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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 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.

  5. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. The macrophage chemotactic activity of Edwardsiella tarda extracellular products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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)....

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. [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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. 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.

  9. Edwardsiella Septicaemias

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. A developing model for Edwardsiella ictaluri pathogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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, ...

  17. 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

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

    PubMed

    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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. A mutation in rcsB, a gene encoding the core component of the Rcs cascade, enhances the virulence of Edwardsiella tarda.

    PubMed

    Xu, Ying; Xu, Tingting; Wang, Bin; Dong, Xue; Sheng, Aibo; Zhang, Xiao-Hua

    2014-04-01

    Edwardsiella tarda, a Gram-negative bacterium of the family Enterobacteriaceae, is the causative agent of the systemic disease edwardsiellosis, which is a major problem in aquaculture industry worldwide. Many virulence-related genes in E. tarda have been investigated, but the Rcs phosphorelay, a two-component pathway, which regulates several cell-surface-associated structures related to invasion and survival in host cells, has not yet been thoroughly studied. In the present study, an rcsB in-frame deletion mutant ΔrcsB was constructed through double-crossover allelic exchange. To complement the rcsB mutation, the ΔrcsB (pACYC184K-rcsB) mutant was constructed by transformation of a low-copy plasmid carrying the intact rcsB into the ΔrcsB mutant of E. tarda. Several virulence-associated characters of the mutants and wild-type strain were tested. Compared with wild-type strain EIB202, biofilm formation decreased significantly in ΔrcsB, while ΔrcsB (pACYC184K-rcsB) recovered the phenotype to some extent. In addition, the capacity for autoagglutination, the percentage of adherence and internalization to Epithelioma papulosum cyprini cells and lethality toward zebrafish embryos significantly increased in ΔrcsB. All these phenomena displayed by mutant ΔrcsB showed a certain degree of recovery, though incomplete, in strain ΔrcsB (pACYC184K-rcsB). Present results indicate that rcsB is involved in regulating the gene expression of virulence factors in E. tarda, as shown in other members of Enterobacteriaceae.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  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. 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.

  5. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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.

  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. 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.

  10. 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.

  11. [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.

  12. 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.

  13. 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.

  14. 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 ...

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Complete genome sequence of Edwardsiella hoshinae ATCC 35051

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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....

  8. 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.

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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).

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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% ...

  12. 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.

  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. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. 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.

  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. 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.

  1. 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

    ... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne...

  2. 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

    ... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne...

  3. 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

    ... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne...

  4. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  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. 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).

  18. 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

  19. 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

  20. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. 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.

  13. 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.

  14. Molecular Genetic Evaluation of Bacterial Pathogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. [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

  19. 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

  20. 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.

  1. 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

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Pathogenesis of Salmonellosis: Salmonella Exotoxins

    DTIC Science & Technology

    1982-03-08

    77Z7I AD _ REPORT NUMBER 3 0 Pathogenesis of Salmonellosis : Salmonella Exotoxins Annual Progress Report (9/1/79-8/31/80) M Johnny W. Peterson, Ph.D...OVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4. TITLE (nd Subtitle) S. TYPE OF REPORT &PERIOD COVERED Pathogenesis of Salmonellosis : Salmonella... salmonellosis , One of the rapid, in vitro assays measures biological activity in terms of Salmonella toxin’s capacity to stimulate adenylate cyclase in Chinese

  11. 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.

  12. 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.

  13. Porphyria Cutanea Tarda (PCT)

    MedlinePlus

    ... abnormally susceptible to damage of the skin from sunlight (photosensitivity). Extremely fragile skin that can peel or ... when porphyrins accumulate in the skin, they absorb sunlight and enter an excited state (photoactivation). This abnormal ...

  14. 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 ...

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. FAMMM syndrome: pathogenesis and management.

    PubMed

    Czajkowski, Rafał; Placek, Waldemar; Drewa, Gerard; Czajkowska, Aldona; Uchańska, Grazyna

    2004-02-01

    Familial atypical multiple mole melanoma (FAMMM) syndrome is an autosomal dominant disorder with variable incomplete penetrance of the clinical phenotypes. Pathogenesis of this syndrome has not been fully investigated. Across multiple studies, germline mutations in the INK4a antioncogene encoding p16 protein were found on average in approximately 40% of the FAMMM syndrome. Patients with the FAMMM syndrome are genetically loaded with an increased risk of developing melanoma and other malignant neoplasms, for example, a pancreatic cancer. Melanoma can develop from numerous atypical moles as well as de novo. A proper diagnosis of the syndrome and early application of prophylactics decreases the risk of neoplastic transformation of melanocytes.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. [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.

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1980-01-01

    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...PATHOGENESIS OF DENGUE VACCINE VIRUSES ’ z Progress Report IN MOSQUITOES July 1, 1979-Jan 1, 1980 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(@) S. CONTRACT

  4. An Odyssey to Viral Pathogenesis.

    PubMed

    Oldstone, Michael B A

    2016-05-23

    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1982-07-01

    r AD Af29 019 PA I4OGENESIS OF DENGUE VACCINE VIRUSES IN MOSQITOES U) YALE UNIV NEW YIAVEN CONN SCHOOL OF MEDICINE B JBEAT ET AL 01 JUL 82 DAMD1779...1963-A ’UNCLASS IFIET) .AD.- PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES FINAL REPORT Barry J. Beaty, Ph.D. Thomas H. G. Aitken, Ph.D. July 1...NUMBER 4. TITLE (mid Subdl.) S. KVPE OF REPORT & PERIOD COVERED PATHOGENESIS OF DENGUE VACCINE VIRUSES Final Scientific Report IN MOSQUITOES 6/1/79 to 6

  10. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    DTIC Science & Technology

    1984-01-01

    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...TYPE OF REPORT & PERIOD COVERED Anhual Progress Report PATHOGENESIS OF DENGUE VACCINE VIRUSES 1/1/83 to 1/1/84 IN MOSQUITOES &. PERFORMING O1G. REPORT...19. KEY WORDS (Continue on reverse side if nec.eary nd Identify by block number) Dengue -i candidate vaccines; TP-56; 45AZ5; Dengue -i parent virus

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. [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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. [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.

  6. 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

  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. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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."

  2. 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

  3. 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.

  4. 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.

  5. [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.

  6. 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

  7. [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.

  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. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. [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.

  18. [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.

  19. Impact of cocaine abuse on HIV pathogenesis

    PubMed Central

    Dash, Sabyasachi; Balasubramaniam, Muthukumar; Villalta, Fernando; Dash, Chandravanu; Pandhare, Jui

    2015-01-01

    Over 1.2 million people in the United States are infected with the human immunodeficiency virus type 1 (HIV-1). Tremendous progress has been made over the past three decades on many fronts in the prevention and treatment of HIV-1 disease. However, HIV-1 infection is incurable and antiretroviral drugs continue to remain the only effective treatment option for HIV infected patients. Unfortunately, only three out of ten HIV-1 infected individuals in the US have the virus under control. Thus, majority of HIV-1 infected individuals in the US are either unaware of their infection status or not connected/retained to care or are non-adherent to antiretroviral therapy (ART). This national public health crisis, as well as the ongoing global HIV/AIDS pandemic, is further exacerbated by substance abuse, which serves as a powerful cofactor at every stage of HIV/AIDS including transmission, diagnosis, pathogenesis, and treatment. Clinical studies indicate that substance abuse may increase viral load, accelerate disease progression and worsen AIDS-related mortality even among ART-adherent patients. However, confirming a direct causal link between substance abuse and HIV/AIDS in human patients remains a highly challenging endeavor. In this review we will discuss the recent and past developments in clinical and basic science research on the effects of cocaine abuse on HIV-1 pathogenesis. PMID:26539167

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. [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.

  8. 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

  9. 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

  10. Mechanisms of pathogenesis: differences amongst Leishmania species.

    PubMed

    Colmenares, Maria; Kar, Sujata; Goldsmith-Pestana, Karen; McMahon-Pratt, Diane

    2002-04-01

    One of the features of the genus Leishmania is the diversity of tropism/disease resulting from infection. With notable exceptions, the form (visceral, cutaneous, diffuse cutaneous, mucocutaneous) and severity of disease is a function of the infecting Leishmania species together with host genetics and consequent inflammatory and immune responses. It has become evident from genetic and immunological studies using the murine model that the various members of the genus Leishmania differ in aspects of their 'approach' to the host immune system. We are just beginning to appreciate the complexities of these interactions, which have import for the development of a vaccine against leishmaniasis. In this paper, what is currently understood concerning the mechanisms of leishmanial pathogenesis (based upon studies employing the murine model) is briefly summarized.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. [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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  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. [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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  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. Environmental contaminants in pathogenesis of breast cancer.

    PubMed

    Mukherjee, Shyamali; Koner, Bidhan Chandra; Ray, Sanhita; Ray, Amitabha

    2006-08-01

    This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors. Estrogens are closely related to the pathogenesis of breast cancer. Oxidative catabolism of estrogen, mediated by various cytochrome P450 enzymes, generates reactive free radicals that can cause oxidative damage. The same enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (xenobiotic) chemicals. Xenobiotic chemicals may exert their pathological effects through generation of reactive free radicals. Breast tissue can be a target of several xenobiotic agents. DNA-reactive metabolites of different xenobiotic compounds have been detected in breast tissue. Many phase I and II xenobiotic metabolizing enzymes are expressed in both normal and cancerous breast tissues. These enzymes play a significant role in the activation/detoxification of xenobiotic and endogenous compounds including estrogens. More than 30 carcinogenic chemicals are present in tobacco smoke; many of them are fat-soluble, resistant to metabolism and can be stored in breast adipose tissue. Similarly, pesticides are also known to cause oxidative stress; while some act as endocrine disruptor, some are shown to suppress apoptosis in estrogen sensitive cell lines. Reports have shown an association of smoking (both active and passive) and pesticides with breast cancer risk. However, the issues have remained controversial. Different mutagenic substances that are generated in the cooking process e.g., heterocyclic amines and polycyclic aromatic hydrocarbons (PAHs) can be a threat to breast tissue. PAHs and dioxins exert their adverse effects through the aryl hydrocarbon receptor (AhR), which activates several genes involved in the metabolisms of xenobiotic compounds and endogenous

  12. 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

  13. 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

  14. Nitrosative stress and pathogenesis of insulin resistance.

    PubMed

    Kaneki, Masao; Shimizu, Nobuyuki; Yamada, Daisuke; Chang, Kyungho

    2007-03-01

    Insulin resistance is a major causative factor for type 2 diabetes and is associated with increased risk of cardiovascular disease. Despite intense investigation for a number of years, molecular mechanisms underlying insulin resistance remain to be determined. Recently, chronic inflammation has been highlighted as a culprit for obesity-induced insulin resistance. Nonetheless, upstream regulators and downstream effectors of chronic inflammation in insulin resistance remain unclarified. Inducible nitric oxide synthase (iNOS), a mediator of inflammation, has emerged as an important player in insulin resistance. Obesity is associated with increased iNOS expression in insulin-sensitive tissues in rodents and humans. Inhibition of iNOS ameliorates obesity-induced insulin resistance. However, molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Protein S-nitrosylation, a covalent attachment of NO moiety to thiol sulfhydryls, has emerged as a major mediator of a broad array of NO actions. S-nitrosylation is elevated in patients with type 2 diabetes, and increased S-nitrosylation of insulin signaling molecules, including insulin receptor, insulin receptor substrate-1, and Akt/PKB, has been shown in skeletal muscle of obese, diabetic mice. Akt/PKB is reversibly inactivated by S-nitrosylation. Based on these findings, S-nitrosylation has recently been proposed to play an important role in the pathogenesis of insulin resistance.

  15. [Transthyretin: it's miracle function and pathogenesis].

    PubMed

    Ando, Yukio

    2009-03-01

    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  16. 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

  17. Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

    PubMed Central

    Chai, Chou; Lim, Kah-Leong

    2013-01-01

    Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. α-synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared. PMID:24532982

  18. Pathogenesis and pathophysiology of bacterial meningitis.

    PubMed Central

    Tunkel, A R; Scheld, W M

    1993-01-01

    Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder. Images PMID:8472245

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options

    PubMed Central

    Grace, Eddie; Asbill, Scott

    2015-01-01

    Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. PMID:26259797

  4. 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.

  5. 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.

  6. Nuclear receptors and pathogenesis of pancreatic cancer

    PubMed Central

    Polvani, Simone; Tarocchi, Mirko; Tempesti, Sara; Galli, Andrea

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease. PMID:25232244

  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. 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.

  9. Zika virus genome biology and molecular pathogenesis.

    PubMed

    Wang, Anyou; Thurmond, Stephanie; Islas, Leonel; Hui, Kingyung; Hai, Rong

    2017-03-22

    Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human disease, including neurological disorders, triggering public and scientific attention. Understanding how ZIKV causes disease is the highest priority, yet little is known about this virus. Here we examine the currently published data from ZIKV studies to provide the latest understanding of ZIKV genome biology and molecular pathogenesis. The ZIKV genome evolved rapidly from the Flavivirus genus and diverged from the members of this genus, even within the dengue virus cluster to which ZIKV belongs. Genome variations and divergences also exist among ZIKV strains/isolates. These genome divergences might account for the uniqueness of Zika disease. ZIKV infection activates not only the antiviral immune response but also the pro-inflammatory responses associated with disease symptoms. Strikingly, ZIKV activates protein complexes that are functionally associated with disease process, such as glial cell activation and proliferation (for example, Toll-like receptors), apoptosis and cell death, and inflammation. The activation of these complexes may critically contribute to Zika disease. The novel insights into ZIKV genome divergence and disease mechanisms summarized in this review will help accelerate the development of anti-ZIKV strategies.

  10. Prion Pathogenesis is Independent of Caspase-12

    PubMed Central

    Steele, Andrew D; Hetz, Claudio; Yi, Caroline H; Jackson, Walker S; Borkowski, Andrew W; Yuan, Junying; Wollmann, Robert H

    2007-01-01

    The pathogenic mechanism(s) underlying neurodegenerative diseases associated with protein misfolding is unclear. Several studies have implicated ER stress pathways in neurodegenerative conditions, including prion disease, amyotrophic lateral sclerosis, Alzheimer's disease and many others. The ER stress response and upregulation of ER stress-responsive chaperones is observed in the brains of patients affected with Creutzfeldt-Jacob disease and in mouse models of prion diseases. In particular, the processing of caspase-12, an ER-localized caspase, correlates with neuronal cell death in prion disease. However, the contribution of caspase-12 to neurodegeneration has not been directly addressed in vivo. We confirm that ER stress is induced and that caspase-12 is proteolytically processed in a murine model of infectious prion disease. To address the causality of caspase-12 in mediating infectious prion pathogenesis, we inoculated mice deficient in caspase-12 with prions. The survival, behavior, pathology and accumulation of proteinase K-resistant PrP are indistinguishable between caspase-12 knockout and control mice, suggesting that caspase-12 is not necessary for mediating the neurotoxic effects of prion protein misfolding. PMID:19164919

  11. Naegleria fowleri: pathogenesis, diagnosis, and treatment options.

    PubMed

    Grace, Eddie; Asbill, Scott; Virga, Kris

    2015-11-01

    Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America.

  12. Thyroid Cancer: Pathogenesis and Targeted Therapy

    PubMed Central

    Liebner, David A.; Shah, Manisha H.

    2011-01-01

    Therapeutic options for advanced, unresectable radioiodine-resistant thyroid cancers have historically been limited. Recent progress in understanding the pathogenesis of the various subtypes of thyroid cancer has led to increased interest in the development of targeted therapies, with potential strategies including angiogenesis inhibition, inhibition of aberrant intracellular signaling in the MAPK and PI3K/AKT/mTOR pathways, radioimmunotherapy, and redifferentiation agents. On the basis of a recent positive phase III clinical trial, the RET, vascular endothelial growth factor receptor (VEGFR), and epidermal growth factor receptor (EGFR) inhibitor vandetanib has received FDA approval as of April 2011 for use in the treatment of advanced medullary thyroid cancer. Several other recent phase II clinical trials in advanced thyroid cancer have demonstrated significant activity, and multiple other promising therapeutic strategies are in earlier phases of clinical development. The recent progress in targeted therapy is already revolutionizing management paradigms for advanced thyroid cancer, and will likely continue to dramatically expand treatment options in the coming years. PMID:23148184

  13. Deep endometriosis: definition, pathogenesis, and clinical management.

    PubMed

    Vercellini, Paolo; Frontino, Giada; Pietropaolo, Giuliana; Gattei, Umberto; Daguati, Raffaella; Crosignani, Pier Giorgio

    2004-05-01

    "Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. The available evidence suggests the same pathogenesis for deep infiltrating vesical and rectovaginal endometriosis (i.e., intraperitoneal seeding of regurgitated endometrial cells, which collect and implant in the most dependent portions of the peritoneal cavity and the anterior and posterior cul-de-sac, and trigger an inflammatory process leading to adhesion of contiguous organs with creation of false peritoneal bottoms). According to anatomic, surgical, and pathologic findings, deep endometriotic lesions seem to originate intraperitoneally rather than extraperitoneally. Also the lateral asymmetry in the occurrence of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomic differences of the left and right hemipelvis. Peritoneal, ovarian, and deep endometriosis may be diverse manifestations of a disease with a single origin (i.e., regurgitated endometrium). Based on different pathogenetic hypotheses, several schemes have been proposed to classify deep endometriosis, but further data are needed to demonstrate their validity and reliability. Drugs induce temporary quiescence of active deep lesions and may be useful in selected circumstances. Progestins should be considered as first-line medical treatment for temporary pain relief. However, in most cases of severely infiltrating disease, surgery is the final solution. Great importance must be given to complete and balanced counseling, as awareness of the real possibilities of different treatments will enhance the patient's collaboration.

  14. 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

  15. 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

  16. 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

  17. Pulmonary fibrosis: pathogenesis, etiology and regulation

    PubMed Central

    Wilson, MS; Wynn, TA

    2009-01-01

    Pulmonary fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The etiology of pulmonary fibrotic diseases is varied, with an array of triggers including allergens, chemicals, radiation and environmental particles. However, the cause of one of the most common pulmonary fibrotic conditions, idiopathic pulmonary fibrosis (IPF), is still unclear. This review examines common mechanisms of pulmonary wound-healing responses following lung injury, and highlights the pathogenesis of some of the most widespread pulmonary fibrotic diseases. A three phase model of wound repair is reviewed that includes; (1) injury; (2) inflammation; and (3) repair. In most pulmonary fibrotic conditions dysregulation at one or more of these phases has been reported. Chronic inflammation can lead to an imbalance in the production of chemokines, cytokines, growth factors, and disrupt cellular recruitment. These changes coupled with excessive pro-fibrotic IL-13 and/or TGFβ1 production can turn a well-controlled healing response into a pathogenic fibrotic response. Endogenous regulatory mechanisms are discussed including novel areas of therapeutic intervention. Restoring homeostasis to these dysregulated healing responses, or simply neutralizing the key pro-fibrotic mediators may prevent or slow the progression of pulmonary fibrosis. PMID:19129758

  18. [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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Fibromyalgia Pathogenesis and Treatment Options Update.

    PubMed

    Chinn, Steven; Caldwell, William; Gritsenko, Karina

    2016-04-01

    This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

  4. 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.

  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. Obesity, Cholesterol Metabolism and Breast Cancer Pathogenesis

    PubMed Central

    McDonnell, Donald P.; Park, Sunghee; Goulet, Matthew T.; Jasper, Jeff; Wardell, Suzanne E.; Chang, Ching-yi; Norris, John D.; Guyton, John R.; Nelson, Erik R.

    2014-01-01

    Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor (LXR) in macrophages and possibly other cells is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor (ER) agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. PMID:25060521

  7. Pathogenesis of Multiple Organ Failure in Sepsis.

    PubMed

    Rossaint, Jan; Zarbock, Alexander

    2015-01-01

    Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality. Importantly, no specific treatment strategy exists to efficiently prevent the development of MODS during sepsis. In this review, we aim to identify the relevant molecular immunological pathways involved in the pathogenesis of MODS during sepsis. We believe that a detailed understanding of this mechanism is necessary for the development of new treatment approaches for septic patients. In particular, knowledge of the endogenous regulators keeping the balance between necessary immune system activation to combat infections and prevention of host tissue damage would greatly improve the chances for the development of effective interventions.

  8. Recent advances in understanding ichthyosis pathogenesis

    PubMed Central

    Marukian, Nareh V.; Choate, Keith A.

    2016-01-01

    The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis. PMID:27408699

  9. Hemophagocytic Lymphohistiocytosis in Children: Pathogenesis and Treatment

    PubMed Central

    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. PMID:27242976

  10. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis

    PubMed Central

    Hwang, Hyun Sook; Kim, Hyun Ah

    2015-01-01

    Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid

  11. IRE1 signaling exacerbates Alzheimer's disease pathogenesis.

    PubMed

    Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Espinoza, Sandra; Ardiles, Álvaro O; Medinas, Danilo B; Salazar, Claudia; Foley, Andrew; Gajardo, Ivana; Thielen, Peter; Iwawaki, Takao; Scheper, Wiep; Soto, Claudio; Palacios, Adrian G; Hoozemans, Jeroen J M; Hetz, Claudio

    2017-03-24

    Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress. IRE1 signaling controls the expression of the transcription factor XBP1, in addition to degrade several RNAs. Importantly, a polymorphism in the XBP1 promoter was suggested as a risk factor to develop AD. Here, we demonstrate a positive correlation between the progression of AD histopathology and the activation of IRE1 in human brain tissue. To define the significance of the UPR to AD, we targeted IRE1 expression in a transgenic mouse model of AD. Despite initial expectations that IRE1 signaling may protect against AD, genetic ablation of the RNase domain of IRE1 in the nervous system significantly reduced amyloid deposition, the content of amyloid β oligomers, and astrocyte activation. IRE1 deficiency fully restored the learning and memory capacity of AD mice, associated with improved synaptic function and improved long-term potentiation (LTP). At the molecular level, IRE1 deletion reduced the expression of amyloid precursor protein (APP) in cortical and hippocampal areas of AD mice. In vitro experiments demonstrated that inhibition of IRE1 downstream signaling reduces APP steady-state levels, associated with its retention at the ER followed by proteasome-mediated degradation. Our findings uncovered an unanticipated role of IRE1 in the pathogenesis of AD, offering a novel target for disease intervention.

  12. Fetal alcohol syndrome: overview of pathogenesis.

    PubMed

    Henderson, G I; Patwardhan, R V; Hoyumpa, A M; Schenker, S

    1981-01-01

    The pathogenesis of Fetal Alcohol Syndrome (FAS) has been reviewed briefly in terms of factors which can influence its development and specific mechanisms. FAS was defined arbitrarily to include a wide spectrum ranging from the fully expressed clinical syndrome to growth and developmental impairment seen in fetal and neonatal animals exposed to ethanol. The available evidence suggests that ethanol per se in the absence of nutritional deficit can cause some from of FAS. Acetaldehyde may contribute to the FAS, but there is lack of knowledge concerning the levels of acetaldehyde needed to achieve fetal damage and the effect of this agent on the placenta and its placental transfer to the fetal organs. There is no specific data at this time to incriminate nutritional impairment, although further studies in animal models and man of the role of possible deficiencies of certain vitamins (i.e., folate) and of trace minerals (i.e., zinc) are needed. There is some evidence that alcohol or its metabolites may alter placental transport function. The relevance of this to FAS needs further investigation. The possible additive roles of caffeine, nicotine and other drugs on fetal development and viability deserve more consideration. The specific mechanism(s) of FAS are unknown. Of those considered--mutagenic (paternal) effect, abnormal protein synthesis, altered cerebral neurotransmitter balance, hormonal and other effects--impairment of protein synthesis at present seems best documented, but all clearly require further evaluation. When specific mechanisms are investigated it will be essential also to determine the dose-response relationship and the effects of a given dose of alcohol at various stages of gestation.

  13. Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

    PubMed Central

    Keller, Lance E.; Robinson, D. Ashley

    2016-01-01

    ABSTRACT While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulated Streptococcus pneumoniae (NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci. PMID:27006456

  14. [Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy].

    PubMed

    Schuppan, Detlef

    2016-07-01

    Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.

  15. Hepatitis B virus molecular biology and pathogenesis

    PubMed Central

    Lamontagne, R. Jason; Bagga, Sumedha; Bouchard, Michael J.

    2016-01-01

    As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350–500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, we provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and we highlight the functions of HBx that may

  16. Pathogenesis of noroviruses, emerging RNA viruses.

    PubMed

    Karst, Stephanie M

    2010-03-01

    Human noroviruses in the family Caliciviridae are a major cause of epidemic gastroenteritis. They are responsible for at least 95% of viral outbreaks and over 50% of all outbreaks worldwide. Transmission of these highly infectious plus-stranded RNA viruses occurs primarily through contaminated food or water, but also through person-to-person contact and exposure to fomites. Norovirus infections are typically acute and self-limited. However, disease can be much more severe and prolonged in infants, elderly, and immunocompromised individuals. Norovirus outbreaks frequently occur in semi-closed communities such as nursing homes, military settings, schools, hospitals, cruise ships, and disaster relief situations. Noroviruses are classified as Category B biodefense agents because they are highly contagious, extremely stable in the environment, resistant to common disinfectants, and associated with debilitating illness. The number of reported norovirus outbreaks has risen sharply since 2002 suggesting the emergence of more infectious strains. There has also been increased recognition that noroviruses are important causes of childhood hospitalization. Moreover, noroviruses have recently been associated with multiple clinical outcomes other than gastroenteritis. It is unclear whether these new observations are due to improved norovirus diagnostics or to the emergence of more virulent norovirus strains. Regardless, it is clear that human noroviruses cause considerable morbidity worldwide, have significant economic impact, and are clinically important emerging pathogens. Despite the impact of human norovirus-induced disease and the potential for emergence of highly virulent strains, the pathogenic features of infection are not well understood due to the lack of a cell culture system and previous lack of animal models. This review summarizes the current understanding of norovirus pathogenesis from the histological to the molecular level, including contributions from new model

  17. Immunopathology of primary hypophysitis: implications for pathogenesis.

    PubMed

    Gutenberg, A; Buslei, R; Fahlbusch, R; Buchfelder, M; Brück, W

    2005-03-01

    The etiology of primary hypophysitis is still not fully elucidated. Histologically, primary hypophysitis includes three different main subtypes: lymphocytic (LYH), granulomatous (GRH), and xanthomatous (XH) hypophysitis. Clinical and laboratory findings suggest an autoimmune basis in primary hypophysitis. Controversy still exists about the composition of the inflammatory infiltrate and the relevant immunopathogenic effector mechanisms. Therefore, 21 cases of primary hypophysitis of different subtypes were analyzed with respect to the expression of lymphocyte and macrophage antigens as well as MHC class I and II molecules of the inflammatory infiltrate and the resident pituitary acinar cells. Lymphocyte infiltration in LYH (n = 15), but also in GRH (n = 4) and XH (n = 2), mainly consisted of T cells, while B cells were rare. Independent from the histopathologic subtype, T cell subsets showed equal ratios of CD4+ to CD8+ T cells. Highest numbers of activated CD8+ T cells were observed in LYH presenting during pregnancy, surrounding or even infiltrating preserved pituitary acinar cells. Moreover, an increased rate of activated CD8+ T cells correlated with a shorter duration of clinical symptoms. In LYH, aberrant expression of MHC class II antigens as well as overexpression of MHC class I molecules on pituitary cells were observed. Independent of the histologic subtype, macrophages mostly expressed markers of chronic activation and showed MHC class II positivity. LYH, GRH, and XH, although heterogeneous in their histologic appearance and in age distribution, exhibit a similar if not identical immunohistologic profile. It is highly likely that direct T cell-mediated cytotoxicity through CD8+ T cells, with the initial help of CD4+ T cells, is pivotal in the pathogenesis of primary hypophysitis, implicating a target autoantigen expressed by pituitary cells.

  18. Pathogenesis of Warthin’s tumors

    PubMed Central

    Kuzenko, Yevhen V.; Romanuk, Anatoly M.; Dyachenko, Olena Olegivna; Hudymenko, Olena

    2016-01-01

    Introduction Warthin’s tumor, also known as papillary cystadenoma lymphomatosum, monomorphic adenoma, or adenolymphoma, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and lymph node-like stroma. It is named after the pathologist Aldred Scott Warthin, who described two cases in 1929. Objective The aim of this study is to analyze the pathogenesis of Warthin’s tumor. Methods A total of 15 patients with Warthin’s tumor were studied. Hematoxylin and eosin stains, which have been used for at least a century and are still essential for recognizing various tissue types and the morphologic changes for cancer diagnosis, were used. Warthin’s tumor was evaluated for the expression of MGMT, CD3, HSP90AA1, MMP-1, Bcl-2, CD79A, IgG, Ki-67, p53, IgM, OPN, S100, myeloperoxidase, and VEGF by immunohistochemistry. Results Immunohistochemical staining confirmed that the immune cells within the follicles of Warthin’s tumor were positive for MGMT (10.0 ± 0.34%), Ki-67 (13.3 ± 0.45%), Bcl-2 (42.6 ± 8.33), and p53 (11.6 ± 2.3). The immune cells associated with CD3 were present at the stroma of residual cells (47.3 ± 3.89); however, they were not present in the epithelium cell layers. B cells (CD79A) consistent with germinal centers were present within the immune cells and formed follicles (43.2 ± 13.5%). Conclusions Histopathological analysis of the stroma and parenchyma revealed balanced distribution of epithelial and stromal component. Epithelial component of the Warthin’s tumor is the trigger for the tumor process. This study indicates that the Warthin tumor is a consequence of inflammatory etiology. PMID:28386459

  19. Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy.

    PubMed

    Parekh, Parth J; Balart, Luis A

    2015-08-01

    Hepatic encephalopathy (HE) is a commonly encountered sequela of chronic liver disease and cirrhosis with significant associated morbidity and mortality. Although ammonia is implicated in the pathogenesis of HE, the exact underlying mechanisms still remain poorly understood. Its role in the urea cycle, astrocyte swelling, and glutamine and gamma-amino-n-butyric acid systems suggests that the pathogenesis is multifaceted. Greater understanding in its underlying mechanism may offer more targeted therapeutic options in the future, and thus further research is necessary to fully understand the pathogenesis of HE.

  20. Aetiology, pathogenesis, and pathology of cervical neoplasia.

    PubMed Central

    Arends, M J; Buckley, C H; Wells, M

    1998-01-01

    typing of cells recovered from cervical scrapes can be made; however, a rigorous cost-benefit analysis of introducing HPV typing into the cervical screening programme is required. Prophylactic and therapeutic HPV vaccines are under development. This article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia, emphasising the role of HPVs. PMID:9602680

  1. Listeria Pathogenesis and Molecular Virulence Determinants

    PubMed Central

    Vázquez-Boland, José A.; Kuhn, Michael; Berche, Patrick; Chakraborty, Trinad; Domínguez-Bernal, Gustavo; Goebel, Werner; González-Zorn, Bruno; Wehland, Jürgen; Kreft, Jürgen

    2001-01-01

    , rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research. PMID:11432815

  2. Role of perfumes in pathogenesis of autism.

    PubMed

    Bagasra, Omar; Golkar, Zhabiz; Garcia, Miranda; Rice, Lakya N; Pace, Donald Gene

    2013-06-01

    Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents

  3. Water hardness influences Flavobacterium columnare pathogenesis in channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies were conducted to determine aspects of water chemistry responsible for large differences in pathogenesis and mortality rates in challenges of channel catfish Ictalurus punctatus with Flavobacterium columnare; challenges were conducted in water supplying the Stuttgart National Aquaculture Res...

  4. Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

    PubMed

    Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

    2013-04-01

    Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

  5. Acquired Secondary Events in the Pathogenesis of Hereditary Breast Cancer.

    DTIC Science & Technology

    1997-09-01

    pathogenesis of lung carcinoma. JAMA, 273: 558-563,1995. 16. Sambrook, J., Fritsch, E. and Maniatis, T. Molecular Cloning , a Laboratory Manual. Plainview, New York: Cold Spring Harbor Laboratory Press, 1989.

  6. Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-12-1-0590 TITLE: SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA PRINCIPAL INVESTIGATOR: KATHLEEN M...SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0590 SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES None 14. ABSTRACT: Diamond Blackfan Anemia (DBA) is a disorder that results in pure red cell aplasia, congenital

  7. Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0590 TITLE: SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA PRINCIPAL...5a. CONTRACT NUMBER W81XWH-12-1-0590 SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA 5b. GRANT NUMBER 5c...SUPPLEMENTARY NOTES None 14. ABSTRACT Diamond Blackfan Anemia (DBA) is a disorder that results in pure red cell aplasia, congenital abnormalities, and

  8. Epigenetics, the holy grail in the pathogenesis of systemic sclerosis.

    PubMed

    Altorok, Nezam; Almeshal, Nawaf; Wang, Yongqing; Kahaleh, Bashar

    2015-10-01

    The objective of this review is to present evidence that supports the central role of epigenetic regulation in the pathogenesis of SSc. SSc is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and obliterative vasculopathy affecting predominantly the microvessels. Remarkable progress has been made in the past few years emphasizing the importance of epigenetic modifications in the pathogenesis of many disorders, including SSc. Current evidence demonstrates alterations in DNA methylation, histone code modifications and changes in microRNA (miRNA) expression levels in SSc cells. Recent reports have described the differential expression of numerous regulatory miRNAs in SSc, mainly in SSc fibroblasts, a number of which are important in TGF-β pathways and downstream signalling cascades. While studies to date have revealed the significant role of epigenetic modifications in the pathogenesis of SSc, the causal nature of epigenetic alterations in SSc pathogenesis remains elusive. Additional longitudinal and comprehensive epigenetic studies designed to evaluate the effect of environmental epigenetic factors on disease pathogenesis are needed.

  9. A Trojan horse mechanism of bacterial pathogenesis against nematodes

    PubMed Central

    Niu, Qiuhong; Huang, Xiaowei; Zhang, Lin; Xu, Jianping; Yang, Dongmei; Wei, Kangbi; Niu, Xuemei; An, Zhiqiang; Bennett, Joan Wennstrom; Zou, Chenggang; Yang, Jinkui; Zhang, Ke-Qin

    2010-01-01

    Understanding the mechanisms of host–pathogen interaction can provide crucial information for successfully manipulating their relationships. Because of its genetic background and practical advantages over vertebrate model systems, the nematode Caenorhabditis elegans model has become an attractive host for studying microbial pathogenesis. Here we report a “Trojan horse” mechanism of bacterial pathogenesis against nematodes. We show that the bacterium Bacillus nematocida B16 lures nematodes by emitting potent volatile organic compounds that are much more attractive to worms than those from ordinary dietary bacteria. Seventeen B. nematocida-attractant volatile organic compounds are identified, and seven are individually confirmed to lure nematodes. Once the bacteria enter the intestine of nematodes, they secrete two proteases with broad substrate ranges but preferentially target essential intestinal proteins, leading to nematode death. This Trojan horse pattern of bacterium–nematode interaction enriches our understanding of microbial pathogenesis. PMID:20733068

  10. Junín Virus Pathogenesis and Virus Replication

    PubMed Central

    Grant, Ashley; Seregin, Alexey; Huang, Cheng; Kolokoltsova, Olga; Brasier, Allan; Peters, Clarence; Paessler, Slobodan

    2012-01-01

    Junín virus, the etiological agent of Argentine hemorrhagic fever, causes significant morbidity and mortality. The virus is spread through the aerosolization of host rodent excreta and endemic to the humid pampas of Argentina. Recently, significant progress has been achieved with the development of new technologies (e.g. reverse genetics) that have expanded knowledge about the pathogenesis and viral replication of Junín virus. We will review the pathogenesis of Junín virus in various animal models and the role of innate and adaptive immunity during infection. We will highlight current research regarding the role of molecular biology of Junín virus in elucidating virus attenuation. We will also summarize current knowledge on Junín virus pathogenesis focusing on the recent development of vaccines and potential therapeutics. PMID:23202466

  11. Gut microflora in the pathogenesis of the complications of cirrhosis.

    PubMed

    Garcia-Tsao, Guadalupe; Wiest, Reiner

    2004-04-01

    The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Cirrhotic patients are prone to develop bacterial infections, mainly the 'spontaneous' infection of ascites or spontaneous bacterial peritonitis. Other complications of cirrhosis, such as variceal haemorrhage and ascites, occur mostly or solely as a consequence of portal hypertension. Portal pressure increases initially as a consequence of an increased intrahepatic resistance but, once collaterals have formed, high portal pressure is maintained by an increased splanchnic blood inflow secondary to vasodilatation. Splanchnic vasodilatation is the initiating event in the hyperdynamic circulatory state that aggravates the complications of cirrhosis. The gut flora plays a role in both the development of infections and in the hyperdynamic circulatory state of cirrhosis and, although less prominently, it also plays a role in the pathogenesis of hepatic encephalopathy. This chapter presents evidence regarding gut flora and its modification in the pathogenesis and management of these complications of cirrhosis.

  12. Multiple Factors Involved in the Pathogenesis of White Matter Lesions

    PubMed Central

    Lin, Jing; Wang, Dilong; Lan, Linfang

    2017-01-01

    White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention. PMID:28316994

  13. New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma

    PubMed Central

    Patel, Tushar

    2013-01-01

    Intrahepatic cholangiocarcinoma is an aggressive malignancy and is one of the most devastating cancers of the gastrointestinal tract. The molecular mechanisms contributing to the pathogenesis of these cancers are not well understood. The recognition and distinction of these cancers from other tumors such as extrahepatic or ductal cholangiocarcinoma and hepatocellular carcinoma have been important in defining the pathogenesis. New insights into molecular mechanisms contributing to disease pathogenesis are emerging from recent epidemiological, genome-wide profiling and laboratory based studies. These have contributed to an improved understanding of risk factors, genetic mutations and pathophysiological mechanisms that are associated with these tumors. The contribution of well-established risk factors such as biliary tract inflammation and key signaling pathways involved in intrahepatic cholangiocarcinoma are being further defined. These new insights have several important implications for both molecular diagnosis and therapy of these cancers. PMID:24145988

  14. Acute promyelocytic leukemia: new issues on pathogenesis and treatment response.

    PubMed

    Vitoux, Dominique; Nasr, Rihab; de The, Hugues

    2007-01-01

    Pathogenesis of acute promyelocytic leukemia appears to be one of the best understood among human malignancies. The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. A set of recent data has significantly increased the complexity of our view of acute promyelocytic leukemia pathogenesis, as well as of therapeutic response. This review summarizes and discusses these findings, which yield novels questions and models.

  15. Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia.

    PubMed

    Smith, Tyler A; Kirkpatrick, Daniel R; Kovilam, Oormila; Agrawal, Devendra K

    2015-01-01

    Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia has been identified, including endothelial dysfunction, immunological dysregulation and trophoblastic invasion. In this literature review, we have critically reviewed existing literature regarding the research findings that link the role of vitamin D to the pathogenesis and immunoregulation of preeclampsia. The relationship of vitamin D with the suspected etiologies of preeclampsia underscores its clinical potential in the diagnosis and treatment of preeclampsia.

  16. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    PubMed

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  17. Genetic events in the pathogenesis of multiple myeloma

    PubMed Central

    Chng, W. J.; Glebov, O.; Bergsagel, P.L.; Kuehl, W. M.

    2007-01-01

    The genetics of myeloma has been increasingly elucidated in recent years. Recurrent genetic events, and also biologically distinct and clinically relevant genetic subtypes of myeloma have been defined. This has facilitated our understanding of the molecular pathogenesis of the disease. In addition, some genetic abnormalities have proved to be highly reproducible prognostic factors. With the expanding therapeutic armamentarium, it is time to include genetic assessment as part of clinical evaluation of myeloma patients to guide management. In this review we examine the role of various genetic abnormalities in the molecular pathogenesis of myeloma, and the use of such abnormalities in disease classification, prognosis and clinical management. PMID:18070707

  18. Porphyria Cutanea Tarda and Agent Orange

    MedlinePlus

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research ( ... eligible for a free Agent Orange registry health exam . Surviving spouses, dependent children and dependent parents of ...

  19. [Polonium-210 acute and chronic pathomorphology and pathogenesis].

    PubMed

    Kvacheva, Yu E

    2015-01-01

    In the present review, the data on the pathology of acute and chronic polonium injuries available from the an open-access domestic and foreign literature are primarily systemized and analyzed. The historical background of the research is presented in brief. On the basis of clinical and experimental generalizations, the current concept regarding the pathogenesis of polonium intoxication has been developed.

  20. Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Orlikowski, David; Annane, Djillali

    2010-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.

  1. Functional study of gene hp0169 in Helicobacter pylori pathogenesis.

    PubMed

    Zhao, Huilin; Ji, Xiaofei; Chen, Xingxing; Li, Jiaojiao; Zhang, Ying; Du, Zhenzhen; Zhang, Yumei; Li, Boqing

    2017-03-01

    Many virulence genes have been reported to play important roles in Helicobacter pylori pathogenesis. However the detailed mechanisms of many of them have not been completely clear. In this study, we found gene hp0169, encoding a putative collagenase (HpPrtC), was involved in pathogenesis of H. pylori. Recombinant HpPrtC shows activities to both native and heat-denatured collagens. This result indicated that HpPrtC may act as a virulence factor to help the bacterium colonize in their host stomach by degrading surrounding collagens. hp0169 was deleted by homologous recombination to study its function in bacterium-host cell interaction. For the pathogenic functions on the host cells, the hp0169 mutant exhibits no significant changes on inducing apoptosis of GES-1 cells. However, the viability and proliferation rate of GES-1 cells infected with mutant strain were higher than the cells infected with wild-type strain. These results indicated that except for its collagenolytic activity, HpPrtC might participate in H. pylori pathogenesis through an additional pathway. Functional studies on hp0169 involved in pathogenesis would shed light on deep understanding of the pathogenic mechanism of H. pylori.

  2. The pathogenesis of Foot-and-Mouth Disease in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental invest...

  3. Studies of the Tumor Microenvironment in Pathogenesis of Neuroblastoma

    DTIC Science & Technology

    2013-07-01

    of Neuroblastoma PRINCIPAL INVESTIGATOR: Shahab Asgharzadeh, M D CONTRACTING ORGANIZATION: Children’s Hospital Los Angeles Los Angeles...2012 - 30 June 2013 4. TITLE AND SUBTITLE Studies of the Tumor Microenvironment in Pathogenesis of Neuroblastoma 5a. CONTRACT NUMBER 5b...NOTES 14. ABSTRACT The NBL-Tag neuroblastoma tumors were assessed for presence of macrophages and their role in promoting tumor growth

  4. Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

    PubMed

    García Martínez, F J; Menchén, L

    2016-09-01

    Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets.

  5. Pathogenesis and Cerebrospinal Fluid Hydrodynamics of the Chiari I Malformation.

    PubMed

    Buell, Thomas J; Heiss, John D; Oldfield, Edward H

    2015-10-01

    This article summarizes the current understanding of the pathophysiology of the Chiari I malformation that is based on observations of the anatomy visualized by modern imaging with MRI and prospective studies of the physiology of patients before and after surgery. The pathogenesis of a Chiari I malformation of the cerebellar tonsils is grouped into 4 general mechanisms.

  6. [Pathogenesis of human papillomavirus infection in patients with epidermodysplasia verruciformis].

    PubMed

    Liang, Si; Zuo, Ya-Gang; Wang, Bao-Xi

    2009-02-01

    Epidermodysplasia verruciformis (EV), a rare inherited disease, is believed to be associated with human papillomavirus (HPV) infection. EVER1/2 genes, dendritic cells, T lymphocytes, and the biological characteristics of HPV itself may play roles in the pathogenesis of HPV infection.

  7. Pathogenesis of the intravertebral vacuum of Kümmell's disease

    PubMed Central

    He, Dengwei; Yu, Weiyang; Chen, Zhenzhong; Li, Liangchen; Zhu, Kejun; Fan, Shunwu

    2016-01-01

    In this review, we explored the progress of the pathogenesis of Kümmell's disease intravertebral vacuum. Using different expressions of the same disease including ‘Kümmell's disease’, ‘avascular necrosis after vertebral compression fracture (VCF)’, ‘post-traumatic vertebral osteonecrosis’, ‘vertebral pseudarthrosis’, ‘intravertebral vacuum (cleft or gas)’, ‘delayed vertebral collapse’, ‘VCF nonunion’, and by conducting a search of the PubMed database, we analyzed the results to examine the pathogenesis of the intravertebral vacuum of Kümmell's disease after referring to pertinent literature on intravertebral vacuum of ischemic necrosis after VCF, and exploring the progress of pathogenesis of this disease. A number of discrepancies were identified within the pathogenesis of the intravertebral vacuum after VCF. There were statements such as avascular necrosis of the vertebral body, bone biomechanics, gas forming and other types of claims, all of which obtained clinical and biomechanical supporting evidence. Collectively, most of the researchers believe that Kümmell vertebral fracture syndrome was the comprehensive effect of multiple factors including osteoporosis, avascular necrosis of the vertebral body, and biomechanical changes following fracture. However, there are a number of discrepancies to be resolved and future studies are therefore needed. PMID:27446290

  8. Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis

    PubMed Central

    Banerjee, Rebecca; Starkov, Anatoly A.; Beal, M. Flint; Thomas, Bobby

    2010-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with unknown etiology. It is marked by widespread neurodegeneration in the brain with profound loss of A9 midbrain dopaminergic neurons in substantia nigra pars compacta. Several theories of biochemical abnormalities have been linked to pathogenesis of PD of which mitochondrial dysfunction due to an impairment of mitochondrial complex I and subsequent oxidative stress seems to take the center stage in experimental models of PD and in postmortem tissues of sporadic forms of illness. Recent identification of specific gene mutations and their influence on mitochondrial functions has further reinforced the relevance of mitochondrial abnormalities in disease pathogenesis. In both sporadic and familial forms of PD abnormal mitochondrial paradigms associated with disease include impaired functioning of the mitochondrial electron transport chain, aging associated damage to mitochondrial DNA, impaired calcium buffering, and anomalies in mitochondrial morphology and dynamics. Here we provide an overview of specific mitochondrial functions affected in sporadic and familial PD that play a role in disease pathogenesis. We propose to utilize these gained insights to further streamline and focus the research to better understand mitochondria's role in disease development and exploit potential mitochondrial targets for therapeutic interventions in PD pathogenesis. PMID:19059336

  9. Conducting influenza virus pathogenesis studies in avian species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian infection studies with influenza A are an important means of assessing host susceptibility, viral pathogenesis, host responses to infection, mechanisms of transmission and viral pathotype. Complex systems and natural settings may also be explored with carefully designed infection studies. In ...

  10. [Pathogenesis and prognosis of pyoderma gangrenosum (dermatitis ulcerosa) (author's transl)].

    PubMed

    Odeh, F

    1981-12-15

    The diagnosis of p. g. is based on clinical appearance. P. g. is frequently associated with systemic disease. This paper presents 23 cases of p. g. associated with other sufferings and a review of the Literature in which pathogenesis, prognosis, age and sex of this cutaneous disorder are standing in foreground for a discussion.

  11. POSTNATAL INFLAMMATION IN THE PATHOGENESIS OF BRONCHOPULMONARY DYSPLASIA

    PubMed Central

    Bhandari, Vineet

    2014-01-01

    Exposure to hyperoxia, invasive mechanical ventilation and systemic/local sepsis are important antecedents of postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD). This review will summarize information obtained from animal (baboon, lamb/sheep, rat and mouse) models that pertain to the specific inflammatory agents and signaling molecules that predispose a premature infant to BPD. PMID:24578018

  12. Dementia in 2012: Further insights into Alzheimer disease pathogenesis.

    PubMed

    Weiner, Michael W

    2013-02-01

    In 2012, studies of autosomal dominant Alzheimer disease (AD), late-onset AD, and a rare genetic mutation of amyloid precursor protein provided support for the critical role of amyloid in AD pathogenesis. Increasing evidence implicated cell-to-cell transmission in the spread of tau and amyloid, highlighting novel targets for therapeutic intervention.

  13. Taming the Elephant: Salmonella Biology, Pathogenesis, and Prevention▿

    PubMed Central

    Andrews-Polymenis, Helene L.; Bäumler, Andreas J.; McCormick, Beth A.; Fang, Ferric C.

    2010-01-01

    Salmonella infections continue to cause substantial morbidity and mortality throughout the world. However, recent discoveries and new paradigms promise to lead to novel strategies to diagnose, treat, and prevent Salmonella infections. This review provides an update of the Salmonella field based on oral presentations given at the recent 3rd ASM Conference on Salmonella: Biology, Pathogenesis and Prevention. PMID:20385760

  14. Deciphering the pathogenesis of tendinopathy: a three-stages process

    PubMed Central

    2010-01-01

    Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments. PMID:21144004

  15. Behavioral contributions to the pathogenesis of type 2 diabetes.

    PubMed

    Spruijt-Metz, Donna; O'Reilly, Gillian A; Cook, Lauren; Page, Kathleen A; Quinn, Charlene

    2014-04-01

    Behavioral contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions, which change each of the lifestyle behaviors, is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies, which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes.

  16. Genetic determinants of pathogenesis by feline infectious peritonitis virus.

    PubMed

    Brown, Meredith A

    2011-10-15

    Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive viral disease of cats associated with feline coronavirus (FCoV). Viral genetic determinants specifically associated with FIPV pathogenesis have not yet been discovered. Viral gene signatures in the spike, non-structural protein 3c, and membrane of the coronavirus genome have been shown to often correlate with disease manifestation. An "in vivo mutation transition hypothesis" is widely accepted and postulates that de novo virus mutation occurs in vivo giving rise to virulence. The existence of "distinct circulating avirulent and virulent strains" is an alternative hypothesis of viral pathogenesis. It may be possible that viral dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic data suggests that the genetic background of the cat contributes to the manifestation of FIP. Further studies exploring both viral and host genetic determinants of disease in FIP offer specific opportunities for the management of this disease.

  17. Celiac disease: pathogenesis of a model immunogenetic disease

    PubMed Central

    Kagnoff, Martin F.

    2007-01-01

    Celiac disease is characterized by small-intestinal mucosal injury and nutrient malabsorption in genetically susceptible individuals in response to the dietary ingestion of wheat gluten and similar proteins in barley and rye. Disease pathogenesis involves interactions among environmental, genetic, and immunological factors. Although celiac disease is predicted by screening studies to affect approximately 1% of the population of the United States and is seen both in children and in adults, 10%–15% or fewer of these individuals have been diagnosed and treated. This article focuses on the role of adaptive and innate immune mechanisms in the pathogenesis of celiac disease and how current concepts of immunopathogenesis might provide alternative approaches for treating celiac disease. PMID:17200705

  18. Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics.

    PubMed

    Dwivedi, Mitesh; Kemp, E Helen; Laddha, Naresh C; Mansuri, Mohmmad Shoab; Weetman, Anthony P; Begum, Rasheedunnisa

    2015-01-01

    Vitiligo is a hypomelanotic autoimmune skin disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses against melanocytes. Regulatory T cells (Tregs) are crucial to the development of self-tolerance and so are major foci in the study of autoimmune pathogenesis of vitiligo. This review will summarise recent findings concerning the role of Tregs in the pathogenesis of vitiligo. In addition, as antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, new strategies that expand or induce de novo generation of Tregs and which are currently being investigated as therapies for other autoimmune diseases, will be discussed. These approaches will highlight the opportunities for Treg cell-based therapeutics in vitiligo.

  19. Pathogenesis of pulmonary emphysema - cellular and molecular events.

    PubMed

    Di Petta, Antonio

    2010-06-01

    Pulmonary emphysema is a chronic obstructive disease, resulting from important alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  20. Cardiovascular Changes in Cirrhosis: Pathogenesis and Clinical Implications

    PubMed Central

    Al-Hamoudi, Waleed K.

    2010-01-01

    Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation, cirrhotic cardiomyopathy, and pulmonary vascular abnormalities. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include neurohumoral and vascular dysregulations. Accumulating evidence suggests that cirrhosis-related cardiovascular abnormalities play a major role in the pathogenesis of multiple life-threatening complications including hepatorenal syndrome, ascites, spontaneous bacterial peritonitis, gastroesophageal varices, and hepatopulmonary syndrome. Treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation. Careful fluid management in the immediate post-transplant period is extremely important to avoid cardiac-related complications. Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to the cardiovascular abnormalities, resulting in restoration of a normal circulation. The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis. PMID:20616408

  1. A Three Signal Model of T-cell Lymphoma Pathogenesis

    PubMed Central

    Wilcox, Ryan A.

    2015-01-01

    T-cell lymphoma pathogenesis and classification have, until recently, remained enigmatic. Recently performed whole-exome sequencing and gene-expression profiling studies have significant implications for their classification and treatment. Recurrent genetic modifications in antigen (“signal 1”), costimulatory (“signal 2”), or cytokine receptors (“signal 3”), and the tyrosine kinases and other signaling proteins they activate, have emerged as important therapeutic targets in these lymphomas. Many of these genetic modifications do not function in a cell-autonomous manner, but require the provision of ligand(s) by constituents of the tumor microenvironment, further supporting the long-appreciated view that these lymphomas are dependent upon and driven by their microenvironment. Therefore, the seemingly disparate fields of genomics and immunology are converging. A unifying “3 signal model” for T-cell lymphoma pathogenesis that integrates these findings will be presented, and its therapeutic implications briefly reviewed. PMID:26408334

  2. The pathogenesis of Achilles tendinopathy: a systematic review.

    PubMed

    Magnan, Bruno; Bondi, Manuel; Pierantoni, Silvia; Samaila, Elena

    2014-09-01

    Achilles tendinopathy is a degenerative, not an inflammatory, condition. It is prevalent in athletes involved in running sports. A systematic literature review on Achilles tendon tendinopathy has been performed according to the intrinsic (age, sex, body weight, tendon temperature, systemic diseases, muscle strength, flexibility, previous injuries and anatomical variants, genetic predisposition and blood supply) and extrinsic risk factors (drugs and overuse), which can cause tendon suffering and degeneration. Different theories have been found: Neurogenic, Angiogenic, Impingement and "Iceberg" Hypotheses. Multiple databases were utilized for articles published between 1964 and 2013. The different hypothesis were analyzed, differently considering those concerning the pathogenesis of tendinopathy and those concerning the etiology of complaints in patients. This review of the literature demonstrates the heterogeneity of Achilles tendinopathy pathogenesis. Various risk factors have been identified and have shown an interaction between them such as genes, age, circulating and local cytokine production, sex, biomechanics and body composition.

  3. Update on Legionnaires' disease: pathogenesis, epidemiology, detection and control.

    PubMed

    Hilbi, Hubert; Jarraud, Sophie; Hartland, Elizabeth; Buchrieser, Carmen

    2010-04-01

    Legionellosis or Legionnaires' disease is an emerging and often-fatal form of pneumonia that is most severe in elderly and immunocompromised people, an ever-increasing risk group for infection. In recent years, the genomics of Legionella spp. has significantly increased our knowledge of the pathogenesis of this disease by providing new insights into the evolution and genetic and physiological basis of Legionella-host interactions. The seventh international conference on Legionella, Legionella 2009, illustrated many recent conceptual advances in epidemiology, pathogenesis and ecology. Experts in different fields presented new findings on basic mechanisms of pathogen-host interactions and bacterial evolution, as well as the clinical management and environmental prevalence and persistence of Legionella. The presentations revealed remarkable facts about the genetic and metabolic basis of the intracellular lifestyle of Legionella and reported on its striking ability to manipulate host cell processes by molecular mimicry. Together, these investigations will lead to new approaches for the treatment and prevention of Legionnaires' disease.

  4. Molecular biology and pathogenesis of animal lentivirus infections.

    PubMed Central

    Clements, J E; Zink, M C

    1996-01-01

    Lentiviruses are a subfamily of retroviruses that are characterized by long incubation periods between infection of the host and the manifestation of clinical disease. Human immunodeficiency virus type 1, the causative agent of AIDS, is the most widely studied lentivirus. However, the lentiviruses that infect sheep, goats, and horses were identified and studied prior to the emergence of human immunodeficiency virus type 1. These and other animal lentiviruses provide important systems in which to investigate the molecular pathogenesis of this family of viruses. This review will focus on two animal lentivirus models: the ovine lentivirus visna virus; and the simian lentivirus, simian immunodeficiency virus. These animal lentiviruses have been used to examine, in particular, the pathogenesis of lentivirus-induced central nervous system disease as models for humans with AIDS as well as other chronic diseases. PMID:8665473

  5. Invasive Mold Infections: Virulence and Pathogenesis of Mucorales

    PubMed Central

    Morace, Giulia; Borghi, Elisa

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses. PMID:22121366

  6. Using 'omics' to define pathogenesis and biomarkers of Parkinson's disease.

    PubMed

    Caudle, W Michael; Bammler, Theo K; Lin, Yvonne; Pan, Sheng; Zhang, Jing

    2010-06-01

    Although great effort has been put forth to uncover the complex molecular mechanisms exploited in the pathogenesis of Parkinson's disease, a satisfactory explanation remains to be discovered. The emergence of several -omics techniques, transcriptomics, proteomics and metabolomics, have been integral in confirming previously identified pathways that are associated with dopaminergic neurodegeneration and subsequently Parkinson's disease, including mitochondrial and proteasomal function and synaptic neurotransmission. Additionally, these unbiased techniques, particularly in the brain regions uniquely associated with the disease, have greatly enhanced our ability to identify novel pathways, such as axon-guidance, that are potentially involved in Parkinson's pathogenesis. A comprehensive appraisal of the results obtained by different -omics has also reconfirmed the increase in oxidative stress as a common pathway likely to be critical in Parkinson's development/progression. It is hoped that further integration of these techniques will yield a more comprehensive understanding of Parkinson's disease etiology and the biological pathways that mediate neurodegeneration.

  7. Uveitis and glaucoma: new insights in the pathogenesis and treatment.

    PubMed

    Sng, Chelvin C A; Ang, Marcus; Barton, Keith

    2015-01-01

    Glaucoma is a potentially blinding complication of uveitis, where intraocular inflammation, secondary corticosteroid response, and varying types and degrees of angle abnormalities contribute to its pathogenesis. Management of uveitic glaucoma remains challenging. Treatment is targeted at reducing the inflammation and lowering the intraocular pressure. Recent studies have highlighted the role of viruses, such as cytomegalovirus, herpes simplex virus, and more recently Ebola virus, in the pathogenesis of uveitic glaucoma. Antiviral therapy may be beneficial in eyes with detectable viral DNA. The success of glaucoma surgery is decreased in eyes with uveitic glaucoma, and surgical interventions are associated with a higher incidence of postoperative complications. Novel glaucoma surgical and laser treatments may improve the predictability of surgery for uveitic glaucoma, but these require further evaluation.

  8. Advanced Mass Spectrometry Technologies for the Study of Microbial Pathogenesis

    PubMed Central

    Moore, Jessica L.; Caprioli, Richard M.; Skaar, Eric P.

    2014-01-01

    Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been successfully applied to the field of microbial pathogenesis with promising results, principally in diagnostic microbiology to rapidly identify bacteria based on the molecular profiles of small cell populations. Direct profiling of molecules from serum and tissue samples by MALDI MS providesa means to study the pathogen-host interaction and to discover potential markers of infection. Systematic molecular profiling across tissue sections represents a new imaging modality, enabling regiospecific molecular measurements to be made in situ, in both two- and three-dimensional analyses. Herein, we briefly summarize work that employs MALDI MS to study the pathogenesis of microbial infection. PMID:24997399

  9. Diagnosis, pathogenesis and treatment of myositis: recent advances

    PubMed Central

    Carstens, P-O; Schmidt, J

    2014-01-01

    Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies – in short myositis. Recent studies have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis-specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up-to-date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management. PMID:23981102

  10. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    PubMed

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

  11. Role of stem cells in spondyloarthritis: Pathogenesis, treatment and complications.

    PubMed

    Wong, Rebecca S Y

    2015-10-01

    Spondyloarthritis (SpA) is a family of interrelated inflammatory arthritis that includes ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, arthritis related to inflammatory bowel disease and undifferentiated SpA. The classification, epidemiology, pathogenesis and treatment of SpA have been extensively reviewed in the published literature. Reviews on the use of stem cells in various autoimmune diseases in general are also common. However, a review on the role of stem cells in SpA is currently lacking. This review focuses on the involvement of stem cells in the pathogenesis of SpA and the application of different types of stem cells in the treatment of SpA. It also addresses some of the complications which may arise as a result of the use of stem cells in the treatment of SpA.

  12. PPAR Could Contribute to the Pathogenesis of Hepatocellular Carcinoma

    PubMed Central

    Kimura, Osamu; Kondo, Yasuteru; Shimosegawa, Tooru

    2012-01-01

    Viral hepatitis with hepatitis C virus or hepatitis B virus and chronic liver disease such as alcoholic or nonalcoholic steatohepatitis are critical factors in the development of hepatocellular carcinoma (HCC). Furthermore, diabetes is known as an independent risk factor for HCC. Peroxisome proliferator-activated receptor (PPAR) is known to have an important role in fatty liver, and the mechanism of carcinogenesis has been clarified. PPAR controls ligand-dependent transcription, and three subtypes (α, δ, and γ) in humans are known. PPARs could contribute to the mechanisms of cell cycling, anti-inflammatory responses, and apoptosis. Therefore, to clarify the pathogenesis of HCC, we should examine PPAR signaling. In this paper, we have summarized the relevance of PPARs to the pathogenesis of HCC and cancer stem cells and possible therapeutic options through modifying PPAR signaling. PMID:23316217

  13. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    SciTech Connect

    Qiao, Wang; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

    2010-05-28

    Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H{sub 2}S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H{sub 2}S and inflammatory processes. The role of H{sub 2}S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H{sub 2}S in atherosclerosis.

  14. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.

    PubMed

    Burgener, Adam; McGowan, Ian; Klatt, Nichole R

    2015-10-01

    The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios.

  15. Sweet Bones: The Pathogenesis of Bone Alteration in Diabetes

    PubMed Central

    2016-01-01

    Diabetic patients have increased fracture risk. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone's strength, metabolism, and structure). Every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study. PMID:27777961

  16. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris.

    PubMed

    Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching; Two, Aimee; Shu, Chih-Wen; Huang, Chun-Ming

    2015-01-01

    Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

  17. Epigenetic mechanisms in Alzheimer's disease: implications for pathogenesis and therapy.

    PubMed

    Wang, Jun; Yu, Jin-Tai; Tan, Meng-Shan; Jiang, Teng; Tan, Lan

    2013-09-01

    The vast majority of Alzheimer's disease (AD) are late-onset forms (LOAD) likely due to the interplay of environmental influences and individual genetic susceptibility. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNAs, constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that epigenetic mechanisms play a pivotal role in aging the pathogenesis of AD. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and AD. Moreover, we also consider how aberrant epigenetic modifications may lead to AD pathogenesis, and we review the therapeutic potential of epigenetic treatments for AD.

  18. Behavioral Contributions to the Pathogenesis of Type 2 Diabetes

    PubMed Central

    Spruijt-Metz, Donna; Cook, Lauren; O’Reilly, Gillian A.; Page, Kathleen A.; Quinn, Charlene

    2014-01-01

    Behavioral Contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions which change each of the lifestyle behaviors is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes. PMID:24604714

  19. One year in review 2016: pathogenesis of rheumatoid arthritis.

    PubMed

    Bellucci, Eleonora; Terenzi, Riccardo; La Paglia, Giuliana Maria Concetta; Gentileschi, Stefano; Tripoli, Alessandra; Tani, Chiara; Alunno, Alessia

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic synovial inflammation leading to joint destruction and bone erosions. Although the pathogenic mechanisms underlying the disease are not fully elucidated, it is known that genetic susceptibility and environmental factors trigger an abnormal autoimmune response. Potentially, any organ and tissue could be affected by RA and the increased cardiovascular (CV) risk represents the major complication responsible for a worse prognosis. In this setting, the shared pathogenic mechanisms between RA pathogenesis and accelerated atherosclerosis further strengthen the rationale for a treat-to-target strategy with synthetic and biologic disease modifying anti-rheumatic drugs. The aim of this review is to provide the novel insights, regarding the pathogenesis of RA, published over the last year.

  20. MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

    PubMed Central

    Lorenzo Pisarello, Maria Jose; Loarca, Lorena; Ivanics, Tommy; Morton, Leslie; LaRusso, Nicholas

    2015-01-01

    The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions. PMID:26343736

  1. The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    2017-01-01

    Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes. PMID:28127155

  2. Chronic cholestatic liver diseases: clues from histopathology for pathogenesis.

    PubMed

    Pollheimer, Marion J; Fickert, Peter; Stieger, Bruno

    2014-06-01

    Chronic cholestatic liver diseases include fibrosing cholangiopathies such as primary biliary cirrhosis or primary sclerosing cholangitis. These and related cholangiopathies clearly display pathologies associated with (auto)immunologic processes. As the cholangiocyte's apical membrane is exposed to the toxic actions of the bile fluid, the interaction of bile with cholangiocytes and the biliary tree in general must be considered to completely understand the pathogenesis of cholangiopathies. While the molecular processes involved in the hepatocellular formation of bile are well understood in both normal and pathophysiologic conditions, those in the bile ducts of normal liver and in livers with cholangiopathies lag behind. This survey highlights key mechanisms known to date that are important for the formation of bile by hepatocytes and its modification by the biliary tree. It also delineates the clinical pathophysiologic findings for cholangiopathies and puts them in perspective with current experimental models to reveal the pathogenesis of cholangiopathies and develop novel therapeutic approaches.

  3. Molecular mechanisms in the pathogenesis of diabetic nephropathy: an update.

    PubMed

    Arora, Mandeep Kumar; Singh, Umesh Kumar

    2013-04-01

    Diabetes mellitus is known to trigger retinopathy, neuropathy and nephropathy. Diabetic nephropathy, a long-term major microvascular complication of uncontrolled hyperglycemia, affects a large population worldwide. Recent findings suggest that numerous pathways are activated during the course of diabetes mellitus and that these pathways individually or collectively play a role in the induction and progression of diabetic nephropathy. However, clinical strategies targeting these pathways to manage diabetic nephropathy remain unsatisfactory, as the number of diabetic patients with nephropathy is increasing yearly. To develop ground-breaking therapeutic options to prevent the development and progression of diabetic nephropathy, a comprehensive understanding of the molecular mechanisms involved in the pathogenesis of the disease is mandatory. Therefore, the purpose of this paper is to discuss the underlying mechanisms and downstream pathways involved in the pathogenesis of diabetic nephropathy.

  4. Actin-associated Proteins in the Pathogenesis of Podocyte Injury.

    PubMed

    He, Fang-Fang; Chen, Shan; Su, Hua; Meng, Xian-Fang; Zhang, Chun

    2013-11-01

    Podocytes have a complex cellular architecture with interdigitating processes maintained by a precise organization of actin filaments. The actin-based foot processes of podocytes and the interposed slit diaphragm form the final barrier to proteinuria. The function of podocytes is largely based on the maintenance of the normal foot process structure with actin cytoskeleton. Cytoskeletal dynamics play important roles during normal podocyte development, in maintenance of the healthy glomerular filtration barrier, and in the pathogenesis of glomerular diseases. In this review, we focused on recent findings on the mechanisms of organization and reorganization of these actin-related molecules in the pathogenesis of podocyte injury and potential therapeutics targeting the regulation of actin cytoskeleton in podocytopathies.

  5. Understanding Anaplasmataceae pathogenesis using “Omics” approaches

    PubMed Central

    Pruneau, Ludovic; Moumène, Amal; Meyer, Damien F.; Marcelino, Isabel; Lefrançois, Thierry; Vachiéry, Nathalie

    2014-01-01

    This paper examines how “Omics” approaches improve our understanding of Anaplasmataceae pathogenesis, through a global and integrative strategy to identify genes and proteins involved in biochemical pathways key for pathogen-host-vector interactions. The Anaplasmataceae family comprises obligate intracellular bacteria mainly transmitted by arthropods. These bacteria are responsible for major human and animal endemic and emerging infectious diseases with important economic and public health impacts. In order to improve disease control strategies, it is essential to better understand their pathogenesis. Our work focused on four Anaplasmataceae, which cause important animal, human and zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia chaffeensis, and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was also included in this review as a model of a non-pathogenic Anaplasmataceae. A gap analysis on “Omics” approaches on Anaplasmataceae was performed, which highlighted a lack of studies on the genes and proteins involved in the infection of hosts and vectors. Furthermore, most of the studies have been done on the pathogen itself, mainly on infectious free-living forms and rarely on intracellular forms. In order to perform a transcriptomic analysis of the intracellular stage of development, researchers developed methods to enrich bacterial transcripts from infected cells. These methods are described in this paper. Bacterial genes encoding outer membrane proteins, post-translational modifications, eukaryotic repeated motif proteins, proteins involved in osmotic and oxidative stress and hypothetical proteins have been identified to play a key role in Anaplasmataceae pathogenesis. Further investigations on the function of these outer membrane proteins and hypothetical proteins will be essential to confirm their role in the pathogenesis. Our work underlines the need for further studies in this domain and on host and vector responses to

  6. Hip Arthroplasty Pseudotumors: Pathogenesis, Imaging, and Clinical Decision Making

    PubMed Central

    Davis, Derik L; Morrison, James J

    2016-01-01

    Pseudotumors are a complication of hip arthroplasty. The goal of this article is to review the clinical presentation, pathogenesis, histology, and the role of diagnostic imaging in clinical decision making for treatment, and surveillance of pseudotumors. We will discuss the multimodal imaging appearances, differential diagnosis, associated complications, treatment, and prognosis of pseudotumors, as an aid to the assessment of orthopedic prostheses at the hip. PMID:27195183

  7. A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.

    2017-01-01

    Blepharospasm (sometimes called “benign essential blepharospasm,” BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to

  8. [EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

    PubMed

    Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

    2015-01-01

    The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

  9. Understanding Zika virus pathogenesis: an interview with Catherine Spong.

    PubMed

    Spong, Catherine Y

    2016-06-06

    A recent outbreak of Zika virus has been linked to fetal abnormalities in pregnant women who have been infected. The scientific community is working toward understanding Zika virus pathogenesis to better manage affected women and children. In an interview with Dr. Catherine Spong, we discuss the aims and challenges of a forthcoming longitudinal study of a cohort of pregnant women in areas of current active Zika virus transmission.

  10. The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches

    PubMed Central

    Pandya, Pankita H.; Murray, Mary E.; Pollok, Karen E.

    2016-01-01

    Interplay among immune activation and cancer pathogenesis provides the framework for a novel subspecialty known as immunooncology. In the rapidly evolving field of immunooncology, understanding the tumor-specific immune response enhances understanding of cancer resistance. This review highlights the fundamentals of incorporating precision medicine to discover new immune biomarkers and predictive signatures. Using a personalized approach may have a significant, positive impact on the use of oncolytics to better guide safer and more effective therapies. PMID:28116316

  11. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture.

    PubMed

    Jiang, Hong; Du, Hong; Wang, Li M; Wang, Ping Z; Bai, Xue F

    2016-01-01

    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed.

  12. SARCOPENIA: ITS ASSESSMENT, ETIOLOGY, PATHOGENESIS, CONSEQUENCES AND FUTURE PERSPECTIVES

    PubMed Central

    ROLLAND, Y.; CZERWINSKI, S.; VAN KAN, G. ABELLAN; MORLEY, J.E.; CESARI, M.; ONDER, G.; WOO, J.; BAUMGARTNER, R.; PILLARD, F.; BOIRIE, Y.; CHUMLEA, W.M.C.; VELLAS, B.

    2014-01-01

    Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people. PMID:18615225

  13. New insights in the pathogenesis of atopic dermatitis.

    PubMed

    Ong, Peck Y

    2014-01-01

    Atopic dermatitis (AD) is characterized by skin barrier defects and increased interleukin (IL)-4/IL-13 expression. Recent evidence also suggests the involvement of innate immunity including Toll-like receptors, IL-33, IL-25, and innate lymphoid cells in the pathogenesis of AD. This article reviews these innate immune components and how they may become an integral part of prognostic factors and therapeutic targets in the treatment of AD.

  14. [Monoamine-hormonal interactions in the pathogenesis of anxious depression].

    PubMed

    Uzbekov, M G; Maksimova, N M

    2015-01-01

    Biochemical aspects of the relationship between monoaminergic and hormonal systems in the pathogenesis of anxious depression are analyzed on the basis of literature and own results published earlier. Significant alterations in biogenic monoamine metabolism and changes in the hormonal status, that reflects homeostasis disturbance in whole, are inherent to anxious depression. The biochemical mechanisms of imbalance between serotonergic and noradrenergic systems and a role of cortisol in this process are discussed.

  15. [Immune response in the pathogenesis of hepatitis C virus infection].

    PubMed

    Chalupa, P; Holub, M; Davidová, A; Arientová, S; Beran, O

    2015-10-01

    The pathogenesis of hepatitis C virus (HCV) infection is regulated by the host immunity and several metabolic factors affecting liver metabolism, including oxidative stress, insulin resistance, and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV infection. Cytotoxic lymphocytes have a crucial role in viral eradication or viral persistence. Major cause of viral persistence during HCV infection could be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells.

  16. Pathogenesis and Treatment of Immune-Mediated Neuropathies

    PubMed Central

    Lehmann, Helmar C.; zu Horste, Gerd Meyer; Kieseier, Bernd C.

    2009-01-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

  17. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors.

    PubMed

    Two, Aimee M; Wu, Wiggin; Gallo, Richard L; Hata, Tissa R

    2015-05-01

    Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea.

  18. Current concepts in the pathogenesis of traumatic temporomandibular joint ankylosis

    PubMed Central

    2014-01-01

    Traumatic temporomandibular joint (TMJ) ankylosis can be classified into fibrous, fibro-osseous and bony ankylosis. It is still a huge challenge for oral and maxillofacial surgeons due to the technical difficulty and high incidence of recurrence. The poor outcome of disease may be partially attributed to the limited understanding of its pathogenesis. The purpose of this article was to comprehensively review the literature and summarise results from both human and animal studies related to the genesis of TMJ ankylosis. PMID:25189735

  19. T cell-dependence of Lassa fever pathogenesis.

    PubMed

    Flatz, Lukas; Rieger, Toni; Merkler, Doron; Bergthaler, Andreas; Regen, Tommy; Schedensack, Mariann; Bestmann, Lukas; Verschoor, Admar; Kreutzfeldt, Mario; Brück, Wolfgang; Hanisch, Uwe-Karsten; Günther, Stephan; Pinschewer, Daniel D

    2010-03-26

    Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.

  20. Booster vaccinations: can immunologic memory outpace disease pathogenesis?

    PubMed

    Pichichero, Michael E

    2009-12-01

    Almost all current vaccines work by the induction of antibodies in serum or on the mucosa to block adherence of pathogens to epithelial cells or interfere with microbial invasion of the bloodstream. However, antibody levels usually decline after vaccination to undetectable amounts if further vaccination does not occur. Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing "natural" boosting or other immunologic mechanisms. The production of memory B and T cells is of clear importance, but the likelihood that a memory response will be fast enough in the absence of a protective circulating antibody level likely depends on the pace of pathogenesis of a specific organism. This concept is discussed with regard to Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis; hepatitis A and B; diphtheria, tetanus, and pertussis; polio, measles, mumps, rubella, and varicella; rotavirus; and human papilloma virus. With infectious diseases for which the pace of pathogenesis is less rapid, some individuals will contract infection before the memory response is fully activated and implemented. With infectious diseases for which the pace of pathogenesis is slow, immune memory should be sufficient to prevent disease.

  1. [Role of IL-22 in the pathogenesis of skin diseases].

    PubMed

    Fujita, Hideki

    2012-01-01

    IL-22 is an IL-10 family cytokine that acts mainly on epithelial cells. It is produced by immune cell subsets, including CD4⁺ T cells, natural killer cells, and natural killer T cells. In the skin, IL-22 mediates keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and induces the production of antimicrobial proteins. Although IL-22 production was initially linked with IL-17 expression in Th17 cells, IL-22 production can also occur in an apparently unique subset of cells that lacks the production of IL-17 and IFN-γ (Th22). Interestingly, Th22 cells express skin homing chemokine receptors CCR4 and CCR10. Indeed, Th22 cells reside in the normal skin and are shown to be enriched in the lesional skin of inflammatory skin diseases, indicating the importance of IL-22 in skin homeostasis and pathogenesis of skin diseases. Although psoriasis is the first example of an organ-specific immune disorder for which the role of IL-22 has been comprehensively studied, a growing body of evidence indicates that this cytokine also plays a critical role in the pathogenesis of atopic dermatitis. In this review, we discuss the role of IL-22 in the pathogenesis of skin diseases, particularly focusing on psoriasis and atopic dermatitis. Targeting IL-22 may have promise as a potential therapeutic for various skin diseases.

  2. Current Overview of Allergens of Plant Pathogenesis Related Protein Families

    PubMed Central

    Sinha, Mau; Singh, Rashmi Prabha; Kushwaha, Gajraj Singh; Iqbal, Naseer; Singh, Avinash; Kaushik, Sanket; Sharma, Sujata; Singh, Tej P.

    2014-01-01

    Pathogenesis related (PR) proteins are one of the major sources of plant derived allergens. These proteins are induced by the plants as a defense response system in stress conditions like microbial and insect infections, wounding, exposure to harsh chemicals, and atmospheric conditions. However, some plant tissues that are more exposed to environmental conditions like UV irradiation and insect or fungal attacks express these proteins constitutively. These proteins are mostly resistant to proteases and most of them show considerable stability at low pH. Many of these plant pathogenesis related proteins are found to act as food allergens, latex allergens, and pollen allergens. Proteins having similar amino acid sequences among the members of PR proteins may be responsible for cross-reactivity among allergens from diverse plants. This review analyzes the different pathogenesis related protein families that have been reported as allergens. Proteins of these families have been characterized in regard to their biological functions, amino acid sequence, and cross-reactivity. The three-dimensional structures of some of these allergens have also been evaluated to elucidate the antigenic determinants of these molecules and to explain the cross-reactivity among the various allergens. PMID:24696647

  3. Concept of the pathogenesis and treatment of cholelithiasis

    PubMed Central

    Reshetnyak, Vasiliy Ivanovich

    2012-01-01

    Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids, which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct, or gallbladder. GD is one of the most prevalent gastrointestinal diseases with a substantial burden to health care systems. GD can result in serious outcomes, such as acute gallstone pancreatitis and gallbladder cancer. The epidemiology, pathogenesis and treatment of GD are discussed in this review. The prevalence of GD varies widely by region. The prevalence of gallstone disease has increased in recent years. This is connected with a change in lifestyle: reduction of motor activity, reduction of the physical load and changes to diets. One of the important benefits of early screening for gallstone disease is that ultrasonography can detect asymptomatic cases, which results in early treatment and the prevention of serious outcomes. The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. It suggests that corticosteroids and oral contraceptives, which contain hormones related to steroid hormones, may be regarded as a model system of cholelithiasis development in man. The achievement in the study of the physiology of bile formation and the pathogenesis of GD has allowed expanding indications for therapeutic treatment of GD. PMID:22400083

  4. Eosinophils in vasculitis: characteristics and roles in pathogenesis.

    PubMed

    Khoury, Paneez; Grayson, Peter C; Klion, Amy D

    2014-08-01

    Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides.

  5. Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis

    PubMed Central

    Jiao, Chun-Lei; Chen, Xu-Yong; Feng, Jie-Xiong

    2016-01-01

    Objective: To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results. Data Sources: Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords “Hirschsprung enterocolitis”, “Hirschsprung's enterocolitis”, “Hirschsprung's-associated enterocolitis”, “Hirschsprung-associated enterocolitis”, “HAEC”, and “EC”. Study Selection: Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Results: Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC. Conclusions: The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system. PMID:27270548

  6. The pathogenesis of transfusion-related acute lung injury (TRALI).

    PubMed

    Bux, Jürgen; Sachs, Ulrich J H

    2007-03-01

    In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

  7. Semi-automated confocal imaging of fungal pathogenesis on plants: microscopic analysis of macroscopic specimens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contextualizing natural genetic variation in plant disease resistance in terms of pathogenesis can provide information about the function of causal genes. Cellular mechanisms associated with pathogenesis can be elucidated with confocal microscopy, but systematic phenotyping platforms—from sample pro...

  8. Structural studies of human glioma pathogenesis-related protein 1

    SciTech Connect

    Asojo, Oluwatoyin A.; Koski, Raymond A.; Bonafé, Nathalie

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  9. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

    PubMed

    Taylor, Steve M; Cerami, Carla; Fairhurst, Rick M

    2013-01-01

    Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite

  10. Role of FGFR2-signaling in the pathogenesis of acne

    PubMed Central

    2009-01-01

    It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen- and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne. PMID:20436882

  11. The epidemiology of multiple sclerosis: insights to disease pathogenesis.

    PubMed

    Goodin, Douglas S

    2014-01-01

    The purpose of studying the epidemiology of multiple sclerosis (MS) is twofold. First, it is important to understand clearly the natural history of the illness in order to assist patients in making decisions about their future with respect to issues such as family planning, the importance of securing lifelong healthcare, their ability to get and maintain employment, and making appropriate choices of therapy for their particular circumstances. This is not to suggest that, even with the best possible information, the ultimate prognosis for any individual can be predicted with absolute accuracy. It cannot. Nevertheless, accurate information can be very helpful both to reassure patients that many individuals with MS do remarkably well in the long term (perhaps, especially, with current and future therapies) and also to empower individuals with respect to their ability to make their own life choices. Second, and arguably the more important purpose for studying the epidemiology of MS, is to gain insights to the underlying causes of the disease. Indeed, if the principal mechanisms of disease pathogenesis were to be understood clearly, then it might be possible to entertain notions of either a cure for existing disease or the primary prevention of future disease. Much of our current understanding of disease pathogenesis, as discussed in other chapters of this volume, has been derived from basic science investigations of animal models of MS such as experimental autoimmune encephalomyelitis (EAE), and these models have provided considerable insight both to the complexity of the mammalian immune system and to the mechanisms underlying its dysfunction in inflammatory autoimmune conditions. Nevertheless, MS is a disease of humans without any known, naturally occurring, counterpart in any nonhuman species. For this reason, the clues to disease pathogenesis provided by a study of basic epidemiologic facts regarding MS (and by a systematic consideration of their implications) are

  12. Sirtuins as novel players in the pathogenesis of diabetes mellitus

    PubMed Central

    Turkmen, Kultigin; Karagoz, Ali; Kucuk, Adem

    2014-01-01

    Diabetes mellitus (DM) is a systemic and complex disease with micro and macrovascular complications that result from impaired metabolic pathways and genetic susceptibilities. DM has been accepted as an epidemic worldwide during the last two decades. A substantial gap in our knowledge exists regarding the pathophysiology of this metabolic disorder despite the improved diagnostic tools and therapeutic approaches. Sirtuins are a group of NAD+ dependent enzymes that are involved in cellular homeostasis due to their deacetylating activity. In the present review, we aimed to discuss the role of associated sirtuins in the pathogenesis and treatment of diabetes mellitus. PMID:25512793

  13. Obesity, autophagy and the pathogenesis of liver and pancreatic cancers.

    PubMed

    Aghajan, Mariam; Li, Ning; Karin, Michael

    2012-03-01

    Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor-κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma.

  14. Anthrax lethal and edema toxins in anthrax pathogenesis.

    PubMed

    Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H

    2014-06-01

    The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis protein 2 (CMG2) as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.

  15. Role of platelets in the pathogenesis of canine endotoxin shock.

    PubMed Central

    From, A H; Fong, J S; Chiu, T; Good, R A

    1976-01-01

    Endotoxin-platelet interactions are thought to be of major importance in the response of dogs and other species to bacterial endotoxin; the mechanisms postulated are: (i) the release of vasoactive substances, (ii) the formation of occlusive platelet aggregates, and (iii) induction of intravascular coagulation. The role of platelets in canine endotoxin shock was examined in animals with thrombocytopenia induced by estrogen pretreatment (less than 10,000 platelets/mm3) and in controls. After intravenously administered endotoxin, the hemodynamic responses, mortality, and gross necropsy findings were similar in both groups. These data indicate that endotoxin-platelet interactions are not determinative in the pathogenesis of canine endotoxin shock. PMID:786877

  16. Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications.

    PubMed

    Palermo, Nadine E; Gianchandani, Roma Y; McDonnell, Marie E; Alexanian, Sara M

    2016-03-01

    Numerous studies have demonstrated an association between hyperglycemia in the perioperative period and adverse clinical outcomes. Many patients who experience hyperglycemia while hospitalized do not have a known history of diabetes and experience a transient phenomenon often described as "stress hyperglycemia" (SH). We discuss the epidemiology and pathogenesis of SH as well as evidence to date regarding predisposing factors and outcomes. Further research is needed to identify the long-term sequelae of SH as well as perioperative measures that may modulate glucose elevations and optimal treatment strategies.

  17. Elevated cerebral lactate: Implications in the pathogenesis of hepatic encephalopathy.

    PubMed

    Bosoi, Cristina R; Rose, Christopher F

    2014-12-01

    Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome, is a frequent complication of liver failure/disease. Increased concentrations of lactate are commonly observed in HE patients, in the systemic circulation, but also in the brain. Traditionally, increased cerebral lactate is considered a marker of energy failure/impairment however alterations in lactate homeostasis may also lead to a rise in brain lactate and result in neuronal dysfunction. The latter may involve the development of brain edema. This review will target the significance of increased cerebral lactate in the pathogenesis of HE.

  18. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.

    PubMed

    Horner, Mary E; Alikhan, Ali; Tintle, Suzanne; Tortorelli, Silvia; Davis, Dawn Marie R; Hand, Jennifer L

    2013-12-01

    The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.

  19. Genetic Variations of Tyrosine Hydroxylase in the Pathogenesis of Hypertension

    PubMed Central

    Lee, Yu Ho; Kim, Yang Gyun; Moon, Ju-Young; Kim, Jin Sug; Jeong, Kyung-Hwan; Lee, Tae Won; Ihm, Chun-Gyoo

    2016-01-01

    One of the major pathophysiological features of primary hypertension is an inappropriate activation of the sympathetic nervous system, which is mediated by excessive synthesis and secretion of catecholamine into the blood. Tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of catecholamine, has been highlighted because genetic variations of TH could alter the activity of the sympathetic nervous system activity and subsequently contribute to the pathogenesis of hypertension. Here, we discuss the role of TH as a regulator of sympathetic activity and review several studies that investigated the relationship between genetic variations of TH and hypertension. PMID:28275384

  20. Glomerular Dynamic Studies of the Pathogenesis of Acute Renal Failure.

    DTIC Science & Technology

    1984-06-30

    IAD-A174 113 GLOMERULAR DYNAMIC STUDIES OF THE PATHOGENESIS OF ANOTE 1/1 RENAL FAILURE(U) VIRGINIA COMNWEALTH UNIV RICHMOND I D E OKEN 3e JUN 84...8217i1 . d /or 1 Special June 30, 1984 Supported by U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND Fort Detrick, Frederick, Maryland 21701-5012 Contract...values might be underestimated by tubular inulin leakage if measured in the customary fashion.) Nephron filtration fraction was estimated from the

  1. Pathogenesis of veno-occlusive liver disease after radiation

    SciTech Connect

    Fajardo, L.F.; Colby, T.V.

    1980-11-01

    Radiation-induced liver disease is characterized structurally by progressive fibrous obliteration of central veins (veno-occlusive disease (VOD)). The pathogenesis is unknown. Samples of liver from 11 patients with radiation-induced VOD were studied by light and electron microscopy for evidence of central vein thrombosis. The patients had received fractionated radiation with total doses of 1850 to 4050 rads, or single doses of 1000 rads. In addition, six patients had received chemotherapy. We postulate that ionizing radiation injures preferentially the endothelial cells of central veins, which leads to focal deposition of fibrin. The resulting fibrin network is eventually replaced by collagen, causing fibrous occlusion.

  2. Insights into the pathogenesis of disease in human lymphatic filariasis.

    PubMed

    Nutman, Thomas B

    2013-09-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from the host inflammatory response to the parasites but also perhaps from the host inflammatory response to the parasite's Wolbachia endosymbiont and as a consequence of superimposed bacterial or fungal infections. This review will attempt to shed light on disease pathogenesis in lymphatic filariasis.

  3. [Role of complement system in the pathogenesis of AMD].

    PubMed

    Machalińska, Anna; Karczewicz, Danuta

    2009-01-01

    Age related macular degeneration (AMD), is the leading cause of blindness in individuals over age 50 years old. The pathogenesis of AMD is still not well understood with both genetic and environmental factors known to influence susceptibility to this condition. Data accumulated in the last decade implicate the chronic inflammatory processes as playing an important role in the progression of AMD. According to the recent findings, complement system is suggested to be a triggering point of the initiation of pathologic inflammatory response in the development and clinical course of AMD.

  4. Copper in microbial pathogenesis: meddling with the metal.

    PubMed

    Samanovic, Marie I; Ding, Chen; Thiele, Dennis J; Darwin, K Heran

    2012-02-16

    Transition metals such as iron, zinc, copper, and manganese are essential for the growth and development of organisms ranging from bacteria to mammals. Numerous studies have focused on the impact of iron availability during bacterial and fungal infections, and increasing evidence suggests that copper is also involved in microbial pathogenesis. Not only is copper an essential cofactor for specific microbial enzymes, but several recent studies also strongly suggest that copper is used to restrict pathogen growth in vivo. Here, we review evidence that animals use copper as an antimicrobial weapon and that, in turn, microbes have developed mechanisms to counteract the toxic effects of copper.

  5. [Immunologic disorders in pathogenesis of chronic generalized parodontitis].

    PubMed

    Volozhin, A I; Poriadin, G V; Kazimiski, T I; Barer, G M; Askerova, S Sh; Salmasi, Zh M

    2005-01-01

    Systemic immunity was studied in patients with chronic generalized parodontitis. This group of patients had distinct changes in immunologic system: depression of T- and stimulation of B-cellular immunity without accumulation of plasma cells and initiation of effective humoral response. Increased peripheral blood number of lymphocytes expressing induction of apoptosis CD95 receptors and ligand for this receptor CD95L (Fas-L) can lead to intensification of lymphocyte apoptosis and may be the reason for T-cell deficit development. The results of the study confirm the important role of immune system disturbances in pathogenesis of chronic generalized parodontitis.

  6. Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis

    PubMed Central

    Terrin, Gianluca; Scipione, Antonella; De Curtis, Mario

    2014-01-01

    Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives. PMID:25147804

  7. Cerebral malaria: insight into pathogenesis, complications and molecular biomarkers

    PubMed Central

    Yusuf, Farah Hafiz; Hafiz, Muhammad Yusuf; Shoaib, Maria; Ahmed, Syed Ahsanuddin

    2017-01-01

    Cerebral malaria is a medical emergency. All patients with Plasmodium falciparum malaria with neurologic manifestations of any degree should be urgently treated as cases of cerebral malaria. Pathogenesis of cerebral malaria is due to damaged vascular endothelium by parasite sequestration, inflammatory cytokine production and vascular leakage, which result in brain hypoxia, as indicated by increased lactate and alanine concentrations. The levels of the biomarkers’ histidine-rich protein II, angiopoietin-Tie-2 system and plasma osteoprotegrin serve as diagnostic and prognostic markers. Brain imaging may show neuropathology around the caudate and putamen. Mortality is high and patients who survive sustain brain injury which manifests as long-term neurocognitive impairments. PMID:28203097

  8. Chagas disease: role of parasite genetic variation in pathogenesis.

    PubMed

    Macedo, Andra M; Oliveira, Riva P; Pena, Srgio D J

    2002-03-05

    Chagas disease, caused by the parasite protozoan Trypanosoma cruzi, is characterised by a variable clinical course, from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. This variability has been attributed both to differences in the host response and to genomic heterogeneity of the parasite. This article reviews the evidence in favour of an important role of the genetic constitution of T. cruzi in determining the clinical characteristics of Chagas disease and discusses the basis of the 'Clonal-Histotropic Model' for the pathogenesis of this disease.

  9. Roles of Rack1 Proteins in Fungal Pathogenesis

    PubMed Central

    Zhang, Xue

    2016-01-01

    Pathogenic fungi cause diseases on various organisms. Despite their differences in life cycles, fungal pathogens use well-conserved proteins and pathways to regulate developmental and infection processes. In this review, we focus on Rack1, a multifaceted scaffolding protein involved in various biological processes. Rack1 is well conserved in eukaryotes and plays important roles in fungi, though limited studies have been conducted. To accelerate the study of Rack1 proteins in fungi, we review the functions of Rack1 proteins in model and pathogenic fungi and summarize recent progress on how Rack1 proteins are involved in fungal pathogenesis. PMID:27656651

  10. Role of autophagy in the pathogenesis of inflammatory bowel disease

    PubMed Central

    Iida, Tomoya; Onodera, Kei; Nakase, Hiroshi

    2017-01-01

    Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. Recently, some studies provided strong evidence that the process of autophagy affects several aspects of mucosal immune responses. Autophagy is a cellular stress response that plays key roles in physiological processes, such as innate and adaptive immunity, adaptation to starvation, degradation of aberrant proteins or organelles, antimicrobial defense, and protein secretion. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including IBD. Autophagy plays multiple roles in IBD pathogenesis by altering processes that include intracellular bacterial killing, antimicrobial peptide secretion by Paneth cells, goblet cell function, proinflammatory cytokine production by macrophages, antigen presentation by dendritic cells, and the endoplasmic reticulum stress response in enterocytes. Recent studies have identified susceptibility genes involved in autophagy, such as NOD2, ATG16L1, and IRGM, and active research is ongoing all over the world. The aim of this review is a systematic appraisal of the current literature to provide a better understanding of the role of autophagy in the pathogenesis of IBD. Understanding these mechanisms will bring about new strategies for the treatment and prevention of IBD. PMID:28373760

  11. Molecular aspects of bovine cystic ovarian disease pathogenesis.

    PubMed

    Ortega, Hugo H; Marelli, Belkis E; Rey, Florencia; Amweg, Ayelen N; Díaz, Pablo U; Stangaferro, Matías L; Salvetti, Natalia R

    2015-06-01

    Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/R251/suppl/DC1.

  12. [The role of gut microbiota in the pathogenesis of obesity].

    PubMed

    Zak-Gołąb, Agnieszka; Olszanecka-Glinianowicz, Magdalena; Kocełak, Piotr; Chudek, Jerzy

    2014-01-24

    Obesity is a disease that develops as a result of long-term positive energy balance. In recent years, the influence of gut microflora composition, as a potential factor affecting the energy balance and contributing to fat accumulation, has been studied. It seems that bacteria can affect host energy balance through several mechanisms, such as increased fermentation of undigested polysaccharides and obtaining extra energy from the portion of food, reduced expression of FIAF (fasting-induced adipocyte factor) in the enterocytes with inhibitory activity towards intestinal lipoprotein lipase, and the increased release of peptide YY that slows the intestinal motility. It is also believed that changes in the composition of gut microflora may be one of the factors that induce systemic microinflammation in the obese, an important link in the pathogenesis of obesity related complications, including dyslipidaemia, hypertension and type 2 diabetes. However, the results of previous studies are inconclusive. Many of them have been carried out in an animal model and were not confirmed in studies involving humans. These discrepancies may be due to different composition of the diet, distinct physiological gut microflora and the methodology used in these studies. The present article reviews the current literature on the potential role of gut microflora in the pathogenesis of obesity.

  13. Streptococcus mitis: walking the line between commensalism and pathogenesis.

    PubMed

    Mitchell, J

    2011-04-01

    Streptococcus mitis is a viridans streptococcus and a normal commensal of the human oropharynx. However, S. mitis can escape from this niche and cause a variety of infectious complications including infective endocarditis, bacteraemia and septicaemia. It uses a variety of strategies to effectively colonize the human oropharynx. These include expression of adhesins, immunoglobulin A proteases and toxins, and modulation of the host immune system. These various colonization factors allow S. mitis to compete for space and nutrients in the face of its more pathogenic oropharyngeal microbial neighbours. However, it is likely that in vulnerable immune-compromised patients S. mitis will use the same colonization and immune modulation factors as virulence factors promoting its opportunistic pathogenesis. The recent publication of a complete genome sequence for S. mitis strain B6 will allow researchers to thoroughly investigate which genes are involved in S. mitis host colonization and pathogenesis. Moreover, it will help to give insight into where S. mitis fits in the complicated oral microbiome. This review will discuss the current knowledge of S. mitis factors involved in host colonization, their potential role in virulence and what needs to be done to fully understand how a an oral commensal successfully transitions to a virulent pathogen.

  14. Impaired Mitochondrial Function and Dynamics in the Pathogenesis of FXTAS.

    PubMed

    Alvarez-Mora, M I; Rodriguez-Revenga, L; Madrigal, I; Guitart-Mampel, M; Garrabou, G; Milà, M

    2016-10-22

    Mitochondrial involvement plays an important role in neurodegenerative diseases. At least one-third of adult carriers of a FMR1 premutation (55-200 CGG repeats) are at risk of presenting an adult-onset neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). In an attempt to provide new insights into the mechanisms involved in the pathogenesis of FXTAS, we characterized mitochondrial function and dynamics by the assessment of oxidative respiratory chain function, mitochondrial content, oxidative stress levels, and mitochondrial network complexity. Regarding mitochondrial function, we found that mitochondrial respiratory capacity is compromised in skin fibroblasts whereas in blood, no differences were observed between the FXTAS and control groups. Furthermore, fibroblasts from FXTAS patients presented altered mitochondrial architecture, with more circular and less interconnected mitochondria being observed. Mitochondrial function and dynamics deregulation and characteristic of neurological disorders are present in FXTAS patients. These features might be limiting temporal and spatial bioenergetics cells supply and thus contributing to disease pathogenesis.

  15. Expression of NDUFA13 in asthenozoospermia and possible pathogenesis.

    PubMed

    Yang, Yang; Cheng, Laiyang; Wang, Ying; Han, Yilong; Liu, Jin; Deng, Xiaohui; Chao, Lan

    2017-01-01

    Asthenozoospermia is a common cause of male infertility, which is characterized by reduced forward motility of spermatozoa. The cause and pathogenesis of asthenozoospermia are not fully understood. The purpose of this study was to investigate the expression of nicotinamide adenine dinucleotide (NADH) dehydrogenase (ubiquinone) 1 alpha subcomplex, 13 (NDUFA13) in the spermatozoa of men with asthenozoospermia and its possible pathogenesis. Protein content of NDUFA13 in spermatozoa was measured by Western blot analysis. The results showed that NDUFA13 expression in spermatozoa was significantly lower in men with asthenozoospermic than in men with normozoospermia (P < 0.01). Immunofluorescence experiments showed that NDUFA13 was expressed predominantly in the sperm mid-piece. A lower mitochondrial membrane potential, a higher intracellular reactive oxygen species (ROS) level and more apoptotic cells were also detected in men with asthenozoospermia. NDUFA13-specific small interfering RNA was used in the mouse spermatocyte GC2-spd cell line to down-regulate the expression of NDUFA13. The knockdown of NDUFA13 in the GC2-spd cells caused a collapse of mitochondrial membrane potential, an increase in ROS level and more apoptotic cells. Our study showed that NDUFA13 deficiency may be associated with asthenozoospermia through the disturbance of spermatozoa mitochondrial membrane potential and by increasing apoptosis and intracellular ROS.

  16. Structural studies of human glioma pathogenesis-related protein 1.

    PubMed

    Asojo, Oluwatoyin A; Koski, Raymond A; Bonafé, Nathalie

    2011-10-01

    Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  17. Neurogenesis, NSCs, pathogenesis and therapies for Alzheimer's disease.

    PubMed

    Taupin, Philippe

    2011-01-01

    Neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS) of mammals. Adult NSCs offer tremendous potential for cellular therapy for the treatment of neurological diseases and injuries, particularly of Alzheimer's disease (AD). The contribution of newly generated neuronal cells of the adult brain to the functioning of the nervous system remains to be elucidated. Neurogenesis is enhanced in the brain of patients with AD. Enhanced neurogenesis would contribute to regenerative attempts in AD, to compensate for the neuronal loss. Adult neurogenesis holds the potential to generate aneuploid cells, a landmark of AD pathology. Aneuploid newly generated neuronal cells in the adult brain would contribute to the pathogenesis of AD. Adult neurogenesis would not only be beneficial, but also detrimental for patients with AD. We will review and discuss the potential of adult NSCs for the treatment of AD and their contribution to the pathogenesis of the disease, as well as the development of novel drugs and therapies for treating AD.

  18. IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

    PubMed Central

    Mager, Lukas F.; Riether, Carsten; Schürch, Christian M.; Banz, Yara; Wasmer, Marie-Hélène; Stuber, Regula; Theocharides, Alexandre P.; Li, Xiaohong; Xia, Yu; Saito, Hirohisa; Nakae, Susumu; Baerlocher, Gabriela M.; Manz, Markus G.; McCoy, Kathy D.; Macpherson, Andrew J.; Ochsenbein, Adrian F.; Beutler, Bruce; Krebs, Philippe

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34+ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs. PMID:26011644

  19. Epigenetic regulation of development and pathogenesis in fungal plant pathogens.

    PubMed

    Dubey, Akanksha; Jeon, Junhyun

    2016-10-17

    Evidently, epigenetics is at forefront in explaining the mechanisms underlying the success of human pathogens and in the identification of pathogen-induced modifications within host plants. However, there is a lack of studies highlighting the role of epigenetics in the modulation of the growth and pathogenicity of fungal plant pathogens. In this review, we attempt to highlight and discuss the role of epigenetics in the regulation of the growth and pathogenicity of fungal phytopathogens using Magnaporthe oryzae, a devastating fungal plant pathogen, as a model system. With the perspective of wide application in the understanding of the development, pathogenesis and control of other fungal pathogens, we attempt to provide a synthesized view of the epigenetic studies conducted on M. oryzae to date. First, we discuss the mechanisms of epigenetic modifications in M. oryzae and their impact on fungal development and pathogenicity. Second, we highlight the unexplored epigenetic mechanisms and areas of research that should be considered in the near future to construct a holistic view of epigenetic functioning in M. oryzae and other fungal plant pathogens. Importantly, the development of a complete understanding of the modulation of epigenetic regulation in fungal pathogens can help in the identification of target points to combat fungal pathogenesis.

  20. Role of oxidative stress in pathogenesis of metabolic syndrome

    PubMed Central

    Mahjoub, Soleiman; Masrour-Roudsari, Jila

    2012-01-01

    The metabolic syndrome (MS) recognized as a major cause of type 2 diabetes and cardiovascular diseases, has become one of the major public health challenges worldwide. The pathogenesis of the metabolic syndrome is multiple and still poorly understood. No single factor has yet been identified as an underlying causal factor. There is a growing belief, however, that obesity, especially visceral obesity, may play an important role in the development of the syndrome. Visceral adiposity seems to be an independent predictor of insulin sensitivity, impaired glucose tolerance, dyslipidemia and elevated blood pressure. An increasing number of studies confirm that oxidative stress, chronic inflammation and angiogenesis all play important roles in the pathogenesis of MS. Chronic hyperglycemia causes oxidative stress in tissues prone to complications in patients with diabetes. Oxidative stress occurs in a cellular system when the production of free radical moieties exceeds the antioxidant capacity of that system. If cellular antioxidants do not remove free radicals, radicals attack and damage proteins, lipids, and nucleic acids. The oxidized or nitrosylated products of free radical attack have decreased biological activity, leading to loss of energy metabolism, cell signaling, transport, and other major functions. These altered products are also targeted for proteosome degradation, further decreasing cellular function. Accumulation of such injury ultimately leads a cell to die through necrotic or apoptotic mechanisms. In conclusion, a puzzle of many pieces of evidence suggests that free radical overgeneration may be considered the key in the generation of insulin resistance, diabetes, and cardiovascular disease. PMID:26557292