientific Manuscript database

    Researchers have proposed the adoption of 3 distinct genetic taxa among bacteria previously classified as Edwardsiella tarda; namely E. tarda, E. piscicida, and a taxon presently termed E. piscicida–like. Individual real-time polymerase chain reaction (qPCR) assays were developed, based on published...

  13. Real-time PCR assays for detection and quactification of Edwardsiella tarda, Edwardsiella piscicida, Edwardsiella piscicida-like sp. in catfish tissues and pond water

    USDA-ARS?s Scientific Manuscript database

    Researchers have proposed the adoption of 3 distinct genetic taxa among bacteria previously classified as Edwardsiella tarda; namely E. tarda, E. piscicida, and a taxon presently termed E. piscicida–like. Individual real-time polymerase chain reaction (qPCR) assays were developed, based on published...

  14. Glucose enhances tilapia against Edwardsiella tarda infection through metabolome reprogramming.

    PubMed

    Zeng, Zhao-Hai; Du, Chao-Chao; Liu, Shi-Rao; Li, Hui; Peng, Xuan-Xian; Peng, Bo

    2017-02-01

    We have recently reported that the survival of tilapia, Oreochromis niloticus, during Edwardsiella tarda infection is tightly associated with their metabolome, where the survived O. niloticus has distinct metabolomic profile to dying O. niloticus. Glucose is the key metabolite to distinguish the survival- and dying-metabolome. More importantly, exogenous administration of glucose to the fish greatly enhances their survival for the infection, indicating the functional roles of glucose in metabolome repurposing, known as reprogramming metabolomics. However, the underlying information for the reprogramming is not yet available. Here, GC/MS based metabolomics is used to understand the mechanisms by which how exogenous glucose elevates O. niloticus, anti-infectious ability to E. tarda. Results showed that exogenous glucose promotes stearic acid and palmitic acid biosynthesis but attenuates TCA cycle to potentiate O. niloticus against bacterial infection, which is confirmed by the fact that exogenous stearic acid increases immune protection in O. niloticus against E. tarda infection in a manner of Mx protein. These results indicate that exogenous glucose reprograms O. niloticus anti-infective metabolome that characterizes elevation of stearic acid and palmitic acid and attenuation of the TCA cycle. Therefore, our results proposed a novel mechanism that glucose promotes unsaturated fatty acid biosynthesis to cope with infection, thereby highlighting a potential way of enhancing fish immunity in aquaculture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. In vitro model to estimate Edwardsiella tarda-macrophage interactions using RAW264.7 cells.

    PubMed

    Qin, Lei; Sun, Yuying; Zhao, Yanjing; Xu, Jing; Bi, Keran

    2017-01-01

    Edwardsiella tarda has been recognized as an important facultative intracellular pathogen of fish with capability of survival and replication within macrophages. E. tarda-macrophage interactions play a very important role in the defense mechanism of fish against infection. The mechanisms that E. tarda use to infect and persist inside macrophages are not well characterized. To gain insight concerning this process, RAW264.7 cells was used to investigate the interactions between E. tarda and macrophages. Using an in vitro model involving RAW264.7 cells, internalization assay demonstrated that MOIs of 10:1 and 100:1 could result in a satisfactory infection rate after a 2 h infection period. Consistent with the performance in fish macrophages, E. tarda could survive, replicate and induce iNOS-mediated NO production in RAW264.7 cells. Light and electron microscopy confirmed the internalization and replication of E. tarda in RAW264.7 cells, showing once inside macrophages, numberous bacteria may be destroyed within phagolysosomes and those that successfully subvert phagocyte defenses are capable of extensively replicating within the vacuolar-like compartment in macrophages. In addition, E. tarda-induced apoptosis was observed in RAW264.7 cells in a dose-and time-dependent manner, characterized by increased Annexin V binding and the activation of caspase-3. The results described here indicate that RAW264.7 cells could model the behavior of fish macrophages in response to E. tarda in many ways and may serve as a cell model for study on interactions between E. tarda and macrophages. The successful establishment of E. tarda-invaded RAW264.7 cells model may contribute to providing a basis for more detailed understanding of E. tarda pathogenesis.

  16. Complete genome sequence of Edwardsiella tarda (isolate FL95-01)recovered from channel catfish

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella tarda is a Gram-negative facultative anaerobe isolated from fish, reptiles, amphibians, and mammals, including humans. This is a report of the complete and annotated genome of E. tarda isolate FL95-01, recovered from channel catfish (Ictalurus punctatus)....

  17. Complete Genome Sequence of Channel Catfish Gastrointestinal Septicemia Isolate Edwardsiella tarda C07-087

    PubMed Central

    Tekedar, Hasan C.; Karsi, Attila; Williams, Michele L.; Vamenta, Stefanie; Banes, Michelle M.; Duke, Mary; Scheffler, Brian E.

    2013-01-01

    Edwardsiella tarda is a Gram-negative facultative anaerobe causing disease in animals and humans. Here, we announce the complete genome sequence of the channel catfish isolate E. tarda strain C07-87, which was isolated from an outbreak of gastrointestinal septicemia on a commercial catfish farm. PMID:24265493

  18. Generation of safety enhanced Edwardsiella tarda ghost vaccine.

    PubMed

    Lee, Dong Jin; Kwon, Se Ryun; Zenke, Kosuke; Lee, Eun Hye; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

    2008-09-24

    A dual vector expressing the ghost-inducing PhiX174 lysis E gene and the bacterial DNA degrading staphylococcal nuclease A (SNA) gene was constructed to solve the problem of remnant antibiotic resistance genes and genomic DNA with intact pathogenic islands in the final product of Edwardsiella tarda ghosts (ETG). The SNA (devoid of secretion signal sequence and the nuclease B amino terminus sequence), fused with the 26 amino acid N-terminal sequence of the lambda phage Cro gene, showed successful degradation of bacterial nucleic acids. Furthermore, the nuclease activity of SNA in E. tarda was enhanced by codon optimization of the SNA gene using site-directed mutagenesis. ETG were generated via coexpression of the SNA gene and lysis gene E under the control of each lambdaP(R) promoter. The ghost bacteria generation system we describe is advantageous as it allows the use of a single plasmid, improves safety and vaccine purity by limiting residual genetic content from the ghost bacteria, and reduces production costs through cheap means of induction that use only temperature shifts.

  19. Full-genome sequence of a novel myovirus, GF-2, infecting Edwardsiella tarda: comparison with other Edwardsiella myoviral genomes.

    PubMed

    Yasuike, Motoshige; Nishiki, Issei; Iwasaki, Yuki; Nakamura, Yoji; Fujiwara, Atushi; Sugaya, Emi; Kawato, Yasuhiko; Nagai, Satoshi; Kobayashi, Takanori; Ototake, Mitsuru; Nakai, Toshihiro

    2015-08-01

    Edwardsiellosis, which is caused by Edwardsiella tarda, a Gram-negative bacterium, is one of the most serious infectious diseases in both marine and freshwater fish farms worldwide. Previously, we reported the complete genome sequences of three E. tarda-lytic bacteriophages (two podoviruses and a myovirus), which were isolated from fish tissues and fish-rearing seawater. Further genomic information regarding E. tarda phages is important for understanding phage-host interactions as well as for applications of the phages for the control of disease. Here, we report the complete genome sequence of a novel E. tarda phage (GF-2) of myovirus morphology (family Myoviridae), isolated from tissue homogenates of a cultured Japanese flounder (Paralichthys olivaceus) that succumbed to edwardsiellosis in Japan. The size of the entire genome was 43,129 bp, with a GC content of 51.3 % and containing 82 open reading frames (ORFs). The GF-2 genome possesses lysogeny-related genes that have not been found in the reported Edwardsiella phage genomes. Comparative genomics of Edwardsiella myophages suggest that the C-terminal domains of the tail fiber proteins have relevance to their host specificity. Thus, GF-2 genome information provides a novel resource for our understanding of the molecular mechanisms involved in their host specificity and for detection of E. tarda in aquaculture environments.

  20. Protection of tilapia (Oreochromis mosambicus) from edwardsiellosis by vaccination with Edwardsiella tarda ghosts.

    PubMed

    Kwon, Se Ryun; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

    2006-04-01

    The vaccine potential of Edwardsiella tarda ghosts produced by gene E mediated lysis was investigated using tilapia (Oreochromis mosambicus). Tilapia immunized with E. tarda ghosts (ETG) and formalin killed E. tarda (FKC) vaccines showed significantly higher serum agglutination titers than control fish. Fish immunized with ETG showed no significant differences with fish immunized with FKC in serum agglutination titers, but showed significantly higher bactericidal activity than fish immunized with FKC. Furthermore, fish immunized with ETG showed higher protection than fish immunized with FKC. As this promising type of a non-living whole cell envelope preparation seems to be favorable over conventional vaccines, we suggest E. tarda ghosts as a new vaccine candidate.

  1. The serine protease autotransporter Tsh contributes to the virulence of Edwardsiella tarda.

    PubMed

    Hu, Yong-Hua; Zhou, Hai-Zhen; Jin, Qian-Wen; Zhang, Jian

    2016-06-30

    The temperature-sensitive hemagglutinin (Tsh), identified as serine protease autotransporters of the Enterobacteriaceae (SPATEs) proteins, is an important virulence factor for avian-pathogenic Escherichia coli (APEC) and uropathogenic E. coli. However, little is known about the role of Tsh as a virulence factor in Edwardsiella tarda, a severe fish pathogen. In this study, we characterized the Tsh of E. tarda (named TshEt) and examined its function and vaccine potential. TshEt is composed of 1224 residues and has three functional domains typical for autotransporters. Quantitative real-time reverse transcriptase-PCR analysis showed that expression of tshEt was upregulated under conditions of high temperature, increased cell density, high pH, and iron starvation and during the infection of host cells. A markerless tsh in-frame mutant strain, TX01Δtsh, was constructed to determine whether TshEt participates in the pathogenicity of E. tarda, Compared to the wild type TX01, TX01Δtsh exhibited (i) retarded biofilm growth, (ii) decreased resistance against serum killing, (iii) impaired ability to block the host immune response, (iv) attenuated tissue and cellular infectivity. Introduction of a trans-expressed tsh gene restored the lost virulence of TX01Δtsh. The passenger domain of TshEt contains a putative serine protease (PepS) that exhibits apparent proteolytic activity when expressed in and purified from E. coli as a recombinant protein (rPepS). When used as a subunit vaccine to immunize Japanese flounder, rPepS was able to induce effective immune protection. This is the first study of Tsh in a fish pathogen, and the results suggest that TshEt exerts pleiotropic effects on the pathogenesis of E. tarda.

  2. Edwardsiella tarda sepsis in a live-stranded sperm whale (Physeter macrocephalus).

    PubMed

    Cools, Piet; Haelters, Jan; Lopes dos Santos Santiago, Guido; Claeys, Geert; Boelens, Jerina; Leroux-Roels, Isabel; Vaneechoutte, Mario; Deschaght, Pieter

    2013-09-27

    Whale strandings remain poorly understood, although bacterial infections have been suggested to contribute. We isolated Edwardsiella tarda from the blood of a stranded sperm whale. The pathogen was identified with MALDI-TOF MS, confirmed by 16S rRNA gene sequencing and quantified in blood by qPCR. We report the first case of sepsis in a sperm whale. The zoonotic potential of E. tarda and the possible role of bacterial infections in the enigmatic strandings of cetaceans are discussed.

  3. Complete Genome Sequences of Edwardsiella tarda-Lytic Bacteriophages KF-1 and IW-1

    PubMed Central

    Yasuike, Motoshige; Sugaya, Emi; Nakamura, Yoji; Shigenobu, Yuya; Kawato, Yasuhiko; Kai, Wataru; Sano, Motohiko; Kobayashi, Takanori; Nakai, Toshihiro

    2013-01-01

    We report the complete genome sequences of two Edwardsiella tarda-lytic bacteriophages isolated from flounder kidney (KF-1) and seawater (IW-1). These newly sequenced phage genomes provide a novel resource for future studies on phage-host interaction mechanisms and various applications of the phages for control of edwardsiellosis in aquaculture. PMID:23405297

  4. What is a species a species? Genetic variability of Edwardsiella tarda in the Southeastern United States

    USDA-ARS?s Scientific Manuscript database

    The intra-specific variability of Edwardsiella tarda isolates from fish in the eastern United States was assessed. Repetitive sequence mediated PCR (rep-PCR) and multi-locus sequence analysis identified two distinct genotypes (DNA group I; DNA group II). This was supported by fluorometric estimatio...

  5. Complete genome sequence of channel catfish gastrointestinal sepicemia isolate Edwardsiella tarda C07-087

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella tarda is the etiologic agent of acute to chronic edwardsiellosis in fish and other species (1). It is a gram-negative facultative anaerobe that is motile by peritrichous flagella. Edwardsiellosis is an important fish disease that negatively impacts aquaculture industries throughout the...

  6. Real-time assays for detection and quantification of Edwardsiella tarda, Edwardsilla piscicida and Edwardsiella piscicida-like sp. in catfish tissues and pond water

    USDA-ARS?s Scientific Manuscript database

    Researchers have proposed the adoption of 3 distinct genetic taxa among bacteria previously classified as Edwardsiella tarda; namely E. tarda, E. piscicida, and a taxon presently termed E. piscicida–like. Individual real-time polymerase chain reaction (qPCR) assays were developed, based on previousl...

  7. Identification and functional characterization of the novel Edwardsiella tarda effector EseJ.

    PubMed

    Xie, Hai-Xia; Lu, Jin-Fang; Zhou, Ying; Yi, Jia; Yu, Xiu-Jun; Leung, Ka Yin; Nie, Pin

    2015-04-01

    Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and gastro- and extraintestinal infections in humans. The type III secretion system (T3SS) of E. tarda has been identified as a key virulence factor that contributes to pathogenesis in fish. However, little is known about the associated effectors translocated by this T3SS. In this study, by comparing the profile of secreted proteins of the wild-type PPD130/91 and its T3SS ATPase ΔesaN mutant, we identified a new effector by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. This effector consists of 1,359 amino acids, sharing high sequence similarity with Orf29/30 of E. tarda strain EIB202, and is renamed EseJ. The secretion and translocation of EseJ depend on the T3SS. A ΔeseJ mutant strain adheres to epithelioma papillosum of carp (EPC) cells 3 to 5 times more extensively than the wild-type strain does. EseJ inhibits bacterial adhesion to EPC cells from within bacterial cells. Importantly, the ΔeseJ mutant strain does not replicate efficiently in EPC cells and fails to replicate in J774A.1 macrophages. In infected J774A.1 macrophages, the ΔeseJ mutant elicits higher production of reactive oxygen species than wild-type E. tarda. The replication defect is consistent with the attenuation of the ΔeseJ mutant in the blue gourami fish model: the 50% lethal dose (LD50) of the ΔeseJ mutant is 2.34 times greater than that of the wild type, and the ΔeseJ mutant is less competitive than the wild type in mixed infection. Thus, EseJ represents a novel effector that contributes to virulence by reducing bacterial adhesion to EPC cells and facilitating intracellular bacterial replication. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. [Finding of the bacterial species Edwardsiella tarda in the aquarium fish Betta splendens].

    PubMed

    Vladík, P; Prouza, A; Vítovec, J

    1983-01-01

    A case of the mass occurrence of a disease in the aquarium fish species Betta splendens is described; morphologically the disease was characterized by the finding of large dermal changes located mainly in the dorsal part and by miliary granulomata in liver, spleen and kidneys. The granulomata consisted of epitheloid light cells with centrally located necrosis. Gram-negative bacteria with morphological and biochemical characteristics corresponding to the bacterial species Edwardsiella tarda were isolated from the kidneys, liver and from the dermal lesion. The characteristics of the strains isolated by us were compared with the reference Edwardsiella strain (Bth 1/64) obtained from the Czechoslovak collection of type cultures, Prague.

  9. Insights into the virulence-related genes of Edwardsiella tarda isolated from turbot in Europe: genetic homogeneity and evidence for vibrioferrin production.

    PubMed

    Castro, N; Osorio, C R; Buján, N; Fuentes, J C; Rodríguez, J; Romero, M; Jiménez, C; Toranzo, A E; Magariños, B

    2016-05-01

    Edwardsiella tarda has long been known as a pathogen that causes severe economic losses in aquaculture industry. Insights gained on E. tarda pathogenesis may prove useful in the development of new methods for the treatment of infections as well as preventive measures against future outbreaks. In this report, we have established the correlation between the presence of virulence genes, related with three aspects typically involved in bacterial pathogenesis (chondroitinase activity, quorum sensing and siderophore-mediated ferric uptake systems), in the genome of E. tarda strains isolated from turbot in Europe and their phenotypic traits. A total of 8 genes were tested by PCR for their presence in 73 E. tarda isolates. High homogeneity was observed in the presence/absence pattern of all the strains. Positive results in the amplification of virulence-related genes were correlated with the detection of chondroitinase activity in agar plates, in vivo AHL production during fish infection and determination of type of siderophore produced by E. tarda. To the best of our knowledge, this is the first study carried out with European strains on potential virulence factors. Furthermore, we demonstrated for the first time that E. tarda produces the siderophore vibrioferrin. © 2015 John Wiley & Sons Ltd.

  10. Novel brain lesions caused by Edwardsiella tarda in a red tilapia (Oreochromis spp.).

    PubMed

    Iregui, Carlos A; Guarín, Marlly; Tibatá, Victor M; Ferguson, Hugh W

    2012-03-01

    The histological lesions caused by Edwardsiella tarda in a variety of fish species, including tilapia, have been well characterized. There are apparent differences in the type of inflammatory response manifested by these different species, which may be due to the fish species itself, the phase of infection, or the virulence factors produced by different strains of E. tarda. In catfish, systemic abscesses involving muscles of the flank or caudal peduncle are the most common lesions. By contrast, infection in tilapia and red sea bream is more likely to be associated with granulomatous inflammation. Necrotic meningitis, encephalitis, and vasculitis with fibrinoid necrosis of the blood vessels walls, as well as the formation of a plaque-like structure in the brain, are described in the current study. The presence of E. tarda was confirmed by microbiological isolation and a positive nested polymerase chain reaction in paraffin wax-embedded tilapia tissues.

  11. Quantitative proteomic analysis of Edwardsiella tarda in response to oxytetracycline stress in biofilm.

    PubMed

    Sun, Lina; Chen, Huarong; Lin, Wenxiong; Lin, Xiangmin

    2017-01-06

    Edwardsiella tarda is a virulent fish pathogen that causes extensive economic losses in the aquaculture industry worldwide. The antibiotic resistance status of E. tarda is high, especially in the biofilm status; however, the mechanisms underlying its resistance remain largely unknown. In this study, isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to compare the differential expression of E. tarda in response to oxytetracycline (OXY) stress in biofilm. Additional bioinformatics analysis demonstrated an increasing abundance of translation-related proteins, especially ribosomal subunits, and a decreasing abundance of key metabolic pathways underlying the adaptation of E. tarda to OXY in biofilm. We performed Western blotting and quantitative PCR (qPCR) analyses to validate selected proteomics results, and measured enzyme activity to verify the antibiotic resistance functions of central metabolic pathways. In addition, we examined the antibiotic susceptibility of a mutant of an NADP-dependent malic enzyme (MaeB), which is involved in the bacterial tricarboxylic acid cycle, and found significantly increased resistance to OXY in biofilm. Our findings demonstrate the importance of central metabolic pathways in the antibiotic resistance of E. tarda to bacterial biofilms and provide insight into the prevention of this resistance, which would aid in disease control.

  12. Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

    PubMed Central

    Xie, Hai-Xia; Lu, Jin-Fang; Rolhion, Nathalie; Holden, David W.; Zhou, Ying

    2014-01-01

    Many Gram-negative bacteria utilize a type III secretion system (T3SS) to translocate virulence proteins into host cells to cause diseases. In responding to infection, macrophages detect some of the translocated proteins to activate caspase-1-mediated cell death, called pyroptosis, and secretion of proinflammatory cytokines to control the infection. Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. In this study, we report that the T3SS of E. tarda facilitates its survival and replication in murine bone marrow-derived macrophages, and E. tarda infection triggers pyroptosis of infected macrophages from mice and fish and increased secretion of the cytokine interleukin 1β in a T3SS-dependent manner. Deletion of the flagellin gene fliC of E. tarda results in decreased cytotoxicity for infected macrophages and does not attenuate its virulence in a fish model of infection, whereas upregulated expression of FliC in the fliC mutant strain reduces its virulence. We propose that the host controls E. tarda infection partially by detecting FliC translocated by the T3SS, whereas the bacteria downregulate the expression of FliC to evade innate immunity. PMID:24891103

  13. Optimization of protectant, salinity and freezing condition for freeze-drying preservation of Edwardsiella tarda

    NASA Astrophysics Data System (ADS)

    Yu, Yongxiang; Zhang, Zheng; Wang, Yingeng; Liao, Meijie; Li, Bin; Xue, Liangyi

    2017-10-01

    Novel preservation condition without ultra-low temperature is needed for the study of pathogen in marine fishes. Freeze-drying is such a method usually used for preservation of terrigenous bacteria. However, studies using freeze-drying method to preserving marine microorganisms remain very limited. In this study, we optimized the composition of protectants during the freeze-drying of Edwardsiella tarda, a fish pathogen that causes systemic infection in marine fishes. We found that the optimal composition of protectant mixture contained trehalose (8.0%), skim milk (12.0%), sodium citrate (2.0%), serum (12.0%) and PVP (2.0%). Orthogonal and interaction analyses demonstrated the interaction between serum and skim milk or sodium citrate. The highest survival rate of E. tarda was observed when the concentration of NaCl was 10.0, 30.0 and between 5.0 and 10.0 g L-1 for preparing TSB medium, E. tarda suspension and protectant mixture, respectively. When E. tarda was frozen at -80°C or -40°C for 6 h, its survival rate was higher than that under other tested conditions. Under the optimized conditions, when the protectant mixture was used during freeze-drying process, the survival rate (79.63%-82.30%) of E. tarda was significantly higher than that obtained using single protectant. Scanning electron microscopy (SEM) image indicated that E. tarda was embedded in thick matrix with detectable aggregation. In sum, the protectant mixture may be used as a novel cryoprotective additive for E. tarda.

  14. Fructose restores susceptibility of multidrug-resistant Edwardsiella tarda to kanamycin.

    PubMed

    Su, Yu-bin; Peng, Bo; Han, Yi; Li, Hui; Peng, Xuan-xian

    2015-03-06

    Edwardsiella tarda, the causative agent of Edwardsiellosis, imposes medical challenges in both the clinic and aquaculture. The emergence of multidrug resistant strains makes antibiotic treatment impractical. The identification of molecules that facilitate or promote antibiotic efficacy is in high demand. In the present study, we aimed to identify small molecules whose abundance is correlated with kanamycin resistance in E. tarda by gas chromatography-mass spectrometry. We found that the abundance of fructose was greatly suppressed in kanamycin-resistant strains. The incubation of kanamycin-resistant bacteria with exogenous fructose sensitized the bacteria to kanamycin. Moreover, the fructose also functioned in bacteria persisters and biofilm. The synergistic effects of fructose and kanamycin were validated in a mouse model. Furthermore, the mechanism relies on fructose in activating TCA cycle to produce NADH, which generates proton motive force to increase the uptake of the antibiotics. Therefore, we present a novel approach in fighting against multidrug resistant bacteria through exploration of antibiotic-suppressed molecules.

  15. Upper extremity myonecrosis caused by Edwardsiella tarda resulting in transhumeral amputation: case report.

    PubMed

    Crosby, Samuel N; Snoddy, Mark C; Atkinson, Cameron T; Lee, Donald H; Weikert, Douglas R

    2013-01-01

    Necrotizing soft tissue infections are rapidly progressive infections with a high rate of mortality. One type of necrotizing soft tissue infection is caused by marine gram-negative bacteria and commonly occurs in immunocompromised hosts. These types of infections are more common in patients with chronic liver disease, possibly because of impaired iron metabolism. We present the case of a rapidly progressive necrotizing soft tissue infection caused by Edwardsiella tarda, a marine gram-negative pathogen common in catfish. Few extraintestinal infections of E tarda have been described previously. Our patient had hepatitis C and was exposed to the bacteria by a puncture injury from a wild catfish. His infection required multiple debridements and ultimately required a transhumeral amputation for local control of the infection.

  16. Identification and validation of sRNAs in Edwardsiella tarda S08

    PubMed Central

    Sun, Yuying; Zhang, Jiquan; Qin, Lei; Yan, Cui; Zhang, Xiaojun; Liu, Dandan

    2017-01-01

    Bacterial small non-coding RNAs (sRNAs) are known as novel regulators involved in virulence, stress responsibility, and so on. Recently, a lot of new researches have highlighted the critical roles of sRNAs in fine-tune gene regulation in both prokaryotes and eukaryotes. Edwardsiella tarda (E. tarda) is a gram-negative, intracellular pathogen that causes edwardsiellosis in fish. Thus far, no sRNA has been reported in E. tarda. The present study represents the first attempt to identify sRNAs in E. tarda S08. Ten sRNAs were validated by RNA sequencing and quantitative PCR (qPCR). ET_sRNA_1 and ET_sRNA_2 were homolous to tmRNA and GcvB, respectively. However, the other candidate sRNAs have not been reported till now. The cellular abundance of 10 validated sRNA was detected by qPCR at different growth phases to monitor their biosynthesis. Nine candidate sRNAs were expressed in the late-stage of exponential growth and stationary stages of growth (36~60 h). And the expression of the nine sRNAs was growth phase-dependent. But ET_sRNA_10 was almost expressed all the time and reached the highest peak at 48 h. Their targets were predicted by TargetRNA2 and each sRNA target contains some genes that directly or indirectly relate to virulence. These results preliminary showed that sRNAs probably play a regulatory role of virulence in E. tarda. PMID:28267754

  17. Evaluation of an in vitro cell assay to select attenuated bacterial mutants of Aeromonas hydrophila and Edwardsiella tarda to channel catfish

    USDA-ARS?s Scientific Manuscript database

    Both Aeromonas hydrophila (causative agent of motile aeromonas septicemia) and Edwardsiella tarda (causative agent of enteric septicemia) are Gram-negative bacteria widely distributed in aquatic environments, affecting many fish species worldwide, including channel catfish and tilapia. To control ba...

  18. A real-time PCR targeted to the upstream regions of HlyB for specific detection of Edwardsiella tarda

    NASA Astrophysics Data System (ADS)

    Xie, Guosi; Huang, Jie; Zhang, Qingli; Han, Nana; Shi, Chengyin; Wang, Xiuhua; Liu, Qinghui

    2012-09-01

    Edwardsiella tarda has become one of the most important emerging pathogens in aquaculture industry. Therefore, a rapid, reproducible, and sensitive method for detection and quantification of this pathogen is needed urgently. To achieve this purpose, we developed a TaqMan-based real-time PCR assay for detection and quantification of E. tarda. The assay targets the hemolysin activator HlyB domain protein of E. tarda. Our optimized TaqMan assay is capable of detecting as little as 40 fg of genomic DNA per reaction. A standard curve was generated from the threshold cycle values ( y) against log10 ( E. tarda genomic DNA concentration) as x. The intra- and inter-assay coefficient of variation (CV) values were less than 2.06% and 1.05% respectively, indicating that the assay had good reproducibility. This method is highly specific to E. tarda strains, as it shows no cross-reactivity to Edwardsiella ictaluri, a member of the same genus, or to nine other fish-pathogenic bacteria species belonging to three other genera. This sensitive and specific real-time PCR assay provides a valuable tool for diagnostic quantitation of E. tarda in clinical samples.

  19. Edwardsiella Septicaemias

    USDA-ARS?s Scientific Manuscript database

    The genus Edwardsiella includes two species of bacteria that cause major diseases in fish: Edwardsiella tarda (1965) infects fish and other animals and Edwardsiella ictaluri (Hawke 1979; Hawke et al. 1981) infects primarily fish. A third species, Edwardsiella hoshinae (Grimont et al. 1980), infects ...

  20. Genome Sequence of the Versatile Fish Pathogen Edwardsiella tarda Provides Insights into its Adaptation to Broad Host Ranges and Intracellular Niches

    PubMed Central

    Xiao, Jingfan; Wu, Haizhen; Wang, Xin; Lv, Yuanzhi; Xu, Lili; Zheng, Huajun; Wang, Shengyue; Zhao, Guoping; Liu, Qin; Zhang, Yuanxing

    2009-01-01

    Background Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. Methodology/Principal Findings E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. Conclusion/Significance Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis. PMID:19865481

  1. Development of a multiplex PCR assay to detect Edwardsiella tarda, Streptococcus parauberis, and Streptococcus iniae in olive flounder (Paralichthys olivaceus).

    PubMed

    Park, Seong Bin; Kwon, Kyoung; Cha, In Seok; Jang, Ho Bin; Nho, Seong Won; Fagutao, Fernand F; Kim, Young Kyu; Yu, Jong Earn; Jung, Tae Sung

    2014-01-01

    A multiplex PCR protocol was established to simultaneously detect major bacterial pathogens in olive flounder (Paralichthys olivaceus) including Edwardsiella (E.) tarda, Streptococcus (S.) parauberis, and S. iniae. The PCR assay was able to detect 0.01 ng of E. tarda, 0.1 ng of S. parauberis, and 1 ng of S. iniae genomic DNA. Furthermore, this technique was found to have high specificity when tested with related bacterial species. This method represents a cheaper, faster, and reliable alternative for identifying major bacterial pathogens in olive flounder, the most important farmed fish in Korea.

  2. Edwardsiella tarda Endocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality.

    PubMed

    Litton, Kayleigh M; Rogers, Bret A

    2016-01-01

    Edwardsiella tarda is a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- ((111)In-) labeled white blood cell (WBC) scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp.) for diagnosing acute and chronic infection. We describe a case of suspected E. tarda prosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of (111)In-labeled WBC scintigraphy.

  3. Isolation and characterization of Edwardsiella tarda from fall chinook salmon (Oncorhynchus tshawytscha).

    PubMed Central

    Amandi, A; Hiu, S F; Rohovec, J S; Fryer, J L

    1982-01-01

    A new bacterial pathogen of chinook salmon (oncorhynchus tshawytscha) was isolated from fish in Oregon's Rogue River. The bacteria are biochemically and serologically related to strains of Edwardsiella tarda. Initially isolated from chinook salmon, the bacteria were also pathogenic for steelhead and rainbow trout (Salmo gairdneri), and channel catfish (Ictalurus punctatus). The 50% lethal doses for chinook salmon, steelhead trout, and channel catfish injected intraperitoneally and maintained in 18 degrees C water were 4.1 x 10(6), 5.6 x 10(6), and 4.0 x 10(5) respectively. When chinook salmon and rainbow trout were injected intraperitoneally and held in 12 degrees C water, the mean lethal doses were 6.4 x 10(7) and 1.7 x 10(6), respectively. The invasiveness of the organism was low in steelhead trout exposed to the bacteria by the waterborne route. The optimum growth temperature of the bacteria in brain heart infusion broth was approximately 35 degrees C. The guanine plus cytosine content of DNA obtained from E. tarda isolated from salmon was 59 mol%. PMID:7103490

  4. Edwardsiella tarda Hfq: impact on host infection and global protein expression

    PubMed Central

    2014-01-01

    Hfq is an RNA-binding protein that plays an important role in many cellular processes. In this study, we examined the biological effect of the Hfq of Edwardsiella tarda, a severe fish pathogen with a broad host range that includes humans. To facilitate the study, a markerless hfq in-frame deletion wild type, TXhfq, was constructed. Compared to the wild type TX01, TXhfq exhibited (i) retarded planktonic and biofilm growth, (ii) decreased resistance against oxidative stress, (iii) attenuated overall virulence and tissue dissemination and colonization capacity, (iv) impaired ability to replicate in host macrophages and to block host immune response. Introduction of a trans-expressed hfq gene into TXhfq restored the lost virulence of TXhfq. To identify potential Hfq targets, comparative global proteomic analysis was conducted, which revealed that 20 proteins belonging to different functional categories were differentially expressed in TXhfq and TX01. Quantitative real time RT-PCR analysis showed that the mRNA levels of two thirds of the genes of the identified proteins were consistent with the proteomic results. Since TXhfq is dramatically attenuated in virulence, we further examined its potential as a naturally delivered vaccine administered via the immersion route in a flounder model. The results showed that TXhfq induced effective protection against lethal E. tarda challenge. Taken together, our study indicated that Hfq is required for the normal operation of E. tarda in multiple aspects, and that Hfq probably exerts a regulatory effect on a wide range of target genes at both transcription and post-transcription levels. PMID:24568370

  5. Three-dimensional visualization of green fluorescence protein-labelled Edwardsiella tarda in whole Medaka larvae.

    PubMed

    Kataoka, C; Tomiyama, H; Kashiwada, S

    2017-04-01

    The invasive fish pathogen Edwardsiella tarda is common in aquatic environments and causes the environmentally and economically destructive emphysematous putrefactive disease called edwardsiellosis. In order to understand the organism's infection pathway, medaka larvae (Oryzias latipes) were immersion-infected with E. tarda labelled with green fluorescence protein (GFP) and then visualized in three dimensions under confocal laser microscopy and light-sheet fluorescence microscopy. Confocal microscopy revealed GFP-labelled E. tarda in the mouth, head, gill bridges, gill cover, skin, membrane fin, gastrointestinal tract and air bladder, and in the caudal vein, somite veins, caudal artery and caudal capillaries. Light-sheet microscopy additionally showed GFP-labelled E. tarda in the pharyngeal cavity, muscle of the pectoral fin and cardiac atrium and ventricle. These findings suggest that during its infection of fish, E. tarda initially adheres to, and invades, the epithelial cells of the skin, gills and gastrointestinal tract (through the pharyngeal cavity); E. tarda then enters the blood vessels to access organs, including the air bladder and heart.

  6. Computer-aided vaccine designing approach against fish pathogens Edwardsiella tarda and Flavobacterium columnare using bioinformatics softwares

    PubMed Central

    Mahendran, Radha; Jeyabaskar, Suganya; Sitharaman, Gayathri; Michael, Rajamani Dinakaran; Paul, Agnal Vincent

    2016-01-01

    Edwardsiella tarda and Flavobacterium columnare are two important intracellular pathogenic bacteria that cause the infectious diseases edwardsiellosis and columnaris in wild and cultured fish. Prediction of major histocompatibility complex (MHC) binding is an important issue in T-cell epitope prediction. In a healthy immune system, the T-cells must recognize epitopes and induce the immune response. In this study, T-cell epitopes were predicted by using in silico immunoinformatics approach with the help of bioinformatics tools that are less expensive and are not time consuming. Such identification of binding interaction between peptides and MHC alleles aids in the discovery of new peptide vaccines. We have reported the potential peptides chosen from the outer membrane proteins (OMPs) of E. tarda and F. columnare, which interact well with MHC class I alleles. OMPs from E. tarda and F. columnare were selected and analyzed based on their antigenic and immunogenic properties. The OMPs of the genes TolC and FCOL_04620, respectively, from E. tarda and F. columnare were taken for study. Finally, two epitopes from the OMP of E. tarda exhibited excellent protein–peptide interaction when docked with MHC class I alleles. Five epitopes from the OMP of F. columnare had good protein–peptide interaction when docked with MHC class I alleles. Further in vitro studies can aid in the development of potential peptide vaccines using the predicted peptides. PMID:27284239

  7. A developing model for Edwardsiella ictaluri pathogenesis

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri, the causative agent of Enteric Septicemia of Catfish (ESC), belongs to a rather short list of bacteria known to survive and replicate in macrophages. Macrophages are ameboid-like cells that engulf and then digest cellular debris and pathogens, including bacteria. The process, ...

  8. EscC is a chaperone for the Edwardsiella tarda type III secretion system putative translocon components EseB and EseD.

    PubMed

    Zheng, Jun; Li, Nan; Tan, Yuen Peng; Sivaraman, J; Mok, Yu-Keung; Mo, Zhao Lan; Leung, Ka Yin

    2007-06-01

    Edwardsiella tarda is a Gram-negative enteric pathogen that causes disease in both humans and animals. Recently, a type III secretion system (T3SS) has been found to contribute to Ed. tarda pathogenesis. EseB, EseC and EseD were shown to be secreted by the T3SS and to be the major components of the extracellular proteins (ECPs). Based on sequence similarity, they have been proposed to function as the 'translocon' of the T3SS needle structure. In this study, it was shown that EseB, EseC and EseD formed a protein complex after secretion, which is consistent with their possible roles as translocon components. The secretion of EseB and EseD was dependent on EscC (previously named Orf2). EscC has the characteristics of a chaperone; it is a small protein (13 kDa), located next to the translocators in the T3SS gene cluster, and has a coiled-coil structure at the N-terminal region as predicted by coils. An in-frame deletion of escC abolished the secretion of EseB and EseD, and complementation of DeltaescC restored the export of EseB and EseD into the culture supernatant. Further studies showed that EscC is not a secreted protein and is located on the membrane and in the cytoplasm. Mutation of escC did not affect the transcription of eseB but reduced the amount of EseB as measured by using an EseB-LacZ fusion protein in Ed. tarda. Co-purification studies demonstrated that EscC formed complexes with EseB and EseD. The results suggest that EscC functions as a T3SS chaperone for the putative translocon components EseB and EseD in Ed. tarda.

  9. Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda

    PubMed Central

    Peng, Bo; Wang, Chao; Li, Hui; Su, Yu-bin; Ye, Jin-zhou; Yang, Man-jun; Jiang, Ming; Peng, Xuan-xian

    2017-01-01

    Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication. PMID:28210241

  10. Immunization of olive flounder (Paralichthys olivaceus) with an auxotrophic Edwardsiella tarda mutant harboring the VHSV DNA vaccine.

    PubMed

    Choi, Seung Hyuk; Kim, Min Sun; Kim, Ki Hong

    2012-09-01

    The aims of the present study were to find more powerful promoter for DNA vaccines in olive flounder (Paralichthys olivaceus) and to evaluate the availability of the auxotrophic Edwardsiella tarda mutant (Δalr Δasd E. tarda) as a delivery vehicle for DNA vaccine against VHSV in olive flounder. The marine medaka (Oryzias dancena) β-actin promoter was clearly stronger than cytomegalovirus (CMV) promoter when the vectors were transfected to Epithelioma papulosum cyprini (EPC) cells or injected into the muscle of olive flounder, suggesting that marine medaka β-actin promoter would be more appropriate promoter for DNA vaccines in olive flounder than CMV promoter. Olive flounder immunized with the Δalr Δasd E. tarda harboring viral hemorrhagic septicemia virus (VHSV) DNA vaccine vector driven by the marine medaka β-actin promoter showed significantly higher serum neutralization titer and higher survival rates against challenge with VHSV than fish immunized with the bacteria carrying VHSV DNA vaccine vector driven by CMV promoter. These results indicate that auxotrophic E. tarda mutant harboring marine medaka β-actin promoter-driven DNA vaccine vectors would be a potential system for prophylactics of infectious diseases in olive flounder.

  11. Comparison of static immersion and intravenous injection systems for exposure of zebrafish embryos to the natural pathogen Edwardsiella tarda

    PubMed Central

    2011-01-01

    Background The zebrafish embryo is an important in vivo model to study the host innate immune response towards microbial infection. In most zebrafish infectious disease models, infection is achieved by micro-injection of bacteria into the embryo. Alternatively, Edwardsiella tarda, a natural fish pathogen, has been used to treat embryos by static immersion. In this study we used transcriptome profiling and quantitative RT-PCR to analyze the immune response induced by E. tarda immersion and injection. Results Mortality rates after static immersion of embryos in E. tarda suspension varied between 25-75%, while intravenous injection of bacteria resulted in 100% mortality. Quantitative RT-PCR analysis on the level of single embryos showed that expression of the proinflammatory marker genes il1b and mmp9 was induced only in some embryos that were exposed to E. tarda in the immersion system, whereas intravenous injection of E. tarda led to il1b and mmp9 induction in all embryos. In addition, microarray expression profiles of embryos subjected to immersion or injection showed little overlap. E. tarda-injected embryos displayed strong induction of inflammatory and defense genes and of regulatory genes of the immune response. E. tarda-immersed embryos showed transient induction of the cytochrome P450 gene cyp1a. This gene was also induced after immersion in Escherichia coli and Pseudomonas aeruginosa suspensions, but, in contrast, was not induced upon intravenous E. tarda injection. One of the rare common responses in the immersion and injection systems was induction of irg1l, a homolog of a murine immunoresponsive gene of unknown function. Conclusions Based on the differences in mortality rates between experiments and gene expression profiles of individual embryos we conclude that zebrafish embryos cannot be reproducibly infected by exposure to E. tarda in the immersion system. Induction of il1b and mmp9 was consistently observed in embryos that had been systemically

  12. Frequent isolation of Edwardsiella tarda and Pleisiomonas shigelloides from healthy Zairese freshwater fish: a possible source of sporadic diarrhea in the tropics.

    PubMed Central

    Van Damme, L R; Vandepitte, J

    1980-01-01

    The intestinal contents of 59 Zairese freshwater fish were examined for the presence of potential human enteric pathogens. Edwardsiella tarda and Plesiomonas shigelloides were isolated from 57 and 59% of them, respectively. For both microorganisms there was a significant difference between the isolation rates from lake and river fish: whereas E. tarda was much more frequently isolated from lake fish than was P. shigelloides, the reverse was observed for river fish. The authors hypothesize that sporadic cases of tropical diarrhea with E. tarda or P. shigelloides can be traced to contact with or consumption of freshwater fish. PMID:7387150

  13. Vaccine efficacy of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Edwardsiella ictaluri against E. tarda in tilapia.

    PubMed

    Trung Cao, Thanh; Tsai, Ming-An; Yang, Chung-Da; Wang, Pei-Chyi; Kuo, Tsun-Yung; Gabriel Chen, Hsu-Chung; Chen, Shih-Chu

    2014-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), derived from the outer-membrane protein (OMP) fraction, has been used as a potential candidate for vaccine development. The gene-encoding 37 kDa GAPDH outer membrane protein (OMP) from Edwardsiella ictaluri was amplified using polymerase chain reaction (PCR) and was cloned and expressed in Escherichia coli BL21 (DE3). Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting, and nucleotide and amino acid sequencing were used to analyze the expressed antigenic protein and gene encoding this protein. Comparative DNA and protein sequence analysis of GAPDH from E. ictaluri GAPDHs from several Gram-negative bacterial species within the Enterobacteriaceae family revealed that the GAPDHs within this group are highly conserved and share a sequence similarity of 75-100% with E. ictaluri GDPDH. Rabbit antiserum raised against the E. ictaluri recombinant GAPDH (rGAPDH) protein recognized purified GADPH, indicating that it has a strong immunogenicity. Tilapia fish were intraperitoneally immunized with formalin-killed E. ictaluri whole cells, and rGAPDH (30 μg fish(-1)) from E. ictaluri, both of which were emulsified in ISA 763A adjuvant. At 3 months after immunization, fish were challenged with the E. tarda strain to assess vaccine efficacy; the relative percent survival (RPS) values were found to exceed 71.4%. The specific mean antibody titer log2 level of groups vaccinated with rGAPDH at 3 months was significantly higher than that of non-vaccinated fish (control group). Therefore, this recombinant protein can be considered a multi-purpose candidate vaccine against several pathogenic bacteria.

  14. Quantitative trait loci detection of Edwardsiella tarda resistance in Japanese flounder Paralichthys olivaceus using bulked segregant analysis

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoxia; Xu, Wenteng; Liu, Yang; Wang, Lei; Sun, Hejun; Wang, Lei; Chen, Songlin

    2016-11-01

    In recent years, Edwardsiella tarda has become one of the most deadly pathogens of Japanese flounder ( Paralichthys olivaceus), causing serious annual losses in commercial production. In contrast to the rapid advances in the aquaculture of P. olivaceus, the study of E. tarda resistance-related markers has lagged behind, hindering the development of a disease-resistant strain. Thus, a marker-trait association analysis was initiated, combining bulked segregant analysis (BSA) and quantitative trait loci (QTL) mapping. Based on 180 microsatellite loci across all chromosomes, 106 individuals from the F1333 (♀: F0768 ×♂: F0915) (Nomenclature rule: F+year+family number) were used to detect simple sequence repeats (SSRs) and QTLs associated with E. tarda resistance. After a genomic scan, three markers (Scaffold 404-21589, Scaffold 404-21594 and Scaffold 270-13812) from the same linkage group (LG)-1 exhibited a significant difference between DNA, pooled/bulked from the resistant and susceptible groups (P <0.001). Therefore, 106 individuals were genotyped using all the SSR markers in LG1 by single marker analysis. Two different analytical models were then employed to detect SSR markers with different levels of significance in LG1, where 17 and 18 SSR markers were identified, respectively. Each model found three resistance-related QTLs by composite interval mapping (CIM). These six QTLs, designated qE1-6, explained 16.0%-89.5% of the phenotypic variance. Two of the QTLs, qE-2 and qE-4, were located at the 66.7 cM region, which was considered a major candidate region for E. tarda resistance. This study will provide valuable data for further investigations of E. tarda resistance genes and facilitate the selective breeding of disease-resistant Japanese flounder in the future.

  15. Protective effects and mechanisms of a probiotic bacterium Lactobacillus rhamnosus against experimental Edwardsiella tarda infection in tilapia (Oreochromis niloticus).

    PubMed

    Pirarat, Nopadon; Kobayashi, Takeshi; Katagiri, Takayuki; Maita, Masashi; Endo, Makoto

    2006-10-15

    In recent years, probiotics, especially lactic acid bacteria, have been used as dietary supplements to protect fish from various infections. Here, we examined the protective effects of Lactobacillus rhamnosus against experimental Edwardsiella tarda infection in tilapia (Oreochromis niloticus). Cumulative mortality was significantly lower in probiotic-supplemented fish than in control fish. In a histopathological survey, pyogranulomatous responses were observed at an earlier stage and to a greater extent in the probiotic-supplemented fish than in the control fish. Immunohistochemistry using an anti-E. tarda antibody revealed a larger number of positive signals in pyogranuloma-participating cells, indicating an enhanced phagocytic ability. Alternative complement activity was significantly higher in the probiotic groups than in the control. These results suggest that L. rhamnosus enhanced the alternative complement system of the fish, enabling phagocytic cell aggregation, increasing phagocytic activity and subsequently protecting the fish from acute septicemic death by E. tarda infection. Prevention of thymic necrosis by the probiotic supplement seems to minimize immunosuppression and to initiate an immune response against edwardsiellosis.

  16. Generation of two auxotrophic genes knock-out Edwardsiella tarda and assessment of its potential as a combined vaccine in olive flounder (Paralichthys olivaceus).

    PubMed

    Choi, Seung Hyuk; Kim, Ki Hong

    2011-07-01

    Two auxotrophic genes that play essential roles in bacterial cell wall biosynthesis--alanine racemase (alr) gene and aspartate semialdehyde dehydrogenase (asd) gene--knock-out Edwardsiella tarda (Δalr Δasd E. tarda) was generated by the allelic exchange method to develop a combined vaccine system. Green fluorescent protein (GFP) was used as a model foreign protein, and was expressed by transformation of the mutant E. tarda with antibiotic resistant gene-free plasmids harboring cassettes for GFP and asd expression (pG02-ASD-EtPR-GFP). In vitro growth of the mutant E. tarda was similar to wild-type E. tarda when D-alanine and diaminopimelic acid (DAP) were supplemented to growth medium. However, without d-alanine and/or DAP supplementation, the mutant showed very limited growth. The Δalr Δasd E. tarda transformed with pG02-ASD-EtPR-GFP showed a similar growth pattern of wild-type E. tarda when D-alanine was supplemented in the medium, and the expression of GFP could be observed even with naked eyes. The virulence of the auxotrophic mutant E. tarda was decreased, which was demonstrated by approximately 10⁶ fold increase of LD₅₀ dose compared to wild-type E. tarda. To assess vaccine potential of the present combined vaccine system, olive flounder (Paralichthys olivaceus) were immunized with the GFP expressing mutant E. tarda, and analyzed protection efficacy against E. tarda challenge and antibody titers against E. tarda and GFP. Groups of fish immunized with 10⁷ CFU of the Δalr Δasd E. tarda harboring pG02-ASD-EtPR-GFP showed no mortality, which was irrespective to boost immunization. The cumulative mortality rates of fish immunized with 10⁶ or 10⁵ CFU of the mutant bacteria were lowered by a boost immunization. Fish immunized with the mutant E. tarda at doses of 10⁶-10⁷ CFU/fish showed significantly higher serum agglutination activities against formalin-killed E. tarda than PBS-injected control fish. Furthermore, fish immunized with 10⁶-10

  17. Attenuation of Edwardsiella tarda virulence by small peptides that interfere with LuxS/autoinducer type 2 quorum sensing.

    PubMed

    Zhang, Min; Jiao, Xu-dong; Hu, Yong-hua; Sun, Li

    2009-06-01

    Edwardsiella tarda is a gram-negative pathogen with a broad host range that includes humans, animals, and fish. Recent studies have shown that the LuxS/autoinducer type 2 (AI-2) quorum sensing system is involved in the virulence of E. tarda. In the present study, it was found that the E. tarda LuxS mutants bearing deletions of the catalytic site (C site) and the tyrosine kinase phosphorylation site, respectively, are functionally inactive and that these dysfunctional mutants can interfere with the activity of the wild-type LuxS. Two small peptides, 5411 and 5906, which share sequence identities with the C site of LuxS, were identified. 5411 and 5906 proved to be inhibitors of AI-2 activity and could vitiate the infectivity of the pathogenic E. tarda strain TX1. The inhibitory effect of 5411 and 5906 on AI-2 activity is exerted on LuxS, with which these peptides specifically interact. The expression of 5411 and 5906 in TX1 has multiple effects (altering biofilm production and the expression of certain virulence-associated genes), which are similar to those caused by interruption of luxS expression. Further study found that it is very likely that 5411 and 5906 can be released from the strains expressing them and, should TX1 be in the vicinity, captured by TX1. Based on this observation, a constitutive 5411 producer (Pseudomonas sp. strain FP3/pT5411) was constructed in the form of a fish commensal isolate that expresses 5411 from a plasmid source. The presence of FP3/pT5411 in fish attenuates the virulence of TX1. Finally, it was demonstrated that fish expressing 5411 directly from tissues exhibit enhanced resistance against TX1 infection.

  18. Influence of catfish skin mucus on trisodium phosphate inactivation of attached Salmonella Typhimurium, Edwardsiella tarda, and Listeria monocytogenes.

    PubMed

    Kim, Jangho; Marshall, Douglas L

    2002-07-01

    This study examined the antimicrobial effectiveness of trisodium phosphate (TSP) on Edwardsiella tarda, Listeria monocytogenes, and Salmonella Typhimurium attached to catfish skin with and without mucus. Salmonella Typhimurium and E. tarda attached more readily to catfish skin than did L monocytogenes. At high inoculum levels (10(7) CFU/ml), TSP treatments (at 2 to 6%) for 10 min reduced bacterial counts of E. tarda by >2.5 to >3.3 log10 CFU per skin sample for firmly attached cells and by 3.5 to 3.6 log10 CFU per skin sample for loosely attached cells. Counts of L. monocytogenes declined by 0.6 to >1.8 log10 CFU per skin sample for firmly attached cells and by 1.2 to 2.2 log10 CFU per skin sample for loosely attached cells. Counts of Salmonella Typhimurium were reduced by 3.6 to >3.8 log10 CFU per skin sample for firmly attached cells and by 3.5 to >3.8 log10 CFU per skin sample for loosely attached cells. Overall, counts of firmly attached bacteria on TSP-treated skins with mucus were higher than counts on skin without mucus. Firmly attached L. monocytogenes was more resistant to TSP than was firmly attached Salmonella Typhimurium or E. tarda. The presence of mucus on skins slightly decreased the antimicrobial effect of TSP Significant (P < 0.05) reduction in the numbers of all three bacteria can be achieved by treatment with 6% TSP for 10 min.

  19. Comparative analysis of Edwardsiella isolates from fish in the eastern United States identifies two distinct genetic taxa amongst organisms phenotypically classified as E. tarda

    USGS Publications Warehouse

    Griffin, Matt J.; Quiniou, Sylvie M.; Cody, Theresa; Tabuchi, Maki; Ware, Cynthia; Cipriano, Rocco C.; Mauel, Michael J.; Soto, Esteban

    2013-01-01

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, has been implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of E. tarda isolates from 4 different fish species in the eastern United States. Repetitive sequence mediated PCR (rep-PCR) using 4 different primer sets (ERIC I & II, ERIC II, BOX, and GTG5) and multi-locus sequence analysis of 16S SSU rDNA, groEl, gyrA, gyrB, pho, pgi, pgm, and rpoA gene fragments identified two distinct genotypes of E. tarda (DNA group I; DNA group II). Isolates that fell into DNA group II demonstrated more similarity to E. ictaluri than DNA group I, which contained the reference E. tarda strain (ATCC #15947). Conventional PCR analysis using published E. tarda-specific primer sets yielded variable results, with several primer sets producing no observable amplification of target DNA from some isolates. Fluorometric determination of G + C content demonstrated 56.4% G + C content for DNA group I, 60.2% for DNA group II, and 58.4% for E. ictaluri. Surprisingly, these isolates were indistinguishable using conventional biochemical techniques, with all isolates demonstrating phenotypic characteristics consistent with E. tarda. Analysis using two commercial test kits identified multiple phenotypes, although no single metabolic characteristic could reliably discriminate between genetic groups. Additionally, anti-microbial susceptibility and fatty acid profiles did not demonstrate remarkable differences between groups. The significant genetic variation (<90% similarity at gyrA, gyrB, pho, phi and pgm; <40% similarity by rep-PCR) between these groups suggests organisms from DNA group II may represent an unrecognized, genetically distinct taxa of Edwardsiella that is phenotypically indistinguishable from E. tarda.

  20. Adhesive and invasive capacities of Edwardsiella tarda isolated from South American sea lion.

    PubMed

    Fernández, Araceli; Villanueva, María Paz; González, Mario; Fernández, Fabiola; Latif, Fadua; Flores, Sandra Nonier; Fernández, Heriberto

    2014-01-01

    Edwarsiella tarda is a zoonotic bacterium that can be isolated from humans, animals and the environment. Although E. tarda is primarily considered a fish pathogen, it is the only species of its genus considered to be pathogenic for humans as well. A survey of zoonotic intestinal bacteria in fresh feces from South American sea lions (SASL) Otaria flavescens, reported E. tarda as the most frequently isolated species. In this study, we used HEp-2 cells to establish in vitro the adherence and invasive ability of 17 E. tarda strains isolated from SASL fecal material. All the strains were able to adhere and invade HEp-2 cells with adhesion and invasion percentages ranging from 56 to 100% and 21 to 74%, respectively. Despite the expression of these pathogenic factors, further investigation is needed to determine whether this bacterium could play a role as primary pathogen for this and other species of pinnipeds.

  1. Suppression subtractive hybridization coupled with microarray analysis to examine differential expression of genes in Japanese flounder Paralichthys olivaceus leucocytes during Edwardsiella tarda and viral hemorrhagic septicemia virus infection.

    PubMed

    Matsuyama, Tomomasa; Fujiwara, Atushi; Takano, Tomokazu; Nakayasu, Chihaya

    2011-10-01

    Transcriptional changes in the peripheral blood leucocytes (PBL) of Japanese flounder Paralichthys olivaceus challenged by Edwardsiella tarda and viral hemorrhagic septicemia virus (VHSV) were investigated using suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis. First, we constructed an SSH cDNA library using mRNA samples isolated from PBL of P. olivaceus that had been experimentally infected with E. tarda. We then examined the transcriptional changes occurring in the PBL due to E. tarda and VHSV infection using a cDNA microarray produced using clones produced from the SSH library. A total of 565 and 180 cDNA sequences corresponding to mRNA species that are either up- or down-regulated by E. tarda infection were isolated by SSH. While host gene expression responses in response to E. tarda and VHSV infection share several response elements, distinct patterns of gene expression were also observed. Specifically, E. tarda infection enhanced the expression of cell adhesion molecules while VHSV enhanced the expression of interferon and proteasome-related genes. In challenge trials of the two infectious agents, expression profiles of chemokines were also observed to differ. The results indicated that distinguishing between viral and bacterial infection is possible based on the RNA expression profiles of PBL from infected fish.

  2. EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC-eseE Operon.

    PubMed

    Yi, Jia; Xiao, Shui Bing; Zeng, Zhi Xiong; Lu, Jin Fang; Liu, Lu Yi; Laghari, Zubair Ahmed; Nie, Pin; Yu, Hong Bing; Xie, Hai Xia

    2016-08-01

    Edwardsiella tarda is an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. An eseE deletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion of eseE resulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operon escC-eseE, comprising escC, eseB, escA, eseC, eseD, and eseE These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the ΔeseE strain was outcompeted by wild-type E. tarda in a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operon escC-eseE, thus contributing to the pathogenesis of E. tarda in fish.

  3. EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC-eseE Operon

    PubMed Central

    Yi, Jia; Xiao, Shui Bing; Zeng, Zhi Xiong; Lu, Jin Fang; Liu, Lu Yi; Laghari, Zubair Ahmed; Nie, Pin; Yu, Hong Bing

    2016-01-01

    Edwardsiella tarda is an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. An eseE deletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion of eseE resulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operon escC-eseE, comprising escC, eseB, escA, eseC, eseD, and eseE. These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the ΔeseE strain was outcompeted by wild-type E. tarda in a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operon escC-eseE, thus contributing to the pathogenesis of E. tarda in fish. PMID:27271743

  4. Characterization of ampicillin-stressed proteomics and development of a direct method for detecting drug-binding proteins in Edwardsiella tarda.

    PubMed

    Liu, Xian-jie; Zhu, Wei-cong; Su, Yu-bin; Guo, Chang; Zeng, Zhao-hai; Zhu, Hai; Li, Hui; Peng, Xuan-xian

    2015-02-26

    Antibiotic-resistant Edwardsiella tarda poses a severe challenge to aquaculture. An understanding for antibiotic-resistant mechanisms is crucial to control the disease. The present study characterizes E. tarda ampicillin-stressed proteome and shows the importance of energy metabolism including the TCA cycle and glycolysis/gluconeogenesis in the antibiotic resistance. Further combination with antibiotic measurement develops a new method for identification of antibiotic-binding proteins out of differential abundances of proteins and results in determination of ETAE_0175 and ETAE_3367 as ampicillin-binding proteins in E. tarda. Genes of the two proteins are cloned and recombinant proteins are purified for validation of antibiotic-binding capability. Results show that higher binding capability is detected in ETAE_3367 than ETAE_0175. Out of the two proteins, ETAE_3367 is first reported here to be an antibiotic-binding protein, while ETAE_0175 homology in other bacteria has been shown to bind with other antibiotics. Bioinformatics analysis shows that ETAE_3367 may closely interact with aceF and sucA belonging to the TCA cycle and glycolysis/gluconeogenesis, respectively. These results indicate that energy metabolism contributes to ampicillin resistance in E. tarda and a new method to identify antibiotic-binding proteins is developed. These findings highlight the way to an understanding of antibiotic-resistant mechanisms in content of antibiotic-binding proteins. Our data characterizes Edwardsiella tarda ampicillin-stressed proteome and shows the importance of energy metabolism including the TCA cycle and glycolysis/gluconeogenesis in the antibiotic resistance. Furthermore, a new method based 2-DE proteomics is developed for identification of antibiotic-binding proteins, which results in determination of ETAE_0175 and ETAE_3367 as ampicillin-binding proteins in E. tarda. ETAE_3367 is closely interacted with proteins of the TCA cycle and glycolysis

  5. An improved method for detection of Edwardsiella tarda by loop-mediated isothermal amplification by targeting the EsrB gene

    NASA Astrophysics Data System (ADS)

    Xie, Guosi; Zhang, Qingli; Han, Nana; Shi, Chengyin; Wang, Xiuhua; Liu, Qinghui; Huang, Jie

    2012-07-01

    Edwardsiella tarda is a major pathogen in aquatic environments that can cause heavy economic losses. An improved method for quick and accurate detection of E. tarda by loop-mediated isothermal amplification (LAMP) with two additional loop primers was developed by targeting the EsrB gene ( EsrB — LAMP). In this method, the Mg2+ concentration, reaction temperature, and reaction time were optimized to 8 mmol/L, 61°C, and 40 min, respectively. The detection limit with the EsrB gene was as low as 10 copies, which is 100 times more sensitive than that of conventional polymerase chain reaction (PCR). The EsrB-LAMP assay was shown more sensitive and rapid than previously reported LAMP assays targeting the hemolysin gene ( hemolysin -LAMP) for detection of E. tarda. The EsrB -LAMP was also highly specific to E. tarda and had no cross-reaction with 13 other strains of bacteria. The assay can be carried out in a simple heating device and the EsrB-LAMP products can be visually detected by adding fluorescent dye to the reaction mixture. Taken together, the improved EsrB-LAMP diagnostic protocol has the potential for detection of E. tarda from indoor and outdoor samples.

  6. Potential of auxotrophic Edwardsiella tarda double-knockout mutant as a delivery vector for DNA vaccine in olive flounder (Paralichthys olivaceus).

    PubMed

    Choi, Seung Hyuk; Kim, Ki Hong

    2012-02-15

    To evaluate potential of an auxotrophic Edwardsiella tarda mutant (Δalr Δasd E. tarda) as a delivery vehicle for DNA vaccine in fish, olive flounder (Paralichthys olivaceus) were immunized with the E. tarda mutant harboring plasmids (pG02-ASD-CMV-eGFP) for eukaryotic expression of the enhanced green fluorescent protein (eGFP) gene through either intraperitoneal (i.p.) or oral route, and the expression of eGFP in the internal organs and generation of antibody against eGFP in fish were analyzed. In fish i.p. injected with 2×10(7)CFU/fish of Δalr Δasd E. tarda harboring pG02-ASD-CMV-eGFP, expression of eGFP was detected in liver, kidney, and spleen from 1 day to 28 days post-injection. In fish orally administered with 1×10(9)CFU/fish of the bacteria, the eGFP band was detected in liver, kidney, and spleen from 1 day to 14 days post-administration, whereas, in intestine, the band was detected only at 1 day post-administration. Either oral or i.p. immunization of olive flounder with recombinant E. tarda that carried eGFP-expressing eukaryotic plasmids was successful to induce humoral adaptive immunity against not only E. tarda that was used as a delivery vehicle but also eGFP that was used as the reporter protein of DNA vaccine, suggesting attenuated E. tarda-vectored DNA vaccine has a potential to be used as a combined vaccine against infectious diseases in fish. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Studies on expression pattern of toll-like receptor 5 (TLR5) in Edwardsiella tarda infected Pangasianodon hypophthalmus.

    PubMed

    Jayaramu, Poojashree Kachigere; Tripathi, Gayatri; Pavan Kumar, A; Keezhedath, Jeena; Pathan, Mujahid Khan; Kurcheti, Pani Prasad

    2017-04-01

    TLR5 is one of the important PRR (pathogen recognition receptors) and plays a fundamental role in pathogen recognition and activation of innate immune responses. It recognizes bacterial flagellin and stimulates the production of proinflammatory cytokines, through signalling via the adaptor protein MyD88. In this study, we characterized partial TLR5 (soluble form) gene from Pangasianodon hypophthalmus and analysed its expression profile upon challenge by Edwardsiella tarda. Bioinformatic analysis of gene sequence revealed a putative protein of 266 amino acids with four Leucine rich repeats. Quantitative expression analysis of TLR 5S showed its wide distribution in various organs and tissues. However, significant expression of TLR5S was observed in liver and spleen at 12 h (∼207.8 fold, p < 0.05). Significant upregulation was observed in kidney at 72 h.p.i. (50 folds, p < 0.05) indicating that the kidney provides longer protection almost till the activation of the adaptive immune system. This study enriches the knowledge of TLR5S in boosting the innate immunity against bacterial invasion in fish.

  8. TolC plays a crucial role in immune protection conferred by Edwardsiella tarda whole-cell vaccines

    PubMed Central

    Wang, Chao; Peng, Bo; Li, Hui; Peng, Xuan-xian

    2016-01-01

    Although vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified, and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated-30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines. PMID:27406266

  9. Endoscopic ultrasonography-guided transmural drainage of an infected hepatic cyst due to Edwardsiella tarda: a case report.

    PubMed

    Taguchi, Hiroki; Tamai, Tsutomu; Numata, Masatsugu; Maeda, Hitomi; Ohshige, Akihiko; Iwaya, Hiromichi; Hashimoto, Shinichi; Kanmura, Shuji; Funakawa, Keita; Fujita, Hiroshi; Ido, Akio; Tsubouchi, Hirohito

    2014-10-01

    Infected hepatic cysts are very rare compared to simple liver cysts and abscesses. We treated a 77-year-old man with an infected hepatic cyst in the lateral segment caused by Edwardsiella tarda, which has not been previously reported as a pathogenic organism associated with infected hepatic cysts. Percutaneous drainage was temporarily effective, but infection recurred after the drainage tube was removed. We then inserted two drainage tubes into the cyst using an endoscopic ultrasonography (EUS)-guided technique, which was developed from EUS-guided fine needle aspiration (EUS-FNA). The internal drainage tube was a 7 Fr double pigtail stent, and the external tube was a 6 Fr nasobiliary drainage tube. Lavage through the external drainage tube was carried out for one week. The external drainage tube was discontinued when the patient's condition improved significantly. Sixteen days after tube insertion, he was discharged with the internal tube draining the hepatic cyst into the stomach. Fifteen months after EUS-guided drainage, CT examination showed no recurrence of the hepatic cyst. EUS-guided drainage is an effective treatment for infected hepatic cysts.

  10. A prebiotic role of Ecklonia cava improves the mortality of Edwardsiella tarda-infected zebrafish models via regulating the growth of lactic acid bacteria and pathogen bacteria.

    PubMed

    Lee, WonWoo; Oh, Jae Young; Kim, Eun-A; Kang, Nalae; Kim, Kil-Nam; Ahn, Ginnae; Jeon, You-Jin

    2016-07-01

    In this study, the beneficial prebiotic roles of Ecklonia cava (E. cava, EC) were evaluated on the growth of lactic acid bacteria (LAB) and pathogen bacteria and the mortality of pathogen-bacteria infected zebrafish model. The result showed that the original E. cava (EC) led to the highest growth effects on three LABs (Lactobacillus brevis, L. brevis; Lactobacillus pentosus, L. pentosus; Lactobacillus plantarum; L. plantarum) and it was dose-dependent manners. Also, EC, its Celluclast enzymatic (ECC) and 100% ethanol extracts (ECE) showed the anti-bacterial activities on the fish pathogenic bacteria such as (Edwardsiella tarda; E. tarda, Streptococcus iniae; S. iniae, and Vibrio harveyi; V. harveyi). Interestingly, EC induced the higher production of the secondary metabolites from L. plantarum in MRS medium. The secondary metabolites produced by EC significantly inhibited the growth of pathogen bacteria. In further in vivo study, the co-treatment of EC and L. plantarum improved the growth and mortality of E. tarda-infected zebrafish as regulating the expression of inflammatory molecules such as iNOS and COX2. Taken together, our present study suggests that the EC plays an important role as a potential prebiotic and has a protective effect against the infection caused by E. tarda injection in zebrafish. Also, our conclusion from this evidence is that EC can be used and applied as a useful prebiotic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Starvation beneficially influences the liver physiology and nutrient metabolism in Edwardsiella tarda infected red sea bream (Pagrus major).

    PubMed

    Mohapatra, Sipra; Chakraborty, Tapas; Shimizu, Sonoko; Urasaki, Shintaro; Matsubara, Takahiro; Nagahama, Yoshitaka; Ohta, Kohei

    2015-11-01

    Dietary compromises, especially food restrictions, possess species-specific effects on the health status and infection control in several organisms, including fish. To understand the starvation-mediated physiological responses in Edwardsiella tarda infected red sea bream, especially in the liver, we performed a 20-day starvation experiment using 4 treatment (2 fed and 2 starved) groups, namely, fed-placebo, starved-placebo, fed-infected, and starved-infected, wherein bacterial exposure was done on the 11th day. In the present study, the starved groups showed reduced hepatosomatic index and drastic depletion in glycogen storage and vacuole formation. The fed-infected fish showed significant (P<0.05) increase in catalase and superoxide dismutase activity in relation to its starved equivalent. Significant (P<0.05) alteration in glucose and energy metabolism, as evident from hexokinase and glucose-6-phosphate dehydrogenase activity, was recorded in the starved groups. Interestingly, coinciding with the liver histology, PPAR (peroxisome proliferator activated receptors) α transcription followed a time-dependent activation in starved groups while PPARγ exhibited an opposite pattern. The transcription of hepcidin 1 and transferrin, initially increased in 0dai (days after infection) starved fish but reduced significantly (P<0.05) at later stages. Two-color immunohistochemistry and subsequent cell counting showed significant increase in P63-positive cells at 0dai and 5dai but later reduced slightly at 10dai. Similar results were also obtained in the lysosomal (cathepsin D) and non-lysosomal (ubiquitin) gene transcription level. All together, our data suggest that starvation exerts multidirectional responses, which allows for better physiological adaptations during any infectious period, in red sea bream. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Edwardsiella tarda OmpA Encapsulated in Chitosan Nanoparticles Shows Superior Protection over Inactivated Whole Cell Vaccine in Orally Vaccinated Fringed-Lipped Peninsula Carp (Labeo fimbriatus).

    PubMed

    Dubey, Saurabh; Avadhani, Kiran; Mutalik, Srinivas; Sivadasan, Sangeetha Madambithara; Maiti, Biswajit; Girisha, Shivani Kallappa; Venugopal, Moleyur Nagarajappa; Mutoloki, Stephen; Evensen, Øystein; Karunasagar, Indrani; Munang’andu, Hetron Mweemba

    2016-11-07

    The use of oral vaccination in finfish has lagged behind injectable vaccines for a long time as oral vaccines fall short of injection vaccines in conferring protective immunity. Biodegradable polymeric nanoparticles (NPs) have shown potential to serve as antigen delivery systems for oral vaccines. In this study the recombinant outer membrane protein A (rOmpA) of Edwardsiella tarda was encapsulated in chitosan NPs (NP-rOmpA) and used for oral vaccination of Labeo fimbriatus. The rOmpA purity was 85%, nanodiameter <500 nm, encapsulation efficiency 60.6%, zeta potential +19.05 mV, and there was an in vitro release of 49% of encapsulated antigen within 48 h post incubation in phosphate-buffered saline. Empty NPs and a non-formulated, inactivated whole cell E. tarda (IWC-ET) vaccine were used as controls. Post-vaccination antibody levels were significantly (p = 0.0458) higher in the NP-rOmpA vaccinated fish (Mean OD450 = 2.430) than in fish vaccinated with inactivated whole cell E. tarda (IWC-ET) vaccine (Mean OD450 = 1.735), which corresponded with post-challenge survival proportions (PCSP) of 73.3% and 48.28% for the NP-rOmpA and IWC-ET groups, respectively. Serum samples from NP-rOmpA-vaccinated fish had a higher inhibition rate for E. tarda growth on tryptic soy agar (TSA) than the IWC-ET group. There was no significant difference (p = 0.989) in PCSPs between fish vaccinated with empty NPs and the unvaccinated control fish, while serum from both groups showed no detectable antibodies against E. tarda. Overall, these data show that the NP-rOmpA vaccine produced higher antibody levels and had superior protection over the IWC-ET vaccine, showing that encapsulating OmpA in chitosan NPs confer improved protection against E. tarda mortality in L. fimbriatus. There is a need to elucidate the possible adjuvant effects of chitosan NPs and the immunological mechanisms of protective immunity induced by OMPs administered orally to fish.

  13. Edwardsiella tarda OmpA Encapsulated in Chitosan Nanoparticles Shows Superior Protection over Inactivated Whole Cell Vaccine in Orally Vaccinated Fringed-Lipped Peninsula Carp (Labeo fimbriatus)

    PubMed Central

    Dubey, Saurabh; Avadhani, Kiran; Mutalik, Srinivas; Sivadasan, Sangeetha Madambithara; Maiti, Biswajit; Girisha, Shivani Kallappa; Venugopal, Moleyur Nagarajappa; Mutoloki, Stephen; Evensen, Øystein; Karunasagar, Indrani; Mweemba Munang′andu, Hetron

    2016-01-01

    The use of oral vaccination in finfish has lagged behind injectable vaccines for a long time as oral vaccines fall short of injection vaccines in conferring protective immunity. Biodegradable polymeric nanoparticles (NPs) have shown potential to serve as antigen delivery systems for oral vaccines. In this study the recombinant outer membrane protein A (rOmpA) of Edwardsiella tarda was encapsulated in chitosan NPs (NP-rOmpA) and used for oral vaccination of Labeo fimbriatus. The rOmpA purity was 85%, nanodiameter <500 nm, encapsulation efficiency 60.6%, zeta potential +19.05 mV, and there was an in vitro release of 49% of encapsulated antigen within 48 h post incubation in phosphate-buffered saline. Empty NPs and a non-formulated, inactivated whole cell E. tarda (IWC-ET) vaccine were used as controls. Post-vaccination antibody levels were significantly (p = 0.0458) higher in the NP-rOmpA vaccinated fish (Mean OD450 = 2.430) than in fish vaccinated with inactivated whole cell E. tarda (IWC-ET) vaccine (Mean OD450 = 1.735), which corresponded with post-challenge survival proportions (PCSP) of 73.3% and 48.28% for the NP-rOmpA and IWC-ET groups, respectively. Serum samples from NP-rOmpA-vaccinated fish had a higher inhibition rate for E. tarda growth on tryptic soy agar (TSA) than the IWC-ET group. There was no significant difference (p = 0.989) in PCSPs between fish vaccinated with empty NPs and the unvaccinated control fish, while serum from both groups showed no detectable antibodies against E. tarda. Overall, these data show that the NP-rOmpA vaccine produced higher antibody levels and had superior protection over the IWC-ET vaccine, showing that encapsulating OmpA in chitosan NPs confer improved protection against E. tarda mortality in L. fimbriatus. There is a need to elucidate the possible adjuvant effects of chitosan NPs and the immunological mechanisms of protective immunity induced by OMPs administered orally to fish. PMID:27827990

  14. The protection effect of LEAP-2 on the mudskipper (Boleophthalmus pectinirostris) against Edwardsiella tarda infection is associated with its immunomodulatory activity on monocytes/macrophages.

    PubMed

    Chen, Jie; Chen, Qiang; Lu, Xin-Jiang; Chen, Jiong

    2016-12-01

    Liver-expressed antimicrobial peptide 2 (LEAP-2) is a cationic peptide that plays an important role in the host's innate immune system. However, the mechanism by which LEAP-2 modulates/regulates the host defense against pathogens remains largely unknown. In this study, we identified a cDNA sequence encoding LEAP-2 homolog (BpLEAP-2) in the mudskipper, Boleophthalmus pectinirostris. Sequence analysis revealed that BpLEAP-2 belonged to the fish LEAP-2A cluster and that it was closely related to ayu LEAP-2. BpLEAP-2 mRNA was detected in a wide range of tissues, with the highest level of transcripts found in the liver. Upon infection with Edwardsiella tarda, BpLEAP-2 mRNA expression was significantly increased in the liver, kidney, spleen, and gill, but decreased in the intestine. Chemically synthesized BpLEAP-2 mature peptide did not exhibit antibacterial activity against E. tarda in vitro. Intraperitoneal injection of BpLEAP-2 (1.0 or 10.0 μg/g) resulted in significantly improved survival rate and reduced tissue bacterial load in E. tarda-infected mudskippers. In E. tarda-infected fish, BpLEAP-2 (0.1, 1.0, or 10.0 μg/g) eliminated E. tarda-induced tissue mRNA expression of BpTNF-α and BpIL-1β. In monocytes/macrophages (MO/MФ), BpLEAP-2 (1.0 or 10.0 μg/ml) induced chemotaxis, enhanced respiratory burst, and inhibited E. tarda-induced mRNA expression of BpTNF-α and BpIL-1β. At a concentration of 10.0 μg/ml, BpLEAP-2 also significantly enhanced the bacterial killing efficiency of MO/MФ. No significant effect was seen in the phagocytic activity of MO/MФ upon treatment with BpLEAP-2. Our study provides evidence, for the first time, that LEAP-2 exhibited immunomodulatory effects on immune cells, and protected the host from pathogenic infections independent of direct bacterial killing function.

  15. Feeding of nano scale oats β-glucan enhances the host resistance against Edwardsiella tarda and protective immune modulation in zebrafish larvae.

    PubMed

    Udayangani, R M C; Dananjaya, S H S; Fronte, Baldassare; Kim, Cheol-Hee; Lee, Jehee; De Zoysa, Mahanama

    2017-01-01

    In this study, we prepared and characterized the oats origin of nano scale β-glucan (NBG) and investigated the immunomodulatory properties in zebrafish larvae. Newly prepared NBG (average particle size of 465 nm) was fully soluble in water. Zebrafish larvae survival rate was increased against pathogenic bacteria Edwardsiella tarda, when NBG was added to the water (500 μg/mL) compared to NBG non-exposed controls. Moreover, quantitative real time PCR (qRT-PCR) results showed up-regulation of immune functional genes including TNF-α, IL-1β, β-defensin, lysozyme, IL 10, IL 12 and C-Rel indicating higher survival rate could be due to stronger immunomodulatory function of NBG (500 μg/mL). Thus, non-toxic, water soluble and biodegradable NBG from oats could be considered as the potential immunostimulant for larval aquaculture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Mutations in the gyrB, parC, and parE genes of quinolone-resistant isolates and mutants of Edwardsiella tarda.

    PubMed

    Kim, Myoung Sug; Jun, Lyu Jin; Shin, Soon Bum; Park, Myoung Ae; Jung, Sung Hee; Kim, Kwangil; Moon, Kyung Ho; Jeong, Hyun Do

    2010-12-01

    The full length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in Edwardsiella tarda were cloned by PCR with degenerate primers based on the sequence of the respective quinolone resistance-determining region (QRDR), followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved gyrase/topoisomerase features and motifs important for enzymatic function. The ORFs were preceded by putative promoters, ribosome binding sites, and inverted repeats with the potential to form cruciform structures for binding of DNA-binding proteins. When comparing the deduced amino acid sequences of E. tarda GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria, they were found to be most closely related to Escherichia coli GyrB (87.6% identity), Klebsiella pneumoniae ParC (78.8% identity) and Salmonella typhimurium ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE, were found to be contiguous on the E. tarda chromosome. All 18 quinoloneresistant isolates obtained from Korea thus far did not contain subunit alternations apart from a substitution in GyrA (Ser83→Arg). However, an alteration in the QRDR of ParC (Ser84→Ile) following an amino acid substitution in GyrA (Asp87→Gly) was detected in E. tarda mutants selected in vitro at 8 microng/ml ciprofloxacin (CIP). A mutant with a GyrB (Ser464→Leu) and GyrA (Asp87→Gly) substitution did not show a significant increase in the minimum inhibitory concentration (MIC) of CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and parC should be considered to be the primary and secondary targets, respectively, of quinolones in E. tarda.

  17. A cDNA microarray analysis to identify genes involved in the acute-phase response pathway of the olive flounder after infection with Edwardsiella tarda.

    PubMed

    Moon, Ji Young; Hong, Yong-Ki; Kong, Hee Jeong; Kim, Dong-Gyun; Kim, Young-Ok; Kim, Woo-Jin; Ji, Young Joo; An, Cheul Min; Nam, Bo-Hye

    2014-09-15

    The acute-phase response (APR) is an important systemic reaction that occurs within hours of an inflammatory signal caused by physical bodily injury or microbial infection. To investigate the APR of the olive flounder (Paralichthys olivaceus) following infection with a pathogen, we established an expressed sequence tag (EST)-based cDNA microarray chip composed of 13,061 PCR-amplified cDNAs encoding unique genes selected from an olive flounder EST analysis. Microarray analyses showed that the set of genes involved in the APR was strongly up-regulated in the liver of the olive flounder after infection with Edwardsiella tarda. Among the up-regulated genes, catechol-O-methyltransferase domain-containing protein 1, six-transmembrane prostate protein, haptoglobin precursor, and toll-like receptor 5 soluble form were particularly strongly up-regulated. Interestingly, the toll-like receptor 5 soluble form, which has not yet been detected in mammals, was up-regulated as much as 250-fold upon E. tarda infection. These results suggest that the APR mechanism of fish may be regulated differently from that of mammals. The data described here contribute toward our collective understanding of APR, especially in fish.

  18. Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection.

    PubMed

    Chigwechokha, Petros Kingstone; Tabata, Mutsumi; Shinyoshi, Sayaka; Oishi, Kazuki; Araki, Kyosuke; Komatsu, Masaharu; Itakura, Takao; Shiozaki, Kazuhiro

    2015-11-01

    Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. Sialidase NanA expressed endogenously in E. tarda is glycosidase removing sialic acids from glycoconjugates. Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. As a result, infection of HeLa cells by E. tarda was significantly reduced when compared to GAKS cells. Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing

  19. Transcriptome profiling based on protein-protein interaction networks provides a core set of genes for understanding blood immune response mechanisms against Edwardsiella tarda infection in Japanese flounder (Paralichthys olivaceus).

    PubMed

    Li, Zan; Liu, Xiumei; Liu, Jinxiang; Zhang, Kai; Yu, Haiyang; He, Yan; Wang, Xubo; Qi, Jie; Wang, Zhigang; Zhang, Quanqi

    2017-09-18

    Marine organisms are commonly under threat from various pathogens. Edwardsiella tarda is one of the fish pathogens that can infect both cultured and wild fish species. E. tarda can also infect other vertebrates, including amphibians, reptiles, and mammals. Bacteremia caused by E. tarda can be a fatal disease in humans. Blood acts as a pipeline for the fish immune system. Generating blood transcriptomic resources from fish challenged by E. tarda is crucial for understanding molecular mechanisms underlying blood immune response process. In this study, we performed transcriptome-wide gene expression profiling of Japanese flounder (Paralichthys olivaceus) challenged by 8 and 48 h E. tarda stress. An average of 37 million clean reads per library was obtained, and approximately 85.6% of these reads were successfully mapped to the reference genome. In addition, 808 and 1265 differential expression genes (DEGs) were found at 8 and 48 h post-injection, respectively. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to search immune-related DEGs. A protein-protein interaction network was constructed to obtain the interaction relationship of immune genes during pathogens stress. Based on KEGG and protein association networks analysis, 30 hub genes were discovered and validated by quantitative RT-PCR. This study represents the first transcriptome analysis based on protein-protein interaction networks in fish and provides us with valuable gene resources for the research of fish blood immunity, which can significantly assist us to further understand the molecular mechanisms of humans and other vertebrates against E. tarda. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Edwardsiella tarda bacteremia. A rare but fatal water- and foodborne infection: Review of the literature and clinical cases from a single centre

    PubMed Central

    Hirai, Yuji; Asahata-Tago, Sayaka; Ainoda, Yusuke; Fujita, Takahiro; Kikuchi, Ken

    2015-01-01

    BACKGROUND: Edwardsiella tarda bacteremia (ETB) can be a fatal disease in humans. OBJECTIVES: To determine the significant risk factors associated with death caused by ETB, and to examine the geographical, seasonal, environmental and dietary factors of the disease. METHODS: A retrospective, observational, case control study was performed. The PubMed MEDLINE and Japanese Medical Abstract Society (www.jamas.or.jp) databases were searched for ETB case reports and meeting abstracts. In additon, retrospective chart reviews of patients with ETB at the Tokyo Women’s Medical University Hospital (Tokyo, Japan) were conducted to evaluate the risk factors associated with death using multivariate analyses. RESULTS: The literature search yielded 46 publications, comprising 72 cases from the English (n=30), French (n=1), Spanish (n=1) and Japanese (n=14) literature. Five cases at the Tokyo Women’s Medical University Hospital were also included. Of the included 77 cases, the mean age was 61 years and 39% of patients were female; 77.2% of the cases occurred between June and November, and 45.5% were reported in Japan. Dietary factors (raw fish/meat exposure) were reported for 10.4% of patients and 12.9% reported environmental (ie, brackish water) exposure. The overall mortality rate was 44.6%; however, this rate increased to 61.1% for ETB patients with soft tissue infections. Liver cirrhosis was determined to be an independent risk factor associated with death (OR 12.0 [95% CI 2.46 to 58.6]; P=0.00213) using multivariate analyses. DISCUSSION: To our knowledge, the present analysis was the first and largest multi-language review of ETB. Clinical characteristics of ETB resemble those of Aeromonas, typhoid fever and Vibrio vulnificus infections, in addition to sharing similar risk factors. CONCLUSION: ETB should be categorized as a severe food- and waterborne infection, which results in high mortality for patients with liver cirrhosis. PMID:26744588

  1. Characterization of CD3(+) T lymphocytes of Japanese flounder (Paralichthys olivaceus) and its response after immunization with formalin-inactivated Edwardsiella tarda.

    PubMed

    Tang, Xiaoqian; Qin, Yinghui; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2017-04-01

    The CD3 complex is an important cell surface marker of T lymphocytes and essential for T lymphocytes activation in higher vertebrates. In the present work, the CD3ε of Japanese flounder (Paralichthys olivaceus) was recombinantly expressed in E. coli BL21 (DE3) and used as an immunogen to produce mouse anti-rCD3ε polyclonal antibodies, which could specifically recognize a 20 kDa protein in the membrane proteins of peripheral blood lymphocytes (PBL) of Japanese flounder by co-immunoprecipitation assay. Mass spectrometric analysis showed the 20 kDa protein was the native CD3ε of Japanese flounder. Both the flow cytometric analysis and double immunofluorescence assay (DIFA) showed that the CD3(+) T lymphocytes could be identified specifically by the mouse anti-rCD3ε polyclonal antibodies, which didn't cross-react with the sIgM(+) lymphocytes. Immunohistochemistry showed that CD3(+) T lymphocytes could be detected in gill, skin, stomach, intestine, spleen, liver, head-kidney and mid-kidney. Flow cytometric analysis showed the percentages of CD3(+) T lymphocytes in the PBL, spleen lymphocytes (SL) and head-kidney lymphocytes (HKL) of Japanese flounder increased rapidly after immunization with formalin-inactivated Edwardsiella tarda, and reached their peak levels at 5th day with 12.6%, 9.7% and 8.7%, respectively, and then decreased gradually. These results suggested that CD3(+) T lymphocytes play important roles in mucosal and cell-mediated immunity, and the results would deepen our understanding on the roles of teleost T lymphocytes in the immune response.

  2. Systematic mutation analysis of two-component signal transduction systems reveals EsrA-EsrB and PhoP-PhoQ as the major virulence regulators in Edwardsiella tarda.

    PubMed

    Lv, Yuanzhi; Xiao, Jingfan; Liu, Qin; Wu, Haizhen; Zhang, Yuanxing; Wang, Qiyao

    2012-05-25

    Edwardsiella tarda is a Gram-negative broad-host-range pathogen that causes hemorrhagic septicemia in many commercially important fish species. Its ability to adapt to and thrive in diverse environments outside and inside of its hosts prompts us to investigate the roles of the previously identified 33 putative two-component signal transduction systems (TCSs) in E. tarda. In this work, we successfully constructed deletion mutations in each of the response regulator genes, suggesting that none of the TCSs are essential for cell viability in E. tarda. The mutants were further examined for roles in biofilm formation, antibiotic resistance, stress response, expression and secretion of proteins involved in either the type III secretion system (T3SS) or type VI secretion system (T6SS), as well as virulence. Through these assays, we identified four regulators of biofilm development, two regulators of antibiotic resistance, and four regulators involved in stress responses. We found that two regulators, EsrB and PhoP, are essential for the pathogenicity of E. tarda and further demonstrated that these two regulators have codependent and independent contributions to E. tarda virulence. Mutation of EsrB resulted in the complete loss of both the T3SS and T6SS proteins, while PhoP partially regulated the expression of T3SS and T6SS genes through EsrB, and was essential for resistance to antimicrobial peptides. This work suggested that these two response regulators are involved in the regulation of the complex virulence network of this bacterium and merit as candidate genes for live attenuated vaccine construction. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Effects of dietary supplementation of citrus by-products fermented with a probiotic microbe on growth performance, innate immunity and disease resistance against Edwardsiella tarda in juvenile olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

    PubMed

    Lee, B-J; Kim, S-S; Song, J-W; Oh, D-H; Cha, J-H; Jeong, J-B; Heo, M-S; Kim, K-W; Lee, K-J

    2013-07-01

    Two consecutive studies were conducted to evaluate the dietary supplementation of citrus by-products (CB) fermented with probiotic bacteria on growth performance, feed utilization, innate immune responses and disease resistance of juvenile olive flounder. In Experiment I, five diets were formulated to contain 0% (control) or 3% four different CB fermented with Bacillus subtilis (BS), Enterococcus faecium (EF), Lactobacillus rhamnosus (LR) and L. plantarum (LP) (designated as CON, CBF-BS, CBF-EF, CBF-LR and CBF-LP, respectively). During 10 weeks of a feeding trial, growth performance and feed efficiency were not significantly different among all the fish groups. However, fish fed CBF containing diets had significantly higher survivals than the CON group. Disease resistance of fish against Edwardsiella tarda was increased by the fermentation of CB. In Experiment II, we chose the BS as a promising probiotic and formulated five diets to contain 0%, 2%, 4%, 6% and 8% CBF-BS. Growth performance was not significantly affected by the CBF-BS supplementation during 6 weeks of a feeding trial. Innate immunity of fish was significantly enhanced by CBF-BS supplementation. Myeloperoxidase and lysozyme activities were increased in a dose-dependent manner by dietary CBF-BS inclusions. In a consecutive challenge test against E. tarda, an increased disease resistance was found by CBF-BS supplementation. These studies indicate that the fermentation process of CB with probiotic has beneficial effects on innate immunity and thereby increases disease resistance of olive flounder against E. tarda. Bacillus subtilis can be used as a promising probiotic microbe for by-product fermentation in fish feeds.

  4. Production of RNase III-knockout, auxotrophic Edwardsiella tarda mutant for delivery of long double-stranded RNA and evaluation of its immunostimulatory potential.

    PubMed

    Kim, Min Sun; Choi, Seung Hyuk; Yang, Jeong In; Kim, Ki Hong

    2017-09-01

    The artificially synthesized polyinosinic-polycytidylic acid (poly IC) has been widely used to induce type I IFN responses in various vertebrates including fish. However, as poly IC is too expensive to use in aquaculture, the development of another economical long dsRNA producing method is needed to practically use long dsRNAs in aquaculture farms for the control of infectious diseases. In the present study, to produce long dsRNAs economically, we developed a novel long dsRNA production system based on the RNase III gene deleted auxotrophic mutant E. tarda (ΔalrΔrncΔasd E. tarda) and a long dsRNA-producing vector that was equipped with two modified λ phage PR promoters arranged in a head-to-head fashion. As the present genetically engineered E. tarda cannot live without supplementation of d-alanine and DAP, environmental and medicinal risks are minimized. Olive flounder (Paralichthys olivaceus) fingerlings administered the long dsRNA-producing auxotrophic E. tarda mutant (Δalr ΔrncΔasd E. tarda) showed significantly higher expressions of TLR22, Mx1, and ISG15 genes, indicating a potential to increase type I interferon responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Effect of multiple mutations in tricarboxylic acid cycle and one-carbon metabolism pathways on Edwardsiella ictaluri pathogenesis.

    PubMed

    Dahal, N; Abdelhamed, H; Lu, J; Karsi, A; Lawrence, M L

    2014-02-21

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of catfish (ESC). We have shown recently that tricarboxylic acid cycle (TCA) and one-carbon (C1) metabolism are involved in E. ictaluri pathogenesis. However, the effect of multiple mutations in these pathways is unknown. Here, we report four novel E. ictaluri mutants carrying double gene mutations in TCA cycle (EiΔmdhΔsdhC, EiΔfrdAΔsdhC), C1 metabolism (EiΔglyAΔgcvP), and both TCA and C1 metabolism pathways (EiΔgcvPΔsdhC). In-frame gene deletions were constructed by allelic exchange and mutants' virulence and vaccine efficacy were evaluated using in vivo bioluminescence imaging (BLI) as well as end point mortality counts in catfish fingerlings. Results indicated that all the double gene mutants were attenuated compared to wild-type (wt) E. ictaluri. There was a 1.39-fold average reduction in bioluminescence, and hence bacterial numbers, from all the mutants except for EiΔfrdAΔsdhC at 144 h post-infection. Vaccination with mutants was very effective in protecting channel catfish against subsequent infection with virulent E. ictaluri 93-146 strain. In particular, immersion vaccination resulted in complete protection. Our results provide further evidence on the importance of TCA and C1 metabolism pathways in bacterial pathogenesis.

  6. Lymphedema tarda.

    PubMed

    Majeski, J

    1986-08-01

    Lymphedema tarda is a rare form of primary lymphedema. Its cause is unknown; an autoimmune destruction of lymphatic channels can be hypothesized. A case of lymphedema tarda in which direct immunofluorescent studies of involved tissue showed no immune deposits is presented. The differential diagnosis of this condition is also discussed.

  7. Identification and characterization of an intervening sequence within the 23S ribosomal RNA genes of Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Comparison of the 23S rRNA gene sequences of Edwardsiella tarda and Edwardsiella ictaluri confirmed a close phylogenetic relationship between these two fish pathogen species and a distant relation with the 'core' members of the Enterobacteriaceae family. Analysis of the rrl gene for 23S rRNA in E. i...

  8. Fur-Regulated Iron Uptake System of Edwardsiella ictaluri and Its Influence on Pathogenesis and Immunogenicity in the Catfish Host

    PubMed Central

    Golden, Greg; Wanda, Soo-Young; Curtiss, Roy

    2012-01-01

    The ability of bacterial pathogens to take up iron from the host during infection is necessary for their multiplication within the host. However, host high-affinity iron binding proteins limit levels of free iron in fluids and tissues. To overcome this deficiency of iron during infection, bacterial pathogens have developed iron uptake systems that are upregulated in the absence of iron, typically tightly controlled by the ferric uptake regulator (Fur) protein. The iron uptake system of Edwardsiella ictaluri, a host-restricted pathogen of channel catfish (Ictalurus punctatus) and the main pathogen of this fish in aquaculture, is unknown. Here we describe the E. ictaluri Fur protein, the iron uptake machinery controlled by Fur, and the effects of fur gene deletion on virulence and immunogenicity in the fish host. Analysis of the E. ictaluri Fur protein shows that it lacks the N-terminal region found in the majority of pathogen-encoded Fur proteins. However, it is fully functional in regulated genes encoding iron uptake proteins. E. ictaluri grown under iron-limited conditions upregulates an outer membrane protein (HemR) that shows heme-hemoglobin transport activity and is tightly regulated by Fur. In vivo studies showed that an E. ictaluri Δfur mutant is attenuated and immune protective in zebrafish (Danio rerio) and catfish (Ictalurus punctatus), triggering systemic immunity. We conclude that an E. ictaluri Δfur mutant could be an effective component of an immersion-oral vaccine for the catfish industry. PMID:22615248

  9. Fur-regulated iron uptake system of Edwardsiella ictaluri and its influence on pathogenesis and immunogenicity in the catfish host.

    PubMed

    Santander, Javier; Golden, Greg; Wanda, Soo-Young; Curtiss, Roy

    2012-08-01

    The ability of bacterial pathogens to take up iron from the host during infection is necessary for their multiplication within the host. However, host high-affinity iron binding proteins limit levels of free iron in fluids and tissues. To overcome this deficiency of iron during infection, bacterial pathogens have developed iron uptake systems that are upregulated in the absence of iron, typically tightly controlled by the ferric uptake regulator (Fur) protein. The iron uptake system of Edwardsiella ictaluri, a host-restricted pathogen of channel catfish (Ictalurus punctatus) and the main pathogen of this fish in aquaculture, is unknown. Here we describe the E. ictaluri Fur protein, the iron uptake machinery controlled by Fur, and the effects of fur gene deletion on virulence and immunogenicity in the fish host. Analysis of the E. ictaluri Fur protein shows that it lacks the N-terminal region found in the majority of pathogen-encoded Fur proteins. However, it is fully functional in regulated genes encoding iron uptake proteins. E. ictaluri grown under iron-limited conditions upregulates an outer membrane protein (HemR) that shows heme-hemoglobin transport activity and is tightly regulated by Fur. In vivo studies showed that an E. ictaluri Δfur mutant is attenuated and immune protective in zebrafish (Danio rerio) and catfish (Ictalurus punctatus), triggering systemic immunity. We conclude that an E. ictaluri Δfur mutant could be an effective component of an immersion-oral vaccine for the catfish industry.

  10. Edwardsiella piscicida-like pathogen in cultured grouper.

    PubMed

    Ucko, Michal; Colorni, Angelo; Dubytska, Lidiya; Thune, Ronald L

    2016-09-26

    An Edwardsiella sp. was isolated from the kidney of diseased groupers (Epinephelus aeneus and E. marginatus) cultured in Eilat (Israel, Red Sea). Affected fish presented a severe suppurative nephritis with large abscesses occasionally spreading into the surrounding musculature. Biochemical profiles and phenotypic comparisons failed to provide a clear identification to the species level, and genetic analysis of the 16S subunit failed to discriminate between Edwardsiella piscicida, E. tarda and E. ictaluri. Analysis of the gyrB gene, however, placed the grouper isolates into the E. piscicida-like group, a newly recognized taxon which also encompasses the non-motile strains previously classified as atypical E. tarda. Initial genomic analysis revealed the presence of the Edwardsiella type 3 secretion system (T3SS) but also revealed a pathogenicity island encoding a second T3SS with homology to the locus of enterocyte effacement of Escherichia coli. Further analysis revealed 3 different type 6 secretion systems that were also present in all sequenced isolates of Edwardsiella piscicida-like strains. Based on estimated DNA-DNA hybridization values and the average nucleotide index, the grouper strain fits into the E. piscicida-like phylogroup described as E. anguillarum sp. nov. The peculiarities associated with this isolate and the association of other conspecific piscine isolates from multiple marine and brackish water species suggest a link of the entire E. piscicida-like phylogroup to the marine environment.

  11. Acquired Porphyria Cutanea Tarda

    PubMed Central

    Koval, Andrew; Danby, C. W. E.; Petermann, H.

    1965-01-01

    Currently, the porphyrias are classified in four main groups: congenital porphyria, acute intermittent porphyria, porphyria cutanea tarda hereditaria, and porphyria cutanea tarda symptomatica. The acquired form of porphyria (porphyria cutanea tarda symptomatica) occurs in older males and is nearly always associated with chronic alcoholism and hepatic cirrhosis. The main clinical changes are dermatological, with excessive skin fragility and photosensitivity resulting in erosions and bullae. Biochemically, high levels of uroporphyrin are found in the urine and stools. Treatment to date has been symptomatic and usually unsuccessful. A case of porphyria cutanea tarda symptomatica is presented showing dramatic improvement of both the skin lesions and porphyrin levels in urine and blood following repeated phlebotomy. Possible mechanisms of action of phlebotomy on porphyria cutanea tarda symptomatica are discussed. ImagesFig. 1Fig. 2 PMID:14341652

  12. DNA shuffling approach for recombinant polyvalent OmpAs against V. alginolyticus and E. tarda infections.

    PubMed

    Li, Hui; Chu, Xiao; Peng, Bo; Peng, Xuan-Xian

    2016-11-01

    Molecular breeding via DNA shuffling directs the evolution of vaccines with desired traits. In the present study, polyvalent OmpA vaccines were generated by DNA shuffling of five ompA genes from four species of bacteria Vibrio parahaemolyticus, V. alginolyticus, Edwardsiella tarda and Escherichia coli. First, a new hybrid OmpA was constructed using VA0764 primers and used for construction of a prokaryotic expressing library PompAs-FV containing 84 ompAs, which were validated by PCR and SDS/PAGE. Then, the 84 ompAs were used to construct a eukaryotic expressing library EompAs-FV for preparing DNA vaccines. Third, extracellular bacterium V. alginolyticus challenge post active immunization using these DNA vaccines was carried out to identify genes with high immunoprotection. Among the 84 ompAs, 17 showed higher or equal immune protection against infection caused by V. alginolyticus than control VA0764. Finally, immune protection against infection caused by intracellular bacterium Edwardsiella tarda was assessed further using the top seven out of the 17 ompAs. This led to identification of three efficient polyvalent vaccines against infections caused by the extracellular bacterium V. alginolyticus and intracellular bacterium E. tarda. In addition, we sequenced genes for understanding mechanisms of the polyvalent vaccines, but association of immune protection with mutation of gene and amino acids is not determined. These results indicate that DNA shuffling is an efficient way to develop polyvalent vaccines against microbial infections.

  13. Porphyria cutanea tarda and Sjogren's syndrome*

    PubMed Central

    Fang, Su; Sun, Xiao Jie; Wang, ZanFeng; Song, DanYang; Li, TieNan

    2014-01-01

    Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome. PMID:25054769

  14. [Acne tarda. Acne in adults].

    PubMed

    Jansen, T; Janßen, O E; Plewig, G

    2013-04-01

    Acne is one of the most common skin diseases in the general population, especially among adolescents. Acne tarda (adult acne) is defined as acne that develops (late-onset acne) or continues (persistent acne) after 25 years of age. The disease is more common in women. The clinical features are quite specific: inflammatory acne in the lower facial region or macrocomedones (microcysts) spread over the face. Involvement of the trunk is much more common in men. The etiology of acne tarda is still controversial, as cosmetics, drugs, smoking, stress, diet, and endocrine abnormalities have been implicated. Women with acne tarda and other symptoms of hyperandrogenism have a high probability of endocrine abnormalities such as polycystic ovary syndrome. Treatment is similar to that of acne in adolescence. Long-term treatment over years or decades may be required.

  15. Histologic and molecular characterization of Edwardsiella piscicida infection in largemouth bass (Micropterus salmoides).

    PubMed

    Fogelson, Susan B; Petty, Barbara D; Reichley, Stephen R; Ware, Cynthia; Bowser, Paul R; Crim, Marcus J; Getchell, Rodman G; Sams, Kelly L; Marquis, Hélène; Griffin, Matt J

    2016-05-01

    The genus Edwardsiella is composed of a diverse group of facultative anaerobic, gram-negative bacteria that can produce disease in a wide variety of hosts, including birds, reptiles, mammals, and fish. Our report describes the isolation and identification of Edwardsiella piscicida associated with chronic mortality events in 2 separate captive largemouth bass (Micropterus salmoides) populations in New York and Florida. Wet-mount biopsies of skin mucus, gill, kidney, and spleen from several affected largemouth bass contained significant numbers of motile bacteria. Histologic examination revealed multifocal areas of necrosis scattered throughout the heart, liver, anterior kidney, posterior kidney, and spleen. Many of the necrotic foci were encapsulated or replaced by discrete granulomas and associated with colonies of gram-negative bacteria. Initial phenotypic and matrix-assisted laser desorption ionization-time of flight mass spectrometric analysis against existing spectral databases of recovered isolates identified these bacteria as Edwardsiella tarda Subsequent molecular analysis using repetitive sequence mediated and species-specific PCR, as well as 16S rRNA, rpoB, and gyrB sequences, classified these isolates as E. piscicida As a newly designated taxon, E. piscicida should be considered as a differential for multiorgan necrosis and granulomas in largemouth bass.

  16. Spondyloepiphyseal dysplasia tarda in Turner syndrome.

    PubMed

    Massa, G; Vanderschueren-Lodeweyckx, M

    1989-11-01

    A girl with short stature is described in whom chromosomal analysis revealed a 45,X/46,XX mosaicism and in whom radiological investigations disclosed the diagnosis of X-linked spondyloepiphyseal dysplasia tarda. This is the first report of the occurrence of X-linked spondyloepiphyseal dysplasia tarda in a child with Turner syndrome.

  17. Rifampicin-induced porphyria cutanea tarda.

    PubMed

    Millar, J W

    1980-10-01

    A patient who developed porphyria cutanea tarda and disturbed liver function tests following treatment with rifampicin and isoniazid for a tuberculous psoas abscess is reported. The patient had normal liver function tests prior to receiving anti-tuberculosis chemotherapy, but was subsequently demonstrated to have cholelithiasis. Challenge testing with both drugs incriminated rifampicin as the agent precipitating porphyria cutanea tarda and disturbance of the liver function tests particularly the serum bilirubin. The association between rifampicin and porphyria cutanea tarda has not previously been described but might be expected because of the ability of rifampicin to induce various liver enzyme systems including delta aminolevulinic acid synthetase activity. This further illustration of rifampicin hepatotoxicity emphasizes the need for regular monitoring of liver function when rifampicin is prescribed. Rifampicin should be used with extreme caution in any patient with a previous history of porphyria cutanea tarda.

  18. Porphyria Cutanea Tarda and Agent Orange

    MedlinePlus

    ... survivors' benefits . Research on porphyria cutanea tarda and herbicides The Health and Medicine Division (HMD) (formally known ... on " Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam " that there was sufficient evidence ...

  19. Isolated primary lymphedema tarda of the upper limb.

    PubMed

    Shariati, Farzaneh; Ravari, Hasan; Kazemzadeh, Gholamhossein; Sadeghi, Ramin

    2013-03-01

    Primary lymphedema tarda is considered as a congenital disease with late presentation. Primary lymphedema tarda usually affects lower limbs, and primary lymphedema tarda of the upper limbs usually accompanies lower limb lymphedema. In the current case report, we present an 80-year-old male patient with isolated left upper limb swelling that lymphoscintigraphy imaging proved to be lymphedema.

  20. Urease Activity and Virulence in Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri encodes a urease complex that is required for infection of the channel catfish host and for replication in channel catfish macrophages. The complex is comprised of nine genes, including ureA, B and C, which encode the primary enzymatic subunits, ureD, E, F and G, which encode ...

  1. Three Cases of Spondyloepiphyseal Dysplasia Tarda in One Korean Family.

    PubMed

    Chung, Sang Wan; Kang, Eun Ha; Lee, Yun Jong; Ha, You Jung; Song, Yeong Wook

    2016-09-01

    Spondyloepiphyseal dysplasia (SED) tarda is an inherited skeletal arthropathy. Because SED tarda involves the joints and resemble the clinical findings of chronic arthropathies, this disease is frequently misdiagnosed as juvenile idiopathic arthritis (JIA). We report here on three patients (father and his two daughters) in one family with SED tarda. All patients had back pain and polyarthralgia. Their radiographs revealed typical changes for SED tarda including platyspondyly and dysplastic bone changes. This rare disease has major clinical importance in that it is similar with JIA or rheumatoid arthritis.

  2. Porphyria cutanea tarda: clinical and laboratory features.

    PubMed Central

    Sweeney, G. D.; Jones, K. G.

    1979-01-01

    Eleven patients with porphyria cutanea tarda were studied. Biochemical confirmation of the clinical diagnosis required only determination of the total urine porphyrin concentration in a sample of urine voided on rising in the morning. The patients were divided for convenience of discussion into four groups differing in age, sex and etiologic factors. Of the six patients in whom a liver biopsy was done one was shown to have micronodular cirrhosis. Except for a modest elevation in the serum glutamic oxaloacetic transaminase values when the patients were first seen, no evidence was found for liver disease apart from the presence of porphyria cutanea tarda. One patient recovered solely by abstaining from alcohol consumption. Five patients underwent phlebotomy; their iron stores had been found to be between 2 and 3 g. Decreasing urine porphyrin values correlated well with decreasing serum ferritin values during the course of phlebotomy. Porphyria cutanea tarda, which is due to a deficiency of uroporphyrinogen decarboxylase, is manifested in association with alcohol abuse, estrogen therapy, exposure to chlorinated hydrocarbons or increased tissue iron stores, or a combination of these factors. Although relatively uncommon, this condition raises important and unresolved issues regarding the hepatotoxicity of alcohol, estrogens, chlorinated hydrocarbons and iron. PMID:427687

  3. Detection of Quorum Sensing Signal Molecules in Edwardsiella ictaluri Ei-151.

    PubMed

    Yang, Qian; Han, Yin; Tinh, Nguyen Thi Ngoc; Hien, Nguyen Thi; Bossier, Peter

    2012-12-01

    Edwardsiella ictaluri is a Gram-negative pathogenic bacterium in the family Enterobacteriaceae that causes enteric septicemia of catfish, which has become a significant problem in the aquaculture of striped catfish (Pangasianodon hypophthalmus) in Vietnam. In this study, a bacterium designated as Ei-151 was isolated from diseased striped catfish and proved to be virulent. Based on 16S rDNA sequencing and phenotypic tests, the pathogenic bacterium was identified as Edw. ictaluri. The presence of quorum sensing signal molecules in Edw. ictaluri Ei-151 was detected with different biosensor strains. The results showed that Ei-151 produced at least three kinds of acylated homoserine lactone (AHL) signal molecules as detected with the biosensor Agrobacterium tumefaciens KYC55, and the AHLs fingerprint was similar to that of Edw. tarda. During its entire growth, the levels of AHLs and autoinducer-2 produced by Ei-151 peaked at the stationary phase (OD600 1.8), which suggested that both of them may function at the stationary phase. No Cholerae autoinducer-1-like activity (including Edw. ictaluri LMG7860(T)) was detected.

  4. Hair darkening in porphyria cutanea tarda.

    PubMed

    Shaffrali, F C G; McDonagh, A J G; Messenger, A G

    2002-02-01

    Repigmentation of grey hair is rare, but has been described in several clinical settings. It has most often been reported as a postinflammatory effect, but several drugs, chronic arsenic exposure and coeliac disease have also been cited in addition to darkening as a spontaneous phenomenon. We report two patients with sustained repigmentation of the hair in association with porphyria cutanea tarda. The mechanism for this repigmentation remains elusive, but presumably involves recruitment of outer root sheath melanocytes, which are then activated to form functional hair bulb melanocytes.

  5. Hepatitis C, Porphyria Cutanea Tarda, and Liver Iron: An Update

    PubMed Central

    Caballes, F Ryan; Sendi, Hossein; Bonkovsky, Herbert L.

    2012-01-01

    Porphyria cutanea tarda (PCT) is the most common form of porphyria across the world. Unlike other forms of porphyria, which are inborn errors of metabolism, PCT is usually an acquired liver disease caused by exogenous factors, chief among which are excess alcohol intake, iron overload, chronic hepatitis C, estrogen therapy, and cigarette smoking. The pathogenesis of PCT is complex and varied, but hereditary or acquired factors that lead to hepatic iron loading and increased oxidative stress are of central importance. Iron loading is usually only mild or moderate in degree (less than that associated with full-blown hemochromatosis) and is usually acquired and/or due to mutations in HFE. Among acquired factors are excessive alcohol intake and chronic hepatitis C infection, which, like mutations in HFE, decrease hepcidin production by hepatocytes. The decrease in hepcidin leads to increased iron absorption from the gut. In the liver, iron-loading and increased oxidative stress leads to the formation of non-porphyrin inhibitor(s) of uroporphyrinogen decarboxylase and to oxidation of porphyrinogens to porphyrins. The treatment of choice of active PCT is iron reduction by phlebotomy and maintenance of a mildly iron-reduced state without anemia. Low-dose anti-malarials (cinchona alkaloids) are also useful as additional therapy or as alternative therapy for active PCT in those without hemochromatosis or chronic hepatitis C. In this review, we provide an update of PCT with special emphasis upon the important role often played by the hepatitis C virus. PMID:22510500

  6. Porphyria cutanea tarda in a HIV- positive patient*

    PubMed Central

    Franzon, Valéria Aparecida Zanela; Mikilita, Emanuella Stella; Camelo, Fernanda Henriques; Camargo, Rosana

    2016-01-01

    This is a case report about Porphyria cutanea tarda (PCT) and its relationship with the infection caused by the human immunodeficiency virus (HIV). Cutaneous porphyria is an illness caused by enzymatic modification that results in partial deficiency of uroporphyrinogen decarboxylase (Urod), which may be hereditary or acquired. Several studies suggest that HIV infection associated with cofactors might trigger the development of porphyria cutanea tarda. In this case report, we present a patient infected with HIV, who after the introduction of antiretroviral therapy (ART) enjoyed clinical improvement of porphyria cutanea tarda symptoms. PMID:27579753

  7. Porphyria cutanea tarda in a HIV- positive patient.

    PubMed

    Franzon, Valéria Aparecida Zanela; Mikilita, Emanuella Stella; Camelo, Fernanda Henriques; Camargo, Rosana

    2016-01-01

    This is a case report about Porphyria cutanea tarda (PCT) and its relationship with the infection caused by the human immunodeficiency virus (HIV). Cutaneous porphyria is an illness caused by enzymatic modification that results in partial deficiency of uroporphyrinogen decarboxylase (Urod), which may be hereditary or acquired. Several studies suggest that HIV infection associated with cofactors might trigger the development of porphyria cutanea tarda. In this case report, we present a patient infected with HIV, who after the introduction of antiretroviral therapy (ART) enjoyed clinical improvement of porphyria cutanea tarda symptoms.

  8. Inflammatory Effects of Edwardsiella ictaluri Lipopolysaccharide Modifications in Catfish Gut

    PubMed Central

    Kilbourne, Jacquelyn; Park, Jie-Yeun; Martin, Taylor; Loh, Amanda; Diaz, Ignacia; Rojas, Robert; Segovia, Cristopher; DeNardo, Dale; Curtiss, Roy

    2014-01-01

    Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to

  9. Basilar impression in osteogenesis imperfecta tarda. Case report.

    PubMed

    Kurimoto, M; Ohara, S; Takaku, A

    1991-01-01

    A case is presented of basilar impression secondary to osteogenesis imperfecta tarda, associated with hemifacial spasm and brain-stem compression syndrome. The symptoms improved with posterior fossa decompression and posterior fusion.

  10. Ocular manifestations in porphyria cutanea tarda.

    PubMed

    Gogri, Pratik Yeshwant; Misra, Neeta Somen; Misra, Somen

    2014-05-08

    A 24-year-old man presented with pain, sticky discharge and loss of vision in the right eye. He has had typical skin manifestations of porphyria cutanea tarda (PCT) since 6 years and ophthalmological symptom for 6 weeks. On ophthalmological examination, visual acuity was light perception in the right eye and 6/12 in the left. There were bilateral, symmetrical temporal scleromalacia along with temporal corneal melting in both eyes and perforation in the right eye. Ultrasonography B-scan (USG B-scan) revealed a retinal detachment in the right eye. Artificial tear instillation was started every hour along with topical antibiotic coverage in both eyes. Additionally, ultraviolet protective sunglasses and hat for photo-protection was advised. The vision in the right eye improved to 5/60 along with subsidence of retinal detachment on repeat USG B-scan after 3 weeks.

  11. Edwardsiella tarda and Aeromonas hydrophila isolated from diseased Southern flounder (Paralichthys lethostigma) are virulent to channel catfish and Nile tilapia

    USDA-ARS?s Scientific Manuscript database

    The aim of this study is to identify bacterial pathogens isolated from diseased Southern flounder and determine their virulence to channel catfish and Nile tilapia. Twenty five Gram-negative bacteria isolates were recovered from five tissues (skin lesions, brain, liver, intestine, and posterior kidn...

  12. Insulin resistance in porphyria cutanea tarda.

    PubMed

    Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

    1989-06-01

    It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

  13. Complete genome sequence of Edwardsiella hoshinae ATCC 35051

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella hoshinae is a Gram-negative, facultative anaerobe that has been primarily isolated from avians and reptiles. We report here the complete and annotated genome of an isolate from a monitor lizard (Varanus sp.), which contains a chromosome of 3,811,650 bp and no plasmids....

  14. Complete Genome Sequence of Edwardsiella hoshinae ATCC 35051

    PubMed Central

    Waldbieser, Geoffrey C.; Lawrence, Mark L.

    2017-01-01

    ABSTRACT Edwardsiella hoshinae is a Gram-negative facultative anaerobe that has primarily been isolated from avians and reptiles. We report here the complete and annotated genome sequence of an isolate from a monitor lizard (Varanus sp.), which contains a chromosome of 3,811,650 bp and no plasmids. PMID:28183769

  15. Towards the intelligent design of a vaccine against Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri is the leading cause of disease loss in the catfish industry in the United States, accounting for an estimated 20.2 % loss in 2009. Previous work to establish live-attenuated vaccines for E. ictaluri demonstrated a relatively weak channel catfish immune response, with better im...

  16. Complete Genome Sequence of Edwardsiella hoshinae ATCC 35051.

    PubMed

    Reichley, Stephen R; Waldbieser, Geoffrey C; Lawrence, Mark L; Griffin, Matt J

    2017-02-09

    Edwardsiella hoshinae is a Gram-negative facultative anaerobe that has primarily been isolated from avians and reptiles. We report here the complete and annotated genome sequence of an isolate from a monitor lizard (Varanus sp.), which contains a chromosome of 3,811,650 bp and no plasmids. Copyright © 2017 Reichley et al.

  17. Inadequate cortisol synthesis in prophyria cutanea tarda.

    PubMed

    Pereţianu, D; Sava, D; Giurcăneanu, C; Grigorie, D

    1991-01-01

    Many common clinical features suggest that between corticosuprarenal insufficiency (CSRI) and porphyria cutanea tarda (PCT) there may be some pathogenic relationships. In order to further understand these relations we have performed the ACTH-depot stimulation test (1 mg, i.m.) in 9 patients (from 13 males) with PCT. In 8 patients cortisolemia was assayed 1, 2, (12) and 24 hours post-stimulation. In all 13 cases the basal eliminations of cortisol metabolite (17-OH-corticosteroids) were under normal limits: 2.88 mg/24 h/g creatinine vs 15 controls with 7.06 mg/24h/g creatinine. After ACTH four cases showed lack of stimulation, considered on the second day for 17-OH-corticosteroids. In one case, after one year of PCT treatment, the early post-stimulation level is only moderately decreased. In one case, the test was normal. In four cases the ACTH stimulation was over-normal, i.e., greater than on the first day, suggesting supraphysiological responses. In this group 2 patients showed unexpectedly low early stimulation slopes on cortisolemia (at 1 and 2 hours) associated with concordant high late stimulation levels. This later phenomenon suggests a functional impaired secretion of cortisol in PCT, which seems to be similar to that of insulinemia after glucose in NIDDM, as a receptor lesion. The lesions of cortisol secretion in PCT could have been made by porphyrin storage, impaired hem-enzyme synthesis (cyt P-450) and as a new and attractive hypothesis, could be due to mitochondrial porphyrin receptor decreased activity.

  18. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    PubMed Central

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  19. Possible cantharidin poisoning of a great bustard (Otis tarda).

    PubMed

    Sánchez-Barbudo, Inés S; Camarero, Pablo R; García-Montijano, Marino; Mateo, Rafael

    2012-01-01

    A possible cantharidin intoxication of a great bustard (Otis tarda) was described. This wild bird died by a traumatism, but also presented diarrhoea, congestion of the gastrointestinal tract and kidneys and had ingested several blister beetles of the species Berberomeloe majalis. The analysis of the stomach content by GC-MS revealed the presence of cantharidin at a concentration of 1.37 μg/g of wet weight, a similar level than in other birds poisoned in captivity.

  20. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within one...

  1. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within one...

  2. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within one...

  3. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within one...

  4. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within one...

  5. Bacterial distribution and tissue targets following experimental Edwardsiella ictaluri infection in Nile tilapia Oreochromis niloticus.

    PubMed

    Soto, Esteban; Illanes, Oscar; Revan, Floyd; Griffin, Matt; Riofrio, Andrés

    2013-05-27

    Edwardsiella ictaluri, a Gram-negative enteric bacterium, is the known etiological agent of enteric septicemia of catfish. In the last few years, different strains have been implicated as the causative agent of mortality events in cultured fish, including Nile tilapia Oreochromis niloticus L. Due to the emergent nature of edwardsiellosis in non-ictalurid fish, little is known about the dynamics of E. ictaluri infection in tilapia. The purpose of this study was to gain a better understanding of the pathogenesis of edwardsiellosis in tilapia by determining the median lethal and infective doses, tissue targets of infection, rate of bacterial dissemination, and the specific tissue response to E. ictaluri following an immersion challenge with bacterial strains recovered from outbreak events in tilapia. In addition to histopathology assessment, the bacterial burdens in several tissues of infected fish were determined over a 2 wk course of infection using quantitative real-time PCR (qPCR). The collected data suggest the cutaneous and oral routes as the main ports of entry for the organism, which later spreads hematogenously throughout the body. Even though histopathological assessment of infected fish revealed involvement of a wide range of tissues, the severity of the necrotizing and granulomatous lesions in the spleen and head kidney, with concomitant high levels of bacterial DNA in these organs determined by qPCR, identifies them as the main targets of infection.

  6. Localized bullous pemphigoid in a patient with primary lymphoedema tarda.

    PubMed

    Perez, A; Clements, S E; Benton, E; Robson, A; Bhogal, B; Stefanato, C M; McGibbon, D

    2009-12-01

    We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.

  7. Major and trace elements in whole blood of phlebotomized patients with porphyria cutanea tarda.

    PubMed

    Dinya, Mariann; Székely, E; Szentmihályi, K; Tasnádi, Gy; Blázovics, A

    2005-01-01

    Porphyria cutanea tarda (PCT) is a disorder of hem biosynthesis resulting from a decreased activity of the uroporphyrinogen decarboxylase enzyme. Hem precursors are accumulated in the blood, liver and skin. Inherited and acquired factors also contribute to the pathogenesis of PCT. Hem precursors and porphyrins are excreted with urine and faeces. Whole blood of 8 PCT patients and 6 volunteers of Caucasian origin were analysed. In addition to routine laboratory measurements, 19 elements (Al, B, Ba, Ca, Cd, Co, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, S, V, Zn) were determined by means of inductively coupled plasma optical emission spectrometry (ICP-OES). Mg, P and S concentrations in whole blood were decreased significantly (p<0.05), whereas Ba was increased in PCT patients compared to controls. Metabolic alterations are reflected in the correlation of parameters. Positive correlations were found between the element pairs of Zn-Al, Zn-Mg, Zn-Mn, B-S, Fe-Mg, K-P, Mg-Mn for PCT patients, whereas in the control group Al-Mn, Ca-Cu, Ca-Na, Cu-Mg, Fe-K, Mg-Na, Zn-P showed positive correlations.

  8. Comparative genomic analysis of bacteriophages specific to the channel catfish pathogen Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Background: The bacterial pathogen Edwardsiella ictaluri is a primary cause of mortality in channel catfish raised commercially in aquaculture farms. Additional treatment and diagnostic regimes are needed for this enteric pathogen, motivating the discovery and characterization of bacteriophages spe...

  9. Naturally infected catfish concurrently transmit Ichthyophthirius multifiliis and Edwardsiella ictaluri to naive catfish

    USDA-ARS?s Scientific Manuscript database

    Bacterium Edwardsiella ictaluri and parasite Ichthyophthirius multifiliis (Ich) are two common pathogens of channel catfish (Ictalurus punctatus) which cause major losses to catfish aquaculture. There is limited information available whether fish naturally coinfected with Ich and E. ictaluri can con...

  10. Induction of bulb organogenesis in in vitro cultures of tarda tulip (Tulipa tarda Stapf.) from seed-derived explants.

    PubMed

    Maślanka, Małgorzata; Bach, Anna

    2014-01-01

    A protocol for obtaining bulbs via in vitro organogenesis was developed for tarda tulip (Tulipa tarda Stapf). Scale explants were obtained from bulbs formed at the base of seedlings or from adventitious bulbs that developed from callus tissue forming on stolons or on germinating seeds. Some explants were subjected to chilling at 5°C for 12 wk. The culture media contained 3 or 6% sucrose and was supplemented with either no growth regulators, either 0.5 μM 6-benzyl-aminopurine (BAP) or 18.9 or 94.6 μM abscisic acid (ABA). Cultures were maintained in the dark at 20°C. Callus tissue developed mainly on media without growth regulators or with BAP. Callus was formed from up to 96% of explants derived from non-chilled adventitious bulbs that were treated with 3% sucrose and 0.5 μM BAP. Less callus was formed from chilled explants compared with non-chilled explants. Newly formed adventitious bulbs appeared on the explants via direct and indirect organogenesis. The media with BAP promoted the formation of adventitious bulbs at a rate of 56-92% from non-chilled explants, whereas a maximum rate of 36% was observed from chilled explants. ABA inhibited the induction of adventitious bulbs and callus. The adventitious bulbs obtained in these experiments contained a meristem, which was evidence that they had developed properly.

  11. Adhesive and invasive capacities of Edwarsiella tarda isolated from South American sea lion

    PubMed Central

    Fernández, Araceli; Villanueva, María Paz; González, Mario; Fernández, Fabiola; Latif, Fadua; Flores, Sandra Nonier; Fernández, Heriberto

    2014-01-01

    Edwarsiella tarda is a zoonotic bacterium that can be isolated from humans, animals and the environment. Although E. tarda is primarily considered a fish pathogen, it is the only species of its genus considered to be pathogenic for humans as well. A survey of zoonotic intestinal bacteria in fresh feces from South American sea lions (SASL) Otaria flavescens, reported E. tarda as the most frequently isolated species. In this study, we used HEp-2 cells to establish in vitro the adherence and invasive ability of 17 E. tarda strains isolated from SASL fecal material. All the strains were able to adhere and invade HEp-2 cells with adhesion and invasion percentages ranging from 56 to 100% and 21 to 74%, respectively. Despite the expression of these pathogenic factors, further investigation is needed to determine whether this bacterium could play a role as primary pathogen for this and other species of pinnipeds. PMID:25477948

  12. [Porphyria cutanea tarda: the benefit of additional diagnostics].

    PubMed

    Vossen, Allard R J V; Boesten, Lianne S M; Siersema, Peter D; Nellen, Ruud G L

    2016-01-01

    The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma.

  13. Basilar impression and platybasia in osteogenesis imperfecta tarda.

    PubMed

    Frank, E; Berger, T; Tew, J M

    1982-02-01

    Osteogenesis imperfecta, a rare, genetically transmitted disorder of bone, is known to be associated with the development of basilar impression and platybasia. These deformities of the base of the skull may cause neurosurgical abnormalities secondary to compression of the brainstem and hydrocephalus. The case is presented of a young boy with a family history of osteogenesis imperfecta tarda who suffered respiratory arrest during hospitalization. Cranial nerves and pyramidal tract signs were demonstrated. Roentgenograms showed severe basilar impression and hydrocephalus. Decompression of the brainstem and shunting were performed with improvement in the patient's neurological status. This case represents a rare by significant central nervous system complication of osteogenesis imperfecta. Early recognition and implementation of aggressive treatment are important if irreversible neurological deficits are to be avoided.

  14. Edwardsiella piscicida identified in the southeastern United States by gyrB sequence, species specific and repetitive sequence mediated PCR

    USDA-ARS?s Scientific Manuscript database

    A new taxa of Edwardsiella has recently been described from fishes of Europe and Asia. Researchers have determined this new strain does not belong to any established taxa within the genus Edwardsiella and have proposed the adoption of a new taxon, E. piscicida. A similar study in the United State...

  15. Ayurvedic management of spondyloepiphyseal dysplasia tarda, a rare hereditary disorder.

    PubMed

    Singh, Sarvesh Kumar; Rajoria, Kshipra

    Spondyloepiphyseal dysplasia tarda (SEDT) is a rare genetic disease in which patient suffers from short stature, short trunk and neck with disproportionately long arms, coxa vara, skeletal features such as barrel shaped chest, kyphosis, scoliosis and early arthropathy. Only limited medical and surgical management is available in modern medicine. A 15 years old male suffering from SEDT and diagnosed as Vata vyadhi was treated with Panchakarma therapy and selected Ayurvedic oral medicines. Ayurvedic treatment was directed to ameliorate the orthopaedic clinical conditions in this case. Panchakarma procedures such as Shalishastika pinda svedana for a month and Mustadi yapana basti for 16 days were given along with oral Ayurvedic medicines. Same Panchakarma procedures were repeated after an interval of 2 months. A combination of Ayurvedic oral medicines such as Trayodashanga guggulu-500 mg twice a day, Dashmool kvatha (decoction of roots of 10 herbs) 40 ml twice a day, Eranda paka 10 g twice a day, Shiva gutika-500 mg twice a day and Dashmoolarista-20 ml (with equal water) twice a day were prescribed. Eight scales based Medical outcome study (MOS) - 36 item short form - health surveys was assessed for outcome which shows good improvement. Kyphosis, scoliosis and pain were moderately reduced. Clinical experience of this case indicates that Ayurvedic herbs along with Panchakarma can play a major role in the management of hereditary disorder SEDT. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  16. [Pansclerotic porphyria cutanea tarda after chronic exposure to organic solvents].

    PubMed

    Karamfilov, T; Buslau, M; Dürr, C; Weyers, W

    2003-05-01

    A 63 year old man developed generalized scleroderma with massive sclerotic areas, particularly in the abdominal region, four years after being diagnosed with porphyria cutanea tarda (PCT). He had almost daily exposure to organic solvents (benzene, trichlorethylene) for many years. The cutaneous fibrosis progressed dramatically leading to a pansclerosis, even though the uroporphyrin levels were borderline and the liver enzyme values were normal. Organic solvents are among those substances which can cause a cutaneous fibrosis. The unusually complicated clinical development in our patient was a combination of the two initial factors, the PCT and the long term exposure to organic solvents. The pansclerotic PCT was differentiated from a systemic sclerosis, a disabling pansclerotic morphea and a generalized morphea by means of histological examinations, the absence of a Raynaud phenomenon and the non-involvement of additional organs. Auto-antibodies typical for systemic sclerosis were negative. Using a medium dosage of UVA1 phototherapy and intensive physiotherapy, the progression of the skin disease was stopped and the sclerosis improved.

  17. Clinical haematology of the great bustard (Otis tarda).

    PubMed

    Jimenez, A; Barrera, R; Sanchez, J; Cuenca, R; Rodriguez, J; Andres, S; Mane, M C

    1991-12-01

    The haematological parameters of healthy great bustards (Otis tarda L.) have been determined. The values obtained were red cell count (3.0 x 10(12) +/- 0.2 x 10(12/)1), white cell count (33.0 x 10(9) +/- 2.6 x 10(9)/1), haematocrit value (0.51 +/- 0.01 1/1), haemoglobin (13.0 +/- 0.3 g/dl), mean corpuscular volume (178.7 +/- 12.5 fl), mean cell haemoglobin concentration (25.0 +/- 0.6 g/dl), mean corpuscular haemoglobin (42.5 +/- 3.2 pg), differential white cell count: heterophils (22.5 x 10(9) +/- 0.7 x 10(9)/1), lymphocytes (6.0 x 10(9)+/-0.7 x 10(9)/1), eosinophils (2.7 x 10(9) +/- 0.3 x 10(9)/1) and monocytes (1.8 x 10(9)+/-0.2 x 10(9)/1).

  18. Comparison of Vietnamese and US isolates of Edwardsiella ictaluri.

    PubMed

    Rogge, Matthew L; Dubytska, Lidiya; Jung, Tae Sung; Wiles, Judy; Elkamel, Ahmad A; Rennhoff, Amelia; Oanh, Dang Thi; Thune, Ronald L

    2013-09-24

    We compared Edwardsiella ictaluri from striped catfish in Vietnam with US channel catfish isolates. Biochemical analyses and sequencing of the 16S rRNA gene confirmed that the Vietnamese isolates were E. ictaluri. Comparison using rep-PCR fingerprinting demonstrated no significant differences between the isolates, but plasmid analysis indicated that the Vietnamese isolates grouped into 4 plasmid profiles, each different from the typical pEI1 and pEI2 plasmid profile found in the US isolates. Sequencing plasmids representative of the 4 profiles indicated that all contained derivatives of the E. ictaluri plasmid pEI1, whereas only 1 contained a plasmid derivative of the E. ictaluri plasmid pEI2. The pEI2 encoded type III secretion effector, EseI, and its chaperone, EscD, were found to be present on the chromosome in isolates lacking a pEI2 derivative. In addition, 1 isolate carried a 5023 bp plasmid that does not have homology to either pEI1 or pEI2. Furthermore, Vietnamese isolates were PCR positive for the type III and type VI secretion system genes esrC and evpC, respectively, and the urease enzyme, but were PCR-negative for the putative type IV secretion system gene virD4. A monoclonal antibody against the lipopolysaccharide of E. ictaluri ATCC 33202 did not react with the Asian isolates or with the more recent US isolates. Antibiotic resistance patterns were variable and did not correlate to the presence of any particular plasmid profile. Finally, the Vietnamese isolates were avirulent and had a significantly reduced capacity for intracellular replication within head-kidney-derived channel catfish macrophages.

  19. Efficacy of florfenicol for control of mortality associated with Edwardsiella ictaluri in three species of catfish

    USDA-ARS?s Scientific Manuscript database

    The efficacy of florfenicol against Edwardsiella icatluri infection was studied in channel catfish (Ictalurus puntatus (Delta strain)), hybrid catfish (Ictalurus punctatus (Delta strain) x Ictalurus furcatus (D&B strain)), and blue catfish (Ictalurus furcatus (D&B strain) fingerlings in 65L aquaria....

  20. Effects of Bio-Mos on Growth and Survival of Channel Catfish Challenged with Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    A major problem in the catfish farming industry has been high disease loss to enteric septicemia of catfish (ESC), caused by the bacterium Edwardsiella ictaluri (E. ictaluri). Methods to control this disease include antibiotic therapy, vaccinations, and management strategies such as taking the fish...

  1. Modified live Edwardsiella ictaluri vaccine, AQUAVAC-ESC, lacks multidrug resistance plasmids

    USDA-ARS?s Scientific Manuscript database

    Plasmid mediated antibiotic resistance was first discovered in Edwardsiella ictaluri in the early 1990’s, and in 2007 an E. ictaluri isolate harboring an IncA/C plasmid was recovered from a moribund channel catfish infected with the bacterium. Due to the identification of multidrug resistance plasm...

  2. Chemical and electroporated transformation of Edwardsiella ictaluri using three different plasmids

    USDA-ARS?s Scientific Manuscript database

    Transfer of DNA by conjugation has been the method generally used for genetic manipulation of Edwardsiella ictaluri because, previously, attempts to transform E. ictaluri by the uptake of naked DNA has apparently failed. We report here the successful transformation of seven strains of E. ictaluri us...

  3. Overcoming inconsistencies in mortality rates during winter experimental challenges of channel catfish with Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    One of the goals of the ARS Catfish Genetics Research Unit is to incorporate disease resistance to ESC, caused by the bacterium, Edwardsiella ictaluri, into our selective breeding program. Through repeated experiments we have determined an optimal challenge dose of E. ictaluri that produces 50-70% ...

  4. Construction, characterization, expression and immune responses of flagellar proteins of channel catfish, important pathogen Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Background: Edwardsiella ictaluri causes enteric septicemia of catfish, which is the leading disease in channel catfish (Ictalurus punctatus)and is responsible for $50 - 60 million economic losses to catfish producers annually in the southeastern U.S. Bacterial flagella are complex polymeric structu...

  5. Construction, characterization and use of Edwardsiella ictaluri flagella-type three secretion system protein arrays

    USDA-ARS?s Scientific Manuscript database

    Enteric septicemia of catfish, caused by Edwardsiella ictaluri, is the leading disease in channel catfish (Ictalurus punctatus) that is responsible for $50 - 60 million economic losses to catfish producers annually in the Southeastern U.S. The flagella and type three secretion system (TTSS) in Gram...

  6. Bacterial distribution and tissue targets following experimental Edwardsiella ictaluri infection in nile tilapia Oreochromis niloticus

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri, a Gram-negative enteric bacterium, is the known etiological agent of enteric septicemia of catfish. In the last few years, different strains have been implicated as the causative agent of mortality events in cultured fish, including Nile tilapia Oreochromis niloticus L. Due to...

  7. Identification of differentially regulated proteins of Edwardsiella ictaluri during iron restriction

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri is a Gram-negative facultative anaerobe intracellular bacterium that causes enteric septicemia in channel catfish. Iron is an essential inorganic nutrient of bacteria and is crucial for bacterial invasion. Reduced availability of iron by the host may cause a significant stres...

  8. Characterization of the RRN Operons in the Channel Catfish Pathogen Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Aims: To advance diagnostics and phylogenetics of Edwardsiella ictaluri by sequencing and characterizing its rrn operons. Methods and Results: The Edw. ictaluri rrn operons were identified from a 5-7 kb insert lambda library and from Edw. ictaluri fosmid clones. We present the complete sequences...

  9. Edwardsiella ictaluri as the causative agent of mortality in cultured Nile tilapia

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri was consistently isolated from the spleens, livers, and head kidneys of diseased Nile tilapia Oreochromis niloticus from a farm experiencing mortality events in several culture ponds. We describe the first published outbreak of E. ictaluri–induced Edwardsiellosis in Nile tilapi...

  10. Global gene expression in channel catfish after vaccination with an attenuated Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    To understand the global gene expression in channel catfish after immersion vaccination with an attenuated Edwardsiella ictaluri (AquaVac ESCTM), microarray analysis of 65,182 UniGene transcripts were performed. With a filter of false-discovery rate less than 0.05 and fold change greater than 2, a t...

  11. The role of inherited and acquired factors in the development of porphyria cutanea tarda in the Argentinean population.

    PubMed

    Méndez, Manuel; Rossetti, María V; Del C Batlle, Alcira M; Parera, Victoria E

    2005-03-01

    Inherited and environmental factors are implicated in the expression of porphyria cutanea tarda (PCT); the contribution of each factor depends on the population. To provide a review of PCT cases diagnosed in Argentina over 24 years and evaluate the role of different precipitating factors in its pathogenesis. Methods Plasma and urinary porphyrin levels and erythrocyte uroporphyrinogen decarboxylase (URO-D) activity were determined. Potential precipitating factors were identified in each patient. Additional tests for hepatitis C virus (HCV) and hemochromatosis gene mutations were carried out. Several factors (mainly alcohol abuse in men and estrogen ingestion in women), alone or combined were identified in our patients. Prevalence of HCV infection was 35.2%. Inherited URO-D deficiency occurs in 25.0% of cases. H63D was the most common hemochromatosis gene mutation. High incidence of PCT associated with HIV infection was found. PCT is multifactorial. Therefore, knowledge of all risk factors in each patient is important for the management of the disease.

  12. The Yersinia Yops inhibit invasion of Listeria, Shigella and Edwardsiella but not Salmonella into epithelial cells.

    PubMed

    Mecsas, J; Raupach, B; Falkow, S

    1998-06-01

    Yersinia virulence is dependent on the expression of plasmid-encoded secreted proteins called Yops. After bacterial adherence to receptors on the mammalian cell membrane, several Yops are transported by a type III secretion pathway into the host cell cytoplasm. Two Yops, YopH and YopE, prevent macrophages from phagocytosing Yersinia by disrupting the host cell cytoskeleton and signal transduction pathways. In contrast to this active inhibition of phagocytosis by Yersinia, other pathogens such as Salmonella, Shigella, Listeria and Edwardsiella actively promote their entry into mammalian cells by binding to specific host surface receptors and exploiting existing cell cytoskeletal and signalling pathways. We have tested whether Yersinia Yops can prevent the uptake of these diverse invasive pathogens. We first infected epithelial cells with Yersinia to permit delivery of Yops and subsequently with an invasive pathogen. We then measured the level of bacterial invasion. Preinfection with Yersinia inhibited invasion of Edwardsiella, Shigella and Listeria, but not Salmonella. Furthermore, we found that either YopE or YopH prevented Listeria invasion, whereas only YopE prevented Edwardsiella and Shigella invasion. We correlated the inhibitory effect of the Yops with the inhibitory action of the cell-signalling inhibitors Wortmannin, LY294002 and NDGA, and concluded that the four invasive pathogenic species enter epithelial cells using at least three distinct host cell pathways. We also speculate that YopE affects the rho pathway.

  13. Primary lymphedema tarda in an 88-year-old African-American male.

    PubMed

    Aslam, Ahmed Faraz; Aslam, Ahmad Kamal; Qamar, Muhammad Umair R; Levey, Robert

    2005-07-01

    Primary lymphedema tarda is considered to be a congenital disease with delayed manifestations. We report a case of isolated lymphedema of the left upper extremity in an 88-year-old African-American male. The diagnosis of lymphedema was confirmed by lymphoscintigraphy, and appropriate diagnostic studies were done to rule out other known causes of lymphedema. Lymphoscintigraphic findings were consistent with idiopathic primary lymphedema. During the course of investigations, the patient was found to have adenocarcinoma in situ of the sigmoid colon with no evidence of metastatic spread. Based on the available data, we were unable to establish a causative relationship between colonic carcinoma and lymphedema in our patient. Therefore, this case can best be described as a case of Idiopathic primary lymphedema tarda. We emphasize the use of histopathologic examination in the diagnostic algorithm to rule out underlying malignant process only in patients with radionuclide findings suggestive of secondary lymphedema with no obvious etiology.

  14. Primary lymphedema tarda in an 88-year-old African-American male.

    PubMed Central

    Aslam, Ahmed Faraz; Aslam, Ahmad Kamal; Qamar, Muhammad Umair R.; Levey, Robert

    2005-01-01

    Primary lymphedema tarda is considered to be a congenital disease with delayed manifestations. We report a case of isolated lymphedema of the left upper extremity in an 88-year-old African-American male. The diagnosis of lymphedema was confirmed by lymphoscintigraphy, and appropriate diagnostic studies were done to rule out other known causes of lymphedema. Lymphoscintigraphic findings were consistent with idiopathic primary lymphedema. During the course of investigations, the patient was found to have adenocarcinoma in situ of the sigmoid colon with no evidence of metastatic spread. Based on the available data, we were unable to establish a causative relationship between colonic carcinoma and lymphedema in our patient. Therefore, this case can best be described as a case of Idiopathic primary lymphedema tarda. We emphasize the use of histopathologic examination in the diagnostic algorithm to rule out underlying malignant process only in patients with radionuclide findings suggestive of secondary lymphedema with no obvious etiology. Images Figure 1 Figure 2 PMID:16080675

  15. Genome sequence of Edwardsiella ictaluri 93-146 a strain associated with a natural channel catfish outbreak of enteric septicemia of catifsh

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri is the cause of extensive mortalities and economic losses to the channel catfish industry of the southeast United States. Here we report the complete genome of Edwardsiella ictaluri 93-146. Whole-genome sequence analysis of E. ictaluri provides a tool for understanding the geno...

  16. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients*

    PubMed Central

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; dos Reis, Vitor Manoel Silva

    2013-01-01

    BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients PMID:24068123

  17. Combined immersion and oral vaccination of Vietnamese catfish (Pangasianodon hypophthalmus) confers protection against mortality caused by Edwardsiella ictaluri.

    PubMed

    Thinh, N H; Kuo, T Y; Hung, L T; Loc, T H; Chen, S C; Evensen, O; Schuurman, H J

    2009-12-01

    Edwardsiella ictaluri septicemia occurs worldwide and causes high mortality and considerable economic damage to the catfish industry especially in Vietnam and the USA. To control Edwardsiella septicemia farmers extensively use antibiotics and various vaccination methods. Vaccination with inactivated vaccines has come with variable efficacy. In this trial the results of an approach of controlling Edwardsiella septicemia of Tra catfish (Pangasianodon hypophthalmus) in Vietnam through vaccination via mucosal surfaces are presented. The results show that a combination of primary vaccination by immersion with inactivated E. ictaluri followed by an oral boost with a formulated antigen preparation induces a statistically significant level of protection against mortality caused by experimental infection 4 weeks post-boost. Fish immunized by immersion only show significantly lower level of protection but significantly higher than the controls. Repeated boosts result in improved duration of immunity with a relative percent survival (RPS) of 47% at 90% control mortality. The immunization procedure provides an alternative for disease control through vaccination.

  18. Astrovirus Pathogenesis

    PubMed Central

    Johnson, Cydney; Hargest, Virginia; Cortez, Valerie; Meliopoulos, Victoria A.; Schultz-Cherry, Stacey

    2017-01-01

    Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1) in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems. PMID:28117758

  19. Edwardsiellosis Caused by Edwardsiella ictaluri in Laboratory Populations of Zebrafish Danio rerio

    PubMed Central

    Hawke, John P.; Kent, Michael; Rogge, Matt; Baumgartner, Wes; Wiles, Judy; Shelley, Johnny; Savolainen, L. Christine; Wagner, Robert; Murray, Katy; Peterson, Tracy S.

    2014-01-01

    We report the first cases of Edwardsiella ictaluri causing epizootics in laboratory populations of Zebrafish Danio rerio. Edwardsiella ictaluri is primarily recognized as a disease of catfish species and is known to cause an economically important bacterial disease of farm-raised catfish in the USA and abroad; however, it has been isolated on occasion from 10 other genera of nonictalurid fishes. We isolated E. ictaluri from moribund Zebrafish held in quarantine at two different universities in two states and from a research facility in a third state between February 23 and December 6, 2011. Edwardsiellosis in Zebrafish can be described as a severe systemic disease characterized by tissue necrosis and the presence of large numbers of extracellular and intracellular bacteria, often within macrophages. The kidneys (pronephros and mesonephros), spleen, nares, and forebrain were the most commonly and severely affected tissues. In outbreaks, mortality was acute and numerous fish died over a 1–2 week period. Mortality continued until the majority of the population was lost, at which time the remaining fish were euthanized. In addition to these cases, four cultures of bacteria isolated from Zebrafish by another diagnostic laboratory were submitted to the Louisiana Aquatic Diagnostic Laboratory for identification and were confirmed as E. ictaluri. In total, eight cultures of E. ictaluri from Zebrafish from Louisiana, Massachusetts, Pennsylvania, and Florida were identified. The isolates were confirmed as E. ictaluri by biochemical phenotype, API 20E (bioMérieux), and amplification and sequencing of a portion of the 16S rRNA gene. Edwardsiella ictaluri isolates from Zebrafish are believed to comprise a unique group and were differentiated from catfish isolates by exhibiting weaker motility, autoaggregation in broth, a different plasmid profile (two plasmids of 4.0 and 3.5 kb), a different API 20E code (4204000), and lack of lipopolysaccharide recognition with Mab Ed9

  20. Influence of Edwardsiella ictaluri Septicemia on nitrite-induced methemoglobinemia in channel catfish (Ictalurus punctatus)

    SciTech Connect

    Tucker, C.S.; MacMillan, J.R.; Schwedler, T.E.

    1984-06-01

    In a previous report, the authors showed that lack of acclimation to nitrite can result in abnormally high levels of methemoglobin in nitrite-exposed channel catfish. They also observed abnormal methemoglobin levels in fish when concurrent bacteremias are present. Enteric Septicemia of Catfish is an acute bacterial disease caused by Edwardsiella ictaluri. Nitrite-induced methemoglobinemia and Enteric Septicemia of Catfish are both economically important diseases of commercially cultured channel catfish. In the present study, the authors investigated the influence of acute infection with E. ictaluri on the level of methemoblobin in nitrite-exposed channel catfish fingerlings.

  1. H-NS binding to evpB and evpC and repressing T6SS expression in fish pathogen Edwardsiella piscicida.

    PubMed

    Cui, Shilei; Xiao, Jingfan; Wang, Qiyao; Zhang, Yuanxing

    2016-09-01

    Edwardsiella piscicida is an important causative agent of hemorrhagic septicemia in fish and infects both cultured and wild fish species. Type VI secretion system (T6SS) was proved to play important roles in pathogenesis of E. piscicida. In this study, it was demonstrated that the expression of T6SS genes evpB and evpC was under control of the global regulator H-NS in E. piscicida and the transcriptional level of evpB and evpC was significantly down-regulated by H-NS. Compared to the wild type, the transcriptional levels of evpB and evpC were up-regulated in hns null mutant, while down-regulated in hns overexpression strain. The results of EMSA and DNase I footprinting revealed that H-NS protein directly bound to upstream region of evpC at multiple sites. A high-affinity motif with a 9-nucleotide sequence 5'-ATATAAAAT-3' was defined for H-NS preferential recognition based on the feature of the binding sites. These results indicated that H-NS acted cooperatively to form extended nucleoprotein filaments on target DNA. Site-directed mutagenesis of H-NS further showed that R86 played an essential role in T6SS gene binding. These findings highlighted the mechanisms underlying the complex regulation network of T6SS by H-NS in E. piscicida.

  2. Advances in the treatment of porphyria cutanea tarda. Effectiveness of slow subcutaneous desferrioxamine infusion.

    PubMed

    Gibertini, P; Rocchi, E; Cassanelli, M; Pietrangelo, A; Ventura, E

    1984-08-01

    The authors present the results of long-term subcutaneous desferrioxamine (DFX) infusion in 16 porphyria cutanea tarda (PCT) patients who cannot undergo repeated phlebotomies because of severe liver damage, haemolytic anemia, cardiovascular impairment or pulmonary and bone tuberculosis. They employed an automatic, portable syringe pump for subcutaneous infusion (8-10 h) to overcome the short half-life of the drug. Photodynamic cutaneous lesions and hyperpigmentation quickly disappeared (2-3 months). Uroporphyrin excretion sharply decreased and normalized within 3-12 months. Also, serum iron and ferritin, as well as liver function, showed a significant improvement. The authors therefore propose subcutaneous DFX therapy in PCT treatment when phlebotomy is contraindicated.

  3. Increased photosensitivity? Case report of porphyria cutanea tarda associated with systemic lupus erythematosus.

    PubMed

    Fritsch, Scheila; Wojcik, Adma Silva de Lima; Schade, Lilian; Machota Junior, Milton Marcio; Brenner, Fabiane Mulinari; Paiva, Eduardo dos Santos

    2012-12-01

    The association of porphyria cutanea tarda (PCT) and systemic lupus erythematosus (SLE) is rare. Systemic lupus erythematosus, of complex pathophysiology and pleomorphic clinical manifestations, is similar to PCT regarding photosensitivity. One finding that can differentiate both diseases is the presence of cutaneous blisters, which are rare in SLE, but characteristic of PCT. We report one case of the association of PCT and SLE and revise the literature, emphasizing pathophysiological, clinical and therapeutic aspects. One relevant information for clinical practice relates to the treatment of SLE with antimalarials, which is a risk for PCT.

  4. Roles for mannose binding lectin and rhamnose binding lectin in channel catfish fed essential oils and challenged with Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    A major problem in the catfish farming industry has been high disease loss to enteric septicemia of catfish (ESC), caused by the bacterium Edwardsiella ictaluri. Methods to control this disease include vaccination, antibiotic therapy, and restricted feeding. Another method that has been examined i...

  5. Complete genome sequence of Edwardsiella ictaluri isolate RUSVM-1 recovered from nile tilapia (Oreochromis niloticus) in the Western Hemisphere

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella ictaluri is a Gram-negative, bacillus that has recently been implicated in disease outbreaks in tilapia and zebrafish. We report here the complete and annotated genome of an isolate from a Nile Tilapia (Oreochromis niloticus), which contains a chromosome of 3,630,639 bp and two plasmids...

  6. Effects of Ichthyophthirius multifiliis parasitism on the survival, hematology and bacterial load in channel catfish previously exposed to Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    The effect of Ichthyophthirius multifiliis (Ich) parasitism on survival, hematology and bacterial load in channel catfish, Ictalurus punctatus, previously exposed to Edwardsiella ictaluri was studied. Fish were exposed to E. ictaluri one day prior to Ich in the following treatments: 1)- infected by...

  7. Changes of serum myeloperoxidase and nitric oxide in the early stage of Edwardsiella ictaluri infection in channel catfish, Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    Enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri, is an important farm-raised channel catfish, Ictalurus punctatus (Rafinesque), disease. The development of a monitoring system for assessing the catfish health status in hatcheries and ponds is in great demanding. Because of the...

  8. Feeding Lactobacillus spp. and Bacillus spp. Does Not Improve Growth or Survival of Channel Catfish Experimentally Challenged with Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    A major problem in the channel catfish industry has been high disease loss to enteric septicemia of catfish, caused by the bacterium Edwardsiella ictaluri. Feeding probiotics may prove beneficial in improving disease resistance. The first study examined the effects of a Lactobacillus probiotic (Flor...

  9. Binding and Phagocytosis by Opsonized and Nonopsonized Channel Catfish Macrophages of Viable DsRed-fluorescent-labeled Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Phagocyte-mediated killing of bacterial pathogens is one of the major defensive mechanisms in fish. The binding, uptake and destruction of recombinant fluorescent protein DsRed transformed Edwardsiella ictaluri by opsonized and nonopsonized channel catfish (Ictalurus punctatus) macrophages was chara...

  10. Effects of a phytogenic feed additive on susceptibility of channel catfish to Edwardsiella ictaluri and levels of mannose binding lectin

    USDA-ARS?s Scientific Manuscript database

    A study was conducted to investigate the effect of a phytogenic feed additive (Digestarom® P.E.P. MGE) on growth performance and disease susceptibility to Edwardsiella ictaluri. Two hundred and fifty juvenile channel catfish (7.2 ± 0.1 g) were allotted into the following treatments: Control (float...

  11. Edwardsiella ictaluri Encodes an Acid Activated Urease that is Required for Intracellular Replication in Channel Catfish Ictalurus punctatus Macrophages

    USDA-ARS?s Scientific Manuscript database

    Genomic analysis indicated that Edwardsiella ictaluri encodes a putative ureasepathogenicity island containing 9 open reading frames, including urea and ammonium transporters. In vitro studies with the wild-type E. ictaluri and a ureG::kan urease mutant strain indicated that E. ictaluri is significa...

  12. Complete genome sequence of an Edwardsiella piscicida-like species recovered from tilapia in the United States

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella piscicida-like sp. is a Gram-negative, facultative anaerobe that causes disease in some fish species. In this report we present the complete and annotated genome of isolate LADL05-105, recovered from cultured tilapia reared in Louisiana, which contains a chromosome of 4,142,037 bp and n...

  13. Complete Genome Sequence of Edwardsiella piscicida Isolate S11-285 Recovered from Channel Catfish (Ictalurus punctatus) in Mississippi, USA

    PubMed Central

    Waldbieser, Geoffrey C.; Tekedar, Hasan C.; Lawrence, Mark L.

    2016-01-01

    Edwardsiella piscicida is a recently described Gram-negative facultative anaerobe and an important pathogen to many wild and cultured fish species worldwide. Here, we report the complete and annotated genome of E. piscicida isolate S11-285 recovered from channel catfish (Ictalurus punctatus), consisting of a chromosome of 3,923,603 bp and 1 plasmid. PMID:27881536

  14. Oral vaccination of channel catfish against enteric septicemia of catfish (ESC) using a live attenuated Edwardsiella ictaluri isolate

    USDA-ARS?s Scientific Manuscript database

    Enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri, is the most problematic bacterial disease affecting catfish aquaculture in the southeastern United States. Efforts to develop an effective ESC vaccine have had limited industrial success. In commercial settings, ESC vaccines are t...

  15. Oral vaccination of channel catfish against enteric septicemia of catfish using a live attenuated Edwardsiella ictaluri isolate

    USDA-ARS?s Scientific Manuscript database

    Enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri, is the most problematic bacterial disease affecting catfish aquaculture in the southeastern United States. Efforts to develop an effective ESC vaccine have had limited industrial success. In commercial settings, ESC vaccines are...

  16. Complete genome sequence of Edwardsiella piscicida isolate S11-285 recovered from channel catfish (Ictalurus punctatus) in Mississippi, USA

    USDA-ARS?s Scientific Manuscript database

    Edwardsiella piscicida is a recently described Gram-negative facultative anaerobe and an important pathogen to many wild and cultured fish species worldwide. Here we report the complete and annotated genome of E. piscicida isolate S11-285 recovered from channel catfish (Ictalurus punctatus) consisti...

  17. Draft Genome Sequence of Edwardsiella piscicida Strain ACC35.1 Isolated from Diseased Turbot (Scophthalmus maximus) in Europe

    PubMed Central

    Toranzo, Alicia E.; Magariños, Beatriz

    2017-01-01

    ABSTRACT   Edwardsiella piscicida is a bacterial fish pathogen with a high degree of virulence. The strain ACC35.1 was isolated from diseased turbot in Europe. The draft genome sequence comprises 3.84 Mb with a G+C content of 59.8% and >3,450 protein-coding genes. PMID:28209828

  18. Comparative genomic analysis of bacteriophages specific to the channel catfish pathogen Edwardsiella ictaluri

    PubMed Central

    2011-01-01

    Background The bacterial pathogen Edwardsiella ictaluri is a primary cause of mortality in channel catfish raised commercially in aquaculture farms. Additional treatment and diagnostic regimes are needed for this enteric pathogen, motivating the discovery and characterization of bacteriophages specific to E. ictaluri. Results The genomes of three Edwardsiella ictaluri-specific bacteriophages isolated from geographically distant aquaculture ponds, at different times, were sequenced and analyzed. The genomes for phages eiAU, eiDWF, and eiMSLS are 42.80 kbp, 42.12 kbp, and 42.69 kbp, respectively, and are greater than 95% identical to each other at the nucleotide level. Nucleotide differences were mostly observed in non-coding regions and in structural proteins, with significant variability in the sequences of putative tail fiber proteins. The genome organization of these phages exhibit a pattern shared by other Siphoviridae. Conclusions These E. ictaluri-specific phage genomes reveal considerable conservation of genomic architecture and sequence identity, even with considerable temporal and spatial divergence in their isolation. Their genomic homogeneity is similarly observed among E. ictaluri bacterial isolates. The genomic analysis of these phages supports the conclusion that these are virulent phages, lacking the capacity for lysogeny or expression of virulence genes. This study contributes to our knowledge of phage genomic diversity and facilitates studies on the diagnostic and therapeutic applications of these phages. PMID:21214923

  19. Malaria Pathogenesis

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Good, Michael F.; Milon, Genevieve

    1994-06-01

    Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity.

  20. Complete Genome Sequence of Methanolinea tarda NOBI-1T, a Hydrogenotrophic Methanogen Isolated from Methanogenic Digester Sludge.

    PubMed

    Yamamoto, Kyosuke; Tamaki, Hideyuki; Cadillo-Quiroz, Hinsby; Imachi, Hiroyuki; Kyrpides, Nikos; Woyke, Tanja; Goodwin, Lynne; Zinder, Stephen H; Kamagata, Yoichi; Liu, Wen-Tso

    2014-09-04

    Here, we report a 2.0-Mb complete genome sequence of Methanolinea tarda NOBI-1(T), a methanogenic archaeon isolated from an anaerobic digested sludge. This is the first genome report of the genus Methanolinea isolate belonging to the family Methanoregulaceae, a recently proposed novel family within the order Methanomicrobiales.

  1. Complete genome sequence of Methanolinea tarda NOBI-1T, a hydrogenotrophic methanogen isolated from methanogenic digester sludge

    DOE PAGES

    Yamamoto, Kyosuke; Tamaki, Hideyuki; Cadillo-Quiroz, Hinsby; ...

    2014-09-04

    In this study, we report a 2.0-Mb complete genome sequence of Methanolinea tarda NOBI-1T, a methanogenic archaeon isolated from an anaerobic digested sludge. This is the first genome report of the genus Methanolinea isolate belonging to the family Methanoregulaceae, a recently proposed novel family within the order Methanomicrobiales.

  2. Iron removal therapy in porphyria cutanea tarda: phlebotomy versus slow subcutaneous desferrioxamine infusion.

    PubMed

    Rocchi, E; Gibertini, P; Cassanelli, M; Pietrangelo, A; Borghi, A; Pantaleoni, M; Jensen, J; Ventura, E

    1986-05-01

    Twenty-five patients with overt clinical and biochemical findings of porphyria cutanea tarda took part in a study comparing intensive phlebotomy with slow subcutaneous desferrioxamine treatment. Fifteen male patients (Group A) had intensive venesection therapy. Ten patients (Group B) with associated diseases (minor thalassemia, cardiovascular impairment, pulmonary tuberculosis or severe liver cirrhosis) received 1.5 g of desferrioxamine by slow subcutaneous infusion using an automatic syringe pump 5 days a week. No patient complained of appreciable side effects. Serum iron, ferritin and uroporphyrins were normalized in all subjects by the end of treatment. The mean time necessary for complete recovery was 13.8 months (range 9-19) and 11.2 months (range 6-14) in Groups A and B, respectively. Liver function significantly improved during and after the treatments in both groups. We conclude that recovery from porphyria cutanea tarda can be achieved equally well using phlebotomy or desferrioxamine subcutaneous infusion. Phlebotomy is easily performed and remains the treatment of choice; slow subcutaneous desferrioxamine treatment, although expensive, is recommended when severe associated diseases contra-indicate venesection.

  3. Production of a reference transcriptome and transcriptomic database (EdwardsiellaBase) for the lined sea anemone, Edwardsiella lineata, a parasitic cnidarian

    PubMed Central

    2014-01-01

    Background The lined sea anemone Edwardsiella lineata is an informative model system for evolutionary-developmental studies of parasitism. In this species, it is possible to compare alternate developmental pathways leading from a larva to either a free-living polyp or a vermiform parasite that inhabits the mesoglea of a ctenophore host. Additionally, E. lineata is confamilial with the model cnidarian Nematostella vectensis, providing an opportunity for comparative genomic, molecular and organismal studies. Description We generated a reference transcriptome for E. lineata via high-throughput sequencing of RNA isolated from five developmental stages (parasite; parasite-to-larva transition; larva; larva-to-adult transition; adult). The transcriptome comprises 90,440 contigs assembled from >15 billion nucleotides of DNA sequence. Using a molecular clock approach, we estimated the divergence between E. lineata and N. vectensis at 215–364 million years ago. Based on gene ontology and metabolic pathway analyses and gene family surveys (bHLH-PAS, deiodinases, Fox genes, LIM homeodomains, minicollagens, nuclear receptors, Sox genes, and Wnts), the transcriptome of E. lineata is comparable in depth and completeness to N. vectensis. Analyses of protein motifs and revealed extensive conservation between the proteins of these two edwardsiid anemones, although we show the NF-κB protein of E. lineata reflects the ancestral structure, while the NF-κB protein of N. vectensis has undergone a split that separates the DNA-binding domain from the inhibitory domain. All contigs have been deposited in a public database (EdwardsiellaBase), where they may be searched according to contig ID, gene ontology, protein family motif (Pfam), enzyme commission number, and BLAST. The alignment of the raw reads to the contigs can also be visualized via JBrowse. Conclusions The transcriptomic data and database described here provide a platform for studying the evolutionary developmental genomics

  4. Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System

    PubMed Central

    Dubytska, Lidiya P.; Rogge, Matthew L.

    2016-01-01

    ABSTRACT Edwardsiella ictaluri, a major pathogen in channel catfish aquaculture, encodes a type III secretion system (T3SS) that is essential for intracellular replication and virulence. Previous work identified three putative T3SS effectors in E. ictaluri, and in silico analysis of the E. ictaluri genome identified six additional putative effectors, all located on the chromosome outside the T3SS pathogenicity island. To establish active translocation by the T3SS, we constructed translational fusions of each effector to the amino-terminal adenylate cyclase (AC) domain of the Bordetella pertussis adenylate cyclase toxin CyaA. When translocated through the membrane of the Edwardsiella-containing vacuole (ECV), the cyclic AMP produced by the AC domain in the presence of calmodulin in the host cell cytoplasm can be measured. Results showed that all nine effectors were translocated from E. ictaluri in the ECV to the cytoplasm of the host cells in the wild-type strain but not in a T3SS mutant, indicating that translocation is dependent on the T3SS machinery. This confirms that the E. ictaluri T3SS is similar to the Salmonella pathogenicity island 2 T3SS in that it translocates effectors through the membrane of the bacterial vacuole directly into the host cell cytoplasm. Additional work demonstrated that both initial acidification and subsequent neutralization of the ECV were necessary for effector translocation, except for two of them that did not require neutralization. Single-gene mutants constructed for seven of the individual effectors were all attenuated for replication in CCO cells, but only three were replication deficient in head kidney-derived macrophages (HKDM). IMPORTANCE The bacterial pathogen Edwardsiella ictaluri causes enteric septicemia of catfish (ESC), an economically significant disease of farm-raised channel catfish. Commercial catfish production accounts for the majority of the total fin fish aquaculture in the United States, with almost 300,000

  5. Experimental challenge studies in Vietnamese catfish, Pangasianodon hypophthalmus (Sauvage), exposed to Edwardsiella ictaluri and Aeromonas hydrophila.

    PubMed

    Crumlish, M; Thanh, P C; Koesling, J; Tung, V T; Gravningen, K

    2010-09-01

    The two main diseases in the pangasius catfish industry are bacillary necrosis of Pangasianodon (BNP) and motile aeromonas septicaemia (MAS), where the aetiological agents have been identified as Edwardsiella ictaluri and Aeromonas hydrophila, respectively. In this study, apparently healthy Pangasianodon hypophthalmus were exposed to E. ictaluri, A. hydrophila or both bacterial species by intraperitoneal injection or immersion. There were 20 fish per treatment group, and the bacterial isolates used for the study were recovered from natural infections of BNP or MAS in farmed Vietnamese P. hypophthalmus. The results of the experimental infections mimicked the natural disease outbreaks reported from these pathogens in P. hypophthalmus. Furthermore, it was clearly demonstrated that E. ictaluri was only recovered from the fish exposed to the bacterium and not recovered from the animals receiving A. hydrophila.

  6. Development of a Defined Minimal Medium for the Growth of Edwardsiella ictaluri

    PubMed Central

    Collins, L. A.; Thune, R. L.

    1996-01-01

    In this report, a complete defined medium and a minimally defined medium are described for Edwardsiella ictaluri. The complete defined medium consists of 46 individual components, including a basal salt solution, glucose, magnesium sulfate, iron sulfate, six trace metals, four nucleotides, 10 vitamins, and 19 amino acids. This medium supports growth in broth and on solid media. Optimal growth at 30(deg)C was obtained at pH 7.0, and at an osmolality of 390 mosmol/kg of H(inf2)O, with a glucose concentration of 4 g/liter. The defined minimal medium reduces the 46 components of the complete medium to eight essential components, including the basal salt solution, glucose, magnesium sulfate, pantothenic acid, and niacinamide. In addition, specific amino acids that depend on the specific requirements of the individual strains of E. ictaluri are added. PMID:16535274

  7. Anthrax Pathogenesis.

    PubMed

    Moayeri, Mahtab; Leppla, Stephen H; Vrentas, Catherine; Pomerantsev, Andrei P; Liu, Shihui

    2015-01-01

    Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides-protective antigen (PA), lethal factor (LF), and edema factor (EF)-that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.

  8. Porphyria cutanea tarda in pre-existent lupus erythematosus--is there an association?

    PubMed

    van Tuyll van Serooskerken, Anne-Moon; Habets, J M Werner; Badeloe, Sadhanna; Poblete-Gutiérrez, Pamela; Frank, Jorge

    2007-11-01

    In lupus erythematosus (LE), vesicles and bullae are only rarely seen. However, in some instances such efflorescences might suggest an association with distinct cutaneous diseases, including erythema multiforme, toxic epidermal necrolysis or autoimmune blistering disorders such as bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis Duhring. Another blistering disease that has been described in association with cutaneous and systemic LE is porphyria cutanea tarda (PCT). PCT is a metabolic disorder caused by a deficiency of the fifth enzyme in heme biosynthesis, uroporphyrinogen decarboxylase. Here, we report on a 57-year-old Caucasian woman of Dutch origin with a medical history of mild cutaneous LE who developed skin fragility, blistering skin lesions, milia, and facial hypertrichosis. Subsequent porphyrin analysis in urine and feces confirmed the suspected simultaneous manifestation of LE and PCT.

  9. Genetic structure of the threatened West-Pannonian population of Great Bustard (Otis tarda).

    PubMed

    Horreo, Jose L; Raab, Rainer; Spakovszky, Péter; Alonso, Juan Carlos

    2016-01-01

    The genetic diversity, population structure and gene flow of the Great Bustards (Otis tarda) living in Austria-Slovakia-West Hungary (West-Pannonian region), one of the few populations of this globally threatened species that survives across the Palaearctic, has been assessed for the first time in this study. Fourteen recently developed microsatellite loci identified one single population in the study area, with high values of genetic diversity and gene flow between two different genetic subunits. One of these subunits (Heideboden) was recognized as a priority for conservation, as it could be crucial to maintain connectivity with the central Hungarian population and thus contribute to keeping contemporary genetic diversity. Current conservation efforts have been successful in saving this threatened population from extinction two decades ago, and should continue to guarantee its future survival.

  10. Genetic structure of the threatened West-Pannonian population of Great Bustard (Otis tarda)

    PubMed Central

    Raab, Rainer; Spakovszky, Péter; Alonso, Juan Carlos

    2016-01-01

    The genetic diversity, population structure and gene flow of the Great Bustards (Otis tarda) living in Austria-Slovakia-West Hungary (West-Pannonian region), one of the few populations of this globally threatened species that survives across the Palaearctic, has been assessed for the first time in this study. Fourteen recently developed microsatellite loci identified one single population in the study area, with high values of genetic diversity and gene flow between two different genetic subunits. One of these subunits (Heideboden) was recognized as a priority for conservation, as it could be crucial to maintain connectivity with the central Hungarian population and thus contribute to keeping contemporary genetic diversity. Current conservation efforts have been successful in saving this threatened population from extinction two decades ago, and should continue to guarantee its future survival. PMID:26966677

  11. Subulura halli (Ascaridida: Subuluridae) from the endangered great bustard Otis tarda Linnaeus (Aves: Gruiformes) in China.

    PubMed

    Du, Li-Qiang; Xu, Zhen; Li, Shun-Cai; Li, Liang

    2014-02-01

    Subulurid nematodes identified as Subulura halli Barreto, 1918 were collected from the endangered bird Otis tarda Linnaeus (Gruiformes: Otididae) in China. A detailed redescription of the hitherto poorly known species is presented using both light and, for the first time, scanning electron microscopy. Previously unreported and erroneous morphological features of taxonomic significance are revealed. This species can be readily distinguished from its congeners by the relatively long oesophagus (1.47-1.92 mm long, representing 10.6-16.9% of body length), the number and arrangement of male caudal papillae (11 pairs in total, arranged as five pairs of precloacal and six pairs of postcloacal papillae), the equal length of spicules (1.35-1.52 mm long, representing 10.7-13.7% of body length) and the presence of a small medioventral, precloacal papilla in the male.

  12. Lymphedema tarda after liver transplantation: a case report and review of the literature.

    PubMed

    Saab, Sammy; Nguyen, Stephen; Collins, James; Kunder, Gregg; Busuttil, Ronald W

    2006-12-01

    We present a patient with lymphedema that developed after orthotopic liver transplantation. The cause of the posttransplant lymphedema was likely related to a developmental abnormality of the lymphatic system that was exaggerated by refractory chylous ascites. A peritoneal fluid with a milky appearance, chylous ascites is rich in triglyceride and is caused by the obstruction or disruption of abdominal lymphatic channels. It is a rare complication that may develop after trauma or abdominal surgery or as a result of a malignant disease, and it is even more uncommon after liver transplantation. Therapy for chylous ascites involves treating its underlying cause. In the patient we describe, lymphedema tarda, which was diagnosed 6 months after liver transplantation, was likely caused by chylous ascites and a developmental abnormality of the lymphatic system.

  13. Acne tarda and male-pattern baldness unmasking primary ovarian insufficiency: a case and review.

    PubMed

    Zouboulis, Christos C; Achenbach, Alexander; Makrantonaki, Eugenia

    2014-01-01

    A 30-year-old woman presented with recurrent acne lesions and progressing male-pattern baldness. Furthermore, she reported amenorrhea, weight loss, mucosal xerosis and dyspareunia since discontinuation of hormonal contraception 6 months earlier in order to conceive. Acne tarda and androgenetic alopecia of female pattern were diagnosed. Hormonal and immunologic serological and ultrasound examinations revealed an autoimmune hypergonadotropic primary ovarian insufficiency (POI) with no ovarian cysts but ovarian fibrosis with marked reduced follicle pool. Immediate ovarian stimulation and in vitro fertilization led to pregnancy and the patient gave birth to a healthy child. Though presenting with clinical findings similar to menopause, 50% of patients with POI exhibit varying and unpredictable ovarian function, and only 5-10% are able to accomplish pregnancy. Genetic disorders affect the X chromosome. In 14-30% of cases POI has been associated with autoimmunity. POI may occur after discontinuation of hormonal contraception, like in our case.

  14. Lymphedema tarda.

    PubMed

    Segal, J; Turner, A F

    1976-05-03

    The clinical recognition and evaluation of congenital lymphedema of the lower extremities with abrupt onset in a 51-year-old man are reviewed. A rational, systematic approach is outlined and exemplifies the use of an interdisciplinary effort to achieve accurate diagnosis through readily available diagnostic procedures.

  15. Tricarboxylic acid cycle and one-carbon metabolism pathways are important in Edwardsiella ictaluri virulence.

    PubMed

    Dahal, Neeti; Abdelhamed, Hossam; Lu, Jingjun; Karsi, Attila; Lawrence, Mark L

    2013-01-01

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of channel catfish (ESC). The disease causes considerable economic losses in the commercial catfish industry in the United States. Although antibiotics are used as feed additive, vaccination is a better alternative for prevention of the disease. Here we report the development and characterization of novel live attenuated E. ictaluri mutants. To accomplish this, several tricarboxylic acid cycle (sdhC, mdh, and frdA) and one-carbon metabolism genes (gcvP and glyA) were deleted in wild type E. ictaluri strain 93-146 by allelic exchange. Following bioluminescence tagging of the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, ΔgcvP, and ΔglyA mutants, their dissemination, attenuation, and vaccine efficacy were determined in catfish fingerlings by in vivo imaging technology. Immunogenicity of each mutant was also determined in catfish fingerlings. Results indicated that all of the E. ictaluri mutants were attenuated significantly in catfish compared to the parent strain as evidenced by 2,265-fold average reduction in bioluminescence signal from all the mutants at 144 h post-infection. Catfish immunized with the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, and ΔglyA mutants had 100% relative percent survival (RPS), while E. ictaluri ΔgcvP vaccinated catfish had 31.23% RPS after re-challenge with the wild type E. ictaluri.

  16. Effects of GH on immune and endocrine responses of channel catfish challenged with Edwardsiella ictaluri.

    PubMed

    Peterson, Brian C; Small, Brian C; Bilodeau, Lanie

    2007-01-01

    The effects of GH on immune and endocrine responses to channel catfish challenged with the bacterium Edwardsiella ictaluri were examined. Catfish (11.7+/-1.0 g) treated with recombinant bovine growth hormone (rbGH) and challenged with E. ictaluri experienced similar mortality as control-exposed fish. Plasma activity of lysozyme was higher (P<0.01) in rbGH-exposed fish. Compared to day 0 controls (non-exposed fish), IGF-I levels decreased (P<0.05) in challenged fish while levels were similar (P>0.10) between treatments. Abundance of GH receptor (GHR) mRNA tended to decrease (P=0.055) in liver of challenged fish while toll like receptor 5 (TLR5) mRNA increased (P<0.05) in liver compared to d 0 controls. An increase in lysozyme may suggest GH enhances a nonspecific immune response. A decrease in GHR mRNA and plasma IGF-I suggests a downregulation of the somatotropic axis in response to disease. The increase in TLR5 mRNA suggests that TLR5 may play a role in host response to bacterial challenge. While exogenous rbGH may play a stimulatory role to increase lysozyme levels, there was no apparent effect of rbGH on mortality to E. ictaluri.

  17. Can immunostimulants efficiently replace antibiotic in striped catfish (Pangasianodon hypophthalmus) against bacterial infection by Edwardsiella ictaluri?

    PubMed

    Bich Hang, Bui Thi; Phuong, Nguyen Thanh; Kestemont, Patrick

    2014-10-01

    The present study was performed to determine the efficacy of lipopolysaccharide (LPS) and levamisole on immune response and disease resistance in striped catfish and to compare their respective efficiency with the one of an antibiotic treatment after infection of fish by the bacteria Edwardsiella ictaluri. Fish were divided into 3 groups and each group was injected with LPS (3 mg/kg fish), levamisole (5 mg/kg fish) or phosphate buffer saline as control. At day 21st post immunostimulant injection, fish were bled for assaying immunological variables and then challenged with E. ictaluri. Three days after bacterial infection, an antibiotic treatment was applied into fish subgroups and mortality was compared daily between antibiotic treated and untreated fish until 2 weeks post-challenge. LPS and levamisole significantly enhanced non-specific immune responses such as respiratory burst, lysozyme and complement activity in fish compared with control (p < 0.05). Respiratory burst and complement activity significantly increased in levamisole groups when compared with LPS groups while lysozyme activity did not differ significantly between immunostimulant treatments. Total immunoglobulins significantly increased in levamisole treatment compared with control. After challenge test, accumulated mortality was reduced significantly in both non-antibiotic and antibiotic subgroups of LPS and levamisole compared with control. Moreover, no differences of mortality were observed between fish treated with levamisole or LPS without antibiotics and control fish treated with antibiotics. These results support the possible replacement of antibiotics in striped catfish farming by immunostimulants such as levamisole and LPS.

  18. Tricarboxylic Acid Cycle and One-Carbon Metabolism Pathways Are Important in Edwardsiella ictaluri Virulence

    PubMed Central

    Dahal, Neeti; Abdelhamed, Hossam; Lu, Jingjun; Karsi, Attila; Lawrence, Mark L.

    2013-01-01

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of channel catfish (ESC). The disease causes considerable economic losses in the commercial catfish industry in the United States. Although antibiotics are used as feed additive, vaccination is a better alternative for prevention of the disease. Here we report the development and characterization of novel live attenuated E. ictaluri mutants. To accomplish this, several tricarboxylic acid cycle (sdhC, mdh, and frdA) and one-carbon metabolism genes (gcvP and glyA) were deleted in wild type E. ictaluri strain 93-146 by allelic exchange. Following bioluminescence tagging of the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, ΔgcvP, and ΔglyA mutants, their dissemination, attenuation, and vaccine efficacy were determined in catfish fingerlings by in vivo imaging technology. Immunogenicity of each mutant was also determined in catfish fingerlings. Results indicated that all of the E. ictaluri mutants were attenuated significantly in catfish compared to the parent strain as evidenced by 2,265-fold average reduction in bioluminescence signal from all the mutants at 144 h post-infection. Catfish immunized with the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, and ΔglyA mutants had 100% relative percent survival (RPS), while E. ictaluri ΔgcvP vaccinated catfish had 31.23% RPS after re-challenge with the wild type E. ictaluri. PMID:23762452

  19. Edwardsiella ictaluri infection in Pangasius catfish imported from West Bengal into the Southern Caribbean.

    PubMed

    Phillips, A C N; Reichley, S R; Ware, C; Griffin, M J

    2016-09-05

    In response to a mortality event, seven Pangasius catfish (Pangasianodon hypophthalmus) were submitted to the University of the West Indies, School of Veterinary Medicine, Trinidad and Tobago, for diagnostic evaluation. These fish were part of a consignment that arrived from Kolkata two weeks earlier. Fish presented with perianal haemorrhage and blister-like swellings on the skin which ruptured to leave ulcers. Edwardsiella ictaluri was consistently recovered from the brain and skin. Repetitive sequence-mediated PCR analysis revealed genetic fingerprints consistent with E. ictaluri isolates from farm-raised channel catfish in Mississippi, USA. Plasmid analysis of the case isolates identified two unique plasmids that differ slightly in conformation and content from the pEI1 and pEI2 plasmids described for E. ictaluri from other fish hosts. The case isolates were also PCR negative for several E. ictaluri virulence factors. The biological implications of these genetic differences are unclear and warrant further study. This is the first report and documentation of E. ictaluri infection in Trinidad and Tobago, suggesting the pathogen may have been introduced concurrently with the importation of fish. This report emphasizes the importance of adequate health screenings of imported lots to minimize the threat of introducing E. ictaluri to non-endemic areas.

  20. Edwardsiella ictaluri as the causative agent of mortality in cultured Nile tilapia.

    PubMed

    Soto, Esteban; Griffin, Matt; Arauz, Maziel; Riofrio, Andres; Martinez, Alexis; Cabrejos, Maria Eugenia

    2012-06-01

    Edwardsiella ictaluri was consistently isolated from the spleens, livers, and head kidneys of diseased Nile tilapia Oreochromis niloticus from a farm experiencing mortality events in several culture ponds. We describe the first published outbreak of E. ictaluri-induced edwardsiellosis in Nile tilapia. Pure cultures of the isolated bacteria were characterized both biochemically and molecularly. Biochemical analysis was performed using the API-20E and RapID One systems, and antimicrobial susceptibility was determined by the broth microdilution method. Molecular analysis involved sequencing of the 16S rRNA gene, species-specific real-time polymerase chain reaction (PCR), and PCR-mediated genomic fingerprinting (rep-PCR). Pairwise sequence analysis of the 16S rRNA gene identified the case isolates to be a 100% match to E. ictaluri cultured from channel catfish in the southeastern United States. However, rep-PCR analysis identified the case isolates to be genetically different from representative strains isolated from disease outbreaks in cultured channel catfish in Mississippi. Infectivity challenges (intraperitoneal injection and immersion) demonstrated that a representative E. ictaluri strain isolated from tilapia was pathogenic to naive tilapia, reproducing clinical signs and mortality, thereby establishing Koch's postulates.

  1. Efficacy of Florfenicol for Control of Mortality Associated with Edwardsiella ictaluri in Three Species of Catfish.

    PubMed

    Gaunt, Patricia S; Chatakondi, Nagaraj; Gao, Dana; Endris, Richard

    2015-03-01

    The efficacy of florfenicol for control of mortality associated with Edwardsiella icatluri was studied in fingerlings of Channel Catfish Ictalurus puntatus (Delta strain), Blue Catfish I. furcatus (D&B strain), and a hybrid catfish (Delta strain Channel Catfish × D&B strain Blue Catfish). On day 0, fish were immersion challenged in 65-L aquaria. For each of the three species of catfish, 10 aquaria were randomly assigned to two treatment groups, either treated with florfenicol at 0 mg/kg of body weight (unmedicated feed) or at 10 mg/kg (medicated feed). Fish were treated for 10 consecutive days, monitored for mortality during this treatment period, and observed for 14 d afterwards. Post observation, all survivors were humanely euthanized in tricaine methanesulfonate, cultured for E. ictaluri, and examined for gross pathology. The mean cumulative percent mortality from enteric septicemia of catfish (ESC) challenge among the three genotypes of catfish did not differ between Blue Catfish, hybrid, and Channel Catfish in treated or control groups. However, the florfenicol-treated fish had a significantly lower mean cumulative mortality (6%) than the controls (78%). All genotypes of catfish tested were responsive to treatment with florfenicol-medicated feed for control of mortality associated with ESC. There were no significant differences in mortality associated with hybrid catfish, blue catfish, and Channel Catfish (Delta strain).

  2. Identification of Differentially Abundant Proteins of Edwardsiella ictaluri during Iron Restriction

    PubMed Central

    Dumpala, Pradeep R.; Peterson, Brian C.; Lawrence, Mark L.; Karsi, Attila

    2015-01-01

    Edwardsiella ictaluri is a Gram-negative facultative anaerobe intracellular bacterium that causes enteric septicemia in channel catfish. Iron is an essential inorganic nutrient of bacteria and is crucial for bacterial invasion. Reduced availability of iron by the host may cause significant stress for bacterial pathogens and is considered a signal that leads to significant alteration in virulence gene expression. However, the precise effect of iron-restriction on E. ictaluri protein abundance is unknown. The purpose of this study was to identify differentially abundant proteins of E. ictaluri during in vitro iron-restricted conditions. We applied two-dimensional difference in gel electrophoresis (2D-DIGE) for determining differentially abundant proteins and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS) for protein identification. Gene ontology and pathway-based functional modeling of differentially abundant proteins was also conducted. A total of 50 unique differentially abundant proteins at a minimum of 2-fold (p ≤ 0.05) difference in abundance due to iron-restriction were detected. The numbers of up- and down-regulated proteins were 37 and 13, respectively. We noted several proteins, including EsrB, LamB, MalM, MalE, FdaA, and TonB-dependent heme/hemoglobin receptor family proteins responded to iron restriction in E. ictaluri. PMID:26168192

  3. Transcriptome of intraperitoneal organs of starry flounder Platichthys stellatus challenged by Edwardsiella ictaluri JCM1680

    NASA Astrophysics Data System (ADS)

    Tong, Yanli; Sun, Xiuqin; Wang, Bo; Wang, Ling; Li, Yan; Tian, Jinhu; Zheng, Fengrong; Zheng, Minggang

    2014-09-01

    Platichthys stellatus is an economically important marine bony fish species that is cultured in China on a large scale. However, very little is known about its immune-related genes. In this study, the transcriptome of the immune organs of P. stellatus that were intraperitoneally challenged with the pathogen Edwardsiella ictaluri JCM1680 is analyzed. Total RNA from four tissues (spleen, kidney, liver, and intestine) was mixed equally and then sequenced on an Illumina HiSeq 2000 platform. Overall, 28 465 813 quality reads were generated and assembled into 43 061 unigenes. Similarity searches against public protein sequence databases were used to annotate 28 291 unigenes (65.7% of the total), 368 of which were associated with immunoregulation, including 188 related to immunity response. Additionally, the transcript levels of immunity response unigenes annotated as related to tumor necrosis factor (TNF), TNF receptor, chemokine, major histocompatibility complex, and interleukin-6 were investigated in the different tissues of normal and infected P. stellatus by real-time quantitative PCR. The results confirmed that the unigenes identified in the transcriptome database were indeed expressed and up-regulated in infected P. stellatus. To our knowledge, this is the first report of the sequencing and analysis of the transcriptome of P. stellatus. These findings provide insights into the transcriptomics and immunogenetics of bony fish.

  4. Preliminary data concerning association of porphyria cutanea tarda and adrenocortical insufficiency. Report of two cases.

    PubMed

    Pereţianu, D; Giurcăneanu, C; Deleanu, A

    1984-01-01

    The paper presents two cases in which clinical and laboratory investigations have revealed the simultaneous presence of porphyria cutanea tarda (PCT) and adrenocortical insufficiency (ACI). Whether this association is a coincidence, whether there is a common cause, or a "cause to effect" type relationship between the two entities is a question of debate. Without ignoring other possible causes (tuberculosis, hemochromatosis, autoimmunity, drugs) it is suggested that heme deficit consequent to inefficient protoporphyrin synthesis results in impaired steroidogenesis, due to decreased levels of adrenocortical hemoprotein enzymes, especially cytochrome P-450 dependent hydroxylases. Cytochrome P-450 has a well known sine-qua-non activity in steroid hydroxylations within steroid tissues, and a decrease in the levels of this heme-enzyme might be expected to result in impaired steroidogenesis. However, the association between PCT and ACI (whether pathogenic or not) is pathophysiologically characterized by the coexistence of a disease (PCT) in which the anatomo-clinical manifestations are determined by oxygen derived free radicals ( ODFR ), and a disease (ACI) which, among other consequences, presents a marked reduction in ODFR -scavenge capacity. The authors consider this supposition an attractive working hypothesis, suitable to further clinical laboratory direct testing.

  5. Biomedical and Social Aspects of Spondyloepiphyseal Dysplasia Tarda Cases from Bengkulu District of Indonesia

    PubMed Central

    Ruyani, A.; Karyadi, B.; Muslim, C.; Sipriyadi; Suherlan

    2012-01-01

    BACKGROUND: Although short stature male (SSM) cases are often found in South Bengkulu, no management reports about their existence are available. This paper summarizes the researches of biomedical and social aspects for the human genetic disorders. CASE PRESENTATION: Field survey results indicated that SSM community was located in Kedurang area, and 67 persons with SSM were successfully sampled from a population of 17,357 persons (one of 260). Anthropometric comparative studies, history of the pattern of X-linked inheritance, as well as the study of anatomy through radiology and ultrasound confirmed that SSM is spondyloepiphyseal dysplasia tarda (SEDT). Genomic studies through characterisation of mutations of the SEDL gene revealed that point mutations on SEDT Kedurang are different from the results of previous similar studies, and these people are predicted to come from the same ancestors. It is necessary to notice that persons with SEDT have normal intellectual ability, but the physical conditions make their socio-economic competitiveness very low. Furthermore premature joint pains make persons with SEDT become old faster than the ordinary people by the age of 40 years. Realizing that they are marginalized, some of them try to come together to establish a foundation designed to make a better life. CONCLUSION: It can be concluded that the appropriate management of SEDT should be done by integrating to improve their nutritional status, reduce the suffering of joint pain, develop labelled molecular markers for early detection, and increase their socio-economic competitiveness. PMID:23675282

  6. Biomedical and social aspects of spondyloepiphyseal dysplasia tarda cases from bengkulu district of indonesia.

    PubMed

    Ruyani, A; Karyadi, B; Muslim, C; Sipriyadi; Suherlan

    2012-12-01

    Although short stature male (SSM) cases are often found in South Bengkulu, no management reports about their existence are available. This paper summarizes the researches of biomedical and social aspects for the human genetic disorders. Field survey results indicated that SSM community was located in Kedurang area, and 67 persons with SSM were successfully sampled from a population of 17,357 persons (one of 260). Anthropometric comparative studies, history of the pattern of X-linked inheritance, as well as the study of anatomy through radiology and ultrasound confirmed that SSM is spondyloepiphyseal dysplasia tarda (SEDT). Genomic studies through characterisation of mutations of the SEDL gene revealed that point mutations on SEDT Kedurang are different from the results of previous similar studies, and these people are predicted to come from the same ancestors. It is necessary to notice that persons with SEDT have normal intellectual ability, but the physical conditions make their socio-economic competitiveness very low. Furthermore premature joint pains make persons with SEDT become old faster than the ordinary people by the age of 40 years. Realizing that they are marginalized, some of them try to come together to establish a foundation designed to make a better life. It can be concluded that the appropriate management of SEDT should be done by integrating to improve their nutritional status, reduce the suffering of joint pain, develop labelled molecular markers for early detection, and increase their socio-economic competitiveness.

  7. Re-evaluation of the diagnosis of porphyria cutanea tarda in Admiral Sir Francis Beaufort

    PubMed Central

    Peters, T J; Levell, N J

    2010-01-01

    Objectives Two biographies of Admiral Francis Beaufort (1774–1857) have stated that, aged 20–25 years, he suffered from porphyria cutanea tarda (PCT) that was ‘cured’ following severe blood loss during a naval skirmish. We have examined the evidence concerning the nature of his skin disease. Design Primary records, most notably Beaufort's correspondence with his family, his journals and his father's diaries were sought out and analysed. Setting This case report is discussed in the context of 18th-century naval medicine and concepts and treatment of skin disease. Results The description of his lesions, their age of onset, their progression and response to treatment, particularly topical tar and associated features are quite inconsistent with a diagnosis of PCT. His mother, Mary Waller Beaufort (1739–1821), consulted Dr Robert Darwin in 1803 about a painful skin disease affecting her legs. Detailed description of the lesions and a contemporary diagnosis are not available but possible diagnoses include chronic psoriasis and stasis eczema. Conclusions A more tenable diagnosis is that Francis Beaufort had chronic plaque psoriasis remitted by bed rest and convalescence in the sunny Mediterranean climate with cessation of alcohol consumption and improved nutrition as well as topical and oral medications. PMID:21103105

  8. [Prenatal diagnosis of a case with X-linked spondyloepiphyseal dysplasia tarda].

    PubMed

    Cao, Fang; Wang, Qiu-wei; Yu, Bin; Huang, Rui-ping; Hu, Ya-li; Zhang, Xiao-qing

    2013-10-01

    To analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis. All of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was extracted from amniotic fluid sampled at 18th gestational week. Gender of the fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2 gene was also analyzed. A c.209G>A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father. The fetus of was determined to be a male and also have carried the c.209G>A mutation. A c.209G>A mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this family. The proband is a carrier, and her fetus is a male carrying the same mutation. Prenatal diagnosis is an effective method for the prevention of the disease.

  9. [Early prenatal diagnosis for a family affected with X-linked spondyloepiphyseal dysplasia tarda family].

    PubMed

    Gao, Chao; Wang, Huaili; Kong, Xiangdong; Shang, Qing; Duan, Jiali; Luo, Qiang

    2014-04-01

    X-linked spondyloepiphyseal dysplasia tarda (SEDL) is a rare osteochondrodysplasia caused by mutations of SEDL gene, which usually onset in late childhood without systemic complications. In this study, we have provided prenatal diagnosis for an affected family with a combined strategy including direct sequencing, fetal-sex identification and microsatellite linkage analysis. Two amniotic fluid samples from carrier gravida and 7 blood samples from individuals in this SEDL pedigree were obtained. Genomic DNA was extracted from the samples using standard phenol-chloroform method. SRY and AMEL genes were employed to assess fetal sex. Microsatellite DXS16 was genotyped for linkage analysis. A pathogenic mutation of the SEDL gene was identified by bi-directionally direct sequencing of the third exon as well as its exon/intron boundaries. Two male fetuses were confirmed by fetal-sex assessment. The mutation of the SEDL gene was identified as a nucleotide substitution of the splice acceptor site in intron 2, IVS2-2A>C. DNA sequencing indicated that one fetus is hemizygote carrying the mutation, whilst another is not a carrier. Linkage analysis was identical with the sequencing results. Follow-up also confirmed the result of prenatal diagnosis. Fetal-sex assessment combined with microsatellite linkage analysis and bi-directionally direct sequencing is a more accurate and ready strategy for prenatal diagnosis of families affected with SEDL.

  10. Mechanisms of intrinsic resistance to antimicrobial peptides of Edwardsiella ictaluri and its influence on fish gut inflammation and virulence

    PubMed Central

    Martin, Taylor; Loh, Amanda; Pohlenz, Camilo; Gatlin, Delbert M.; Curtiss, Roy

    2013-01-01

    The genus Edwardsiella comprises a genetically distinct taxon related to other members of the family Enterobacteriaceae. It consists of bacteria differing strongly in their biochemical and physiological features, natural habitats, and pathogenic properties. Intrinsic resistance to cationic antimicrobial peptides (CAMPs) is a specific property of the genus Edwardsiella. In particular, Edwardsiella ictaluri, an important pathogen of the catfish (Ictalurus punctatus) aquaculture and the causative agent of a fatal systemic infection, is highly resistant to CAMPs. E. ictaluri mechanisms of resistance to CAMPs are unknown. We hypothesized that E. ictaluri lipopolysaccharide (LPS) plays a role in both virulence and resistance to CAMPs. The putative genes related to LPS oligo-polysaccharide (O-PS) synthesis were in-frame deleted. Individual deletions of wibT, gne and ugd eliminated synthesis of the O-PS, causing auto-agglutination, rough colonies, biofilm-like formation and motility defects. Deletion of ugd, the gene that encodes the UDP-glucose dehydrogenase enzyme responsible for synthesis of UDP-glucuronic acid, causes sensitivity to CAMPs, indicating that UDP-glucuronic acid and its derivatives are related to CAMP intrinsic resistance. E. ictaluri OP-S mutants showed different levels of attenuation, colonization of lymphoid tissues and immune protection in zebrafish (Danio rerio) and catfish. Orally inoculated catfish with O-PS mutant strains presented different degrees of gut inflammation and colonization of lymphoid tissues. Here we conclude that intrinsic resistance to CAMPs is mediated by Ugd enzyme, which has a pleiotropic effect in E. ictaluri influencing LPS synthesis, motility, agglutination, fish gut inflammation and virulence. PMID:23676433

  11. Attenuation, persistence, and vaccine potential of an Edwardsiella ictaluri purA mutant.

    PubMed Central

    Lawrence, M L; Cooper, R K; Thune, R L

    1997-01-01

    In this study, an adenine-auxotrophic strain of Edwardsiella ictaluri was constructed and its virulence, tissue persistence, and vaccine efficacy were evaluated. A clone containing the purA gene was isolated from an E. ictaluri genomic library, sequenced, and shown to have an overall sequence identity of 79.3% at the nucleotide level and 85.7% at the amino acid level with the Escherichia coli purA gene. The cloned E. ictaluri purA gene was mutated by deleting a 598-bp segment of the gene and inserting the kanamycin resistance gene from Tn903 into the gap. The delta purA::Km(r) gene was subcloned into the suicide plasmid pGP704, and the resulting plasmid was used to deliver the modified gene into a virulent strain of E. ictaluri by conjugation. Homologous recombination replaced the chromosomal purA gene with the mutated gene to create an adenine-auxotrophic strain (LSU-E2). Compared to wild-type E. ictaluri, LSU-E2 was highly attenuated by the injection, immersion, and oral routes of exposure. By the injection route, LSU-E2 had a 50% lethal dose (LD50) that was greater than 5 logs10 higher than the LD50 for wild-type E. ictaluri. In a tissue persistence study, LSU-E2 was able to invade channel catfish by the immersion route and persist in internal organs for at least 48 h. Channel catfish that were vaccinated with a single immersion dose of LSU-E2 had mortality significantly lower (P < 0.01) following a wild-type E. ictaluri challenge than that of nonvaccinated fish. PMID:9353045

  12. Construction and evaluation of an Edwardsiella ictaluri fhuC mutant.

    PubMed

    Abdelhamed, Hossam; Lu, Jingjun; Shaheen, Adel; Abbass, Amany; Lawrence, Mark L; Karsi, Attila

    2013-03-23

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia in channel catfish. Iron is an essential micronutrient needed for bacterial virulence, and to acquire iron, many Gram-negative bacteria secrete ferric iron chelating siderophores. The ferric hydroxamate uptake (Fhu) system consists of four genes (fhuC, fhuD, fhuB, and fhuA), and is involved in the uptake of hydroxamate type siderophores across bacterial membranes. However, the Fhu system and its importance in E. ictaluri virulence have been uninvestigated. Here, we present construction and evaluation of an E. ictaluri ΔfhuC mutant. The E. ictaluri fhuC gene was deleted in-frame by allelic exchange, and the mutant's growth in media and virulence in catfish were determined. Our results indicated that deletion of the E. ictaluri fhuC gene did not affect the growth of E. ictaluri largely in both iron-replete and iron-depleted media. Addition of ferric iron sources into the iron-depleted medium improved the growth of both E. ictaluri ΔfhuC and wild type (WT). Catfish mortalities indicated that E. ictaluri ΔfhuC mutant was attenuated 2.05-fold compared with the parent strain. The catfish immunized with the E. ictaluri ΔfhuC mutant showed a high relative percent survival rate (97.50%) after re-challenge with the WT E. ictaluri strain. Taken together, our data indicates that the fhuC gene contributes to E. ictaluri virulence.

  13. Early interactions of Edwardsiella ictaluri, with Pangasianodon catfish and its invasive ability in cell lines.

    PubMed

    Dung, T T; Chiers, K; Tuan, N A; Sorgeloos, P; Haesebrouck, F; Decostere, A

    2012-06-01

    Commercial Pangasianodon catfish production is heavily impacted by Bacillary Necrosis of Pangasius (BNP) caused by Edwardsiella ictaluri. This study aimed to investigate the early bacterium-host interactions following immersion challenge and to compare the retrieved data with the invasion ability of the used isolates in fish cell lines. Firstly, Pangasianodon hypophthalmus fingerlings were challenged via immersion using E. ictaluri isolate HO2 or 223. At different times post inoculation, fish were sacrificed and gill and internal organ samples were taken for bacteriological, histological and immunohistochemical evaluation. The bacterial load was higher for fish inoculated with isolate HO2 compared with 223. Histological and immunohistochemical analysis revealed multifocal necrotic areas in kidney, spleen and liver of HO2 inoculated fish at 72 h post inoculation with short rod-shaped immunoperoxidase positive bacteria clustered inside cells respectively. Bacteria especially were present in the gills and intestinal tract of HO2 inoculated fish, suggesting the gastrointestinal tract and gills act as portals of entry. Following, the ability of HO2, 223 and four additional isolates to invade a Chinook salmon embryo cell line, a fat head minnow cell line and a rainbow trout liver cell line was tested. All E. ictaluri isolates were invasive in all cell lines albeit at different degrees. Isolate HO2 was highly invasive in all cell lines with a significantly higher invasion capacity than isolate 223 in the Chinook salmon embryo cell line. A correlation between in vivo virulence and in vitro invasiveness hence is suggested although further studies are needed to confirm this hypothesis.

  14. Effects of a phytogenic feed additive on growth and susceptibility of channel catfish to Edwardsiella ictaluri and levels of mannose and rhamnose binding lectin

    USDA-ARS?s Scientific Manuscript database

    A study was conducted to investigate the effect of essential oils (EO) on growth and disease susceptibility to Edwardsiella ictaluri. Weight gain and food conversion ratio were similar. After exposing fish to virulent E. ictaluri, survival was higher (69.5 vs 48.4%) in fish fed EO (P < 0.05). In ...

  15. Evaluation of a loop-mediated isothermal amplification method for rapid detection of channel catfish Ictalurus punctatus important bacterial pathogen Edwardsiella ictaluri.

    USDA-ARS?s Scientific Manuscript database

    Channel catfish Ictalurus punctatus infected with Edwardsiella ictaluri results in $40 - 50 million annual losses in profits to catfish producers. Early detection of this pathogen is necessary for disease control and reduction of economic loss. In this communication, the loop-mediated isothermal a...

  16. Growth Performance and Resistance to Edwardsiella ictaluri of Channel Catfish (Ictalurus punctatus)Fed Diets Containing Distiller's Dried Grains with Solubles

    USDA-ARS?s Scientific Manuscript database

    A study was conducted to examine the effect of dietary levels of distiller’s dried grains with solubles (DDGS) on growth, body composition, hematology, immune response and resistance of channel catfish, Ictalurus punctatus, to Edwardsiella ictaluri challenge. Five diets containing 0, 10, 20, 30 and ...

  17. Vaccination of full-sib channel catfish families against enteric septicemia of catfish with an oral live attenuated Edwardsiella ictaluri vaccine

    USDA-ARS?s Scientific Manuscript database

    The study evaluated the efficacy of an oral live-attenuated Edwardsiella ictaluri vaccine against enteric septicemia of catfish in 20 full-sib fingerling channel catfish families. Each family was split into vaccinated and non-vaccinated groups. The vaccine was delivered orally by feeding fish diet...

  18. TLR5, NRAMP, TNF, AND Hepcidin Response to Challenge with Edwardsiella ictaluri in Channel Catfish Families with High and Low Susceptibility to Infection

    USDA-ARS?s Scientific Manuscript database

    Responses of toll-like receptor 5 (TLR5), tumor necrosis factor (TNF), natural resistance-associated macrophage protein (Nramp), and hepcidin to experimental challenge with Edwardsiella ictaluri in two families of channel catfish were measured in order to understand the mechanisms through which E. i...

  19. Identification of in vitro upregulated genes in a modified live vaccine strain of Edwardsiella ictaluri compared to a virulent parent strain

    USDA-ARS?s Scientific Manuscript database

    Using PCR-select subtractive cDNA hybridization technique, 41 expressed sequence tags (ESTs) were isolated from a modified live vaccine strain (AQUAVAC-ESC©, formerly RE-33) vs a virulent parent strain (EILO) of Edwardsiella ictaluri. Transcriptional levels of the 41 ESTs in the vaccine strain and t...

  20. Identification of upregulated genes in a modified live vaccine strain of Edwardsiella ictaluri compared to a virulent parent strain and characterization of novel DNA vaccine candidates

    USDA-ARS?s Scientific Manuscript database

    Using PCR-select subtractive cDNA hybridization technique, 41 expressed sequence tags (EST's) were isolated from a modified live vaccine strain (AQUAVAC-ESC formerly RD-33) vs a virulent parent strain (EILO) of Edwardsiella ictaluri. Transcriptional levels of the 41 ESTs in the vaccine strain and th...

  1. Is there a genetic correlation between the resistance of channel catfish to Edwardsiella ictaluri and Flavobacterium columnare, and how do we get there?

    USDA-ARS?s Scientific Manuscript database

    Two major problems in the channel catfish (Ictalurus punctatus) aquaculture industry have been high disease losses to enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri and columnaris disease, caused by Flavobacterium columnare. Methods to control and prevent these diseases includ...

  2. A real time polymerase chain reaction assay for quantification of Edwardsiella ictaluri in catfish pond water and genetic homogeneity of diagnostic case isolates from Mississippi

    USDA-ARS?s Scientific Manuscript database

    A quantitative polymerase chain reaction (qPCR) assay was developed for the detection and quantification of Edwardsiella ictaluri in channel catfish Ictalurus punctatus pond water using modifications to a published E. ictaluri–specific qPCR assay and previously established protocols for the molecula...

  3. In vitro and in vivo interaction of macrophages from vaccinated and non-vaccinated channel catfish (Ictalurus punctatus) to Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    Macrophages from modified live vaccinated and non-vaccinated catfish were used in in vitro and in vivo studies with red fluorescent Edwardsiella ictaluri to assess phagocytic ability, reactive oxygen and nitric oxide production and bactericidal activity. In the in vitro experiment, macrophages were...

  4. Associations among Behavior-Related Susceptibility Factors in Porphyria Cutanea Tarda

    PubMed Central

    Jalil, Sajid; Grady, James J.; Lee, Chul; Anderson, Karl E.

    2009-01-01

    Background & Aims Porphyria cutanea tarda (PCT) is the most common of the human porphyrias and results from an acquired deficiency of hepatic uroporphyrinogen decarboxylase (UROD). Some susceptibility factors have been identified; we examined associations among multiple factors in a large cohort of patients. Methods Multiple known or suspected susceptibility factors and demographic and clinical features of 143 patients (mean age 52 years, 66% male, 88% Caucasian) with documented PCT (mean onset at 41±8.8 yrs) were tabulated; associations were examined by contingency tables, classification and regression tree (CART) analysis and logistic regression. Results The most common susceptibility factors for PCT were ethanol use (87%), smoking (81%), chronic hepatitis C virus (HCV) infection (69%), and HFE mutations (53%; 6% C282Y/C282Y and 8% C282Y/H63D). Of those who underwent hepatic biopsy or ultrasound, 56% had evidence of hepatic steatosis. Of those with PCT, 66% of females took estrogen, 8% were diabetic, 13% had human immunodeficiency virus (HIV) infection, and 17% had inherited uroporphyrinogen decarboxylase (UROD) deficiency (determined by low erythrocyte UROD activity). HCV infection in patients with PCT was significantly associated with other behavior-related factors such as ethanol use (odds ratio [OR] 6.3) and smoking (OR 11.9). Conclusions Susceptibility factors for PCT were similar to previous studies; most patients had 3 or more. Associations between PCT and HCV, ethanol or smoking could be accounted for by a history of multiple substance abuse; other factors are distributed more randomly amongpatients. PMID:19948245

  5. Molecular Genetic Evaluation of Bacterial Pathogenesis

    USDA-ARS?s Scientific Manuscript database

    Commercial catfish production accounts for 85-90% of the total fin fish aquaculture production in the United States, with almost 300,000 tonnes produced in 2003. Significant losses caused by the Gram negative bacterial pathogen Edwardsiella ictaluri were reported on over 60% of all farms in operatio...

  6. Complete genome sequence of Methanolinea tarda NOBI-1T, a hydrogenotrophic methanogen isolated from methanogenic digester sludge

    SciTech Connect

    Yamamoto, Kyosuke; Tamaki, Hideyuki; Cadillo-Quiroz, Hinsby; Imachi, Hiroyuki; Kyrpides, Nikos; Woyke, Tanja; Goodwin, Lynne; Zinder, Stephen H.; Kamagata, Yoichi; Liu, Wen -Tso

    2014-09-04

    In this study, we report a 2.0-Mb complete genome sequence of Methanolinea tarda NOBI-1T, a methanogenic archaeon isolated from an anaerobic digested sludge. This is the first genome report of the genus Methanolinea isolate belonging to the family Methanoregulaceae, a recently proposed novel family within the order Methanomicrobiales.

  7. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  8. Pathogenesis of Acanthamoeba infections.

    PubMed

    Khan, Naveed Ahmed

    2003-06-01

    Acanthamoeba are free-living, harmless organisms, however, given the opportunity and the appropriate conditions, they can cause painful, sight-threatening as well as fatal infections and, thus, are considered opportunistic pathogens. Acanthamoeba infections have become increasingly important in the past few years due to increasing populations of contact lens users and AIDS patients. The mechanisms associated with the pathogenesis of Acanthamoeba tend to be highly complex, depending on parasite, host and the environmental factors. Elucidation of the biochemical, cellular and molecular basis of the pathogenesis of diseases caused by Acanthamoeba may lead to the development of therapeutic interventions.

  9. Proteases in bacterial pathogenesis.

    PubMed

    Ingmer, Hanne; Brøndsted, Lone

    2009-11-01

    Bacterial pathogens rely on proteolysis for protein quality control under adverse conditions experienced in the host, as well as for the timely degradation of central virulence regulators. We have focused on the contribution of the conserved Lon, Clp, HtrA and FtsH proteases to pathogenesis and have highlighted common biological processes for which their activities are important for virulence.

  10. Hepatitis E Pathogenesis

    PubMed Central

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  11. The effects of feeding β-glucan to Pangasianodon hypophthalmus on immune gene expression and resistance to Edwardsiella ictaluri.

    PubMed

    Sirimanapong, Wanna; Thompson, Kim D; Ooi, Ei Lin; Bekaert, Michaël; Collet, Bertrand; Taggart, John B; Bron, James E; Green, Darren M; Shinn, Andrew P; Adams, Alexandra; Leaver, Michael J

    2015-11-01

    Pangasianodon hypophthalmus (striped catfish) is an important aquaculture species and intensification of farming has increased disease problems, particularly Edwardsiella ictaluri. The effects of feeding β-glucans on immune gene expression and resistance to E. ictaluri in P. hypophthalmus were explored. Fish were fed 0.1% fungal-derived β-glucan or 0.1% commercial yeast-derived β-glucan or a basal control diet without glucan. After 14 days of feeding, the mRNA expression of immune genes (transferrin, C-reactive protein, precerebellin-like protein, Complement C3 and factor B, 2a MHC class II and interleukin-1 beta) in liver, kidney and spleen were determined. Following this fish from each of the three diet treatment groups were infected with E. ictaluri and further gene expression measured 24 h post-infection (h.p.i.), while the remaining fish were monitored over 2 weeks for mortalities. Cumulative percentage mortality at 14 days post-infection (d.p.i.) was less in β-glucan fed fish compared to controls. There was no difference in gene expression between dietary groups after feeding for 14 days, but there was a clear difference between infected and uninfected fish at 24 h.p.i., and based on principal component analysis β-glucans stimulated the overall expression of immune genes in the liver, kidney and spleen at 24 h.p.i. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Use of bioluminescence mutant screening for identification of Edwardsiella ictaluri genes involved in channel catfish (Ictalurus punctatus) skin colonization.

    PubMed

    Menanteau-Ledouble, Simon; Lawrence, Mark L

    2013-03-23

    Initial invasion of the host is the first and vital part of any infection process. We have demonstrated that Edwardsiella ictaluri is capable of colonizing and penetrating catfish skin. Therefore, a mutant library was constructed by random insertion of the Mar2xT7 transposon into the chromosome of E. ictaluri harboring the bioluminescence plasmid pAKgfplux1. This library was then screened through a series of three consecutive challenges for mutants showing a decreased ability to colonize the catfish epithelium. Eighteen mutants were identified that have decreased adhesion and virulence. Mutated genes encoded one sensor protein, two transport proteins, five enzymes, two regulatory proteins, and five hypothetical proteins. Among the mutated genes, the first one identified was a gene encoding for RstA/B, which is known to play a role in regulating the expression of invasion genes in Salmonella enterica Typhimurium. Another mutant was lacking a putative ribonuclease similar to a Shigella protein that regulates the expression of adhesin. A third mutant was defective in a protein similar to a Brucella protein that was initially identified as a transporter, but actually is a member of a newly discovered adhesin family. Results from this study could enable development of a new strategy for blocking E. ictaluri invasion at the initial adherence stage. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Tissue persistence and vaccine efficacy of tricarboxylic acid cycle and one-carbon metabolism mutant strains of Edwardsiella ictaluri.

    PubMed

    Dahal, Neeti; Abdelhamed, Hossam; Karsi, Attila; Lawrence, Mark L

    2014-06-30

    Edwardsiella ictaluri causes enteric septicemia in fish. Recently, we reported construction of E. ictaluri mutants with single and double gene deletions in tricarboxylic acid cycle (TCA) and one-carbon (C-1) metabolism. Here, we report the tissue persistence, virulence, and vaccine efficacy of TCA cycle (EiΔsdhC, EiΔfrdA, and EiΔmdh), C-1 metabolism (EiΔgcvP and EiΔglyA), and combination mutants (EiΔfrdAΔsdhC, EiΔgcvPΔsdhC, EiΔmdhΔsdhC, and EiΔgcvPΔglyA) in channel catfish. The tissue persistence study showed that EiΔsdhC, EiΔfrdA, EiΔfrdAΔsdhC, and EiΔgcvPΔsdhC were able to invade catfish and persist until 11 days post-infection. Vaccination of catfish fingerlings with all nine mutants provided significant (P<0.05) protection against subsequent challenge with the virulent parental strain. Vaccinated catfish fingerlings had 100% survival when subsequently challenged by immersion with wild-type E. ictaluri except for EiΔgcvPΔglyA and EiΔgcvP. Mutant EiΔgcvPΔsdhC was found to be very good at protecting catfish fry, as evidenced by 10-fold higher survival compared to non-vaccinated fish.

  14. Mortality and pathology in brown bullheads Amieurus nebulosus associated with a spontaneous Edwardsiella ictaluri outbreak under tank culture conditions

    USGS Publications Warehouse

    Iwanowicz, L.R.; Griffin, A.R.; Cartwright, Deborah D.; Blazer, V.S.

    2006-01-01

    Brown bullheads Amieurus nebulosus (family Ictaluridae) are commonly used as a sentinel of environmental contamination. These fish are not generally cultured under laboratory conditions and little is known about their disease susceptibility. Here we report an outbreak of disease due to Edwardsiella ictaluri in a laboratory population of tank-reared, wild-caught brown bullheads. The isolate was positively identified as E. ictaluri using standard bacteriological substrate utilization tests and a monoclonal antibody specific for this bacterium. This pathogen causes a significant disease in channel catfish Ictalurus punctatus and is associated with disease in other ictalurid and non-ictalurid fishes. It appears that E. ictaluri is also a significant pathogen in brown bullheads and produces clinical signs and lesions similar but not identical to those observed in channel catfish. Since commercial sources of bullheads for laboratory tank studies are not available, precautions should be taken to prevent potential E. ictaluri disease outbreaks from wild-caught bullheads intended for laboratory research. ?? Inter-Research 2006.

  15. Antimicrobial susceptibility pattern of Edwardsiella ictaluri isolates from natural outbreaks of bacillary necrosis of Pangasianodon hypophthalmus in Vietnam.

    PubMed

    Tu, Thanh Dung; Haesebrouck, Freddy; Nguyen, Anh Tuan; Sorgeloos, Patrick; Baele, Margo; Decostere, Annemie

    2008-12-01

    The purpose of this study was to assess the in vitro susceptibility of 64 Vietnamese isolates of Edwardsiella ictaluri, the causal agent of the infectious disease Bacillus Necrosis Pangasius in Pangasianodon hypophthalmus, using the agar dilution technique. All isolates originated from different farms and were collected between 2002 and 2005. None of the isolates displayed acquired resistance to amoxicillin, amoxicillin-clavulanic acid, chloramphenicol, florfenicol, gentamicin, kanamycin, neomycin, and nitrofurantoin. Acquired resistance to streptomycin was detected in 83%, to oxytetracycline in 81%, and to trimethoprim in 71% of the isolates, as indicated by a bimodal distribution of the minimal inhibitory concentrations (MICs) of these antimicrobials. The MICs of enrofloxacin displayed a monomodal distribution with tailing toward the higher MIC values, possibly indicating reduced susceptibility of a minority of isolates (3 out of the 64). For the quinolone antimicrobial agents flumequin and oxolinic acid, acquired resistance was encountered in 8% and 6% of the strains, respectively. All strains were intrinsically resistant to the polypeptide antimicrobial agent colistin. Seventy-three percent of the isolates were shown to have acquired resistance to at least three antimicrobial agents. The results of this study emphasize the strict need to control both the prophylactic and curative use of antimicrobial agents in Vietnamese aquaculture.

  16. Intraspecific diversity of Edwardsiella ictaluri isolates from diseased freshwater catfish, Pangasianodon hypophthalmus (Sauvage), cultured in the Mekong Delta, Vietnam.

    PubMed

    Bartie, K L; Austin, F W; Diab, A; Dickson, C; Dung, T T; Giacomini, M; Crumlish, M

    2012-09-01

    A molecular epidemiology study was conducted on 90 Edwardsiella ictaluri isolates recovered from diseased farmed freshwater catfish, Pangasianodon hypophthalmus, cultured in the Mekong Delta, Vietnam. Thirteen isolates of E. ictaluri derived from diseased channel catfish, Ictalurus punctatus, cultured in the USA were included for comparison. All the E.ictaluri isolates tested were found to be biochemically indistinguishable. A repetitive (rep)-PCR using the single (GTG)(5) primer was shown to possess limited discriminatory power, yielding two similar DNA profiles categorized as (GTG)(5) -PCR group 1 or 2 among the Vietnam isolates and (GTG)(5) -PCR group 1 within the USA isolates. Macrorestriction analysis identified 14 and 22 unique pulsotypes by XbaI and SpeI, respectively, among a subset of 59 E. ictaluri isolates. Numerical analysis of the combined macrorestriction profiles revealed three main groups: a distinct cluster formed exclusively of the USA isolates, and a major and minor cluster with outliers contained the Vietnam isolates. Antibiotic susceptibility and plasmid profiling supported the existence of the three groups. The results indicate that macrorestriction analysis may be regarded as a suitable typing method among the E. ictaluri species of limited intraspecific diversity. Furthermore, the findings suggest that E. ictaluri originating from Vietnam may constitute a distinct genetic group.

  17. Phenotype, virulence and immunogenicity of Edwardsiella ictaluri cyclic adenosine 3',5'-monophosphate receptor protein (Crp) mutants in catfish host.

    PubMed

    Santander, Javier; Mitra, Arindam; Curtiss, Roy

    2011-12-01

    Edwardsiella ictaluri is an Enterobacteriaceae that causes lethal enteric septicemia in catfish. Being a mucosal facultative intracellular pathogen, this bacterium is an excellent candidate to develop immersion-oral live attenuated vaccines for the catfish aquaculture industry. Deletion of the cyclic 3',5'-adenosine monophosphate (cAMP) receptor protein (crp) gene in several Enterobacteriaceae has been utilized in live attenuated vaccines for mammals and birds. Here we characterize the crp gene and report the effect of a crp deletion in E. ictaluri. The E. ictaluri crp gene and encoded protein are similar to other Enterobacteriaceae family members, complementing Salmonella enterica Δcrp mutants in a cAMP-dependent fashion. The E. ictaluri Δcrp-10 in-frame deletion mutant demonstrated growth defects, loss of maltose utilization, and lack of flagella synthesis. We found that the E. ictaluri Δcrp-10 mutant was attenuated, colonized lymphoid tissues, and conferred immune protection against E. ictaluri infection to zebrafish (Danio rerio) and catfish (Ictalurus punctatus). Evaluation of the IgM titers indicated that bath immunization with the E. ictaluri Δcrp-10 mutant triggered systemic and skin immune responses in catfish. We propose that deletion of the crp gene in E. ictaluri is an effective strategy to develop immersion live attenuated antibiotic-sensitive vaccines for the catfish aquaculture industry.

  18. A novel splicing mutation in the SEDL gene causes spondyloepiphyseal dysplasia tarda in a large Chinese pedigree.

    PubMed

    Wang, Hui; Wu, Weiqing; Xu, Zhiyong; Xie, Jiansheng

    2013-10-21

    The X-linked form of spondyloepiphyseal dysplasia tarda (SEDT, OMIM# 313400) is a rare osteochondrodysplasia caused by mutations in the SEDL (TRAPPC2, OMIM# 300202) gene. It is clinically characterized by disproportionate short stature, barrel-shaped chests and early development of degenerative joint disease. We report here a novel mutation in the intron 3 splice-donor site (c. 93+5G>C) segregated in an X-link pattern in a large Chinese family with SEDT. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the mutation causes an aberrant splicing of exon 3, resulting in the elimination of 31 codons in the exon and a considerable loss function of the SEDL protein. This mutation was not detected in the 100 healthy controls. This novel mutation adds to the spectrum of previously-identified disease-causing mutations. Pre-symptomatic molecular diagnosis and prenatal diagnosis of the pregnant carriers could be helpful to families with SEDT. © 2013 Elsevier B.V. All rights reserved.

  19. [Mutation analysis of the TRAPPC2 gene in a Chinese family with X-linked spondyloepiphyseal dysplasia tarda].

    PubMed

    Wu, Xian; Deng, Kaixian; Wang, Chunjiao; Li, Guifang; Lin, Jing; Wang, Rongpin; Wu, Haili; Huang, Shengwen

    2015-08-01

    To identify potential mutation of TRAPPC2 gene in a Chinese family affected with X-linked spondyloepiphyseal dysplasia tarda (X-SEDL), and explore its underlying molecular mechanism. Peripheral blood samples were collected from 32 members of the family and 50 healthy adults to extract genomic DNA. DNA sequences of exons 3 to 6 and their exon/intron boundaries were amplified with PCR amplification. Direct bi-directional sequencing analysis was performed on the PCR products. The sequences were aligned to the reference sequences from the GenBank to determine mutation site and type. A nucleotide substitution of the splice-donor in TRAPPC2 intron 3, c.93+5G>A, was detected in the proband, but no sequence change was detected in TRAPPC2 exons 3 to 6. All of the 6 male patients and 8 female carriers from the family were detected to have carried this mutation. The same mutation was not found in the remaining 18 family members with a normal phenotype and 50 healthy controls. We have detected a c.93+5G>A mutation in the TRAPPC2 gene in a Chinese family affected with X-SEDL. Our results have expanded the spectrum of TRAPPC2 mutations and is helpful for presymptomatic and prenatal diagnoses of this disease.

  20. Intestinal bacterial flora of the household lizard, Gecko gecko.

    PubMed

    Tan, R J; Lim, E W; Ishak, B

    1978-03-01

    A total of 114 isolates was recovered from the intestines of 43 househould lizards, Gecko gecko. Among the important ones were Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Proteus mirabilis and Edwardsiella tarda.

  1. Chronic Rhinosinusitis Pathogenesis

    PubMed Central

    Stevens, Whitney W.; Lee, Robert J.; Schleimer, Robert P.; Cohen, Noam A.

    2015-01-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation including chronic rhinosinusitis (CRS) and cystic fibrosis. CRS in particular can be divided into two major subgroups based upon whether nasal polyps are present (CRSwNP) or absent (CRSsNP). Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier and tissue remodeling all contribute to the chronic inflammatory and tissue deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and may be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review with special focus placed on the roles of epithelial cells and the host immune response in cystic fibrosis, CRSsNP and CRSwNP. PMID:26654193

  2. Comparative anatomy and histology of developmental and parasitic stages in the life cycle of the lined sea anemone Edwardsiella lineata.

    PubMed

    Reitzel, Adam M; Daly, Marymegan; Sullivan, James C; Finnerty, John R

    2009-02-01

    The evolution of parasitism is often accompanied by profound changes to the developmental program. However, relatively few studies have directly examined the developmental evolution of parasitic species from free-living ancestors. The lined sea anemone Edwardsiella lineata is a relatively recently evolved parasite for which closely related free-living outgroups are known, including the starlet sea anemone Nematostella vectensis. The larva of E. lineata parasitizes the ctenophore Mnemiopsis leidyi, and, once embedded in its host, the anemone assumes a novel vermiform body plan. That we might begin to understand how the developmental program of this species has been transformed during the evolution of parasitism, we characterized the gross anatomy, histology, and cnidom of the parasitic stage, post-parasitic larval stage, and adult stage of the E. lineata life cycle. The distinct parasitic stage of the life cycle differs from the post-parasitic larva with respect to overall shape, external ciliation, cnida frequency, and tissue architecture. The parasitic stage and planula both contain holotrichs, a type of cnida not previously reported in Edwardsiidae. The internal morphology of the post-parasitic planula is extremely similar to the adult morphology, with a complete set of mesenterial tissue and musculature despite this stage having little external differentiation. Finally, we observed 2 previously undocumented aspects of asexual reproduction in E. lineata: (1) the parasitic stage undergoes transverse fission via physal pinching, the first report of asexual reproduction in a pre-adult stage in the Edwardsiidae; and (2) the juvenile polyp undergoes transverse fission via polarity reversal, the first time this form of fission has been reported in E. lineata.

  3. The Aspartate-Semialdehyde Dehydrogenase of Edwardsiella ictaluri and Its Use as Balanced-Lethal System in Fish Vaccinology

    PubMed Central

    Santander, Javier; Xin, Wei; Yang, Zhao; Curtiss, Roy

    2010-01-01

    asdA mutants of Gram-negative bacteria have an obligate requirement for diaminopimelic acid (DAP), which is an essential constituent of the peptidoglycan layer of the cell wall of these organisms. In environments deprived of DAP, i.e., animal tissues, they will undergo lysis. Deletion of the asdA gene has previously been exploited to develop antibiotic-sensitive strains of live attenuated recombinant bacterial vaccines. Introduction of an Asd+ plasmid into a ΔasdA mutant makes the bacterial strain plasmid-dependent. This dependence on the Asd+ plasmid vector creates a balanced-lethal complementation between the bacterial strain and the recombinant plasmid. E. ictaluri is an enteric Gram-negative fish pathogen that causes enteric septicemia in catfish. Because E. ictaluri is a nasal/oral invasive intracellular pathogen, this bacterium is a candidate to develop a bath/oral live recombinant attenuated Edwardsiella vaccine (RAEV) for the catfish aquaculture industry. As a first step to develop an antibiotic-sensitive RAEV strain, we characterized and deleted the E. ictaluri asdA gene. E. ictaluri ΔasdA01 mutants exhibit an absolute requirement for DAP to grow. The asdA gene of E. ictaluri was complemented by the asdA gene from Salmonella. Several Asd+ expression vectors with different origins of replication were transformed into E. ictaluri ΔasdA01. Asd+ vectors were compatible with the pEI1 and pEI2 E. ictaluri native plasmids. The balanced-lethal system was satisfactorily evaluated in vivo. Recombinant GFP, PspA, and LcrV proteins were synthesized by E. ictaluri ΔasdA01 harboring Asd+ plasmids. Here we constructed a balanced-lethal system, which is the first step to develop an antibiotic-sensitive RAEV for the aquaculture industry. PMID:21209920

  4. Effects of ammonia stress, dietary linseed oil and Edwardsiella ictaluri challenge on juvenile darkbarbel catfish Pelteobagrus vachelli.

    PubMed

    Li, Ming; Yu, Na; Qin, Jian G; Li, Erchao; Du, Zhenyu; Chen, Liqiao

    2014-05-01

    A two-stage study was carried out to test the response of juvenile darkbarbel catfish Pelteobagrus vachelli to ammonia stress, dietary lipid and bacterial challenge. At stage 1, the catfish (0.99 ± 0.01 g) fed a commercial diet were exposed to 0.01 and 5.70 mg L(-1) total ammonia nitrogen in nine replicates for 14 days. At stage 2, all fish previously exposed to either low or high ammonia were separately transferred into low ammonia (<0.01 mg L(-1)), and divided into three feeding groups. Fish were then fed three levels of linseed oil (0, 2 and 4%) in triplicate for 46 days. Fish growth performance and immune response were low in high ammonia at stage 1. At stage 2, fish growth and immune response were not significantly different between fish previously exposed to low and high ammonia in all diets. Fish fed 4% linseed oil showed the greatest weight gain, feed efficiency ratio, red blood cells, hemoglobin and hematocrit, and achieved higher lysozyme activity, phagocytic index, respiratory burst and total immunoglobulin than fish fed 0% linseed oil, but did not differ from fish fed 2% linseed oil regardless of previous ammonia exposure. After 14-day infection of Edwardsiella ictaluri, cumulative mortality of fish previously exposed to low ammonia was lower than that of fish exposed to high ammonia in all diets. Cumulative mortality of fish fed 0% linseed oil was highest, but the antibody titer of fish fed 4% linseed oil was highest regardless of previous ammonia treatments. This study indicates that ammonia stress has a lasting effect even after ammonia is lowed, but the adverse effect on fish can be mitigated through manipulation of dietary oil inclusion, especially under the challenge of pathogenic bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Effects of cortisol and stress on channel catfish (Ictalurus punctatus) pathogen susceptibility and lysozyme activity following exposure to Edwardsiella ictaluri.

    PubMed

    Small, Brian C; Bilodeau, A Lelania

    2005-05-15

    Periods of stress are often associated with disease outbreaks in cultured fish, and stress is often characterized by the secretion of cortisol. Although stress and cortisol secretion are highly correlated in fish, the role of cortisol in affecting channel catfish (Ictalurus punctatus) pathogen susceptibility is unclear. The effects of short-term stress and exogenous cortisol administration on channel catfish susceptibility to Edwardsiella ictaluri, the etiologic agent of enteric septicemia of catfish (ESC), were investigated. Channel catfish were exposed to virulent E. ictaluri following a standardized 30-min low-water stress or administration of dietary cortisol (100 mg/kg feed) and compared to a pathogen-challenged control group of catfish. Pathogen susceptibility increased in stressed catfish (43.3% mortality) when compared to cortisol-fed catfish (26.7%) and controls (26.7%). A greater (P<0.05) percentage of stressed catfish (25.9%) tested positive for E. ictaluri relative to cortisol-fed catfish (13.0%) over the course of the study, however, average levels of circulating bacteria were not different (P>0.05) among the treatments. Catfish challenged by the low-water stress event had elevated (P<0.05) circulating levels of cortisol 1-day post-pathogen exposure and elevated (P<0.05) lysozyme activity 4 and 14 days post-pathogen exposure when compared to cortisol-fed and control-challenged catfish. Cortisol concentrations were not correlated (P>0.05) to either lysozyme activity or bacterial levels; however, lysozyme activity was positively correlated (P=0.0197) to blood bacterial concentrations. These results implicate other stress factors or pathways, separate from or possibly in conjunction with cortisol, in the stress-associated immunosuppression of channel catfish as it relates to ESC susceptibility.

  6. Modulation of vacuolar pH is required for replication of Edwardsiella ictaluri in channel catfish macrophages.

    PubMed

    Baumgartner, Wes A; Dubytska, Lidiya; Rogge, Matthew L; Mottram, Peter J; Thune, Ronald L

    2014-06-01

    Previous in vitro work demonstrated that Edwardsiella ictaluri produces an acid-activated urease that can modulate environmental pH through the production of ammonia from urea. Additional work revealed that expression of the E. ictaluri type III secretion system (T3SS) is upregulated by acidic pH. Both the urease and the T3SS were previously shown to be essential to intracellular replication. In this work, fluorescence microscopy with LysoTracker Red DND-99 (LTR) indicated that E. ictaluri-containing vacuoles (ECV) became acidified following ingestion by head kidney-derived macrophages (HKDM). In vivo ratiometric imaging demonstrated a lowered ECV pH, which fell to as low as pH 4 but subsequently increased to pH 6 or greater. Inhibition of vacuolar H(+)-ATPases by use of the specific inhibitor bafilomycin A1 abrogated both ECV acidification and intracellular replication in HKDM. Failure of an E. ictaluri urease knockout mutant to increase the ECV pH in the in vivo ratiometric assay suggests that ammonia produced by the urease reaction mediates the pH increase. Additionally, when the specific arginase inhibitor l-norvaline was used to treat E. ictaluri-infected HKDM, the ECV failed to neutralize and E. ictaluri was unable to replicate. This indicates that the HKDM-encoded arginase enzyme produces the urea used by the E. ictaluri urease enzyme. Failure of the ECV to acidify would prevent both upregulation of the T3SS and activation of the urease enzyme, either of which would prevent E. ictaluri from replicating in HKDM. Failure of the ECV to neutralize would result in a vacuolar pH too low to support E. ictaluri replication.

  7. Low-Dose Hydroxychloroquine is as Effective as Phlebotomy in Treatment of Patients with Porphyria Cutanea Tarda

    PubMed Central

    Singal, Ashwani K.; Kormos-Hallberg, Csilla; Lee, Chul; Sadagoparamanujam, V.-M.; Grady, James J.; Freeman, Daniel H.; Anderson, Karl E.

    2012-01-01

    Background & Aims Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. Methods We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. Results The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. Conclusions Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. PMID:22985607

  8. CYP1A2*1F and GSTM1 Alleles Are Associated with Susceptibility to Porphyria Cutanea Tarda

    PubMed Central

    Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z; Lee, Chul; Kormos-Hallberg, Csilla; Sood, Gagan; Rondelli, Catherine M; Grady, James J; Desnick, Robert J; Anderson, Karl E

    2011-01-01

    Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1. PCT diagnosis was based on urinary or plasma porphyrin profiles. Patients were classified as type 1 or 2 PCT based on UROD mutation analysis. The CYP1A2*1F promoter A allele frequency was significantly higher (P < 0.022) and the A/A genotype frequency marginally higher in PCT patients overall (P < 0.057), with the A/A genotype significantly more common in type 1 PCT (P < 0.043). The presence of the wild-type GSTM1 allele also was associated significantly with PCT (P < 0.019). Neither hemochromatosis (HFE) mutations, tobacco smoking, hepatitis C and HIV infection, ethanol consumption, nor estrogen use were associated with these allelic variants. Age at onset was significantly lower in type 2 PCT patients (P < 0.001), as observed previously. Thus, positive associations between PCT and the CYP1A2*1F promoter A allele and A/A genotype and the wild-type GSTM1 allele indicates that these functional hepatic biotransformation enzymes are risk factors for the development of this disease. PMID:20957336

  9. The D519G Polymorphism of Glyceronephosphate O-Acyltransferase Is a Risk Factor for Familial Porphyria Cutanea Tarda

    PubMed Central

    Farrell, Colin P.; Overbey, Jessica R.; Naik, Hetanshi; Nance, Danielle; McLaren, Gordon D.; McLaren, Christine E.; Zhou, Luming; Desnick, Robert J.; Parker, Charles J.

    2016-01-01

    Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G, rs11558492) of glyceronephosphate O-acyltransferase (GNPAT) was shown to be enriched in male patients with type I hereditary hemochromatosis (HFE C282Y homozygotes) who presented with a high iron phenotype, suggesting that GNPAT D519G, like HFE C282Y, is a modifier of iron homeostasis that favors iron absorption. To challenge this hypothesis, we investigated the frequency of GNPAT D519G in patients with both familial and sporadic PCT. Patients were screened for GNPAT D519G and allelic variants of HFE (both C282Y and H63D). Nucleotide sequencing of uroporphyrinogen decarboxylase (URO-D) identified mutant alleles. Patients with low erythrocyte URO-D activity or a damaging URO-D variant were classified as familial PCT (fPCT) and those with wild-type URO-D were classified as sporadic PCT (sPCT). GNPAT D519G was significantly enriched in the fPCT patient population (p = 0.0014) but not in the sPCT population (p = 0.4477). Both HFE C282Y and H63D (c.187C>G, rs1799945) were enriched in both PCT patient populations (p<0.0001) but showed no greater association with fPCT than with sPCT. Conclusion: GNPAT D519G is a risk factor for fPCT, but not for sPCT. PMID:27661980

  10. Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles.

    PubMed Central

    Mendez, M; Sorkin, L; Rossetti, M V; Astrin, K H; del C Batlle, A M; Parera, V E; Aizencang, G; Desnick, R J

    1998-01-01

    Familial porphyria cutanea tarda (f-PCT) results from the half-normal activity of uroporphyrinogen decarboxylase (URO-D). Heterozygotes for this autosomal dominant trait are predisposed to photosensitive cutaneous lesions by various ecogenic factors, including iron overload and alcohol abuse. The 3.6-kb URO-D gene was completely sequenced, and a long-range PCR method was developed to amplify the entire gene for mutation analysis. Four missense mutations (M165R, L195F, N304K, and R332H), a microinsertion (g10insA), a deletion (g645Delta1053), and a novel exonic splicing defect (E314E) were identified. Expression of the L195F, N304K, and R332H polypeptides revealed significant residual activity, whereas reverse transcription-PCR and sequencing demonstrated that the E314E lesion caused abnormal splicing and exon 9 skipping. Haplotyping indicated that three of the four families with the g10insA mutation were unrelated, indicating that these microinsertions resulted from independent mutational events. Screening of nine f-PCT probands revealed that 44% were heterozygous or homozygous for the common hemochromatosis mutations, which suggests that iron overload may predispose to clinical expression. However, there was no clear correlation between f-PCT disease severity and the URO-D and/or hemochromatosis genotypes. These studies doubled the number of known f-PCT mutations, demonstrated that marked genetic heterogeneity underlies f-PCT, and permitted presymptomatic molecular diagnosis and counseling in these families to enable family members to avoid disease-precipitating factors. PMID:9792863

  11. Pathogenesis of microbial keratitis.

    PubMed

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-03-01

    Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field.

  12. Pathogenesis of Rhinovirus Infection

    PubMed Central

    Kennedy, Joshua L; Turner, Ronald B.; Braciale, Thomas; Heymann, Peter W.; Borish, Larry

    2012-01-01

    Summary Since its discovery in 1956, rhinovirus (RV) has been recognized as the most important virus producing the common cold syndrome. Despite its ubiquity, little is known concerning the pathogenesis of RV infections, and some of the research in this area has led to contradictions regarding the molecular and cellular mechanisms of RV-induced illness. In this article, we discuss the pathogenesis of this virus as it relates to RV-induced illness in the upper and lower airway, an issue of considerable interest in view of the minimal cytopathology associated with RV infection. We endeavor to explain why many infected individuals exhibit minimal symptoms or remain asymptomatic, while others, especially those with asthma, may have severe, even life-threatening, complications (sequelae). Finally, we discuss the immune responses to RV in the normal and asthmatic host focusing on RV infection and epithelial barrier integrity and maintenance as well as the impact of the innate and adaptive immune responses to RV on epithelial function. PMID:22542099

  13. Update on mucormycosis pathogenesis

    PubMed Central

    Ibrahim, Ashraf S.; Kontoyiannis, Dimitrios P.

    2014-01-01

    Purpose of review Mucormycosis is an increasingly common fungal infection with unacceptably high mortality. The recent sequencing genome projects of Mucorales and the development of gene manipulation have enabled significant advances in understanding the pathogenesis of mucormycosis. Therefore, we review the pathogenesis of mucormycosis and highlight potential development of novel diagnostic and therapeutic modalities against this lethal disease. Recent findings Much of the work has been focused on the role of iron uptake in the virulence of Mucorales. Additionally, host receptors and fungal ligands involved in the process of tissue invasion as well as sporangiospore size and sex loci and their contribution to virulence of Mucorales are discussed. Finally, the role of innate and adaptive immunity in protection against Mucorales and new evidence about drug-induced apoptosis in these fungi are discussed. Summary Recent discoveries introduce several potentially novel diagnostic and therapeutic modalities, which are likely to improve management and outcome for mucormycosis. Future preclinical and clinical research is warranted to develop these diagnostic and therapeutic strategies. PMID:24126718

  14. Pathogenesis of Raynaud's phenomenon.

    PubMed

    Herrick, A L

    2005-05-01

    The pathogenesis of Raynaud's phenomenon is not fully understood. However, the last 20 yr have witnessed enormous increases in our understanding of different mechanisms which, singly or in combination, may contribute. A key point is that Raynaud's phenomenon can be either primary (idiopathic) or secondary to a number of underlying conditions, and that the pathogenesis and pathophysiology vary between these conditions. This review concentrates upon those subtypes of Raynaud's phenomenon of most interest to rheumatologists: systemic sclerosis-related Raynaud's phenomenon, primary Raynaud's phenomenon and Raynaud's phenomenon secondary to hand-arm vibration syndrome. In this review, I shall discuss the main mechanisms thought to be important in pathophysiology under the three broad headings of 'vascular', 'neural' and 'intravascular'. While these are false distinctions because all interrelate, they facilitate discussion of the key elements: the blood vessel wall (particularly the endothelium), the neural control of vascular tone, and the many circulating factors which can impair blood flow and/or cause endothelial injury. Vascular abnormalities include those of both structure and function. Neural abnormalities include deficiency of the vasodilator calcitonin gene-related peptide (released from sensory afferents), alpha(2)-adrenoreceptor activation (possibly with up-regulation of the normally 'silent' alpha(2C)-adrenoreceptor) and a central nervous system component. Intravascular abnormalities include platelet activation, impaired fibrinolysis, increased viscosity and probably oxidant stress. As our understanding of the pathophysiology of Raynaud's phenomenon increases, so do our possibilities for identifying effective treatments.

  15. Porphyria Cutanea Tarda in a Patient with End-Stage Renal Disease: A Case of Successful Treatment with Deferoxamine and Ferric Carboxymaltose.

    PubMed

    Rodrigues, Natacha; Caeiro, Fernando; Santana, Alice; Mendes, Teresa; Lopes, Leonor

    2017-01-01

    Porphyria cutanea tarda (PCT) is a rare disease, with a strong association with hepatitis C virus. PCT is particularly problematic in end-stage renal disease patients as they have no renal excretion of porphyrins and these are poorly dialyzed. Also, conventional treatment of PCT is compromised in these patients as hydroxychloroquine is contraindicated, phlebotomies with the stipulated frequency are poorly tolerated in already anaemia-prone patients, and iron-chelating agents are less efficient in removing iron and contribute to worsening anaemia. The authors report a patient on haemodialysis, with hepatitis C infection, that is diagnosed with PCT. Despite the good clinical results with deferoxamine, she became dependent on blood transfusions because of her ferropenic state. Every time oxide iron was started, the patient developed clinical features of the disease, resolving after the suspension of the drug. A decision was made to start the patient on ferric carboxymaltose, which was well tolerated without disease symptoms and need of further blood transfusions. This case suggests that deferoxamine is efficient in treatment of porphyria cutanea tarda. Also, ferric carboxymaltose may be a valuable option for refractory anaemia in patients with this disease and end-stage renal disease, as it seems to provide iron without clinical relapse of the disease.

  16. Porphyria Cutanea Tarda in a Patient with End-Stage Renal Disease: A Case of Successful Treatment with Deferoxamine and Ferric Carboxymaltose

    PubMed Central

    Caeiro, Fernando; Santana, Alice; Mendes, Teresa; Lopes, Leonor

    2017-01-01

    Porphyria cutanea tarda (PCT) is a rare disease, with a strong association with hepatitis C virus. PCT is particularly problematic in end-stage renal disease patients as they have no renal excretion of porphyrins and these are poorly dialyzed. Also, conventional treatment of PCT is compromised in these patients as hydroxychloroquine is contraindicated, phlebotomies with the stipulated frequency are poorly tolerated in already anaemia-prone patients, and iron-chelating agents are less efficient in removing iron and contribute to worsening anaemia. The authors report a patient on haemodialysis, with hepatitis C infection, that is diagnosed with PCT. Despite the good clinical results with deferoxamine, she became dependent on blood transfusions because of her ferropenic state. Every time oxide iron was started, the patient developed clinical features of the disease, resolving after the suspension of the drug. A decision was made to start the patient on ferric carboxymaltose, which was well tolerated without disease symptoms and need of further blood transfusions. This case suggests that deferoxamine is efficient in treatment of porphyria cutanea tarda. Also, ferric carboxymaltose may be a valuable option for refractory anaemia in patients with this disease and end-stage renal disease, as it seems to provide iron without clinical relapse of the disease. PMID:28210512

  17. Controversies in dengue pathogenesis

    PubMed Central

    Halstead, Scott B

    2012-01-01

    Research into the pathogenesis of dengue fever has exploded over the last half-century, with issues that were considered simple becoming more complex as additional data are found. This has led to the development of a number of controversies that are being studied across the globe and debated in the literature. In this paper, the following six controversies are analysed and, where possible, resolved: the 1997 World Health Organization (WHO) case definition of dengue haemorrhagic fever (DHF) is not useful; DHF is not significantly associated with secondary dengue infection; DHF results from infection with a ‘virulent’ dengue virus; DHF is owing to abnormal T-cell responses; DHF results from auto-immune responses; and DHF results from direct infection of endothelial cells. PMID:22668442

  18. Pathogenesis of Lassa fever.

    PubMed

    Yun, Nadezhda E; Walker, David H

    2012-10-09

    Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.

  19. The Pathogenesis of Sepsis

    PubMed Central

    Stearns-Kurosawa, Deborah J.; Osuchowski, Marcin F.; Valentine, Catherine; Kurosawa, Shinichiro; Remick, Daniel G.

    2013-01-01

    Sepsis is a serious clinical condition that represents a patient’s response to a severe infection and has a very high mortality rate. Normal immune and physiologic responses eradicate pathogens, and the pathophysiology of sepsis is due to the inappropriate regulation of these normal reactions. In an ideal scenario, the first pathogen contact with the inflammatory system should eliminate the microbe and quickly return the host to homeostasis. The septic response may accelerate due to continued activation of neutrophils and macrophages/monocytes. Upregulation of lymphocyte costimulatory molecules and rapid lymphocyte apoptosis, delayed apoptosis of neutrophils, and enhanced necrosis of cells/tissues also contribute to the pathogenesis of sepsis. The coagulation system is closely tied to the inflammatory response, with cross talk between the two systems driving the dysregulated response. Biomarkers may be used to help diagnose patients with sepsis, and they may also help to identify patients who would benefit from immunomodulatory therapies. PMID:20887193

  20. Pathogenesis of Lassa Fever

    PubMed Central

    Yun, Nadezhda E.; Walker, David H.

    2012-01-01

    Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. PMID:23202452

  1. Molecular pathogenesis of emphysema

    PubMed Central

    Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.

    2008-01-01

    Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema. PMID:18246188

  2. Molecular Pathogenesis of NASH

    PubMed Central

    Caligiuri, Alessandra; Gentilini, Alessandra; Marra, Fabio

    2016-01-01

    Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. PMID:27657051

  3. Molecular pathogenesis of emphysema.

    PubMed

    Taraseviciene-Stewart, Laimute; Voelkel, Norbert F

    2008-02-01

    Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema.

  4. Pathogenesis of infantile haemangioma.

    PubMed

    Greenberger, S; Bischoff, J

    2013-07-01

    Haemangioma is a vascular tumour of infancy that is well known for its rapid growth during the first weeks to months of a child's life, followed by a spontaneous but slow involution. During the proliferative phase, the vessels are disorganized and composed of immature endothelial cells. When the tumour involutes, the vessels mature and enlarge but are reduced in number. Fat, fibroblasts and connective tissue replace the vascular tissue, with few, large, feeding and draining vessels evident. Both angiogenesis and vasculogenesis have been proposed as mechanisms contributing to the neovascularization in haemangioma tumours. In recent years, several of the 'building blocks', the cells comprising the haemangioma, have been isolated. Among them are haemangioma progenitor/stem cells, endothelial cells and pericytes. This review focuses on these cell types, and the molecular pathways within these cells that have been implicated in driving the pathogenesis of infantile haemangioma.

  5. [Pathogenesis of rheumatoid arthritis].

    PubMed

    Branimir Anić; Miroslav Mayer

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc

  6. Pathogenesis of acne.

    PubMed

    Toyoda, M; Morohashi, M

    2001-03-01

    Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous

  7. Pathogenesis of nasal polyposis

    PubMed Central

    Hulse, K. E.; Stevens, W. W.; Tan, B. K.; Schleimer, R. P.

    2015-01-01

    Summary Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world-wide and is associated with high cost of management and significant morbidity. Yet, there is a lack of population-based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL-5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease. PMID:25482020

  8. The two channel catfish intelectin genes exhibit highly differential patterns of tissue expression and regulation after infection with Edwardsiella ictaluri.

    PubMed

    Takano, Tomokazu; Sha, Zhenxia; Peatman, Eric; Terhune, Jeffery; Liu, Hong; Kucuktas, Huseyin; Li, Ping; Edholm, Eva-Stina; Wilson, Melanie; Liu, Zhanjiang

    2008-01-01

    Intelectins (IntL) are Ca(2+)-dependent secretory glycoproteins that play a role in the innate immune response. The mammalian IntL is also known as lactoferrin receptor (LfR) that is involved in iron metabolism. The objective of this study was to characterize the intelectin genes in both channel catfish and blue catfish, to determine their genomic organization and copy numbers, to determine their patterns of tissue expression, and to establish if they are involved in defense responses of catfish after bacterial infection. Two types of IntL genes have been identified from catfish, and IntL2 was completely sequenced. The genomic structure and organization of IntL2 were similar to those of the mammalian species and of zebrafish and grass carp, but orthologies cannot be established with mammalian IntL genes. The IntL genes are highly conserved through evolution. Sequence analysis also indicated the presence of the fibrinogen-related domain in the catfish IntL genes, suggesting their structural conservations. Phylogenetic analysis suggested the presence of at least two prototypes of IntL genes in teleosts, but only one in mammals. The catfish IntL genes exhibited drastically different patterns of expression as compared to those of the mammalian species, or even with the grass carp gene. The catfish IntL1 gene is widely expressed in various tissues, whereas the channel catfish IntL2 gene was mainly expressed in the liver. While the catfish IntL1 is constitutively expressed, the catfish IntL2 was drastically induced by intraperitoneal injection of Edwardsiella ictaluri and/or iron dextran. Such induction was most dramatic when the fish were treated with both the bacteria and iron dextran. While IntL1 was expressed in all leukocyte cell lines, no expression of IntL2 was detected in any of the leukocyte cell lines, suggesting that the up-regulated channel catfish IntL2 expression after bacterial infection may be a consequence of the initial immune response, and/or a

  9. Pathogenesis of liver cirrhosis.

    PubMed

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-06-21

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

  10. Acromegaly pathogenesis and treatment

    PubMed Central

    Melmed, Shlomo

    2009-01-01

    Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly — a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder. PMID:19884662

  11. Pathogenesis of liver cirrhosis

    PubMed Central

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-01-01

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

  12. Pathogenesis of tinea.

    PubMed

    Brasch, Jochen

    2010-10-01

    Dermatophytes are hyphomycetes that can degrade keratin. This puts them in a position to cause infections of the keratin-containing superficial skin. The resulting clinical picture is called tinea. The pathogenesis and course of tinea is decisively determined by pathogen-related factors and by the defense mechanisms of the host. An infection starts with an adherence of fungal propagules, followed by the formation of hyphae that can spread within the tissue. This process is accompanied by a release of fungal enzymes and other pathogenic factors. Next keratinocytes are activated, the epidermal barrier is destroyed, epidermal proliferation is enhanced and defensins are expressed within the epidermis. In addition, innate and specific immune responses are initiated, involving neutrophilic granulocytes, macrophages, antibodies and T cells. The cellular mechanisms are thought to be crucial for healing. Special conditions apply to nail infections, because within nail plates the fungi are not accessible to effective defense mechanisms, as well as to infections of hair follicles that contain specific concentrations of steroid hormones. Dermatophytes that penetrate into the dermis can cause granulomatous inflammatory reactions and systemic immune reactions are supposed to be a trigger of so-called id reactions. © The Author • Journal compilation © Blackwell Verlag GmbH, Berlin.

  13. Pathogenesis of Mucormycosis

    PubMed Central

    Spellberg, Brad; Walsh, Thomas J.; Kontoyiannis, Dimitrios P.

    2012-01-01

    Mucormycosis is a life-threatening infection that occurs in patients who are immunocompromised because of diabetic ketoacidosis, neutropenia, organ transplantation, and/or increased serum levels of available iron. Because of the increasing prevalence of diabetes mellitus, cancer, and organ transplantation, the number of patients at risk for this deadly infection is increasing. Despite aggressive therapy, which includes disfiguring surgical debridement and frequently adjunctive toxic antifungal therapy, the overall mortality rate is high. New strategies to prevent and treat mucormycosis are urgently needed. Understanding the pathogenesis of mucormycosis and the host response to invading hyphae ultimately will provide targets for novel therapeutic interventions. In this supplement, we review the current knowledge about the virulence traits used by the most common etiologic agent of mucormycosis, Rhizopus oryzae. Because patients with elevated serum levels of available iron are uniquely susceptible to mucormycosis and these infections are highly angioinvasive, emphasis is placed on the ability of the organism to acquire iron from the host and on its interactions with endothelial cells lining blood vessels. Several promising therapeutic strategies in preclinical stages are identified. PMID:22247441

  14. Kaposi sarcoma herpesvirus pathogenesis

    PubMed Central

    Koch, Sandra; Schulz, Thomas F.

    2017-01-01

    Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

  15. Staphylococcus epidermidis pathogenesis.

    PubMed

    Otto, Michael

    2014-01-01

    Staphylococcus epidermidis is the most frequently encountered member of the coagulase-negative staphylococci on human epithelial surfaces. It has emerged as an important nosocomial pathogen, especially in infections of indwelling medical devices. The mechanisms that S. epidermidis uses to survive during infection are in general of a passive nature, reflecting their possible origin in the commensal life of this bacterium. Most importantly, S. epidermidis excels in forming biofilms, sticky agglomerations that inhibit major host defense mechanisms. Furthermore, S. epidermidis produces a series of protective surface polymers and exoenzymes. Moreover, S. epidermidis has the capacity to secrete strongly cytolytic members of the phenol-soluble modulin (PSM) family, but PSMs in S. epidermidis overall appear to participate primarily in biofilm development. Finally, there is evidence for a virulence gene reservoir function of S. epidermidis, as it appears to have transferred important immune evasion and antibiotic resistance factors to Staphylococcus aureus. Conversely, S. epidermidis also has a beneficial role in balancing the microflora on human epithelial surfaces by controlling outgrowth of harmful bacteria such as in particular S. aureus. Recent research yielded detailed insight into key S. epidermidis virulence determinants and their regulation, in particular as far as biofilm formation is concerned, but we still have a serious lack of understanding of the in vivo relevance of many pathogenesis mechanisms and the factors that govern the commensal life of S. epidermidis.

  16. Recent progress in melasma pathogenesis.

    PubMed

    Lee, Ai-Young

    2015-11-01

    Melasma is a common skin pigmentation condition. Given therapeutic difficulty as one of the biggest concerns, understanding of the etiology and pathogenesis of melasma becomes essential. UV irradiation, female sex hormones, and inflammatory processes are addressed as triggering factors with genetic predisposition. The mechanism of UV-induced melanogenesis has been extensively investigated as a model system to study melasma pathogenesis. Hitherto, treatment modalities for melasma are similar to other hyperpigmentation disorders. However, individual triggering factors induce a separate pigmentation disease, whose pathogenic mechanisms and clinical phenotypes are different from the ones encountered in melasma. Fortunately, there have been ongoing updates on melasma pathogenesis with regard to major triggering factors. Presence of certain factors working independently of UV exposure and role of dermal factors and microRNAs are being identified as novel discoveries about melasma pathogenesis. In this review, the melasma pathogenesis is reviewed in association with updated and new findings.

  17. Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: a case report and literature review

    PubMed Central

    Gunn, G. Brandon; Anderson, Karl E.; Patel, Abhilasha J.; Gallegos, Juan; Hallberg, Csilla K.; Sood, Gagan; Hatch, Sandra S.; Sanguineti, Giuseppe

    2009-01-01

    Background Some porphyrias are associated with cutaneous phototoxicity due to photoactivation of porphyrins, but whether ionizing radiation can have an additive effect is not clear. We report a case of severe radiation therapy-related toxicity in a patient with porphyria cutanea tarda and review the literature. Methods A 50 year-old man with porphyria cutanea was treated for lower lip squamous cell carcinoma with definitive radiation therapy. During radiation therapy acute toxicity was of an expected onset and severity. Six months after treatment completion, he developed skin hypopigmentation, soft tissue fibrosis, and areas of painful denuded skin and crusting within the previous treatment field. Results Reports of 7 porphyria patients receiving radiation therapy to at least 9 separate sites were reviewed, with only one previous report suggestive of increased radiation therapy-related toxicity. Conclusions Based on this report and one other, caution is warranted when considering radiation therapy in patients with active porphyria. PMID:19536857

  18. Highlights in pathogenesis of vitiligo.

    PubMed

    Mohammed, Ghada F; Gomaa, Amal Ha; Al-Dhubaibi, Mohammed Saleh

    2015-03-16

    Vitiligo is a common pigmentary disorder. Many studies across decades and all over the world have attempted to illustrate the pathogenesis behind it; however, the pathogenesis of vitiligo remains elusive. This review article, we present the findings behind the most and updated theories behind this psychologically debilitating and disfiguring disease. The discussion begun with the role of genetic predisposition followed by neural theory first proposed in the 1950s. We highlight the autoimmune hypothesis, followed by the reactive oxygen species model, zinc-α2-glycoprotein deficiency hypothesis, viral theory, intrinsic theory and biochemical, molecular and cellular alterations accounting for loss of functioning melanocytes in vitiligo. Many theories were elaborated to clarify vitiligo pathogenesis. It is a multifactorial disease involving the interplay of several factors. Future research is needed to clarify the interaction of these factors for better understanding of vitiligo pathogenesis and subsequent successful treatment.

  19. Highlights in pathogenesis of vitiligo

    PubMed Central

    Mohammed, Ghada F; Gomaa, Amal HA; Al-Dhubaibi, Mohammed Saleh

    2015-01-01

    Vitiligo is a common pigmentary disorder. Many studies across decades and all over the world have attempted to illustrate the pathogenesis behind it; however, the pathogenesis of vitiligo remains elusive. This review article, we present the findings behind the most and updated theories behind this psychologically debilitating and disfiguring disease. The discussion begun with the role of genetic predisposition followed by neural theory first proposed in the 1950s. We highlight the autoimmune hypothesis, followed by the reactive oxygen species model, zinc-α2-glycoprotein deficiency hypothesis, viral theory, intrinsic theory and biochemical, molecular and cellular alterations accounting for loss of functioning melanocytes in vitiligo. Many theories were elaborated to clarify vitiligo pathogenesis. It is a multifactorial disease involving the interplay of several factors. Future research is needed to clarify the interaction of these factors for better understanding of vitiligo pathogenesis and subsequent successful treatment. PMID:25789295

  20. Concepts in viral pathogenesis II

    SciTech Connect

    Notkins, A.L.; Oldstone, M.B.A.

    1986-01-01

    This paper contains papers divided among 10 sections. The section titles are: Viral Structure and Function; Viral Constructs; Oncogenes, Transfection, and Differentiation; Viral Tropism and Entry into Cells; Immune Recognition of Viruses; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Plant and Animal Models; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Diseases in Humans; New Trends in Diagnosis and Epidemiology; and Vaccines and Antiviral Therapy.

  1. Porphyria Cutanea Tarda (PCT)

    MedlinePlus

    ... symptoms. Most forms of porphyria are genetic inborn errors of metabolism. PCT is an acquired liver disease, ... novo) mutation in the affected individual with no family history. The risk of passing the abnormal gene ...

  2. Porphyria Cutanea Tarda

    MedlinePlus

    ... Sections of the JAOCD JAOCD Archive Published Members Online Dermatology Journals Edit This Favorite Name: Category: Share: Yes ... 1/2017 2017 AOCD Spring Current Concepts in Dermatology Meeting more Latest News ... Surveys About AOCD The AOCD was recognized in ...

  3. Huntington disease: pathogenesis and treatment.

    PubMed

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment.

  4. Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

    PubMed Central

    Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

    2014-01-01

    Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

  5. Evaluation of a loop-mediated isothermal amplification method for rapid detection of channel catfish Ictalurus punctatus important bacterial pathogen Edwardsiella ictaluri.

    PubMed

    Yeh, Hung-Yueh; Shoemaker, Craig A; Klesius, Phillip H

    2005-10-01

    Channel catfish Ictalurus punctatus infected with Edwardsiella ictaluri results in 40--50 million dollars annual losses in profits to catfish producers. Early detection of this pathogen is necessary for disease control and reduction of economic loss. In this communication, the loop-mediated isothermal amplification method (LAMP) that amplifies DNA with high specificity and rapidity at an isothermal condition was evaluated for rapid detection of E. ictaluri. A set of four primers, two outer and two inner, was designed specifically to recognize the eip 18 gene of this pathogen. The LAMP reaction mix was optimized. Reaction temperature and time of the LAMP assay for the eip 18 gene were also optimized at 65 degrees C for 60 min, respectively. Our results show that the ladder-like pattern of bands sizes from 234 bp specifically to the E. ictaluri gene was amplified. The detection limit of this LAMP assay was about 20 colony forming units. In addition, this optimized LAMP assay was used to detect the E. ictaluri eip 18 gene in brains of experimentally challenged channel catfish. Thus, we concluded that the LAMP assay can potentially be used for rapid diagnosis in hatcheries and ponds.

  6. Matrix-assisted laser desorption ionization-time of flight mass spectrometry based identification of Edwardsiella ictaluri isolated from Vietnamese striped catfish (Pangasius hypothalamus)

    PubMed Central

    Nhu, Truong Quynh; Park, Seong Bin; Kim, Si Won; Lee, Jung Seok; Im, Se Pyeong; Lazarte, Jassy Mary S.; Seo, Jong Pyo; Lee, Woo-Jai; Kim, Jae Sung

    2016-01-01

    Edwardsiella (E.) ictaluri is a major bacterial pathogen that affects commercially farmed striped catfish (Pangasius hypothalamus) in Vietnam. In a previous study, 19 strains of E. ictaluri collected from striped catfish were biochemically identified with an API-20E system. Here, the same 19 strains were used to assess the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS; applied using a MALDI Biotyper) to conduct rapid, easy and accurate identification of E. ictaluri. MALDI-TOF MS could directly detect the specific peptide patterns of cultured E. ictaluri colonies with high (> 2.0, indicating species-level identification) scores. MALDI Biotyper 3.0 software revealed that all of the strains examined in this study possessed highly similar peptide peak patterns. In addition, electrophoresis (SDS-PAGE) and subsequent immuno-blotting using a specific chicken antibody (IgY) against E. ictaluri revealed that the isolates had highly similar protein profiles and antigenic banding profiles. The results of this study suggest that E. ictaluri isolated from striped catfish in Vietnam have homologous protein compositions. This is important, because it indicates that MALDI-TOF MS analysis could potentially outperform the conventional methods of identifying E. ictaluri. PMID:26726022

  7. A skin disease, a blood disease or something in between? An exploratory focus group study of patients' experiences with porphyria cutanea tarda*

    PubMed Central

    Andersen, J; Gjengedal, E; Sandberg, S; Råheim, M

    2015-01-01

    Background Porphyria cutanea tarda (PCT) is characterized by fragile skin with blistering on sun-exposed areas. Symptoms typically develop in late adulthood and can be triggered by iron overload, alcohol intake, oestrogens and various liver diseases. Treatment consists of phlebotomy to reduce iron, or increasing urinary porphyrin excretion by administering chlorochin. To optimize patient care, health personnel need to understand the subjective experiences of PCT. Objectives To explore the experiences of persons with PCT with regard to symptoms, treatment, follow-up and prevention of the disease. Methods Interpretive description was used as a qualitative approach. Twenty-one participants attended three focus groups. All participants had experienced PCT symptoms during the last 5 years. Results Participants' experiences varied from trivializing symptoms and fragile skin to what was described as a desperate situation, with huge blisters, skin falling off and feeling as if one was in a ‘horror movie’. For some, itching was very troublesome, preventing sleep and delaying skin healing. In managing PCT a shift in focus from skin to blood was described. PCT was perceived as a chronic and systemic disease causing a range of health problems. Strategies for preventing symptoms ranged from doing nothing to frequent controls and check-ups. Conclusions Participants had a systemic perception of PCT, and a tendency to attribute a range of health problems to the condition. This study adds insight into the experiences patients have with PCT. PMID:24958197

  8. Nutritional rickets: pathogenesis and prevention.

    PubMed

    Pettifor, John M

    2013-06-01

    Nutritional rickets remains a public health concern in many areas of the world despite cheap and effective means of preventing the disease. The roles of vitamin D deficiency, low dietary calcium intakes and the interrelationships between the two in the pathogenesis of the disease are discussed. It is now recognized that vitamin D deficiency in the pregnant and lactating mother predisposes to the development of rickets in the breastfed infant, and that cultural and social factors are important in the pathogenesis of the disease during the adolescent growth spurt. Prevention of rickets is dependent on the awareness of the medical profession and the general public of the need to ensure adequate intakes of vitamin D in at-risk populations, and of the importance of increasing dietary intakes of calcium using locally available and inexpensive foods in communities in which dietary calcium deficiency rickets is prevalent.

  9. Vitiligo: symptoms, pathogenesis and treatment.

    PubMed

    Ghafourian, A; Ghafourian, S; Sadeghifard, N; Mohebi, R; Shokoohini, Y; Nezamoleslami, S; Hamat, R A

    2014-01-01

    Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of 0.5% to 2% worldwide. There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive of each other: biochemical/cytotoxic, neural and autoimmune. Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major effect on quality of life, treatment can be considered and should preferably begin early when then disease is active. Current treatment modalities are directed towards stopping progression of the disease and achieving repigmentation. Therapies include corticosteroids, topical immunomodulators, photo(chemo)therapy, surgery, combination therapies and depigmentation of normally pigmented skin. It seems that traditional Chinese medicine could be more effective than the current treatment for vitligo.

  10. Vitiligo: Symptoms, Pathogenesis and Treatment.

    PubMed

    Ghafourian, E; Ghafourian, S; Sadeghifard, N; Mohebi, R; Shokoohini, Y; Nezamoleslami, S; Hamat, R A

    2014-10-01

    Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of 0.5% to 2% worldwide. There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive of each other: biochemical/cytotoxic, neural and autoimmune. Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major effect on quality of life, treatment can be considered and should preferably begin early when then disease is active. Current treatment modalities are directed towards stopping progression of the disease and achieving repigmentation. Therapies include corticosteroids, topical immunomodulators, photo(chemo)therapy, surgery, combination therapies and depigmentation of normally pigmented skin. It seems that traditional Chinese medicine could be more effective than the current treatment for vitligo.

  11. Pathogenesis of arenavirus hemorrhagic fevers.

    PubMed

    Moraz, Marie-Laurence; Kunz, Stefan

    2011-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.

  12. Pathogenesis of listeriosis during pregnancy.

    PubMed

    Poulsen, Keith P; Czuprynski, Charles J

    2013-06-01

    Listeria monocytogenes causes several clinical manifestations in humans and domestic animals. This bacterium is a saprophyte in soil and ensiled feeds, which are sources of infection for food producing animals (i.e. ruminants). The most common route of infection for people is via ingestion of contaminated ready-to-eat food products such as produce, soft cheeses and deli meats. In the United States, L. monocytogenes causes relatively few cases of clinical disease compared to other food-borne pathogens. However, clinical listeriosis is associated with high mortality, especially in immunocompromised patients, pregnant women, neonates, and the elderly. Listeria is an intracellular pathogen, which has been widely used in basic research to elucidate mechanisms of molecular pathogenesis and protective cell-mediated immunity. Despite the sizeable knowledge on L. monocytogenes pathogenesis, key points regarding listeriosis during pregnancy and the perinatal period remain unknown. This review summarizes listeriosis in humans and domestic animals during pregnancy, and animal models used to study the pathogenesis and immune response to L. monocytogenes infection during these periods.

  13. Regulation of the Edwardsiella ictaluri Type III Secretion System by pH and Phosphate Concentration through EsrA, EsrB, and EsrC ▿

    PubMed Central

    Rogge, Matthew L.; Thune, Ronald L.

    2011-01-01

    A recently described Edwardsiella ictaluri type III secretion system (T3SS) with functional similarity to the Salmonella pathogenicity island 2 T3SS is required for replication in channel catfish head-kidney-derived macrophages (HKDM) and virulence in channel catfish. Quantitative PCR and Western blotting identified low pH and phosphate limitation as conducive to expression of the E. ictaluri T3SS, growth conditions that mimic the phagosomal environment. Mutagenesis studies demonstrated that expression is under the control of the EsrAB two-component regulatory system. EsrB also induces upregulation of the AraC-type regulatory protein EsrC, which enhances expression of the EscB/EseG chaperone/effector operon in concert with EsrB and induces expression of the pEI1-encoded effector, EseH. EsrC also induces expression of a putative type VI secretion system translocon protein, EvpC, which is secreted under the same low-pH conditions as the T3SS translocon proteins. The pEI2-encoded effector, EseI, was upregulated under low-pH and low-phosphate conditions but not in an EsrB- or EsrC-dependent manner. Mutations of EsrA and EsrB both resulted in loss of the ability to replicate in HKDM and full attenuation in the channel catfish host. Mutation of EsrC did not affect intracellular replication but did result in attenuation in catfish. Although EsrB is the primary transcriptional regulator for E. ictaluri genes within the T3SS pathogenicity island, EsrC regulates expression of the plasmid-carried effector eseH and appears to mediate coordinated expression of the T6SS with the T3SS. PMID:21551284

  14. Effects of a phytogenic feed additive on growth performance, susceptibility of channel catfish to Edwardsiella ictaluri and levels of mannose binding lectin.

    PubMed

    Peterson, Brian C; Peatman, E; Ourth, D D; Waldbieser, G C

    2015-05-01

    A study was conducted to investigate the effect of a phytogenic feed additive (Digestarom® P.E.P. MGE; containing the essential oils carvacrol, thymol, anethol, and limonene) on growth performance and disease susceptibility to Edwardsiella ictaluri. Two hundred and fifty juvenile channel catfish, Ictalurus punctatus (7.2 ± 0.1 g) were allotted into the following treatments: Control (floating diet) and EO (floating diet supplemented with essential oils). The fish were fed their respective diets for 6 weeks. At the end of the study, all fish were exposed to virulent E. ictaluri by bath immersion (1.9 × 10(7) cfu/mL; final concentration). Plasma and tissue samples were taken to quantify protein and mRNA expression levels of mannose binding lectin (MBL). Weight gain and food conversion ratio were similar between treatments. After exposing fish to virulent E. ictaluri and monitoring mortality for 21 days, survival was 43% higher (69.5 vs 48.4%) in fish fed EO compared to fish not treated with EO (P < 0.05). One day after challenge, plasma MBL levels were down-regulated in the non-treated fish compared to non-challenged fish. In the EO fish, MBL levels were similar to non-challenged fish but significantly higher than non-treated fed fish (P < 0.001). By d 7, plasma MBL levels increased in non-treated fed fish to levels observed in the EO and non-challenged fish. On d 14, MBL mRNA levels were upregulated 15-fold in fish fed EO compared to non-treated fed fish and non-challenged fish (P < 0.001). The results demonstrate that essential oils improved survival of channel catfish challenged with E. ictaluri. Mechanisms through which essential oils improve survival may involve MBL.

  15. Biology and pathogenesis of Acanthamoeba.

    PubMed

    Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2012-01-10

    Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

  16. Biology and pathogenesis of Acanthamoeba

    PubMed Central

    2012-01-01

    Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens. PMID:22229971

  17. Climate envelope predictions indicate an enlarged suitable wintering distribution for Great Bustards (Otis tarda dybowskii) in China for the 21st century

    PubMed Central

    Mi, Chunrong; Falk, Huettmann

    2016-01-01

    The rapidly changing climate makes humans realize that there is a critical need to incorporate climate change adaptation into conservation planning. Whether the wintering habitats of Great Bustards (Otis tarda dybowskii), a globally endangered migratory subspecies whose population is approximately 1,500–2,200 individuals in China, would be still suitable in a changing climate environment, and where this could be found, is an important protection issue. In this study, we selected the most suitable species distribution model for bustards using climate envelopes from four machine learning models, combining two modelling approaches (TreeNet and Random Forest) with two sets of variables (correlated variables removed or not). We used common evaluation methods area under the receiver operating characteristic curves (AUC) and the True Skill Statistic (TSS) as well as independent test data to identify the most suitable model. As often found elsewhere, we found Random Forest with all environmental variables outperformed in all assessment methods. When we projected the best model to the latest IPCC-CMIP5 climate scenarios (Representative Concentration Pathways (RCPs) 2.6, 4.5 and 8.5 in three Global Circulation Models (GCMs)), and averaged the project results of the three models, we found that suitable wintering habitats in the current bustard distribution would increase during the 21st century. The Northeast Plain and the south of North China were projected to become two major wintering areas for bustards. However, the models suggest that some currently suitable habitats will experience a reduction, such as Dongting Lake and Poyang Lake in the Middle and Lower Yangtze River Basin. Although our results suggested that suitable habitats in China would widen with climate change, greater efforts should be undertaken to assess and mitigate unstudied human disturbance, such as pollution, hunting, agricultural development, infrastructure construction, habitat fragmentation, and

  18. Climate envelope predictions indicate an enlarged suitable wintering distribution for Great Bustards (Otis tarda dybowskii) in China for the 21st century.

    PubMed

    Mi, Chunrong; Falk, Huettmann; Guo, Yumin

    2016-01-01

    The rapidly changing climate makes humans realize that there is a critical need to incorporate climate change adaptation into conservation planning. Whether the wintering habitats of Great Bustards (Otis tarda dybowskii), a globally endangered migratory subspecies whose population is approximately 1,500-2,200 individuals in China, would be still suitable in a changing climate environment, and where this could be found, is an important protection issue. In this study, we selected the most suitable species distribution model for bustards using climate envelopes from four machine learning models, combining two modelling approaches (TreeNet and Random Forest) with two sets of variables (correlated variables removed or not). We used common evaluation methods area under the receiver operating characteristic curves (AUC) and the True Skill Statistic (TSS) as well as independent test data to identify the most suitable model. As often found elsewhere, we found Random Forest with all environmental variables outperformed in all assessment methods. When we projected the best model to the latest IPCC-CMIP5 climate scenarios (Representative Concentration Pathways (RCPs) 2.6, 4.5 and 8.5 in three Global Circulation Models (GCMs)), and averaged the project results of the three models, we found that suitable wintering habitats in the current bustard distribution would increase during the 21st century. The Northeast Plain and the south of North China were projected to become two major wintering areas for bustards. However, the models suggest that some currently suitable habitats will experience a reduction, such as Dongting Lake and Poyang Lake in the Middle and Lower Yangtze River Basin. Although our results suggested that suitable habitats in China would widen with climate change, greater efforts should be undertaken to assess and mitigate unstudied human disturbance, such as pollution, hunting, agricultural development, infrastructure construction, habitat fragmentation, and oil

  19. A novel nonsense mutation in the sedlin gene (SEDL) causes severe spondyloepiphyseal dysplasia tarda in a five-generation Chinese pedigree.

    PubMed

    Xia, X Y; Yu, J; Li, W W; Li, N; Wu, Q Y; Zhou, X; Cui, Y X; Li, X J

    2014-04-29

    Spondyloepiphyseal dysplasia tarda (SEDT) is an X-linked recessive osteochondrodysplasia characterized by disproportionately short stature and degenerative joint disease. The objective of this study was to describe a novel nonsense mutation in the sedlin gene (SEDL) causing severe SEDT in a large Chinese pedigree. The clinical features of all affected individuals and female carriers were presented. Four affected males of the family were diagnosed with SEDT according to their clinical and radiological features. Direct DNA sequencing of SEDL was performed. Reverse-transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed to confirm the defect in SEDL. DNA sequencing revealed that all of the affected males carried a nonsense mutation (c.61G>T) in SEDL that has not been previously reported. The c.61G>T mutation resulted in a premature translation termination codon (GAG>TAG) at amino acid position 21 (p.E21*), and was predicted to initiate the degradation of mutant transcripts through the nonsense-mediated mRNA decay pathway. Two female carriers showed typical sequencing chromatograms of a heterozygote. Following genetic counseling, individual IV7 gave birth to a healthy baby. Therefore, identification of the novel nonsense mutation (c.61G>T) in the SEDT family enables carrier detection, genetic counseling, and prenatal diagnosis. The detailed genotype/phenotype descriptions contribute to the SEDL mutation spectrum. The continued identification of mutations in SEDT patients will greatly aid further elucidation of the role of the sedlin protein in normal bone growth.

  20. Pathogenesis of Helicobacter pylori infection

    PubMed Central

    Sgouras, Dionyssios N.; Trang, Tran Thi Huyen; Yamaoka, Yoshio

    2015-01-01

    Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infections. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cag PAI, CagA, VacA and gastrointestinal microbiota. PMID:26372819

  1. Molecular Pathogenesis of Neuromyelitis Optica

    PubMed Central

    Bukhari, Wajih; Barnett, Michael H; Prain, Kerri; Broadley, Simon A

    2012-01-01

    Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies. PMID:23202933

  2. Pathogenesis of middle ear adhesions.

    PubMed

    Cayé-Thomasen, P; Hermansson, A; Tos, M; Prellner, K

    1996-04-01

    Middle ear adhesions are well-known to the ear surgeon, although data on etiology, pathogenesis, and significance are lacking in current literature. This study on experimental acute otitis media presents histopathological data on these aspects. Pneumococci were inoculated in the right middle ear bulla of 25 rats; the left ear served as control. At days 4, 8, 16, 90, and 180, respectively, 5 rats were decapitated, and the bullae were removed, opened, and stained with periodic acid-Schiff (PAS)/alcian blue. The entire middle ear mucosae were dissected from the bone, embedded as whole mounts in colophonium chambers, and examined by light microscopy. Representative parts of the mucosae were sectioned and examined in the same way. All inoculated ears from day 8 and later (20 in total), contained mucosal adhesions of various sizes, shapes, and locations. None were found in control ears. The site of predilection for the development of adhesions was the hypotympanum, followed by the anterior epitympanum, the attic, the drum, the interossicular spaces, and the tubal orifice. Based on present histopathological findings, we conclude that the middle ear adhesion is a pathological phenomenon caused by infection, and we propose a six-stage hypothesis of pathogenesis: 1. Localized epithelial rupture; 2. Prolapse of subepithelial tissue; 3. Epithelialization of the prolapse; resulting in a polypous/fold-like prominence; 4. Growth and elongation of the prominence; 5. Fusion of the end/tip of the prominence with another part of the mucosa; 6. Formation of an adhesion.

  3. Pathogenesis of varicelloviruses in primates.

    PubMed

    Ouwendijk, Werner J D; Verjans, Georges M G M

    2015-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation.

  4. Pathogenesis of Helicobacter pylori Infection.

    PubMed

    Sgouras, Dionyssios N; Trang, Tran Thi Huyen; Yamaoka, Yoshio

    2015-09-01

    Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence, and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA, and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infection. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cagPAI, CagA, VacA, and gastrointestinal microbiota. © 2015 John Wiley & Sons Ltd.

  5. Pathogenesis of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Sarah; Orrell, Richard W

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition. Peer-reviewed journal articles and reviews. PubMed.gov The pathogenesis of ALS remains largely unknown. There are a wide range of potential mechanisms related to neurodegeneration. An increasing number of genetic factors are recognized. There remains controversy, or lack of knowledge, in explaining how cellular events manifest as the complex human disease. There is controversy as to how well cellular and animal models of disease relate to the human disease. Large-scale international collaborative genetic epidemiological studies are replacing local studies. Therapies related to pathogenesis remain elusive, with the greatest advances to date relating to provision of care (including multidisciplinary management) and supportive care (nutrition and respiratory support). The identification of C9orf72 hexanucleotide repeats as the most frequent genetic background to ALS, and the association with frontotemporal dementia, gives the potential of a genetic background against which to study other risk factors, triggers and pathogenic mechanisms, and to develop potential therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Pathogenesis and Immunobiology of Brucellosis

    PubMed Central

    de Figueiredo, Paul; Ficht, Thomas A.; Rice-Ficht, Allison; Rossetti, Carlos A.; Adams, L. Garry

    2016-01-01

    This review of Brucella–host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. PMID:25892682

  7. Pathogenesis of Focal Segmental Glomerulosclerosis

    PubMed Central

    Lim, Beom Jin; Yang, Jae Won; Do, Woo Sung; Fogo, Agnes B.

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice. PMID:27744657

  8. Pathogenesis of Helicobacter pylori infection.

    PubMed

    Camilo, Vania; Sugiyama, Toshiro; Touati, Eliette

    2017-09-01

    Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs. © 2017 John Wiley & Sons Ltd.

  9. Henipavirus pathogenesis and antiviral approaches.

    PubMed

    Mathieu, Cyrille; Horvat, Branka

    2015-03-01

    Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field.

  10. Pathogenesis of Brain Arteriovenous Malformations

    PubMed Central

    KOMIYAMA, Masaki

    2016-01-01

    Brain arteriovenous malformations (bAVMs) represent a high risk of intracranial hemorrhages, which are substantial causes of morbidity and mortality of bAVMs, especially in children and young adults. Although a variety of factors leading to hemorrhages of bAVMs are investigated extensively, their pathogenesis is still not well elucidated. The author has reviewed the updated data of genetic aspects of bAVMs, especially focusing on clinical and experimental knowledge from hereditary hemorrhagic telangiectasia, which is the representative genetic disease presenting with bAVMs caused by loss-of-function in one of the two genes: endoglin and activin receptor-like kinase 1. This knowledge may allow us to infer the pathogensis of sporadic bAVMs and in the development of new medical therapies for them. PMID:27076383

  11. Pathogenesis of Salmonellosis: Salmonella Exotoxins

    DTIC Science & Technology

    1982-03-08

    OVT ACCESSION NO. 3 . RECIPIENT’S CATALOG NUMBER 4 . TITLE (nd Subtitle) S. TYPE OF REPORT &PERIOD COVERED Pathogenesis of Salmonellosis: Salmonella...J .• ..- o . -. - ° "-o Figure 1 E a’. CL ’ u-E: U~ 0 (. 3 0 -0.- ".5 Clio CL! Ud Figure 2 0 X in 4 (D U - Untreated CHO cells 0...U. 3 o I- 2 00 0.001 0.01 0.1 1 10 Cholera Toxin (ng) lu I II I 1 11 IIII III I I III II I II IIIII II II I III I I I I I I Figure3 el , 4 "I

  12. Molecular Pathogenesis of Hepatocellular Carcinoma

    PubMed Central

    Ho, Daniel Wai-Hung; Lo, Regina Cheuk-Lam; Chan, Lo-Kong; Ng, Irene Oi-Lin

    2016-01-01

    The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis. Taken together, multiple key genetic and non-genetic factors, as well as liver CSCs, result in the development and progression of HCC. PMID:27781201

  13. [Vitiligo: Clinical presentation and pathogenesis].

    PubMed

    Schild, M; Meurer, M

    2016-02-01

    Vitiligo is a chronic skin disorder with depigmentation of circumscribed areas due to structural and functional damage to melanocytes. There is international consensus on the classification in nonsegmental and segmental vitiligo. The influence of vitiligo on the quality of life is significant and is influenced by ethnic and sociocultural factors. There is a new insight into the genetic susceptibility, mechanisms and targets of the autoimmune inflammation, the altered morphology and function of melanocytes and into the association of vitiligo with other autoimmune diseases, skin cancer and skin cancer therapy. The recognition of associated autoimmune disorders is as important as is the assessment of changes in the quality of life. New insight into the pathogenesis may have therapeutic consequences. The relationship between vitiligo and skin cancer and between vitiligo and immunotherapies in patients with metastatic melanoma warrants close clinical monitoring of affected patients and further scientific studies.

  14. Neisseria meningitidis: pathogenesis and immunity.

    PubMed

    Pizza, Mariagrazia; Rappuoli, Rino

    2015-02-01

    The recent advances in cellular microbiology, genomics, and immunology has opened new horizons in the understanding of meningococcal pathogenesis and in the definition of new prophylactic intervention. It is now clear that Neissera meningitidis has evolved a number of surface structures to mediate interaction with host cells and a number of mechanisms to subvert the immune system and escape complement-mediated killing. In this review we report the more recent findings on meningococcal adhesion and on the bacteria-complement interaction highlighting the redundancy of these mechanisms. An effective vaccine against meningococcus B, based on multiple antigens with different function, has been recently licensed. The antibodies induced by the 4CMenB vaccine could mediate bacterial killing by activating directly the classical complement pathway or, indirectly, by preventing binding of fH on the bacterial surface and interfering with colonization. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  15. [Pathogenesis of retinopathy of prematurity].

    PubMed

    Stahl, A; Lagrèze, W A; Agostini, H T

    2012-12-01

    Retinopathy of prematurity (ROP) is a complex disease with a multifactorial pathogenetic cascade that is still only partially understood. Important pathogenetic factors are gestational age at birth and birth weight. Potent postnatal factors are exposure to supplemental oxygen, slow weight gain and expression of angiogenic growth factors. Some of these crucial aspects of ROP pathogenesis will be discussed in this article and put into clinical context. With the introduction of intravitreal anti-VEGF (vascular endothelial growth factor) treatment into ROP therapy, the pathomechanistic role of VEGF in ROP deserves a special focus. Apart from VEGF, other factors will be discussed that may precede VEGF upregulation and thus may represent targets for an earlier and potentially protective intervention. Among these insulin-like growth factor 1 (IGF-1) appears to be most prominent. Finally, factors such as postnatal weight gain will be discussed in light of their potential role as screening parameters and their ability to predict ROP severity.

  16. Ion channelopathies and migraine pathogenesis.

    PubMed

    Albury, Cassie L; Stuart, Shani; Haupt, Larisa M; Griffiths, Lyn R

    2017-08-01

    Migraine is a common neurological disorder that affects approximately 12-20% of the general adult population. Migraine pathogenesis is complex and not wholly understood. Molecular genetic investigations, imaging and biochemical studies, have unveiled a number of interconnected neurological pathways which seem to have a cause and effect component integral to its cause. Much weight of migraine attack initiation can be placed on the initial trigger and the pathways involved in its neuronal counter reaction. Ion channels play a large role in the generation, portrayal and mitigation of the brains response to external triggers. Several genetic studies have identified and implicated a number of ion channelopathy genes which may contribute to this generalised process. This review will focus on the genetics of migraine with particular emphasis placed on the potentially important role genes HEPH (responsible for iron transport and homeostasis) and KCNK18 (important for the transport and homeostasis of potassium) play in migraine cause.

  17. Pathogenesis of idiopathic pulmonary fibrosis.

    PubMed

    Wolters, Paul J; Collard, Harold R; Jones, Kirk D

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated.

  18. Pathogenesis of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  19. Molecular Pathogenesis of Myelodysplastic Syndromes

    PubMed Central

    Visconte, Valeria; Selleri, Carmine; Maciejewski, Jaroslaw P.; Tiu, Ramon V.

    2014-01-01

    Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders characterized by inefficient hematopoiesis, hypercellular bone marrow, dysplasia of blood cells and cytopenias. Most patients are diagnosed in their late 60s to early 70s. MDS is a risk factor for the development of acute myeloid leukemia which can occur in 10-15% of patients with MDS. A variety of pathophysiologic mechanisms contributes to the genesis and persistence of MDS including immunologic, epigenetic, cytogenetic and genetic factors. The only potential curative option for MDS is hematopoietic cell transplantation which is suitable for only a few patients. Currently approved therapeutic options for MDS, including lenalidomide, decitabine, and 5-azacytidine, are targeted to improve transfusion requirements and quality of life. Moreover, 5-azacytidine has also been demonstrated to improve survival in some patients with higher risk MDS. New ways to predict which patients will better gain benefit from currently available therapeutic agents are the primary challenges in MDS. In the last 10 years, chromosome scanning and high throughput technologies (single nucleotide polymorphism array genotyping, comparative genomic hybridization, and whole genome/ exome sequencing) have tremendously increased our knowledge of MDS pathogenesis. Indeed, the molecular heterogeneity of MDS supports the idea of different therapeutic approaches which will take into account the diverse morphologic and clinical presentations of MDS patients rather than a restricted therapeutic strategy. This review will summarize the molecular abnormalities in key relevant components of the biology and pathogenesis of MDS and will provide an update on the clinical impact and therapeutic response in MDS patients. PMID:24778995

  20. The Pathogenesis of Diabetes Mellitus - USSR -.

    DTIC Science & Technology

    1960-05-09

    Our ideas of the pathogenesis of diabetes mellitus have changed considerably during the past 40 years. Our current concept result from the...acquisition of new data on the role of the central nervous and endocrine systems in the pathogenesis of diabetes mellitus ; new data on the metabolic processes... diabetes mellitus develops basically as the result of pancreatic insufficiency, it is impossible at the present time to visualize the pathogenesis of

  1. Type VI Secretion is a Major Virulence Determinant in Burkholderia Mallei

    DTIC Science & Technology

    2007-06-01

    coli (Aec), V. cholerae (Vas), Edwardsiella tarda (Evp), Salmonella enterica (Sci) and Rhizobium legumi- nosarum (Imp). 1468 M. A. Schell et al...tarda (Evp), Salmonella enterica (Sci), Francisella tularensis (Igl) and Rhizobium leguminosarum (Imp), are also shown. Proteins that do not have a COG...Bladergroen, M.R., Badelt, K., and Spaink, H.P. (2003) Infection-blocking genes of a symbiotic Rhizobium legumi- nosarum strain that are involved in

  2. A real-time polymerase chain reaction assay for quantification of Edwardsiella ictaluri in catfish pond water and genetic homogeneity of diagnostic case isolates from Mississippi.

    PubMed

    Griffin, Matt J; Mauel, Michael J; Greenway, Terrence E; Khoo, Lester H; Wise, David J

    2011-12-01

    A quantitative polymerase chain reaction (qPCR) assay was developed for the detection and quantification of Edwardsiella ictaluri in channel catfish Ictalurus punctatus pond water using modifications to a published E. ictaluri-specific qPCR assay and previously established protocols for the molecular detection of myxozoan parasites in catfish ponds. Genomic DNA equivalents indicative of the number of bacteria in a sample were determined and standard curves correlating to bacterial numbers were established. The assay was found to be highly repeatable and reproducible, with a linear dynamic range of five orders of magnitude. There was no interference of the assay from the presence of large quantities of nontarget DNA. Known quantities of bacteria were added to sample volumes of 40 or 500 mL of pond water collected from several different ponds. The minimum level of detection was approximately 100 cell equivalents (CE) in 40 (2.5 CE/mL) or 500 mL of pond water (0.2 CE/mL). Sample volumes of 40 mL yielded the most consistent results, which were not significantly different from those obtained from broth culture alone. Cell equivalents determined by qPCR in 40-mL pond water samples spiked with known quantities of bacteria were within one order of magnitude of the actual number of cells added. Repetitive element-based polymerase chain reaction analysis of archived isolates demonstrated the genetic homogeneity of E. ictaluri, and consistent amplification of these isolates by qPCR analysis demonstrated the stability of the PCR target. The assay described here provides a reliable method for the detection and quantification of E. ictaluri in pond water and will be an invaluable tool in epidemiological studies. Additionally, the assay provides a way to evaluate the effects that vaccination, antibiotic treatments, and restricted feeding practices have on E. ictaluri populations during an outbreak. Information obtained with these tools will aid in optimizing disease management

  3. Type 1 diabetes pathogenesis - Prevention???

    PubMed

    Krishna, C S Muralidhara; Srikanta, S

    2015-04-01

    Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction ("Primary autoimmune insulitis"), culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb) are an important hallmark of this disease. Assays for islet cell autoantibodies have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have extended into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently, surprisingly, differences in insulin content between T1DM islets, as well as, 'patchy' or 'lobular' destruction of islets have been described. These unique pathobiological phenomena, suggest that beta cell destruction may not always be inexorable and inevitably complete/total, and thus raise hopes for possible therapeutic interruption of beta cell autoimmunity - destruction and cure of type 1 diabetes. "Recurrent or secondary autoimmune insulitis" refers to the rapid reappearance of islet cell autoantibodies post pancreas transplant, and selective islet beta cell destruction in the grafted pancreas [never forgetting or "anamnestic" beta cell destructive memory], in the absence of any graft pancreas rejection [monozygotic twin to twin transplantation]. The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The putative predisposing factors are viruses, gluten and cow's milk. The putative protective factors include gut flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can include: Primary prevention strategies before the development of

  4. Pathogenesis of feline diabetes mellitus.

    PubMed

    Lutz, T A; Rand, J S

    1995-05-01

    Cats are one of the few species that develop a form of diabetes mellitus that is clinically and histologically analogous to human type 2 diabetes mellitus. Figure 9 summarizes the etiologic factors thought to be involved in the development of feline and human type 2 diabetes. The main metabolic characteristics of type 2 diabetes mellitus are impaired insulin secretion and resistance to the action of insulin in its target tissues. Impaired beta cell function occurs before histologic changes become evident. The characteristic histologic finding in cats with type 2 diabetes is deposition of amyloid in pancreatic islets. Amyloid deposition occurs before the onset of clinical signs, but does not seem to be the primary defect. Pancreatic amyloid is derived form the recently discovered pancreatic hormone amylin. Amylin is synthesized in pancreatic beta cells, and is co-stored and co-secreted with insulin. Amylin has been postulated to be involved in the pathogenesis of feline diabetes mellitus both through its metabolic effects, which include inhibition of insulin secretion and induction of insulin resistance, and via progressive amyloid deposition and beta cell degeneration. Increased amylin concentration has been documented intracellularly in cats with impaired glucose tolerance and in the plasma of diabetic cats, and supports the hypothesis that amylin is involved in the pathogenesis of type 2 diabetes. Obesity is a common finding in diabetic felines and is a contributing factor to the insulin resistance present in type 2 diabetes. Clinical signs of diabetes develop once total insulin secretion decreases to 20% to 25% of normal levels. Many diabetic cats have been treated successfully with oral hypoglycemics, but 50% to 70% of diabetic cats are insulin dependent. Based on histologic evidence, this is the result of extensive amyloid deposition and subsequent beta cell degeneration, rather than autoimmune destruction of pancreatic beta cells associated with type 1

  5. The Pathogenesis of Cardiac Fibrosis

    PubMed Central

    Kong, Ping; Christia, Panagiota; Frangogiannis, Nikolaos G

    2013-01-01

    Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review manuscript discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins and growth factors (such as TGF-β and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease. PMID:23649149

  6. Molecular mechanisms of Ebola pathogenesis.

    PubMed

    Rivera, Andrea; Messaoudi, Ilhem

    2016-11-01

    Ebola viruses (EBOVs) and Marburg viruses (MARVs) are among the deadliest human viruses, as highlighted by the recent and widespread Ebola virus outbreak in West Africa, which was the largest and longest epidemic of Ebola virus disease (EVD) in history, resulting in significant loss of life and disruptions across multiple continents. Although the number of cases has nearly reached its nadir, a recent cluster of 5 cases in Guinea on March 17, 2016, has extended the enhanced surveillance period to June 15, 2016. New, enhanced 90-d surveillance windows replaced the 42-d surveillance window to ensure the rapid detection of new cases that may arise from a missed transmission chain, reintroduction from an animal reservoir, or more important, reemergence of the virus that has persisted in an EVD survivor. In this review, we summarize our current understanding of EBOV pathogenesis, describe vaccine and therapeutic candidates in clinical trials, and discuss mechanisms of viral persistence and long-term health sequelae for EVD survivors. © Society for Leukocyte Biology.

  7. Molecular Pathogenesis of MALT Lymphoma

    PubMed Central

    Troppan, Katharina; Wenzl, Kerstin; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. PMID:25922601

  8. The Pathogenesis of Lupus Nephritis

    PubMed Central

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  9. Pathogenicity Islands in Bacterial Pathogenesis

    PubMed Central

    Schmidt, Herbert; Hensel, Michael

    2004-01-01

    In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections. PMID:14726454

  10. Vasculitis update: pathogenesis and biomarkers.

    PubMed

    Brogan, Paul; Eleftheriou, Despina

    2017-08-07

    Better understanding of the pathogenesis and treatment of primary systemic vasculitides (PSV) has led to the development of many potentially clinically relevant biomarkers. Genome-wide association studies have highlighted that MHC class II polymorphisms may influence the development of particular anti-neutrophil cytoplasmic antibody (ANCA) serotypes, but not the clinical phenotype of ANCA-associated vasculitis (AAV). Although ANCAs are overall poor biomarkers of disease activity, they may be useful for the prediction of flares of renal and/or pulmonary vasculitis. Moreover, patients with proteinase 3 (PR3)-AAV may respond better to rituximab than cyclophosphamide. Newer biomarkers of renal vasculitis in AAV include urinary soluble CD163, and may in the future reduce the requirement for renal biopsy. Better understanding of dysregulated neutrophil activation in AAV has led to the identification of novel biomarkers including circulating microparticles, and neutrophil extracellular traps (NETs), although their clinical utility has not yet been realised. Studies examining endothelial injury and repair responses have additionally revealed indices that may have utility as disease activity and/or prognostic biomarkers. Last, next-generation sequencing technologies are revealing monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), and are profoundly influencing the approach to the diagnosis and treatment of vasculitis in the young.

  11. Achondroplasia: Development, pathogenesis, and therapy.

    PubMed

    Ornitz, David M; Legeai-Mallet, Laurence

    2017-04-01

    Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc.

  12. Pathogenesis of Helicobacter pylori Infection

    PubMed Central

    Kusters, Johannes G.; van Vliet, Arnoud H. M.; Kuipers, Ernst J.

    2006-01-01

    Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori. PMID:16847081

  13. CELLULAR PATHOGENESIS OF DIABETIC GASTROENTEROPATHY

    PubMed Central

    Ördög, Tamás; Hayashi, Yujiro; Gibbons, Simon J.

    2010-01-01

    SUMMARY Gastroenteropathy manifesting in upper gastrointestinal symptoms, delayed gastric emptying, constipation, diarrhea and fecal incontinence occurs frequently in patients with diabetes mellitus and represents a significant health care burden. Current treatments are largely symptomatic and ineffective. Better understanding of the cellular and molecular pathogenesis of these disorders is required for the development of more effective therapies. Recent advances in our understanding of the inherent, high-level complexities of the control systems that execute and regulate gastrointestinal motility, together with the utilization of new experimental models and sophisticated physiological, morphological and molecular techniques have lead to the realization that diabetic gastroenteropathies cannot be ascribed to any singular defect or dysfunction. In fact, these disorders are multifactorial and involve a spectrum of metabolic and dystrophic changes that can potentially affect all key components of motor control including the systemic autonomic and enteric nervous systems, interstitial cells of Cajal and smooth muscle cells. Candidate pathomechanisms are also varied and include imbalance between pro- and anti-oxidative factors, altered trophic stimuli to mature cells and their progenitors, and, possibly, autoimmune factors. The goal of this paper is to review the cellular changes underlying diabetic gastroenteropathies and their potential causes, with particular focus on functional interactions between various cell types. It is proposed that diabetic gastroenteropathies should be considered a form of gastrointestinal neuromuscular dystrophy rather than a “functional” disorder. Future research should identify ways to block cytotoxic factors, support the regeneration of damaged cells and translate the experimental findings into new treatment modalities. PMID:19829287

  14. Pathogenesis and Prediction of Future Rheumatoid Arthritis

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis ...5a. CONTRACT NUMBER Pathogenesis and Prediction of Future Rheumatoid Arthritis 5b. GRANT NUMBER W81XWH-13-1-0408 5c...SUPPLEMENTARY NOTES 14. ABSTRACT It is now well established that there is a preclinical period of rheumatoid arthritis (RA) development that is

  15. The pathogenesis of Charcot neuroarthropathy: current concepts.

    PubMed

    Larson, Shelly A M; Burns, Patrick R

    2012-01-01

    The pathogenesis of Charcot neuroarthropathy (CN) has been poorly understood by clinicians and scientists alike. Current researchers have made progress toward understanding the cause of CN and possible treatment options. The authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation, bone metabolism, and advanced glycation end products.

  16. The pathogenesis of hyaline arteriolosclerosis.

    PubMed Central

    Gamble, C. N.

    1986-01-01

    Although hyaline arteriolosclerosis is very common and has been of interest to pathologists for well over 100 years, its pathogenesis has never been determined. This study demonstrates that iC3b bound via an ester linkage to hydroxyl groups on the repeating disaccharide units of hyaluronic acid is a major component of arteriolar hyaline. The deposition of iC3b within the walls of arterioles appears to be due to slow spontaneous activation of the alternative complement pathway and random binding of metastable C3b to proximate hyaluronic acid within the arteriolar wall. Since hyaluronic acid does not activate the alternative complement pathway, bound C3b is rapidly inactivated by factors I and H to iC3b, which, along with factor H, remains bound to hyaluronic acid. The hyaline in some hyalinized arterioles also contains IgM and early and late classical complement pathway components. Indirect evidence suggests that the IgM represents immunoconglutinin, an autoantibody to neoantigens on iC3b and that their interaction results in activation of the classical complement pathway. The gradual accumulation of iC3b, factor H, and, at times, IgM and classical complement pathway components within the walls of arterioles is considered to be a physiologic consequence of aging and probably cannot be prevented, because interruption of the initial binding of metastable C3b to hyaluronic acid would require abrogation of the critically important functions of the alternative complement pathway. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:2420184

  17. Redox biology of tuberculosis pathogenesis.

    PubMed

    Trivedi, Abhishek; Singh, Nisha; Bhat, Shabir Ahmed; Gupta, Pawan; Kumar, Ashwani

    2012-01-01

    Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Mtb is persistently exposed to numerous oxidoreductive stresses during its pathogenic cycle of infection and transmission. The distinctive ability of Mtb, not only to survive the redox stress manifested by the host but also to use it for synchronizing the metabolic pathways and expression of virulence factors, is central to its success as a pathogen. This review describes the paradigmatic redox and hypoxia sensors employed by Mtb to continuously monitor variations in the intracellular redox state and the surrounding microenvironment. Two component proteins, namely, DosS and DosT, are employed by Mtb to sense changes in oxygen, nitric oxide, and carbon monoxide levels, while WhiB3 and anti-sigma factor RsrA are used to monitor changes in intracellular redox state. Using these and other unidentified redox sensors, Mtb orchestrates its metabolic pathways to survive in nutrient-deficient, acidic, oxidative, nitrosative, and hypoxic environments inside granulomas or infectious lesions. A number of these metabolic pathways are unique to mycobacteria and thus represent potential drug targets. In addition, Mtb employs versatile machinery of the mycothiol and thioredoxin systems to ensure a reductive intracellular environment for optimal functioning of its proteins even upon exposure to oxidative stress. Mtb also utilizes a battery of protective enzymes, such as superoxide dismutase (SOD), catalase (KatG), alkyl hydroperoxidase (AhpC), and peroxiredoxins, to neutralize the redox stress generated by the host immune system. This chapter reviews the current understanding of mechanisms employed by Mtb to sense and neutralize redox stress and their importance in TB pathogenesis and drug development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Current Understanding in Pathogenesis of Atopic Dermatitis

    PubMed Central

    McPherson, Tess

    2016-01-01

    There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process. PMID:27904184

  19. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1980-01-01

    1973). Sabin (1948) showed that attenuated dpngiie, passed through mosquitoes, did not revert to pathogenicity frnr man. -7- Thus even if the vaccine ...AD-A138 518 PATHOGENESIS OF DENGUE VACCINE YIRUSES IN MOSQUITOES 1/ (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 9i JAN 80 DRND7...34 ’ UNCLASSIFIED 0{) AD 0Pathogenesis of dengue vaccine viruses in mosquitoes -First Annual Report Barry I. Beaty, Ph.D. Thomas H. G

  20. Pathogenesis and Prediction of Future Rheumatoid Arthritis

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Kevin D. Deane, MD/PhD...SUBTITLE 5a. CONTRACT NUMBER Pathogenesis and Prediction of Rheumatoid Arthritis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...preclinical period of rheumatoid arthritis (RA) development that is characterized by abnormalities of the immune system prior to the onset of the

  1. Autophagy in lung disease pathogenesis and therapeutics.

    PubMed

    Ryter, Stefan W; Choi, Augustine M K

    2015-01-01

    Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  2. Pathogenesis of Crimean-Congo hemorrhagic fever.

    PubMed

    Akıncı, Esragül; Bodur, Hürrem; Leblebicioglu, Hakan

    2013-07-01

    Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

  3. Animal models of papillomavirus pathogenesis.

    PubMed

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  4. Gram-negative, aerobic, enteric pathogens among intestinal microflora of wild turkey vultures (Cathartes aura) in west central Texas.

    PubMed Central

    Winsor, D K; Bloebaum, A P; Mathewson, J J

    1981-01-01

    The prevalence of gram-negative bacterial species in the intestines of 20 apparently healthy turkey vultures (Cathartes aura) was determined. Edwardsiella tarda, Plesiomonas shigelloides, Salmonella, and Arizona hinshawii (Salmonella arizonae) were each recovered from 15% of these birds. Turkey vultures may be important reservoirs of these bacterial pathogens. PMID:7032423

  5. Pathogenesis and Nomenclature of Odontogenic Carcinomas: Revisited

    PubMed Central

    Panda, Swagatika; Sahoo, Sujit Ranjan; Srivastav, Gunjan; Padhiary, Subrat; Dhull, Kanika Singh; Aggarwal, Sonia

    2014-01-01

    Odontogenic carcinoma is rare group of malignant epithelial odontogenic neoplasms with characteristic clinical behavior and histological features, which requires an aggressive surgical approach. The pathogenesis of this rare group remains still controversial and there have been many varied opinions over the classification of this rare group of lesions. As there have not been many reviews on odontogenic carcinoma, the existing knowledge is mostly derived from the published case reports. This review is discussing the pathogenetic mechanisms and is updating the knowledge on nomenclature system of less explored odontogenic carcinomas. This review might throw light on the pathogenesis and nomenclature system of odontogenic carcinoma and this knowledge may be applied therapeutically. PMID:24799899

  6. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1981-01-01

    AD-AI30 52S PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES i/I (U) VALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 81 JAN 81 DAMDi...UNCLASSIFIED PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES Second Annual Report Barry J. Beaty, Ph.D. D T IC ; Thomas H.G. Aitken, Ph.D...REPORT NUMBER 2. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED PATHOMMSIS CF DENGUE

  7. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1982-01-01

    AD-R38 519 PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES i/i (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 81 JAN 82 DAMDI...NATIONAL BUREAU OF STANDARDS 1963-A i UNCLASSIFIED ":’:" AD 2 0. PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES Third Annual Report Barry J. Beaty...SUPPLEMENTARY NOTES 1 7 Y NORDS (rontinue on reverq , side if necessary and identify by hlock numb-) Dengue -2 S-1 vaccine, PR-159 parent; IDenque-1

  8. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1984-01-01

    type 2 (Price, 1973), and attenuated Japanese encephalitis vaccine virus (Chen and Beaty, 1982). Sabin (1948) showed that attenuated dengue virus...M194 992 PATHOGENESIS OF DENGUJE VACCINE VIRUSES IN NOSSUITOES vi1 (u) COLORADO STATE UNIV FORT COLLINS DEPT OF MICROBIOLOGY AND ENVIRONMENTAL...IW AV wWW W N A A~~ Nq .. mcFILE COPY 0)0 AD PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES Annual Report Barry J. Beaty, Ph.D. D T IC ELECTE

  9. Endometriosis: new concepts in the pathogenesis.

    PubMed

    Signorile, Pietro G; Baldi, Alfonso

    2010-06-01

    Endometriosis is a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Though there are several theories, research scientists remain unsure as to the definitive cause(s) of endometriosis. Considering the relevant health problems caused by endometriosis, all new information on the pathogenesis of this disease, may have important clinical implications. Goal of this article is to summarize the latest advances in the pathogenesis of endometriosis, with particular emphasis on the embryological theory, that has been recently re-proposed. The possible clinical implications of these findings will be discussed.

  10. The pathogenesis of ulnar polydactyly in humans.

    PubMed

    Al-Qattan, M M; Al-Motairi, M I

    2013-11-01

    The pathogenesis of ulnar polydactyly in humans is not known. There are numerous syndromes that are associated with ulnar polydactyly. We have noted that the genetic defects in these syndromes lead to a disturbance of the normal balance between the two forms of the Gli3 protein (the active and repressor forms of Gli3, which are known as Gli3-A and Gli3-R, respectively), leading to a relative increase in the Gli3-R protein. We offer the hypothesis of a unified pathogenesis of ulnar polydactyly through the relative predominance of Gli3-R.

  11. Bordetella pertussis pathogenesis: current and future challenges

    PubMed Central

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  12. Clostridium difficile colitis: pathogenesis and host defence.

    PubMed

    Abt, Michael C; McKenney, Peter T; Pamer, Eric G

    2016-10-01

    Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C. difficile infection and pathogenesis.

  13. Apoptotic cells enhance pathogenesis of Listeria monocytogenes.

    PubMed

    Pattabiraman, Goutham; Palasiewicz, Karol; Visvabharathy, Lavanya; Freitag, Nancy E; Ucker, David S

    2017-04-01

    Infections by pathogenic microorganisms elicit host immune responses, which crucially limit those infections. Pathogens employ various strategies to evade host immunity. We have identified the exploitation of the repertoire of potent immunosuppressive responses elicited normally by apoptotic cells ("Innate Apoptotic Immunity"; IAI) as one of these strategies. In the case of Listeria monocytogenes, an environmentally ubiquitous, foodborne bacterial pathogen capable of causing life-threatening invasive disease in immunocompromised and elderly individuals, the induction of host cell apoptosis appears to play an important role in pathogenesis. Previous studies have documented extensive lymphocyte apoptosis resulting from L. monocytogenes infection and demonstrated paradoxically that lymphocyte-deficient animals exhibit diminished susceptibility to listerial pathogenicity. We speculated that the triggering of IAI following the induction of host cell apoptosis was responsible for enhanced pathogenesis, and that the administration of exogenous apoptotic cells would serve to exert this effect. Importantly, apoptotic cells, which are not susceptible to L. monocytogenes infection, do not provide a niche for bacterial replication. Our experiments confirm that apoptotic cells, including exogenous apoptotic cells induced to die independently of the pathogen, specifically enhance pathogenesis. The recognition of a role of apoptotic cells and Innate Apoptotic Immunity in microbial pathogenesis provides an intriguing and novel insight for therapeutic approaches for the control of pathogenic infections.

  14. Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment

    PubMed Central

    Volkova, Maria; Russell, Raymond

    2011-01-01

    Anthracyclines, such as doxorubicin and idarubicin, remain an important class of chemotherapeutic agents. Unfortunately, their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity, which can cause irreversible heart failure. In this review, we discuss the pathogenesis and incidence of anthracycline-induced cardiotoxicity as well as methods to detect, prevent and treat the condition. PMID:22758622

  15. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

  16. [Purulent corneal ulcers: etiology, pathogenesis, classification].

    PubMed

    Kasparova, Evg A

    2015-01-01

    Advanced purulent corneal ulcer, as well as abscess, is a serious vision-threatening condition notable for its fulminant course and possible loss of the eye due to endophthalmitis. Its leading causes, pathogenesis, and classifications are described and analyzed in this paper.

  17. The pathogenesis and biomechanics of turf toe.

    PubMed

    Childs, Sharon G

    2006-01-01

    Sprain injury to the 1st metatarsophalangeal joint is referred to as turf toe. The incidence of this injury has increased over the years secondary to athletic fields being covered by artificial turf and also by increased flexibility of the toe box in athletic shoes. The pathogenesis of turf toe will be presented in this article.

  18. Bacterial pathogenesis and mediators in apical periodontitis.

    PubMed

    Siqueira, José F; Rôças, Isabela N

    2007-01-01

    Apical periodontitis is a group of inflammatory diseases caused by microorganisms (mainly bacteria) infecting the necrotic root canal system. The pathogenesis of different types of apical periodontitis and even the same type in different individuals is unlikely to follow a stereotyped fashion with regard to the involved bacterial mediators. Disease pathogenesis is rather complex and involves a multitude of bacteria- and host-related factors. This review article discusses the bacterial pathogenesis of acute and chronic apical periodontitis, with the main focus on the bacterial mediators conceivably involved in the different stages of the infectious process, including secreted products (enzymes, exotoxins, N-formyl-methionyl-leucyl-phenylalanine peptides, heat-shock proteins and metabolic end-products) and structural components (lipopolysaccharide, peptidoglycan, lipoteichoic acid, lipoproteins, fimbriae, flagella, outer membrane proteins and vesicles, DNA, and exopolysaccharides). Knowledge of the bacterial factors involved in the pathogenesis of apical periodontitis is important to the understanding of the disease process and to help establishing proper therapeutic measures to inactivate this bacterial "artillery".

  19. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    progression; 2-) To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is...understanding of the infectious pathogenesis of prostate cancer. Aim II. To characterize the role of the infectious protozoa T. vaginalis in prostate

  20. Mumps virus pathogenesis: Insights and knowledge gaps.

    PubMed

    Gouma, Sigrid; Koopmans, Marion P G; van Binnendijk, Rob S

    2016-12-01

    The recent mumps outbreaks among MMR vaccinated persons have raised questions about the biological mechanisms related to mumps symptoms and complications in the background of waning immunity. Contrary to other paramyxoviruses, the understanding of mumps virus pathogenesis is limited, and further in-depth clinical studies are required to provide answers to important research questions.

  1. Hepatitis E: Molecular Virology and Pathogenesis

    PubMed Central

    Panda, Subrat K.; Varma, Satya P.K.

    2013-01-01

    Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5′ distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3′ distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV. PMID:25755485

  2. Leukocyte chemoattractant receptors in human disease pathogenesis.

    PubMed

    Zabel, Brian A; Rott, Alena; Butcher, Eugene C

    2015-01-01

    Combinations of leukocyte attractant ligands and cognate heptahelical receptors specify the systemic recruitment of circulating cells by triggering integrin-dependent adhesion to endothelial cells, supporting extravasation, and directing specific intratissue localization via gradient-driven chemotaxis. Chemoattractant receptors also control leukocyte egress from lymphoid organs and peripheral tissues. In this article, we summarize the fundamental mechanics of leukocyte trafficking, from the evolution of multistep models of leukocyte recruitment and navigation to the regulation of chemoattractant availability and function by atypical heptahelical receptors. To provide a more complete picture of the migratory circuits involved in leukocyte trafficking, we integrate a number of nonchemokine chemoattractant receptors into our discussion. Leukocyte chemoattractant receptors play key roles in the pathogenesis of autoimmune diseases, allergy, inflammatory disorders, and cancer. We review recent advances in our understanding of chemoattractant receptors in disease pathogenesis, with a focus on genome-wide association studies in humans and the translational implications of mechanistic studies in animal disease models.

  3. Pancreatic cancer: Pathogenesis, prevention and treatment

    SciTech Connect

    Sarkar, Fazlul H. Banerjee, Sanjeev; Li, Yiwei

    2007-11-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-{kappa}B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-{kappa}B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

  4. Helicobacter pylori virulence and cancer pathogenesis.

    PubMed

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  5. Pathogenesis of diabetic cerebral vascular disease complication

    PubMed Central

    Xu, Ren-Shi

    2015-01-01

    Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease (CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators, vascular smooth muscle dysfunction, oxidative stress, and the downregulation of miRs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication. PMID:25685278

  6. Vascular mechanisms in the pathogenesis of stroke.

    PubMed

    Sierra, Cristina; Coca, Antonio; Schiffrin, Ernesto L

    2011-06-01

    Stroke is one of the most devastating manifestations of two common diseases, atherosclerosis and hypertension. It represents the second leading cause of death and a major cause of disability worldwide. Besides age (a nonmodifiable risk factor), hypertension is the most important cardiovascular risk factor for developing both ischemic and hemorrhagic stroke, as well as small vessel disease predisposing to lacunar infarction, white matter lesions, and cerebral microbleeds. In addition, hypertension predisposes to atherosclerosis and cardiac diseases (notably atrial fibrillation), thereby promoting cerebral embolism. Inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Endothelial dysfunction, in part resulting from excessive production of reactive oxygen species, is an important mechanism of cerebrovascular damage. This article reviews recent data on vascular mechanisms that participate in the pathogenesis of stroke.

  7. Acne Scars: Pathogenesis, Classification and Treatment

    PubMed Central

    Fabbrocini, Gabriella; Annunziata, M. C.; D'Arco, V.; De Vita, V.; Lodi, G.; Mauriello, M. C.; Pastore, F.; Monfrecola, G.

    2010-01-01

    Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%–14% of cases with psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but several hypotheses have been proposed. There are numerous treatments: chemical peels, dermabrasion/microdermabrasion, laser treatment, punch techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy, cryotherapy, and surgery for hypertrophic and keloidal lesions. This paper summarizes acne scar pathogenesis, classification and treatment options. PMID:20981308

  8. Inflammatory bowel disease pathogenesis: where are we?

    PubMed

    Fiocchi, Claudio

    2015-03-01

    Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. [Pathogenesis of adhesions formation after intraabdominal operations].

    PubMed

    Voskanian, S É; Kyzlasov, P S

    2011-01-01

    The article describes the pathogenesis of adhesions formation after intraabdominal operations. Described predisposing factors leading of which is mechanical trauma, resulting from the use of surgical instruments, rough manipulations during surgery, damage to the mesothelium by dry gauze etc, which cause the adhesions. The pathogenesis of adhesions formation after intraabdominal surgery is presented in outline form, which described the changes occurring in the body starting with combination of predisposing factors and ending with the development of adhesions with blood vessels by 7-12 days after surgery. At the genetic level predisposition to adhesions formation and development of adhesive disease is treated as a manifestation of rapid acetylation phenotype, in which the intensity of fibrin formation exceeds normal rate of its catabolism. Thus, according to modem concepts, adhesive disease is a separate nosologic unit that dictates the necessity of its detailed study, development and introduction new universal methods of preventing the adhesions formation after intraabdominal operations.

  10. STAT3 Regulation of Glioblastoma Pathogenesis

    PubMed Central

    de la Iglesia, Núria; Puram, Sidharth V.; Bonni, Azad

    2009-01-01

    Malignant gliomas are the most common primary brain tumors. Despite efforts to find effective treatments, these tumors remain incurable. The failure of malignant gliomas to respond to conventional cancer therapies may reflect the unique biology of these tumors, underscoring the need for new approaches in their investigation. Recently, progress has been made in characterization of the molecular pathogenesis of glioblastoma using a developmental neurobiological perspective, by exploring the role of signaling pathways that control the differentiation of neural stem cells along the glial lineage. The transcription factor STAT3, which has an established function in neural stem cell and astrocyte development, has been found to play dual tumor suppressive and oncogenic roles in glial malignancy depending on the mutational profile of the tumor. These findings establish a novel developmental paradigm in the study of glioblastoma pathogenesis and provide the rationale for patient-tailored therapy in the treatment of this devastating disease. PMID:19601808

  11. [Current views on the pathogenesis of osteoarthritis].

    PubMed

    Łapaj, Łukasz; Markuszewski, Jacek; Wierusz-Kozłowska, Małgorzata

    2010-01-01

    Degenerative joint disease is the most common joint pathology and the main cause of disability of elderly people in developed countries. It is caused by imbalance between degeneration and regeneration of articular cartilage accompanied by pathological changes of other joint structures. No generally recognizable description of the pathogenetic pathway of osteoarthritis (OA) exists so far, however recent studies have widened the knowledge of the underlying pathology. In this review views regarding the role of genetic and mechanical factors in OA pathogenesis were presented. The role of pro-inflammatory mediators such as cytokines (IL-1, TNF-alfa, IL-6), lipid mediators, NO, reactive oxygen species, were discussed. The contribution of adipokines (fat tissue derived hormones with cytokine activity) to the pathogenesis of degenerative joint disease was also described. The role of synovial membrane, articular cartilage, subchondral bone and such structures as osteophytes and infrapatellar fat pad in development of osteoarthritis were presented as well.

  12. Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

    PubMed Central

    Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D

    2011-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319

  13. Pathogenesis and pathobiology of brucellosis in wildlife.

    PubMed

    Rhyan, J C

    2013-04-01

    Natural infections by Brucella spp. have been observed in wild populations. Owing to the similarity of lesions and the course of disease across host and pathogen species, the pathogenesis of brucellosis in wildlife is considered similar to that in domestic animals, which has been studied extensively. Similarities include tropism for reproductive and mammary tissues, trophoblast colonisation by the organism, and similar histopathological findings in organs, especially in the reproductive tract. Differences in the disease course exist and are likely to be attributable to immunological and behavioural differences among species. Further study of the pathogenesis and pathobiology of brucellosis in wildlife is expected to yield unique knowledge with application to disease management in both wild and domestic species.

  14. The epigenetic paradigm in periodontitis pathogenesis

    PubMed Central

    Lavu, Vamsi; Venkatesan, Vettriselvi; Rao, Suresh Ranga

    2015-01-01

    Epigenome refers to “epi” meaning outside the “genome.” Epigenetics is the field of study of the epigenome. Epigenetic modifications include changes in the promoter CpG Islands, modifications of histone protein structure, posttranslational repression by micro-RNA which contributes to the alteration of gene expression. Epigenetics provides an understanding of the role of gene-environment interactions on disease phenotype especially in complex multifactorial diseases. Periodontitis is a chronic inflammatory disorder that affects the supporting structures of the tooth. The role of the genome (in terms of genetic polymorphisms) in periodontitis pathogenesis has been examined in numerous studies, and chronic periodontitis has been established as a polygenic disorder. The potential role of epigenetic modifications in the various facets of pathogenesis of periodontitis is discussed in this paper based on the available literature. PMID:26015662

  15. Insights into the pathogenesis of Mycoplasma pneumoniae

    PubMed Central

    He, Jun; Liu, Mihua; Ye, Zhufeng; Tan, Tianping; Liu, Xinghui; You, Xiaoxing; Zeng, Yanhua; Wu, Yimou

    2016-01-01

    Mycoplasma are the smallest prokaryotic microbes present in nature. These wall-less, malleable organisms can pass through cell filters, and grow and propagate under cell-free conditions in vitro. Of the pathogenic Mycoplasma Mycoplasma pneumoniae has been examined the most. In addition to primary atypical pneumonia and community-acquired pneumonia with predominantly respiratory symptoms, M. pneumoniae can also induce autoimmune hemolytic anemia and other diseases in the blood, cardiovascular system, gastrointestinal tract and skin, and can induce pericarditis, myocarditis, nephritis and meningitis. The pathogenesis of M. pneumoniae infection is complex and remains to be fully elucidated. The present review aimed to summarize several direct damage mechanisms, including adhesion damage, destruction of membrane fusion, nutrition depletion, invasive damage, toxic damage, inflammatory damage and immune damage. Further investigations are required for determining the detailed pathogenesis of M. pneumoniae. PMID:27667580

  16. Genetic and epigenetic basis of psoriasis pathogenesis.

    PubMed

    Chandra, Aditi; Ray, Aditi; Senapati, Swapan; Chatterjee, Raghunath

    2015-04-01

    Psoriasis is a chronic inflammatory skin disease whose prevalence varies among different populations worldwide. It is a complex multi-factorial disease and the exact etiology is largely unknown. Family based studies have indicated a genetic predisposition; however they cannot fully explain the disease pathogenesis. In addition to genetic susceptibility, environmental as well as gender and age related factors were also been found to be associated. Recently, imbalances in epigenetic networks are indicated to be causative elements in psoriasis. The present knowledge of epigenetic involvement, mainly the DNA methylation, chromatin modifications and miRNA deregulation is surveyed here. An integrated approach considering genetic and epigenetic anomalies in the light of immunological network may explore the pathogenesis of psoriasis.

  17. Aetio-pathogenesis of breast cancer

    PubMed Central

    Abdulkareem, Imran Haruna

    2013-01-01

    This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, alcohol, obesity, lifestyle, physical inactivity, as well as endocrine factors. These factors act separately or together in the causation of breast cancer. More recently, triple negative breast cancer has been described in certain categories of patients and is associated with poorer prognosis and earlier recurrence compared with the conventional breast cancer. Therefore, adequate knowledge of these factors is important in identifying high risk groups and individuals, which will help in screening, early detection and follow-up. This will help to decrease the morbidity and mortality from this life-threatening disease. PMID:24665149

  18. Facial Dysostoses: Etiology, Pathogenesis and Management

    PubMed Central

    Trainor, Paul A.; Andrews, Brian T.

    2013-01-01

    Approximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one-third display craniofacial abnormalities which are a significant cause of infant mortality and dramatically affect national health care budgets. To date, more than 700 distinct craniofacial syndromes have been described and in this review, we discuss the etiology, pathogenesis and management of facial dysostoses with a particular emphasis on Treacher Collins, Nager and Miller syndromes. As we continue to develop and improve medical and surgical care for the management of individual conditions, it is essential at the same time to better characterize their etiology and pathogenesis. Here we describe recent advances in our understanding of the development of facial dysostosis with a view towards early in-utero identification and intervention which could minimize the manifestation of anomalies prior to birth. The ultimate management for any craniofacial anomaly however, would be prevention and we discuss this possibility in relation to facial dysostosis. PMID:24123981

  19. Pathogenesis of Cell Injury by Rickettsia conorii

    DTIC Science & Technology

    1985-05-17

    as erzymes associated with tickbite in the pathogenesis of the tache noire. Experimental studies suggest that the dose of Inoculum of r~ckef~ert...and~ host cell mewbrane injury on rickottsial penetration Into and/or release fr~imuthe target cell. Experimental evidiewci indicates that host...uninfected chambers. Thus, in an experimental system In which rickettsiae injured infected host cell’s, we demonstrated no effect of putative toxin

  20. [Chronic tonsillitis--pathogenesis, symptomatology and therapy].

    PubMed

    Andratschke, M; Hagedorn, H

    2005-09-29

    Chronic tonsillitis is a common disease entity which, on account of the possibility of the tonsils becoming a focus of infection, must not be made light of. The patient's complaints are highly uncharacteristic, and it is not always possible to establish the diagnosis on the local findings alone. Rather, the patient's history and general state of health must also be considered when considering the diagnosis. By reason of the pathogenesis, the treatment of choice can only be tonsillectomy.

  1. The Etiology and Pathogenesis of Viral Gastroenteritis.

    DTIC Science & Technology

    1984-07-31

    OF VIRAL GASTROENTERITIS Annual Progress Report by Neil R. Blacklov, M.D. 31 July, 1984 (For the Period 1983 - 1984) Supported By U.S. ARMY MEDICAL...TITLE (and Subtltle) 5. TYPE OF REPORT & PRIOD COVERED ANNUAl, THE ETIOLOGY AND PATHOGENESIS OF VIRAL ug.,1983-July 31, 1984 GASTROENTERITIS S...KEY WORDS (Continue on reverse side It necesary and Identify by block number) Viral gastroenteritis Diarrhea Epidenic gastroenteritis 20. ABSTRACT

  2. Biology and pathogenesis of Naegleria fowleri.

    PubMed

    Siddiqui, Ruqaiyyah; Ali, Ibne Karim M; Cope, Jennifer R; Khan, Naveed Ahmed

    2016-12-01

    Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with primary amoebic meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection.

  3. Pathogenesis of Chronic Urticaria: An Overview

    PubMed Central

    Jain, Sanjiv

    2014-01-01

    The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria. PMID:25120565

  4. [Pathogenesis and treatment of slow transit constipation].

    PubMed

    Zhang, Dongxu; Zhu, Anlong

    2016-12-25

    Slow transit constipation (STC) is generally considered as a complex idiopathic disease affected by multiple factors synergistically. Primarily caused by the condition of gut dysmotility, the transit of intestinal contents turned so slow that the moisture absorption increases, defecation frequency decreases, bowel movement is weakened or even disappeared with or without abdominal distension, dry and hard stool. Its etiology and pathogenesis remains unclear.Recently some researches reported the pathogenesis may be associated with the changes of the enteric nervous system (ENS), such as the change or degeneration of intestinal nerve cells, gut glial cell damage and neurotransmitter changes. Besides, intestinal myopathy, ICC reduction, immune factors, endocrine factors, laxative, mental psychological factors, diet and exercise habits may also be associated with the occurrence and aggravation of STC. The current understanding of STC mechanism can not meet the needs of clinical diagnosis and treatment. Conservative treatment is the main treatment of STC nowadays. For those receiving normative medical treatment but with little effect, surgery is necessary. "Jingling procedure" and "antiperistaltic anastomosis" can both get good efficacy. Treatment aiming at causes of disease will be uncovered as the development of the researches on the pathogenesis and treatment of slow transit constipation.

  5. Streptococcus-Zebrafish Model of Bacterial Pathogenesis

    PubMed Central

    Neely, Melody N.; Pfeifer, John D.; Caparon, Michael

    2002-01-01

    Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcus- zebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 103 CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease. PMID:12065534

  6. Pathogenesis of chronic urticaria: an overview.

    PubMed

    Jain, Sanjiv

    2014-01-01

    The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria.

  7. ATP in the pathogenesis of lung emphysema.

    PubMed

    Mortaz, Esmaeil; Braber, Saskia; Nazary, Maiwand; Givi, Masoumh Ezzati; Nijkamp, Frans P; Folkerts, Gert

    2009-10-01

    Extracellular ATP is a signaling molecule that often serves as a danger signal to alert the immune system of tissue damage. This molecule activates P2 nucleotide receptors, that include the ionotropic P2X receptors and metabotropic P2Y receptors. Recently, it has been reported that ATP accumulates in the airways of both asthmatic patients and sensitized mice after allergen challenge. The role and function of ATP in the pathogenesis of chronic obstructive pulmonary diseases (COPD) are not well understood. In this study we investigated the effect of cigarette smoke on purinergic receptors and ATP release by neutrophils. Neutrophils and their mediators are key players in the pathogenesis of lung emphysema. Here we demonstrated that in an in vivo model of cigarette smoke-induced lung emphysema, the amount of ATP was increased in the bronchoalveolar lavage fluid. Moreover, activation of neutrophils with cigarette smoke extract induced ATP release. Treatment of neutrophils with apyrase (catalyses the hydrolysis of ATP to yield AMP) and suramin (P2-receptor antagonist) abrogated the release of CXCL8 and elastase induced by cigarette smoke extract and exogenous ATP. These observations indicate that activation of purinergic signaling by cigarette smoke may take part in the pathogenesis of lung emphysema.

  8. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

    PubMed Central

    Gomaa, Asmaa Ibrahim; Khan, Shahid A; Toledano, Mireille B; Waked, Imam; Taylor-Robinson, Simon D

    2008-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance. PMID:18666317

  9. The bacterial pathogenesis and treatment of pouchitis

    PubMed Central

    McLaughlin, S. D.; Clark, S. K.; Tekkis, P. P.; Nicholls, R. J.; Ciclitira, P. J.

    2010-01-01

    Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis. Pouchitis is the most common cause of pouch dysfunction. Although the pathogenesis of this disease is not well understood, bacteria have been implicated in the disease process. Numerous bacterial studies have been reported over the last 25 years with few unifying findings. In addition, many different treatments for pouchitis have been reported with varying results. Antibiotic treatment remains the most studied and is the mainstay of treatment. In this article we review the aetiology of pouchitis and the evidenced-based treatment options. PMID:21180613

  10. Nonbacterial Thrombotic Endocarditis: Pathogenesis, Diagnosis, and Management.

    PubMed

    Liu, Joshua; Frishman, William H

    2016-01-01

    Nonbacterial thrombotic endocarditis (NBTE), formerly known as marantic endocarditis, is a potentially overlooked condition that involves the formation of sterile, fibrin vegetations on heart valve leaflets. Often confused with classic infective endocarditis during its early stages, NBTE can lead to valvular dysfunction, heart failure, and systemic embolization when unchecked. The pathogenesis is not entirely clear but involves a preexisting hypercoagulable state. Diagnosis requires ruling out infection and establishing the presence of valvular vegetations using echocardiography. Therapy for NBTE includes treating the underlying disease, systemic anticoagulation and surgical intervention.

  11. Pathogenesis of tendinopathies: inflammation or degeneration?

    PubMed Central

    Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto

    2009-01-01

    The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. PMID:19591655

  12. Chronic urticaria: a focus on pathogenesis.

    PubMed

    Asero, Riccardo; Tedeschi, Alberto; Marzano, Angelo Valerio; Cugno, Massimo

    2017-01-01

    Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients' quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder.

  13. Chronic urticaria: a focus on pathogenesis

    PubMed Central

    Asero, Riccardo; Tedeschi, Alberto; Marzano, Angelo Valerio; Cugno, Massimo

    2017-01-01

    Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients’ quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder. PMID:28751972

  14. The fascinating germ theories on cancer pathogenesis.

    PubMed

    Tsoucalas, G; Laios, K; Karamanou, M; Gennimata, V; Androutsos, G

    2014-01-01

    For more than 100 years, the germ theory of cancer, proposing that microorganisms were at the origin of the disease, dominated medicine. Several eminent scientists like Etienne Burnet, Mikhail Stepanovich Voronin, Charles-Louis Malassez, and Francis-Peyton Rous argued on the pathogenesis presenting their theories that implicated cocci, fungi and parasites. The impact of these theories was culminated by the Nobel Prize in 1926 that was attributed to the Danish scientist Johannes Fibiger for his work on the nematode Spiroptera as a causative agent in cancer. Even if those theories were the result of fantasy and misinterpretation, they paved the way for the scientific research in oncology.

  15. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  16. Recent Advances in Understanding Norovirus Pathogenesis

    PubMed Central

    Karst, Stephanie M.; Tibbetts, Scott A.

    2016-01-01

    Noroviruses constitute a family of ubiquitous and highly efficient human pathogens. In spite of decades of dedicated research, human noroviruses remain a major cause of gastroenteritis and severe diarrheal disease around the world. Recent findings have begun to unravel the complex mechanisms that regulate norovirus pathogenesis and persistent infection, including the important interplay between the virus, the host immune system, and commensal bacteria. Herein, we will summarize recent research developments regarding norovirus cell tropism, the use of M cells, and commensal bacteria to facilitate norovirus infection, and virus, host, and bacterial determinants of persistent norovirus infections. PMID:27110852

  17. [Some aspects of pathogenesis of ankylosing spondylitis].

    PubMed

    Erdes, Sh

    2011-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the spine (spondylitis) and sacroiliac joints (sacroileitis) associated in many cases with inflammatory affection of the peripheral joints (arthritis), entesises (entesitis), eyes (uveitis), intestine (enteritis) and aortic root (aortitis). AS is considered now as a prototype of diseases from the group of seronegative spondyloarthritis. AS is a hereditary disease. Predisposition to AS (90%) is associated with genetic factors the key gene of which is HLA-B27. As pathogenesis of AS is not still verified, three hypotheses are considered basing on HLA-B27 biology. The role of environmental factors involved in AS development (tension in enteses and infection) are discussed.

  18. Cellular and molecular mechanisms of chikungunya pathogenesis.

    PubMed

    Lum, Fok-Moon; Ng, Lisa F P

    2015-08-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus that causes chikungunya fever, a disease characterized by the onset of fever and rashes, with arthralgia as its hallmark symptom. CHIKV has re-emerged over the past decade, causing numerous outbreaks around the world. Since late 2013, CHIKV has reached the shores of the Americas, causing more than a million cases of infection. Despite concentrated efforts to understand the pathogenesis of the disease, further outbreaks remain a threat. This review highlights important findings regarding CHIKV-associated immunopathogenesis and offers important insights into future directions. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."

  19. [Endothelin-1 in pathogenesis of Raynaud's syndrome].

    PubMed

    Knapik-Kordecka, M; Adamiec, R; Ciosek, W

    2001-06-01

    Endothelin is an endogenous vasoconstrictor and plays an important role in pathogenesis of Raynaud's phenomenon. Plasma endothelin-1 (ET-1) and von Willebrand factor (vWF) concentrations following cold exposure in 52 patients with Raynaud's phenomenon were measured. Statistically significant increase of ET-1 and vWF was found in the study group in compare to healthy volunteers. There was positive correlation between ET-1 and vWF in those cases. The dates suggest that ET-changes indicates a vasospastic effect on vascular injury. Treatment with endothelin-receptor antagonist may prevent structural changes in vessel well.

  20. Pathogenesis of postoperative oral surgical pain.

    PubMed Central

    Ong, Cliff K. S.; Seymour, R. A.

    2003-01-01

    Pain is a major postoperative symptom in many oral surgical procedures. It is a complex and variable phenomenon that can be influenced by many factors. Good management of oral surgical pain requires a detailed understanding of the pathogenesis of surgical pain. This article aims at reviewing postoperative pain from a broad perspective by looking into the nociception, neuroanatomy, neurophysiology, and neuropharmacology of pain. Therapeutic recommendations are made after reviewing the evidence from the literature for maximizing the efficacy of pain management techniques for oral surgical pain. PMID:12722900

  1. Urinary Tract Infection: Pathogenesis and Outlook.

    PubMed

    McLellan, Lisa K; Hunstad, David A

    2016-11-01

    The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Pathogenesis and treatment of pseudofolliculitis barbae.

    PubMed

    Brown, L A

    1983-10-01

    Pseudofolliculitis barbae is a condition in which a foreign body inflammatory reaction surrounds an ingrown hair. Shaving is the major cause, especially in persons with wavy or curly hair. Among black men who shave, the disease is of particular concern because of both social pressures and limited medical understanding concerning its treatment. The pathogenesis of the disease as well as treatment modalities are presented. General measures, as well as specific techniques involving use of electric clippers, chemical depilatories, manual razors, and complete epilation are discussed. Adjuvant measures are presented such as antibiotics and, in very special cases, retinoic acid.

  3. Treacher Collins syndrome: etiology, pathogenesis and prevention

    PubMed Central

    Trainor, Paul A; Dixon, Jill; Dixon, Michael J

    2009-01-01

    Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. Identifying potential avenues for rescue and/or repair of TCS depends on a profound appreciation of the etiology and pathogenesis of the syndrome. Recent research using animal models has not only determined the cellular basis of TCS but also, more importantly, unveiled a successful avenue for therapeutic intervention and prevention of the craniofacial anomalies observed in TCS. PMID:19107148

  4. Molecular pathogenesis and mechanisms of thyroid cancer

    PubMed Central

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  5. Physiology and pathogenesis of gastroesophageal reflux disease.

    PubMed

    Mikami, Dean J; Murayama, Kenric M

    2015-06-01

    Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Etiology and Pathogenesis of Psoriatic Arthritis.

    PubMed

    Barnas, Jennifer L; Ritchlin, Christopher T

    2015-11-01

    The current model of psoriatic arthritis implicates both the IL-23/IL-17 axis and the tumor necrosis factor (TNF) pathways in disease pathogenesis. Although specific major histocompatibility complex class I molecules are associated with the psoriatic disease phenotype, no specific antigen or autoantibody has been identified. Instead, an array of genes may code for an autoinflammatory loop, potentially activated by mechanical stress and dysbiosis in the skin or gut. Danger signals released by innate immune cells activate a Th1 and Th17 response that leads to synovitis, enthesitis, axial inflammation, and altered bone homeostasis characterized by pathologic bone resorption and new bone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Metabolic Factors that Contribute to Lupus Pathogenesis

    PubMed Central

    Li, Wei; Sivakumar, Ramya; Titov, Anton A.; Choi, Seung-Chul; Morel, Laurence

    2017-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism. PMID:27480903

  8. Cytokines and Chemokines in Cerebral Malaria Pathogenesis.

    PubMed

    Dunst, Josefine; Kamena, Faustin; Matuschewski, Kai

    2017-01-01

    Cerebral malaria is among the major causes of malaria-associated mortality and effective adjunctive therapeutic strategies are currently lacking. Central pathophysiological processes involved in the development of cerebral malaria include an imbalance of pro- and anti-inflammatory responses to Plasmodium infection, endothelial cell activation, and loss of blood-brain barrier integrity. However, the sequence of events, which initiates these pathophysiological processes as well as the contribution of their complex interplay to the development of cerebral malaria remain incompletely understood. Several cytokines and chemokines have repeatedly been associated with cerebral malaria severity. Increased levels of these inflammatory mediators could account for the sequestration of leukocytes in the cerebral microvasculature present during cerebral malaria, thereby contributing to an amplification of local inflammation and promoting cerebral malaria pathogenesis. Herein, we highlight the current knowledge on the contribution of cytokines and chemokines to the pathogenesis of cerebral malaria with particular emphasis on their roles in endothelial activation and leukocyte recruitment, as well as their implication in the progression to blood-brain barrier permeability and neuroinflammation, in both human cerebral malaria and in the murine experimental cerebral malaria model. A better molecular understanding of these processes could provide the basis for evidence-based development of adjunct therapies and the definition of diagnostic markers of disease progression.

  9. Cytokines and Chemokines in Cerebral Malaria Pathogenesis

    PubMed Central

    Dunst, Josefine; Kamena, Faustin; Matuschewski, Kai

    2017-01-01

    Cerebral malaria is among the major causes of malaria-associated mortality and effective adjunctive therapeutic strategies are currently lacking. Central pathophysiological processes involved in the development of cerebral malaria include an imbalance of pro- and anti-inflammatory responses to Plasmodium infection, endothelial cell activation, and loss of blood-brain barrier integrity. However, the sequence of events, which initiates these pathophysiological processes as well as the contribution of their complex interplay to the development of cerebral malaria remain incompletely understood. Several cytokines and chemokines have repeatedly been associated with cerebral malaria severity. Increased levels of these inflammatory mediators could account for the sequestration of leukocytes in the cerebral microvasculature present during cerebral malaria, thereby contributing to an amplification of local inflammation and promoting cerebral malaria pathogenesis. Herein, we highlight the current knowledge on the contribution of cytokines and chemokines to the pathogenesis of cerebral malaria with particular emphasis on their roles in endothelial activation and leukocyte recruitment, as well as their implication in the progression to blood-brain barrier permeability and neuroinflammation, in both human cerebral malaria and in the murine experimental cerebral malaria model. A better molecular understanding of these processes could provide the basis for evidence-based development of adjunct therapies and the definition of diagnostic markers of disease progression. PMID:28775960

  10. [Etiology and pathogenesis of primary hyperparathyroidism.

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2017-01-01

    Primary hyperparathyroidism(pHPT)is a frequent endocrine disease in which abnormal calcium(Ca)regulation leads to hypercalcemia. The most frequent cause of pHPT in more than 80% of patients is an adenoma, followed by hyperplasia in about 15%, and cancer in 1~5%. Although most cases of pHPT are sporadic, a few are familial(hereditary), and this is known as familial hyperparathyroidism(FHPT). Gene abnormalities that affect cyclin D1 signaling(CCND1, CDC73, CDKN1B), Wnt/β-catenin signaling(MEN1), and calcium-sensing receptor signaling(CaSR, GNA11, AP2S1)play a role in the etiology and pathogenesis of pHPT. Vitamin D insufficiency/deficiency and CaSR dysfunction also play a role in pHPT severity. Continued elucidation of the etiology and pathogenesis of pHPT may lead to development of new treatments for pHPT as well as further understanding of Ca regulation.

  11. Measles Virus Host Invasion and Pathogenesis

    PubMed Central

    Laksono, Brigitta M.; de Vries, Rory D.; McQuaid, Stephen; Duprex, W. Paul; de Swart, Rik L.

    2016-01-01

    Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150+ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis. PMID:27483301

  12. OXIDANTS AND THE PATHOGENESIS OF LUNG DISEASES

    PubMed Central

    Ciencewicki, Jonathan; Trivedi, Shweta; Kleeberger, Steven R.

    2009-01-01

    The increasing number of population-based and epidemiological associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid (ELF) of the lung. Furthermore, it is clear that inter-individual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (e.g. asthma, COPD, and ARDS), and the potential risk factors (e.g. age, genetics) for enhanced susceptibility to oxidant-induced disease. PMID:18774381

  13. Irritable bowel syndrome: Diagnosis and pathogenesis

    PubMed Central

    El-Salhy, Magdy

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

  14. Transport proteins promoting Escherichia coli pathogenesis.

    PubMed

    Tang, Fengyi; Saier, Milton H

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies.

  15. [Risk factors and pathogenesis of Hashimoto's thyroiditis].

    PubMed

    Paknys, Gintaras; Kondrotas, Anatolijus Juozas; Kevelaitis, Egidijus

    2009-01-01

    The aim of this review is to summarize the current knowledge on Hashimoto's thyroiditis and its pathogenesis and to introduce the readers to the basic concept of autoimmune thyroid disease. Hashimoto's thyroiditis and Graves' disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient. During this response, cytotoxic autoantibodies, stimulatory autoantibodies, blocking autoantibodies, or cell-mediated autoimmunity may be observed. Persons with classic Hashimoto's thyroiditis have serum antibodies reacting with thyroglobulin and thyroid peroxidase. These antibodies (particularly antibodies against thyroid peroxidase) are complement-fixing immunoglobulins and may be cytotoxic. In addition, many patients have cell-mediated immunity directed against thyroid antigens. Cell mediated-immunity is also a feature of experimental thyroiditis induced in animals by injection of thyroid antigen with adjuvants. Hashimoto's thyroiditis is predominantly the clinical expression of cell-mediated immunity leading to destruction of thyroid cells, which in its severest form causes thyroid failure. The significance of genetic component and nongenetic risk factors (pregnancy, drugs, age, sex, infection, and irradiation) in the development of Hashimoto's thyroiditis is also reviewed. Epidemiologic studies have demonstrated that the genetic component is important in the pathogenesis of Hashimoto's thyroiditis, although the pattern of inheritance is non-Mendelian and is likely to be influenced by subtle variations in the functions of multiple genes. Nongenetic risk factors (environmental factors) are also etiologically important, because the concordance rate in monozygotic twins is below 1.

  16. Redox control of prion and disease pathogenesis.

    PubMed

    Singh, Neena; Singh, Ajay; Das, Dola; Mohan, Maradumane L

    2010-06-01

    Imbalance of brain metal homeostasis and associated oxidative stress by redox-active metals like iron and copper is an important trigger of neurotoxicity in several neurodegenerative conditions, including prion disorders. Whereas some reports attribute this to end-stage disease, others provide evidence for specific mechanisms leading to brain metal dyshomeostasis during disease progression. In prion disorders, imbalance of brain-iron homeostasis is observed before end-stage disease and worsens with disease progression, implicating iron-induced oxidative stress in disease pathogenesis. This is an unexpected observation, because the underlying cause of brain pathology in all prion disorders is PrP-scrapie (PrP(Sc)), a beta-sheet-rich conformation of a normal glycoprotein, the prion protein (PrP(C)). Whether brain-iron dyshomeostasis occurs because of gain of toxic function by PrP(Sc) or loss of normal function of PrP(C) remains unclear. In this review, we summarize available evidence suggesting the involvement of oxidative stress in prion-disease pathogenesis. Subsequently, we review the biology of PrP(C) to highlight its possible role in maintaining brain metal homeostasis during health and the contribution of PrP(Sc) in inducing brain metal imbalance with disease progression. Finally, we discuss possible therapeutic avenues directed at restoring brain metal homeostasis and alleviating metal-induced oxidative stress in prion disorders.

  17. The pathogenesis of obstructive sleep apnea

    PubMed Central

    Schwartz, Alan R.

    2015-01-01

    Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality, and represents an increasing burden on health care resources. Understanding underlying pathogenic mechanisms of OSA will ultimately allow for the development of rational therapeutic strategies. In this article, we review current concepts about the pathogenesis of OSA. Specifically, we consider the evidence that the upper airway plays a primary role in OSA pathogenesis and provide a framework for modelling its biomechanical properties and propensity to collapse during sleep. Anatomical and neuromuscular factors that modulate upper airway obstruction are also discussed. Finally, we consider models of periodic breathing, and elaborate generalizable mechanisms by which upper airway obstruction destabilizes respiratory patterns during sleep. In our model, upper airway obstruction triggers a mismatch between ventilatory supply and demand. In this model, trade-offs between maintaining sleep stability or ventilation can account for a full range of OSA disease severity and expression. Recurrent arousals and transient increases in airway patency may restore ventilation between periods of sleep, while alterations in neuromuscular and arousal responses to upper airway obstruction may improve sleep stability at still suboptimal levels of ventilation. PMID:26380762

  18. Transport proteins promoting Escherichia coli pathogenesis

    PubMed Central

    Tang, Fengyi; Saier, Milton H.

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. PMID:24747185

  19. Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma

    PubMed Central

    Rizvi, Sumera; Gores, Gregory J.

    2013-01-01

    Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic (iCCA), perihilar (pCCA), or distal CCA (dCCA). These subtypes differ not only in their anatomic location but in epidemiology, origin, etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has been increasing over the past 3 decades, and only a low percentage of patients survive until 5 y after diagnosis. Geographic variations in the incidence of CCA are related to variations in risk factors. Changes in oncogene and inflammatory signaling pathways, as well as genetic and epigenetic alterations and chromosome aberrations, have been shown to contribute to development of CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer-associated fibroblasts, which promotes their progression. We have gained a better understanding of the imaging characteristics of iCCAs and have developed advanced cytologic techniques to detect pCCAs. Patients with iCCAs are usually treated surgically, whereas liver transplantation following neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology, pathogenesis, of CCA, along with advances in classification, diagnosis and treatment. PMID:24140396

  20. Measles Virus Host Invasion and Pathogenesis.

    PubMed

    Laksono, Brigitta M; de Vries, Rory D; McQuaid, Stephen; Duprex, W Paul; de Swart, Rik L

    2016-07-28

    Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150⁺ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis.

  1. Eosinophilic oesophagitis: clinical presentation and pathogenesis

    PubMed Central

    Bystrom, Jonas; O'Shea, Nuala R

    2014-01-01

    Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available. PMID:24647582

  2. [Analyzing the Chinese medicine pathogenesis of stroke].

    PubMed

    Zhang, Jiu-Liang; Li, Ying-Zi; Yang, Hai-Ying

    2012-01-01

    Both ischemic and hemorrhage stroke pertain to the category of wind stroke in Chinese medicine (CM). Up to date, it is deemed that the etiology and pathogenesis of wind stroke are wind, fire, sputum, qi, stasis, and deficiency. Among them, it is regarded that wind and fire are the key factors triggering wind stroke. By analyzing the time order and causality, it is found that wind stroke is prior to the onset of wind and fire, wind and fire are the secondary outcomes of wind stroke. By parallel comparing stroke with thromboembolism and hemorrhagic diseases in other Zang-organs, it can be comprehended that the reason why wind symptoms appear in stroke is due to its physiological feature of brain itself. Based on Neijing, the pathogenesis of wind stroke is proposed as follows. Tunnels of viscera (vessels) get lesions. The old pathogenic factors of sputum and stasis or the stasis formed by bleeding inside viscera consume qi, and blood of viscera and damage the spirits hidden in them. The damage of Gan-spirit causes symptoms of stroke, such as hemiplegia, deviation of eyes and mouth, and so on. Wind and fire symptoms are caused by the injury of Gan blood and yin, and/or the stagnation of fire in pericardium (the pathway organ) due to obstruction by old pathogenic factors and stasis (formed by bleeding).

  3. Exosomes: Implications in HIV-1 Pathogenesis

    PubMed Central

    Madison, Marisa N.; Okeoma, Chioma M.

    2015-01-01

    Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging therapeutic options based on exosomal cargos that may have promise in preventing HIV-1 transmission. PMID:26205405

  4. Redox Control of Prion and Disease Pathogenesis

    PubMed Central

    Singh, Ajay; Das, Dola; Mohan, Maradumane L.

    2010-01-01

    Abstract Imbalance of brain metal homeostasis and associated oxidative stress by redox-active metals like iron and copper is an important trigger of neurotoxicity in several neurodegenerative conditions, including prion disorders. Whereas some reports attribute this to end-stage disease, others provide evidence for specific mechanisms leading to brain metal dyshomeostasis during disease progression. In prion disorders, imbalance of brain-iron homeostasis is observed before end-stage disease and worsens with disease progression, implicating iron-induced oxidative stress in disease pathogenesis. This is an unexpected observation, because the underlying cause of brain pathology in all prion disorders is PrP-scrapie (PrPSc), a β-sheet–rich conformation of a normal glycoprotein, the prion protein (PrPC). Whether brain-iron dyshomeostasis occurs because of gain of toxic function by PrPSc or loss of normal function of PrPC remains unclear. In this review, we summarize available evidence suggesting the involvement of oxidative stress in prion-disease pathogenesis. Subsequently, we review the biology of PrPC to highlight its possible role in maintaining brain metal homeostasis during health and the contribution of PrPSc in inducing brain metal imbalance with disease progression. Finally, we discuss possible therapeutic avenues directed at restoring brain metal homeostasis and alleviating metal-induced oxidative stress in prion disorders. Antioxid. Redox Signal. 12, 1271–1294. PMID:19803746

  5. Exosomes: Implications in HIV-1 Pathogenesis.

    PubMed

    Madison, Marisa N; Okeoma, Chioma M

    2015-07-20

    Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging therapeutic options based on exosomal cargos that may have promise in preventing HIV-1 transmission.

  6. Pathogenesis and treatment modalities of localized scleroderma.

    PubMed

    Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

    2010-01-01

    Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

  7. Epidemiology, pathogenesis, and management of takotsubo syndrome.

    PubMed

    Y-Hassan, Shams; Tornvall, Per

    2017-09-15

    Takotsubo syndrome is a recently recognized acute cardiac disease entity with a clinical presentation resembling that of an acute coronary syndrome. The typical takotsubo syndrome patient has a unique circumferential left (bi-) ventricular contraction abnormality profile that extends beyond a coronary artery supply territory and appears to follow the anatomical cardiac sympathetic innervation. The syndrome predominantly affects postmenopausal women and is often preceded by emotional or physical stress. Patients with predisposing factors such as malignancy and other chronic comorbidities are more prone to suffer from takotsubo syndrome. The pathogenesis of takotsubo syndrome is elusive. Several pathophysiological mechanisms involving myocardial ischemia (multivessel coronary artery spasm, microvascular dysfunction, aborted myocardial infarction), left ventricular outlet tract obstruction, blood-borne catecholamine myocardial toxicity, epinephrine-induced switch in signal trafficking, and autonomic nervous system dysfunction have been proposed. The syndrome is usually reversible; nevertheless, during the acute stage, a substantial number of patients develop severe complications such as arrhythmias, heart failure including pulmonary edema and cardiogenic shock, thromboembolism, cardiac arrest, and rupture. Treatment of precipitating factors, predisposing diseases, and complications is fundamental during the acute stage of the disease. The epidemiology, pathogenesis, and management of takotsubo syndrome are reviewed in this paper.

  8. [Pathogenesis and clinical features of polypous rhinosinusitis].

    PubMed

    Trofimenko, S L

    2010-01-01

    The paper presents recommendations of the current European and Russian documents concerning pathogenesis of polypous rhinosinusitis (International Consensus Conference on Nasal Polyposis (2006), European documents EAACI - EP3OS (2007), and Summit of the Russian Society of Rhinologists "Nasal polyposis and inflammation" (2009)). The bilateral polypous process in the nasal cavity is considered to be a "special form of rhinosinusitis" in which bacterial superantigens or fungal infection induce chronic eosinophilic inflammation. Researchers of the ENT Department, Rostov State Medical University, undertook analysis of the results of long-term comprehensive examination of patients with polypous rhinosinusitis that included clinical, bacteriological, histomorphological, and allergological studies as well as evaluation of local and systemic immunity. The data obtained allowed to describe one of the forms of polypous rhinosinusitis as chronic infection-dependent allergic rhinosinusitis with the manifestation of all four types of allergic reactions, formation of the autoimmune component, and development of persistent immune inflammation leading to remodeling of endonasal mucosa. In all these cases, the process progressed parallel to the development of combined secondary immune deficiency (SID). A hypothetical scheme of pathogenesis of chronic polypous allergic rhinosinusitis is proposed.

  9. Proteasome functional insufficiency in cardiac pathogenesis

    PubMed Central

    Li, Jie; Zheng, Hanqiao; Su, Huabo; Powell, Saul R.

    2011-01-01

    The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past several years, remarkable progress in understanding the mechanisms that regulate UPS-mediated protein degradation has been achieved. A transgenic mouse model of benign enhancement of cardiac proteasome proteolytic function has been created. This has led to the first demonstration of the necessity of proteasome functional insufficiency in the genesis of important pathological processes. Cardiomyocyte-restricted enhancement of proteasome proteolytic function by overexpression of proteasome activator 28α protects against cardiac proteinopathy and myocardial ischemia-reperfusion injury. Additionally, exciting advances have recently been achieved in the search for a pharmacological agent to activate the proteasome. These breakthroughs are expected to serve as an impetus to further investigation into the involvement of UPS dysfunction in molecular pathogenesis and to the development of new therapeutic strategies for combating heart disease. An interplay between the UPS and macroautophagy is increasingly suggested in noncardiac systems but is not well understood in the cardiac system. Further investigations into the interplay are expected to provide a more comprehensive picture of cardiac protein quality control and degradation. PMID:21949118

  10. Channelopathy pathogenesis in autism spectrum disorders

    PubMed Central

    Schmunk, Galina; Gargus, J. Jay

    2013-01-01

    Autism spectrum disorder (ASD) is a syndrome that affects normal brain development and is characterized by impaired social interaction as well as verbal and non-verbal communication and by repetitive, stereotypic behavior. ASD is a complex disorder arising from a combination of multiple genetic and environmental factors that are independent from racial, ethnic and socioeconomical status. The high heritability of ASD suggests a strong genetic basis for the disorder. Furthermore, a mounting body of evidence implies a role of various ion channel gene defects (channelopathies) in the pathogenesis of autism. Indeed, recent genome-wide association, and whole exome- and whole-genome resequencing studies linked polymorphisms and rare variants in calcium, sodium and potassium channels and their subunits with susceptibility to ASD, much as they do with bipolar disorder, schizophrenia and other neuropsychiatric disorders. Moreover, animal models with these genetic variations recapitulate endophenotypes considered to be correlates of autistic behavior seen in patients. An ion flux across the membrane regulates a variety of cell functions, from generation of action potentials to gene expression and cell morphology, thus it is not surprising that channelopathies have profound effects on brain functions. In the present work, we summarize existing evidence for the role of ion channel gene defects in the pathogenesis of autism with a focus on calcium signaling and its downstream effects. PMID:24204377

  11. Pathogenesis of Guillain-Barré syndrome.

    PubMed

    Hughes, R A; Hadden, R D; Gregson, N A; Smith, K J

    1999-12-01

    Recent neurophysiological and pathological studies have led to a reclassification of the diseases that underlie Guillain-Barré syndrome (GBS) into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). The Fisher syndrome of ophthalmoplegia, ataxia and areflexia is the most striking of several related conditions. Significant antecedent events include Campylobacter jejuni (4-66%), cytomegalovirus (5-15%), Epstein-Barr virus (2-10%), and Mycoplasma pneumoniae (1-5%) infections. These infections are not uniquely associated with any clinical subtype but severe axonal degeneration is more common following C. jejuni and severe sensory impairment following cytomegalovirus. Strong evidence supports an important role for antibodies to gangliosides in pathogenesis. In particular antibodies to ganglioside GM1 are present in 14-50% of patients with GBS, and are more common in cases with severe axonal degeneration associated with any subtype. Antibodies to ganglioside GQ1b are very closely associated with Fisher syndrome, its formes frustes and related syndromes. Ganglioside-like epitopes exist in the bacterial wall of C. jejuni. Infection by this and other organisms triggers an antibody response in patients with GBS but not in those with uncomplicated enteritis. The development of GBS is likely to be a consequence of special properties of the infecting organism, since some strains such as Penner 0:19 and 0:41 are particularly associated with GBS but not with enteritis. It is also likely to be a consequence of the immunogenetic background of the patient since few patients develop GBS after infection even with one of these strains. Attempts to match the subtypes of GBS to the fine specificity of anti-ganglioside antibodies and to functional effects in experimental models continue but have not yet fully explained the pathogenesis. T cells are also involved in the pathogenesis of

  12. Neuromyelitis optica pathogenesis and aquaporin 4

    PubMed Central

    Graber, David J; Levy, Michael; Kerr, Douglas; Wade, William F

    2008-01-01

    Neuromyelitis optica (NMO) is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord. An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been identified in the sera of a significant number of NMO patients, as well as in patients with two related neurologic conditions, bilateral optic neuritis (ON), and longitudinal extensive transverse myelitis (LETM), that are generally considered to lie within the NMO spectrum of diseases. NMO-IgG is not the only autoantibody found in NMO patient sera, but the correlation of pathology in central nervous system (CNS) with tissues that normally express high levels of AQP4 suggests NMO-IgG might be pathogenic. If this is the case, it is important to identify and understand the mechanism(s) whereby an immune response is induced against AQP4. This review focuses on open questions about the "events" that need to be understood to determine if AQP4 and NMO-IgG are involved in the pathogenesis of NMO. These questions include: 1) How might AQP4-specific T and B cells be primed by either CNS AQP4 or peripheral pools of AQP4? 2) Do the different AQP4-expressing tissues and perhaps the membrane structural organization of AQP4 influence NMO-IgG binding efficacy and thus pathogenesis? 3) Does prior infection, genetic predisposition, or underlying immune dysregulation contribute to a confluence of events which lead to NMO in select individuals? A small animal model of NMO is essential to demonstrate whether AQP4 is indeed the incipient autoantigen capable of inducing NMO-IgG formation and NMO. If the NMO model is consistent with the human disease, it can be used to examine how changes in AQP4 expression and blood-brain barrier (BBB) integrity, both of which can be regulated by CNS inflammation, contribute to inductive events for anti-AQP4-specific immune response. In this review, we identify reagents and experimental questions that need to be developed and addressed

  13. Pathogenesis of acne vulgaris: recent advances.

    PubMed

    Bhambri, Sanjay; Del Rosso, James Q; Bhambri, Avani

    2009-07-01

    Acne vulgaris is the most common disorder seen in ambulatory dermatology practice. Acne causes significant morbidity and the direct costs associated with it exceed $2.2 billion per year in the United States (U.S.). The pathogenesis is multifactorial, and our understanding of the mechanisms involved in the development of acne lesions has improved with time. Follicular hyperkeratinization, sebum production, presence of Propionibacterium acnes (P. acnes), inflammatory mediators, and androgens have been identified as key components of acne pathophysiology. Recent advances have been made in this area with the discovery of P. acnes interaction with Toll-like receptors (TLRs), vaccines targeting P. acnes or its components, antimicrobial peptides and the role of hormones.

  14. Huntingtin processing in pathogenesis of Huntington disease.

    PubMed

    Qin, Zheng-Hong; Gu, Zhen-Lun

    2004-10-01

    Huntingtons disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin. The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis. Copyright 2004 Acta Pharmacologica Sinica

  15. Pathogenesis of Staphylococcus aureus Bloodstream Infections

    PubMed Central

    Thomer, Lena; Schneewind, Olaf; Missiakas, Dominique

    2016-01-01

    Staphylococcus aureus , a Gram-positive bacterium colonizing nares, skin, and the gastrointestinal tract, frequently invades the skin, soft tissues, and bloodstreams of humans. Even with surgical and antibiotic therapy, bloodstream infections are associated with significant mortality. The secretion of coagulases, proteins that associate with and activate the host hemostatic factor prothrombin, and the bacterial surface display of agglutinins, proteins that bind polymerized fibrin, are key virulence strategies for the pathogenesis of S. aureus bloodstream infections, which culminate in the establishment of abscess lesions. Pathogen-controlled processes, involving a wide spectrum of secreted factors, are responsible for the recruitment and destruction of immune cells, transforming abscess lesions into purulent exudate, with which staphylococci disseminate to produce new infectious lesions or to infect new hosts. Research on S. aureus bloodstream infections is a frontier for the characterization of protective vaccine antigens and the development of immune therapeutics aiming to prevent disease or improve outcomes. PMID:26925499

  16. The Pathogenesis of Rift Valley Fever

    PubMed Central

    Ikegami, Tetsuro; Makino, Shinji

    2011-01-01

    Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. PMID:21666766

  17. Cerebral malaria--clinical manifestations and pathogenesis.

    PubMed

    Hora, Rachna; Kapoor, Payal; Thind, Kirandeep Kaur; Mishra, Prakash Chandra

    2016-04-01

    One of the most common central nervous system diseases in tropical countries is cerebral malaria (CM). Malaria is a common protozoan infection that is responsible for enormous worldwide mortality and economic burden on the society. Episodes of Plasmodium falciparum (Pf) caused CM may be lethal, while survivors are likely to suffer from persistent debilitating neurological deficits, especially common in children. In this review article, we have summarized the various symptoms and manifestations of CM in children and adults, and entailed the molecular basis of the disease. We have also emphasized how pathogenesis of the disease is effected by the parasite and host responses including blood brain barrier (BBB) disruption, endothelial cell activation and apoptosis, nitric oxide bioavailability, platelet activation and apoptosis, and neuroinflammation. Based on a few recent studies carried out in experimental mouse malaria models, we propose a basis for the neurological deficits and sequelae observed in human cerebral malaria, and summarize how existing drugs may improve prognosis in affected individuals.

  18. The Molecular Pathogenesis of Osteosarcoma: A Review

    PubMed Central

    Broadhead, Matthew L.; Clark, Jonathan C. M.; Myers, Damian E.; Dass, Crispin R.; Choong, Peter F. M.

    2011-01-01

    Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management. PMID:21559216

  19. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.

    PubMed

    Su, Shuo; Wong, Gary; Shi, Weifeng; Liu, Jun; Lai, Alexander C K; Zhou, Jiyong; Liu, Wenjun; Bi, Yuhai; Gao, George F

    2016-06-01

    Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Pathogenesis and Molecular Mechanisms of Zika Virus.

    PubMed

    Nayak, Shriddha; Lei, Jun; Pekosz, Andrew; Klein, Sabra; Burd, Irina

    2016-09-01

    Zika virus (ZIKV) is one of the most important emerging viruses of 2016. A developing outbreak in the Americas has demonstrated an association between the virus and serious clinical manifestations, such as Guillain-Barré syndrome in adults and congenital malformations in infants born to infected mothers. Pathogenesis and mechanisms of neurologic or immune disease by ZIKV have not been clearly delineated. However, several pathways have been described to explain viral involvement in brain and immune system as well as other organ systems such as eye, skin, and male and female reproductive tracts. ZIKV activates toll-like receptor 3 and several pathways have been described to explain the mechanisms at a molecular level. The mechanism of microcephaly has been more difficult to demonstrate experimentally, likely due to the multifactorial and complex nature of the phenotype. This article provides an overview of existing literature on ZIKV pathogenicity and possible molecular mechanisms of disease as outlined to date.

  1. The pathogenesis of Rift Valley fever.

    PubMed

    Ikegami, Tetsuro; Makino, Shinji

    2011-05-01

    Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis.

  2. MicroRNA involvement in glioblastoma pathogenesis

    SciTech Connect

    Novakova, Jana; Slaby, Ondrej; Vyzula, Rostislav; Michalek, Jaroslav

    2009-08-14

    MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

  3. Pathogenesis of chronic obstructive pulmonary disease

    PubMed Central

    Tuder, Rubin M.; Petrache, Irina

    2012-01-01

    The current epidemic of chronic obstructive pulmonary disease (COPD) has produced a worldwide health care burden, approaching that imposed by transmittable infectious diseases. COPD is a multidimensional disease, with varied intermediate and clinical phenotypes. This Review discusses the pathogenesis of COPD, with particular focus on emphysema, based on the concept that pulmonary injury involves stages of initiation (by exposure to cigarette smoke, pollutants, and infectious agents), progression, and consolidation. Tissue damage entails complex interactions among oxidative stress, inflammation, extracellular matrix proteolysis, and apoptotic and autophagic cell death. Lung damage by cigarette smoke ultimately leads to self-propagating processes, resulting in macromolecular and structural alterations — features similar to those seen in aging. PMID:22850885

  4. Epidemiology and Pathogenesis of Bolivian Hemorrhagic Fever

    PubMed Central

    Patterson, Michael; Grant, Ashley; Paessler, Slobodan

    2014-01-01

    The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25 to 35%. First identified in 1959, BHF was the cause of a localized outbreak in San Joaquin until rodent population controls were implemented in 1964. The rodent Calomys collosus was identified as the primary vector and reservoir for the virus. Multiple animal models were considered during the 1970’s with the most human-like disease identified in Rhesus macaques but minimal characterization of the pathogenesis has been published since. A reemergence of reported BHF cases has been reported in recent years, which necessitates the further study and development of a vaccine to prevent future outbreaks. PMID:24636947

  5. Etiology and pathogenesis of Parkinson disease.

    PubMed

    Schapira, Anthony H V

    2009-08-01

    The etiology of Parkinson disease (PD) is multifactorial and is likely to involve different causes in different patients. Several different genes have been identified as causes of familial PD, including alpha-synuclein gene mutations and multiplications, and mutations of parkin, PINK1, DJ1, and LRRK2. The biochemical consequences of these mutations have served to reinforce the relevance of the pathways to pathogenesis previously characterized, for example, mitochondrial dysfunction, oxidative stress, and protein misfolding and aggregation. The recognition that glucocerebrosidase mutations represent a significant risk factor for PD has focused attention on lysosomal function and autophagy as relevant to PD. Several environmental factors have also been shown to influence the risk for PD, although odds ratios remain relatively modest. Specific toxins can cause dopaminergic cell death in man and animals, but they probably have limited relevance to the etiology of PD.

  6. Kidney Stones 2012: Pathogenesis, Diagnosis, and Management

    PubMed Central

    Maalouf, Naim M.; Sinnott, Bridget

    2012-01-01

    Context: The pathogenetic mechanisms of kidney stone formation are complex and involve both metabolic and environmental risk factors. Over the past decade, major advances have been made in the understanding of the pathogenesis, diagnosis, and treatment of kidney stone disease. Evidence Acquisition and Synthesis: Both original and review articles were found via PubMed search reporting on pathophysiology, diagnosis, and management of kidney stones. These resources were integrated with the authors' knowledge of the field. Conclusion: Nephrolithiasis remains a major economic and health burden worldwide. Nephrolithiasis is considered a systemic disorder associated with chronic kidney disease, bone loss and fractures, increased risk of coronary artery disease, hypertension, type 2 diabetes mellitus, and the metabolic syndrome. Further understanding of the pathophysiological link between nephrolithiasis and these systemic disorders is necessary for the development of new therapeutic options. PMID:22466339

  7. Olfactory pathogenesis of idiopathic Parkinson disease revisited.

    PubMed

    Lerner, Alicja; Bagic, Anto

    2008-06-15

    Idiopathic Parkinson disease (PD) is traditionally considered a movement disorder with hallmark lesions located in the substantia nigra pars compacta (SNpc). However, recent histopathological studies of some PD cases suggest the possibility of a multisystem disorder which progresses in a predictable sequence as described in Braak's staging criteria. The disease process starts in the dorsal motor nucleus of the vagus (dmX) and anterior olfactory nucleus and bulb, and from there, spreads through the brainstem nuclei to ultimately reach the SNpc, which then presents as symptomatic PD. In this article, we would like to revisit the olfactory pathogenesis of PD based on Braak's staging system and review anatomical pathways supporting such a possibility. We also suggest some biomarkers for early stages of PD. Additionally, we present and discuss the possibility that a prion-like process underlies the neurodegenerative changes in PD.

  8. Vibrio cholerae Biofilms and Cholera Pathogenesis

    PubMed Central

    Silva, Anisia J.; Benitez, Jorge A.

    2016-01-01

    Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i) the evidence for biofilm formation during infection, (ii) the coordinate regulation of biofilm and virulence gene expression, and (iii) the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv) we discuss a model for the role of V. cholerae biofilms in pathogenicity. PMID:26845681

  9. Pathogenesis of Epilepsy: Challenges in Animal Models

    PubMed Central

    Hui Yin, Yow; Ahmad, Nurulumi; Makmor-Bakry, Mohd

    2013-01-01

    Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models. PMID:24494063

  10. [Pathogenesis of chronic inflammatory demyelinating polyneuropathy].

    PubMed

    Aranami, Toshimasa; Yamamura, Takashi

    2013-05-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is considered to be a demyelinating autoimmune disorder in the peripheral nervous system. Concerning cellular immune response, activity of IFN-gamma producing Th1 and IL-17 producing Th17 cells might be accelerated in patients with CIDP, while regulatory function of CD4+ CD25(high) Foxp3+ regulatory T cells might be diminished. Humoral immune responses against several myelin components such as myelin protein zero and gangliosides such as GM1 might be also induced in a part of patients with CIDP. Besides, growing body of evidences suggest that immune response against several molecules expressed in the noncompact myelin might be involved in the pathogenesis of CIDP.

  11. Pathogenesis of Thromboembolism and Endovascular Management.

    PubMed

    Behravesh, Sasan; Hoang, Peter; Nanda, Alisha; Wallace, Alex; Sheth, Rahul A; Deipolyi, Amy R; Memic, Adnan; Naidu, Sailendra; Oklu, Rahmi

    2017-01-01

    Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

  12. Understanding the pathogenesis of abdominal aortic aneurysms

    PubMed Central

    Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

    2016-01-01

    Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA. PMID:26308600

  13. Zika Virus Pathogenesis and Tissue Tropism.

    PubMed

    Miner, Jonathan J; Diamond, Michael S

    2017-02-08

    Although Zika virus (ZIKV) was isolated approximately 70 years ago, few experimental studies had been published prior to 2016. The recent spread of ZIKV to countries in the Western Hemisphere is associated with reports of microcephaly, congenital malformations, and Guillain-Barré syndrome. This has resulted in ZIKV being declared a public health emergency and has greatly accelerated the pace of ZIKV research and discovery. Within a short time period, useful mouse and non-human primate disease models have been established, and pre-clinical evaluation of therapeutics and vaccines has begun. Unexpectedly, ZIKV exhibits a broad tropism and persistence in body tissues and fluids, which contributes to the clinical manifestations and epidemiology that have been observed during the current epidemic. In this Review, we highlight recent advances in our understanding of ZIKV pathogenesis, tissue tropism, and the resulting pathology and discuss areas for future investigation.

  14. [The pathogenesis of acne vulgaris (author's transl)].

    PubMed

    Gloor, M; Habedank, W D

    1976-05-14

    Stickl's method of oral treatment of acne vulgaris with antigens has been carried out on 26 test persons. During the treatment the number of comedones increased significantly and the number of papules decreased significantly. Biochemically, a significant increase of the free fatty acids and a significant decrease of the triglycerides could be demonstrated in the skin surface lipids, the total amount remaining unchanged. The following important conclusions for the pathogenesis of acne may be drawn: 1. The living conditions for Corynebacterium acnes on the surface of the skin or in the ducts of sebaceous glands respectively are influenced by the immunological system of the host. 2. The free fatty acids have a comedogenic effect in vivo. 3. The free fatty acids are not responsible for the development of inflammatory acne efflorescences.

  15. Sunlight exposure and pathogenesis of uveal melanoma.

    PubMed

    Singh, Arun D; Rennie, Ian G; Seregard, Stefan; Giblin, Michael; McKenzie, John

    2004-01-01

    Uveal melanoma is the most frequent primary malignant intraocular tumor of adults. Among various non-modifiable risk factors, Caucasian race seems to be the most significant with light skin color, blond hair, and blue eyes being specific risk factors. The racial predisposition to uveal melanoma have been explained on the basis of susceptibility of Caucasian race to oncogenic effects of sunlight. Although there is ample evidence in support of this hypothesis in regard to skin melanoma, the evidence in regard to uveal melanoma is insufficient and contradictory. In the following review, we examine physiologic, epidemiological, and genetic data in order to determine the role of sunlight exposure in the pathogenesis of uveal melanoma.

  16. Vibrio cholerae Biofilms and Cholera Pathogenesis.

    PubMed

    Silva, Anisia J; Benitez, Jorge A

    2016-02-01

    Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i) the evidence for biofilm formation during infection, (ii) the coordinate regulation of biofilm and virulence gene expression, and (iii) the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv) we discuss a model for the role of V. cholerae biofilms in pathogenicity.

  17. Advances in the Pathogenesis of Adhesion Development

    PubMed Central

    Awonuga, Awoniyi O.; Belotte, Jimmy; Abuanzeh, Suleiman; Fletcher, Nicole M.; Diamond, Michael P.

    2014-01-01

    Over the past several years, there has been increasing recognition that pathogenesis of adhesion development includes significant contributions of hypoxia induced at the site of surgery, the resulting oxidative stress, and the subsequent free radical production. Mitochondrial dysfunction generated by surgically induced tissue hypoxia and inflammation can lead to the production of reactive oxygen and nitrogen species as well as antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase which when optimal have the potential to abrogate mitochondrial dysfunction and oxidative stress, preventing the cascade of events leading to the development of adhesions in injured peritoneum. There is a significant cross talk between the several processes leading to whether or not adhesions would eventually develop. Several of these processes present avenues for the development of measures that can help in abrogating adhesion formation or reformation after intraabdominal surgery. PMID:24520085

  18. Pathogenesis of Goodpasture syndrome: a molecular perspective.

    PubMed

    Borza, Dorin-Bogdan; Neilson, Eric G; Hudson, Billy G

    2003-11-01

    Goodpasture (GP) syndrome is a form of anti-glomerular basement membrane (GBM) disease, in which autoantibodies bind to alpha3(IV) collagen in GBM causing rapidly progressive glomerulonephritis and pulmonary hemorrhage. The conformational GP epitopes have been mapped to 2 regions within the noncollagenous (NC1) domain of the alpha3(IV) chain. Recently, we described the molecular organization of the autoantigen in the native alpha3alpha4alpha5(IV) collagen network of the GBM. The crystal structure of the NC1 domain has revealed how the GP epitopes are sequestered in the native GBM. Further insight into the pathogenesis of disease has been obtained from better animal models. These advances provide a foundation for the development of new specific therapies.

  19. Foodborne Campylobacter: Infections, Metabolism, Pathogenesis and Reservoirs

    PubMed Central

    Epps, Sharon V. R.; Harvey, Roger B.; Hume, Michael E.; Phillips, Timothy D.; Anderson, Robin C.; Nisbet, David J.

    2013-01-01

    Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions. PMID:24287853

  20. Enzymes and isoenzymes in pathogenesis and diagnosis

    SciTech Connect

    Goldberg, D.M.; Werner, M.; Zaidman, J.L.

    1987-01-01

    This book, based on 19 review articles discusses how enzymes and isoenzymes can be used in diagnosis, and the role they play in the pathogenesis of disease. The opening reports concentrate on the digestive system. Topics covered are advances in the diagnostic use of alkaline phosphatase isoenzymes, enzymes of value in pancreatic disease, and the modulation by steroids of gamma-glutamyltransferase in fetal hepatocytes. Advances are described such as the multiplicity of enzyme defects at the root of common inherited metabolic diseases. Newer applications of enzymology are shown, as in the role of purine-related enzymes in leukemia and immunodeficiency states. The role of enzymes in metabolic abnormalities such as oxylate formation, disorders of peroxisomal metabolism, hyperphenylalaninemia, and methemoglobinemia is explored.

  1. Pathogenesis of Thromboembolism and Endovascular Management

    PubMed Central

    Behravesh, Sasan; Hoang, Peter; Nanda, Alisha; Wallace, Alex; Sheth, Rahul A.; Deipolyi, Amy R.; Memic, Adnan; Naidu, Sailendra

    2017-01-01

    Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted. PMID:28154761

  2. Diversity and disease pathogenesis in Mycobacterium tuberculosis.

    PubMed

    Warner, Digby F; Koch, Anastasia; Mizrahi, Valerie

    2015-01-01

    The increasing availability of whole-genome sequence (WGS) data for Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), suggests that circulating genotypes have been molded by three dominant evolutionary forces: long-term persistence within the human population, which requires a core programme of infection, disease, and transmission; selective pressure on specific genomic loci, which provides evidence of lineage-specific adaptation to host populations; and drug exposure, which has driven the rapid emergence of resistant isolates following the global implementation of anti-TB chemotherapy. Here, we provide an overview of these factors in considering the implications of genotypic diversity for disease pathogenesis, vaccine efficacy, and drug treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Neural tube defects: pathogenesis and folate metabolism.

    PubMed

    Pulikkunnel, Scaria T; Thomas, S V

    2005-02-01

    Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex aetio-pathogenesis. Animal studies indicate that there may be four sites of initiation of neural tube closure (NTC). Selective involvement of these sites may lead to defects varying from anencephaly to spina bifida. The NTC involves formation of medial and dorsolateral hinge points, convergent extension and a zipper release process. Proliferation and migration of neuroectodermal cells and its morphological changes brought about by microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional and teratogenic mechanisms have been implicated in the pathogenesis of NTDs. Folate is an important component in one carbon metabolism that provides active moieties for synthesis of nucleic acids and proteins. Several gene defects affecting enzymes and proteins involved in transport and metabolism of folate have been associated with NTDs. It may be possible in future, to identify individuals at higher risk of NTDs by genetic studies. Epidemiological and clinical studies have shown that dietary supplementation or food fortification with folic acid would reduce the incidence of NTDs. The protective effect of folic acid may be by overcoming these metabolic blocks through unidentified mechanisms. Genetic and biochemical studies on foetal cells may supplement currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs), particularly valproate and carbamazepine have been shown to increase the risk of NTDs by possibly increasing the oxidative stress and deranging the folate metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5 mg folic acid daily in the pre conception period and through pregnancy.

  4. Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis.

    PubMed

    Tekes, G; Thiel, H-J

    2016-01-01

    Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV). The review summarizes our current knowledge of the genome and proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike) protein S and the five accessory proteins. We also review the current classification of FCoVs into distinct serotypes and biotypes, cellular receptors of FCoVs and their presumed role in viral virulence, and discuss other aspects of FIPV-induced pathogenesis. Our current knowledge of genetic differences between FECVs and FIPVs has been mainly based on comparative sequence analyses that revealed "discriminatory" mutations that are present in FIPVs but not in FECVs. Most of these mutations result in amino acid substitutions in the S protein and these may have a critical role in the switch from FECV to FIPV. In most cases, the precise roles of these mutations in the molecular pathogenesis of FIP have not been tested experimentally in the natural host, mainly due to the lack of suitable experimental tools including genetically engineered virus mutants. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies. © 2016 Elsevier Inc. All rights reserved.

  5. The pathogenesis of burn wound conversion.

    PubMed

    Singh, Vijay; Devgan, Lara; Bhat, Satyanarayan; Milner, Stephen M

    2007-07-01

    Burn wound progression is a poorly understood process by which certain superficial partial-thickness burns spontaneously advance into deep partial-thickness or full-thickness wounds. Progression of an injury into deeper tissue is an important phenomenon in the treatment of thermal injury due to the fact that burn wound depth may be a significant determinant of morbidity and treatment. This article reviews current knowledge of the pathogenesis, molecular and cellular mechanisms, local and systemic factors, and treatment modalities related to wound conversion. All peer-reviewed, original, and review articles published in English-language literature relevant to the topic of burn wound conversion on animals and human subjects were selected for this review. After assessing data relevance, independent extraction by a sole reviewer was performed. Data were tabulated according to the following categories: pathogenesis, mechanisms, local and systemic factors, and treatment. Burn wound progression is complex and caused by additive effects of inadequate tissue perfusion, free radical damage, and systemic alterations in the cytokine milieu of burn patients, leading to protein denaturation and necrosis. Even though insufficient evidence exists for causal inferences, infection, tissue desiccation, edema, circumferential eschar, impaired wound perfusion, metabolic derangements, advanced age, and poor general health play important roles. Although consensus-building research is ongoing, current mainstays of treatment include adequate fluid resuscitation, nutritional support, and local wound care, with an emphasis on topical antimicrobial agents and biosynthetic dressings. Identifying early indicators by elucidating possible interacting or synergistic mechanisms and by developing preventative strategies will enhance prevention and treatment.

  6. Understanding dengue pathogenesis: implications for vaccine design.

    PubMed Central

    Stephenson, John R.

    2005-01-01

    In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease. PMID:15868023

  7. Pathogenesis of IgA nephropathy.

    PubMed

    Lai, Kar Neng

    2012-03-20

    Since its first description in 1968, IgA nephropathy has remained the most common form of idiopathic glomerulonephritis leading to chronic kidney disease in developed countries. The exact pathogenesis of IgA nephropathy is still not well defined. Current data implicate an important genetic factor, especially in promoting the overproduction of an aberrant form of IgA1. The immunochemical aberrancy of IgA nephropathy is characterized by the undergalactosylation of O-glycans in the hinge region of IgA1. However, such aberrant glycosylation alone does not cause renal injury. The next stage of disease development requires the formation of glycan-specific IgG and IgA antibodies that recognize the undergalactosylated IgA1 molecule. These antibodies often have reactivity against antigens from extrinsic microorganisms and might arise from recurrent mucosal infection. B cells that respond to mucosal infections, particularly tonsillitis, might produce the nephritogenic IgA1 molecule. With increased immune-complex formation and decreased clearance owing to reduced uptake by the liver, IgA1 binds to the glomerular mesangium via an as yet unidentified receptor. Glomerular IgA1 deposits trigger the local production of cytokines and growth factors, leading to the activation of mesangial cells and the complement system. Emerging data suggest that mesangial-derived mediators following glomerular deposition of IgA1 lead to podocyte and tubulointerstitial injury via mesangio-podocytic-tubular crosstalk. This Review summarizes the latest findings in the pathogenesis of IgA nephropathy.

  8. Henipavirus pathogenesis in human respiratory epithelial cells.

    PubMed

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz; Rockx, Barry

    2013-03-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection.

  9. Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

    PubMed Central

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J. Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz

    2013-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection. PMID:23302882

  10. Pathogenesis, Diagnosis and Treatment of Hemochromatosis.

    PubMed

    Zoller, Heinz; Henninger, Benjamin

    Hemochromatosis is a common cause of chronic liver disease and HFE genotyping allows decisive and non-invasive diagnosis. Molecular and clinical genetic studies have led to the identification of genes other than HFE in patients with inherited diseases associated with increased hepatic iron storage that can cause hemochromatosis, which adds complexity to a diagnostic approach to patients with suspected hemochromatosis. Despite major advances in genetics, hepatic iron quantification by non-invasive methods therefore remains the key to the diagnosis of hemochromatosis. Although associated with homozygosity for the C282Y polymorphism in the HFE gene in >80% of patients, hemochromatosis is a complex genetic disease with strong environmental disease modifiers. Testing for mutations in the non-HFE hemochromatosis genes transferrin receptor 2, hemojuvelin, HAMP and SLC40A1 is complex, costly and time-consuming. Demonstration of hepatic iron overload by liver biopsy or MRI is therefore required before such complex tests are carried out. The pathogenesis of chronic liver disease in hemochromatosis is mainly attributed to the redox potential of tissue iron, and only the more recent studies have focused on the toxic properties of circulating iron. Considering the fact that an increased saturation of transferrin and high iron in plasma are the hallmark of all hemochromatosis forms, an alternative view would be that toxic iron in the circulation is involved in the pathogenesis of hemochromatosis. Recent studies have shown an increased concentration of redox-active iron in plasma in patients with increased transferrin saturation. This finding supports the hypothesis that tissue iron may be the 'smoking gun' of iron-induced organ damage. Taken together, caring for patients with suspected or established hemochromatosis still remains a challenge, where understanding the genetics, biochemistry and cell biology of hemochromatosis will aid better diagnosis and treatment of affected

  11. Bovine viral diarrhoea: pathogenesis and diagnosis.

    PubMed

    Lanyon, Sasha R; Hill, Fraser I; Reichel, Michael P; Brownlie, Joe

    2014-02-01

    Bovine viral diarrhoea virus (BVDV) is the most prevalent infectious disease of cattle. It causes financial losses from a variety of clinical manifestations and is the subject of a number of mitigation and eradication schemes around the world. The pathogenesis of BVDV infection is complex, with infection pre- and post-gestation leading to different outcomes. Infection of the dam during gestation results in fetal infection, which may lead to embryonic death, teratogenic effects or the birth of persistently infected (PI) calves. PI animals shed BVDV in their excretions and secretions throughout life and are the primary route of transmission of the virus. These animals can usually be readily detected by virus or viral antigen detection assays (RT-PCR, ELISA), except in the immediate post-natal period where colostral antibodies may mask virus presence. PI calves in utero (the 'Trojan cow' scenario) currently defy detection with available diagnostic tests, although dams carrying PI calves have been shown to have higher antibody levels than seropositive cows carrying non-PI calves. Acute infection with BVDV results in transient viraemia prior to seroconversion and can lead to reproductive dysfunction and immunosuppression leading to an increased incidence of secondary disease. Antibody assays readily detect virus exposure at the individual level and can also be used in pooled samples (serum and milk) to determine herd exposure or immunity. Diagnostic tests can be used to diagnose clinical cases, establish disease prevalence in groups and detect apparently normal but persistently infected animals. This review outlines the pathogenesis and pathology of BVD viral infection and uses this knowledge to select the best diagnostic tests for clinical diagnosis, monitoring, control and eradication efforts. Test methods, types of samples and problems areas of BVDV diagnosis are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment.

    PubMed

    Sicherer, Scott H; Sampson, Hugh A

    2014-02-01

    This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.

  13. [Pathogenesis and Clinical Examination of Autoinflammatory Syndrome].

    PubMed

    Ida, Hiroaki

    2015-10-01

    Autoinflammatory syndrome is characterized by: 1) episodes of seemingly unprovoked inflammation, 2) the absence of a high titer of autoantibodies or auto-reactive T cells, and 3) an inborn error of innate immunity. In this decade, many autoinflammatory syndromes have been reported in Japan, and so many Japanese physicians have become aware of this syndrome. Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. The main monogenic autoinflammatory syndromes are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), cryopyrin-associated periodic syndrome (CAPS), Blau syndrome, and syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). We diagnosed these syndromes as clinical manifestations and performed genetic screening. Many serum cytokines are elevated in patients with autoinflammatory syndrome, but this is not disease-specific. The pathogeneses of many autoinflammatory syndromes are known to be related to inflammasomes, which are multiprotein complexes that serve as a platform for caspase 1 activation and interleukin-1β(IL-1β) and IL-18 maturation. Especially, NLRP3 inflammasomes may play a crucial role in the initiation and progression of FMF and CAPS. Recently, it was reported that NETs (neutrophil extracellular traps) derived from neutrophils may also play an important role in the pathogenesis of FMF. In the future, we hope to discover new clinical examinations which can provide evidence of inflammasome activation independent of genetic screening. In this issue, I introduce autoinflammatory syndromes and discuss the pathogenesis and clinical examination of these syndromes.

  14. Type 1 diabetes pathogenesis – Prevention???

    PubMed Central

    Krishna, C. S. Muralidhara; Srikanta, S.

    2015-01-01

    Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction (“Primary autoimmune insulitis”), culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb) are an important hallmark of this disease. Assays for islet cell autoantibodies have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have extended into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently, surprisingly, differences in insulin content between T1DM islets, as well as, ‘patchy’ or ‘lobular’ destruction of islets have been described. These unique pathobiological phenomena, suggest that beta cell destruction may not always be inexorable and inevitably complete/total, and thus raise hopes for possible therapeutic interruption of beta cell autoimmunity – destruction and cure of type 1 diabetes. “Recurrent or secondary autoimmune insulitis” refers to the rapid reappearance of islet cell autoantibodies post pancreas transplant, and selective islet beta cell destruction in the grafted pancreas [never forgetting or “anamnestic” beta cell destructive memory], in the absence of any graft pancreas rejection [monozygotic twin to twin transplantation]. The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The putative predisposing factors are viruses, gluten and cow's milk. The putative protective factors include gut flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can include: Primary prevention strategies before

  15. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

    PubMed Central

    Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

    2012-01-01

    Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

  16. Hemophagocytic Lymphohistiocytosis in Children: Pathogenesis and Treatment.

    PubMed

    Ishii, Eiichi

    2016-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder in children that is characterized by persistent fever, splenomegaly with cytopenia, hypertriglyceridemia, and hypofibrinogenemia. Increased levels of various cytokines and soluble interleukin-2 receptor are biological markers of HLH. HLH can be classified into two major forms: primary and secondary. Familial hemophagocytic lymphohistiocytosis (FHL), a type of primary HLH, is an autosomal recessive disorder that typically occurs in infancy and can be classified into five different subtypes (FHL types 1-5). In Japan, >80% of patients with FHL have either PRF1 (FHL type 2) or UNC13D (FHL type 3) defects. FHL is considered to be a disorder of T-cell function because the activity of NK cells or cytotoxic T lymphocytes as target cells is usually impaired. Moreover, Epstein-Barr virus-associated HLH (EBV-HLH) is considered a major subtype of secondary HLH. Any genetic background could have an effect on the pathogenesis of secondary HLH because EBV-HLH is considered to be particularly prevalent in Asian countries. For primary HLH, hematopoietic stem cell transplantation is the only accepted curative therapy, although cord blood transplantation with a reduced-conditioning regimen has been used with superior outcomes. For secondary HLH, including EBV-HLH, immunochemotherapy based on the HLH-2004 protocol has been used. In the near future, the entire mechanism of HLH should be clarified to establish less toxic therapies, including cell therapy and gene targeting therapy.

  17. Molecular genetics and pathogenesis of Clostridium perfringens.

    PubMed Central

    Rood, J I; Cole, S T

    1991-01-01

    Clostridium perfringens is the causative agent of a number of human diseases, such as gas gangrene and food poisoning, and many diseases of animals. Recently significant advances have been made in the development of C. perfringens genetics. Studies on bacteriocin plasmids and conjugative R plasmids have led to the cloning and analysis of many C. perfringens genes and the construction of shuttle plasmids. The relationship of antibiotic resistance genes to similar genes from other bacteria has been elucidated. A detailed physical map of the C. perfringens chromosome has been prepared, and numerous genes have been located on that map. Reproducible transformation methods for the introduction of plasmids into C. perfringens have been developed, and several genes coding for the production of extracellular toxins and enzymes have been cloned. Now that it is possible to freely move genetic information back and forth between C. perfringens and Escherichia coli, it will be possible to apply modern molecular methods to studies on the pathogenesis of C. perfringens infections. PMID:1779929

  18. Achondroplasia: pathogenesis and implications for future treatment.

    PubMed

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  19. The Pathogenesis of Ebola Virus Disease.

    PubMed

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  20. Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis

    PubMed Central

    Garfoot, Andrew L.; Rappleye, Chad A.

    2016-01-01

    The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are readily controlled by phagocytic cells, H. capsulatum yeasts are able to infect macrophages, survive antimicrobial defenses, and proliferate as an intracellular pathogen. In this review, we discuss some of the molecular mechanisms that enable H. capsulatum yeasts to overcome obstacles to intracellular pathogenesis. H. capsulatum yeasts gain refuge from extracellular obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid triggering signaling receptors such as the β-glucan receptor Dectin-1. H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense enzymes including an extracellular superoxide dismutase and an extracellular catalase. Within the phagosome, H. capsulatum yeasts block phagosome acidification, acquire essential metals such as iron and zinc, and utilize de novo biosynthesis pathways to overcome nutritional limitations. These mechanisms explain how H. capsulatum yeasts avoid and negate macrophage defense strategies and establish a hospitable intracellular niche, making H. capsulatum a successful intracellular pathogen of macrophages. PMID:26235362

  1. Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

    PubMed Central

    Hauer-Jensen, Martin; Denham, James W.; Andreyev, H. Jervoise N.

    2015-01-01

    There has been only modest change in cancer incidence and mortality during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to prevent, diagnose, and manage side effects of cancer therapy in general and, specifically those of radiation therapy have intensified. Many cancer survivors have undergone radiation therapy of tumors in the pelvis or abdomen, thus rendering the bowel at risk for injury. In fact, the current prevalence of patients with long term radiation-induced intestinal side effects exceeds that of ulcerative colitis and Crohn’s disease combined. Significant progress toward reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which allow more precise delivery of the radiation beam. Moreover, new insight into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This article discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, reviews current management options, and outlines priorities for future research. The gastroenterologist by adding insight into molecular and cellular mechanisms of related bowel disorders can substantially strengthen these efforts. PMID:24686268

  2. [Periostin in the Pathogenesis of Proliferative Vitreoretinopathy].

    PubMed

    Ishikawa, Keijiro

    2015-11-01

    Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery. The hallmark of PVR is the formation of subretinal and epiretinal fibrotic membranes that can lead to traction retinal detachment due to their contractile properties. Surgical removal of the fibrotic membranes and retinal detachment repair are the first choice treatments for PVR. Despite recent progress in surgical techniques, recurrent detachment can lead to irreversible damage and a poor prognosis for visual acuity. Therefore, it is important to develop new molecular targeting therapies based on the exact pathogenesis of PVR. In order to determine the genes responsible for development of PVR, we performed gene expression profiling of fibrous membranes excised from PVR patients using DNA microarray analysis. This analysis revealed significant up-regulation of periostin. We also found increased periostin expression in the vitreous and retinal pigment epithelial (RPE) cells in fibrous membranes of PVR patients. In vitro, periostin increased proliferation, adhesion, migration and collagen production in primary human RPE cells through integrin αV-mediated FAK and AKT phosphorylation. Blockade of periostin suppressed migration and adhesion induced by TGF-β2 and PVR vitreous. In vivo, periostin inhibition had the inhibitory effect on progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells. These results identified the novel causal link between periostin and the generation of PVR membranes as well as a promising therapeutic target for PVR.

  3. Modeling neuroinflammatory pathogenesis of Parkinson's disease.

    PubMed

    Barnum, Christopher J; Tansey, Malú G

    2010-01-01

    The molecular mechanisms underlying the pathogenesis of idiopathic Parkinson's disease (PD) have not been completely elucidated; however, some progress has been made in identifying factors that compromise survival of the dopaminergic neurons in the substantia nigra (SN) the death of which give rise to the motor symptoms that enable clinicians to diagnose the disease in its mid- to late stages. The prevailing theory regarding processes that are likely to account for degeneration of the nigrostriatal system centers around mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation. Of these, neuroinflammation is one candidate that appears to accumulate more support with each passing year. A number of researchers have attempted to manipulate inflammation in various animal PD models with varying levels of success. Still others have used inflammatory stimuli to elicit nigral cell death (NCD), a disturbing finding that has prompted much interest. In this chapter, we attempt to integrate what is known about the role of neuroinflammation in PD with the factors we feel are critical for understanding how inflammation modulates disease progression.

  4. Extramammary Paget disease - clinical appearance, pathogenesis, management.

    PubMed

    Wagner, Gunnar; Sachse, Michael Max

    2011-06-01

    Extramammary Paget disease is a rare malignant neoplasm. With regard to the pathogenesis, two prognostically different forms can be distinguished. The primary form of extramammary Paget disease is an in situ carcinoma of the apocrine gland ducts. In contrast, the secondary form is characterized by an intraepithelial spread due to an underlying carcinoma of the skin or other organ systems. Extramammary Paget disease occurs in older patients. The predilection sites include the entire anogenital skin and less often the axillary region. We present five different patients with this disease, thereby demonstrating its variation in clinical morphology. The lesion usually presents as an erythematous sharply defined spot. The polygonal borders, caused by the centrifugal growth of the tumor, may provide a diagnostic clue. The treatment of choice for extramammary Paget disease remains Mohs' microscopic surgery. However, radiotherapy or topical applications may be alternative treatment options in selected cases. In patients with the secondary form of extramam-mary Paget disease, treatment of the primary tumor is the main approach.

  5. Causes and pathogenesis of focal segmental glomerulosclerosis

    PubMed Central

    Fogo, Agnes B.

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. The initial injuries vary widely. Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Varying phenotypes of the sclerosis are also manifest, with varying prognosis. The so-called tip lesion has the best prognosis, whereas the collapsing type of FSGS has the worst prognosis. New insights into glomerular cell injury response and repair may pave the way for possible therapeutic strategies. PMID:25447132

  6. Molecular pathogenesis of sporadic duodenal cancer.

    PubMed Central

    Achille, A.; Baron, A.; Zamboni, G.; Orlandini, S.; Bogina, G.; Bassi, C.; Iacono, C.; Scarpa, A.

    1998-01-01

    Whether duodenal adenocarcinoma should be considered as a gastrointestinal or as a peripancreatic cancer is a matter of debate, as is the opportunity and type of treatment. We investigated 12 such cancers for the genetic anomalies involved in the pathogenesis of gastrointestinal malignancies, including (a) those occurring in common-type cancers - allelic losses at chromosomes 3p, 5q, 17p and 18q, and Ki-ras and p53 alterations; and (b) those characteristic of mutator-phenotype cancers - microsatellite instability and TGF-betaRII gene mutations. We found Ki-ras and p53 mutations in five (42%) and eight cancers (67%), respectively; chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten (60%), six of nine (67%) and three of ten (30%) informative cancers, respectively. Finally, three cancers (25%) showed widespread microsatellite instability and two of them had a TGF-betaRII gene mutation. Our data suggest that duodenal cancers may arise from either of the two known pathogenetic molecular pathways of gastric and colorectal cancers. The majority of our cases were highly aggressive cancers with frequent chromosomal changes and p53 mutations as observed in the common-type gastrointestinal malignancies, while widespread subtle alterations characteristic of mutator-phenotype cancers occurred in a minority, which also showed a favourable long-term outcome. Images Figure 1 Figure 2 Figure 3 PMID:9514055

  7. Raynaud's phenomenon: from molecular pathogenesis to therapy.

    PubMed

    Prete, Marcella; Fatone, Maria Celeste; Favoino, Elvira; Perosa, Federico

    2014-06-01

    Raynaud's phenomenon (RP) is a well defined clinical syndrome characterized by recurrent episodes of digital vasospasm triggered by exposure to physical/chemical or emotional stress. RP has been classified as primary or secondary, depending on whether it occurs as an isolated condition (pRP) or is associated to an underlying disease, mainly a connective tissue disease (CTD-RP). In both cases, it manifests with unique "triple" (pallor, cyanosis and erythema), or "double" color changes. pRP is usually a benign condition, while sRP can evolve and be complicated by acral digital ulcers and gangrene, which may require surgical treatment. The pathogenesis of RP has not yet been entirely clarified, nor is it known whether autoantibodies have a role in RP. Even so, recent advances in our understanding of the pathophysiology have highlighted novel potential therapeutic targets. The aim of this review is to discuss the etiology, epidemiology, risk factors, clinical manifestations, recently disclosed pathogenic mechanisms underlying RP and their correlation with the available therapeutic options, focusing primarily on pRP and CTD-RP.

  8. Apoptosis in cancer: from pathogenesis to treatment

    PubMed Central

    2011-01-01

    Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects. PMID:21943236

  9. EPIDEMIOLOGY, PATHOGENESIS and DIAGNOSIS of LYMPHANGIOLEIOMYOMATOSIS

    PubMed Central

    Taveira-DaSilva, Angelo M.; Moss, Joel

    2016-01-01

    Introduction Lymphangioleiomyomatosis (LAM) is a disease of women characterized by cystic lung destruction, lymphatic involvement, and renal angiomyolipomas. Areas covered LAM is caused by proliferation of abnormal smooth muscle-like LAM cells containing mutations and perhaps epigenetic modifications of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins controlling the mechanistic target of rapamycin (mTOR) signaling pathway. LAM occurs sporadically or in association with tuberous sclerosis complex. LAM may present with dyspnea, recurrent pneumothorax or chylothorax. Pulmonary function tests show reduced flow rates and lung diffusion capacity. Exercise testing may reveal hypoxemia and ventilatory limitation. The severity and progression of disease may be assessed by computer tomography, and pulmonary function and exercise testing. mTOR inhibitors, (e.g., sirolimus) are effective in stabilizing lung function, and reducing the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas. Expert opinion Different clinical phenotypes including variable rates of disease progression and variable responses to therapy are seen in LAM patients. No one test is available that predicts the course of disease at the time of diagnosis. Further research regarding the molecular biology of LAM clinical phenotypes is warranted. Recent advances in the characterization of the pathogenesis of LAM are leading to the development of new therapies. PMID:27833825

  10. JNK pathway in osteosarcoma: pathogenesis and therapeutics.

    PubMed

    Li, Yu-Sheng; Deng, Zhen-Han; Zeng, Chao; Lei, Guang-Hua

    2016-10-01

    The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein-1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients.

  11. Neisseria prophage repressor implicated in gonococcal pathogenesis.

    PubMed

    Daou, Nadine; Yu, Chunxiao; McClure, Ryan; Gudino, Cynthia; Reed, George W; Genco, Caroline A

    2013-10-01

    Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus NgoΦ4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the -10 and -35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis.

  12. Pathogenesis of atherosclerosis: A multifactorial process

    PubMed Central

    Singh, Raja B; Mengi, Sushma A; Xu, Yan-Jun; Arneja, Amarjit S; Dhalla, Naranjan S

    2002-01-01

    Atherosclerosis is a leading cause of mortality and morbidity in the western world. It has been recognized for over a century, and the understanding of its pathogenesis has undergone many changes. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis. The focus has shifted to the novel risk factors as well as characteristics and stability of atherosclerotic plaque; the genetic predisposition has further broadened the pathogenetic mechanisms. This review focuses on the molecular mechanisms involved in the evolution of the atherosclerotic plaque that may pave the way for selecting optimal therapies and preventing plaque complications. Atherosclerosis is no longer a disease attributed mainly to the high lipid content of the body. New insight into the disease pathology has shown it to be a disease of much greater ramifications. Endothelial damage and reactive oxygen species (and other free radicals) have predominantly emerged as factors in virtually all pathways leading to the development of atherosclerosis due to hyperlipidemia, diabetes, hypertension or smoking. Novel risk factors such as hyperhomocysteinemia, infections and systemic lupus erythematosus have emerged. Atherosclerosis has come to be regarded as a chronic inflammatory disease with an autoimmune component. The genetic basis of the disease assumes significance as candidate genes are identified and gene therapy becomes a promising new addition to the existing, less substantial conventional therapies. PMID:19644578

  13. Pathogenesis of ANCA-associated vasculitides.

    PubMed

    Kallenberg, Cees G M

    2011-03-01

    Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterised by necrotising inflammation of small vessels in conjunction with ANCA directed to either proteinase 3 (PR3) or myeloperoxidase (MPO). The aetiopathogenesis of these disorders is still not fully elucidated but clinical as well as in vitro and in vivo experimental data strongly suggest a role for the autoimmune responses to PR3 and MPO in disease development. Clinically, PR3-ANCA are strongly associated with granulomatous vasculitis as in Wegener's granulomatosis, and MPO-ANCA with necrotising small vessel vasculitis as in microscopic polyangiitis. Levels of PR3-ANCA and MPO-ANCA do, however, not fully reflect disease activity. In vitro, ANCA activate primed neutrophils to release lytic enzymes and reactive oxygen species, a process reinforced by the alternative pathway of complement. In the context of endothelial cells, this process leads to endothelial detachment and lysis. In vivo experimental studies have clearly demonstrated the pathogenic potential of MPO-ANCA for necrotising glomerulonephritis and pulmonary capillaritis. For PR3-ANCA-associated granulomatous vasculitis, an animal model is lacking. Here, effector T cells, in particular Th17 cells, appear to have a major pathogenic role in addition to ANCA. Finally, microbial factors, derived in particular from S aureus and Gram-negative bacteria, could play a part in disease induction and expression. These new insights into the pathogenesis of ANCA-associated vasculitides have opened new ways for targeted treatment.

  14. Neisseria Prophage Repressor Implicated in Gonococcal Pathogenesis

    PubMed Central

    Daou, Nadine; Yu, Chunxiao; Mcclure, Ryan; Gudino, Cynthia; Reed, George W.

    2013-01-01

    Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus NgoΦ4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the −10 and −35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis. PMID:23876804

  15. Pathogenesis of Middle East respiratory syndrome coronavirus.

    PubMed

    van den Brand, Judith M A; Smits, Saskia L; Haagmans, Bart L

    2015-01-01

    Human coronaviruses (CoVs) mostly cause a common cold that is mild and self-limiting. Zoonotic transmission of CoVs such as the recently identified Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome (SARS)-CoV, on the other hand, may be associated with severe lower respiratory tract infection. This article reviews the clinical and pathological data available on MERS and compares it to SARS. Most importantly, chest radiographs and imaging results of patients with MERS show features that resemble the findings of organizing pneumonia, different from the lesions in SARS patients, which show fibrocellular intra-alveolar organization with a bronchiolitis obliterans organizing pneumonia-like pattern. These findings are in line with differences in the induction of cytopathological changes, induction of host gene responses and sensitivity to the antiviral effect of interferons in vitro when comparing both MERS-CoV and SARS-CoV. The challenge will be to translate these findings into an integrated picture of MERS pathogenesis in humans and to develop intervention strategies that will eventually allow the effective control of this newly emerging infectious disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Molecular pathogenesis of Bernard-Soulier syndrome.

    PubMed

    Hayashi, T; Suzuki, K

    2000-01-01

    Bernard-Soulier syndrome (BSS), a hereditary qualitative platelet disorder, is now proved to be caused by a qualitative or quantitative abnormality of the platelet glycoprotein (GP) Ib/IX/V complex. We investigated the genetic background of two Japanese females with BSS and identified the molecular defects underlying this disease. The first case was a single base pair deletion within seven adenine repeats at position 4464-4470 (EMBL, no. M22403) of the GPIbalpha gene resulting in a frameshift and a premature stop codon. The second case was a single T-->C substitution at nucleotide 1856 (EMBL, no. M80478) of the GPIX gene resulting in Phe55(TTT)-->Ser(TCT) substitution. The latter case is of interest in considering the pathogenesis of BSS, because all four GPs consisting of the GPIb/IX/V complex have the same structural unit called leucine-rich repeat (LRR). Because this mutation is located within the LRR of the GPIX polypeptide, Phe55-->Ser substitution may result in an alteration of the LRR that leads to impaired surface expression of the GPIb/IX/V complex. To clarify the effect of this mutation on surface expression of the GPIb/IX complex, we performed transfection studies with a plasmid having this mutation. Mutant GPIX could not increase surface expression of the GPIb/IX complex, thus demonstrating an important role of the LRR of the GPIX polypeptide during biosynthesis.

  17. The pathogenesis of bornaviral diseases in mammals.

    PubMed

    Tizard, Ian; Ball, Judith; Stoica, George; Payne, Susan

    2016-12-01

    Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.

  18. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS

    PubMed Central

    Johnson, Richard T.

    1964-01-01

    The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection. PMID:14164487

  19. Treatment and pathogenesis of acute hyperkalemia

    PubMed Central

    Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

    2012-01-01

    This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

  20. Pathogenesis of Malaria and Clinically Similar Conditions

    PubMed Central

    Clark, Ian A.; Alleva, Lisa M.; Mills, Alison C.; Cowden, William B.

    2004-01-01

    There is now wide acceptance of the concept that the similarity between many acute infectious diseases, be they viral, bacterial, or parasitic in origin, is caused by the overproduction of inflammatory cytokines initiated when the organism interacts with the innate immune system. This is also true of certain noninfectious states, such as the tissue injury syndromes. This review discusses the historical origins of these ideas, which began with tumor necrosis factor (TNF) and spread from their origins in malaria research to other fields. As well the more established proinflammatory mediators, such as TNF, interleukin-1, and lymphotoxin, the roles of nitric oxide and carbon monoxide, which are chiefly inhibitory, are discussed. The established and potential roles of two more recently recognized contributors, overactivity of the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the escape of high-mobility-group box 1 (HMGB1) protein from its normal location into the circulation, are also put in context. The pathogenesis of the disease caused by falciparum malaria is then considered in the light of what has been learned about the roles of these mediators in these other diseases, as well as in malaria itself. PMID:15258091